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MM: First CAR T-Cell Therapy to Exhibit OS Benefit
“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.
A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.
The significant OS benefit was sustained across all prespecified subgroups, she noted.
The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.
“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”
At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.
The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.
Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).
Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.
Safety at the latest update was consistent with prior analyses.
The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.
Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.
“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.
“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.
“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”
Toxicity is also a concern, he said.
“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.
For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.
“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”
Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
A version of this article first appeared on Medscape.com.
“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.
A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.
The significant OS benefit was sustained across all prespecified subgroups, she noted.
The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.
“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”
At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.
The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.
Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).
Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.
Safety at the latest update was consistent with prior analyses.
The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.
Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.
“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.
“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.
“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”
Toxicity is also a concern, he said.
“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.
For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.
“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”
Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
A version of this article first appeared on Medscape.com.
“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.
A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.
The significant OS benefit was sustained across all prespecified subgroups, she noted.
The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.
“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”
At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.
The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.
Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).
Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.
Safety at the latest update was consistent with prior analyses.
The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.
Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.
“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.
“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.
“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”
Toxicity is also a concern, he said.
“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.
For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.
“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”
Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
A version of this article first appeared on Medscape.com.
FROM IMS 2024
First Patient-Derived Stem Cell Transplant a Success in T1D
The chemically induced pluripotent stem cell–derived islets came from the somatic cells of the patient, a 25-year-old woman who had lived for 11 years with unstable T1D with less than 50% time-in-target glucose range despite intensive insulin therapy. By 1 year following the transplantation of the cells into her abdomen, her glucose levels were nearly 100% in range, and her hemoglobin A1c had come down from 7.4%-8.0% to nondiabetic range (~5%).
Of note, she was already under immunosuppression for a prior liver transplant and remained on it throughout. There were no major safety concerns.
“We are very encouraged by the positive clinical findings seen in this first patient using this combination of technologies. These findings set a strong foundation for further development of stem cell–derived islet transplantation as a feasible treatment modality for diabetes,” study authors Soon Yi Liew, PhD, and Hongkui Deng, PhD, both of Peking University Health Science Center, Beijing, China, told this news organization in an email. Dr. Deng, the lead author, is the director of the university’s Institute of Stem Cell Research.
The findings were published in Cell.
What’s New With This Approach?
The use of the patient’s own cells is one of several ways in which this approach differs from other ongoing efforts in treating T1D with pluripotent stem cell–derived islets, such as those of the companies Vertex and Sernova, Dr. Liew and Dr. Deng explained.
Another difference is that “the patient-specific stem cell–derived islets used in this study were produced from induced pluripotent stem cells generated using chemical reprogramming, which is a nontransgenic approach to inducing pluripotent stem cells from somatic cells that uses only small molecules, different from the conventional method of viral transduction of transcription factors. ... Employing small molecules as reprogramming factors provides a greater degree of control — small molecules have defined structures easily manufactured and standardized, are not genome integrating, and are cost effective,” Dr. Liew and Dr. Deng said.
A third difference, they noted, is the placement of the stem cell–derived islets underneath the abdominal anterior rectus sheath of the patient, as opposed to the more commonly used hepatic portal vein. In addition to better ease of visualization, prior evidence suggested that this approach could lead to an improved engraftment and graft function and could circumvent graft loss from blood-mediated inflammatory responses associated with the liver site.
Moreover, they added, “to our knowledge, the rapidity with which insulin-independence was achieved post transplantation of stem cell–derived islets, 75 days post-transplantation, is also a first.”
Immunosuppression Remains a Challenge
Asked to comment, David M. Harlan, MD, the William and Doris Krupp professor of medicine and codirector of the Diabetes Center of Excellence at the University of Massachusetts Chan Medical School, Worcester, told this news organization, “on the one hand, it seems like a great breakthrough that you could take each individual cells and use those to make islets, but ... that process takes a long time, is very, very expensive, and then the T1D recipient still needs to be immunosuppressed. From a business point of view, I just don’t see it as getting any legs.”
Dr. Harlan, who had been involved in the islet transplantation field for several decades, pointed out that the additional autoimmunity of T1D poses a challenge beyond that of the body’s immune reaction to foreign tissue. “Because transplants have been around since the 1950s, we know a lot about how to prevent allogeneic rejection, from one person to another, but we know very little about how to prevent autoimmunity, so that’s still a very difficult nut to crack. I actually think the major effort should be focused on making the beta cells more hardy [via genetic modification] as opposed to focusing on the immune system. And there’s a lot of data to support that now, and that’s what we’re working on.”
Indeed, Dr. Liew and Dr. Deng said, “New immunomodulatory strategies to address graft longevity without immunosuppression remain to be established and tested. With reports of therapeutic efficacy of stem cell–derived islet transplantation such as with our study, stem cell–derived therapy without need for immunosuppression would be a meaningful next step in the treatment of this disease.”
The team has now performed the same procedure in two more patients and will report their data “in due course.”
Dr. Liew had no disclosures. Dr. Deng is a scientific adviser at Hangzhou Reprogenix Bioscience. Two coauthors are employees of Hangzhou Reprogenix Bioscience. Another is a former employee of Hangzhou Reprogenix Bioscience and is now affiliated with the Hangzhou Institute of Medicine, Chinese Academy of Sciences. Four coauthors have patent applications related to this work. Dr. Harlan is chief scientific officer and cofounder of Stability Health. He had no other disclosures.
A version of this article first appeared on Medscape.com.
The chemically induced pluripotent stem cell–derived islets came from the somatic cells of the patient, a 25-year-old woman who had lived for 11 years with unstable T1D with less than 50% time-in-target glucose range despite intensive insulin therapy. By 1 year following the transplantation of the cells into her abdomen, her glucose levels were nearly 100% in range, and her hemoglobin A1c had come down from 7.4%-8.0% to nondiabetic range (~5%).
Of note, she was already under immunosuppression for a prior liver transplant and remained on it throughout. There were no major safety concerns.
“We are very encouraged by the positive clinical findings seen in this first patient using this combination of technologies. These findings set a strong foundation for further development of stem cell–derived islet transplantation as a feasible treatment modality for diabetes,” study authors Soon Yi Liew, PhD, and Hongkui Deng, PhD, both of Peking University Health Science Center, Beijing, China, told this news organization in an email. Dr. Deng, the lead author, is the director of the university’s Institute of Stem Cell Research.
The findings were published in Cell.
What’s New With This Approach?
The use of the patient’s own cells is one of several ways in which this approach differs from other ongoing efforts in treating T1D with pluripotent stem cell–derived islets, such as those of the companies Vertex and Sernova, Dr. Liew and Dr. Deng explained.
Another difference is that “the patient-specific stem cell–derived islets used in this study were produced from induced pluripotent stem cells generated using chemical reprogramming, which is a nontransgenic approach to inducing pluripotent stem cells from somatic cells that uses only small molecules, different from the conventional method of viral transduction of transcription factors. ... Employing small molecules as reprogramming factors provides a greater degree of control — small molecules have defined structures easily manufactured and standardized, are not genome integrating, and are cost effective,” Dr. Liew and Dr. Deng said.
A third difference, they noted, is the placement of the stem cell–derived islets underneath the abdominal anterior rectus sheath of the patient, as opposed to the more commonly used hepatic portal vein. In addition to better ease of visualization, prior evidence suggested that this approach could lead to an improved engraftment and graft function and could circumvent graft loss from blood-mediated inflammatory responses associated with the liver site.
Moreover, they added, “to our knowledge, the rapidity with which insulin-independence was achieved post transplantation of stem cell–derived islets, 75 days post-transplantation, is also a first.”
Immunosuppression Remains a Challenge
Asked to comment, David M. Harlan, MD, the William and Doris Krupp professor of medicine and codirector of the Diabetes Center of Excellence at the University of Massachusetts Chan Medical School, Worcester, told this news organization, “on the one hand, it seems like a great breakthrough that you could take each individual cells and use those to make islets, but ... that process takes a long time, is very, very expensive, and then the T1D recipient still needs to be immunosuppressed. From a business point of view, I just don’t see it as getting any legs.”
Dr. Harlan, who had been involved in the islet transplantation field for several decades, pointed out that the additional autoimmunity of T1D poses a challenge beyond that of the body’s immune reaction to foreign tissue. “Because transplants have been around since the 1950s, we know a lot about how to prevent allogeneic rejection, from one person to another, but we know very little about how to prevent autoimmunity, so that’s still a very difficult nut to crack. I actually think the major effort should be focused on making the beta cells more hardy [via genetic modification] as opposed to focusing on the immune system. And there’s a lot of data to support that now, and that’s what we’re working on.”
Indeed, Dr. Liew and Dr. Deng said, “New immunomodulatory strategies to address graft longevity without immunosuppression remain to be established and tested. With reports of therapeutic efficacy of stem cell–derived islet transplantation such as with our study, stem cell–derived therapy without need for immunosuppression would be a meaningful next step in the treatment of this disease.”
The team has now performed the same procedure in two more patients and will report their data “in due course.”
Dr. Liew had no disclosures. Dr. Deng is a scientific adviser at Hangzhou Reprogenix Bioscience. Two coauthors are employees of Hangzhou Reprogenix Bioscience. Another is a former employee of Hangzhou Reprogenix Bioscience and is now affiliated with the Hangzhou Institute of Medicine, Chinese Academy of Sciences. Four coauthors have patent applications related to this work. Dr. Harlan is chief scientific officer and cofounder of Stability Health. He had no other disclosures.
A version of this article first appeared on Medscape.com.
The chemically induced pluripotent stem cell–derived islets came from the somatic cells of the patient, a 25-year-old woman who had lived for 11 years with unstable T1D with less than 50% time-in-target glucose range despite intensive insulin therapy. By 1 year following the transplantation of the cells into her abdomen, her glucose levels were nearly 100% in range, and her hemoglobin A1c had come down from 7.4%-8.0% to nondiabetic range (~5%).
Of note, she was already under immunosuppression for a prior liver transplant and remained on it throughout. There were no major safety concerns.
“We are very encouraged by the positive clinical findings seen in this first patient using this combination of technologies. These findings set a strong foundation for further development of stem cell–derived islet transplantation as a feasible treatment modality for diabetes,” study authors Soon Yi Liew, PhD, and Hongkui Deng, PhD, both of Peking University Health Science Center, Beijing, China, told this news organization in an email. Dr. Deng, the lead author, is the director of the university’s Institute of Stem Cell Research.
The findings were published in Cell.
What’s New With This Approach?
The use of the patient’s own cells is one of several ways in which this approach differs from other ongoing efforts in treating T1D with pluripotent stem cell–derived islets, such as those of the companies Vertex and Sernova, Dr. Liew and Dr. Deng explained.
Another difference is that “the patient-specific stem cell–derived islets used in this study were produced from induced pluripotent stem cells generated using chemical reprogramming, which is a nontransgenic approach to inducing pluripotent stem cells from somatic cells that uses only small molecules, different from the conventional method of viral transduction of transcription factors. ... Employing small molecules as reprogramming factors provides a greater degree of control — small molecules have defined structures easily manufactured and standardized, are not genome integrating, and are cost effective,” Dr. Liew and Dr. Deng said.
A third difference, they noted, is the placement of the stem cell–derived islets underneath the abdominal anterior rectus sheath of the patient, as opposed to the more commonly used hepatic portal vein. In addition to better ease of visualization, prior evidence suggested that this approach could lead to an improved engraftment and graft function and could circumvent graft loss from blood-mediated inflammatory responses associated with the liver site.
Moreover, they added, “to our knowledge, the rapidity with which insulin-independence was achieved post transplantation of stem cell–derived islets, 75 days post-transplantation, is also a first.”
Immunosuppression Remains a Challenge
Asked to comment, David M. Harlan, MD, the William and Doris Krupp professor of medicine and codirector of the Diabetes Center of Excellence at the University of Massachusetts Chan Medical School, Worcester, told this news organization, “on the one hand, it seems like a great breakthrough that you could take each individual cells and use those to make islets, but ... that process takes a long time, is very, very expensive, and then the T1D recipient still needs to be immunosuppressed. From a business point of view, I just don’t see it as getting any legs.”
Dr. Harlan, who had been involved in the islet transplantation field for several decades, pointed out that the additional autoimmunity of T1D poses a challenge beyond that of the body’s immune reaction to foreign tissue. “Because transplants have been around since the 1950s, we know a lot about how to prevent allogeneic rejection, from one person to another, but we know very little about how to prevent autoimmunity, so that’s still a very difficult nut to crack. I actually think the major effort should be focused on making the beta cells more hardy [via genetic modification] as opposed to focusing on the immune system. And there’s a lot of data to support that now, and that’s what we’re working on.”
Indeed, Dr. Liew and Dr. Deng said, “New immunomodulatory strategies to address graft longevity without immunosuppression remain to be established and tested. With reports of therapeutic efficacy of stem cell–derived islet transplantation such as with our study, stem cell–derived therapy without need for immunosuppression would be a meaningful next step in the treatment of this disease.”
The team has now performed the same procedure in two more patients and will report their data “in due course.”
Dr. Liew had no disclosures. Dr. Deng is a scientific adviser at Hangzhou Reprogenix Bioscience. Two coauthors are employees of Hangzhou Reprogenix Bioscience. Another is a former employee of Hangzhou Reprogenix Bioscience and is now affiliated with the Hangzhou Institute of Medicine, Chinese Academy of Sciences. Four coauthors have patent applications related to this work. Dr. Harlan is chief scientific officer and cofounder of Stability Health. He had no other disclosures.
A version of this article first appeared on Medscape.com.
FROM CELL
Daratumumab Quadruplet Supported Transplant-Ineligible MM
“CEPHEUS is the first phase 3 daratumumab trial with a primary endpoint of MRD negativity,” said first author Saad Z. Usmani, MD, of Memorial Sloan Kettering Cancer Center, New York City, in presenting late-breaking findings at the annual meeting of the International Myeloma Society in Rio de Janeiro, Brazil in late September.
“We found that adding daratumumab to VRd significantly improved depth and duration of response,” Dr. Usmani said. “[The quadruplet regimen] has the potential to improve clinical outcomes for transplant-ineligible or transplant-deferred patients with newly diagnosed MM who can tolerate bortezomib.”
For newly diagnosed patients with MM who are not eligible for a stem cell transplant, the triplet MAIA regimen of daratumumab, lenalidomide, and dexamethasone is a recommended standard of care, having shown a median overall survival of 7.5 years.
However, for those who are transplant eligible, the PERSEUS regimen of D-VRd followed by daratumumab/lenalidomide maintenance, has shown significant progress-free survival benefits compared with the standard of care.
For the ongoing, multicenter, open-label CEPHEUS study, Dr. Usmani and his colleagues investigated the efficacy of the quadruplet D-VRd regimen compared with VRd alone among newly diagnosed patients who are transplant-ineligible or deferred (not planned as initial therapy).
In the trial, 395 adult patients with transplant-ineligible or transplant-deferred newly diagnosed MM all were initially treated with eight 21-day cycles of VRd, followed by 28-day cycles of lenalidomide until disease progression.
The patients were then randomized to VRd either with (n = 197) or without (n = 198) subcutaneous daratumumab.
Those receiving daratumumab received the subcutaneous therapy weekly in cycles 1 and 2, every 3 weeks in cycles 3-8, and every 4 weeks in cycles 9 or more, until disease progression.
The patients had a median age of 70 years; 28.1% had International Staging System stage III disease, and 13.2% had high-risk cytogenetics.
For the primary endpoint, with a median follow-up of 58.7 months, those in the daratumumab group had a significantly higher rate of being MRD-negative (60.9%) than the VRd-only group (39.4%; odds ratio [OR], 2.37; P < .0001).
Likewise, progression-free survival (PFS) was significantly improved with the daratumumab regimen vs VRd (hazard ratio [HR], 0.57; P = .0005).
A median PFS was not reached for daratumumab plus VRd, compared with 52.6 months for the VRd group, while estimated 54-month PFS rates were 68.1% vs 49.5%, respectively.
A complete response or better was achieved among 81.2% in the daratumumab regimen vs 61.6% with VRd alone (P < .0001) and a sustained rate of MRD-negativity was achieved in 48.7% vs 26.3%, respectively (P < .0001).
There was a trend of overall survival in favor of daratumumab plus VRd (HR, 0.85), with an HR of 0.69 in a sensitivity analysis adjusting for deaths related to COVID-19.
Patients in the daratumumab group had a substantially longer median duration of treatment (56.3 months) than the VRd-only group (34.3 months), with the most common reason for treatment discontinuation being disease progression.
The benefit of daratumumab was generally consistent across the study’s prespecified subgroups, and the relative dose intensity of VRd was not affected by combination with daratumumab.
In terms of safety, treatment-emergent adverse events (TEAEs) were consistent with the known profile of daratumumab and VRd, with grade 5 TEAEs comparable between the two groups after adjusting for treatment exposure.
Quality of life, as measured by EORTC QLQ-C30 score, was improved in both arms over time, with no detriment related to treatment with daratumumab.
Of note, frail patients were not included in the trial. Asked in the Q and A why they were excluded, Dr. Usmani explained that “all of these options are wonderful for our patients, and we are entering a phase where quadruplet therapies will become a mainstay for majority of patients.
“But we have to be careful as we think about not overtreating patients or giving too many side effects of therapies, and that’s why it made sense for us to exclude the frail patients.”
Along those lines, he noted that a key concern in the CEPHEUS trial was tolerance of bortezomib.
“Peripheral sensory neuropathy tends to occur in about half of the patients receiving bortezomib, and about half of that number is grade 2 or higher,” he noted in an interview.
“In some patients, the symptoms do not completely resolve. [Therefore], in transplant-ineligible patients, quadruple regimens may be more relevant for the fit or intermediate-fit patients.”
He concluded that “the CEPHEUS trial compliments the MAIA regimen in supporting a daratumumab-based quadruplet or triplet standard-of-care option across transplant-ineligible patients and those deferring transplant.”
Commenting on the study, Philippe Moreau, MD, who is president of the IMS, noted that “the CEPHEUS study is important because [determining] the best treatment upfront for elderly patients is very important.”
“We need confirmation of the very good results achieved with the IMROZ trial, which showed an estimated 5-year PFS of 63.2%, said Dr. Moreau, professor of clinical hematology and head of the translational research program in hematology and oncology at the University Hospital of Nantes, France.
“If we can achieve the same results, we will have the confirmation that quadruplet is probably here to stay,” Dr. Moreau said.
Dr. Usmani disclosed relationships with Abbvie, Amgen, BioPharma, Bristol Myers Squibb, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineOx, and Takeda.
A version of this article first appeared on Medscape.com.
“CEPHEUS is the first phase 3 daratumumab trial with a primary endpoint of MRD negativity,” said first author Saad Z. Usmani, MD, of Memorial Sloan Kettering Cancer Center, New York City, in presenting late-breaking findings at the annual meeting of the International Myeloma Society in Rio de Janeiro, Brazil in late September.
“We found that adding daratumumab to VRd significantly improved depth and duration of response,” Dr. Usmani said. “[The quadruplet regimen] has the potential to improve clinical outcomes for transplant-ineligible or transplant-deferred patients with newly diagnosed MM who can tolerate bortezomib.”
For newly diagnosed patients with MM who are not eligible for a stem cell transplant, the triplet MAIA regimen of daratumumab, lenalidomide, and dexamethasone is a recommended standard of care, having shown a median overall survival of 7.5 years.
However, for those who are transplant eligible, the PERSEUS regimen of D-VRd followed by daratumumab/lenalidomide maintenance, has shown significant progress-free survival benefits compared with the standard of care.
For the ongoing, multicenter, open-label CEPHEUS study, Dr. Usmani and his colleagues investigated the efficacy of the quadruplet D-VRd regimen compared with VRd alone among newly diagnosed patients who are transplant-ineligible or deferred (not planned as initial therapy).
In the trial, 395 adult patients with transplant-ineligible or transplant-deferred newly diagnosed MM all were initially treated with eight 21-day cycles of VRd, followed by 28-day cycles of lenalidomide until disease progression.
The patients were then randomized to VRd either with (n = 197) or without (n = 198) subcutaneous daratumumab.
Those receiving daratumumab received the subcutaneous therapy weekly in cycles 1 and 2, every 3 weeks in cycles 3-8, and every 4 weeks in cycles 9 or more, until disease progression.
The patients had a median age of 70 years; 28.1% had International Staging System stage III disease, and 13.2% had high-risk cytogenetics.
For the primary endpoint, with a median follow-up of 58.7 months, those in the daratumumab group had a significantly higher rate of being MRD-negative (60.9%) than the VRd-only group (39.4%; odds ratio [OR], 2.37; P < .0001).
Likewise, progression-free survival (PFS) was significantly improved with the daratumumab regimen vs VRd (hazard ratio [HR], 0.57; P = .0005).
A median PFS was not reached for daratumumab plus VRd, compared with 52.6 months for the VRd group, while estimated 54-month PFS rates were 68.1% vs 49.5%, respectively.
A complete response or better was achieved among 81.2% in the daratumumab regimen vs 61.6% with VRd alone (P < .0001) and a sustained rate of MRD-negativity was achieved in 48.7% vs 26.3%, respectively (P < .0001).
There was a trend of overall survival in favor of daratumumab plus VRd (HR, 0.85), with an HR of 0.69 in a sensitivity analysis adjusting for deaths related to COVID-19.
Patients in the daratumumab group had a substantially longer median duration of treatment (56.3 months) than the VRd-only group (34.3 months), with the most common reason for treatment discontinuation being disease progression.
The benefit of daratumumab was generally consistent across the study’s prespecified subgroups, and the relative dose intensity of VRd was not affected by combination with daratumumab.
In terms of safety, treatment-emergent adverse events (TEAEs) were consistent with the known profile of daratumumab and VRd, with grade 5 TEAEs comparable between the two groups after adjusting for treatment exposure.
Quality of life, as measured by EORTC QLQ-C30 score, was improved in both arms over time, with no detriment related to treatment with daratumumab.
Of note, frail patients were not included in the trial. Asked in the Q and A why they were excluded, Dr. Usmani explained that “all of these options are wonderful for our patients, and we are entering a phase where quadruplet therapies will become a mainstay for majority of patients.
“But we have to be careful as we think about not overtreating patients or giving too many side effects of therapies, and that’s why it made sense for us to exclude the frail patients.”
Along those lines, he noted that a key concern in the CEPHEUS trial was tolerance of bortezomib.
“Peripheral sensory neuropathy tends to occur in about half of the patients receiving bortezomib, and about half of that number is grade 2 or higher,” he noted in an interview.
“In some patients, the symptoms do not completely resolve. [Therefore], in transplant-ineligible patients, quadruple regimens may be more relevant for the fit or intermediate-fit patients.”
He concluded that “the CEPHEUS trial compliments the MAIA regimen in supporting a daratumumab-based quadruplet or triplet standard-of-care option across transplant-ineligible patients and those deferring transplant.”
Commenting on the study, Philippe Moreau, MD, who is president of the IMS, noted that “the CEPHEUS study is important because [determining] the best treatment upfront for elderly patients is very important.”
“We need confirmation of the very good results achieved with the IMROZ trial, which showed an estimated 5-year PFS of 63.2%, said Dr. Moreau, professor of clinical hematology and head of the translational research program in hematology and oncology at the University Hospital of Nantes, France.
“If we can achieve the same results, we will have the confirmation that quadruplet is probably here to stay,” Dr. Moreau said.
Dr. Usmani disclosed relationships with Abbvie, Amgen, BioPharma, Bristol Myers Squibb, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineOx, and Takeda.
A version of this article first appeared on Medscape.com.
“CEPHEUS is the first phase 3 daratumumab trial with a primary endpoint of MRD negativity,” said first author Saad Z. Usmani, MD, of Memorial Sloan Kettering Cancer Center, New York City, in presenting late-breaking findings at the annual meeting of the International Myeloma Society in Rio de Janeiro, Brazil in late September.
“We found that adding daratumumab to VRd significantly improved depth and duration of response,” Dr. Usmani said. “[The quadruplet regimen] has the potential to improve clinical outcomes for transplant-ineligible or transplant-deferred patients with newly diagnosed MM who can tolerate bortezomib.”
For newly diagnosed patients with MM who are not eligible for a stem cell transplant, the triplet MAIA regimen of daratumumab, lenalidomide, and dexamethasone is a recommended standard of care, having shown a median overall survival of 7.5 years.
However, for those who are transplant eligible, the PERSEUS regimen of D-VRd followed by daratumumab/lenalidomide maintenance, has shown significant progress-free survival benefits compared with the standard of care.
For the ongoing, multicenter, open-label CEPHEUS study, Dr. Usmani and his colleagues investigated the efficacy of the quadruplet D-VRd regimen compared with VRd alone among newly diagnosed patients who are transplant-ineligible or deferred (not planned as initial therapy).
In the trial, 395 adult patients with transplant-ineligible or transplant-deferred newly diagnosed MM all were initially treated with eight 21-day cycles of VRd, followed by 28-day cycles of lenalidomide until disease progression.
The patients were then randomized to VRd either with (n = 197) or without (n = 198) subcutaneous daratumumab.
Those receiving daratumumab received the subcutaneous therapy weekly in cycles 1 and 2, every 3 weeks in cycles 3-8, and every 4 weeks in cycles 9 or more, until disease progression.
The patients had a median age of 70 years; 28.1% had International Staging System stage III disease, and 13.2% had high-risk cytogenetics.
For the primary endpoint, with a median follow-up of 58.7 months, those in the daratumumab group had a significantly higher rate of being MRD-negative (60.9%) than the VRd-only group (39.4%; odds ratio [OR], 2.37; P < .0001).
Likewise, progression-free survival (PFS) was significantly improved with the daratumumab regimen vs VRd (hazard ratio [HR], 0.57; P = .0005).
A median PFS was not reached for daratumumab plus VRd, compared with 52.6 months for the VRd group, while estimated 54-month PFS rates were 68.1% vs 49.5%, respectively.
A complete response or better was achieved among 81.2% in the daratumumab regimen vs 61.6% with VRd alone (P < .0001) and a sustained rate of MRD-negativity was achieved in 48.7% vs 26.3%, respectively (P < .0001).
There was a trend of overall survival in favor of daratumumab plus VRd (HR, 0.85), with an HR of 0.69 in a sensitivity analysis adjusting for deaths related to COVID-19.
Patients in the daratumumab group had a substantially longer median duration of treatment (56.3 months) than the VRd-only group (34.3 months), with the most common reason for treatment discontinuation being disease progression.
The benefit of daratumumab was generally consistent across the study’s prespecified subgroups, and the relative dose intensity of VRd was not affected by combination with daratumumab.
In terms of safety, treatment-emergent adverse events (TEAEs) were consistent with the known profile of daratumumab and VRd, with grade 5 TEAEs comparable between the two groups after adjusting for treatment exposure.
Quality of life, as measured by EORTC QLQ-C30 score, was improved in both arms over time, with no detriment related to treatment with daratumumab.
Of note, frail patients were not included in the trial. Asked in the Q and A why they were excluded, Dr. Usmani explained that “all of these options are wonderful for our patients, and we are entering a phase where quadruplet therapies will become a mainstay for majority of patients.
“But we have to be careful as we think about not overtreating patients or giving too many side effects of therapies, and that’s why it made sense for us to exclude the frail patients.”
Along those lines, he noted that a key concern in the CEPHEUS trial was tolerance of bortezomib.
“Peripheral sensory neuropathy tends to occur in about half of the patients receiving bortezomib, and about half of that number is grade 2 or higher,” he noted in an interview.
“In some patients, the symptoms do not completely resolve. [Therefore], in transplant-ineligible patients, quadruple regimens may be more relevant for the fit or intermediate-fit patients.”
He concluded that “the CEPHEUS trial compliments the MAIA regimen in supporting a daratumumab-based quadruplet or triplet standard-of-care option across transplant-ineligible patients and those deferring transplant.”
Commenting on the study, Philippe Moreau, MD, who is president of the IMS, noted that “the CEPHEUS study is important because [determining] the best treatment upfront for elderly patients is very important.”
“We need confirmation of the very good results achieved with the IMROZ trial, which showed an estimated 5-year PFS of 63.2%, said Dr. Moreau, professor of clinical hematology and head of the translational research program in hematology and oncology at the University Hospital of Nantes, France.
“If we can achieve the same results, we will have the confirmation that quadruplet is probably here to stay,” Dr. Moreau said.
Dr. Usmani disclosed relationships with Abbvie, Amgen, BioPharma, Bristol Myers Squibb, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineOx, and Takeda.
A version of this article first appeared on Medscape.com.
FROM IMS 2024
Dermatomyositis Cancer Screening Guidelines Get Real-World Validation
Newly issued guidelines for cancer screening in patients with dermatomyositis had 100% sensitivity in a single institution’s cohort, though most of the cancers found would have been detected with standard cancer screenings recommended for the general population, according to a research letter published in JAMA Dermatology.
“These early results emphasize the continued need to refine risk assessment and cancer screening for patients with dermatomyositis while balancing resource use and outcomes,” concluded Caroline J. Stone and her colleagues at the Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Patients with dermatomyositis have approximately a 4.7 times greater risk for cancer than those without it, according to a 2016 meta-analysis. Despite the well-established link between cancer and dermatomyositis, cancer in people with idiopathic inflammatory myopathies is commonly diagnosed at a later stage and is the leading cause of death in people with these conditions.
Guidelines First Presented in 2022 and Published in 2023
A wide variability in screening practices eventually led the International Myositis Assessment & Clinical Studies Group (IMACS) to present the first evidence-based and consensus-based guidelines for cancer screening of patients with idiopathic inflammatory myopathies, including those with dermatomyositis, at the 2022 annual meeting of the American College of Rheumatology and publish them in 2023 in Nature Reviews Rheumatology. The guidelines advise low-risk patients to undergo basic cancer screening with routine blood and urine studies, liver function tests, plain chest radiography, and age- and sex-appropriate cancer screening.
Intermediate- and high-risk patients are recommended to undergo enhanced screening that can include mammography, Pap tests, endoscopy/colonoscopy, pelvic and transvaginal ultrasonography, prostate-specific antigen or cancer antigen 125 blood tests, fecal occult blood tests, and CT of the neck, thorax, abdomen, and pelvis.
But because the guidelines are new, little evidence exists regarding their validation in real-world cohorts. Researchers, therefore, assessed the IMACS guidelines in 370 patients, aged 18-80 years, who visited the University of Pennsylvania rheumatology-dermatology specialty clinic between July 2008 and January 2024. All participants had dermatomyositis and at least 3 years of follow-up and were an average 48 years old. The vast majority were women (87%) and White participants (89%).
Most (68.6%) had myositis-specific autoantibody test results, one of the factors included in the guidelines for determining whether the patient should be classified as low, intermediate, or high risk. Other factors for risk stratification included myositis subtype, age at disease onset, and clinical features. About half (49.2%) had classic dermatomyositis, 42.4% had amyopathic dermatomyositis, 3.8% had juvenile dermatomyositis, 3.2% had hypomyopathic dermatomyositis, 0.8% had antisynthetase syndrome, and 0.5% had immune-mediated necrotizing myopathy.
Just over half the patients (54%) were classified as high risk, while 37.3% were classified as intermediate risk and 8.9% as low risk using the guidelines. Among the 18 patients (4.9%) with paraneoplastic dermatomyositis, 15 were classified as high risk and 3 as intermediate risk.
Of the patients diagnosed with cancer, 55% of cases were diagnosed about a year before their dermatomyositis diagnosis. In three patients, symptoms “suggestive of cancer at the time of dermatomyositis diagnosis, including lymphadenopathy and unexplained weight loss,” led to diagnostic testing that found an underlying cancer.
In the eight patients diagnosed with cancer after their dermatomyositis diagnosis, 75% of the cancers were identified during the first year of follow-up and 25% in the second year. Five were identified based on basic cancer screening and three on enhanced screening.
A total of 11 patients (3%) developed intravenous contrast allergies, and no other adverse events were reported to be associated with cancer screening, but the study was not designed to capture other types of adverse screening effects, such as cost, quality of life, or risk from radiation exposure.
The most common neoplasm identified was breast cancer, found in nine (50%) of the patients using mammography. Two patients had lung cancer identified with chest radiography and two had ovarian cancer identified with abdominal radiography and CT. The remaining five patients included one each with bladder cancer, papillary thyroid cancer, renal cell carcinoma, non-Hodgkin lymphoma, and adenocarcinoma with unknown primary.
The sensitivity of the guidelines in detecting cancer related to dermatomyositis was 100%, though the authors noted that the “IMACS risk-stratification scheme may overestimate cancer risk and encourage enhanced screening protocols of unclear benefit.” Most of the cancers found after dermatomyositis diagnosis were detected with routine age- and sex-related screening that already falls under basic cancer screening recommendations for the general population. Nonetheless, 90% of the participants fell into the intermediate- and high-risk groups, warranting a more comprehensive and costly enhanced screening protocol.
Will the Guidelines Lead to Overscreening?
The 4.9% cancer prevalence is considerably lower than the typical 15%-25% prevalence among patients with dermatomyositis, but the findings, regardless, suggest the guidelines will lead to overscreening, wrote Andrea D. Maderal, MD, University of Miami Miller School of Medicine in Florida, and Alisa Femia, MD, New York University Grossman School of Medicine, New York City, in an accompanying editorial. Given that the median age in patients with cancer in the study was 58 years — 18 years older than the age cutoff for high-risk criteria — one way to refine the guidelines may be to increase the age for the high-risk category, they suggested.
“While these guidelines led to many ultimately unnecessary screening tests based on currently recommended designations of intermediate-risk and high-risk patients, these guidelines reflect a more conservative approach to screening than was previously performed,” Dr. Maderal and Dr. Femia wrote.
Jeff Gehlhausen, MD, PhD, an assistant professor of dermatology at Yale School of Medicine, New Haven, Connecticut, said he is not concerned about overscreening in patients, however, and is “very enthusiastic” about the findings.
“Patients are very anxious for good reason,” given the typical cancer prevalence of 25% in this population, he said in an interview. “I think therein lies the challenge — with that risk, what is ‘enough’ screening?” Yet this “incredibly impressive” study “provides real insights into the applicability of the IMACS screenings to our dermatomyositis management,” including relevance to his own patients. “Their findings are instructive for how to better evaluate these patients in a more mindful fashion,” he said, and they are particularly welcome, given how widely variable practice has historically been before the guidelines were issued.
“This question has been an outstanding one for decades, and nearly every doctor has a different answer,” Dr. Gehlhausen said. “The introduction of the guidelines alone are now much more actionable with this study, and that’s why it’s such an important one for our community.”
Benedict Wu, DO, PhD, director of Inpatient Dermatology and an assistant professor at Montefiore Einstein and a member of the Montefiore Einstein Comprehensive Cancer Center in New York City, similarly regarded the findings as reassuring, though he was surprised at the low prevalence of cancer in the patients.
“The most reassuring finding was that the detection of most malignancies was possible by using routine age- and sex-related screening combined with basic cancer screening,” Wu said in an interview. “Basic cancer screening can reduce costs while keeping patients safe.”
He also found it reassuring that all the paraneoplastic dermatomyositis was in intermediate- or high-risk patients, and while he does not see the IMACS guidelines as overestimating cancer risk, he does think “the risk stratification and recommended screening tests could be revised to be less ‘aggressive.’ ”
The overall low rate of cancer in the group “calls into question the need for stringent and annual cancer screening,” he said. “In this large cohort of patients, the fact that malignancy was detected within 2 years of dermatomyositis diagnosis will help guide us with long-term screening recommendations.”
Despite the study’s small size and single-center design, the demographics of the patients nearly represents exactly what is found in the United States more broadly, Wu noted. He also drew attention to how many patients lacked the myositis antibody profile performed, and he agreed with the authors that more extensive and prospective studies need to be conducted. He also emphasized the need to keep in mind that “the primary goal of dermatomyositis management should focus on controlling/reducing the disease burden.”
The research was funded by the National Institutes of Health and the US Department of Veterans Affairs. The authors had no disclosures. Dr. Maderal reported personal fees from argenx. No disclosures were noted for Dr. Gehlhausen and Dr. Wu.
A version of this article appeared on Medscape.com.
Newly issued guidelines for cancer screening in patients with dermatomyositis had 100% sensitivity in a single institution’s cohort, though most of the cancers found would have been detected with standard cancer screenings recommended for the general population, according to a research letter published in JAMA Dermatology.
“These early results emphasize the continued need to refine risk assessment and cancer screening for patients with dermatomyositis while balancing resource use and outcomes,” concluded Caroline J. Stone and her colleagues at the Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Patients with dermatomyositis have approximately a 4.7 times greater risk for cancer than those without it, according to a 2016 meta-analysis. Despite the well-established link between cancer and dermatomyositis, cancer in people with idiopathic inflammatory myopathies is commonly diagnosed at a later stage and is the leading cause of death in people with these conditions.
Guidelines First Presented in 2022 and Published in 2023
A wide variability in screening practices eventually led the International Myositis Assessment & Clinical Studies Group (IMACS) to present the first evidence-based and consensus-based guidelines for cancer screening of patients with idiopathic inflammatory myopathies, including those with dermatomyositis, at the 2022 annual meeting of the American College of Rheumatology and publish them in 2023 in Nature Reviews Rheumatology. The guidelines advise low-risk patients to undergo basic cancer screening with routine blood and urine studies, liver function tests, plain chest radiography, and age- and sex-appropriate cancer screening.
Intermediate- and high-risk patients are recommended to undergo enhanced screening that can include mammography, Pap tests, endoscopy/colonoscopy, pelvic and transvaginal ultrasonography, prostate-specific antigen or cancer antigen 125 blood tests, fecal occult blood tests, and CT of the neck, thorax, abdomen, and pelvis.
But because the guidelines are new, little evidence exists regarding their validation in real-world cohorts. Researchers, therefore, assessed the IMACS guidelines in 370 patients, aged 18-80 years, who visited the University of Pennsylvania rheumatology-dermatology specialty clinic between July 2008 and January 2024. All participants had dermatomyositis and at least 3 years of follow-up and were an average 48 years old. The vast majority were women (87%) and White participants (89%).
Most (68.6%) had myositis-specific autoantibody test results, one of the factors included in the guidelines for determining whether the patient should be classified as low, intermediate, or high risk. Other factors for risk stratification included myositis subtype, age at disease onset, and clinical features. About half (49.2%) had classic dermatomyositis, 42.4% had amyopathic dermatomyositis, 3.8% had juvenile dermatomyositis, 3.2% had hypomyopathic dermatomyositis, 0.8% had antisynthetase syndrome, and 0.5% had immune-mediated necrotizing myopathy.
Just over half the patients (54%) were classified as high risk, while 37.3% were classified as intermediate risk and 8.9% as low risk using the guidelines. Among the 18 patients (4.9%) with paraneoplastic dermatomyositis, 15 were classified as high risk and 3 as intermediate risk.
Of the patients diagnosed with cancer, 55% of cases were diagnosed about a year before their dermatomyositis diagnosis. In three patients, symptoms “suggestive of cancer at the time of dermatomyositis diagnosis, including lymphadenopathy and unexplained weight loss,” led to diagnostic testing that found an underlying cancer.
In the eight patients diagnosed with cancer after their dermatomyositis diagnosis, 75% of the cancers were identified during the first year of follow-up and 25% in the second year. Five were identified based on basic cancer screening and three on enhanced screening.
A total of 11 patients (3%) developed intravenous contrast allergies, and no other adverse events were reported to be associated with cancer screening, but the study was not designed to capture other types of adverse screening effects, such as cost, quality of life, or risk from radiation exposure.
The most common neoplasm identified was breast cancer, found in nine (50%) of the patients using mammography. Two patients had lung cancer identified with chest radiography and two had ovarian cancer identified with abdominal radiography and CT. The remaining five patients included one each with bladder cancer, papillary thyroid cancer, renal cell carcinoma, non-Hodgkin lymphoma, and adenocarcinoma with unknown primary.
The sensitivity of the guidelines in detecting cancer related to dermatomyositis was 100%, though the authors noted that the “IMACS risk-stratification scheme may overestimate cancer risk and encourage enhanced screening protocols of unclear benefit.” Most of the cancers found after dermatomyositis diagnosis were detected with routine age- and sex-related screening that already falls under basic cancer screening recommendations for the general population. Nonetheless, 90% of the participants fell into the intermediate- and high-risk groups, warranting a more comprehensive and costly enhanced screening protocol.
Will the Guidelines Lead to Overscreening?
The 4.9% cancer prevalence is considerably lower than the typical 15%-25% prevalence among patients with dermatomyositis, but the findings, regardless, suggest the guidelines will lead to overscreening, wrote Andrea D. Maderal, MD, University of Miami Miller School of Medicine in Florida, and Alisa Femia, MD, New York University Grossman School of Medicine, New York City, in an accompanying editorial. Given that the median age in patients with cancer in the study was 58 years — 18 years older than the age cutoff for high-risk criteria — one way to refine the guidelines may be to increase the age for the high-risk category, they suggested.
“While these guidelines led to many ultimately unnecessary screening tests based on currently recommended designations of intermediate-risk and high-risk patients, these guidelines reflect a more conservative approach to screening than was previously performed,” Dr. Maderal and Dr. Femia wrote.
Jeff Gehlhausen, MD, PhD, an assistant professor of dermatology at Yale School of Medicine, New Haven, Connecticut, said he is not concerned about overscreening in patients, however, and is “very enthusiastic” about the findings.
“Patients are very anxious for good reason,” given the typical cancer prevalence of 25% in this population, he said in an interview. “I think therein lies the challenge — with that risk, what is ‘enough’ screening?” Yet this “incredibly impressive” study “provides real insights into the applicability of the IMACS screenings to our dermatomyositis management,” including relevance to his own patients. “Their findings are instructive for how to better evaluate these patients in a more mindful fashion,” he said, and they are particularly welcome, given how widely variable practice has historically been before the guidelines were issued.
“This question has been an outstanding one for decades, and nearly every doctor has a different answer,” Dr. Gehlhausen said. “The introduction of the guidelines alone are now much more actionable with this study, and that’s why it’s such an important one for our community.”
Benedict Wu, DO, PhD, director of Inpatient Dermatology and an assistant professor at Montefiore Einstein and a member of the Montefiore Einstein Comprehensive Cancer Center in New York City, similarly regarded the findings as reassuring, though he was surprised at the low prevalence of cancer in the patients.
“The most reassuring finding was that the detection of most malignancies was possible by using routine age- and sex-related screening combined with basic cancer screening,” Wu said in an interview. “Basic cancer screening can reduce costs while keeping patients safe.”
He also found it reassuring that all the paraneoplastic dermatomyositis was in intermediate- or high-risk patients, and while he does not see the IMACS guidelines as overestimating cancer risk, he does think “the risk stratification and recommended screening tests could be revised to be less ‘aggressive.’ ”
The overall low rate of cancer in the group “calls into question the need for stringent and annual cancer screening,” he said. “In this large cohort of patients, the fact that malignancy was detected within 2 years of dermatomyositis diagnosis will help guide us with long-term screening recommendations.”
Despite the study’s small size and single-center design, the demographics of the patients nearly represents exactly what is found in the United States more broadly, Wu noted. He also drew attention to how many patients lacked the myositis antibody profile performed, and he agreed with the authors that more extensive and prospective studies need to be conducted. He also emphasized the need to keep in mind that “the primary goal of dermatomyositis management should focus on controlling/reducing the disease burden.”
The research was funded by the National Institutes of Health and the US Department of Veterans Affairs. The authors had no disclosures. Dr. Maderal reported personal fees from argenx. No disclosures were noted for Dr. Gehlhausen and Dr. Wu.
A version of this article appeared on Medscape.com.
Newly issued guidelines for cancer screening in patients with dermatomyositis had 100% sensitivity in a single institution’s cohort, though most of the cancers found would have been detected with standard cancer screenings recommended for the general population, according to a research letter published in JAMA Dermatology.
“These early results emphasize the continued need to refine risk assessment and cancer screening for patients with dermatomyositis while balancing resource use and outcomes,” concluded Caroline J. Stone and her colleagues at the Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Patients with dermatomyositis have approximately a 4.7 times greater risk for cancer than those without it, according to a 2016 meta-analysis. Despite the well-established link between cancer and dermatomyositis, cancer in people with idiopathic inflammatory myopathies is commonly diagnosed at a later stage and is the leading cause of death in people with these conditions.
Guidelines First Presented in 2022 and Published in 2023
A wide variability in screening practices eventually led the International Myositis Assessment & Clinical Studies Group (IMACS) to present the first evidence-based and consensus-based guidelines for cancer screening of patients with idiopathic inflammatory myopathies, including those with dermatomyositis, at the 2022 annual meeting of the American College of Rheumatology and publish them in 2023 in Nature Reviews Rheumatology. The guidelines advise low-risk patients to undergo basic cancer screening with routine blood and urine studies, liver function tests, plain chest radiography, and age- and sex-appropriate cancer screening.
Intermediate- and high-risk patients are recommended to undergo enhanced screening that can include mammography, Pap tests, endoscopy/colonoscopy, pelvic and transvaginal ultrasonography, prostate-specific antigen or cancer antigen 125 blood tests, fecal occult blood tests, and CT of the neck, thorax, abdomen, and pelvis.
But because the guidelines are new, little evidence exists regarding their validation in real-world cohorts. Researchers, therefore, assessed the IMACS guidelines in 370 patients, aged 18-80 years, who visited the University of Pennsylvania rheumatology-dermatology specialty clinic between July 2008 and January 2024. All participants had dermatomyositis and at least 3 years of follow-up and were an average 48 years old. The vast majority were women (87%) and White participants (89%).
Most (68.6%) had myositis-specific autoantibody test results, one of the factors included in the guidelines for determining whether the patient should be classified as low, intermediate, or high risk. Other factors for risk stratification included myositis subtype, age at disease onset, and clinical features. About half (49.2%) had classic dermatomyositis, 42.4% had amyopathic dermatomyositis, 3.8% had juvenile dermatomyositis, 3.2% had hypomyopathic dermatomyositis, 0.8% had antisynthetase syndrome, and 0.5% had immune-mediated necrotizing myopathy.
Just over half the patients (54%) were classified as high risk, while 37.3% were classified as intermediate risk and 8.9% as low risk using the guidelines. Among the 18 patients (4.9%) with paraneoplastic dermatomyositis, 15 were classified as high risk and 3 as intermediate risk.
Of the patients diagnosed with cancer, 55% of cases were diagnosed about a year before their dermatomyositis diagnosis. In three patients, symptoms “suggestive of cancer at the time of dermatomyositis diagnosis, including lymphadenopathy and unexplained weight loss,” led to diagnostic testing that found an underlying cancer.
In the eight patients diagnosed with cancer after their dermatomyositis diagnosis, 75% of the cancers were identified during the first year of follow-up and 25% in the second year. Five were identified based on basic cancer screening and three on enhanced screening.
A total of 11 patients (3%) developed intravenous contrast allergies, and no other adverse events were reported to be associated with cancer screening, but the study was not designed to capture other types of adverse screening effects, such as cost, quality of life, or risk from radiation exposure.
The most common neoplasm identified was breast cancer, found in nine (50%) of the patients using mammography. Two patients had lung cancer identified with chest radiography and two had ovarian cancer identified with abdominal radiography and CT. The remaining five patients included one each with bladder cancer, papillary thyroid cancer, renal cell carcinoma, non-Hodgkin lymphoma, and adenocarcinoma with unknown primary.
The sensitivity of the guidelines in detecting cancer related to dermatomyositis was 100%, though the authors noted that the “IMACS risk-stratification scheme may overestimate cancer risk and encourage enhanced screening protocols of unclear benefit.” Most of the cancers found after dermatomyositis diagnosis were detected with routine age- and sex-related screening that already falls under basic cancer screening recommendations for the general population. Nonetheless, 90% of the participants fell into the intermediate- and high-risk groups, warranting a more comprehensive and costly enhanced screening protocol.
Will the Guidelines Lead to Overscreening?
The 4.9% cancer prevalence is considerably lower than the typical 15%-25% prevalence among patients with dermatomyositis, but the findings, regardless, suggest the guidelines will lead to overscreening, wrote Andrea D. Maderal, MD, University of Miami Miller School of Medicine in Florida, and Alisa Femia, MD, New York University Grossman School of Medicine, New York City, in an accompanying editorial. Given that the median age in patients with cancer in the study was 58 years — 18 years older than the age cutoff for high-risk criteria — one way to refine the guidelines may be to increase the age for the high-risk category, they suggested.
“While these guidelines led to many ultimately unnecessary screening tests based on currently recommended designations of intermediate-risk and high-risk patients, these guidelines reflect a more conservative approach to screening than was previously performed,” Dr. Maderal and Dr. Femia wrote.
Jeff Gehlhausen, MD, PhD, an assistant professor of dermatology at Yale School of Medicine, New Haven, Connecticut, said he is not concerned about overscreening in patients, however, and is “very enthusiastic” about the findings.
“Patients are very anxious for good reason,” given the typical cancer prevalence of 25% in this population, he said in an interview. “I think therein lies the challenge — with that risk, what is ‘enough’ screening?” Yet this “incredibly impressive” study “provides real insights into the applicability of the IMACS screenings to our dermatomyositis management,” including relevance to his own patients. “Their findings are instructive for how to better evaluate these patients in a more mindful fashion,” he said, and they are particularly welcome, given how widely variable practice has historically been before the guidelines were issued.
“This question has been an outstanding one for decades, and nearly every doctor has a different answer,” Dr. Gehlhausen said. “The introduction of the guidelines alone are now much more actionable with this study, and that’s why it’s such an important one for our community.”
Benedict Wu, DO, PhD, director of Inpatient Dermatology and an assistant professor at Montefiore Einstein and a member of the Montefiore Einstein Comprehensive Cancer Center in New York City, similarly regarded the findings as reassuring, though he was surprised at the low prevalence of cancer in the patients.
“The most reassuring finding was that the detection of most malignancies was possible by using routine age- and sex-related screening combined with basic cancer screening,” Wu said in an interview. “Basic cancer screening can reduce costs while keeping patients safe.”
He also found it reassuring that all the paraneoplastic dermatomyositis was in intermediate- or high-risk patients, and while he does not see the IMACS guidelines as overestimating cancer risk, he does think “the risk stratification and recommended screening tests could be revised to be less ‘aggressive.’ ”
The overall low rate of cancer in the group “calls into question the need for stringent and annual cancer screening,” he said. “In this large cohort of patients, the fact that malignancy was detected within 2 years of dermatomyositis diagnosis will help guide us with long-term screening recommendations.”
Despite the study’s small size and single-center design, the demographics of the patients nearly represents exactly what is found in the United States more broadly, Wu noted. He also drew attention to how many patients lacked the myositis antibody profile performed, and he agreed with the authors that more extensive and prospective studies need to be conducted. He also emphasized the need to keep in mind that “the primary goal of dermatomyositis management should focus on controlling/reducing the disease burden.”
The research was funded by the National Institutes of Health and the US Department of Veterans Affairs. The authors had no disclosures. Dr. Maderal reported personal fees from argenx. No disclosures were noted for Dr. Gehlhausen and Dr. Wu.
A version of this article appeared on Medscape.com.
FROM JAMA DERMATOLOGY
Study Supports Efficacy of Home-Based Phototherapy for Psoriasis
TOPLINE:
study.
METHODOLOGY:
- The pragmatic, investigator-initiated, open-label, noninferiority, randomized trial compared the effectiveness of 12 weeks of treatment with narrow-band ultraviolet B phototherapy administered at home (n = 393) vs at the doctor’s office (n = 390).
- Overall, 783 patients with plaque or guttate psoriasis (mean age, 48 years; 48% women) were enrolled at 42 academic and private clinical dermatology practices in the United States from March 1, 2019, to December 4, 2023, and were followed up through June 2024. At baseline, the mean Physician Global Assessment (PGA) and the mean Dermatology Life Quality Index (DLQI) scores were 2.7 and 12.2, respectively.
- The two co-primary endpoints were a PGA score ≤ 1 indicating clear or almost clear skin and a DLQI score ≤ 5.
TAKEAWAY:
- At 12 weeks, a PGA score ≤ 1 was achieved in 32.8% of patients using home-based phototherapy and in 25.6% of those who received office-based phototherapy (P < .001).
- At 12 weeks, a DLQI score ≤ 5 was achieved in 52.4% and 33.6% of home- and office-treated patients, respectively (P < .001).
- Similar benefits were seen across all Fitzpatrick skin types.
- A higher percentage of patients were adherent to home-based (51.4%) vs office-based (15.9%) phototherapy (P < .001).
IN PRACTICE:
“These data support the use of home phototherapy as a first-line treatment option for psoriasis,” and “efforts are needed to make home and office phototherapy more available to patients,” said the study’s lead author.
SOURCE:
Joel M. Gelfand, MD, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, presented the findings at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis meeting during the annual meeting of the European Academy of Dermatology and Venereology, with simultaneous publication in JAMA Dermatology.
LIMITATIONS:
This was an open-label trial and because of its pragmatic design, outcome data were missing. The cost of the home-based phototherapy equipment used in the study was $6040.88, which was mostly covered by Medicare, but direct costs to patients may have varied depending on their insurance plan.
DISCLOSURES:
The Patient-Centered Outcomes Research Institute funded the study. Daavlin provided and shipped machines for home-based phototherapy to patients at no cost. Dr. Gelfand disclosed serving as a consultant for AbbVie, Artax, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, and other companies. The full list of author disclosures can be found in the published study.
A version of this article first appeared on Medscape.com.
TOPLINE:
study.
METHODOLOGY:
- The pragmatic, investigator-initiated, open-label, noninferiority, randomized trial compared the effectiveness of 12 weeks of treatment with narrow-band ultraviolet B phototherapy administered at home (n = 393) vs at the doctor’s office (n = 390).
- Overall, 783 patients with plaque or guttate psoriasis (mean age, 48 years; 48% women) were enrolled at 42 academic and private clinical dermatology practices in the United States from March 1, 2019, to December 4, 2023, and were followed up through June 2024. At baseline, the mean Physician Global Assessment (PGA) and the mean Dermatology Life Quality Index (DLQI) scores were 2.7 and 12.2, respectively.
- The two co-primary endpoints were a PGA score ≤ 1 indicating clear or almost clear skin and a DLQI score ≤ 5.
TAKEAWAY:
- At 12 weeks, a PGA score ≤ 1 was achieved in 32.8% of patients using home-based phototherapy and in 25.6% of those who received office-based phototherapy (P < .001).
- At 12 weeks, a DLQI score ≤ 5 was achieved in 52.4% and 33.6% of home- and office-treated patients, respectively (P < .001).
- Similar benefits were seen across all Fitzpatrick skin types.
- A higher percentage of patients were adherent to home-based (51.4%) vs office-based (15.9%) phototherapy (P < .001).
IN PRACTICE:
“These data support the use of home phototherapy as a first-line treatment option for psoriasis,” and “efforts are needed to make home and office phototherapy more available to patients,” said the study’s lead author.
SOURCE:
Joel M. Gelfand, MD, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, presented the findings at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis meeting during the annual meeting of the European Academy of Dermatology and Venereology, with simultaneous publication in JAMA Dermatology.
LIMITATIONS:
This was an open-label trial and because of its pragmatic design, outcome data were missing. The cost of the home-based phototherapy equipment used in the study was $6040.88, which was mostly covered by Medicare, but direct costs to patients may have varied depending on their insurance plan.
DISCLOSURES:
The Patient-Centered Outcomes Research Institute funded the study. Daavlin provided and shipped machines for home-based phototherapy to patients at no cost. Dr. Gelfand disclosed serving as a consultant for AbbVie, Artax, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, and other companies. The full list of author disclosures can be found in the published study.
A version of this article first appeared on Medscape.com.
TOPLINE:
study.
METHODOLOGY:
- The pragmatic, investigator-initiated, open-label, noninferiority, randomized trial compared the effectiveness of 12 weeks of treatment with narrow-band ultraviolet B phototherapy administered at home (n = 393) vs at the doctor’s office (n = 390).
- Overall, 783 patients with plaque or guttate psoriasis (mean age, 48 years; 48% women) were enrolled at 42 academic and private clinical dermatology practices in the United States from March 1, 2019, to December 4, 2023, and were followed up through June 2024. At baseline, the mean Physician Global Assessment (PGA) and the mean Dermatology Life Quality Index (DLQI) scores were 2.7 and 12.2, respectively.
- The two co-primary endpoints were a PGA score ≤ 1 indicating clear or almost clear skin and a DLQI score ≤ 5.
TAKEAWAY:
- At 12 weeks, a PGA score ≤ 1 was achieved in 32.8% of patients using home-based phototherapy and in 25.6% of those who received office-based phototherapy (P < .001).
- At 12 weeks, a DLQI score ≤ 5 was achieved in 52.4% and 33.6% of home- and office-treated patients, respectively (P < .001).
- Similar benefits were seen across all Fitzpatrick skin types.
- A higher percentage of patients were adherent to home-based (51.4%) vs office-based (15.9%) phototherapy (P < .001).
IN PRACTICE:
“These data support the use of home phototherapy as a first-line treatment option for psoriasis,” and “efforts are needed to make home and office phototherapy more available to patients,” said the study’s lead author.
SOURCE:
Joel M. Gelfand, MD, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, presented the findings at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis meeting during the annual meeting of the European Academy of Dermatology and Venereology, with simultaneous publication in JAMA Dermatology.
LIMITATIONS:
This was an open-label trial and because of its pragmatic design, outcome data were missing. The cost of the home-based phototherapy equipment used in the study was $6040.88, which was mostly covered by Medicare, but direct costs to patients may have varied depending on their insurance plan.
DISCLOSURES:
The Patient-Centered Outcomes Research Institute funded the study. Daavlin provided and shipped machines for home-based phototherapy to patients at no cost. Dr. Gelfand disclosed serving as a consultant for AbbVie, Artax, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, and other companies. The full list of author disclosures can be found in the published study.
A version of this article first appeared on Medscape.com.
Autonomy Versus Safety in Cognitive Impairment Decision-Making
DUBLIN – As healthcare systems across Europe deal with an increasing prevalence of cognitive impairment, family doctors are emerging as key players in assessing and supporting patients’ decision-making capacities.
This was a central theme at the 29th WONCA Europe Conference, where the European Young Family Doctors Movement (EYFDM) presented insights from a project conducted across Europe, involving young general practitioners who participated in workshops held in multiple countries.
“Family doctors are the linchpin in these decisions,” said Alina Zidaru, MD, from the Irish College of Physicians, Dublin. “They understand the patient’s history, build long-term relationships, and are best positioned to ensure that decisions reflect the patient’s values, not just what the law or the family might say.”
Dr. Zidaru and her colleague, Nick Mamo, MD, member of EYFDM in Glasgow, Scotland, emphasized the central role family doctors play in ensuring that patient rights and preferences are respected, regardless of their cognitive state. They are often the first to identify cognitive impairments and must carefully navigate the legal and ethical landscape of decision-making support.
“Often, we focus too much on avoiding harm and overlook the principle of autonomy,” said Dr. Mamo. “But it’s essential to give patients the right to make their own decisions, even when those decisions might seem unwise to us.”
The Case of Jay
Dr. Zidaru said: “We’ve conducted workshops in Brussels, Vienna, and Sydney, focusing on how to build habits that support patients. We presented real-life cases, like Jay, a 43-year-old man with trisomy and a moderate intellectual disability who must decide whether to undergo surgery for a hernia. The most significant challenge was ensuring continuity of care and respecting his autonomy, despite cognitive limitations.”
Jay’s case illustrates the complex ethical dilemmas faced by family doctors when balancing autonomy with patient safety. In many cases, cognitive impairments raise concerns about whether a patient can make decisions independently.
During the session, the audience was asked to share their thoughts on the case and to indicate whether they would allow Jay to make his own decision, and if they felt confident in assessing his cognitive capacity. The responses revealed a range of mixed feelings.
Legal and Cultural Variations Across Europe
The session also explored how different European countries approach decision-making for cognitively impaired individuals. A clear divide exists between nations that give family members automatic decision-making rights and those that require legal appointments.
In the United Kingdom, the Mental Capacity Act 2005 presumes capacity unless proven otherwise. Family doctors can assess patients’ decision-making abilities using any validated tool they find suitable. They should also aim to ensure that decisions are made in the patient’s best interests if they lack capacity. Family members only have legal authority if appointed through formal means, such as a lasting power of attorney.
In Spain and Italy, functional assessments are performed when patients retain decision-making authority in areas where they demonstrate competence. Legal guardianship can be appointed by the courts, sometimes limited to specific areas, but it is intended to support rather than replace the patient’s autonomy.
In France and Portugal, guardianship may be implemented in specific domains, but the patient’s ability to participate in decisions is always prioritized.
In Turkey, according to Turkish general practitioners in the audience, the courts and close family members often share the decision-making responsibility.
Dr. Zidaru added that Ireland’s Assisted Decision-Making (Capacity) Act 2015 introduced significant changes to how cognitive impairment is managed there. “Ireland adopted a standardized functional test of capacity, used by any doctor. A person can still make decisions as long as they understand, retain, and weigh the information needed to make that choice. If their capacity diminishes, a decision-making assistant, co–decision-maker, or representative can be appointed, but the patient’s will and preferences always come first.”
Family Doctors, a Growing Responsibility
“It’s not just about the legal framework: it’s about cultural awareness and early communication,” added Dr. Mamo. “We have to ask ourselves: Do patients have the right to make bad decisions? And how do we, as family doctors, respect that while still ensuring their safety?”
The session concluded with a discussion on how the role of family doctors in decision-making for cognitively impaired patients will evolve as populations age and the incidence of conditions like dementia increases. The workload is rising, and the need for clear, consistent guidelines is critical.
“Family doctors will continue to play a central role in managing these challenges,” Dr. Zidaru emphasized. “But we need more resources, more education, and more support to ensure we can respect patient autonomy without compromising their well-being.”
A version of this article first appeared on Medscape.com.
DUBLIN – As healthcare systems across Europe deal with an increasing prevalence of cognitive impairment, family doctors are emerging as key players in assessing and supporting patients’ decision-making capacities.
This was a central theme at the 29th WONCA Europe Conference, where the European Young Family Doctors Movement (EYFDM) presented insights from a project conducted across Europe, involving young general practitioners who participated in workshops held in multiple countries.
“Family doctors are the linchpin in these decisions,” said Alina Zidaru, MD, from the Irish College of Physicians, Dublin. “They understand the patient’s history, build long-term relationships, and are best positioned to ensure that decisions reflect the patient’s values, not just what the law or the family might say.”
Dr. Zidaru and her colleague, Nick Mamo, MD, member of EYFDM in Glasgow, Scotland, emphasized the central role family doctors play in ensuring that patient rights and preferences are respected, regardless of their cognitive state. They are often the first to identify cognitive impairments and must carefully navigate the legal and ethical landscape of decision-making support.
“Often, we focus too much on avoiding harm and overlook the principle of autonomy,” said Dr. Mamo. “But it’s essential to give patients the right to make their own decisions, even when those decisions might seem unwise to us.”
The Case of Jay
Dr. Zidaru said: “We’ve conducted workshops in Brussels, Vienna, and Sydney, focusing on how to build habits that support patients. We presented real-life cases, like Jay, a 43-year-old man with trisomy and a moderate intellectual disability who must decide whether to undergo surgery for a hernia. The most significant challenge was ensuring continuity of care and respecting his autonomy, despite cognitive limitations.”
Jay’s case illustrates the complex ethical dilemmas faced by family doctors when balancing autonomy with patient safety. In many cases, cognitive impairments raise concerns about whether a patient can make decisions independently.
During the session, the audience was asked to share their thoughts on the case and to indicate whether they would allow Jay to make his own decision, and if they felt confident in assessing his cognitive capacity. The responses revealed a range of mixed feelings.
Legal and Cultural Variations Across Europe
The session also explored how different European countries approach decision-making for cognitively impaired individuals. A clear divide exists between nations that give family members automatic decision-making rights and those that require legal appointments.
In the United Kingdom, the Mental Capacity Act 2005 presumes capacity unless proven otherwise. Family doctors can assess patients’ decision-making abilities using any validated tool they find suitable. They should also aim to ensure that decisions are made in the patient’s best interests if they lack capacity. Family members only have legal authority if appointed through formal means, such as a lasting power of attorney.
In Spain and Italy, functional assessments are performed when patients retain decision-making authority in areas where they demonstrate competence. Legal guardianship can be appointed by the courts, sometimes limited to specific areas, but it is intended to support rather than replace the patient’s autonomy.
In France and Portugal, guardianship may be implemented in specific domains, but the patient’s ability to participate in decisions is always prioritized.
In Turkey, according to Turkish general practitioners in the audience, the courts and close family members often share the decision-making responsibility.
Dr. Zidaru added that Ireland’s Assisted Decision-Making (Capacity) Act 2015 introduced significant changes to how cognitive impairment is managed there. “Ireland adopted a standardized functional test of capacity, used by any doctor. A person can still make decisions as long as they understand, retain, and weigh the information needed to make that choice. If their capacity diminishes, a decision-making assistant, co–decision-maker, or representative can be appointed, but the patient’s will and preferences always come first.”
Family Doctors, a Growing Responsibility
“It’s not just about the legal framework: it’s about cultural awareness and early communication,” added Dr. Mamo. “We have to ask ourselves: Do patients have the right to make bad decisions? And how do we, as family doctors, respect that while still ensuring their safety?”
The session concluded with a discussion on how the role of family doctors in decision-making for cognitively impaired patients will evolve as populations age and the incidence of conditions like dementia increases. The workload is rising, and the need for clear, consistent guidelines is critical.
“Family doctors will continue to play a central role in managing these challenges,” Dr. Zidaru emphasized. “But we need more resources, more education, and more support to ensure we can respect patient autonomy without compromising their well-being.”
A version of this article first appeared on Medscape.com.
DUBLIN – As healthcare systems across Europe deal with an increasing prevalence of cognitive impairment, family doctors are emerging as key players in assessing and supporting patients’ decision-making capacities.
This was a central theme at the 29th WONCA Europe Conference, where the European Young Family Doctors Movement (EYFDM) presented insights from a project conducted across Europe, involving young general practitioners who participated in workshops held in multiple countries.
“Family doctors are the linchpin in these decisions,” said Alina Zidaru, MD, from the Irish College of Physicians, Dublin. “They understand the patient’s history, build long-term relationships, and are best positioned to ensure that decisions reflect the patient’s values, not just what the law or the family might say.”
Dr. Zidaru and her colleague, Nick Mamo, MD, member of EYFDM in Glasgow, Scotland, emphasized the central role family doctors play in ensuring that patient rights and preferences are respected, regardless of their cognitive state. They are often the first to identify cognitive impairments and must carefully navigate the legal and ethical landscape of decision-making support.
“Often, we focus too much on avoiding harm and overlook the principle of autonomy,” said Dr. Mamo. “But it’s essential to give patients the right to make their own decisions, even when those decisions might seem unwise to us.”
The Case of Jay
Dr. Zidaru said: “We’ve conducted workshops in Brussels, Vienna, and Sydney, focusing on how to build habits that support patients. We presented real-life cases, like Jay, a 43-year-old man with trisomy and a moderate intellectual disability who must decide whether to undergo surgery for a hernia. The most significant challenge was ensuring continuity of care and respecting his autonomy, despite cognitive limitations.”
Jay’s case illustrates the complex ethical dilemmas faced by family doctors when balancing autonomy with patient safety. In many cases, cognitive impairments raise concerns about whether a patient can make decisions independently.
During the session, the audience was asked to share their thoughts on the case and to indicate whether they would allow Jay to make his own decision, and if they felt confident in assessing his cognitive capacity. The responses revealed a range of mixed feelings.
Legal and Cultural Variations Across Europe
The session also explored how different European countries approach decision-making for cognitively impaired individuals. A clear divide exists between nations that give family members automatic decision-making rights and those that require legal appointments.
In the United Kingdom, the Mental Capacity Act 2005 presumes capacity unless proven otherwise. Family doctors can assess patients’ decision-making abilities using any validated tool they find suitable. They should also aim to ensure that decisions are made in the patient’s best interests if they lack capacity. Family members only have legal authority if appointed through formal means, such as a lasting power of attorney.
In Spain and Italy, functional assessments are performed when patients retain decision-making authority in areas where they demonstrate competence. Legal guardianship can be appointed by the courts, sometimes limited to specific areas, but it is intended to support rather than replace the patient’s autonomy.
In France and Portugal, guardianship may be implemented in specific domains, but the patient’s ability to participate in decisions is always prioritized.
In Turkey, according to Turkish general practitioners in the audience, the courts and close family members often share the decision-making responsibility.
Dr. Zidaru added that Ireland’s Assisted Decision-Making (Capacity) Act 2015 introduced significant changes to how cognitive impairment is managed there. “Ireland adopted a standardized functional test of capacity, used by any doctor. A person can still make decisions as long as they understand, retain, and weigh the information needed to make that choice. If their capacity diminishes, a decision-making assistant, co–decision-maker, or representative can be appointed, but the patient’s will and preferences always come first.”
Family Doctors, a Growing Responsibility
“It’s not just about the legal framework: it’s about cultural awareness and early communication,” added Dr. Mamo. “We have to ask ourselves: Do patients have the right to make bad decisions? And how do we, as family doctors, respect that while still ensuring their safety?”
The session concluded with a discussion on how the role of family doctors in decision-making for cognitively impaired patients will evolve as populations age and the incidence of conditions like dementia increases. The workload is rising, and the need for clear, consistent guidelines is critical.
“Family doctors will continue to play a central role in managing these challenges,” Dr. Zidaru emphasized. “But we need more resources, more education, and more support to ensure we can respect patient autonomy without compromising their well-being.”
A version of this article first appeared on Medscape.com.
FROM WONCA EUROPEAN CONFERENCE 2024
Millennial Clinicians Face Pay Disparities by Specialty, Other Factors
Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.
Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.
The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.
“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.
The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.
“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”
Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.
Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.
Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.
“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”
Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.
Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.
Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.
A version of this article first appeared on Medscape.com.
Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.
Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.
The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.
“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.
The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.
“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”
Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.
Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.
Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.
“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”
Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.
Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.
Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.
A version of this article first appeared on Medscape.com.
Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.
Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.
The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.
“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.
The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.
“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”
Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.
Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.
Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.
“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”
Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.
Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.
Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.
A version of this article first appeared on Medscape.com.
Severe Autoimmune Diseases Linked to Premature Ovarian Insufficiency
TOPLINE:
Women with premature ovarian insufficiency (POI) have a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis and a 2- to 3-fold increased risk for these diseases after diagnosis.
METHODOLOGY:
- Researchers conducted a population-based registry study including 3972 women diagnosed with spontaneous POI between 1988 and 2017.
- A total of 15,708 female population controls matched by age and municipality of residence were included for comparison.
- Autoimmune disease diagnoses were evaluated from childhood until the end of 2017 using the Hospital Discharge Registry.
- Women with a history of cancer or bilateral oophorectomy were excluded from the study.
TAKEAWAY:
- Women with POI had a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis compared to controls (odds ratio [OR], 2.6; 95% CI, 2.2-3.1).
- The prevalence of specific autoimmune diseases such as polyglandular autoimmune diseases (OR, 25.8; 95% CI, 9.0-74.1) and Addison disease (OR, 22.9; 95% CI, 7.9-66.1) was significantly higher in women with POI.
- The standardized incidence ratios for being diagnosed with a severe autoimmune disease after POI diagnosis was 2.8 (95% CI, 2.3-3.4) during the first 3 years, decreasing to 1.3 (95% CI, 1.1-1.6) after 12 years.
- No significant difference was found in the prevalence of diabetes type 1 and ankylosing spondylitis between women with POI and the reference cohort.
IN PRACTICE:
“The study results strengthen the hypothesis that autoimmune mechanisms play an important role in the pathogenesis of POI. Future studies should focus on the immunological mechanism of POI from preventative and curative perspectives,” wrote the authors of the study.
SOURCE:
The study was led by Susanna M. Savukoski, Oulu University Hospital in Finland. It was published online in Human Reproduction.
LIMITATIONS:
The study included only autoimmune disorders diagnosed in specialized health care, which may underestimate the overall prevalence of autoimmune disorders in women with POI. Additionally, the study did not account for confounders such as body mass index and smoking, which are associated with the risk for autoimmune disease and POI.
DISCLOSURES:
Ms. Savukoski received grants from the Finnish Menopause Society, the Finnish Medical Foundation, and the Juho Vainio Foundation. 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:
Women with premature ovarian insufficiency (POI) have a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis and a 2- to 3-fold increased risk for these diseases after diagnosis.
METHODOLOGY:
- Researchers conducted a population-based registry study including 3972 women diagnosed with spontaneous POI between 1988 and 2017.
- A total of 15,708 female population controls matched by age and municipality of residence were included for comparison.
- Autoimmune disease diagnoses were evaluated from childhood until the end of 2017 using the Hospital Discharge Registry.
- Women with a history of cancer or bilateral oophorectomy were excluded from the study.
TAKEAWAY:
- Women with POI had a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis compared to controls (odds ratio [OR], 2.6; 95% CI, 2.2-3.1).
- The prevalence of specific autoimmune diseases such as polyglandular autoimmune diseases (OR, 25.8; 95% CI, 9.0-74.1) and Addison disease (OR, 22.9; 95% CI, 7.9-66.1) was significantly higher in women with POI.
- The standardized incidence ratios for being diagnosed with a severe autoimmune disease after POI diagnosis was 2.8 (95% CI, 2.3-3.4) during the first 3 years, decreasing to 1.3 (95% CI, 1.1-1.6) after 12 years.
- No significant difference was found in the prevalence of diabetes type 1 and ankylosing spondylitis between women with POI and the reference cohort.
IN PRACTICE:
“The study results strengthen the hypothesis that autoimmune mechanisms play an important role in the pathogenesis of POI. Future studies should focus on the immunological mechanism of POI from preventative and curative perspectives,” wrote the authors of the study.
SOURCE:
The study was led by Susanna M. Savukoski, Oulu University Hospital in Finland. It was published online in Human Reproduction.
LIMITATIONS:
The study included only autoimmune disorders diagnosed in specialized health care, which may underestimate the overall prevalence of autoimmune disorders in women with POI. Additionally, the study did not account for confounders such as body mass index and smoking, which are associated with the risk for autoimmune disease and POI.
DISCLOSURES:
Ms. Savukoski received grants from the Finnish Menopause Society, the Finnish Medical Foundation, and the Juho Vainio Foundation. 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:
Women with premature ovarian insufficiency (POI) have a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis and a 2- to 3-fold increased risk for these diseases after diagnosis.
METHODOLOGY:
- Researchers conducted a population-based registry study including 3972 women diagnosed with spontaneous POI between 1988 and 2017.
- A total of 15,708 female population controls matched by age and municipality of residence were included for comparison.
- Autoimmune disease diagnoses were evaluated from childhood until the end of 2017 using the Hospital Discharge Registry.
- Women with a history of cancer or bilateral oophorectomy were excluded from the study.
TAKEAWAY:
- Women with POI had a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis compared to controls (odds ratio [OR], 2.6; 95% CI, 2.2-3.1).
- The prevalence of specific autoimmune diseases such as polyglandular autoimmune diseases (OR, 25.8; 95% CI, 9.0-74.1) and Addison disease (OR, 22.9; 95% CI, 7.9-66.1) was significantly higher in women with POI.
- The standardized incidence ratios for being diagnosed with a severe autoimmune disease after POI diagnosis was 2.8 (95% CI, 2.3-3.4) during the first 3 years, decreasing to 1.3 (95% CI, 1.1-1.6) after 12 years.
- No significant difference was found in the prevalence of diabetes type 1 and ankylosing spondylitis between women with POI and the reference cohort.
IN PRACTICE:
“The study results strengthen the hypothesis that autoimmune mechanisms play an important role in the pathogenesis of POI. Future studies should focus on the immunological mechanism of POI from preventative and curative perspectives,” wrote the authors of the study.
SOURCE:
The study was led by Susanna M. Savukoski, Oulu University Hospital in Finland. It was published online in Human Reproduction.
LIMITATIONS:
The study included only autoimmune disorders diagnosed in specialized health care, which may underestimate the overall prevalence of autoimmune disorders in women with POI. Additionally, the study did not account for confounders such as body mass index and smoking, which are associated with the risk for autoimmune disease and POI.
DISCLOSURES:
Ms. Savukoski received grants from the Finnish Menopause Society, the Finnish Medical Foundation, and the Juho Vainio Foundation. 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.
In Crohn’s Disease, Early Anti-TNF Levels May be Crucial
“The relationship between drug concentrations, immunogenicity and clinical response is likely to be multidirectional; as an observational study, we cannot definitively show the low drug levels are causative. However, our data are consistent with those from elsewhere and confirm the importance of achieving good drug levels to maximize the chances of success with anti-TNF therapy,” said Nicholas Kennedy, MBBS, PhD, a consultant gastroenterologist at Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom, and coauthor of the study published in The Lancet Gastroenterology & Hepatology .
“We also showed that adequate dosing of thiopurines was needed to prevent immunogenicity, along the lines typically used to treat Crohn’s disease rather than the lower doses sometimes proposed,” he added.
The findings come from the Personalized Anti-TNF Therapy in Crohn’s Disease (PANTS) study conducted in the UK, which included 955 patients treated with infliximab and 655 treated with adalimumab between March 2014 and September 2017. The participants were 6 years or older, the median age was 32.5 years, and 51% were female.
The latest findings come from a 2-year extension of the original 1-year PANTS study, published in 2019, which found that low drug concentrations predicted anti-TNF treatment failure — a result likely attributable in part to immunogenicity, since low-drug concentrations predicted the presence of anti-drug antibodies, and anti-drug antibodies in turn predicted low drug concentrations, according to Miguel Regueiro, MD, AGAF, chief of the Digestive Diseases Institute and a professor of medicine at the Cleveland Clinic, Ohio.
“This is one of the more important studies looking at the longitudinal care of patients with Crohn’s disease on infliximab and adalimumab,” said Dr. Regueiro, who was not involved with the study.
The extension study found that anti-drug antibodies and undetectable drug levels were associated with both treatment without an accompanying immunomodulator and carriage of the HLA-DQA1*05 genetic risk factor, though the latter was true only for treatment with infliximab.
Dr. Regueiro noted that the study demonstrates that “getting it right in induction is probably the most important part” of treating Crohn’s disease.
“Getting patients in remission early has probably a long-term prediction [of treatment success]. I do think that is practice changing. My practice has changed over the years, largely based on the initial PANTS study. I am measuring infliximab and adalimumab levels after induction, and I am using that number to decide if I dose intensify the drug, or if I’ve hit that sweet spot,” said Dr. Regueiro.
The study highlights a debate among clinicians, about whether higher drug levels are associated with remission because of the effects of higher doses, or because patients who respond have reduced leakiness in the gut, leading to greater retention of protein therapeutics.
“What the study clearly says is that the drug [level] after induction is important. It implies that there are higher remission rates early. The only thing that it didn’t really tell you is the total inflammatory burden in the body, and [if] lower inflammation equals higher drug level,” said Dr. Regueiro. He did note that the study found that obesity was a negative predictor of long-term remission, which could be attributable to the pro-inflammatory nature of adipose tissue, but he emphasized that the new study doesn’t prove causation.
The study also emphasizes the importance of the HLA-DQA1*05 genetic risk factor.
“I think it confirms that if you’re a carrier of that HLA-DQA1*05, especially with infliximab, if you’re not on an immunomodulator like a thiopurine, you have a very high likelihood of having very high antibodies against infliximab,” Dr. Regueiro said. “The long-term rates bear that out, meaning if you have one of those carriers and you’re not on a thiopurine, the likelihood of having 3-year success on infliximab — to a lesser degree, adalimumab — is very, very low.”
After exclusion of patients who had no initial response, among infliximab patients, the loss of response was 34.4% at 1 year (95% CI, 30.4-38.2%), 54.5% at 2 years (95% CI, 49.4-59%), and 60% at 3 years (95% CI, 54.1-65.2%). For adalimumab, the loss of response rates were 32.1% (95% CI, 26.7-37.1%), 47.2% (95% CI, 40.2-53.4%), and 68.4% (95% CI, 50.9-79.7%), respectively.
Drug concentrations were measured at week 14, and concentration ranges of 6.1-10 mg/L for infliximab and 10.1-12 mg/L for adalimumab were associated with remission at year 2 (infliximab odds ratio [OR], 2.2; 95% CI, 1.38-3.56. Adalimumab OR, 3.65; 95% CI, 1.83-8.67) and year 3 (infliximab OR, 1.89; 95% CI, 1.16-3.11; adalimumab OR, 6.15; 95% CI, 2.5-23.19). A multivariate analysis found that each ten-fold increase in drug concentration at week 14 predicted lower odds of loss of response at year 2 or 3, both for infliximab (hazard ratio [HR], 0.45; 95% CI, 0.3-0.67) and adalimumab (HR, 0.39; 95% CI, 0.22-0.7).
Among patients taking infliximab, loss of response at year 2 or 3 was associated with female sex (HR, 1.47; 95% CI, 1.11-1.95) and obesity (HR, 1.62; 95% CI, 1.08-2.42). After the researchers controlled for week 14 drug and antibody concentrations, as well as interaction between baseline immunomodulator and HLA-DQA1*05 risk variant, low thiopurine dose was associated with a higher risk of loss of response.
In the adalimumab group, there was an association between presence of the HLA-DQA1*05 risk variant and loss of response (HR, 1.95; 95% CI, 1.17-3.25).
Use of the anti-TNF drug without an immunomodulator was associated with development of anti-drug antibodies for infliximab (HR, 0.4; 95% CI, 0.31-0.52) and adalimumab (HR, 0.42; 95% CI, 0.24-0.75). Development of anti-drug antibodies was also associated with the presence of HLA-DQA1*05 for infliximab (HR, 1.46; 95% CI, 1.13-1.88), but not adalimumab (HR, 1.6; 95% CI, 0.92-2.77). Use of an immunomodulator the day before or day of treatment with infliximab was associated with a delay in development of anti-drug antibodies and undetectable drug concentrations compared to only infliximab (HR, 2.87; 95% CI, 2.2-3.74) and to use of the immunomodulator following infliximab treatment (HR, 1.7; 95% CI, 1.11-2.59).
“We suggest aiming to start thiopurines alongside infliximab; our data suggest that later introduction is less effective,” said Dr. Kennedy, who is currently chair of the British Society of Gastroenterology IBD Clinical Research Group.
Dr. Kennedy reported institutional grants or contracts, personal consulting fees, and personal payments or honoraria from a variety of pharmaceutical companies. See the original article for a complete list.
Dr. Regueiro reported that he has been on advisory boards and consulted for Abbvie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celltrion, and Roche.
A version of this article appeared on Medscape.com.
“The relationship between drug concentrations, immunogenicity and clinical response is likely to be multidirectional; as an observational study, we cannot definitively show the low drug levels are causative. However, our data are consistent with those from elsewhere and confirm the importance of achieving good drug levels to maximize the chances of success with anti-TNF therapy,” said Nicholas Kennedy, MBBS, PhD, a consultant gastroenterologist at Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom, and coauthor of the study published in The Lancet Gastroenterology & Hepatology .
“We also showed that adequate dosing of thiopurines was needed to prevent immunogenicity, along the lines typically used to treat Crohn’s disease rather than the lower doses sometimes proposed,” he added.
The findings come from the Personalized Anti-TNF Therapy in Crohn’s Disease (PANTS) study conducted in the UK, which included 955 patients treated with infliximab and 655 treated with adalimumab between March 2014 and September 2017. The participants were 6 years or older, the median age was 32.5 years, and 51% were female.
The latest findings come from a 2-year extension of the original 1-year PANTS study, published in 2019, which found that low drug concentrations predicted anti-TNF treatment failure — a result likely attributable in part to immunogenicity, since low-drug concentrations predicted the presence of anti-drug antibodies, and anti-drug antibodies in turn predicted low drug concentrations, according to Miguel Regueiro, MD, AGAF, chief of the Digestive Diseases Institute and a professor of medicine at the Cleveland Clinic, Ohio.
“This is one of the more important studies looking at the longitudinal care of patients with Crohn’s disease on infliximab and adalimumab,” said Dr. Regueiro, who was not involved with the study.
The extension study found that anti-drug antibodies and undetectable drug levels were associated with both treatment without an accompanying immunomodulator and carriage of the HLA-DQA1*05 genetic risk factor, though the latter was true only for treatment with infliximab.
Dr. Regueiro noted that the study demonstrates that “getting it right in induction is probably the most important part” of treating Crohn’s disease.
“Getting patients in remission early has probably a long-term prediction [of treatment success]. I do think that is practice changing. My practice has changed over the years, largely based on the initial PANTS study. I am measuring infliximab and adalimumab levels after induction, and I am using that number to decide if I dose intensify the drug, or if I’ve hit that sweet spot,” said Dr. Regueiro.
The study highlights a debate among clinicians, about whether higher drug levels are associated with remission because of the effects of higher doses, or because patients who respond have reduced leakiness in the gut, leading to greater retention of protein therapeutics.
“What the study clearly says is that the drug [level] after induction is important. It implies that there are higher remission rates early. The only thing that it didn’t really tell you is the total inflammatory burden in the body, and [if] lower inflammation equals higher drug level,” said Dr. Regueiro. He did note that the study found that obesity was a negative predictor of long-term remission, which could be attributable to the pro-inflammatory nature of adipose tissue, but he emphasized that the new study doesn’t prove causation.
The study also emphasizes the importance of the HLA-DQA1*05 genetic risk factor.
“I think it confirms that if you’re a carrier of that HLA-DQA1*05, especially with infliximab, if you’re not on an immunomodulator like a thiopurine, you have a very high likelihood of having very high antibodies against infliximab,” Dr. Regueiro said. “The long-term rates bear that out, meaning if you have one of those carriers and you’re not on a thiopurine, the likelihood of having 3-year success on infliximab — to a lesser degree, adalimumab — is very, very low.”
After exclusion of patients who had no initial response, among infliximab patients, the loss of response was 34.4% at 1 year (95% CI, 30.4-38.2%), 54.5% at 2 years (95% CI, 49.4-59%), and 60% at 3 years (95% CI, 54.1-65.2%). For adalimumab, the loss of response rates were 32.1% (95% CI, 26.7-37.1%), 47.2% (95% CI, 40.2-53.4%), and 68.4% (95% CI, 50.9-79.7%), respectively.
Drug concentrations were measured at week 14, and concentration ranges of 6.1-10 mg/L for infliximab and 10.1-12 mg/L for adalimumab were associated with remission at year 2 (infliximab odds ratio [OR], 2.2; 95% CI, 1.38-3.56. Adalimumab OR, 3.65; 95% CI, 1.83-8.67) and year 3 (infliximab OR, 1.89; 95% CI, 1.16-3.11; adalimumab OR, 6.15; 95% CI, 2.5-23.19). A multivariate analysis found that each ten-fold increase in drug concentration at week 14 predicted lower odds of loss of response at year 2 or 3, both for infliximab (hazard ratio [HR], 0.45; 95% CI, 0.3-0.67) and adalimumab (HR, 0.39; 95% CI, 0.22-0.7).
Among patients taking infliximab, loss of response at year 2 or 3 was associated with female sex (HR, 1.47; 95% CI, 1.11-1.95) and obesity (HR, 1.62; 95% CI, 1.08-2.42). After the researchers controlled for week 14 drug and antibody concentrations, as well as interaction between baseline immunomodulator and HLA-DQA1*05 risk variant, low thiopurine dose was associated with a higher risk of loss of response.
In the adalimumab group, there was an association between presence of the HLA-DQA1*05 risk variant and loss of response (HR, 1.95; 95% CI, 1.17-3.25).
Use of the anti-TNF drug without an immunomodulator was associated with development of anti-drug antibodies for infliximab (HR, 0.4; 95% CI, 0.31-0.52) and adalimumab (HR, 0.42; 95% CI, 0.24-0.75). Development of anti-drug antibodies was also associated with the presence of HLA-DQA1*05 for infliximab (HR, 1.46; 95% CI, 1.13-1.88), but not adalimumab (HR, 1.6; 95% CI, 0.92-2.77). Use of an immunomodulator the day before or day of treatment with infliximab was associated with a delay in development of anti-drug antibodies and undetectable drug concentrations compared to only infliximab (HR, 2.87; 95% CI, 2.2-3.74) and to use of the immunomodulator following infliximab treatment (HR, 1.7; 95% CI, 1.11-2.59).
“We suggest aiming to start thiopurines alongside infliximab; our data suggest that later introduction is less effective,” said Dr. Kennedy, who is currently chair of the British Society of Gastroenterology IBD Clinical Research Group.
Dr. Kennedy reported institutional grants or contracts, personal consulting fees, and personal payments or honoraria from a variety of pharmaceutical companies. See the original article for a complete list.
Dr. Regueiro reported that he has been on advisory boards and consulted for Abbvie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celltrion, and Roche.
A version of this article appeared on Medscape.com.
“The relationship between drug concentrations, immunogenicity and clinical response is likely to be multidirectional; as an observational study, we cannot definitively show the low drug levels are causative. However, our data are consistent with those from elsewhere and confirm the importance of achieving good drug levels to maximize the chances of success with anti-TNF therapy,” said Nicholas Kennedy, MBBS, PhD, a consultant gastroenterologist at Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom, and coauthor of the study published in The Lancet Gastroenterology & Hepatology .
“We also showed that adequate dosing of thiopurines was needed to prevent immunogenicity, along the lines typically used to treat Crohn’s disease rather than the lower doses sometimes proposed,” he added.
The findings come from the Personalized Anti-TNF Therapy in Crohn’s Disease (PANTS) study conducted in the UK, which included 955 patients treated with infliximab and 655 treated with adalimumab between March 2014 and September 2017. The participants were 6 years or older, the median age was 32.5 years, and 51% were female.
The latest findings come from a 2-year extension of the original 1-year PANTS study, published in 2019, which found that low drug concentrations predicted anti-TNF treatment failure — a result likely attributable in part to immunogenicity, since low-drug concentrations predicted the presence of anti-drug antibodies, and anti-drug antibodies in turn predicted low drug concentrations, according to Miguel Regueiro, MD, AGAF, chief of the Digestive Diseases Institute and a professor of medicine at the Cleveland Clinic, Ohio.
“This is one of the more important studies looking at the longitudinal care of patients with Crohn’s disease on infliximab and adalimumab,” said Dr. Regueiro, who was not involved with the study.
The extension study found that anti-drug antibodies and undetectable drug levels were associated with both treatment without an accompanying immunomodulator and carriage of the HLA-DQA1*05 genetic risk factor, though the latter was true only for treatment with infliximab.
Dr. Regueiro noted that the study demonstrates that “getting it right in induction is probably the most important part” of treating Crohn’s disease.
“Getting patients in remission early has probably a long-term prediction [of treatment success]. I do think that is practice changing. My practice has changed over the years, largely based on the initial PANTS study. I am measuring infliximab and adalimumab levels after induction, and I am using that number to decide if I dose intensify the drug, or if I’ve hit that sweet spot,” said Dr. Regueiro.
The study highlights a debate among clinicians, about whether higher drug levels are associated with remission because of the effects of higher doses, or because patients who respond have reduced leakiness in the gut, leading to greater retention of protein therapeutics.
“What the study clearly says is that the drug [level] after induction is important. It implies that there are higher remission rates early. The only thing that it didn’t really tell you is the total inflammatory burden in the body, and [if] lower inflammation equals higher drug level,” said Dr. Regueiro. He did note that the study found that obesity was a negative predictor of long-term remission, which could be attributable to the pro-inflammatory nature of adipose tissue, but he emphasized that the new study doesn’t prove causation.
The study also emphasizes the importance of the HLA-DQA1*05 genetic risk factor.
“I think it confirms that if you’re a carrier of that HLA-DQA1*05, especially with infliximab, if you’re not on an immunomodulator like a thiopurine, you have a very high likelihood of having very high antibodies against infliximab,” Dr. Regueiro said. “The long-term rates bear that out, meaning if you have one of those carriers and you’re not on a thiopurine, the likelihood of having 3-year success on infliximab — to a lesser degree, adalimumab — is very, very low.”
After exclusion of patients who had no initial response, among infliximab patients, the loss of response was 34.4% at 1 year (95% CI, 30.4-38.2%), 54.5% at 2 years (95% CI, 49.4-59%), and 60% at 3 years (95% CI, 54.1-65.2%). For adalimumab, the loss of response rates were 32.1% (95% CI, 26.7-37.1%), 47.2% (95% CI, 40.2-53.4%), and 68.4% (95% CI, 50.9-79.7%), respectively.
Drug concentrations were measured at week 14, and concentration ranges of 6.1-10 mg/L for infliximab and 10.1-12 mg/L for adalimumab were associated with remission at year 2 (infliximab odds ratio [OR], 2.2; 95% CI, 1.38-3.56. Adalimumab OR, 3.65; 95% CI, 1.83-8.67) and year 3 (infliximab OR, 1.89; 95% CI, 1.16-3.11; adalimumab OR, 6.15; 95% CI, 2.5-23.19). A multivariate analysis found that each ten-fold increase in drug concentration at week 14 predicted lower odds of loss of response at year 2 or 3, both for infliximab (hazard ratio [HR], 0.45; 95% CI, 0.3-0.67) and adalimumab (HR, 0.39; 95% CI, 0.22-0.7).
Among patients taking infliximab, loss of response at year 2 or 3 was associated with female sex (HR, 1.47; 95% CI, 1.11-1.95) and obesity (HR, 1.62; 95% CI, 1.08-2.42). After the researchers controlled for week 14 drug and antibody concentrations, as well as interaction between baseline immunomodulator and HLA-DQA1*05 risk variant, low thiopurine dose was associated with a higher risk of loss of response.
In the adalimumab group, there was an association between presence of the HLA-DQA1*05 risk variant and loss of response (HR, 1.95; 95% CI, 1.17-3.25).
Use of the anti-TNF drug without an immunomodulator was associated with development of anti-drug antibodies for infliximab (HR, 0.4; 95% CI, 0.31-0.52) and adalimumab (HR, 0.42; 95% CI, 0.24-0.75). Development of anti-drug antibodies was also associated with the presence of HLA-DQA1*05 for infliximab (HR, 1.46; 95% CI, 1.13-1.88), but not adalimumab (HR, 1.6; 95% CI, 0.92-2.77). Use of an immunomodulator the day before or day of treatment with infliximab was associated with a delay in development of anti-drug antibodies and undetectable drug concentrations compared to only infliximab (HR, 2.87; 95% CI, 2.2-3.74) and to use of the immunomodulator following infliximab treatment (HR, 1.7; 95% CI, 1.11-2.59).
“We suggest aiming to start thiopurines alongside infliximab; our data suggest that later introduction is less effective,” said Dr. Kennedy, who is currently chair of the British Society of Gastroenterology IBD Clinical Research Group.
Dr. Kennedy reported institutional grants or contracts, personal consulting fees, and personal payments or honoraria from a variety of pharmaceutical companies. See the original article for a complete list.
Dr. Regueiro reported that he has been on advisory boards and consulted for Abbvie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celltrion, and Roche.
A version of this article appeared on Medscape.com.
How Experts Predicts This COVID and Flu Season Will Unfold
What’s the outlook for COVID-19 and flu this fall and winter? It’ll probably be a lot like last year, experts say.
“We currently expect this flu season to be comparable to last year’s season,” said Adrienne Keen, PhD, of the Centers for Disease Control and Prevention’s (CDC) Center for Forecasting and Outbreak Analytics. “We expect this year’s COVID-19 season peak to be similar to last year’s or lower.” The CDC is still analyzing COVID surveillance data from the summer and will update the forecast as more is learned.
For COVID, that means it won’t be as bad as the pandemic years, and for the flu, it’s a typical pre-pandemic season. But status quo does not mean great.
Between October 2023 and April 2024, as many as 75 million people got the flu in the United States, according to CDC estimates, resulting in up to 900,000 hospitalizations and between 17,000 and 100,000 deaths. In 2023, about 900,000 Americans were hospitalized with COVID and 75,000 died.
Getting vaccinated remains crucial, public health officials stressed.
Predicting COVID
Two key predictors of how bad an upcoming COVID season will be are the cycling of new variants and the population’s immunity (protection from an infectious disease that happens when a population is immune through vaccination or previous infection).
When new variants go up and immunity goes down, “we tend to see the increase in cases,” said Michael T. Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy and a professor of public health at the University of Minnesota, Minneapolis. But if the number of variants goes down and immunity levels go up, the outlook is more favorable.
The new COVID variant called XEC has been found in at least 25 states. On September 27, the CDC added the variant to the COVID tracker. It now accounts for 6% of US cases. This was expected, as the variant has been circulating in Europe, said Amesh Adalja, MD, a senior scholar and infectious disease expert at the Center for Health Security at Johns Hopkins University, Baltimore, Maryland.
“There will always be a new variant appearing, and one falling,” he said. “So the fact that this is happening is not surprising.”
Meanwhile, the summer COVID surge has provided postinfection immunity for some people. “What’s likely is, we are going to see substantial protection of the population for several months based on previous infection and in some cases vaccination,” Dr. Osterholm said. That means protection from serious illness, hospitalizations, and deaths (but not necessarily infection). That protection could last through the year or into early 2025.
The timing of 2024’s winter surge will likely be a bit later than 2023’s, said Andrew Pekosz, PhD, a professor and vice chair of molecular microbiology and immunology at Johns Hopkins University, Baltimore, “peaking just after the Christmas/New Year holiday.”
During the 2023-2024 season, weekly COVID hospitalizations peaked the week of Dec. 30, said Justin Lessler, PhD, a professor of epidemiology at the University of North Carolina at Chapel Hill and a member of the COVID-19 Scenario Modeling Hub.
But variants are unpredictable. “There’s a chance that the XEC variant may take off and spread, or might not,” said Dr. Adalja. As of September 28, the Omicron variant KP.3.1.1 was leading, accounting for 58.7% of US cases, according to the CDC.
While Dr. Adalja agreed that 2024’s COVID season will probably be like 2023’s, “we have to be prepared for cases and hospitalizations going up,” he said, “but not to the point of a crisis.” A return to lockdowns and social distancing is unlikely.
Still, older adults and others at higher risk of getting very sick from COVID should consider masking during travel, said Rajendram Rajnarayanan, PhD, MSc, an associate professor at the New York Institute of Technology College of Osteopathic Medicine at Arkansas State University, Jonesboro.
Flu Forecasts
Predicting flu season this early is hard, said Jeffrey Shaman, PhD, a professor of environmental health sciences and professor of climate at Colombia University, New York.
“You can look at the CDC forecast and use it as a very loose guide right now,” said Dr. Shaman, who won the CDC’s first “Predict the Influenza Season Challenge” in 2014. “Until there is actually flu, it’s like trying to predict the landfall of a hurricane.” Flu activity remained low as of September 14 (the most current data available), according to the CDC.
When flu activity picks up, typically in mid-October or November, experts look at the dominant strain, exposure to similar strains in previous years, and how well-matched the current flu vaccine is to that dominant strain, Dr. Shaman said. Vaccine makers must make an educated guess months in advance regarding which strain to target, to allow time for production.
The vaccination rate plays a role, too, but that tends to remain constant, Dr. Shaman said. According to the CDC, less than half of adults age 18 and up got a flu vaccination last year.
Experts also consider flu patterns in the Southern Hemisphere, where 2024 flu activity has mostly involved two subtypes of influenza A — H1N1 and H3N2 — and some influenza B, the CDC found.
How Well Do This Year’s Vaccines and Viruses Match Up?
The FDA has authorized three updated COVID vaccines for this fall. Novavax targets the JN.1 strain of SARS-CoV-2, the virus that causes COVID-19. Both mRNA vaccines, Moderna and Pfizer, target KP.2, a descendant of JN.1. All three target current predominant variants, and any one of them is recommended by the CDC.
The vaccines are a good “though not perfect match to virtually all the circulating variants of SARS-CoV-2,” said Dr. Pekosz.
Experts said that the shots will protect against the XEC variant.
“XEC and its sublineages are expected to be the dominant fall/winter variant group,” said Dr. Rajnarayanan.
This year’s flu vaccines, all trivalent (protecting against three viruses), will target the three strains expected to circulate — H1N1, H3N2, and influenza B (Victoria), according to the CDC.
People should still get vaccinated, Dr. Adalja said, and use home tests for flu and COVID and take antivirals promptly when needed. The goal should not be status quo but rather fewer COVID and flu hospitalizations and deaths.
A version of this article first appeared on WebMD.com.
What’s the outlook for COVID-19 and flu this fall and winter? It’ll probably be a lot like last year, experts say.
“We currently expect this flu season to be comparable to last year’s season,” said Adrienne Keen, PhD, of the Centers for Disease Control and Prevention’s (CDC) Center for Forecasting and Outbreak Analytics. “We expect this year’s COVID-19 season peak to be similar to last year’s or lower.” The CDC is still analyzing COVID surveillance data from the summer and will update the forecast as more is learned.
For COVID, that means it won’t be as bad as the pandemic years, and for the flu, it’s a typical pre-pandemic season. But status quo does not mean great.
Between October 2023 and April 2024, as many as 75 million people got the flu in the United States, according to CDC estimates, resulting in up to 900,000 hospitalizations and between 17,000 and 100,000 deaths. In 2023, about 900,000 Americans were hospitalized with COVID and 75,000 died.
Getting vaccinated remains crucial, public health officials stressed.
Predicting COVID
Two key predictors of how bad an upcoming COVID season will be are the cycling of new variants and the population’s immunity (protection from an infectious disease that happens when a population is immune through vaccination or previous infection).
When new variants go up and immunity goes down, “we tend to see the increase in cases,” said Michael T. Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy and a professor of public health at the University of Minnesota, Minneapolis. But if the number of variants goes down and immunity levels go up, the outlook is more favorable.
The new COVID variant called XEC has been found in at least 25 states. On September 27, the CDC added the variant to the COVID tracker. It now accounts for 6% of US cases. This was expected, as the variant has been circulating in Europe, said Amesh Adalja, MD, a senior scholar and infectious disease expert at the Center for Health Security at Johns Hopkins University, Baltimore, Maryland.
“There will always be a new variant appearing, and one falling,” he said. “So the fact that this is happening is not surprising.”
Meanwhile, the summer COVID surge has provided postinfection immunity for some people. “What’s likely is, we are going to see substantial protection of the population for several months based on previous infection and in some cases vaccination,” Dr. Osterholm said. That means protection from serious illness, hospitalizations, and deaths (but not necessarily infection). That protection could last through the year or into early 2025.
The timing of 2024’s winter surge will likely be a bit later than 2023’s, said Andrew Pekosz, PhD, a professor and vice chair of molecular microbiology and immunology at Johns Hopkins University, Baltimore, “peaking just after the Christmas/New Year holiday.”
During the 2023-2024 season, weekly COVID hospitalizations peaked the week of Dec. 30, said Justin Lessler, PhD, a professor of epidemiology at the University of North Carolina at Chapel Hill and a member of the COVID-19 Scenario Modeling Hub.
But variants are unpredictable. “There’s a chance that the XEC variant may take off and spread, or might not,” said Dr. Adalja. As of September 28, the Omicron variant KP.3.1.1 was leading, accounting for 58.7% of US cases, according to the CDC.
While Dr. Adalja agreed that 2024’s COVID season will probably be like 2023’s, “we have to be prepared for cases and hospitalizations going up,” he said, “but not to the point of a crisis.” A return to lockdowns and social distancing is unlikely.
Still, older adults and others at higher risk of getting very sick from COVID should consider masking during travel, said Rajendram Rajnarayanan, PhD, MSc, an associate professor at the New York Institute of Technology College of Osteopathic Medicine at Arkansas State University, Jonesboro.
Flu Forecasts
Predicting flu season this early is hard, said Jeffrey Shaman, PhD, a professor of environmental health sciences and professor of climate at Colombia University, New York.
“You can look at the CDC forecast and use it as a very loose guide right now,” said Dr. Shaman, who won the CDC’s first “Predict the Influenza Season Challenge” in 2014. “Until there is actually flu, it’s like trying to predict the landfall of a hurricane.” Flu activity remained low as of September 14 (the most current data available), according to the CDC.
When flu activity picks up, typically in mid-October or November, experts look at the dominant strain, exposure to similar strains in previous years, and how well-matched the current flu vaccine is to that dominant strain, Dr. Shaman said. Vaccine makers must make an educated guess months in advance regarding which strain to target, to allow time for production.
The vaccination rate plays a role, too, but that tends to remain constant, Dr. Shaman said. According to the CDC, less than half of adults age 18 and up got a flu vaccination last year.
Experts also consider flu patterns in the Southern Hemisphere, where 2024 flu activity has mostly involved two subtypes of influenza A — H1N1 and H3N2 — and some influenza B, the CDC found.
How Well Do This Year’s Vaccines and Viruses Match Up?
The FDA has authorized three updated COVID vaccines for this fall. Novavax targets the JN.1 strain of SARS-CoV-2, the virus that causes COVID-19. Both mRNA vaccines, Moderna and Pfizer, target KP.2, a descendant of JN.1. All three target current predominant variants, and any one of them is recommended by the CDC.
The vaccines are a good “though not perfect match to virtually all the circulating variants of SARS-CoV-2,” said Dr. Pekosz.
Experts said that the shots will protect against the XEC variant.
“XEC and its sublineages are expected to be the dominant fall/winter variant group,” said Dr. Rajnarayanan.
This year’s flu vaccines, all trivalent (protecting against three viruses), will target the three strains expected to circulate — H1N1, H3N2, and influenza B (Victoria), according to the CDC.
People should still get vaccinated, Dr. Adalja said, and use home tests for flu and COVID and take antivirals promptly when needed. The goal should not be status quo but rather fewer COVID and flu hospitalizations and deaths.
A version of this article first appeared on WebMD.com.
What’s the outlook for COVID-19 and flu this fall and winter? It’ll probably be a lot like last year, experts say.
“We currently expect this flu season to be comparable to last year’s season,” said Adrienne Keen, PhD, of the Centers for Disease Control and Prevention’s (CDC) Center for Forecasting and Outbreak Analytics. “We expect this year’s COVID-19 season peak to be similar to last year’s or lower.” The CDC is still analyzing COVID surveillance data from the summer and will update the forecast as more is learned.
For COVID, that means it won’t be as bad as the pandemic years, and for the flu, it’s a typical pre-pandemic season. But status quo does not mean great.
Between October 2023 and April 2024, as many as 75 million people got the flu in the United States, according to CDC estimates, resulting in up to 900,000 hospitalizations and between 17,000 and 100,000 deaths. In 2023, about 900,000 Americans were hospitalized with COVID and 75,000 died.
Getting vaccinated remains crucial, public health officials stressed.
Predicting COVID
Two key predictors of how bad an upcoming COVID season will be are the cycling of new variants and the population’s immunity (protection from an infectious disease that happens when a population is immune through vaccination or previous infection).
When new variants go up and immunity goes down, “we tend to see the increase in cases,” said Michael T. Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy and a professor of public health at the University of Minnesota, Minneapolis. But if the number of variants goes down and immunity levels go up, the outlook is more favorable.
The new COVID variant called XEC has been found in at least 25 states. On September 27, the CDC added the variant to the COVID tracker. It now accounts for 6% of US cases. This was expected, as the variant has been circulating in Europe, said Amesh Adalja, MD, a senior scholar and infectious disease expert at the Center for Health Security at Johns Hopkins University, Baltimore, Maryland.
“There will always be a new variant appearing, and one falling,” he said. “So the fact that this is happening is not surprising.”
Meanwhile, the summer COVID surge has provided postinfection immunity for some people. “What’s likely is, we are going to see substantial protection of the population for several months based on previous infection and in some cases vaccination,” Dr. Osterholm said. That means protection from serious illness, hospitalizations, and deaths (but not necessarily infection). That protection could last through the year or into early 2025.
The timing of 2024’s winter surge will likely be a bit later than 2023’s, said Andrew Pekosz, PhD, a professor and vice chair of molecular microbiology and immunology at Johns Hopkins University, Baltimore, “peaking just after the Christmas/New Year holiday.”
During the 2023-2024 season, weekly COVID hospitalizations peaked the week of Dec. 30, said Justin Lessler, PhD, a professor of epidemiology at the University of North Carolina at Chapel Hill and a member of the COVID-19 Scenario Modeling Hub.
But variants are unpredictable. “There’s a chance that the XEC variant may take off and spread, or might not,” said Dr. Adalja. As of September 28, the Omicron variant KP.3.1.1 was leading, accounting for 58.7% of US cases, according to the CDC.
While Dr. Adalja agreed that 2024’s COVID season will probably be like 2023’s, “we have to be prepared for cases and hospitalizations going up,” he said, “but not to the point of a crisis.” A return to lockdowns and social distancing is unlikely.
Still, older adults and others at higher risk of getting very sick from COVID should consider masking during travel, said Rajendram Rajnarayanan, PhD, MSc, an associate professor at the New York Institute of Technology College of Osteopathic Medicine at Arkansas State University, Jonesboro.
Flu Forecasts
Predicting flu season this early is hard, said Jeffrey Shaman, PhD, a professor of environmental health sciences and professor of climate at Colombia University, New York.
“You can look at the CDC forecast and use it as a very loose guide right now,” said Dr. Shaman, who won the CDC’s first “Predict the Influenza Season Challenge” in 2014. “Until there is actually flu, it’s like trying to predict the landfall of a hurricane.” Flu activity remained low as of September 14 (the most current data available), according to the CDC.
When flu activity picks up, typically in mid-October or November, experts look at the dominant strain, exposure to similar strains in previous years, and how well-matched the current flu vaccine is to that dominant strain, Dr. Shaman said. Vaccine makers must make an educated guess months in advance regarding which strain to target, to allow time for production.
The vaccination rate plays a role, too, but that tends to remain constant, Dr. Shaman said. According to the CDC, less than half of adults age 18 and up got a flu vaccination last year.
Experts also consider flu patterns in the Southern Hemisphere, where 2024 flu activity has mostly involved two subtypes of influenza A — H1N1 and H3N2 — and some influenza B, the CDC found.
How Well Do This Year’s Vaccines and Viruses Match Up?
The FDA has authorized three updated COVID vaccines for this fall. Novavax targets the JN.1 strain of SARS-CoV-2, the virus that causes COVID-19. Both mRNA vaccines, Moderna and Pfizer, target KP.2, a descendant of JN.1. All three target current predominant variants, and any one of them is recommended by the CDC.
The vaccines are a good “though not perfect match to virtually all the circulating variants of SARS-CoV-2,” said Dr. Pekosz.
Experts said that the shots will protect against the XEC variant.
“XEC and its sublineages are expected to be the dominant fall/winter variant group,” said Dr. Rajnarayanan.
This year’s flu vaccines, all trivalent (protecting against three viruses), will target the three strains expected to circulate — H1N1, H3N2, and influenza B (Victoria), according to the CDC.
People should still get vaccinated, Dr. Adalja said, and use home tests for flu and COVID and take antivirals promptly when needed. The goal should not be status quo but rather fewer COVID and flu hospitalizations and deaths.
A version of this article first appeared on WebMD.com.