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The emergence of vorasidenib, the first targeted therapy for certain gliomas with IDH mutations, has ignited a wave of excitement in both patient and physician spaces.

After years with limited treatment options, experts hailed vorasidenib “a promising breakthrough,” “a paradigm shift,” a “new hope,” and “probably the most important advance in the treatment of low-grade gliomas in the last decade.”

Promising results from vorasidenib’s pivotal INDIGO trial fueled petitions and patient advocacy circles to push for the drug’s approval. And, in August 2024, the Food and Drug Administration (FDA) approved vorasidenib for grade 2 astrocytomas or oligodendrogliomas with an IDH1 or IDH2 mutation.

But following the approval, some experts expressed concerns and doubts about the drug and the INDIGO trial, bringing a host of unanswered questions into sharper focus.

In an editorial, Stanislav Lazarev, MD, and Kunal K. Sindhu, MD, both radiation oncologists from Icahn School of Medicine at Mount Sinai, New York City, suggest that the FDA approval “might be premature given the high cost of this drug and lack of clear benefit over standard treatments.”

Another recent critique also pointed to the lack of clear evidence that vorasidenib is superior to the prevailing standard of care, despite the drug’s high cost. These authors noted that “patients want to live longer, and if not, at least live better,” but “based on the INDIGO study, it is impossible to say whether vorasidenib can provide either.”

Vorasidenib is now one of the most expensive cancer therapies, with an annual cost of nearly $500,000, but the INDIGO trial did not explore whether the drug led to improved overall survival or better quality of life. Among the trial’s design flaws, experts called out the use of progression-free survival as the primary outcome, instead of overall survival, and the use of an inappropriate comparator group.

INDIGO was a phase 3 trial that included 331 adult patients (median age, 40.5 years) with grade-2 IDH-mutant recurrent or residual glioma after surgery. To be eligible, patients had to be followed for at least 1 year, and up to 5 years, post surgery and had to be considered appropriate candidates for a watch-and-wait approach.

Participants were randomly assigned to receive either 40 mg of vorasidenib or a matching placebo orally, once daily, in continuous 28-day cycles until imaging-confirmed tumor disease progression or unacceptable toxicity, at which point crossover to vorasidenib from placebo was permitted. Over one third (n = 58) of patients in the placebo group crossed over and 90% of them (n = 52) received vorasidenib.

Median progression-free survival was significantly better in the vorasidenib group at 27.7 months vs 11.1 months in the placebo group (hazard ratio [HR], 0.39).

A key secondary endpoint — time to next intervention — was also significant; the likelihood of being alive and not receiving further treatment at 18 months was 85.6% in the vorasidenib group and 47.4% in the placebo group (HR, 0.26). This finding indicates that most patients receiving vorasidenib could delay chemoradiation for 18 months or longer.

Despite these impressive outcomes, some experts noted that using progression-free survival as the primary endpoint was a major flaw of the INDIGO trial because, currently, there is no evidence that progression-free survival is a reliable surrogate endpoint for overall survival in this setting.

The high rate of crossover to vorasidenib is another issue because it may limit a longer-term analysis of overall survival. If, for instance, overall survival is the same between the groups, it could signal that the drug is effective in both groups or, alternatively, that the drug has no effect on survival in either group.

“That is a legitimate concern,” Seema Nagpal, MD, a neuro-oncologist at Stanford University in California, and a site principal investigator for the INDIGO trial, said in an interview. “We don’t know that this drug changes overall survival, and I think we’re not going to get a super clean answer on that.”

Another major issue centers on the standard of care assigned to control patients in the INDIGO trial.

In the trial, vorasidenib was compared with placebo — an appropriate standard-of-care comparison for patients with low-risk gliomas. These patients often initially undergo watch-and-wait to delay chemoradiation. But Lazarev and Sindhu argue that the patients in INDIGO were really high risk, which means the control group should have received the standard of care for these patients: Chemoradiation following surgery.

This question about the appropriate standard of care stems from ongoing uncertainty about the distinction between high- and low-risk gliomas.

The classification for gliomas falls into either low risk or high risk for early disease progression. The RTOG 9802 criteria, often used for glioma risk stratification, defines low-risk patients as those younger than 40 years with gross total resection and high-risk patients as those aged 40 years or older with any extent of resection or those younger than 40 years with subtotal or biopsy resection.

But an evolving understanding of genetic anomalies that affect prognoses in this tumor type has muddied the current high- and low-risk distinctions.

“People haven’t totally figured out what high and low risk means,” Nagpal acknowledged.

This uncertainty has spilled over into the INDIGO trial.

While the trial excluded patients who had any features indicating high risk, such as brain stem involvement or neurocognitive deficits, the researchers also did not explicitly define patients as low risk. However, the inclusion criteria specified that patients had to be observed for at least 1 year after surgery and be considered appropriate for a watch-and-wait protocol, which does suggest patients were considered low risk, said Nagpal.

Still, some experts argue that the patients in INDIGO were not low risk.

Patients had residual or recurrent disease so “wouldn’t be classified as low risk,” said Sindhu in an interview. The standard of care for these patients is chemoradiation, Lazarev added.

“The definition of a phase 3 clinical trial is that you compare the novel intervention to the standard of care,” said Lazarev. “Level 1 evidence clearly shows that omitting chemoradiation leads to worse outcomes, with patients literally dying sooner. For the investigators to knowingly exclude this proven treatment raises serious ethical and methodological questions about the study’s design.” 

In a recent opinion piece, Nagpal agreed that most patients selected for INDIGO would not have been considered low risk by many providers. All patients selected for INDIGO had postoperative residual/recurrent disease and many were older than 40 years.

But, Nagpal explained, the risk stratification of the INDIGO patients was still lower than what is commonly considered high risk. The patients had all been observed for a year or more already, “so by definition, the clinician treating them already decided they were not high risk,” she said.

In another recent opinion piece, oncologists suggested that, because patients in the INDIGO trial do not squarely fall into either category, instead representing a “grey area,” it’s time to create a new risk category.

“Perhaps the time has come to abandon the old binary risk stratification (“low risk” vs “high risk”), which still contains arbitrary elements (such as the age cutoff), proving impractical in real-world clinical decision-making, and to adopt a new one, also taking into account many emerging prognostic biomarkers,” the authors wrote.

Despite the uncertainty surrounding risk categories, the INDIGO authors justified their study design.

A watch-and-wait period for patients in the trial, which “represents the earliest clinical phase in tumorigenesis of IDH-mutant WHO grade 2 glioma,” is “an opportunity to detect a clear signal of antitumor activity for new therapies in placebo-controlled trials” and “postpone the use of radiation therapy and chemotherapy,” the authors explained.

Lazarev, however, questioned the premise that chemoradiation should be delayed.

Oncologists’ desire to delay chemoradiation for their patients reflects “a limited understanding of modern irradiation therapy,” Lazarev said. “Modern technology has improved dramatically. We’re more precise, our understanding about late side effects is better. So, the big picture is that the absolute risk of late neurocognitive affects that actually will affect patients’ quality of life, their ability to work, go to school, succeed on a personal or professional level is exceedingly low.”

Nagpal strongly disagreed.

“Please come to my clinic and ask an actual patient,” said Nagpal. “Once a radiation oncologist has irradiated the patient, they almost never seen them again. People who are on the medical side, who follow these patients from beginning to end, recognize that delaying radiation is a huge deal.”

Although vorasidenib isn’t a cure, Nagpal said, it is a less toxic way to delay radiation “because that is a real and disabling thing” for patients and is why neuro-oncologists are excited about alternative treatment options.

Another issue surrounding the vorasidenib approval lies in the FDA’s vague prescribing information. The prescribing information does not specify that patients should be followed for at least 1 year post surgery or that patients need to be lower risk. Prescribing physicians may, therefore, think vorasidenib is appropriate for any patient with a grade-2 IDH mutant glioma at any time and defer or not offer chemoradiation to high-risk patients.

Amid lingering questions about the INDIGO trial design and ongoing uncertainties about how to define and treat this patient population, experts remain divided on whether vorasidenib is worth it.

“If vorasidenib is truly transformative, it should be feasible to demonstrate its superiority over chemoradiotherapy,” Lazarev and Sindhu wrote. “For a drug with such a staggering price tag, an imperative should be placed on the investigators and manufacturer to provide clear evidence of efficacy, whether in terms of improved [overall survival] or quality of life, before vorasidenib is recommended for the treatment of IDH-mutant low-grade gliomas.”

The INDIGO trial was supported by Servier, the manufacturer of vorasidenib. Many of the study authors reported employment or support from the company. Nagpal reported consulting fees from Servier and AnHeart Therapeutics. Lazarev and Sindhu reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

The emergence of vorasidenib, the first targeted therapy for certain gliomas with IDH mutations, has ignited a wave of excitement in both patient and physician spaces.

After years with limited treatment options, experts hailed vorasidenib “a promising breakthrough,” “a paradigm shift,” a “new hope,” and “probably the most important advance in the treatment of low-grade gliomas in the last decade.”

Promising results from vorasidenib’s pivotal INDIGO trial fueled petitions and patient advocacy circles to push for the drug’s approval. And, in August 2024, the Food and Drug Administration (FDA) approved vorasidenib for grade 2 astrocytomas or oligodendrogliomas with an IDH1 or IDH2 mutation.

But following the approval, some experts expressed concerns and doubts about the drug and the INDIGO trial, bringing a host of unanswered questions into sharper focus.

In an editorial, Stanislav Lazarev, MD, and Kunal K. Sindhu, MD, both radiation oncologists from Icahn School of Medicine at Mount Sinai, New York City, suggest that the FDA approval “might be premature given the high cost of this drug and lack of clear benefit over standard treatments.”

Another recent critique also pointed to the lack of clear evidence that vorasidenib is superior to the prevailing standard of care, despite the drug’s high cost. These authors noted that “patients want to live longer, and if not, at least live better,” but “based on the INDIGO study, it is impossible to say whether vorasidenib can provide either.”

Vorasidenib is now one of the most expensive cancer therapies, with an annual cost of nearly $500,000, but the INDIGO trial did not explore whether the drug led to improved overall survival or better quality of life. Among the trial’s design flaws, experts called out the use of progression-free survival as the primary outcome, instead of overall survival, and the use of an inappropriate comparator group.

INDIGO was a phase 3 trial that included 331 adult patients (median age, 40.5 years) with grade-2 IDH-mutant recurrent or residual glioma after surgery. To be eligible, patients had to be followed for at least 1 year, and up to 5 years, post surgery and had to be considered appropriate candidates for a watch-and-wait approach.

Participants were randomly assigned to receive either 40 mg of vorasidenib or a matching placebo orally, once daily, in continuous 28-day cycles until imaging-confirmed tumor disease progression or unacceptable toxicity, at which point crossover to vorasidenib from placebo was permitted. Over one third (n = 58) of patients in the placebo group crossed over and 90% of them (n = 52) received vorasidenib.

Median progression-free survival was significantly better in the vorasidenib group at 27.7 months vs 11.1 months in the placebo group (hazard ratio [HR], 0.39).

A key secondary endpoint — time to next intervention — was also significant; the likelihood of being alive and not receiving further treatment at 18 months was 85.6% in the vorasidenib group and 47.4% in the placebo group (HR, 0.26). This finding indicates that most patients receiving vorasidenib could delay chemoradiation for 18 months or longer.

Despite these impressive outcomes, some experts noted that using progression-free survival as the primary endpoint was a major flaw of the INDIGO trial because, currently, there is no evidence that progression-free survival is a reliable surrogate endpoint for overall survival in this setting.

The high rate of crossover to vorasidenib is another issue because it may limit a longer-term analysis of overall survival. If, for instance, overall survival is the same between the groups, it could signal that the drug is effective in both groups or, alternatively, that the drug has no effect on survival in either group.

“That is a legitimate concern,” Seema Nagpal, MD, a neuro-oncologist at Stanford University in California, and a site principal investigator for the INDIGO trial, said in an interview. “We don’t know that this drug changes overall survival, and I think we’re not going to get a super clean answer on that.”

Another major issue centers on the standard of care assigned to control patients in the INDIGO trial.

In the trial, vorasidenib was compared with placebo — an appropriate standard-of-care comparison for patients with low-risk gliomas. These patients often initially undergo watch-and-wait to delay chemoradiation. But Lazarev and Sindhu argue that the patients in INDIGO were really high risk, which means the control group should have received the standard of care for these patients: Chemoradiation following surgery.

This question about the appropriate standard of care stems from ongoing uncertainty about the distinction between high- and low-risk gliomas.

The classification for gliomas falls into either low risk or high risk for early disease progression. The RTOG 9802 criteria, often used for glioma risk stratification, defines low-risk patients as those younger than 40 years with gross total resection and high-risk patients as those aged 40 years or older with any extent of resection or those younger than 40 years with subtotal or biopsy resection.

But an evolving understanding of genetic anomalies that affect prognoses in this tumor type has muddied the current high- and low-risk distinctions.

“People haven’t totally figured out what high and low risk means,” Nagpal acknowledged.

This uncertainty has spilled over into the INDIGO trial.

While the trial excluded patients who had any features indicating high risk, such as brain stem involvement or neurocognitive deficits, the researchers also did not explicitly define patients as low risk. However, the inclusion criteria specified that patients had to be observed for at least 1 year after surgery and be considered appropriate for a watch-and-wait protocol, which does suggest patients were considered low risk, said Nagpal.

Still, some experts argue that the patients in INDIGO were not low risk.

Patients had residual or recurrent disease so “wouldn’t be classified as low risk,” said Sindhu in an interview. The standard of care for these patients is chemoradiation, Lazarev added.

“The definition of a phase 3 clinical trial is that you compare the novel intervention to the standard of care,” said Lazarev. “Level 1 evidence clearly shows that omitting chemoradiation leads to worse outcomes, with patients literally dying sooner. For the investigators to knowingly exclude this proven treatment raises serious ethical and methodological questions about the study’s design.” 

In a recent opinion piece, Nagpal agreed that most patients selected for INDIGO would not have been considered low risk by many providers. All patients selected for INDIGO had postoperative residual/recurrent disease and many were older than 40 years.

But, Nagpal explained, the risk stratification of the INDIGO patients was still lower than what is commonly considered high risk. The patients had all been observed for a year or more already, “so by definition, the clinician treating them already decided they were not high risk,” she said.

In another recent opinion piece, oncologists suggested that, because patients in the INDIGO trial do not squarely fall into either category, instead representing a “grey area,” it’s time to create a new risk category.

“Perhaps the time has come to abandon the old binary risk stratification (“low risk” vs “high risk”), which still contains arbitrary elements (such as the age cutoff), proving impractical in real-world clinical decision-making, and to adopt a new one, also taking into account many emerging prognostic biomarkers,” the authors wrote.

Despite the uncertainty surrounding risk categories, the INDIGO authors justified their study design.

A watch-and-wait period for patients in the trial, which “represents the earliest clinical phase in tumorigenesis of IDH-mutant WHO grade 2 glioma,” is “an opportunity to detect a clear signal of antitumor activity for new therapies in placebo-controlled trials” and “postpone the use of radiation therapy and chemotherapy,” the authors explained.

Lazarev, however, questioned the premise that chemoradiation should be delayed.

Oncologists’ desire to delay chemoradiation for their patients reflects “a limited understanding of modern irradiation therapy,” Lazarev said. “Modern technology has improved dramatically. We’re more precise, our understanding about late side effects is better. So, the big picture is that the absolute risk of late neurocognitive affects that actually will affect patients’ quality of life, their ability to work, go to school, succeed on a personal or professional level is exceedingly low.”

Nagpal strongly disagreed.

“Please come to my clinic and ask an actual patient,” said Nagpal. “Once a radiation oncologist has irradiated the patient, they almost never seen them again. People who are on the medical side, who follow these patients from beginning to end, recognize that delaying radiation is a huge deal.”

Although vorasidenib isn’t a cure, Nagpal said, it is a less toxic way to delay radiation “because that is a real and disabling thing” for patients and is why neuro-oncologists are excited about alternative treatment options.

Another issue surrounding the vorasidenib approval lies in the FDA’s vague prescribing information. The prescribing information does not specify that patients should be followed for at least 1 year post surgery or that patients need to be lower risk. Prescribing physicians may, therefore, think vorasidenib is appropriate for any patient with a grade-2 IDH mutant glioma at any time and defer or not offer chemoradiation to high-risk patients.

Amid lingering questions about the INDIGO trial design and ongoing uncertainties about how to define and treat this patient population, experts remain divided on whether vorasidenib is worth it.

“If vorasidenib is truly transformative, it should be feasible to demonstrate its superiority over chemoradiotherapy,” Lazarev and Sindhu wrote. “For a drug with such a staggering price tag, an imperative should be placed on the investigators and manufacturer to provide clear evidence of efficacy, whether in terms of improved [overall survival] or quality of life, before vorasidenib is recommended for the treatment of IDH-mutant low-grade gliomas.”

The INDIGO trial was supported by Servier, the manufacturer of vorasidenib. Many of the study authors reported employment or support from the company. Nagpal reported consulting fees from Servier and AnHeart Therapeutics. Lazarev and Sindhu reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

The emergence of vorasidenib, the first targeted therapy for certain gliomas with IDH mutations, has ignited a wave of excitement in both patient and physician spaces.

After years with limited treatment options, experts hailed vorasidenib “a promising breakthrough,” “a paradigm shift,” a “new hope,” and “probably the most important advance in the treatment of low-grade gliomas in the last decade.”

Promising results from vorasidenib’s pivotal INDIGO trial fueled petitions and patient advocacy circles to push for the drug’s approval. And, in August 2024, the Food and Drug Administration (FDA) approved vorasidenib for grade 2 astrocytomas or oligodendrogliomas with an IDH1 or IDH2 mutation.

But following the approval, some experts expressed concerns and doubts about the drug and the INDIGO trial, bringing a host of unanswered questions into sharper focus.

In an editorial, Stanislav Lazarev, MD, and Kunal K. Sindhu, MD, both radiation oncologists from Icahn School of Medicine at Mount Sinai, New York City, suggest that the FDA approval “might be premature given the high cost of this drug and lack of clear benefit over standard treatments.”

Another recent critique also pointed to the lack of clear evidence that vorasidenib is superior to the prevailing standard of care, despite the drug’s high cost. These authors noted that “patients want to live longer, and if not, at least live better,” but “based on the INDIGO study, it is impossible to say whether vorasidenib can provide either.”

Vorasidenib is now one of the most expensive cancer therapies, with an annual cost of nearly $500,000, but the INDIGO trial did not explore whether the drug led to improved overall survival or better quality of life. Among the trial’s design flaws, experts called out the use of progression-free survival as the primary outcome, instead of overall survival, and the use of an inappropriate comparator group.

INDIGO was a phase 3 trial that included 331 adult patients (median age, 40.5 years) with grade-2 IDH-mutant recurrent or residual glioma after surgery. To be eligible, patients had to be followed for at least 1 year, and up to 5 years, post surgery and had to be considered appropriate candidates for a watch-and-wait approach.

Participants were randomly assigned to receive either 40 mg of vorasidenib or a matching placebo orally, once daily, in continuous 28-day cycles until imaging-confirmed tumor disease progression or unacceptable toxicity, at which point crossover to vorasidenib from placebo was permitted. Over one third (n = 58) of patients in the placebo group crossed over and 90% of them (n = 52) received vorasidenib.

Median progression-free survival was significantly better in the vorasidenib group at 27.7 months vs 11.1 months in the placebo group (hazard ratio [HR], 0.39).

A key secondary endpoint — time to next intervention — was also significant; the likelihood of being alive and not receiving further treatment at 18 months was 85.6% in the vorasidenib group and 47.4% in the placebo group (HR, 0.26). This finding indicates that most patients receiving vorasidenib could delay chemoradiation for 18 months or longer.

Despite these impressive outcomes, some experts noted that using progression-free survival as the primary endpoint was a major flaw of the INDIGO trial because, currently, there is no evidence that progression-free survival is a reliable surrogate endpoint for overall survival in this setting.

The high rate of crossover to vorasidenib is another issue because it may limit a longer-term analysis of overall survival. If, for instance, overall survival is the same between the groups, it could signal that the drug is effective in both groups or, alternatively, that the drug has no effect on survival in either group.

“That is a legitimate concern,” Seema Nagpal, MD, a neuro-oncologist at Stanford University in California, and a site principal investigator for the INDIGO trial, said in an interview. “We don’t know that this drug changes overall survival, and I think we’re not going to get a super clean answer on that.”

Another major issue centers on the standard of care assigned to control patients in the INDIGO trial.

In the trial, vorasidenib was compared with placebo — an appropriate standard-of-care comparison for patients with low-risk gliomas. These patients often initially undergo watch-and-wait to delay chemoradiation. But Lazarev and Sindhu argue that the patients in INDIGO were really high risk, which means the control group should have received the standard of care for these patients: Chemoradiation following surgery.

This question about the appropriate standard of care stems from ongoing uncertainty about the distinction between high- and low-risk gliomas.

The classification for gliomas falls into either low risk or high risk for early disease progression. The RTOG 9802 criteria, often used for glioma risk stratification, defines low-risk patients as those younger than 40 years with gross total resection and high-risk patients as those aged 40 years or older with any extent of resection or those younger than 40 years with subtotal or biopsy resection.

But an evolving understanding of genetic anomalies that affect prognoses in this tumor type has muddied the current high- and low-risk distinctions.

“People haven’t totally figured out what high and low risk means,” Nagpal acknowledged.

This uncertainty has spilled over into the INDIGO trial.

While the trial excluded patients who had any features indicating high risk, such as brain stem involvement or neurocognitive deficits, the researchers also did not explicitly define patients as low risk. However, the inclusion criteria specified that patients had to be observed for at least 1 year after surgery and be considered appropriate for a watch-and-wait protocol, which does suggest patients were considered low risk, said Nagpal.

Still, some experts argue that the patients in INDIGO were not low risk.

Patients had residual or recurrent disease so “wouldn’t be classified as low risk,” said Sindhu in an interview. The standard of care for these patients is chemoradiation, Lazarev added.

“The definition of a phase 3 clinical trial is that you compare the novel intervention to the standard of care,” said Lazarev. “Level 1 evidence clearly shows that omitting chemoradiation leads to worse outcomes, with patients literally dying sooner. For the investigators to knowingly exclude this proven treatment raises serious ethical and methodological questions about the study’s design.” 

In a recent opinion piece, Nagpal agreed that most patients selected for INDIGO would not have been considered low risk by many providers. All patients selected for INDIGO had postoperative residual/recurrent disease and many were older than 40 years.

But, Nagpal explained, the risk stratification of the INDIGO patients was still lower than what is commonly considered high risk. The patients had all been observed for a year or more already, “so by definition, the clinician treating them already decided they were not high risk,” she said.

In another recent opinion piece, oncologists suggested that, because patients in the INDIGO trial do not squarely fall into either category, instead representing a “grey area,” it’s time to create a new risk category.

“Perhaps the time has come to abandon the old binary risk stratification (“low risk” vs “high risk”), which still contains arbitrary elements (such as the age cutoff), proving impractical in real-world clinical decision-making, and to adopt a new one, also taking into account many emerging prognostic biomarkers,” the authors wrote.

Despite the uncertainty surrounding risk categories, the INDIGO authors justified their study design.

A watch-and-wait period for patients in the trial, which “represents the earliest clinical phase in tumorigenesis of IDH-mutant WHO grade 2 glioma,” is “an opportunity to detect a clear signal of antitumor activity for new therapies in placebo-controlled trials” and “postpone the use of radiation therapy and chemotherapy,” the authors explained.

Lazarev, however, questioned the premise that chemoradiation should be delayed.

Oncologists’ desire to delay chemoradiation for their patients reflects “a limited understanding of modern irradiation therapy,” Lazarev said. “Modern technology has improved dramatically. We’re more precise, our understanding about late side effects is better. So, the big picture is that the absolute risk of late neurocognitive affects that actually will affect patients’ quality of life, their ability to work, go to school, succeed on a personal or professional level is exceedingly low.”

Nagpal strongly disagreed.

“Please come to my clinic and ask an actual patient,” said Nagpal. “Once a radiation oncologist has irradiated the patient, they almost never seen them again. People who are on the medical side, who follow these patients from beginning to end, recognize that delaying radiation is a huge deal.”

Although vorasidenib isn’t a cure, Nagpal said, it is a less toxic way to delay radiation “because that is a real and disabling thing” for patients and is why neuro-oncologists are excited about alternative treatment options.

Another issue surrounding the vorasidenib approval lies in the FDA’s vague prescribing information. The prescribing information does not specify that patients should be followed for at least 1 year post surgery or that patients need to be lower risk. Prescribing physicians may, therefore, think vorasidenib is appropriate for any patient with a grade-2 IDH mutant glioma at any time and defer or not offer chemoradiation to high-risk patients.

Amid lingering questions about the INDIGO trial design and ongoing uncertainties about how to define and treat this patient population, experts remain divided on whether vorasidenib is worth it.

“If vorasidenib is truly transformative, it should be feasible to demonstrate its superiority over chemoradiotherapy,” Lazarev and Sindhu wrote. “For a drug with such a staggering price tag, an imperative should be placed on the investigators and manufacturer to provide clear evidence of efficacy, whether in terms of improved [overall survival] or quality of life, before vorasidenib is recommended for the treatment of IDH-mutant low-grade gliomas.”

The INDIGO trial was supported by Servier, the manufacturer of vorasidenib. Many of the study authors reported employment or support from the company. Nagpal reported consulting fees from Servier and AnHeart Therapeutics. Lazarev and Sindhu reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

US regulators’ use of a speedy clearance pathway for a new frontline indication for asciminib for chronic myeloid leukemia (CML) has raised questions due to the number of medications already available for this condition.

In October, the US Food and Drug Administration (FDA) granted accelerated approval to asciminib (Scemblix, Novartis AG) for adult patients with newly diagnosed Philadelphia chromosome–positive CML in chronic phase.

Asciminib is one of the six tyrosine kinase inhibitor (TKI) drugs used for CML, a class that began with the introduction of imatinib (Gleevec) in 2001. By 2016, researchers reported that TKIs had helped make life expectancy in patients with CML approach that of the general population. Physicians and patients now have several options of second-generation TKI drugs that also can be used in newly diagnosed patients, along with the option to begin with the more affordable option of imatinib.

The FDA in 1992 instituted the accelerated approval pathway to try to speed market drugs for serious conditions that fill unmet medical needs.

The agency and companies essentially make bets on promising study results, often using surrogate markers, to allow sales of medicines while waiting for evidence from confirmatory studies. For example, the FDA in August used the accelerated approval process to clear the first T-cell receptor gene therapy for certain advanced forms of sarcoma, a form of cancer with limited treatment options.

The next accelerated approval of a cancer drug was the indication for asciminib as a frontline therapy. The FDA also used accelerated approval for the initial clearance of asciminib in 2021 for use in CML previously treated with two or more TKIs. By 2022, Novartis presented sufficient evidence of the drug’s merit to win full approval for the drug in this use.

The timeline is longer for the expected confirmatory research for asciminib as a frontline therapy, with a 2028 deadline set for this work. The data presented to date on asciminib have not persuaded some oncologists on the need for the speedy approval of frontline use.

“This boils down to a drug that looks as if it’s just as good as other second-generation TKIs,” Mikkael A. Sekeres, MD, MS, chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami. “I don’t know how they could use the accelerated approval mechanism to get this through.”

Sekeres, a former chair of the Oncologic Drugs Advisory Committee, explored concerns and challenges involved with the use of the accelerated approval process in his 2022 book, Drugs and the FDA: Safety, Efficacy, and the Public’s Trust.

“The intent of the accelerated approval mechanism is that you’re bringing a new therapy to treat a serious disease in a way that others haven’t previously, where there aren’t existing options,” Sekeres said.

This is a markedly different situation that exists for CML, where medicines have improved dramatically in the 21st century, unlike many other forms of cancer treated by hematologists.

“As someone who specializes in treating people with leukemia, I’d be happy every clinic day of my life if all of my patients came in with chronic phase, chronic myeloid leukemia,” instead of other cancers lacking these robust treatment options, he said.

With CML, physicians select among TKIs considering side effects and other health conditions patients have, including weighing the impact of financial toxicity in some cases, he said.

“If I have a patient with lower risk chronic phase, chronic myeloid leukemia, I’m treating them with imatinib,” Sekeres said.

 

Questions About Surrogate Endpoints

Sekeres is not alone in questioning the use of the speedier FDA pathway for a new indication for a TKI in CML.

“Where is the ‘unmet need’ justifying an accelerated approval in this setting?” Timothée Olivier, MD, who is affiliated with both the Hôpitaux universitaires de Genève and the VK Prasad Laboratory funded by Vinay Prasad, MD, MPH, wrote in a November 3 post on X.

Olivier, Prasad, and coauthors in a September correspondence to the American Journal of Hematology raised questions about the study design for a key asciminib study, ASC4FIRST. They noted what they consider a weakness with the endpoints used.

“Molecular milestones like the 48-week MMR [major molecular response] are often used in clinical trials due to their convenience and shorter timeline for assessment,” they wrote. “However, these milestones are not definitive indicators of long-term survival or overall clinical benefit.”

There has been rising concern in recent years about the evidence gap between initial accelerated approvals and the completion of studies that show whether these promising therapies actually help patients live longer or better. Researchers including Bishal Gyawali, MD, PhD, a Medscape Medical News contributor, also have questioned the degree of reliance on surrogate endpoints in accelerated approvals.

In response, the FDA’s Cancer Division and the US Congress have taken steps to try to force drugmakers to more quickly answer the key question in accelerated approvals: Does this medicine produce the expected benefits? For example, the FDA in March appears to have turned down a bid for accelerated approval of a lymphoma drug due to concerns about the timing of completion of confirmatory research.

The use of accelerated approval will continue to be a balancing act, due in part to demand for newer agents, Ravi Bhatia, MD, of the O’Neal Comprehensive Cancer Center at The University of Alabama at Birmingham, told this news organization.

“Accelerated approval of agents for up-front treatment of CML does not appear well justified, given the high degree of efficacy of existing agents,” said Bhatia, vice chair of the National Comprehensive Cancer Network’s Clinical Practice Guidelines in Oncology Panel for Chronic Myeloid Leukemia.

“On the other hand, there is greater urgency for developing agents for patients who have failed existing agents and patients with advanced phase disease, and the use of accelerated approval may be justified in this setting,” Bhatia said.

In an interview with this news organization, Richard A. Larson, MD, a professor in the Department of Hematology/Oncology at The University of Chicago, who is an ASC4FIRST investigator, noted the 96-week follow-up data from the trial will be presented at the annual meeting of the American Society of Hematology in December in San Diego.

Larson said data from this trial will show continued benefit with the frontline use of asciminib. Larson also is an author of a New England Journal of Medicine article in May about the ASC4FIRST trial.

“The data speak for themselves, that asciminib is at least as effective or more so and at least as well tolerated as what’s already on the market,” Larson said. “So their argument, at the end of the day, really boils down to the cost of a new drug and whether we need a new drug.”

From the point of view of patients with cancer, the answer to that is clear, he said.

“If you talk to cancer patients, they’d like to see new drugs become available as quickly as possible. And I think that was the original rationale for the accelerated approval pathway, that a drug that has been shown to be safe and effective in a prospective clinical trial could get accelerated approval based on a surrogate endpoint.”

The remarkable success seen in developing TKI drugs for CML creates difficulties in testing later entrants in this class due to their prolonged survival, Larson said.

“If you look on a population basis, the overall survival of newly diagnosed CML patients with all of these therapeutic options available to them now approximate that of the non-CML population.”

“For most anticancer drugs, the FDA would like to see an overall survival benefit, but patients with newly diagnosed CML are surviving 20 or 30 years, and they’re not dying at an accelerated rate the way they were. So it’d be impractical to require a clinical trial to show a survival benefit, a randomized trial.”

“That’s where the use of a surrogate endpoint, which is the major molecular response at 1 year, has been so valuable, gets the drugs approved, gets them into patients far earlier than if there was a survival end point requirement,” he said.

Larson reported ties with AbbVie, Amgen, Astellas, Celgene, Cellectis, Curis, CVS Caremark, Daiichi Sankyo, ImmunoGen, Jazz, MorphoSys, Rigel, Servier, Forty Seven/Gilead, Novartis, and Rafael Pharmaceuticals. Sekeres disclosed relationships with BMS, Kurome, and Novartis Advisory Boards. Bhatia reported no relevant disclosures.

 

A version of this article appeared on Medscape.com.

US regulators’ use of a speedy clearance pathway for a new frontline indication for asciminib for chronic myeloid leukemia (CML) has raised questions due to the number of medications already available for this condition.

In October, the US Food and Drug Administration (FDA) granted accelerated approval to asciminib (Scemblix, Novartis AG) for adult patients with newly diagnosed Philadelphia chromosome–positive CML in chronic phase.

Asciminib is one of the six tyrosine kinase inhibitor (TKI) drugs used for CML, a class that began with the introduction of imatinib (Gleevec) in 2001. By 2016, researchers reported that TKIs had helped make life expectancy in patients with CML approach that of the general population. Physicians and patients now have several options of second-generation TKI drugs that also can be used in newly diagnosed patients, along with the option to begin with the more affordable option of imatinib.

The FDA in 1992 instituted the accelerated approval pathway to try to speed market drugs for serious conditions that fill unmet medical needs.

The agency and companies essentially make bets on promising study results, often using surrogate markers, to allow sales of medicines while waiting for evidence from confirmatory studies. For example, the FDA in August used the accelerated approval process to clear the first T-cell receptor gene therapy for certain advanced forms of sarcoma, a form of cancer with limited treatment options.

The next accelerated approval of a cancer drug was the indication for asciminib as a frontline therapy. The FDA also used accelerated approval for the initial clearance of asciminib in 2021 for use in CML previously treated with two or more TKIs. By 2022, Novartis presented sufficient evidence of the drug’s merit to win full approval for the drug in this use.

The timeline is longer for the expected confirmatory research for asciminib as a frontline therapy, with a 2028 deadline set for this work. The data presented to date on asciminib have not persuaded some oncologists on the need for the speedy approval of frontline use.

“This boils down to a drug that looks as if it’s just as good as other second-generation TKIs,” Mikkael A. Sekeres, MD, MS, chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami. “I don’t know how they could use the accelerated approval mechanism to get this through.”

Sekeres, a former chair of the Oncologic Drugs Advisory Committee, explored concerns and challenges involved with the use of the accelerated approval process in his 2022 book, Drugs and the FDA: Safety, Efficacy, and the Public’s Trust.

“The intent of the accelerated approval mechanism is that you’re bringing a new therapy to treat a serious disease in a way that others haven’t previously, where there aren’t existing options,” Sekeres said.

This is a markedly different situation that exists for CML, where medicines have improved dramatically in the 21st century, unlike many other forms of cancer treated by hematologists.

“As someone who specializes in treating people with leukemia, I’d be happy every clinic day of my life if all of my patients came in with chronic phase, chronic myeloid leukemia,” instead of other cancers lacking these robust treatment options, he said.

With CML, physicians select among TKIs considering side effects and other health conditions patients have, including weighing the impact of financial toxicity in some cases, he said.

“If I have a patient with lower risk chronic phase, chronic myeloid leukemia, I’m treating them with imatinib,” Sekeres said.

 

Questions About Surrogate Endpoints

Sekeres is not alone in questioning the use of the speedier FDA pathway for a new indication for a TKI in CML.

“Where is the ‘unmet need’ justifying an accelerated approval in this setting?” Timothée Olivier, MD, who is affiliated with both the Hôpitaux universitaires de Genève and the VK Prasad Laboratory funded by Vinay Prasad, MD, MPH, wrote in a November 3 post on X.

Olivier, Prasad, and coauthors in a September correspondence to the American Journal of Hematology raised questions about the study design for a key asciminib study, ASC4FIRST. They noted what they consider a weakness with the endpoints used.

“Molecular milestones like the 48-week MMR [major molecular response] are often used in clinical trials due to their convenience and shorter timeline for assessment,” they wrote. “However, these milestones are not definitive indicators of long-term survival or overall clinical benefit.”

There has been rising concern in recent years about the evidence gap between initial accelerated approvals and the completion of studies that show whether these promising therapies actually help patients live longer or better. Researchers including Bishal Gyawali, MD, PhD, a Medscape Medical News contributor, also have questioned the degree of reliance on surrogate endpoints in accelerated approvals.

In response, the FDA’s Cancer Division and the US Congress have taken steps to try to force drugmakers to more quickly answer the key question in accelerated approvals: Does this medicine produce the expected benefits? For example, the FDA in March appears to have turned down a bid for accelerated approval of a lymphoma drug due to concerns about the timing of completion of confirmatory research.

The use of accelerated approval will continue to be a balancing act, due in part to demand for newer agents, Ravi Bhatia, MD, of the O’Neal Comprehensive Cancer Center at The University of Alabama at Birmingham, told this news organization.

“Accelerated approval of agents for up-front treatment of CML does not appear well justified, given the high degree of efficacy of existing agents,” said Bhatia, vice chair of the National Comprehensive Cancer Network’s Clinical Practice Guidelines in Oncology Panel for Chronic Myeloid Leukemia.

“On the other hand, there is greater urgency for developing agents for patients who have failed existing agents and patients with advanced phase disease, and the use of accelerated approval may be justified in this setting,” Bhatia said.

In an interview with this news organization, Richard A. Larson, MD, a professor in the Department of Hematology/Oncology at The University of Chicago, who is an ASC4FIRST investigator, noted the 96-week follow-up data from the trial will be presented at the annual meeting of the American Society of Hematology in December in San Diego.

Larson said data from this trial will show continued benefit with the frontline use of asciminib. Larson also is an author of a New England Journal of Medicine article in May about the ASC4FIRST trial.

“The data speak for themselves, that asciminib is at least as effective or more so and at least as well tolerated as what’s already on the market,” Larson said. “So their argument, at the end of the day, really boils down to the cost of a new drug and whether we need a new drug.”

From the point of view of patients with cancer, the answer to that is clear, he said.

“If you talk to cancer patients, they’d like to see new drugs become available as quickly as possible. And I think that was the original rationale for the accelerated approval pathway, that a drug that has been shown to be safe and effective in a prospective clinical trial could get accelerated approval based on a surrogate endpoint.”

The remarkable success seen in developing TKI drugs for CML creates difficulties in testing later entrants in this class due to their prolonged survival, Larson said.

“If you look on a population basis, the overall survival of newly diagnosed CML patients with all of these therapeutic options available to them now approximate that of the non-CML population.”

“For most anticancer drugs, the FDA would like to see an overall survival benefit, but patients with newly diagnosed CML are surviving 20 or 30 years, and they’re not dying at an accelerated rate the way they were. So it’d be impractical to require a clinical trial to show a survival benefit, a randomized trial.”

“That’s where the use of a surrogate endpoint, which is the major molecular response at 1 year, has been so valuable, gets the drugs approved, gets them into patients far earlier than if there was a survival end point requirement,” he said.

Larson reported ties with AbbVie, Amgen, Astellas, Celgene, Cellectis, Curis, CVS Caremark, Daiichi Sankyo, ImmunoGen, Jazz, MorphoSys, Rigel, Servier, Forty Seven/Gilead, Novartis, and Rafael Pharmaceuticals. Sekeres disclosed relationships with BMS, Kurome, and Novartis Advisory Boards. Bhatia reported no relevant disclosures.

 

A version of this article appeared on Medscape.com.

US regulators’ use of a speedy clearance pathway for a new frontline indication for asciminib for chronic myeloid leukemia (CML) has raised questions due to the number of medications already available for this condition.

In October, the US Food and Drug Administration (FDA) granted accelerated approval to asciminib (Scemblix, Novartis AG) for adult patients with newly diagnosed Philadelphia chromosome–positive CML in chronic phase.

Asciminib is one of the six tyrosine kinase inhibitor (TKI) drugs used for CML, a class that began with the introduction of imatinib (Gleevec) in 2001. By 2016, researchers reported that TKIs had helped make life expectancy in patients with CML approach that of the general population. Physicians and patients now have several options of second-generation TKI drugs that also can be used in newly diagnosed patients, along with the option to begin with the more affordable option of imatinib.

The FDA in 1992 instituted the accelerated approval pathway to try to speed market drugs for serious conditions that fill unmet medical needs.

The agency and companies essentially make bets on promising study results, often using surrogate markers, to allow sales of medicines while waiting for evidence from confirmatory studies. For example, the FDA in August used the accelerated approval process to clear the first T-cell receptor gene therapy for certain advanced forms of sarcoma, a form of cancer with limited treatment options.

The next accelerated approval of a cancer drug was the indication for asciminib as a frontline therapy. The FDA also used accelerated approval for the initial clearance of asciminib in 2021 for use in CML previously treated with two or more TKIs. By 2022, Novartis presented sufficient evidence of the drug’s merit to win full approval for the drug in this use.

The timeline is longer for the expected confirmatory research for asciminib as a frontline therapy, with a 2028 deadline set for this work. The data presented to date on asciminib have not persuaded some oncologists on the need for the speedy approval of frontline use.

“This boils down to a drug that looks as if it’s just as good as other second-generation TKIs,” Mikkael A. Sekeres, MD, MS, chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami. “I don’t know how they could use the accelerated approval mechanism to get this through.”

Sekeres, a former chair of the Oncologic Drugs Advisory Committee, explored concerns and challenges involved with the use of the accelerated approval process in his 2022 book, Drugs and the FDA: Safety, Efficacy, and the Public’s Trust.

“The intent of the accelerated approval mechanism is that you’re bringing a new therapy to treat a serious disease in a way that others haven’t previously, where there aren’t existing options,” Sekeres said.

This is a markedly different situation that exists for CML, where medicines have improved dramatically in the 21st century, unlike many other forms of cancer treated by hematologists.

“As someone who specializes in treating people with leukemia, I’d be happy every clinic day of my life if all of my patients came in with chronic phase, chronic myeloid leukemia,” instead of other cancers lacking these robust treatment options, he said.

With CML, physicians select among TKIs considering side effects and other health conditions patients have, including weighing the impact of financial toxicity in some cases, he said.

“If I have a patient with lower risk chronic phase, chronic myeloid leukemia, I’m treating them with imatinib,” Sekeres said.

 

Questions About Surrogate Endpoints

Sekeres is not alone in questioning the use of the speedier FDA pathway for a new indication for a TKI in CML.

“Where is the ‘unmet need’ justifying an accelerated approval in this setting?” Timothée Olivier, MD, who is affiliated with both the Hôpitaux universitaires de Genève and the VK Prasad Laboratory funded by Vinay Prasad, MD, MPH, wrote in a November 3 post on X.

Olivier, Prasad, and coauthors in a September correspondence to the American Journal of Hematology raised questions about the study design for a key asciminib study, ASC4FIRST. They noted what they consider a weakness with the endpoints used.

“Molecular milestones like the 48-week MMR [major molecular response] are often used in clinical trials due to their convenience and shorter timeline for assessment,” they wrote. “However, these milestones are not definitive indicators of long-term survival or overall clinical benefit.”

There has been rising concern in recent years about the evidence gap between initial accelerated approvals and the completion of studies that show whether these promising therapies actually help patients live longer or better. Researchers including Bishal Gyawali, MD, PhD, a Medscape Medical News contributor, also have questioned the degree of reliance on surrogate endpoints in accelerated approvals.

In response, the FDA’s Cancer Division and the US Congress have taken steps to try to force drugmakers to more quickly answer the key question in accelerated approvals: Does this medicine produce the expected benefits? For example, the FDA in March appears to have turned down a bid for accelerated approval of a lymphoma drug due to concerns about the timing of completion of confirmatory research.

The use of accelerated approval will continue to be a balancing act, due in part to demand for newer agents, Ravi Bhatia, MD, of the O’Neal Comprehensive Cancer Center at The University of Alabama at Birmingham, told this news organization.

“Accelerated approval of agents for up-front treatment of CML does not appear well justified, given the high degree of efficacy of existing agents,” said Bhatia, vice chair of the National Comprehensive Cancer Network’s Clinical Practice Guidelines in Oncology Panel for Chronic Myeloid Leukemia.

“On the other hand, there is greater urgency for developing agents for patients who have failed existing agents and patients with advanced phase disease, and the use of accelerated approval may be justified in this setting,” Bhatia said.

In an interview with this news organization, Richard A. Larson, MD, a professor in the Department of Hematology/Oncology at The University of Chicago, who is an ASC4FIRST investigator, noted the 96-week follow-up data from the trial will be presented at the annual meeting of the American Society of Hematology in December in San Diego.

Larson said data from this trial will show continued benefit with the frontline use of asciminib. Larson also is an author of a New England Journal of Medicine article in May about the ASC4FIRST trial.

“The data speak for themselves, that asciminib is at least as effective or more so and at least as well tolerated as what’s already on the market,” Larson said. “So their argument, at the end of the day, really boils down to the cost of a new drug and whether we need a new drug.”

From the point of view of patients with cancer, the answer to that is clear, he said.

“If you talk to cancer patients, they’d like to see new drugs become available as quickly as possible. And I think that was the original rationale for the accelerated approval pathway, that a drug that has been shown to be safe and effective in a prospective clinical trial could get accelerated approval based on a surrogate endpoint.”

The remarkable success seen in developing TKI drugs for CML creates difficulties in testing later entrants in this class due to their prolonged survival, Larson said.

“If you look on a population basis, the overall survival of newly diagnosed CML patients with all of these therapeutic options available to them now approximate that of the non-CML population.”

“For most anticancer drugs, the FDA would like to see an overall survival benefit, but patients with newly diagnosed CML are surviving 20 or 30 years, and they’re not dying at an accelerated rate the way they were. So it’d be impractical to require a clinical trial to show a survival benefit, a randomized trial.”

“That’s where the use of a surrogate endpoint, which is the major molecular response at 1 year, has been so valuable, gets the drugs approved, gets them into patients far earlier than if there was a survival end point requirement,” he said.

Larson reported ties with AbbVie, Amgen, Astellas, Celgene, Cellectis, Curis, CVS Caremark, Daiichi Sankyo, ImmunoGen, Jazz, MorphoSys, Rigel, Servier, Forty Seven/Gilead, Novartis, and Rafael Pharmaceuticals. Sekeres disclosed relationships with BMS, Kurome, and Novartis Advisory Boards. Bhatia reported no relevant disclosures.

 

A version of this article appeared on Medscape.com.

Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.

“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”

That was 21 years ago. Today, her current cancer status is “no evidence of disease.”

Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.

In that time, Gerber has had one constant: Her oncologist, Kandhasamy Jagathambal, MD, or Dr. Jaga, as she’s often called. 

“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.

Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.

The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.

Gerber isn’t alone in calling out the depth of the oncologist-patient bond.

Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.

“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.

 

Connecting Through Stress

Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.

Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.

The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.

“I consider my patient’s battles to be my battles,” Khan wrote.

The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.

According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.

The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.

With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”

What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.

“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.

In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.

“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”

 

A ‘Special Relationship’

Ralph V. Boccia, MD, is often asked what he does.

The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.

“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”

Boccia thinks about one long-term patient who captures this bond.

Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.

Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.

Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.

“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”

Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.

Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.

Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.

More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.

“He has kept me alive,” said Pinson.

 

The Dying Patient

Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.

After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.

Several months later, Vyas was called for an inpatient consult. It was the same woman.

Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.

The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.

“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”

From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.

For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.

“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.

Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.

Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.

“Doc, I don’t want to die and my kids find me dead. What can we do about it?”

Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.

When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”

But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”

Khan had no relevant disclosures. Boccia and Vyas had no disclosures.

A version of this article appeared on Medscape.com.

Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.

“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”

That was 21 years ago. Today, her current cancer status is “no evidence of disease.”

Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.

In that time, Gerber has had one constant: Her oncologist, Kandhasamy Jagathambal, MD, or Dr. Jaga, as she’s often called. 

“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.

Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.

The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.

Gerber isn’t alone in calling out the depth of the oncologist-patient bond.

Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.

“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.

 

Connecting Through Stress

Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.

Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.

The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.

“I consider my patient’s battles to be my battles,” Khan wrote.

The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.

According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.

The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.

With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”

What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.

“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.

In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.

“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”

 

A ‘Special Relationship’

Ralph V. Boccia, MD, is often asked what he does.

The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.

“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”

Boccia thinks about one long-term patient who captures this bond.

Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.

Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.

Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.

“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”

Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.

Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.

Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.

More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.

“He has kept me alive,” said Pinson.

 

The Dying Patient

Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.

After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.

Several months later, Vyas was called for an inpatient consult. It was the same woman.

Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.

The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.

“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”

From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.

For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.

“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.

Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.

Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.

“Doc, I don’t want to die and my kids find me dead. What can we do about it?”

Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.

When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”

But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”

Khan had no relevant disclosures. Boccia and Vyas had no disclosures.

A version of this article appeared on Medscape.com.

Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.

“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”

That was 21 years ago. Today, her current cancer status is “no evidence of disease.”

Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.

In that time, Gerber has had one constant: Her oncologist, Kandhasamy Jagathambal, MD, or Dr. Jaga, as she’s often called. 

“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.

Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.

The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.

Gerber isn’t alone in calling out the depth of the oncologist-patient bond.

Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.

“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.

 

Connecting Through Stress

Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.

Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.

The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.

“I consider my patient’s battles to be my battles,” Khan wrote.

The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.

According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.

The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.

With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”

What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.

“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.

In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.

“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”

 

A ‘Special Relationship’

Ralph V. Boccia, MD, is often asked what he does.

The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.

“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”

Boccia thinks about one long-term patient who captures this bond.

Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.

Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.

Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.

“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”

Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.

Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.

Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.

More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.

“He has kept me alive,” said Pinson.

 

The Dying Patient

Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.

After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.

Several months later, Vyas was called for an inpatient consult. It was the same woman.

Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.

The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.

“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”

From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.

For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.

“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.

Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.

Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.

“Doc, I don’t want to die and my kids find me dead. What can we do about it?”

Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.

When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”

But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”

Khan had no relevant disclosures. Boccia and Vyas had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Lichen planus (LP) affects an estimated 0.15% of US adults, and more than half of patients do not receive treatment within a year of diagnosis by a dermatologist.

METHODOLOGY:

• To evaluate the prevalence of LP, researchers analyzed 566,851 eligible patients from the Explorys database, comprising electronic medical records from over 40 healthcare networks and 53 million patients across the United States.
• They also assessed treatment plans separately among 1998 newly diagnosed patients with LP between October 2015 and January 2020, who required at least one dermatology encounter within the first year following diagnosis.
• The primary outcome was overall prevalence of LP in the United States, including prevalence across specific age, sex, and racial subgroups. Additionally, dermatologist-prescribed treatments for non-oral LP were also reported.

TAKEAWAY:

• Overall, there were 1098 cases of LP (median age, 66 years; 74% women); the crude prevalence of LP was 0.19% and the age- and sex-standardized overall prevalence was 0.15%. Prevalence in women was 1.77 times higher than in men.
• Asian patients showed the highest standardized prevalence (0.2%), followed by Black patients (0.16). Prevalence increased with age, ranging from 0.04% among those aged 18-29 years to 0.26% among those aged 60-69 years and 0.33% among those aged 70-79 years.

IN PRACTICE:

“LP is a fairly common disease, which disproportionately affects women and individuals older than 60 years of age,” the authors wrote. “Future research to help identify patients who may need systemic treatment and determine appropriate treatments for patients with LP to limit sequelae is important as no medication is currently FDA approved for LP.”

SOURCE:

The study was led by Natalia Pelet Del Toro, MD, Department of Dermatology, Northwell Health, New Hyde Park, New York, and was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The absence of a precise diagnosis code for non-oral LP introduces potential misclassification risks. Additionally, the study design did not allow for the establishment of disease severity levels, limiting the ability to correlate treatment choices with disease severity.

DISCLOSURES:

The study did not receive any funding. Two authors reported to have received advisory fees, grants, and/or honoraria from several pharmaceutical companies. Pelet Del Toro and another author did not declare any conflict of interests.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Lichen planus (LP) affects an estimated 0.15% of US adults, and more than half of patients do not receive treatment within a year of diagnosis by a dermatologist.

METHODOLOGY:

• To evaluate the prevalence of LP, researchers analyzed 566,851 eligible patients from the Explorys database, comprising electronic medical records from over 40 healthcare networks and 53 million patients across the United States.
• They also assessed treatment plans separately among 1998 newly diagnosed patients with LP between October 2015 and January 2020, who required at least one dermatology encounter within the first year following diagnosis.
• The primary outcome was overall prevalence of LP in the United States, including prevalence across specific age, sex, and racial subgroups. Additionally, dermatologist-prescribed treatments for non-oral LP were also reported.

TAKEAWAY:

• Overall, there were 1098 cases of LP (median age, 66 years; 74% women); the crude prevalence of LP was 0.19% and the age- and sex-standardized overall prevalence was 0.15%. Prevalence in women was 1.77 times higher than in men.
• Asian patients showed the highest standardized prevalence (0.2%), followed by Black patients (0.16). Prevalence increased with age, ranging from 0.04% among those aged 18-29 years to 0.26% among those aged 60-69 years and 0.33% among those aged 70-79 years.

IN PRACTICE:

“LP is a fairly common disease, which disproportionately affects women and individuals older than 60 years of age,” the authors wrote. “Future research to help identify patients who may need systemic treatment and determine appropriate treatments for patients with LP to limit sequelae is important as no medication is currently FDA approved for LP.”

SOURCE:

The study was led by Natalia Pelet Del Toro, MD, Department of Dermatology, Northwell Health, New Hyde Park, New York, and was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The absence of a precise diagnosis code for non-oral LP introduces potential misclassification risks. Additionally, the study design did not allow for the establishment of disease severity levels, limiting the ability to correlate treatment choices with disease severity.

DISCLOSURES:

The study did not receive any funding. Two authors reported to have received advisory fees, grants, and/or honoraria from several pharmaceutical companies. Pelet Del Toro and another author did not declare any conflict of interests.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Lichen planus (LP) affects an estimated 0.15% of US adults, and more than half of patients do not receive treatment within a year of diagnosis by a dermatologist.

METHODOLOGY:

• To evaluate the prevalence of LP, researchers analyzed 566,851 eligible patients from the Explorys database, comprising electronic medical records from over 40 healthcare networks and 53 million patients across the United States.
• They also assessed treatment plans separately among 1998 newly diagnosed patients with LP between October 2015 and January 2020, who required at least one dermatology encounter within the first year following diagnosis.
• The primary outcome was overall prevalence of LP in the United States, including prevalence across specific age, sex, and racial subgroups. Additionally, dermatologist-prescribed treatments for non-oral LP were also reported.

TAKEAWAY:

• Overall, there were 1098 cases of LP (median age, 66 years; 74% women); the crude prevalence of LP was 0.19% and the age- and sex-standardized overall prevalence was 0.15%. Prevalence in women was 1.77 times higher than in men.
• Asian patients showed the highest standardized prevalence (0.2%), followed by Black patients (0.16). Prevalence increased with age, ranging from 0.04% among those aged 18-29 years to 0.26% among those aged 60-69 years and 0.33% among those aged 70-79 years.

IN PRACTICE:

“LP is a fairly common disease, which disproportionately affects women and individuals older than 60 years of age,” the authors wrote. “Future research to help identify patients who may need systemic treatment and determine appropriate treatments for patients with LP to limit sequelae is important as no medication is currently FDA approved for LP.”

SOURCE:

The study was led by Natalia Pelet Del Toro, MD, Department of Dermatology, Northwell Health, New Hyde Park, New York, and was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The absence of a precise diagnosis code for non-oral LP introduces potential misclassification risks. Additionally, the study design did not allow for the establishment of disease severity levels, limiting the ability to correlate treatment choices with disease severity.

DISCLOSURES:

The study did not receive any funding. Two authors reported to have received advisory fees, grants, and/or honoraria from several pharmaceutical companies. Pelet Del Toro and another author did not declare any conflict of interests.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

At 1 year, 82% of patients with breast cancer who received a 1-week ultrahypofractionated breast radiotherapy regimen reported no or mild toxicities. Most patients also reported that the reduced treatment time was a major benefit of the 1-week radiotherapy schedule.

METHODOLOGY:

• In March 2020, during the COVID-19 pandemic, international and national guidelines recommended adopting a 1-week ultrahypofractionated radiotherapy schedule for patients with node-negative breast cancer. Subsequently, a phase 3 trial demonstrated that a 1-week regimen of 26 Gy in five fractions led to similar breast cancer outcomes compared with a standard moderately hypofractionated regimen.
• In this study, researchers wanted to assess real world toxicities following ultrahypofractionated radiotherapy and enrolled 135 consecutive patients who received 1-week ultrahypofractionated adjuvant radiation of 26 Gy in five fractions from March to August 2020 at three centers in Ireland, with 33 patients (25%) receiving a sequential boost.
• Researchers recorded patient-reported outcomes on breast pain, swelling, firmness, and hypersensitivity at baseline, 3, 6, and 12 months. Virtual consultations without video occurred at baseline, 3 months, 6 months, and video consultations were offered at 1 year for a physician-led breast evaluation.
• Researchers assessed patient perspectives on this new schedule and telehealth workflows using questionnaires.
• Overall, 90% of patients completed the 1-year assessment plus another assessment. The primary endpoint was the worst toxicity reported at each time point.

TAKEAWAY:

• Overall, 76% of patients reported no or mild toxicities at 3 and 6 months, and 82% reported no or mild toxicities 12 months.
• At 1 year, 20 patients (17%) reported moderate toxicity, most commonly breast pain, and only two patients (2%) reported marked toxicities, including breast firmness and skin changes.
• Researchers found no difference in toxicities between patients who received only 26 Gy in five fractions and those who received an additional sequential boost.
• Most patients reported reduced treatment time (78.6%) and infection control (59%) as major benefits of the 1-week radiotherapy regimen. Patients also reported high satisfaction with the use of telehealth, with 97.3% feeling well-informed about their diagnosis, 88% feeling well-informed about treatment side effects, and 94% feeling supported by the medical team. However, only 27% agreed to video consultations for breast inspections at 1 year.

IN PRACTICE:

“Ultrahypofractionated whole breast radiotherapy leads to acceptable late toxicity rates at 1 year even when followed by a hypofractionated tumour bed boost,” the authors wrote. “Patient satisfaction with ultrahypofractionated treatment and virtual consultations without video was high.”

SOURCE:

The study, led by Jill Nicholson, MBBS, MRCP, FFFRRCSI, St Luke’s Radiation Oncology Network, St. Luke’s Hospital, Dublin, Ireland, was published online in Advances in Radiation Oncology.

LIMITATIONS:

The short follow-up period might not capture all late toxicities. Variability in patient-reported outcomes could affect consistency. The range in boost received (four to eight fractions) could have influenced patients’ experiences.

DISCLOSURES:

Nicholson received funding from the St. Luke’s Institute of Cancer Research, Dublin, Ireland. No other relevant conflicts of interest were disclosed by the authors.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

At 1 year, 82% of patients with breast cancer who received a 1-week ultrahypofractionated breast radiotherapy regimen reported no or mild toxicities. Most patients also reported that the reduced treatment time was a major benefit of the 1-week radiotherapy schedule.

METHODOLOGY:

• In March 2020, during the COVID-19 pandemic, international and national guidelines recommended adopting a 1-week ultrahypofractionated radiotherapy schedule for patients with node-negative breast cancer. Subsequently, a phase 3 trial demonstrated that a 1-week regimen of 26 Gy in five fractions led to similar breast cancer outcomes compared with a standard moderately hypofractionated regimen.
• In this study, researchers wanted to assess real world toxicities following ultrahypofractionated radiotherapy and enrolled 135 consecutive patients who received 1-week ultrahypofractionated adjuvant radiation of 26 Gy in five fractions from March to August 2020 at three centers in Ireland, with 33 patients (25%) receiving a sequential boost.
• Researchers recorded patient-reported outcomes on breast pain, swelling, firmness, and hypersensitivity at baseline, 3, 6, and 12 months. Virtual consultations without video occurred at baseline, 3 months, 6 months, and video consultations were offered at 1 year for a physician-led breast evaluation.
• Researchers assessed patient perspectives on this new schedule and telehealth workflows using questionnaires.
• Overall, 90% of patients completed the 1-year assessment plus another assessment. The primary endpoint was the worst toxicity reported at each time point.

TAKEAWAY:

• Overall, 76% of patients reported no or mild toxicities at 3 and 6 months, and 82% reported no or mild toxicities 12 months.
• At 1 year, 20 patients (17%) reported moderate toxicity, most commonly breast pain, and only two patients (2%) reported marked toxicities, including breast firmness and skin changes.
• Researchers found no difference in toxicities between patients who received only 26 Gy in five fractions and those who received an additional sequential boost.
• Most patients reported reduced treatment time (78.6%) and infection control (59%) as major benefits of the 1-week radiotherapy regimen. Patients also reported high satisfaction with the use of telehealth, with 97.3% feeling well-informed about their diagnosis, 88% feeling well-informed about treatment side effects, and 94% feeling supported by the medical team. However, only 27% agreed to video consultations for breast inspections at 1 year.

IN PRACTICE:

“Ultrahypofractionated whole breast radiotherapy leads to acceptable late toxicity rates at 1 year even when followed by a hypofractionated tumour bed boost,” the authors wrote. “Patient satisfaction with ultrahypofractionated treatment and virtual consultations without video was high.”

SOURCE:

The study, led by Jill Nicholson, MBBS, MRCP, FFFRRCSI, St Luke’s Radiation Oncology Network, St. Luke’s Hospital, Dublin, Ireland, was published online in Advances in Radiation Oncology.

LIMITATIONS:

The short follow-up period might not capture all late toxicities. Variability in patient-reported outcomes could affect consistency. The range in boost received (four to eight fractions) could have influenced patients’ experiences.

DISCLOSURES:

Nicholson received funding from the St. Luke’s Institute of Cancer Research, Dublin, Ireland. No other relevant conflicts of interest were disclosed by the authors.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

At 1 year, 82% of patients with breast cancer who received a 1-week ultrahypofractionated breast radiotherapy regimen reported no or mild toxicities. Most patients also reported that the reduced treatment time was a major benefit of the 1-week radiotherapy schedule.

METHODOLOGY:

• In March 2020, during the COVID-19 pandemic, international and national guidelines recommended adopting a 1-week ultrahypofractionated radiotherapy schedule for patients with node-negative breast cancer. Subsequently, a phase 3 trial demonstrated that a 1-week regimen of 26 Gy in five fractions led to similar breast cancer outcomes compared with a standard moderately hypofractionated regimen.
• In this study, researchers wanted to assess real world toxicities following ultrahypofractionated radiotherapy and enrolled 135 consecutive patients who received 1-week ultrahypofractionated adjuvant radiation of 26 Gy in five fractions from March to August 2020 at three centers in Ireland, with 33 patients (25%) receiving a sequential boost.
• Researchers recorded patient-reported outcomes on breast pain, swelling, firmness, and hypersensitivity at baseline, 3, 6, and 12 months. Virtual consultations without video occurred at baseline, 3 months, 6 months, and video consultations were offered at 1 year for a physician-led breast evaluation.
• Researchers assessed patient perspectives on this new schedule and telehealth workflows using questionnaires.
• Overall, 90% of patients completed the 1-year assessment plus another assessment. The primary endpoint was the worst toxicity reported at each time point.

TAKEAWAY:

• Overall, 76% of patients reported no or mild toxicities at 3 and 6 months, and 82% reported no or mild toxicities 12 months.
• At 1 year, 20 patients (17%) reported moderate toxicity, most commonly breast pain, and only two patients (2%) reported marked toxicities, including breast firmness and skin changes.
• Researchers found no difference in toxicities between patients who received only 26 Gy in five fractions and those who received an additional sequential boost.
• Most patients reported reduced treatment time (78.6%) and infection control (59%) as major benefits of the 1-week radiotherapy regimen. Patients also reported high satisfaction with the use of telehealth, with 97.3% feeling well-informed about their diagnosis, 88% feeling well-informed about treatment side effects, and 94% feeling supported by the medical team. However, only 27% agreed to video consultations for breast inspections at 1 year.

IN PRACTICE:

“Ultrahypofractionated whole breast radiotherapy leads to acceptable late toxicity rates at 1 year even when followed by a hypofractionated tumour bed boost,” the authors wrote. “Patient satisfaction with ultrahypofractionated treatment and virtual consultations without video was high.”

SOURCE:

The study, led by Jill Nicholson, MBBS, MRCP, FFFRRCSI, St Luke’s Radiation Oncology Network, St. Luke’s Hospital, Dublin, Ireland, was published online in Advances in Radiation Oncology.

LIMITATIONS:

The short follow-up period might not capture all late toxicities. Variability in patient-reported outcomes could affect consistency. The range in boost received (four to eight fractions) could have influenced patients’ experiences.

DISCLOSURES:

Nicholson received funding from the St. Luke’s Institute of Cancer Research, Dublin, Ireland. No other relevant conflicts of interest were disclosed by the authors.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

WASHINGTON — A new guideline for management of lupus nephritis (LN) was unveiled at the annual meeting of the American College of Rheumatology (ACR), updating the 2012 LN guideline to recommend a more aggressive first-line approach to treating the disease.

“The biggest differences are that we are recommending what we’re calling triple therapy, where we incorporate the glucocorticoid therapy with baseline conventional immunosuppressants, usually mycophenolate with cyclophosphamide, and the addition of one of the newer agents more recently approved by the FDA [Food and Drug Administration] — belimumab, voclosporin, or another CNI [calcineurin inhibitor],” said Lisa Sammaritano, MD, director of the Rheumatology Reproductive Health Program of the Barbara Volcker Center for Women and Rheumatic Diseases at the Hospital for Special Surgery and professor of clinical medicine at Weill Cornell Medical College, both in New York City.

“This is a bit of a change from not only our previous guideline but some of the other guidelines out there, and it is based on the fact that we have very convincing evidence that starting with triple therapy yields to better long-term outcomes for our patients than starting with only two agents and waiting to see if they respond before escalating therapy,” she said. Other key updates include recommending use of pulse glucocorticoid therapy with a lower dose and more rapid steroid taper and treating patients with the recommended therapy for 3-5 years.

The guiding principles of the guideline are not only to preserve kidney function and minimize morbidity and mortality but also to ensure collaborative care with nephrology, to utilize shared decision-making that includes patients’ values and preferences, to reduce healthcare disparities, and to consider pediatric and geriatric populations. The guidelines are based on a quantitative synthesis of 105 studies that yielded 7 strong recommendations, 21 conditional recommendations, and 13 good practice statements — those commonly accepted as beneficial or practical advice even if there is little direct evidence to support them. The voting panel of 19 members included not only 3 nephrologists and 2 pediatric rheumatologists but also 2 patient representatives with LN.

The recommendations are just that, “a recommendation, not an order,” Sammaritano said, and strong recommendations are those “where we think, unequivocally, almost everybody should follow that recommendation. When we feel that we cannot make a strong recommendation, then we call our recommendation conditional, and it is conditional on looking at different things,” she said.

“Patients are different, especially lupus patients, and so one lupus nephritis patient may have different clinical characteristics, different thoughts about what therapy will work for them in their lives, or what therapy they really do not want to pursue,” Sammaritano said. “Maybe they can’t conceive of coming to the hospital once a month for intravenous therapy. Maybe they’re concerned about pill burden, which is something that our patient panel really emphasized to us. So, conditional recommendation means this voting panel thought that this was the best overall for most patients and most circumstances, recognizing there will still be a significant number of people, clinicians and patients, who may feel differently for that particular situation. So, that’s where you know the patient-clinician discussion can help with decision-making.”

 

What Are the Recommendations?

All patients with systemic lupus erythematosus (SLE) are strongly recommended to undergo proteinuria screening every 6-12 months or at the time of a flare. Those suspected of having LN should receive a prompt kidney biopsy and treatment with glucocorticoids while awaiting the biopsy and results. Two conditional recommendations for kidney biopsy include patients with SLE with unexplained impaired kidney function or a protein to creatinine ratio > 0.5 g/g, and patients with LN with a suspected flare after initial response or a lack of response or worsening after 6 months of therapy.

The guidelines include a strong recommendation for all patients with SLE to receive hydroxychloroquine and a conditional recommendation for all patients with elevated proteinuria (> 0.5 g/g) to receive renin-angiotensin-aldosterone system inhibitors (RAAS-I). Dosages in patients with LN with decreased glomerular filtration rate (GFR) should be adjusted as needed.

Sammaritano then reviewed the specifics on medication treatment. The glucocorticoid therapy in all patients with LN should begin with Pulse IV Therapy at 250-1000 mg/d for 1-3 days, followed by oral prednisone ≤ 0.5 mg/kg per day up to 40 mg/d, then tapered to a target dose > 5 mg/d within 6 months. The justification for this course comes from a 2024 systematic review finding pulse followed by oral glucocorticoids maximized complete renal response while minimizing toxicities, Sammaritano said.

“We have all become acutely aware of the very high risk of prolonged high dose of glucocorticoids for our patients,” she said, “and importantly, our patient panel participants strongly emphasized their preference for minimizing glucocorticoids dose.”

In addition to the recommendation of all patients receiving hydroxychloroquine and RAAS-I, first-line treatment of active, new-onset, or flaring LN should begin with triple therapy — glucocorticoids with two additional immunosuppressive agents. For patients with class III/IV LN, triple therapy includes the glucocorticoids course with a mycophenolic acid analog (MPAA) and either belimumab or a CNI. Conditional recommendations support MPAA with belimumab for significant extrarenal manifestations and MPAA with CNI for proteinuria ≥ 3 g/g.

An alternative triple therapy for class III/IV is glucocorticoids with low-dose cyclophosphamide and belimumab, but MPAA at 2-3 g/d is preferred over cyclophosphamide. The preferred regimen for cyclophosphamide is derived from the Euro-Lupus Nephritis Trial: Intravenous 500 mg every 2 weeks for six doses and then MPAA. Sammaritano noted that there are some limited data on using cyclophosphamide with belimumab, but “we do not specifically recommend cyclophosphamide with a CNI as one of our options because this combination has not been studied in randomized controlled trials.”

There are less data supporting class V recommendations, Sammaritano said, but for those with proteinuria of at least 1 g/g, the panel still recommends triple therapy with glucocorticoids, a MPAA, and a CNI. A CNI is preferred over belimumab because of its stabilizing effects on the podocyte cytoskeleton. Two alternative triple therapies for class V–only patients are glucocorticoids with belimumab and either low-dose cyclophosphamide or MPAA.

Dual therapy is only recommended if triple therapy is not available or not tolerated. The voting panel chose to recommend triple therapy over dual therapy with escalation for two reasons. First, the BLISS-LN and AURORA 1 trials showed improved outcomes with initial triple therapy over initial dual therapies.

Second, “nephron loss proceeds throughout a person’s lifetime even for those who do not have lupus nephritis, and every case of lupus nephritis or every period of time with uncontrolled lupus nephritis changes the course of that decline for the worse,” Sammaritano said. “So, we feel we can’t wait for nephron loss to implement what has been shown to be the most efficacious therapy. We want to gain rapid control of inflammation using the most effective regimen to prevent further damage and flare and maintain survival.”

Therapy is conditionally recommended for at least 3-5 years because “not only do we want to gain rapid control of disease activity [but we also] want to maintain control of disease activity until there’s sustained inactive disease,” Sammaritano said. “Repeat kidney biopsies show that immunologic activity persists in the kidneys for several years, and the withdrawal of immunosuppression when there is histologic activity predisposes patients to flare.” But immunosuppressive therapy can be tapered over time as determined by renal disease activity and medication tolerability.

For patients with refractory disease, consider additional factors that could be affecting the disease, such as adherence, the presence of other diagnoses, or advanced chronicity.

“If true refractory nephritis is present,” she said, “we recommend escalation to a more intensive regimen,” including the addition of anti-CD20 agents, combination therapy with three immunosuppressives, or referral for investigational therapy.

“We also emphasize the importance of other adjunctive therapies preventing comorbidities, such as cardiovascular disease, changes in bone health, or infection risk,” she said. In older patients, avoid polypharmacy as much as possible and be mindful of age-related GFR, she added.

A strong recommendation supported monitoring patients with LN and proteinuria at least every 3 months if they have not achieved complete renal response and every 3-6 months after sustained complete renal response.

Last, in patients with LN and end-stage kidney disease (ESKD), the voting panel strongly recommends transplant over dialysis and conditionally recommends proceeding to the transplant without requiring a complete clinical or serologic remission as long as no other organs are involved. In patients with LN at risk for ESKD, the guideline conditionally recommends consideration of a preemptive transplant, and patients on dialysis or post transplant are strongly recommended to regularly follow up with rheumatology.

Gabriel Kirsch, MD, a resident rheumatologist at the University of Florida College of Medicine, Jacksonville, said he found the guidelines helpful, “especially the guidance on the dichotomy between using belimumab and voclosporin and the clinical and patient preference that help you make that decision.”

Kirsch had hoped, however, to hear more about the impact of therapeutic drug monitoring of hydroxychloroquine on LN outcomes. He also noted a clinical scenario he’s come across that wasn’t addressed.

“When you’re checking GFR on these folks, a lot of our eGFR calculators are creatinine based, and creatinine at the extremes of muscle mass can be inaccurate,” such as getting artificially low creatinine readings from pediatric patients because of their low muscle mass or from patients with muscle atrophy caused by a lot of glucocorticoid exposure. “I was hoping for some more guidance on that,” he said.

Ellen Ginzler, MD, MPH, chief of rheumatology at SUNY Health Science Center in Brooklyn, New York, said the guidelines were pretty much what she expected them to be. She agreed with the panel’s advice that, when deciding between belimumab or voclosporin, “if it’s pure proteinuria, then you add voclosporin. If the patient has extra renal manifestations, you go with belimumab first.” 

“They really made it quite clear that, despite the fact that people really want to reduce the amount of immunosuppression — and I agree you should taper steroids quickly — you really need to keep the immunosuppression for a prolonged period of time because all of the studies that have been done for years show that the longer you’re on immunosuppression after you achieve remission or a low disease activity state, the better your chance of not flaring,” Ginzler said. “Rapid tapering or discontinuation really increases the risk of flare.”

Sammaritano, Kirsch, and Ginzler had no disclosures. No external funding was used.

A version of this article appeared on Medscape.com.

WASHINGTON — A new guideline for management of lupus nephritis (LN) was unveiled at the annual meeting of the American College of Rheumatology (ACR), updating the 2012 LN guideline to recommend a more aggressive first-line approach to treating the disease.

“The biggest differences are that we are recommending what we’re calling triple therapy, where we incorporate the glucocorticoid therapy with baseline conventional immunosuppressants, usually mycophenolate with cyclophosphamide, and the addition of one of the newer agents more recently approved by the FDA [Food and Drug Administration] — belimumab, voclosporin, or another CNI [calcineurin inhibitor],” said Lisa Sammaritano, MD, director of the Rheumatology Reproductive Health Program of the Barbara Volcker Center for Women and Rheumatic Diseases at the Hospital for Special Surgery and professor of clinical medicine at Weill Cornell Medical College, both in New York City.

“This is a bit of a change from not only our previous guideline but some of the other guidelines out there, and it is based on the fact that we have very convincing evidence that starting with triple therapy yields to better long-term outcomes for our patients than starting with only two agents and waiting to see if they respond before escalating therapy,” she said. Other key updates include recommending use of pulse glucocorticoid therapy with a lower dose and more rapid steroid taper and treating patients with the recommended therapy for 3-5 years.

The guiding principles of the guideline are not only to preserve kidney function and minimize morbidity and mortality but also to ensure collaborative care with nephrology, to utilize shared decision-making that includes patients’ values and preferences, to reduce healthcare disparities, and to consider pediatric and geriatric populations. The guidelines are based on a quantitative synthesis of 105 studies that yielded 7 strong recommendations, 21 conditional recommendations, and 13 good practice statements — those commonly accepted as beneficial or practical advice even if there is little direct evidence to support them. The voting panel of 19 members included not only 3 nephrologists and 2 pediatric rheumatologists but also 2 patient representatives with LN.

The recommendations are just that, “a recommendation, not an order,” Sammaritano said, and strong recommendations are those “where we think, unequivocally, almost everybody should follow that recommendation. When we feel that we cannot make a strong recommendation, then we call our recommendation conditional, and it is conditional on looking at different things,” she said.

“Patients are different, especially lupus patients, and so one lupus nephritis patient may have different clinical characteristics, different thoughts about what therapy will work for them in their lives, or what therapy they really do not want to pursue,” Sammaritano said. “Maybe they can’t conceive of coming to the hospital once a month for intravenous therapy. Maybe they’re concerned about pill burden, which is something that our patient panel really emphasized to us. So, conditional recommendation means this voting panel thought that this was the best overall for most patients and most circumstances, recognizing there will still be a significant number of people, clinicians and patients, who may feel differently for that particular situation. So, that’s where you know the patient-clinician discussion can help with decision-making.”

 

What Are the Recommendations?

All patients with systemic lupus erythematosus (SLE) are strongly recommended to undergo proteinuria screening every 6-12 months or at the time of a flare. Those suspected of having LN should receive a prompt kidney biopsy and treatment with glucocorticoids while awaiting the biopsy and results. Two conditional recommendations for kidney biopsy include patients with SLE with unexplained impaired kidney function or a protein to creatinine ratio > 0.5 g/g, and patients with LN with a suspected flare after initial response or a lack of response or worsening after 6 months of therapy.

The guidelines include a strong recommendation for all patients with SLE to receive hydroxychloroquine and a conditional recommendation for all patients with elevated proteinuria (> 0.5 g/g) to receive renin-angiotensin-aldosterone system inhibitors (RAAS-I). Dosages in patients with LN with decreased glomerular filtration rate (GFR) should be adjusted as needed.

Sammaritano then reviewed the specifics on medication treatment. The glucocorticoid therapy in all patients with LN should begin with Pulse IV Therapy at 250-1000 mg/d for 1-3 days, followed by oral prednisone ≤ 0.5 mg/kg per day up to 40 mg/d, then tapered to a target dose > 5 mg/d within 6 months. The justification for this course comes from a 2024 systematic review finding pulse followed by oral glucocorticoids maximized complete renal response while minimizing toxicities, Sammaritano said.

“We have all become acutely aware of the very high risk of prolonged high dose of glucocorticoids for our patients,” she said, “and importantly, our patient panel participants strongly emphasized their preference for minimizing glucocorticoids dose.”

In addition to the recommendation of all patients receiving hydroxychloroquine and RAAS-I, first-line treatment of active, new-onset, or flaring LN should begin with triple therapy — glucocorticoids with two additional immunosuppressive agents. For patients with class III/IV LN, triple therapy includes the glucocorticoids course with a mycophenolic acid analog (MPAA) and either belimumab or a CNI. Conditional recommendations support MPAA with belimumab for significant extrarenal manifestations and MPAA with CNI for proteinuria ≥ 3 g/g.

An alternative triple therapy for class III/IV is glucocorticoids with low-dose cyclophosphamide and belimumab, but MPAA at 2-3 g/d is preferred over cyclophosphamide. The preferred regimen for cyclophosphamide is derived from the Euro-Lupus Nephritis Trial: Intravenous 500 mg every 2 weeks for six doses and then MPAA. Sammaritano noted that there are some limited data on using cyclophosphamide with belimumab, but “we do not specifically recommend cyclophosphamide with a CNI as one of our options because this combination has not been studied in randomized controlled trials.”

There are less data supporting class V recommendations, Sammaritano said, but for those with proteinuria of at least 1 g/g, the panel still recommends triple therapy with glucocorticoids, a MPAA, and a CNI. A CNI is preferred over belimumab because of its stabilizing effects on the podocyte cytoskeleton. Two alternative triple therapies for class V–only patients are glucocorticoids with belimumab and either low-dose cyclophosphamide or MPAA.

Dual therapy is only recommended if triple therapy is not available or not tolerated. The voting panel chose to recommend triple therapy over dual therapy with escalation for two reasons. First, the BLISS-LN and AURORA 1 trials showed improved outcomes with initial triple therapy over initial dual therapies.

Second, “nephron loss proceeds throughout a person’s lifetime even for those who do not have lupus nephritis, and every case of lupus nephritis or every period of time with uncontrolled lupus nephritis changes the course of that decline for the worse,” Sammaritano said. “So, we feel we can’t wait for nephron loss to implement what has been shown to be the most efficacious therapy. We want to gain rapid control of inflammation using the most effective regimen to prevent further damage and flare and maintain survival.”

Therapy is conditionally recommended for at least 3-5 years because “not only do we want to gain rapid control of disease activity [but we also] want to maintain control of disease activity until there’s sustained inactive disease,” Sammaritano said. “Repeat kidney biopsies show that immunologic activity persists in the kidneys for several years, and the withdrawal of immunosuppression when there is histologic activity predisposes patients to flare.” But immunosuppressive therapy can be tapered over time as determined by renal disease activity and medication tolerability.

For patients with refractory disease, consider additional factors that could be affecting the disease, such as adherence, the presence of other diagnoses, or advanced chronicity.

“If true refractory nephritis is present,” she said, “we recommend escalation to a more intensive regimen,” including the addition of anti-CD20 agents, combination therapy with three immunosuppressives, or referral for investigational therapy.

“We also emphasize the importance of other adjunctive therapies preventing comorbidities, such as cardiovascular disease, changes in bone health, or infection risk,” she said. In older patients, avoid polypharmacy as much as possible and be mindful of age-related GFR, she added.

A strong recommendation supported monitoring patients with LN and proteinuria at least every 3 months if they have not achieved complete renal response and every 3-6 months after sustained complete renal response.

Last, in patients with LN and end-stage kidney disease (ESKD), the voting panel strongly recommends transplant over dialysis and conditionally recommends proceeding to the transplant without requiring a complete clinical or serologic remission as long as no other organs are involved. In patients with LN at risk for ESKD, the guideline conditionally recommends consideration of a preemptive transplant, and patients on dialysis or post transplant are strongly recommended to regularly follow up with rheumatology.

Gabriel Kirsch, MD, a resident rheumatologist at the University of Florida College of Medicine, Jacksonville, said he found the guidelines helpful, “especially the guidance on the dichotomy between using belimumab and voclosporin and the clinical and patient preference that help you make that decision.”

Kirsch had hoped, however, to hear more about the impact of therapeutic drug monitoring of hydroxychloroquine on LN outcomes. He also noted a clinical scenario he’s come across that wasn’t addressed.

“When you’re checking GFR on these folks, a lot of our eGFR calculators are creatinine based, and creatinine at the extremes of muscle mass can be inaccurate,” such as getting artificially low creatinine readings from pediatric patients because of their low muscle mass or from patients with muscle atrophy caused by a lot of glucocorticoid exposure. “I was hoping for some more guidance on that,” he said.

Ellen Ginzler, MD, MPH, chief of rheumatology at SUNY Health Science Center in Brooklyn, New York, said the guidelines were pretty much what she expected them to be. She agreed with the panel’s advice that, when deciding between belimumab or voclosporin, “if it’s pure proteinuria, then you add voclosporin. If the patient has extra renal manifestations, you go with belimumab first.” 

“They really made it quite clear that, despite the fact that people really want to reduce the amount of immunosuppression — and I agree you should taper steroids quickly — you really need to keep the immunosuppression for a prolonged period of time because all of the studies that have been done for years show that the longer you’re on immunosuppression after you achieve remission or a low disease activity state, the better your chance of not flaring,” Ginzler said. “Rapid tapering or discontinuation really increases the risk of flare.”

Sammaritano, Kirsch, and Ginzler had no disclosures. No external funding was used.

A version of this article appeared on Medscape.com.

WASHINGTON — A new guideline for management of lupus nephritis (LN) was unveiled at the annual meeting of the American College of Rheumatology (ACR), updating the 2012 LN guideline to recommend a more aggressive first-line approach to treating the disease.

“The biggest differences are that we are recommending what we’re calling triple therapy, where we incorporate the glucocorticoid therapy with baseline conventional immunosuppressants, usually mycophenolate with cyclophosphamide, and the addition of one of the newer agents more recently approved by the FDA [Food and Drug Administration] — belimumab, voclosporin, or another CNI [calcineurin inhibitor],” said Lisa Sammaritano, MD, director of the Rheumatology Reproductive Health Program of the Barbara Volcker Center for Women and Rheumatic Diseases at the Hospital for Special Surgery and professor of clinical medicine at Weill Cornell Medical College, both in New York City.

“This is a bit of a change from not only our previous guideline but some of the other guidelines out there, and it is based on the fact that we have very convincing evidence that starting with triple therapy yields to better long-term outcomes for our patients than starting with only two agents and waiting to see if they respond before escalating therapy,” she said. Other key updates include recommending use of pulse glucocorticoid therapy with a lower dose and more rapid steroid taper and treating patients with the recommended therapy for 3-5 years.

The guiding principles of the guideline are not only to preserve kidney function and minimize morbidity and mortality but also to ensure collaborative care with nephrology, to utilize shared decision-making that includes patients’ values and preferences, to reduce healthcare disparities, and to consider pediatric and geriatric populations. The guidelines are based on a quantitative synthesis of 105 studies that yielded 7 strong recommendations, 21 conditional recommendations, and 13 good practice statements — those commonly accepted as beneficial or practical advice even if there is little direct evidence to support them. The voting panel of 19 members included not only 3 nephrologists and 2 pediatric rheumatologists but also 2 patient representatives with LN.

The recommendations are just that, “a recommendation, not an order,” Sammaritano said, and strong recommendations are those “where we think, unequivocally, almost everybody should follow that recommendation. When we feel that we cannot make a strong recommendation, then we call our recommendation conditional, and it is conditional on looking at different things,” she said.

“Patients are different, especially lupus patients, and so one lupus nephritis patient may have different clinical characteristics, different thoughts about what therapy will work for them in their lives, or what therapy they really do not want to pursue,” Sammaritano said. “Maybe they can’t conceive of coming to the hospital once a month for intravenous therapy. Maybe they’re concerned about pill burden, which is something that our patient panel really emphasized to us. So, conditional recommendation means this voting panel thought that this was the best overall for most patients and most circumstances, recognizing there will still be a significant number of people, clinicians and patients, who may feel differently for that particular situation. So, that’s where you know the patient-clinician discussion can help with decision-making.”

 

What Are the Recommendations?

All patients with systemic lupus erythematosus (SLE) are strongly recommended to undergo proteinuria screening every 6-12 months or at the time of a flare. Those suspected of having LN should receive a prompt kidney biopsy and treatment with glucocorticoids while awaiting the biopsy and results. Two conditional recommendations for kidney biopsy include patients with SLE with unexplained impaired kidney function or a protein to creatinine ratio > 0.5 g/g, and patients with LN with a suspected flare after initial response or a lack of response or worsening after 6 months of therapy.

The guidelines include a strong recommendation for all patients with SLE to receive hydroxychloroquine and a conditional recommendation for all patients with elevated proteinuria (> 0.5 g/g) to receive renin-angiotensin-aldosterone system inhibitors (RAAS-I). Dosages in patients with LN with decreased glomerular filtration rate (GFR) should be adjusted as needed.

Sammaritano then reviewed the specifics on medication treatment. The glucocorticoid therapy in all patients with LN should begin with Pulse IV Therapy at 250-1000 mg/d for 1-3 days, followed by oral prednisone ≤ 0.5 mg/kg per day up to 40 mg/d, then tapered to a target dose > 5 mg/d within 6 months. The justification for this course comes from a 2024 systematic review finding pulse followed by oral glucocorticoids maximized complete renal response while minimizing toxicities, Sammaritano said.

“We have all become acutely aware of the very high risk of prolonged high dose of glucocorticoids for our patients,” she said, “and importantly, our patient panel participants strongly emphasized their preference for minimizing glucocorticoids dose.”

In addition to the recommendation of all patients receiving hydroxychloroquine and RAAS-I, first-line treatment of active, new-onset, or flaring LN should begin with triple therapy — glucocorticoids with two additional immunosuppressive agents. For patients with class III/IV LN, triple therapy includes the glucocorticoids course with a mycophenolic acid analog (MPAA) and either belimumab or a CNI. Conditional recommendations support MPAA with belimumab for significant extrarenal manifestations and MPAA with CNI for proteinuria ≥ 3 g/g.

An alternative triple therapy for class III/IV is glucocorticoids with low-dose cyclophosphamide and belimumab, but MPAA at 2-3 g/d is preferred over cyclophosphamide. The preferred regimen for cyclophosphamide is derived from the Euro-Lupus Nephritis Trial: Intravenous 500 mg every 2 weeks for six doses and then MPAA. Sammaritano noted that there are some limited data on using cyclophosphamide with belimumab, but “we do not specifically recommend cyclophosphamide with a CNI as one of our options because this combination has not been studied in randomized controlled trials.”

There are less data supporting class V recommendations, Sammaritano said, but for those with proteinuria of at least 1 g/g, the panel still recommends triple therapy with glucocorticoids, a MPAA, and a CNI. A CNI is preferred over belimumab because of its stabilizing effects on the podocyte cytoskeleton. Two alternative triple therapies for class V–only patients are glucocorticoids with belimumab and either low-dose cyclophosphamide or MPAA.

Dual therapy is only recommended if triple therapy is not available or not tolerated. The voting panel chose to recommend triple therapy over dual therapy with escalation for two reasons. First, the BLISS-LN and AURORA 1 trials showed improved outcomes with initial triple therapy over initial dual therapies.

Second, “nephron loss proceeds throughout a person’s lifetime even for those who do not have lupus nephritis, and every case of lupus nephritis or every period of time with uncontrolled lupus nephritis changes the course of that decline for the worse,” Sammaritano said. “So, we feel we can’t wait for nephron loss to implement what has been shown to be the most efficacious therapy. We want to gain rapid control of inflammation using the most effective regimen to prevent further damage and flare and maintain survival.”

Therapy is conditionally recommended for at least 3-5 years because “not only do we want to gain rapid control of disease activity [but we also] want to maintain control of disease activity until there’s sustained inactive disease,” Sammaritano said. “Repeat kidney biopsies show that immunologic activity persists in the kidneys for several years, and the withdrawal of immunosuppression when there is histologic activity predisposes patients to flare.” But immunosuppressive therapy can be tapered over time as determined by renal disease activity and medication tolerability.

For patients with refractory disease, consider additional factors that could be affecting the disease, such as adherence, the presence of other diagnoses, or advanced chronicity.

“If true refractory nephritis is present,” she said, “we recommend escalation to a more intensive regimen,” including the addition of anti-CD20 agents, combination therapy with three immunosuppressives, or referral for investigational therapy.

“We also emphasize the importance of other adjunctive therapies preventing comorbidities, such as cardiovascular disease, changes in bone health, or infection risk,” she said. In older patients, avoid polypharmacy as much as possible and be mindful of age-related GFR, she added.

A strong recommendation supported monitoring patients with LN and proteinuria at least every 3 months if they have not achieved complete renal response and every 3-6 months after sustained complete renal response.

Last, in patients with LN and end-stage kidney disease (ESKD), the voting panel strongly recommends transplant over dialysis and conditionally recommends proceeding to the transplant without requiring a complete clinical or serologic remission as long as no other organs are involved. In patients with LN at risk for ESKD, the guideline conditionally recommends consideration of a preemptive transplant, and patients on dialysis or post transplant are strongly recommended to regularly follow up with rheumatology.

Gabriel Kirsch, MD, a resident rheumatologist at the University of Florida College of Medicine, Jacksonville, said he found the guidelines helpful, “especially the guidance on the dichotomy between using belimumab and voclosporin and the clinical and patient preference that help you make that decision.”

Kirsch had hoped, however, to hear more about the impact of therapeutic drug monitoring of hydroxychloroquine on LN outcomes. He also noted a clinical scenario he’s come across that wasn’t addressed.

“When you’re checking GFR on these folks, a lot of our eGFR calculators are creatinine based, and creatinine at the extremes of muscle mass can be inaccurate,” such as getting artificially low creatinine readings from pediatric patients because of their low muscle mass or from patients with muscle atrophy caused by a lot of glucocorticoid exposure. “I was hoping for some more guidance on that,” he said.

Ellen Ginzler, MD, MPH, chief of rheumatology at SUNY Health Science Center in Brooklyn, New York, said the guidelines were pretty much what she expected them to be. She agreed with the panel’s advice that, when deciding between belimumab or voclosporin, “if it’s pure proteinuria, then you add voclosporin. If the patient has extra renal manifestations, you go with belimumab first.” 

“They really made it quite clear that, despite the fact that people really want to reduce the amount of immunosuppression — and I agree you should taper steroids quickly — you really need to keep the immunosuppression for a prolonged period of time because all of the studies that have been done for years show that the longer you’re on immunosuppression after you achieve remission or a low disease activity state, the better your chance of not flaring,” Ginzler said. “Rapid tapering or discontinuation really increases the risk of flare.”

Sammaritano, Kirsch, and Ginzler had no disclosures. No external funding was used.

A version of this article appeared on Medscape.com.

TOPLINE:

Individuals with normal body mass index (BMI) measurements may still face an increased risk for colorectal cancer if they have central obesity, characterized by excess fat around the abdomen.

METHODOLOGY:

• General obesity, often measured using BMI, is a recognized risk factor for colorectal cancer, but how much of this association is due to central obesity is unclear.
• Researchers assessed the associations between BMI, waist-to-hip ratio (WHR), and waist circumference (WC) with colorectal cancer risk and the degree of independence among these associations in patients aged 40-69 years recruited in the UK Biobank cohort study from 2006 to 2010.
• Anthropometric measurements were performed using standardized methods.
• Cancer registry and hospital data linkage identified colorectal cancer cases in the UK Biobank.

TAKEAWAY:

• Researchers included 460,784 participants (mean age, 56.3 years; 46.7% men), of whom 67.1% had either overweight or obesity, and 49.4% and 60.5% had high or very high WHR and WC, respectively.
• During the median 12.5-year follow-up period, 5977 participants developed colorectal cancer.
• Every SD increase in WHR (hazard ratio [HR], 1.18) showed a stronger association with colorectal cancer risk than in BMI (HR, 1.10).
• After adjustment for BMI, the association between WHR and colorectal cancer risk became slightly attenuated while still staying robust (HR, 1.15); however, after adjusting for WHR, the association between BMI and colorectal cancer risk became substantially weakened (HR, 1.04).
• WHR showed strongly significant associations with colorectal cancer risk across all BMI categories, whereas associations of BMI with colorectal cancer risk were weak and not statistically significant within all WHR categories.
• Central obesity demonstrated consistent associations with both colon and rectal cancer risks in both sexes before and after adjustment for BMI, whereas BMI showed no significant association with colorectal cancer risk in women or with rectal cancer risk after WHR adjustment.

IN PRACTICE:

“[The study] results also underline the importance of integrating additional anthropometric measures such as WHR alongside BMI into routine clinical practice for more effective prevention and management of obesity, whose prevalence is steadily increasing in many countries worldwide, in order to limit the global burden of colorectal cancer and many other obesity-related adverse health outcomes,” the authors wrote.

SOURCE:

The study was led by Fatemeh Safizadeh, German Cancer Research Center (DKFZ), Heidelberg. It was published online in The International Journal of Obesity.

LIMITATIONS:

This study relied on only one-time measurements of anthropometric measures at baseline, without considering previous lifetime history of overweight and obesity or changes during follow-up. Additionally, WHR and WC may not be the most accurate measures of central obesity, as WC includes both visceral and subcutaneous adipose tissue. The study population also showed evidence of healthy volunteer bias, with more health-conscious and socioeconomically advantaged participants being somewhat overrepresented.

DISCLOSURES:

The authors declared no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Individuals with normal body mass index (BMI) measurements may still face an increased risk for colorectal cancer if they have central obesity, characterized by excess fat around the abdomen.

METHODOLOGY:

• General obesity, often measured using BMI, is a recognized risk factor for colorectal cancer, but how much of this association is due to central obesity is unclear.
• Researchers assessed the associations between BMI, waist-to-hip ratio (WHR), and waist circumference (WC) with colorectal cancer risk and the degree of independence among these associations in patients aged 40-69 years recruited in the UK Biobank cohort study from 2006 to 2010.
• Anthropometric measurements were performed using standardized methods.
• Cancer registry and hospital data linkage identified colorectal cancer cases in the UK Biobank.

TAKEAWAY:

• Researchers included 460,784 participants (mean age, 56.3 years; 46.7% men), of whom 67.1% had either overweight or obesity, and 49.4% and 60.5% had high or very high WHR and WC, respectively.
• During the median 12.5-year follow-up period, 5977 participants developed colorectal cancer.
• Every SD increase in WHR (hazard ratio [HR], 1.18) showed a stronger association with colorectal cancer risk than in BMI (HR, 1.10).
• After adjustment for BMI, the association between WHR and colorectal cancer risk became slightly attenuated while still staying robust (HR, 1.15); however, after adjusting for WHR, the association between BMI and colorectal cancer risk became substantially weakened (HR, 1.04).
• WHR showed strongly significant associations with colorectal cancer risk across all BMI categories, whereas associations of BMI with colorectal cancer risk were weak and not statistically significant within all WHR categories.
• Central obesity demonstrated consistent associations with both colon and rectal cancer risks in both sexes before and after adjustment for BMI, whereas BMI showed no significant association with colorectal cancer risk in women or with rectal cancer risk after WHR adjustment.

IN PRACTICE:

“[The study] results also underline the importance of integrating additional anthropometric measures such as WHR alongside BMI into routine clinical practice for more effective prevention and management of obesity, whose prevalence is steadily increasing in many countries worldwide, in order to limit the global burden of colorectal cancer and many other obesity-related adverse health outcomes,” the authors wrote.

SOURCE:

The study was led by Fatemeh Safizadeh, German Cancer Research Center (DKFZ), Heidelberg. It was published online in The International Journal of Obesity.

LIMITATIONS:

This study relied on only one-time measurements of anthropometric measures at baseline, without considering previous lifetime history of overweight and obesity or changes during follow-up. Additionally, WHR and WC may not be the most accurate measures of central obesity, as WC includes both visceral and subcutaneous adipose tissue. The study population also showed evidence of healthy volunteer bias, with more health-conscious and socioeconomically advantaged participants being somewhat overrepresented.

DISCLOSURES:

The authors declared no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Individuals with normal body mass index (BMI) measurements may still face an increased risk for colorectal cancer if they have central obesity, characterized by excess fat around the abdomen.

METHODOLOGY:

• General obesity, often measured using BMI, is a recognized risk factor for colorectal cancer, but how much of this association is due to central obesity is unclear.
• Researchers assessed the associations between BMI, waist-to-hip ratio (WHR), and waist circumference (WC) with colorectal cancer risk and the degree of independence among these associations in patients aged 40-69 years recruited in the UK Biobank cohort study from 2006 to 2010.
• Anthropometric measurements were performed using standardized methods.
• Cancer registry and hospital data linkage identified colorectal cancer cases in the UK Biobank.

TAKEAWAY:

• Researchers included 460,784 participants (mean age, 56.3 years; 46.7% men), of whom 67.1% had either overweight or obesity, and 49.4% and 60.5% had high or very high WHR and WC, respectively.
• During the median 12.5-year follow-up period, 5977 participants developed colorectal cancer.
• Every SD increase in WHR (hazard ratio [HR], 1.18) showed a stronger association with colorectal cancer risk than in BMI (HR, 1.10).
• After adjustment for BMI, the association between WHR and colorectal cancer risk became slightly attenuated while still staying robust (HR, 1.15); however, after adjusting for WHR, the association between BMI and colorectal cancer risk became substantially weakened (HR, 1.04).
• WHR showed strongly significant associations with colorectal cancer risk across all BMI categories, whereas associations of BMI with colorectal cancer risk were weak and not statistically significant within all WHR categories.
• Central obesity demonstrated consistent associations with both colon and rectal cancer risks in both sexes before and after adjustment for BMI, whereas BMI showed no significant association with colorectal cancer risk in women or with rectal cancer risk after WHR adjustment.

IN PRACTICE:

“[The study] results also underline the importance of integrating additional anthropometric measures such as WHR alongside BMI into routine clinical practice for more effective prevention and management of obesity, whose prevalence is steadily increasing in many countries worldwide, in order to limit the global burden of colorectal cancer and many other obesity-related adverse health outcomes,” the authors wrote.

SOURCE:

The study was led by Fatemeh Safizadeh, German Cancer Research Center (DKFZ), Heidelberg. It was published online in The International Journal of Obesity.

LIMITATIONS:

This study relied on only one-time measurements of anthropometric measures at baseline, without considering previous lifetime history of overweight and obesity or changes during follow-up. Additionally, WHR and WC may not be the most accurate measures of central obesity, as WC includes both visceral and subcutaneous adipose tissue. The study population also showed evidence of healthy volunteer bias, with more health-conscious and socioeconomically advantaged participants being somewhat overrepresented.

DISCLOSURES:

The authors declared no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Biosimilars demonstrate comparable drug survival and safety with adalimumab among new users, but patients switching from Humira (the originator product) to biosimilars had a 35% higher discontinuation rate than those who remained on Humira.

 

METHODOLOGY:

• Researchers conducted a cohort study using data on patients with psoriasis who were treated with adalimumab, a tumor necrosis factor alpha inhibitor used to treat moderate to severe psoriasis, from the French National Health Data System, British Association of Dermatologists Biologics and Immunomodulators Register, and Spanish Registry of Systemic Therapy in Psoriasis.
• The analysis included 7387 adalimumab-naive patients who were new users of an adalimumab biosimilar and 3654 patients (switchers) who switched from Humira to a biosimilar. Patients were matched and compared with patients receiving Humira.
• Co-primary outcomes of the study were drug discontinuation and serious adverse events.
• Researchers assessed the following adalimumab biosimilar brands: Amgevita, Imraldi, Hyrimoz, Idacio, and Hulio.

TAKEAWAY:

• All-cause drug discontinuation rates were similar between new users of biosimilars and Humira new users (hazard ratio [HR], 0.99; 95% CI, 0.94-1.04).
• Discontinuation rates were higher among those who switched from Humira to a biosimilar (HR, 1.35; 95% CI, 1.19-1.52) than among those who stayed on Humira. Switching to Amgevita (HR, 1.25; 95% CI, 1.13-1.27), Imraldi (HR, 1.53; 95% CI, 1.33-1.76), and Hyrimoz (HR, 1.80; 95% CI, 1.29-2.52) was associated with higher discontinuation rates.
• Serious adverse events were not significantly different between new users of Humira and biosimilar new users (incidence rate ratio [IRR], 0.91; 95% CI, 0.80-1.05), and between patients who switched from a biosimilar to Humira and those who stayed on Humira (IRR, 0.92; 95% CI, 0.83-1.01).
• No significant differences in discontinuation because of ineffectiveness were found between biosimilar and Humira new users (HR, 0.97; 95% CI, 0.88-1.08). Discontinuation because of adverse events was also comparable for all biosimilars among new users, except for Hyrimoz (HR, 0.54; 95% CI, 0.35-0.85), which showed fewer discontinuations than Humira.

IN PRACTICE:

“This study found comparable drug survival and safety between adalimumab biosimilars and Humira in adalimumab-naive patients, supporting the use of biosimilars as viable alternatives for new patients,” the authors wrote. However, noting that discontinuation was more likely among those who switched from Humira to a biosimilar, they added: “Changes in treatment response, skin or injection site reactions, and nocebo effects may contribute to treatment discontinuation post-switch. Thus, patients who switch from Humira to biosimilars may require closer monitoring and support to alleviate these challenges.”

SOURCE:

The study was led by Duc Binh Phan, Dermatology Centre, Northern Care Alliance NHS Foundation Trust in Manchester, England. It was published online in The British Journal of Dermatology.

LIMITATIONS:

Unmeasured factors including psychological perceptions, regional policies, and drug availability could influence drug survival, making the results not fully reflective of treatment effectiveness or safety. Most Humira users in registries were enrolled before biosimilars became available, making it impractical to match new users on the basis of treatment initiation years. Additionally, reasons for discontinuation were not available in the French National Health Data System.

DISCLOSURES:

In the United Kingdom, the research was funded by the Psoriasis Association PhD studentship and supported by the NIHR Manchester Biomedical Research Centre. In France, the authors are employees of the French National Health Insurance, the French National Agency for the Safety of Medicines and Health Products, and the Assistance Publique — Hôpitaux de Paris and received no funding. The authors reported receiving consulting and speaker fees and clinical trial sponsorship from various pharmaceutical companies. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Biosimilars demonstrate comparable drug survival and safety with adalimumab among new users, but patients switching from Humira (the originator product) to biosimilars had a 35% higher discontinuation rate than those who remained on Humira.

 

METHODOLOGY:

• Researchers conducted a cohort study using data on patients with psoriasis who were treated with adalimumab, a tumor necrosis factor alpha inhibitor used to treat moderate to severe psoriasis, from the French National Health Data System, British Association of Dermatologists Biologics and Immunomodulators Register, and Spanish Registry of Systemic Therapy in Psoriasis.
• The analysis included 7387 adalimumab-naive patients who were new users of an adalimumab biosimilar and 3654 patients (switchers) who switched from Humira to a biosimilar. Patients were matched and compared with patients receiving Humira.
• Co-primary outcomes of the study were drug discontinuation and serious adverse events.
• Researchers assessed the following adalimumab biosimilar brands: Amgevita, Imraldi, Hyrimoz, Idacio, and Hulio.

TAKEAWAY:

• All-cause drug discontinuation rates were similar between new users of biosimilars and Humira new users (hazard ratio [HR], 0.99; 95% CI, 0.94-1.04).
• Discontinuation rates were higher among those who switched from Humira to a biosimilar (HR, 1.35; 95% CI, 1.19-1.52) than among those who stayed on Humira. Switching to Amgevita (HR, 1.25; 95% CI, 1.13-1.27), Imraldi (HR, 1.53; 95% CI, 1.33-1.76), and Hyrimoz (HR, 1.80; 95% CI, 1.29-2.52) was associated with higher discontinuation rates.
• Serious adverse events were not significantly different between new users of Humira and biosimilar new users (incidence rate ratio [IRR], 0.91; 95% CI, 0.80-1.05), and between patients who switched from a biosimilar to Humira and those who stayed on Humira (IRR, 0.92; 95% CI, 0.83-1.01).
• No significant differences in discontinuation because of ineffectiveness were found between biosimilar and Humira new users (HR, 0.97; 95% CI, 0.88-1.08). Discontinuation because of adverse events was also comparable for all biosimilars among new users, except for Hyrimoz (HR, 0.54; 95% CI, 0.35-0.85), which showed fewer discontinuations than Humira.

IN PRACTICE:

“This study found comparable drug survival and safety between adalimumab biosimilars and Humira in adalimumab-naive patients, supporting the use of biosimilars as viable alternatives for new patients,” the authors wrote. However, noting that discontinuation was more likely among those who switched from Humira to a biosimilar, they added: “Changes in treatment response, skin or injection site reactions, and nocebo effects may contribute to treatment discontinuation post-switch. Thus, patients who switch from Humira to biosimilars may require closer monitoring and support to alleviate these challenges.”

SOURCE:

The study was led by Duc Binh Phan, Dermatology Centre, Northern Care Alliance NHS Foundation Trust in Manchester, England. It was published online in The British Journal of Dermatology.

LIMITATIONS:

Unmeasured factors including psychological perceptions, regional policies, and drug availability could influence drug survival, making the results not fully reflective of treatment effectiveness or safety. Most Humira users in registries were enrolled before biosimilars became available, making it impractical to match new users on the basis of treatment initiation years. Additionally, reasons for discontinuation were not available in the French National Health Data System.

DISCLOSURES:

In the United Kingdom, the research was funded by the Psoriasis Association PhD studentship and supported by the NIHR Manchester Biomedical Research Centre. In France, the authors are employees of the French National Health Insurance, the French National Agency for the Safety of Medicines and Health Products, and the Assistance Publique — Hôpitaux de Paris and received no funding. The authors reported receiving consulting and speaker fees and clinical trial sponsorship from various pharmaceutical companies. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Biosimilars demonstrate comparable drug survival and safety with adalimumab among new users, but patients switching from Humira (the originator product) to biosimilars had a 35% higher discontinuation rate than those who remained on Humira.

 

METHODOLOGY:

• Researchers conducted a cohort study using data on patients with psoriasis who were treated with adalimumab, a tumor necrosis factor alpha inhibitor used to treat moderate to severe psoriasis, from the French National Health Data System, British Association of Dermatologists Biologics and Immunomodulators Register, and Spanish Registry of Systemic Therapy in Psoriasis.
• The analysis included 7387 adalimumab-naive patients who were new users of an adalimumab biosimilar and 3654 patients (switchers) who switched from Humira to a biosimilar. Patients were matched and compared with patients receiving Humira.
• Co-primary outcomes of the study were drug discontinuation and serious adverse events.
• Researchers assessed the following adalimumab biosimilar brands: Amgevita, Imraldi, Hyrimoz, Idacio, and Hulio.

TAKEAWAY:

• All-cause drug discontinuation rates were similar between new users of biosimilars and Humira new users (hazard ratio [HR], 0.99; 95% CI, 0.94-1.04).
• Discontinuation rates were higher among those who switched from Humira to a biosimilar (HR, 1.35; 95% CI, 1.19-1.52) than among those who stayed on Humira. Switching to Amgevita (HR, 1.25; 95% CI, 1.13-1.27), Imraldi (HR, 1.53; 95% CI, 1.33-1.76), and Hyrimoz (HR, 1.80; 95% CI, 1.29-2.52) was associated with higher discontinuation rates.
• Serious adverse events were not significantly different between new users of Humira and biosimilar new users (incidence rate ratio [IRR], 0.91; 95% CI, 0.80-1.05), and between patients who switched from a biosimilar to Humira and those who stayed on Humira (IRR, 0.92; 95% CI, 0.83-1.01).
• No significant differences in discontinuation because of ineffectiveness were found between biosimilar and Humira new users (HR, 0.97; 95% CI, 0.88-1.08). Discontinuation because of adverse events was also comparable for all biosimilars among new users, except for Hyrimoz (HR, 0.54; 95% CI, 0.35-0.85), which showed fewer discontinuations than Humira.

IN PRACTICE:

“This study found comparable drug survival and safety between adalimumab biosimilars and Humira in adalimumab-naive patients, supporting the use of biosimilars as viable alternatives for new patients,” the authors wrote. However, noting that discontinuation was more likely among those who switched from Humira to a biosimilar, they added: “Changes in treatment response, skin or injection site reactions, and nocebo effects may contribute to treatment discontinuation post-switch. Thus, patients who switch from Humira to biosimilars may require closer monitoring and support to alleviate these challenges.”

SOURCE:

The study was led by Duc Binh Phan, Dermatology Centre, Northern Care Alliance NHS Foundation Trust in Manchester, England. It was published online in The British Journal of Dermatology.

LIMITATIONS:

Unmeasured factors including psychological perceptions, regional policies, and drug availability could influence drug survival, making the results not fully reflective of treatment effectiveness or safety. Most Humira users in registries were enrolled before biosimilars became available, making it impractical to match new users on the basis of treatment initiation years. Additionally, reasons for discontinuation were not available in the French National Health Data System.

DISCLOSURES:

In the United Kingdom, the research was funded by the Psoriasis Association PhD studentship and supported by the NIHR Manchester Biomedical Research Centre. In France, the authors are employees of the French National Health Insurance, the French National Agency for the Safety of Medicines and Health Products, and the Assistance Publique — Hôpitaux de Paris and received no funding. The authors reported receiving consulting and speaker fees and clinical trial sponsorship from various pharmaceutical companies. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

LAS VEGAS — Onychomycosis, a stubborn fungal infection of the nail bed, is responsible for half of all nail diseases and presents a tricky challenge when it comes to both diagnosis and treatment.

According to Tracey C. Vlahovic, DPM, a professor at the Samuel Merritt University College of Podiatric Medicine, Oakland, California, most cases of onychomycosis are caused by the dermatophytes Trichophyton rubrum and T mentagrophytes, although the cause can also be a mixed infection. “Dermatophytes are going to impact the nails first, and molds may come in and join the party later,” she said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference.

 

“The distal subungual onychomycosis (DSO) type is still the most common, but don’t forget that onychomycosis and nail psoriasis can happen at the same time. What we can’t lose sight of is that onychomycosis is a disease of the nail bed, which ultimately affects the nail plate; it’s not a disease of the nail plate first.”

Her diagnostic approach combines periodic acid-Schiff (PAS) staining with fungal culture “because I like to know the speciation,” she said. “PAS doesn’t give me the speciation; fungal cultures should. PCR can be expensive, but that can give me speciation.”

 

How Does This Happen?

Fungal DSO occurs because of exposure to a dermatophyte, which can be as simple as tinea pedis. “Perhaps it’s the environment in the shoe,” said Vlahovic, one of the authors of a textbook on onychomycosis. “That’s something I’m always concentrating on with the patient. What is your foot hygiene like? What’s your shoe and sock wear? What’s your level of physical activity? You can have trauma to the hyponychium, where the skin and the nail meet. Maybe they trim their nails too close to the skin, or maybe there’s another skin condition like psoriasis.”

The dermatophyte, she continued, enters and invades the nail at the hyponychium and uses the keratinase enzyme to digest keratin in the nail bed. Mild inflammation develops, and pH changes cause focal parakeratosis and subungual hyperkeratosis in the form of onycholysis and subungual debris. “Hyphae then invade the lamina of the nail plate, which causes brittle nails,” she said. “The compromised hyponychium creates a reservoir for molds and bacteria.”

Therapies approved by the Food and Drug Administration (FDA) for onychomycosis include the topical agents efinaconazole, tavaborole, and ciclopirox; the oral agents terbinafine and itraconazole; and laser therapy. Off-label, Vlahovic said that she sometimes uses oral fluconazole, pulsed dosing for terbinafine, and booster doses of terbinafine or any approved oral antifungal agent. Pulse dosing for itraconazole is FDA-approved for fingernails but not for toenails.

“We don’t have any oral antifungals that are approved for children, but we do have weight-based dosing,” she noted. Other off-label treatments for onychomycosis that patients may come across while browsing the internet but do not penetrate the nail plate, include products containing tolnaftate, tree oil, and undecylenic acid, “which is a very long-chain antifungal,” Vlahovic said. “It’s so huge that it can’t get through the nail plate. These products must get through the nail plate into the nail bed where the infection is.”

According to therapeutic recommendations for the treatment of toenail onychomycosis in the United States, published in 2021, terbinafine is the primary choice for oral treatment and efinaconazole 10% for topical treatment. There are no current treatment recommendations for pregnant or lactating patients. “I always defer to the obstetrician,” said Vlahovic, a coauthor of the recommendations. For pediatric patients, there are approved topical medications: Efinaconazole and tavaborole for ages 6 and up and ciclopirox for ages 12 years or older.

Treatment recommendations for adults vary based on clinical presentation and patient characteristics. Questions to consider: Are they older? Do they have diabetes? Are they able to reach their feet to apply medication? What other medications are they taking? Are there any kidney or liver issues that are cause for concern?

Another question to consider is whether they have concurrent nail psoriasis. “When I have those patients, I often treat the onychomycosis first and the nail psoriasis second,” she said.

 

Evidence for Lasers Weak

Though laser therapy is FDA approved for the temporary increase of clear nails in onychomycosis, Vlahovic is underwhelmed by the evidence of its use for onychomycosis. According to a systematic review of 261 studies, only 1 reported treatment success as 16.7%, and clinical cures ranged from 13% to 16%. “Many of the existing studies were so poorly done in terms of protocols; it was frustrating,” she said. “No study has reported complete cure. There’s a lack of standardization across laser companies and a lack of standardization across protocols.”

Before starting oral antifungal therapy, Vlahovic uses the Onychomycosis Severity Index to determine the number of nails involved and the proportion of nails that are affected. She also wants to know if the patient is taking any medication that might interfere with an oral antifungal and gets baseline liver function tests (LFTs) to document results in the chart. “You want to discuss the pros and cons of oral antifungal therapy, and you want to set realistic expectations,” she added. “These medications are not cosmetic products; they are meant to kill fungus. Sometimes patients lose sight of that.”

Vlahovic routinely offers pulse dosing of terbinafine, which is FDA approved at a dose of 250 mg/d for 90 days. Pulse dosing involves taking terbinafine 250 mg twice a day for 1 week, followed by a 3-week break. This cycle is repeated three or four times. A clinical trial found no significant difference in outcome between patients who received pulsed vs continuous terbinafine dosing for the treatment of dermatophyte onychomycosis.

 

What About Oral Antifungal Safety?

For patients who ask about the safety of oral antifungals, Vlahovic characterized them as “well tolerated and safe in an immunocompetent population.” In a meta-analysis of 122 studies of about 22,000 patients, the pooled risk for treatment discontinuation because of adverse events was 3.4% for terbinafine 250 mg/d and 4.21% for itraconazole 200 mg/d. The risk for liver injury requiring termination of treatment and the risk of having symptomatic elevation of LFTs were less than 2% for all regimens.

According to the best available published evidence, Vlahovic said, the onychomycosis recurrence rate ranges from 6% to 40%. “That’s a wild number. We really have no idea what the true recurrence rate is, and that’s a problem.”

Vlahovic disclosed having been a consultant to and an investigator for Ortho Dermatologics and Sagis Diagnostics.

A version of this article appeared on Medscape.com.

LAS VEGAS — Onychomycosis, a stubborn fungal infection of the nail bed, is responsible for half of all nail diseases and presents a tricky challenge when it comes to both diagnosis and treatment.

According to Tracey C. Vlahovic, DPM, a professor at the Samuel Merritt University College of Podiatric Medicine, Oakland, California, most cases of onychomycosis are caused by the dermatophytes Trichophyton rubrum and T mentagrophytes, although the cause can also be a mixed infection. “Dermatophytes are going to impact the nails first, and molds may come in and join the party later,” she said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference.

 

“The distal subungual onychomycosis (DSO) type is still the most common, but don’t forget that onychomycosis and nail psoriasis can happen at the same time. What we can’t lose sight of is that onychomycosis is a disease of the nail bed, which ultimately affects the nail plate; it’s not a disease of the nail plate first.”

Her diagnostic approach combines periodic acid-Schiff (PAS) staining with fungal culture “because I like to know the speciation,” she said. “PAS doesn’t give me the speciation; fungal cultures should. PCR can be expensive, but that can give me speciation.”

 

How Does This Happen?

Fungal DSO occurs because of exposure to a dermatophyte, which can be as simple as tinea pedis. “Perhaps it’s the environment in the shoe,” said Vlahovic, one of the authors of a textbook on onychomycosis. “That’s something I’m always concentrating on with the patient. What is your foot hygiene like? What’s your shoe and sock wear? What’s your level of physical activity? You can have trauma to the hyponychium, where the skin and the nail meet. Maybe they trim their nails too close to the skin, or maybe there’s another skin condition like psoriasis.”

The dermatophyte, she continued, enters and invades the nail at the hyponychium and uses the keratinase enzyme to digest keratin in the nail bed. Mild inflammation develops, and pH changes cause focal parakeratosis and subungual hyperkeratosis in the form of onycholysis and subungual debris. “Hyphae then invade the lamina of the nail plate, which causes brittle nails,” she said. “The compromised hyponychium creates a reservoir for molds and bacteria.”

Therapies approved by the Food and Drug Administration (FDA) for onychomycosis include the topical agents efinaconazole, tavaborole, and ciclopirox; the oral agents terbinafine and itraconazole; and laser therapy. Off-label, Vlahovic said that she sometimes uses oral fluconazole, pulsed dosing for terbinafine, and booster doses of terbinafine or any approved oral antifungal agent. Pulse dosing for itraconazole is FDA-approved for fingernails but not for toenails.

“We don’t have any oral antifungals that are approved for children, but we do have weight-based dosing,” she noted. Other off-label treatments for onychomycosis that patients may come across while browsing the internet but do not penetrate the nail plate, include products containing tolnaftate, tree oil, and undecylenic acid, “which is a very long-chain antifungal,” Vlahovic said. “It’s so huge that it can’t get through the nail plate. These products must get through the nail plate into the nail bed where the infection is.”

According to therapeutic recommendations for the treatment of toenail onychomycosis in the United States, published in 2021, terbinafine is the primary choice for oral treatment and efinaconazole 10% for topical treatment. There are no current treatment recommendations for pregnant or lactating patients. “I always defer to the obstetrician,” said Vlahovic, a coauthor of the recommendations. For pediatric patients, there are approved topical medications: Efinaconazole and tavaborole for ages 6 and up and ciclopirox for ages 12 years or older.

Treatment recommendations for adults vary based on clinical presentation and patient characteristics. Questions to consider: Are they older? Do they have diabetes? Are they able to reach their feet to apply medication? What other medications are they taking? Are there any kidney or liver issues that are cause for concern?

Another question to consider is whether they have concurrent nail psoriasis. “When I have those patients, I often treat the onychomycosis first and the nail psoriasis second,” she said.

 

Evidence for Lasers Weak

Though laser therapy is FDA approved for the temporary increase of clear nails in onychomycosis, Vlahovic is underwhelmed by the evidence of its use for onychomycosis. According to a systematic review of 261 studies, only 1 reported treatment success as 16.7%, and clinical cures ranged from 13% to 16%. “Many of the existing studies were so poorly done in terms of protocols; it was frustrating,” she said. “No study has reported complete cure. There’s a lack of standardization across laser companies and a lack of standardization across protocols.”

Before starting oral antifungal therapy, Vlahovic uses the Onychomycosis Severity Index to determine the number of nails involved and the proportion of nails that are affected. She also wants to know if the patient is taking any medication that might interfere with an oral antifungal and gets baseline liver function tests (LFTs) to document results in the chart. “You want to discuss the pros and cons of oral antifungal therapy, and you want to set realistic expectations,” she added. “These medications are not cosmetic products; they are meant to kill fungus. Sometimes patients lose sight of that.”

Vlahovic routinely offers pulse dosing of terbinafine, which is FDA approved at a dose of 250 mg/d for 90 days. Pulse dosing involves taking terbinafine 250 mg twice a day for 1 week, followed by a 3-week break. This cycle is repeated three or four times. A clinical trial found no significant difference in outcome between patients who received pulsed vs continuous terbinafine dosing for the treatment of dermatophyte onychomycosis.

 

What About Oral Antifungal Safety?

For patients who ask about the safety of oral antifungals, Vlahovic characterized them as “well tolerated and safe in an immunocompetent population.” In a meta-analysis of 122 studies of about 22,000 patients, the pooled risk for treatment discontinuation because of adverse events was 3.4% for terbinafine 250 mg/d and 4.21% for itraconazole 200 mg/d. The risk for liver injury requiring termination of treatment and the risk of having symptomatic elevation of LFTs were less than 2% for all regimens.

According to the best available published evidence, Vlahovic said, the onychomycosis recurrence rate ranges from 6% to 40%. “That’s a wild number. We really have no idea what the true recurrence rate is, and that’s a problem.”

Vlahovic disclosed having been a consultant to and an investigator for Ortho Dermatologics and Sagis Diagnostics.

A version of this article appeared on Medscape.com.

LAS VEGAS — Onychomycosis, a stubborn fungal infection of the nail bed, is responsible for half of all nail diseases and presents a tricky challenge when it comes to both diagnosis and treatment.

According to Tracey C. Vlahovic, DPM, a professor at the Samuel Merritt University College of Podiatric Medicine, Oakland, California, most cases of onychomycosis are caused by the dermatophytes Trichophyton rubrum and T mentagrophytes, although the cause can also be a mixed infection. “Dermatophytes are going to impact the nails first, and molds may come in and join the party later,” she said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference.

 

“The distal subungual onychomycosis (DSO) type is still the most common, but don’t forget that onychomycosis and nail psoriasis can happen at the same time. What we can’t lose sight of is that onychomycosis is a disease of the nail bed, which ultimately affects the nail plate; it’s not a disease of the nail plate first.”

Her diagnostic approach combines periodic acid-Schiff (PAS) staining with fungal culture “because I like to know the speciation,” she said. “PAS doesn’t give me the speciation; fungal cultures should. PCR can be expensive, but that can give me speciation.”

 

How Does This Happen?

Fungal DSO occurs because of exposure to a dermatophyte, which can be as simple as tinea pedis. “Perhaps it’s the environment in the shoe,” said Vlahovic, one of the authors of a textbook on onychomycosis. “That’s something I’m always concentrating on with the patient. What is your foot hygiene like? What’s your shoe and sock wear? What’s your level of physical activity? You can have trauma to the hyponychium, where the skin and the nail meet. Maybe they trim their nails too close to the skin, or maybe there’s another skin condition like psoriasis.”

The dermatophyte, she continued, enters and invades the nail at the hyponychium and uses the keratinase enzyme to digest keratin in the nail bed. Mild inflammation develops, and pH changes cause focal parakeratosis and subungual hyperkeratosis in the form of onycholysis and subungual debris. “Hyphae then invade the lamina of the nail plate, which causes brittle nails,” she said. “The compromised hyponychium creates a reservoir for molds and bacteria.”

Therapies approved by the Food and Drug Administration (FDA) for onychomycosis include the topical agents efinaconazole, tavaborole, and ciclopirox; the oral agents terbinafine and itraconazole; and laser therapy. Off-label, Vlahovic said that she sometimes uses oral fluconazole, pulsed dosing for terbinafine, and booster doses of terbinafine or any approved oral antifungal agent. Pulse dosing for itraconazole is FDA-approved for fingernails but not for toenails.

“We don’t have any oral antifungals that are approved for children, but we do have weight-based dosing,” she noted. Other off-label treatments for onychomycosis that patients may come across while browsing the internet but do not penetrate the nail plate, include products containing tolnaftate, tree oil, and undecylenic acid, “which is a very long-chain antifungal,” Vlahovic said. “It’s so huge that it can’t get through the nail plate. These products must get through the nail plate into the nail bed where the infection is.”

According to therapeutic recommendations for the treatment of toenail onychomycosis in the United States, published in 2021, terbinafine is the primary choice for oral treatment and efinaconazole 10% for topical treatment. There are no current treatment recommendations for pregnant or lactating patients. “I always defer to the obstetrician,” said Vlahovic, a coauthor of the recommendations. For pediatric patients, there are approved topical medications: Efinaconazole and tavaborole for ages 6 and up and ciclopirox for ages 12 years or older.

Treatment recommendations for adults vary based on clinical presentation and patient characteristics. Questions to consider: Are they older? Do they have diabetes? Are they able to reach their feet to apply medication? What other medications are they taking? Are there any kidney or liver issues that are cause for concern?

Another question to consider is whether they have concurrent nail psoriasis. “When I have those patients, I often treat the onychomycosis first and the nail psoriasis second,” she said.

 

Evidence for Lasers Weak

Though laser therapy is FDA approved for the temporary increase of clear nails in onychomycosis, Vlahovic is underwhelmed by the evidence of its use for onychomycosis. According to a systematic review of 261 studies, only 1 reported treatment success as 16.7%, and clinical cures ranged from 13% to 16%. “Many of the existing studies were so poorly done in terms of protocols; it was frustrating,” she said. “No study has reported complete cure. There’s a lack of standardization across laser companies and a lack of standardization across protocols.”

Before starting oral antifungal therapy, Vlahovic uses the Onychomycosis Severity Index to determine the number of nails involved and the proportion of nails that are affected. She also wants to know if the patient is taking any medication that might interfere with an oral antifungal and gets baseline liver function tests (LFTs) to document results in the chart. “You want to discuss the pros and cons of oral antifungal therapy, and you want to set realistic expectations,” she added. “These medications are not cosmetic products; they are meant to kill fungus. Sometimes patients lose sight of that.”

Vlahovic routinely offers pulse dosing of terbinafine, which is FDA approved at a dose of 250 mg/d for 90 days. Pulse dosing involves taking terbinafine 250 mg twice a day for 1 week, followed by a 3-week break. This cycle is repeated three or four times. A clinical trial found no significant difference in outcome between patients who received pulsed vs continuous terbinafine dosing for the treatment of dermatophyte onychomycosis.

 

What About Oral Antifungal Safety?

For patients who ask about the safety of oral antifungals, Vlahovic characterized them as “well tolerated and safe in an immunocompetent population.” In a meta-analysis of 122 studies of about 22,000 patients, the pooled risk for treatment discontinuation because of adverse events was 3.4% for terbinafine 250 mg/d and 4.21% for itraconazole 200 mg/d. The risk for liver injury requiring termination of treatment and the risk of having symptomatic elevation of LFTs were less than 2% for all regimens.

According to the best available published evidence, Vlahovic said, the onychomycosis recurrence rate ranges from 6% to 40%. “That’s a wild number. We really have no idea what the true recurrence rate is, and that’s a problem.”

Vlahovic disclosed having been a consultant to and an investigator for Ortho Dermatologics and Sagis Diagnostics.

A version of this article appeared on Medscape.com.

The drug survival for adalimumab is significantly higher than that of infliximab in pediatric patients with hidradenitis suppurativa (HS), results from a small single-center study showed.

A previous study found that overall drug survival of adalimumab and infliximab in adults with HS at 12 and 24 months was 56.3% and 30.5%, and 58.3% and 48.6%, respectively. “They also found that older age, longer disease duration, higher body mass index (BMI), and surgery during treatment are associated with increased drug survival,” Robyn Guo, a third-year medical student at Duke University, Durham, North Carolina, told this news organization following the annual Symposium on Hidradenitis Suppurativa Advances, where the study was presented during an oral abstract session. “To our knowledge, the drug survival of biologic therapies in pediatric HS patients has not been previously investigated.”

Adalimumab and infliximab are tumor necrosis factor blockers approved for multiple indications; adalimumab is approved for treating moderate to severe HS in patients aged 12 years or older. Infliximab is not approved for HS but is used to treat the disease.

To determine the drug survival of adalimumab and infliximab in pediatric patients with HS and whether patient comorbidities and HS lesion location are associated with length of biologic survival in pediatric patients with HS, Guo and colleagues used Kaplan-Meier survival curves to calculate biologic survival at 12 and 24 months following biologic initiation and Cox proportional hazards regression to analyze potential factors associated with biologic survival. The study population included 49 pediatric patients in the adalimumab cohort and 11 in the infliximab cohort.

The researchers found that drug survival for adalimumab was 90.6% at 12 months (95% CI, 83.0%-98.8%) and 78.3% at 24 months (95% CI, 67.7%-90.6%), while drug survival for infliximab was 54.5% at 12 months (95% CI, 31.8%-93.6%) and 36.4% at 24 months, an overall difference that reached statistical significance (P = .0009). “Our data suggests that adalimumab survival is significantly higher than infliximab survival in pediatric HS patients,” Guo said.

On univariate Cox regression analysis, gluteal HS lesions were associated with shorter adalimumab survival, and obesity was associated with longer infliximab survival.

The researchers acknowledged certain limitations of their study, including the small sample size and that unadjusted Cox regression analysis did not account for baseline HS severity, biologic therapy dosing, and concomitant medication use. Also, there were patients in both cohorts who were not biologic-naive: Two in the adalimumab cohort were previously treated with infliximab, and five patients in the infliximab cohort were previously treated with adalimumab.

“We plan on conducting further analysis using adjusted Cox regression analysis to account for baseline disease severity measured by Hurley stage, BMI, medication dosing, and concomitant medication use,” Guo said.

The researchers reported having no financial disclosures.

A version of this article appeared on Medscape.com.

The drug survival for adalimumab is significantly higher than that of infliximab in pediatric patients with hidradenitis suppurativa (HS), results from a small single-center study showed.

A previous study found that overall drug survival of adalimumab and infliximab in adults with HS at 12 and 24 months was 56.3% and 30.5%, and 58.3% and 48.6%, respectively. “They also found that older age, longer disease duration, higher body mass index (BMI), and surgery during treatment are associated with increased drug survival,” Robyn Guo, a third-year medical student at Duke University, Durham, North Carolina, told this news organization following the annual Symposium on Hidradenitis Suppurativa Advances, where the study was presented during an oral abstract session. “To our knowledge, the drug survival of biologic therapies in pediatric HS patients has not been previously investigated.”

Adalimumab and infliximab are tumor necrosis factor blockers approved for multiple indications; adalimumab is approved for treating moderate to severe HS in patients aged 12 years or older. Infliximab is not approved for HS but is used to treat the disease.

To determine the drug survival of adalimumab and infliximab in pediatric patients with HS and whether patient comorbidities and HS lesion location are associated with length of biologic survival in pediatric patients with HS, Guo and colleagues used Kaplan-Meier survival curves to calculate biologic survival at 12 and 24 months following biologic initiation and Cox proportional hazards regression to analyze potential factors associated with biologic survival. The study population included 49 pediatric patients in the adalimumab cohort and 11 in the infliximab cohort.

The researchers found that drug survival for adalimumab was 90.6% at 12 months (95% CI, 83.0%-98.8%) and 78.3% at 24 months (95% CI, 67.7%-90.6%), while drug survival for infliximab was 54.5% at 12 months (95% CI, 31.8%-93.6%) and 36.4% at 24 months, an overall difference that reached statistical significance (P = .0009). “Our data suggests that adalimumab survival is significantly higher than infliximab survival in pediatric HS patients,” Guo said.

On univariate Cox regression analysis, gluteal HS lesions were associated with shorter adalimumab survival, and obesity was associated with longer infliximab survival.

The researchers acknowledged certain limitations of their study, including the small sample size and that unadjusted Cox regression analysis did not account for baseline HS severity, biologic therapy dosing, and concomitant medication use. Also, there were patients in both cohorts who were not biologic-naive: Two in the adalimumab cohort were previously treated with infliximab, and five patients in the infliximab cohort were previously treated with adalimumab.

“We plan on conducting further analysis using adjusted Cox regression analysis to account for baseline disease severity measured by Hurley stage, BMI, medication dosing, and concomitant medication use,” Guo said.

The researchers reported having no financial disclosures.

A version of this article appeared on Medscape.com.

The drug survival for adalimumab is significantly higher than that of infliximab in pediatric patients with hidradenitis suppurativa (HS), results from a small single-center study showed.

A previous study found that overall drug survival of adalimumab and infliximab in adults with HS at 12 and 24 months was 56.3% and 30.5%, and 58.3% and 48.6%, respectively. “They also found that older age, longer disease duration, higher body mass index (BMI), and surgery during treatment are associated with increased drug survival,” Robyn Guo, a third-year medical student at Duke University, Durham, North Carolina, told this news organization following the annual Symposium on Hidradenitis Suppurativa Advances, where the study was presented during an oral abstract session. “To our knowledge, the drug survival of biologic therapies in pediatric HS patients has not been previously investigated.”

Adalimumab and infliximab are tumor necrosis factor blockers approved for multiple indications; adalimumab is approved for treating moderate to severe HS in patients aged 12 years or older. Infliximab is not approved for HS but is used to treat the disease.

To determine the drug survival of adalimumab and infliximab in pediatric patients with HS and whether patient comorbidities and HS lesion location are associated with length of biologic survival in pediatric patients with HS, Guo and colleagues used Kaplan-Meier survival curves to calculate biologic survival at 12 and 24 months following biologic initiation and Cox proportional hazards regression to analyze potential factors associated with biologic survival. The study population included 49 pediatric patients in the adalimumab cohort and 11 in the infliximab cohort.

The researchers found that drug survival for adalimumab was 90.6% at 12 months (95% CI, 83.0%-98.8%) and 78.3% at 24 months (95% CI, 67.7%-90.6%), while drug survival for infliximab was 54.5% at 12 months (95% CI, 31.8%-93.6%) and 36.4% at 24 months, an overall difference that reached statistical significance (P = .0009). “Our data suggests that adalimumab survival is significantly higher than infliximab survival in pediatric HS patients,” Guo said.

On univariate Cox regression analysis, gluteal HS lesions were associated with shorter adalimumab survival, and obesity was associated with longer infliximab survival.

The researchers acknowledged certain limitations of their study, including the small sample size and that unadjusted Cox regression analysis did not account for baseline HS severity, biologic therapy dosing, and concomitant medication use. Also, there were patients in both cohorts who were not biologic-naive: Two in the adalimumab cohort were previously treated with infliximab, and five patients in the infliximab cohort were previously treated with adalimumab.

“We plan on conducting further analysis using adjusted Cox regression analysis to account for baseline disease severity measured by Hurley stage, BMI, medication dosing, and concomitant medication use,” Guo said.

The researchers reported having no financial disclosures.

A version of this article appeared on Medscape.com.