Circulating tumor DNA (ctDNA) has proven itself as a prognostic tool, but questions remain as to whether it can be used to guide the use of adjuvant chemotherapy in patients with colorectal cancer (CRC). Much of the uncertainty surrounds the sensitivity of ctDNA at the time when decisions regarding adjuvant therapy are being made.

Those were some of the key points made during a series of presentations and discussions on ctDNA at the ASCO Gastrointestinal Cancers Symposium.

In a morning session, Pashtoon Murtaza Kasi, MD, presented the first interim results from the multicenter, prospective observational BESPOKE CRC study, which included 689 patients with stage II or III colorectal cancer. The trial was designed to determine what effect ctDNA results would have on adjuvant chemotherapy treatment decisions. Over a median follow-up of 24.8 months, 623 patients had ctDNA results available. ctDNA positivity was associated with worse 2-year disease-free survival (DFS) at 29.86% versus 91.59% in the stage II/III combined group (hazard ratio [HR], 12.1; P < .0001) and in stage II (HR, 18.8; P < .0001) and stage III (HR, 9.9; P < .0001) analyzed separately.

In ctDNA-positive patients, adjuvant chemotherapy was associated with longer DFS than in those who did not undergo adjuvant chemotherapy (HR, 3.06; P = .0025), but there was no difference in DFS between ctDNA-negative patients who received adjuvant chemotherapy and those who didn’t. Patients who achieved ctDNA clearance had a longer median DFS (24.2 versus 13.8 months; HR, 0.4; P = .045).
 

Patient Anxiety Concerns

Dr. Kasi noted the importance of considering the patient’s view of ctDNA. There may be some concerns that such tests could cause patient anxiety, but he referenced a poster at ASCO GI which suggested the opposite. “It actually reduced anxiety, and 90% of the patients felt confident in the treatment they were receiving. They [said that] they will continue using the assay, and they value the additional information,” said Dr. Kasi, who is a medical oncologist at Weill Cornell Medicine in New York City.

During the Q&A after the talk, David Ellison, MD, a medical oncology and hematology specialist at Memorial Sloan Kettering Cancer Center, also in New York asked Dr. Kasi: “Did this [positive ctDNA] test just prompt earlier imaging? Was it any better than conventional surveillance like CEA (carcinoembryonic antigen) or imaging?” he asked.

Dr. Kasi responded that the data showed ctDNA positivity 6-9 months earlier than cancer detection through traditional imaging.

“It doesn’t necessarily replace the ongoing surveillance. This particular study did not guide or make it as a protocol as to what to do. Everything was done as part of standard of care, the usual surveillance that the cancer center follows, he said. “I think [ctDNA] would help complement the ongoing care and in conjunction with somebody who has, for example, an indeterminant lung nodule, but also has ctDNA positivity, I think it adds confidence to the decisions that one might be making.”

Eujung Kim, MD, PhD, an instructor of medicine at Harvard Medical School, Boston, Massachusetts, wondered if there might be chemoresistant tumor cells remaining that are not shedding DNA. “You have to keep the biology in mind as well make decisions in conjunction with the clinical situation, as opposed to in isolation with ctDNA results,” Dr. Kasi responded.

In the same session, Jeannie Tie, MD, described results from the AGITG DYNAMIC-Rectal trial, which was a randomized study to determine if ctDNA could inform adjuvant chemotherapy decisions in locally advanced rectal cancer. The analysis included 230 patients who were randomized to ctDNA-informed management (n = 155), with a positive test leading to adjuvant chemotherapy, or a standard arm where adjuvant therapy decisions were left to the physician (n = 75).

Adjuvant chemotherapy use was higher in the control arm (77% versus 46%; P < .001). Lymphovascular invasion was more common in the control arm (odds ratio [OR], 3.06; P = .023), and recurrence-free survival was higher in patients who remained ctDNA negative (HR, 0.29; P < .001) despite all ctDNA-positive patients and only 23% of ctDNA-negative patients undergoing chemotherapy.

The sites of relapses were also different, with 78% occurring in patients who were ctDNA negative after surgery occurring only in the lung, versus just 1% of metastases solely in the lung among those who were ctDNA positive.

In ctDNA-positive patients, 50% of relapses were only in the liver and 19% were in the liver and lung.

Over 36 months, 16% of ctDNA-negative patients developed distant relapses and 2.8% developed locoregional relapses, versus 36% and 7.1% in the ctDNA-positive group.

“Regrettably, we could not conclude about the noninferiority of [using ctDNA to guide adjuvant therapy decisions] due to the premature study closure and small sample size. We confirmed the significantly lower risk of recurrence in post-op ctDNA-negative patients compared to ctDNA-positive patients, as well as the differential pattern of relapse where lung metastases predominate in ctDNA-negative patients, while liver metastases were the dominant side of relapse in ctDNA-positive patients,” said Dr. Tie, who is a medical oncologist at the Peter MacCallum Cancer Centre, Victoria, Australia.
 

GALAXY Study Results Updated

In an afternoon session, Hiroki Yukami, MD, PhD, presented updated results of the GALAXY study, which examined 2998 patients with stage I-IV colorectal cancer who underwent ctDNA surveillance over a median 16.14 months following surgery. ctDNA-positive status was associated with worse DFS (HR, 10.53; P < .0001) in all stages as well as in stage II/III (HR, 12.05; P < .0001). The researchers also distinguished between patients with sustained ctDNA clearance and those with transient ctDNA clearance, in which a positive test occurred after an initial negative result. Recurrences occurred in 7.1% of patients with sustained ctDNA clearance, versus 85.2% of patients with transient clearance (P < .0001) and 89.4% of those with no clearance (P < .0001). “Sustained clearance indicates superior DFS compared to transient or no clearance,” said Dr. Yukami during his presentation.

Of 117 patients treated with adjuvant chemotherapy after testing ctDNA positive, subsequent ctDNA clearance was associated with better DFS (HR, 6.72; P < .0001). There were also better DFS outcomes among patients who saw a greater decline in ctDNA plasma levels after adjuvant chemotherapy (0%-50% versus 50%-100% reduction; HR, 2.41; P = .001).

Aparna Raj Parikh, MD, assistant professor of medicine at Harvard Medical School, served as a discussant for the GALAXY study. She acknowledged that ctDNA is the most powerful prognostic marker in oncology, but to be clinically useful it is necessary to consider its utility at the landmark time point, which is when decisions are made whether to treat with adjuvant chemotherapy. At that time point, the sensitivity of ctDNA is about 48% in the GALAXY study, which Dr. Parikh said is consistent with other data.
 

ctDNA ‘not sensitive enough’

“We know that postoperative ctDNA is only capturing 40%-50% of patients with recurrences in non–stage IV patients in multiple datasets to date. I think it’s really important to keep in mind the sensitivity of the different time points when you’re actually thinking about how to use this in clinic. The first generation of tests are certainly promising, but I would make the argument that these are just not sensitive enough,” said Dr. Parikh.

“Landmark testing is not yet sensitive enough to deescalate care in a patient where chemotherapy would otherwise be indicated, and surveillance testing has not yet demonstrated clinical utility. I think our goal to actually deescalate care would be to try to lower the ctDNA-negative population recurrence risk to akin to stage I patients, with that 5-year DFS of 93%-95%,” Dr. Parikh said.

Dr. Parikh offered some advice on how to use ctDNA outside of a clinical trial setting. She said that positive ctDNA results can help drive the decision to initiate adjuvant chemotherapy in concert with clinical and other factors.

“I’m pretty convinced by the data that ctDNA is prognostic, and though we still need outcomes data, in particular scenarios where I’m thinking of not giving chemotherapy, a positive test may sway me in that direction,” she said. She gave examples such as patients with a single high-risk feature, or a stage III patient with marginal performance status, or an elderly patient with low-risk stage III disease.

Dr. Kasi has financial relationships with Precision Biosensors, Elicio Therapeutics, Bayer, BostonGene, Daiichi Sankyo/AstraZeneca, Delcath Systems, Eisai, Elicio Therapeutics, Exact Sciences, Foundation Medicine, Guardant Health, Illumina, Ipsen, Lilly, MSD Oncology, Natera, NeoGenomics, QED Therapeutics, SAGA Diagnostics, Seagen, SERVIER, Taiho Oncology, Taiho Pharmaceutical, Advanced Accelerator Applications, Boston Scientific, and Tersera. Dr. Tie, Dr. Kim, Dr. Ellison, and Dr. Yukami did not disclose conflicts of interest. Dr. Parikh has financial relationships with Abbvie, Bayer, Biofidelity, CheckMate Pharmaceuticals, CVS, Delcath Systems, Foundation Medicine, Guardant Health, Illumina, Lily, SAGA Diagnostics, Scarce, Seagen, Taiho Oncology, Takeda, UpToDate, and Value Analytics Labs.

Circulating tumor DNA (ctDNA) has proven itself as a prognostic tool, but questions remain as to whether it can be used to guide the use of adjuvant chemotherapy in patients with colorectal cancer (CRC). Much of the uncertainty surrounds the sensitivity of ctDNA at the time when decisions regarding adjuvant therapy are being made.

Those were some of the key points made during a series of presentations and discussions on ctDNA at the ASCO Gastrointestinal Cancers Symposium.

In a morning session, Pashtoon Murtaza Kasi, MD, presented the first interim results from the multicenter, prospective observational BESPOKE CRC study, which included 689 patients with stage II or III colorectal cancer. The trial was designed to determine what effect ctDNA results would have on adjuvant chemotherapy treatment decisions. Over a median follow-up of 24.8 months, 623 patients had ctDNA results available. ctDNA positivity was associated with worse 2-year disease-free survival (DFS) at 29.86% versus 91.59% in the stage II/III combined group (hazard ratio [HR], 12.1; P < .0001) and in stage II (HR, 18.8; P < .0001) and stage III (HR, 9.9; P < .0001) analyzed separately.

In ctDNA-positive patients, adjuvant chemotherapy was associated with longer DFS than in those who did not undergo adjuvant chemotherapy (HR, 3.06; P = .0025), but there was no difference in DFS between ctDNA-negative patients who received adjuvant chemotherapy and those who didn’t. Patients who achieved ctDNA clearance had a longer median DFS (24.2 versus 13.8 months; HR, 0.4; P = .045).
 

Patient Anxiety Concerns

Dr. Kasi noted the importance of considering the patient’s view of ctDNA. There may be some concerns that such tests could cause patient anxiety, but he referenced a poster at ASCO GI which suggested the opposite. “It actually reduced anxiety, and 90% of the patients felt confident in the treatment they were receiving. They [said that] they will continue using the assay, and they value the additional information,” said Dr. Kasi, who is a medical oncologist at Weill Cornell Medicine in New York City.

During the Q&A after the talk, David Ellison, MD, a medical oncology and hematology specialist at Memorial Sloan Kettering Cancer Center, also in New York asked Dr. Kasi: “Did this [positive ctDNA] test just prompt earlier imaging? Was it any better than conventional surveillance like CEA (carcinoembryonic antigen) or imaging?” he asked.

Dr. Kasi responded that the data showed ctDNA positivity 6-9 months earlier than cancer detection through traditional imaging.

“It doesn’t necessarily replace the ongoing surveillance. This particular study did not guide or make it as a protocol as to what to do. Everything was done as part of standard of care, the usual surveillance that the cancer center follows, he said. “I think [ctDNA] would help complement the ongoing care and in conjunction with somebody who has, for example, an indeterminant lung nodule, but also has ctDNA positivity, I think it adds confidence to the decisions that one might be making.”

Eujung Kim, MD, PhD, an instructor of medicine at Harvard Medical School, Boston, Massachusetts, wondered if there might be chemoresistant tumor cells remaining that are not shedding DNA. “You have to keep the biology in mind as well make decisions in conjunction with the clinical situation, as opposed to in isolation with ctDNA results,” Dr. Kasi responded.

In the same session, Jeannie Tie, MD, described results from the AGITG DYNAMIC-Rectal trial, which was a randomized study to determine if ctDNA could inform adjuvant chemotherapy decisions in locally advanced rectal cancer. The analysis included 230 patients who were randomized to ctDNA-informed management (n = 155), with a positive test leading to adjuvant chemotherapy, or a standard arm where adjuvant therapy decisions were left to the physician (n = 75).

Adjuvant chemotherapy use was higher in the control arm (77% versus 46%; P < .001). Lymphovascular invasion was more common in the control arm (odds ratio [OR], 3.06; P = .023), and recurrence-free survival was higher in patients who remained ctDNA negative (HR, 0.29; P < .001) despite all ctDNA-positive patients and only 23% of ctDNA-negative patients undergoing chemotherapy.

The sites of relapses were also different, with 78% occurring in patients who were ctDNA negative after surgery occurring only in the lung, versus just 1% of metastases solely in the lung among those who were ctDNA positive.

In ctDNA-positive patients, 50% of relapses were only in the liver and 19% were in the liver and lung.

Over 36 months, 16% of ctDNA-negative patients developed distant relapses and 2.8% developed locoregional relapses, versus 36% and 7.1% in the ctDNA-positive group.

“Regrettably, we could not conclude about the noninferiority of [using ctDNA to guide adjuvant therapy decisions] due to the premature study closure and small sample size. We confirmed the significantly lower risk of recurrence in post-op ctDNA-negative patients compared to ctDNA-positive patients, as well as the differential pattern of relapse where lung metastases predominate in ctDNA-negative patients, while liver metastases were the dominant side of relapse in ctDNA-positive patients,” said Dr. Tie, who is a medical oncologist at the Peter MacCallum Cancer Centre, Victoria, Australia.
 

GALAXY Study Results Updated

In an afternoon session, Hiroki Yukami, MD, PhD, presented updated results of the GALAXY study, which examined 2998 patients with stage I-IV colorectal cancer who underwent ctDNA surveillance over a median 16.14 months following surgery. ctDNA-positive status was associated with worse DFS (HR, 10.53; P < .0001) in all stages as well as in stage II/III (HR, 12.05; P < .0001). The researchers also distinguished between patients with sustained ctDNA clearance and those with transient ctDNA clearance, in which a positive test occurred after an initial negative result. Recurrences occurred in 7.1% of patients with sustained ctDNA clearance, versus 85.2% of patients with transient clearance (P < .0001) and 89.4% of those with no clearance (P < .0001). “Sustained clearance indicates superior DFS compared to transient or no clearance,” said Dr. Yukami during his presentation.

Of 117 patients treated with adjuvant chemotherapy after testing ctDNA positive, subsequent ctDNA clearance was associated with better DFS (HR, 6.72; P < .0001). There were also better DFS outcomes among patients who saw a greater decline in ctDNA plasma levels after adjuvant chemotherapy (0%-50% versus 50%-100% reduction; HR, 2.41; P = .001).

Aparna Raj Parikh, MD, assistant professor of medicine at Harvard Medical School, served as a discussant for the GALAXY study. She acknowledged that ctDNA is the most powerful prognostic marker in oncology, but to be clinically useful it is necessary to consider its utility at the landmark time point, which is when decisions are made whether to treat with adjuvant chemotherapy. At that time point, the sensitivity of ctDNA is about 48% in the GALAXY study, which Dr. Parikh said is consistent with other data.
 

ctDNA ‘not sensitive enough’

“We know that postoperative ctDNA is only capturing 40%-50% of patients with recurrences in non–stage IV patients in multiple datasets to date. I think it’s really important to keep in mind the sensitivity of the different time points when you’re actually thinking about how to use this in clinic. The first generation of tests are certainly promising, but I would make the argument that these are just not sensitive enough,” said Dr. Parikh.

“Landmark testing is not yet sensitive enough to deescalate care in a patient where chemotherapy would otherwise be indicated, and surveillance testing has not yet demonstrated clinical utility. I think our goal to actually deescalate care would be to try to lower the ctDNA-negative population recurrence risk to akin to stage I patients, with that 5-year DFS of 93%-95%,” Dr. Parikh said.

Dr. Parikh offered some advice on how to use ctDNA outside of a clinical trial setting. She said that positive ctDNA results can help drive the decision to initiate adjuvant chemotherapy in concert with clinical and other factors.

“I’m pretty convinced by the data that ctDNA is prognostic, and though we still need outcomes data, in particular scenarios where I’m thinking of not giving chemotherapy, a positive test may sway me in that direction,” she said. She gave examples such as patients with a single high-risk feature, or a stage III patient with marginal performance status, or an elderly patient with low-risk stage III disease.

Dr. Kasi has financial relationships with Precision Biosensors, Elicio Therapeutics, Bayer, BostonGene, Daiichi Sankyo/AstraZeneca, Delcath Systems, Eisai, Elicio Therapeutics, Exact Sciences, Foundation Medicine, Guardant Health, Illumina, Ipsen, Lilly, MSD Oncology, Natera, NeoGenomics, QED Therapeutics, SAGA Diagnostics, Seagen, SERVIER, Taiho Oncology, Taiho Pharmaceutical, Advanced Accelerator Applications, Boston Scientific, and Tersera. Dr. Tie, Dr. Kim, Dr. Ellison, and Dr. Yukami did not disclose conflicts of interest. Dr. Parikh has financial relationships with Abbvie, Bayer, Biofidelity, CheckMate Pharmaceuticals, CVS, Delcath Systems, Foundation Medicine, Guardant Health, Illumina, Lily, SAGA Diagnostics, Scarce, Seagen, Taiho Oncology, Takeda, UpToDate, and Value Analytics Labs.

Circulating tumor DNA (ctDNA) has proven itself as a prognostic tool, but questions remain as to whether it can be used to guide the use of adjuvant chemotherapy in patients with colorectal cancer (CRC). Much of the uncertainty surrounds the sensitivity of ctDNA at the time when decisions regarding adjuvant therapy are being made.

Those were some of the key points made during a series of presentations and discussions on ctDNA at the ASCO Gastrointestinal Cancers Symposium.

In a morning session, Pashtoon Murtaza Kasi, MD, presented the first interim results from the multicenter, prospective observational BESPOKE CRC study, which included 689 patients with stage II or III colorectal cancer. The trial was designed to determine what effect ctDNA results would have on adjuvant chemotherapy treatment decisions. Over a median follow-up of 24.8 months, 623 patients had ctDNA results available. ctDNA positivity was associated with worse 2-year disease-free survival (DFS) at 29.86% versus 91.59% in the stage II/III combined group (hazard ratio [HR], 12.1; P < .0001) and in stage II (HR, 18.8; P < .0001) and stage III (HR, 9.9; P < .0001) analyzed separately.

In ctDNA-positive patients, adjuvant chemotherapy was associated with longer DFS than in those who did not undergo adjuvant chemotherapy (HR, 3.06; P = .0025), but there was no difference in DFS between ctDNA-negative patients who received adjuvant chemotherapy and those who didn’t. Patients who achieved ctDNA clearance had a longer median DFS (24.2 versus 13.8 months; HR, 0.4; P = .045).
 

Patient Anxiety Concerns

Dr. Kasi noted the importance of considering the patient’s view of ctDNA. There may be some concerns that such tests could cause patient anxiety, but he referenced a poster at ASCO GI which suggested the opposite. “It actually reduced anxiety, and 90% of the patients felt confident in the treatment they were receiving. They [said that] they will continue using the assay, and they value the additional information,” said Dr. Kasi, who is a medical oncologist at Weill Cornell Medicine in New York City.

During the Q&A after the talk, David Ellison, MD, a medical oncology and hematology specialist at Memorial Sloan Kettering Cancer Center, also in New York asked Dr. Kasi: “Did this [positive ctDNA] test just prompt earlier imaging? Was it any better than conventional surveillance like CEA (carcinoembryonic antigen) or imaging?” he asked.

Dr. Kasi responded that the data showed ctDNA positivity 6-9 months earlier than cancer detection through traditional imaging.

“It doesn’t necessarily replace the ongoing surveillance. This particular study did not guide or make it as a protocol as to what to do. Everything was done as part of standard of care, the usual surveillance that the cancer center follows, he said. “I think [ctDNA] would help complement the ongoing care and in conjunction with somebody who has, for example, an indeterminant lung nodule, but also has ctDNA positivity, I think it adds confidence to the decisions that one might be making.”

Eujung Kim, MD, PhD, an instructor of medicine at Harvard Medical School, Boston, Massachusetts, wondered if there might be chemoresistant tumor cells remaining that are not shedding DNA. “You have to keep the biology in mind as well make decisions in conjunction with the clinical situation, as opposed to in isolation with ctDNA results,” Dr. Kasi responded.

In the same session, Jeannie Tie, MD, described results from the AGITG DYNAMIC-Rectal trial, which was a randomized study to determine if ctDNA could inform adjuvant chemotherapy decisions in locally advanced rectal cancer. The analysis included 230 patients who were randomized to ctDNA-informed management (n = 155), with a positive test leading to adjuvant chemotherapy, or a standard arm where adjuvant therapy decisions were left to the physician (n = 75).

Adjuvant chemotherapy use was higher in the control arm (77% versus 46%; P < .001). Lymphovascular invasion was more common in the control arm (odds ratio [OR], 3.06; P = .023), and recurrence-free survival was higher in patients who remained ctDNA negative (HR, 0.29; P < .001) despite all ctDNA-positive patients and only 23% of ctDNA-negative patients undergoing chemotherapy.

The sites of relapses were also different, with 78% occurring in patients who were ctDNA negative after surgery occurring only in the lung, versus just 1% of metastases solely in the lung among those who were ctDNA positive.

In ctDNA-positive patients, 50% of relapses were only in the liver and 19% were in the liver and lung.

Over 36 months, 16% of ctDNA-negative patients developed distant relapses and 2.8% developed locoregional relapses, versus 36% and 7.1% in the ctDNA-positive group.

“Regrettably, we could not conclude about the noninferiority of [using ctDNA to guide adjuvant therapy decisions] due to the premature study closure and small sample size. We confirmed the significantly lower risk of recurrence in post-op ctDNA-negative patients compared to ctDNA-positive patients, as well as the differential pattern of relapse where lung metastases predominate in ctDNA-negative patients, while liver metastases were the dominant side of relapse in ctDNA-positive patients,” said Dr. Tie, who is a medical oncologist at the Peter MacCallum Cancer Centre, Victoria, Australia.
 

GALAXY Study Results Updated

In an afternoon session, Hiroki Yukami, MD, PhD, presented updated results of the GALAXY study, which examined 2998 patients with stage I-IV colorectal cancer who underwent ctDNA surveillance over a median 16.14 months following surgery. ctDNA-positive status was associated with worse DFS (HR, 10.53; P < .0001) in all stages as well as in stage II/III (HR, 12.05; P < .0001). The researchers also distinguished between patients with sustained ctDNA clearance and those with transient ctDNA clearance, in which a positive test occurred after an initial negative result. Recurrences occurred in 7.1% of patients with sustained ctDNA clearance, versus 85.2% of patients with transient clearance (P < .0001) and 89.4% of those with no clearance (P < .0001). “Sustained clearance indicates superior DFS compared to transient or no clearance,” said Dr. Yukami during his presentation.

Of 117 patients treated with adjuvant chemotherapy after testing ctDNA positive, subsequent ctDNA clearance was associated with better DFS (HR, 6.72; P < .0001). There were also better DFS outcomes among patients who saw a greater decline in ctDNA plasma levels after adjuvant chemotherapy (0%-50% versus 50%-100% reduction; HR, 2.41; P = .001).

Aparna Raj Parikh, MD, assistant professor of medicine at Harvard Medical School, served as a discussant for the GALAXY study. She acknowledged that ctDNA is the most powerful prognostic marker in oncology, but to be clinically useful it is necessary to consider its utility at the landmark time point, which is when decisions are made whether to treat with adjuvant chemotherapy. At that time point, the sensitivity of ctDNA is about 48% in the GALAXY study, which Dr. Parikh said is consistent with other data.
 

ctDNA ‘not sensitive enough’

“We know that postoperative ctDNA is only capturing 40%-50% of patients with recurrences in non–stage IV patients in multiple datasets to date. I think it’s really important to keep in mind the sensitivity of the different time points when you’re actually thinking about how to use this in clinic. The first generation of tests are certainly promising, but I would make the argument that these are just not sensitive enough,” said Dr. Parikh.

“Landmark testing is not yet sensitive enough to deescalate care in a patient where chemotherapy would otherwise be indicated, and surveillance testing has not yet demonstrated clinical utility. I think our goal to actually deescalate care would be to try to lower the ctDNA-negative population recurrence risk to akin to stage I patients, with that 5-year DFS of 93%-95%,” Dr. Parikh said.

Dr. Parikh offered some advice on how to use ctDNA outside of a clinical trial setting. She said that positive ctDNA results can help drive the decision to initiate adjuvant chemotherapy in concert with clinical and other factors.

“I’m pretty convinced by the data that ctDNA is prognostic, and though we still need outcomes data, in particular scenarios where I’m thinking of not giving chemotherapy, a positive test may sway me in that direction,” she said. She gave examples such as patients with a single high-risk feature, or a stage III patient with marginal performance status, or an elderly patient with low-risk stage III disease.

Dr. Kasi has financial relationships with Precision Biosensors, Elicio Therapeutics, Bayer, BostonGene, Daiichi Sankyo/AstraZeneca, Delcath Systems, Eisai, Elicio Therapeutics, Exact Sciences, Foundation Medicine, Guardant Health, Illumina, Ipsen, Lilly, MSD Oncology, Natera, NeoGenomics, QED Therapeutics, SAGA Diagnostics, Seagen, SERVIER, Taiho Oncology, Taiho Pharmaceutical, Advanced Accelerator Applications, Boston Scientific, and Tersera. Dr. Tie, Dr. Kim, Dr. Ellison, and Dr. Yukami did not disclose conflicts of interest. Dr. Parikh has financial relationships with Abbvie, Bayer, Biofidelity, CheckMate Pharmaceuticals, CVS, Delcath Systems, Foundation Medicine, Guardant Health, Illumina, Lily, SAGA Diagnostics, Scarce, Seagen, Taiho Oncology, Takeda, UpToDate, and Value Analytics Labs.

TOPLINE:

Artificial intelligence (AI) boosts the screening rate for potentially blinding diabetes eye disorders in a diabetes clinic compared with referral to an eye care provider (ECP) in a racially and ethnically diverse youth population with diabetes.

METHODOLOGY:

• Although early screening and treatment can prevent diabetic eye diseases (DEDs), many people with diabetes in the United States lack access to and knowledge about diabetic eye exams.
• The  trial included 164 patients aged 8-21 years (58% female, 35% Black, and 6% Hispanic) with type 1 or 2 diabetes with no known DED and no diabetic eye exam in the last 6 months.
• In a diabetes clinic, patients were randomly assigned to an AI diabetic eye exam (intervention arm) then and there or to standard of care, referred to an ECP with scripted educational material (control).
• Participants in the intervention arm underwent the 5- to 10-minute autonomous AI diabetic eye exam without pharmacologic dilation. The results were generated immediately as either “DED present” or “DED absent.”
• The primary outcome was the completion rate of documented diabetic eye exams within 6 months (“primary gap closure rate”), either by AI or going to the ECP. The secondary outcome was ECP follow-up by intervention participants with DED (intervention) and all control patients.

TAKEAWAY:

• Within 6 months, all the participants (100%) in the intervention arm completed their diabetic eye exam, a primary care gap closure rate of 100% (95% CI, 96%-100%).
• The rate of primary care gap closure was significantly higher in the intervention vs control arm (100% vs 22%; P < .001).
• In the intervention arm, 64% of patients with DED followed up with an eye care provider within 6 months compared with a mere 22% participants in the control arm (P < .001).
• Participants reported high levels of satisfaction with autonomous AI, with 92.5% expressing satisfaction with the exam’s duration and 96% expressing satisfaction with the whole experience.

IN PRACTICE:

“Autonomous AI increases diabetic eye exam completion rates and closes this care gap in a racially and ethnically diverse population of youth with diabetes, compared to standard of care,” the authors wrote.

SOURCE:

This study, which was led by Risa M. Wolf, MD, department of pediatrics, division of endocrinology, Johns Hopkins School of Medicine, Baltimore, was published online on January 11, 2024, in Nature Communications.

LIMITATIONS:

This study used autonomous AI in the youth although it’s not approved by the US Food and Drug Administration for use in individuals aged 21 years and younger. Some of the participants in this study were already familiar with autonomous AI diabetic eye exams, which might have contributed to their willingness to participate in the current study. The autonomous AI used in the study was shown to have a lack of racial and ethnic bias, but any AI bias caused by differences in retinal pigment has potential to increase rather than decrease health disparities.

DISCLOSURES:

The clinical trial was supported by the National Eye Institute of the National Institutes of Health and the Diabetes Research Connection. Wolf, the lead author, declared receiving research support from Boehringer Ingelheim and Novo Nordisk outside the submitted work. Coauthor Michael D. Abramoff, MD, declared serving in various roles such as investor, director, and consultant for Digital Diagnostics Inc., as well as other ties with many sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Artificial intelligence (AI) boosts the screening rate for potentially blinding diabetes eye disorders in a diabetes clinic compared with referral to an eye care provider (ECP) in a racially and ethnically diverse youth population with diabetes.

METHODOLOGY:

• Although early screening and treatment can prevent diabetic eye diseases (DEDs), many people with diabetes in the United States lack access to and knowledge about diabetic eye exams.
• The  trial included 164 patients aged 8-21 years (58% female, 35% Black, and 6% Hispanic) with type 1 or 2 diabetes with no known DED and no diabetic eye exam in the last 6 months.
• In a diabetes clinic, patients were randomly assigned to an AI diabetic eye exam (intervention arm) then and there or to standard of care, referred to an ECP with scripted educational material (control).
• Participants in the intervention arm underwent the 5- to 10-minute autonomous AI diabetic eye exam without pharmacologic dilation. The results were generated immediately as either “DED present” or “DED absent.”
• The primary outcome was the completion rate of documented diabetic eye exams within 6 months (“primary gap closure rate”), either by AI or going to the ECP. The secondary outcome was ECP follow-up by intervention participants with DED (intervention) and all control patients.

TAKEAWAY:

• Within 6 months, all the participants (100%) in the intervention arm completed their diabetic eye exam, a primary care gap closure rate of 100% (95% CI, 96%-100%).
• The rate of primary care gap closure was significantly higher in the intervention vs control arm (100% vs 22%; P < .001).
• In the intervention arm, 64% of patients with DED followed up with an eye care provider within 6 months compared with a mere 22% participants in the control arm (P < .001).
• Participants reported high levels of satisfaction with autonomous AI, with 92.5% expressing satisfaction with the exam’s duration and 96% expressing satisfaction with the whole experience.

IN PRACTICE:

“Autonomous AI increases diabetic eye exam completion rates and closes this care gap in a racially and ethnically diverse population of youth with diabetes, compared to standard of care,” the authors wrote.

SOURCE:

This study, which was led by Risa M. Wolf, MD, department of pediatrics, division of endocrinology, Johns Hopkins School of Medicine, Baltimore, was published online on January 11, 2024, in Nature Communications.

LIMITATIONS:

This study used autonomous AI in the youth although it’s not approved by the US Food and Drug Administration for use in individuals aged 21 years and younger. Some of the participants in this study were already familiar with autonomous AI diabetic eye exams, which might have contributed to their willingness to participate in the current study. The autonomous AI used in the study was shown to have a lack of racial and ethnic bias, but any AI bias caused by differences in retinal pigment has potential to increase rather than decrease health disparities.

DISCLOSURES:

The clinical trial was supported by the National Eye Institute of the National Institutes of Health and the Diabetes Research Connection. Wolf, the lead author, declared receiving research support from Boehringer Ingelheim and Novo Nordisk outside the submitted work. Coauthor Michael D. Abramoff, MD, declared serving in various roles such as investor, director, and consultant for Digital Diagnostics Inc., as well as other ties with many sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Artificial intelligence (AI) boosts the screening rate for potentially blinding diabetes eye disorders in a diabetes clinic compared with referral to an eye care provider (ECP) in a racially and ethnically diverse youth population with diabetes.

METHODOLOGY:

• Although early screening and treatment can prevent diabetic eye diseases (DEDs), many people with diabetes in the United States lack access to and knowledge about diabetic eye exams.
• The  trial included 164 patients aged 8-21 years (58% female, 35% Black, and 6% Hispanic) with type 1 or 2 diabetes with no known DED and no diabetic eye exam in the last 6 months.
• In a diabetes clinic, patients were randomly assigned to an AI diabetic eye exam (intervention arm) then and there or to standard of care, referred to an ECP with scripted educational material (control).
• Participants in the intervention arm underwent the 5- to 10-minute autonomous AI diabetic eye exam without pharmacologic dilation. The results were generated immediately as either “DED present” or “DED absent.”
• The primary outcome was the completion rate of documented diabetic eye exams within 6 months (“primary gap closure rate”), either by AI or going to the ECP. The secondary outcome was ECP follow-up by intervention participants with DED (intervention) and all control patients.

TAKEAWAY:

• Within 6 months, all the participants (100%) in the intervention arm completed their diabetic eye exam, a primary care gap closure rate of 100% (95% CI, 96%-100%).
• The rate of primary care gap closure was significantly higher in the intervention vs control arm (100% vs 22%; P < .001).
• In the intervention arm, 64% of patients with DED followed up with an eye care provider within 6 months compared with a mere 22% participants in the control arm (P < .001).
• Participants reported high levels of satisfaction with autonomous AI, with 92.5% expressing satisfaction with the exam’s duration and 96% expressing satisfaction with the whole experience.

IN PRACTICE:

“Autonomous AI increases diabetic eye exam completion rates and closes this care gap in a racially and ethnically diverse population of youth with diabetes, compared to standard of care,” the authors wrote.

SOURCE:

This study, which was led by Risa M. Wolf, MD, department of pediatrics, division of endocrinology, Johns Hopkins School of Medicine, Baltimore, was published online on January 11, 2024, in Nature Communications.

LIMITATIONS:

This study used autonomous AI in the youth although it’s not approved by the US Food and Drug Administration for use in individuals aged 21 years and younger. Some of the participants in this study were already familiar with autonomous AI diabetic eye exams, which might have contributed to their willingness to participate in the current study. The autonomous AI used in the study was shown to have a lack of racial and ethnic bias, but any AI bias caused by differences in retinal pigment has potential to increase rather than decrease health disparities.

DISCLOSURES:

The clinical trial was supported by the National Eye Institute of the National Institutes of Health and the Diabetes Research Connection. Wolf, the lead author, declared receiving research support from Boehringer Ingelheim and Novo Nordisk outside the submitted work. Coauthor Michael D. Abramoff, MD, declared serving in various roles such as investor, director, and consultant for Digital Diagnostics Inc., as well as other ties with many sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

Men with an inflammatory arthritis (IA) diagnosis are less likely to be childless than healthy comparators, according to an epidemiological study.

METHODS:

• 10,865 men in the Norwegian Arthritis Registry were compared with 54,325 men without IA, matched by age and location.
• In the arthritis group, 37% had rheumatoid arthritis, 33% had psoriatic arthritis, and 30% had spondyloarthritis.
• Researchers used childlessness and number of children as proxies for male fertility.

TAKEAWAY:

• 21% of men with IA were childless compared with 27% in the healthy cohort (P < .001).
• On an average, a man with IA had 1.80 children whereas a man in the control group had 1.69 children (P < .001).
• These findings were consistent over time, but the most pronounced difference between groups was seen in men diagnosed after the year 2000.

IN PRACTICE:

The finding “is novel and generates new hypotheses regarding associations between fertility, inflammatory rheumatic diseases, and immune-modulating drugs,” the authors wrote.

SOURCE:

First author Gudrun David Sigmo, of the department of rheumatology at Stavanger (Norway) University Hospital, and colleagues had their work published online on January 23, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The analysis relied on administrative data, and researchers did not have data on confounding factors.

DISCLOSURES:

The study was funded by the nonprofit organizations Aslaug Anders fond, Astri og Edvard Riisøens legat, Det alminnelige medisinske forskningsfond, Pahles legat, and Fagsenter for medisins-ke kvalitetsregistre i Helse Vest. The authors declared no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE: 

Men with an inflammatory arthritis (IA) diagnosis are less likely to be childless than healthy comparators, according to an epidemiological study.

METHODS:

• 10,865 men in the Norwegian Arthritis Registry were compared with 54,325 men without IA, matched by age and location.
• In the arthritis group, 37% had rheumatoid arthritis, 33% had psoriatic arthritis, and 30% had spondyloarthritis.
• Researchers used childlessness and number of children as proxies for male fertility.

TAKEAWAY:

• 21% of men with IA were childless compared with 27% in the healthy cohort (P < .001).
• On an average, a man with IA had 1.80 children whereas a man in the control group had 1.69 children (P < .001).
• These findings were consistent over time, but the most pronounced difference between groups was seen in men diagnosed after the year 2000.

IN PRACTICE:

The finding “is novel and generates new hypotheses regarding associations between fertility, inflammatory rheumatic diseases, and immune-modulating drugs,” the authors wrote.

SOURCE:

First author Gudrun David Sigmo, of the department of rheumatology at Stavanger (Norway) University Hospital, and colleagues had their work published online on January 23, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The analysis relied on administrative data, and researchers did not have data on confounding factors.

DISCLOSURES:

The study was funded by the nonprofit organizations Aslaug Anders fond, Astri og Edvard Riisøens legat, Det alminnelige medisinske forskningsfond, Pahles legat, and Fagsenter for medisins-ke kvalitetsregistre i Helse Vest. The authors declared no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE: 

Men with an inflammatory arthritis (IA) diagnosis are less likely to be childless than healthy comparators, according to an epidemiological study.

METHODS:

• 10,865 men in the Norwegian Arthritis Registry were compared with 54,325 men without IA, matched by age and location.
• In the arthritis group, 37% had rheumatoid arthritis, 33% had psoriatic arthritis, and 30% had spondyloarthritis.
• Researchers used childlessness and number of children as proxies for male fertility.

TAKEAWAY:

• 21% of men with IA were childless compared with 27% in the healthy cohort (P < .001).
• On an average, a man with IA had 1.80 children whereas a man in the control group had 1.69 children (P < .001).
• These findings were consistent over time, but the most pronounced difference between groups was seen in men diagnosed after the year 2000.

IN PRACTICE:

The finding “is novel and generates new hypotheses regarding associations between fertility, inflammatory rheumatic diseases, and immune-modulating drugs,” the authors wrote.

SOURCE:

First author Gudrun David Sigmo, of the department of rheumatology at Stavanger (Norway) University Hospital, and colleagues had their work published online on January 23, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The analysis relied on administrative data, and researchers did not have data on confounding factors.

DISCLOSURES:

The study was funded by the nonprofit organizations Aslaug Anders fond, Astri og Edvard Riisøens legat, Det alminnelige medisinske forskningsfond, Pahles legat, and Fagsenter for medisins-ke kvalitetsregistre i Helse Vest. The authors declared no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved a wearable belt device for postmenopausal women with osteopenia, the precursor to osteoporosis, according to the company’s manufacturer, Bone Health Technologies.

According to the company, the device (Osteoboost) is the first nonpharmacologic device-based, prescription-only treatment for postmenopausal women with low bone density. It has not been tested for ability to reduce fracture risk.

Bone Health Technologies

The device is worn around the hips and delivers calibrated mild vibrations to the hips and lumbar spine to help preserve bone strength and density. A vibration pack is mounted to the back of the belt.

FDA approval, announced on January 18, was based on the findings of a National Institutes of Health–funded double-blinded, sham-controlled study of 126 women with low bone density conducted at the University of Nebraska Medical Center in Omaha. The data were shared at the 2023 Endocrine Society and American Society for Bone and Mineral Research annual meetings and published in the Journal of the Endocrine Society.

Lead investigator Laura D. Bilek, PT, PhD, associate dean for research and associate professor at the University of Nebraska, and colleagues wrote that the primary outcome measurement was the change in vertebral strength measured by CT scans for women who used the device a minimum of three times per week compared with a sham group who wore a belt that emitted sound but had no vibrations.

Compressive strength and volumetric density of the first lumbar vertebra were analyzed.

In the active-belt group, women lost, on average, 0.48% bone strength, while those in the sham group lost nearly 2.84% (P = .014), about five times as much. Results also showed that participants in the active treatment group who used the device three times per week lost 0.29% bone mineral density (BMD) compared with the 1.97% BMD lost in the control group. No adverse events were reported in the study.

Sonali Khandelwal, MD, a rheumatologist at Rush University in Chicago, told this news organization there’s considerable fear among some patients about long-term use of available medications for bone health, “so any modality that is nontherapeutic — not a pill — is always exciting.”

The endpoints of the study are one good measure, she said, but she emphasized that it will be important to show that the improved bone density from the belt that is described in this study “is a true marker of decreased fracture risk.”

Because there are no apparent side effects, she said it may be effective in combination with weight-bearing exercise, vitamin D and calcium, and/or medication, depending on severity of bone loss.

Current medications on the market for osteoporosis have been shown to improve bone strength and reduce fracture risk, she noted.

“It could help; I just don’t think we have enough evidence that it will completely treat the bone loss,” Dr. Khandelwal said.

She said she sees the potential population most interested in the belt as premenopausal women with a family history of bone loss who may not meet the level of bone loss for medical management but are interested in prevention.

“I also think of individuals who might already meet medication needs but are completely averse to being on medication,” she said. The bulk of her practice is treating bone loss, she said, estimating that 20% of her patients do not want to be on medication.

Bone Health Technologies CEO Laura Yecies, MBA, told this news organization the company has not yet set the price for the device and noted that because it will be available by prescription only, out-of-pocket costs and copays will differ. She said the company expects to begin shipping later this year. Requests for update notifications can be made at the company’s website.

Dr. Bilek told this news organization the device was tested for a year, so it’s unclear how long people with osteopenia would need to wear the belt for maximum benefit.

The theory behind the mechanism of action, she said, “is that the vibration actually inhibits the cells [osteoclasts] that take away bone mass.”

The researchers included only postmenopausal women with osteopenia in the study, but Dr. Bilek said she would like to test the device on other groups, such as men with prostate cancer getting testosterone-blocking therapy, which can result in loss of bone density. An estimated 34 million people in the United States have osteopenia.

Dr. Bilek said a next step for the study is to enroll a more diverse cohort at an additional center to test the device because most of the women in this one were White.

She noted that women’s bone mass peaks at age 30 and then starts to decline.

“When women hit menopause, there’s a really rapid decline [in bone strength] for the next 5-7 years and then the decline levels off. If we can slow that decline, hopefully that woman’s bone density is maintained at a higher level throughout their life,” Dr. Bilek said.

Dr. Bilek is a scientific adviser to Bone Health Technologies. She and many coauthors of the study received grants or fees from the company and own stock in or are employees of the company. Ms. Yecies is the founder and CEO of Bone Health Technologies. Dr. Khandelwal had no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved a wearable belt device for postmenopausal women with osteopenia, the precursor to osteoporosis, according to the company’s manufacturer, Bone Health Technologies.

According to the company, the device (Osteoboost) is the first nonpharmacologic device-based, prescription-only treatment for postmenopausal women with low bone density. It has not been tested for ability to reduce fracture risk.

Bone Health Technologies

The device is worn around the hips and delivers calibrated mild vibrations to the hips and lumbar spine to help preserve bone strength and density. A vibration pack is mounted to the back of the belt.

FDA approval, announced on January 18, was based on the findings of a National Institutes of Health–funded double-blinded, sham-controlled study of 126 women with low bone density conducted at the University of Nebraska Medical Center in Omaha. The data were shared at the 2023 Endocrine Society and American Society for Bone and Mineral Research annual meetings and published in the Journal of the Endocrine Society.

Lead investigator Laura D. Bilek, PT, PhD, associate dean for research and associate professor at the University of Nebraska, and colleagues wrote that the primary outcome measurement was the change in vertebral strength measured by CT scans for women who used the device a minimum of three times per week compared with a sham group who wore a belt that emitted sound but had no vibrations.

Compressive strength and volumetric density of the first lumbar vertebra were analyzed.

In the active-belt group, women lost, on average, 0.48% bone strength, while those in the sham group lost nearly 2.84% (P = .014), about five times as much. Results also showed that participants in the active treatment group who used the device three times per week lost 0.29% bone mineral density (BMD) compared with the 1.97% BMD lost in the control group. No adverse events were reported in the study.

Sonali Khandelwal, MD, a rheumatologist at Rush University in Chicago, told this news organization there’s considerable fear among some patients about long-term use of available medications for bone health, “so any modality that is nontherapeutic — not a pill — is always exciting.”

The endpoints of the study are one good measure, she said, but she emphasized that it will be important to show that the improved bone density from the belt that is described in this study “is a true marker of decreased fracture risk.”

Because there are no apparent side effects, she said it may be effective in combination with weight-bearing exercise, vitamin D and calcium, and/or medication, depending on severity of bone loss.

Current medications on the market for osteoporosis have been shown to improve bone strength and reduce fracture risk, she noted.

“It could help; I just don’t think we have enough evidence that it will completely treat the bone loss,” Dr. Khandelwal said.

She said she sees the potential population most interested in the belt as premenopausal women with a family history of bone loss who may not meet the level of bone loss for medical management but are interested in prevention.

“I also think of individuals who might already meet medication needs but are completely averse to being on medication,” she said. The bulk of her practice is treating bone loss, she said, estimating that 20% of her patients do not want to be on medication.

Bone Health Technologies CEO Laura Yecies, MBA, told this news organization the company has not yet set the price for the device and noted that because it will be available by prescription only, out-of-pocket costs and copays will differ. She said the company expects to begin shipping later this year. Requests for update notifications can be made at the company’s website.

Dr. Bilek told this news organization the device was tested for a year, so it’s unclear how long people with osteopenia would need to wear the belt for maximum benefit.

The theory behind the mechanism of action, she said, “is that the vibration actually inhibits the cells [osteoclasts] that take away bone mass.”

The researchers included only postmenopausal women with osteopenia in the study, but Dr. Bilek said she would like to test the device on other groups, such as men with prostate cancer getting testosterone-blocking therapy, which can result in loss of bone density. An estimated 34 million people in the United States have osteopenia.

Dr. Bilek said a next step for the study is to enroll a more diverse cohort at an additional center to test the device because most of the women in this one were White.

She noted that women’s bone mass peaks at age 30 and then starts to decline.

“When women hit menopause, there’s a really rapid decline [in bone strength] for the next 5-7 years and then the decline levels off. If we can slow that decline, hopefully that woman’s bone density is maintained at a higher level throughout their life,” Dr. Bilek said.

Dr. Bilek is a scientific adviser to Bone Health Technologies. She and many coauthors of the study received grants or fees from the company and own stock in or are employees of the company. Ms. Yecies is the founder and CEO of Bone Health Technologies. Dr. Khandelwal had no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved a wearable belt device for postmenopausal women with osteopenia, the precursor to osteoporosis, according to the company’s manufacturer, Bone Health Technologies.

According to the company, the device (Osteoboost) is the first nonpharmacologic device-based, prescription-only treatment for postmenopausal women with low bone density. It has not been tested for ability to reduce fracture risk.

Bone Health Technologies

The device is worn around the hips and delivers calibrated mild vibrations to the hips and lumbar spine to help preserve bone strength and density. A vibration pack is mounted to the back of the belt.

FDA approval, announced on January 18, was based on the findings of a National Institutes of Health–funded double-blinded, sham-controlled study of 126 women with low bone density conducted at the University of Nebraska Medical Center in Omaha. The data were shared at the 2023 Endocrine Society and American Society for Bone and Mineral Research annual meetings and published in the Journal of the Endocrine Society.

Lead investigator Laura D. Bilek, PT, PhD, associate dean for research and associate professor at the University of Nebraska, and colleagues wrote that the primary outcome measurement was the change in vertebral strength measured by CT scans for women who used the device a minimum of three times per week compared with a sham group who wore a belt that emitted sound but had no vibrations.

Compressive strength and volumetric density of the first lumbar vertebra were analyzed.

In the active-belt group, women lost, on average, 0.48% bone strength, while those in the sham group lost nearly 2.84% (P = .014), about five times as much. Results also showed that participants in the active treatment group who used the device three times per week lost 0.29% bone mineral density (BMD) compared with the 1.97% BMD lost in the control group. No adverse events were reported in the study.

Sonali Khandelwal, MD, a rheumatologist at Rush University in Chicago, told this news organization there’s considerable fear among some patients about long-term use of available medications for bone health, “so any modality that is nontherapeutic — not a pill — is always exciting.”

The endpoints of the study are one good measure, she said, but she emphasized that it will be important to show that the improved bone density from the belt that is described in this study “is a true marker of decreased fracture risk.”

Because there are no apparent side effects, she said it may be effective in combination with weight-bearing exercise, vitamin D and calcium, and/or medication, depending on severity of bone loss.

Current medications on the market for osteoporosis have been shown to improve bone strength and reduce fracture risk, she noted.

“It could help; I just don’t think we have enough evidence that it will completely treat the bone loss,” Dr. Khandelwal said.

She said she sees the potential population most interested in the belt as premenopausal women with a family history of bone loss who may not meet the level of bone loss for medical management but are interested in prevention.

“I also think of individuals who might already meet medication needs but are completely averse to being on medication,” she said. The bulk of her practice is treating bone loss, she said, estimating that 20% of her patients do not want to be on medication.

Bone Health Technologies CEO Laura Yecies, MBA, told this news organization the company has not yet set the price for the device and noted that because it will be available by prescription only, out-of-pocket costs and copays will differ. She said the company expects to begin shipping later this year. Requests for update notifications can be made at the company’s website.

Dr. Bilek told this news organization the device was tested for a year, so it’s unclear how long people with osteopenia would need to wear the belt for maximum benefit.

The theory behind the mechanism of action, she said, “is that the vibration actually inhibits the cells [osteoclasts] that take away bone mass.”

The researchers included only postmenopausal women with osteopenia in the study, but Dr. Bilek said she would like to test the device on other groups, such as men with prostate cancer getting testosterone-blocking therapy, which can result in loss of bone density. An estimated 34 million people in the United States have osteopenia.

Dr. Bilek said a next step for the study is to enroll a more diverse cohort at an additional center to test the device because most of the women in this one were White.

She noted that women’s bone mass peaks at age 30 and then starts to decline.

“When women hit menopause, there’s a really rapid decline [in bone strength] for the next 5-7 years and then the decline levels off. If we can slow that decline, hopefully that woman’s bone density is maintained at a higher level throughout their life,” Dr. Bilek said.

Dr. Bilek is a scientific adviser to Bone Health Technologies. She and many coauthors of the study received grants or fees from the company and own stock in or are employees of the company. Ms. Yecies is the founder and CEO of Bone Health Technologies. Dr. Khandelwal had no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Less than half of patients with rheumatoid arthritis (RA) initiating a first-line tumor necrosis factor inhibitor (TNFi) in clinical practice had a recorded composite disease activity assessment at the start of the treatment, and many remained on that treatment for years without evidence recorded in their electronic medical record of achieving low-disease activity or remission.

METHODOLOGY:

• Researchers reviewed data from 1651 adults aged 18 years and older with moderate to severe RA at baseline or follow-up in the electronic medical record database of the American Rheumatology Network, a large community network of independent practices with > 200 rheumatologists across the United States.
• Patients received a TNFi as their first advanced therapy between January 2014 and August 2021 and were assessed for measurement of disease activity with the Clinical Disease Activity Index (CDAI) or Routine Assessment of Patient Index Data 3 (RAPID3) at baseline and follow-up visits.

TAKEAWAY:

• Among the patients with moderate to severe RA, 47.2% of patients remained on first-line TNFi therapy 1 year after initiation despite no evidence of achieving treatment targets of low disease activity or remission (defined as CDAI ≤ 10 and/or RAPID3 ≤ 2).
• Approximately one third of patients remained on TNFi therapy for 2 (38.1%) or 3 (35.4%) years after initiation despite not achieving these targets. The median times to TNFi discontinuation was 30.4 months and to subsequent therapy initiation 68.3 months.
• A total of 52% discontinued their initial TNFi during the study period; among those who started a second therapy, 15% restarted the same TNFi, 45.6% started another TNFi, 27.6% started a non-TNFi biologic, and 11.5% started a Janus kinase inhibitor.
• The most common reported reasons for discontinuation were a combination of efficacy and intolerance, efficacy only, and intolerance only (26.9%, 25.3%, and 20.3%, respectively).
• Persistent pain was the most common reason for efficacy-related discontinuation (39.0%), followed by persistent inflammation/swelling and overall general discomfort (31.8% for both).

IN PRACTICE:

“Consistent monitoring of treatment response and timely switch to effective therapy as appropriate is needed in patients with RA initiating their first advanced therapies,” the researchers wrote.

SOURCE:

First author Colin Edgerton, MD, of Articularis Healthcare Group and American Rheumatology Network, Charleston, South Carolina, reported their work on January 14, 2024, in ACR Open Rheumatology.

LIMITATIONS:

The findings were limited by several factors including the retrospective design, incomplete data from electronic medical records, and reliance on physician documentation for drivers of discontinuation.

DISCLOSURES:

The study was supported by AbbVie. Lead author Edgerton also disclosed relationships with Novartis and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

TOPLINE:

Less than half of patients with rheumatoid arthritis (RA) initiating a first-line tumor necrosis factor inhibitor (TNFi) in clinical practice had a recorded composite disease activity assessment at the start of the treatment, and many remained on that treatment for years without evidence recorded in their electronic medical record of achieving low-disease activity or remission.

METHODOLOGY:

• Researchers reviewed data from 1651 adults aged 18 years and older with moderate to severe RA at baseline or follow-up in the electronic medical record database of the American Rheumatology Network, a large community network of independent practices with > 200 rheumatologists across the United States.
• Patients received a TNFi as their first advanced therapy between January 2014 and August 2021 and were assessed for measurement of disease activity with the Clinical Disease Activity Index (CDAI) or Routine Assessment of Patient Index Data 3 (RAPID3) at baseline and follow-up visits.

TAKEAWAY:

• Among the patients with moderate to severe RA, 47.2% of patients remained on first-line TNFi therapy 1 year after initiation despite no evidence of achieving treatment targets of low disease activity or remission (defined as CDAI ≤ 10 and/or RAPID3 ≤ 2).
• Approximately one third of patients remained on TNFi therapy for 2 (38.1%) or 3 (35.4%) years after initiation despite not achieving these targets. The median times to TNFi discontinuation was 30.4 months and to subsequent therapy initiation 68.3 months.
• A total of 52% discontinued their initial TNFi during the study period; among those who started a second therapy, 15% restarted the same TNFi, 45.6% started another TNFi, 27.6% started a non-TNFi biologic, and 11.5% started a Janus kinase inhibitor.
• The most common reported reasons for discontinuation were a combination of efficacy and intolerance, efficacy only, and intolerance only (26.9%, 25.3%, and 20.3%, respectively).
• Persistent pain was the most common reason for efficacy-related discontinuation (39.0%), followed by persistent inflammation/swelling and overall general discomfort (31.8% for both).

IN PRACTICE:

“Consistent monitoring of treatment response and timely switch to effective therapy as appropriate is needed in patients with RA initiating their first advanced therapies,” the researchers wrote.

SOURCE:

First author Colin Edgerton, MD, of Articularis Healthcare Group and American Rheumatology Network, Charleston, South Carolina, reported their work on January 14, 2024, in ACR Open Rheumatology.

LIMITATIONS:

The findings were limited by several factors including the retrospective design, incomplete data from electronic medical records, and reliance on physician documentation for drivers of discontinuation.

DISCLOSURES:

The study was supported by AbbVie. Lead author Edgerton also disclosed relationships with Novartis and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

TOPLINE:

Less than half of patients with rheumatoid arthritis (RA) initiating a first-line tumor necrosis factor inhibitor (TNFi) in clinical practice had a recorded composite disease activity assessment at the start of the treatment, and many remained on that treatment for years without evidence recorded in their electronic medical record of achieving low-disease activity or remission.

METHODOLOGY:

• Researchers reviewed data from 1651 adults aged 18 years and older with moderate to severe RA at baseline or follow-up in the electronic medical record database of the American Rheumatology Network, a large community network of independent practices with > 200 rheumatologists across the United States.
• Patients received a TNFi as their first advanced therapy between January 2014 and August 2021 and were assessed for measurement of disease activity with the Clinical Disease Activity Index (CDAI) or Routine Assessment of Patient Index Data 3 (RAPID3) at baseline and follow-up visits.

TAKEAWAY:

• Among the patients with moderate to severe RA, 47.2% of patients remained on first-line TNFi therapy 1 year after initiation despite no evidence of achieving treatment targets of low disease activity or remission (defined as CDAI ≤ 10 and/or RAPID3 ≤ 2).
• Approximately one third of patients remained on TNFi therapy for 2 (38.1%) or 3 (35.4%) years after initiation despite not achieving these targets. The median times to TNFi discontinuation was 30.4 months and to subsequent therapy initiation 68.3 months.
• A total of 52% discontinued their initial TNFi during the study period; among those who started a second therapy, 15% restarted the same TNFi, 45.6% started another TNFi, 27.6% started a non-TNFi biologic, and 11.5% started a Janus kinase inhibitor.
• The most common reported reasons for discontinuation were a combination of efficacy and intolerance, efficacy only, and intolerance only (26.9%, 25.3%, and 20.3%, respectively).
• Persistent pain was the most common reason for efficacy-related discontinuation (39.0%), followed by persistent inflammation/swelling and overall general discomfort (31.8% for both).

IN PRACTICE:

“Consistent monitoring of treatment response and timely switch to effective therapy as appropriate is needed in patients with RA initiating their first advanced therapies,” the researchers wrote.

SOURCE:

First author Colin Edgerton, MD, of Articularis Healthcare Group and American Rheumatology Network, Charleston, South Carolina, reported their work on January 14, 2024, in ACR Open Rheumatology.

LIMITATIONS:

The findings were limited by several factors including the retrospective design, incomplete data from electronic medical records, and reliance on physician documentation for drivers of discontinuation.

DISCLOSURES:

The study was supported by AbbVie. Lead author Edgerton also disclosed relationships with Novartis and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

ORLANDO, FLORIDA — Advances in treating medical conditions rarely emerge in a straight line. Oftentimes, progress comes in fits and starts, and therapies to treat cutaneous lupus erythematosus (CLE) and dermatomyositis are no exception.

Beyond approved treatments that deserve more attention, like belimumab, approved by the Food and Drug Administration (FDA) for systemic lupus erythematosus (SLE) in 2011, and Octagam 10%, an intravenous immune globulin (IVIG) preparation approved for dermatomyositis in 2021, anticipation is growing for emerging therapies and their potential to provide relief to patients, Anthony Fernandez, MD, PhD, said at the ODAC Dermatology, Aesthetic & Surgical Conference. The tyrosine kinase 2 (TYK2) inhibitor deucravacitinib, Janus kinase (JAK) inhibitors brepocitinib and baricitinib, and the monoclonal antibody anifrolumab, he noted, are prime examples.

“There have been significant advances in the development of treatments for lupus erythematosus and dermatomyositis. In my opinion, this is the start of what will be the most exciting decade in the history of these two diseases,” said Dr. Fernandez, director of medical dermatology at the Cleveland Clinic.
 

Emerging Treatments for Cutaneous Lupus

Although SLE can involve many organ systems, the skin is one of the most affected. There are specific cutaneous lesions categorized as either acute cutaneous lupus, subacute cutaneous lupus, or chronic cutaneous lupus.

The oral TYK2 inhibitor deucravacitinib, for example, should be able to dampen interleukin responses in people with CLE, Dr. Fernandez said. Deucravacitinib was approved by the FDA to treat psoriasis in September 2022.

Cleveland Clinic Foundation

A phase 2 study published in 2023 focused on this agent for relief of systemic lupus. Improvements in cutaneous disease were a secondary endpoint. The trial demonstrated that the patients treated with deucravacitinib achieved a 56%-70% CLASI-50 response, depending on dosing, compared with a 17% response among those on placebo at week 48.

Based on the trial results, recruitment has begun for a phase 2 trial to evaluate deucravacitinib, compared with placebo, in patients with discoid and/or subacute cutaneous lupus. “This may be another medicine we have available to give to any of our patients with cutaneous lupus,” Dr. Fernandez said.
 

Anifrolumab Appears Promising

The FDA approval of anifrolumab, a type I interferon (IFN) receptor antagonist, for treating moderate to severe SLE in July 2021, for example, is good news for dermatologists and their patients, added Dr. Fernandez. “Almost immediately after approval, case studies showed marked improvement in patients with refractory cutaneous lupus.” While the therapy was approved for treating systemic lupus, it allows for off-label treatment of the cutaneous predominant form of the disease, he said.

Furthermore, the manufacturer of anifrolumab, AstraZeneca, is launching the LAVENDER clinical trial to assess the monoclonal antibody specifically for treating CLE. “This is a big deal because we may be able to prescribe anifrolumab for our cutaneous lupus patients who don’t have systemic lupus,” Dr. Fernandez said.

Phase 3 data supported use the of anifrolumab in systemic lupus, including the TULIP-2 trial, which demonstrated its superiority to placebo for reducing severity of systemic disease and lowering corticosteroid use. A study published in March 2023 of 11 patients showed that they had a “very fast response” to the agent, Dr. Fernandez said, with a 50% or greater improvement in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score reached by all participants at week 16. Improvements of 50% or more in this scoring system are considered clinically meaningful, he added.
 

Upcoming Dermatomyositis Treatments

Why highlight emerging therapies for CLE and dermatomyositis in the same ODAC presentation? Although distinct conditions, these autoimmune conditions are both mediated by type 1 IFN inflammation.

Dermatomyositis is a relatively rare immune-mediated disease that most commonly affects the skin and muscle. Doctors score disease presentation, activity, and clinical improvements on a scale similar to CLASI for cutaneous lupus, the CDASI or Cutaneous Dermatomyositis Disease Area and Severity Index. Among people with CDASI activity scores of at least 14, which is the threshold for moderate to severe disease, a 20% improvement is clinically meaningful, Dr. Fernandez said. In addition, a 40% or greater improvement correlates with significant improvements in quality of life.

There is now more evidence for the use of IVIG to treat dermatomyositis. “Among those of us who treat dermatomyositis on a regular basis, we believe IVIG is the most potent treatment. We’ve known that for a long time,” Dr. Fernandez said.

Despite this tenet, for years, there was only one placebo-controlled trial, published in 1993, that evaluated IVIG treatment for dermatomyositis, and it included only 15 participants. That was until October 2022, he said, when the New England Journal of Medicine published a study comparing a specific brand of IVIG (Octagam) with placebo in 95 people with dermatomyositis.

In the study, 79% of participants treated with IVIG had a total improvement score of at least 20 (minimal improvement), the primary endpoint, at 16 weeks, compared with 44% of those receiving a placebo. Those treated with IVIG also had significant improvements in the CDASI score, a secondary endpoint, compared with those on placebo, he said.

Based on results of this trial, the FDA approved Octagam 10% for dermatomyositis in adults. Dr. Fernandez noted the approval is restricted to the brand of IVIG in the trial, not all IVIG products. However, “the FDA approval is most important to us because it gives us ammunition to fight for insurers to approve IVIG when we feel our patients with dermatomyositis need it,” regardless of the brand.
 

The Potential of JAK1 Inhibitors

An open-label study of the JAK inhibitor tofacitinib, published in December 2020, showed that mean changes in CDASI activity scores at 12 weeks were statistically significant compared with baseline in 10 people with dermatomyositis. “The importance of this study is that it is proof of concept that JAK inhibition can be effective for treating dermatomyositis, especially with active skin disease,” Dr. Fernandez said.

In addition, two large phase 3 trials are evaluating JAK inhibitor safety and efficacy for treating dermatomyositis. One is the VALOR trial, currently recruiting people with recalcitrant dermatomyositis to evaluate treatment with brepocitinib. Researchers in France are looking at another JAK inhibitor, baricitinib, for treating relapsing or treatment-naive dermatomyositis. Recruitment for the BIRD clinical trial is ongoing.

Monoclonal Antibody Showing Promise

“When it comes to looking specifically at dermatomyositis cutaneous disease, it’s been found that the levels of IFN beta correlate best with not only lesional skin type 1 IFN inflammatory signatures but also overall clinical disease activity,” Dr. Fernandez said. This correlation is stronger than for any other IFN-1-type cytokine active in the disorder.

“Perhaps blocking IFN beta might be best way to get control of dermatomyositis activity,” he added.

With that in mind, a phase 2 trial of dazukibart presented at the American Academy of Dermatology 2023 annual meeting highlighted the promise of this agent that targets type 1 IFN beta.

The primary endpoint was improvement in CDASI at 12 weeks. “This medication has remarkable efficacy,” Dr. Fernandez said. “We were one of the sites for this trial. Despite being blinded, there was no question about who was receiving drug and who was receiving placebo.”

“A minimal clinical improvement in disease activity was seen in more than 90%, so almost every patient who received this medication had meaningful improvement,” he added.

Based on the results, the manufacturer, Pfizer, is recruiting participants for a phase 3 trial to further assess dazukibart in dermatomyositis and polymyositis. Dr. Fernandez said, “This is a story you should pay attention to if you treat any dermatomyositis patients at all.”

Regarding these emerging therapies for CLE and dermatomyositis, “This looks very much like the early days of psoriasis, in the early 2000s, when there was a lot of activity developing treatments,” Dr. Fernandez said. “I will predict that within 10 years, we will have multiple novel agents available that will probably work better than anything we have today.”

Dr. Fernandez reported receiving grant and/or research support from Alexion, Incyte, Mallinckrodt Pharmaceuticals, Novartis, Pfizer, and Priovant Therapeutics; acting as a consultant or advisory board member for AbbVie, Biogen, Mallinckrodt Pharmaceuticals; and being a member of the speaker bureau or receiving honoraria for non-CME from AbbVie, Kyowa Kirin, and Mallinckrodt Pharmaceuticals.

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — Advances in treating medical conditions rarely emerge in a straight line. Oftentimes, progress comes in fits and starts, and therapies to treat cutaneous lupus erythematosus (CLE) and dermatomyositis are no exception.

Beyond approved treatments that deserve more attention, like belimumab, approved by the Food and Drug Administration (FDA) for systemic lupus erythematosus (SLE) in 2011, and Octagam 10%, an intravenous immune globulin (IVIG) preparation approved for dermatomyositis in 2021, anticipation is growing for emerging therapies and their potential to provide relief to patients, Anthony Fernandez, MD, PhD, said at the ODAC Dermatology, Aesthetic & Surgical Conference. The tyrosine kinase 2 (TYK2) inhibitor deucravacitinib, Janus kinase (JAK) inhibitors brepocitinib and baricitinib, and the monoclonal antibody anifrolumab, he noted, are prime examples.

“There have been significant advances in the development of treatments for lupus erythematosus and dermatomyositis. In my opinion, this is the start of what will be the most exciting decade in the history of these two diseases,” said Dr. Fernandez, director of medical dermatology at the Cleveland Clinic.
 

Emerging Treatments for Cutaneous Lupus

Although SLE can involve many organ systems, the skin is one of the most affected. There are specific cutaneous lesions categorized as either acute cutaneous lupus, subacute cutaneous lupus, or chronic cutaneous lupus.

The oral TYK2 inhibitor deucravacitinib, for example, should be able to dampen interleukin responses in people with CLE, Dr. Fernandez said. Deucravacitinib was approved by the FDA to treat psoriasis in September 2022.

Cleveland Clinic Foundation

A phase 2 study published in 2023 focused on this agent for relief of systemic lupus. Improvements in cutaneous disease were a secondary endpoint. The trial demonstrated that the patients treated with deucravacitinib achieved a 56%-70% CLASI-50 response, depending on dosing, compared with a 17% response among those on placebo at week 48.

Based on the trial results, recruitment has begun for a phase 2 trial to evaluate deucravacitinib, compared with placebo, in patients with discoid and/or subacute cutaneous lupus. “This may be another medicine we have available to give to any of our patients with cutaneous lupus,” Dr. Fernandez said.
 

Anifrolumab Appears Promising

The FDA approval of anifrolumab, a type I interferon (IFN) receptor antagonist, for treating moderate to severe SLE in July 2021, for example, is good news for dermatologists and their patients, added Dr. Fernandez. “Almost immediately after approval, case studies showed marked improvement in patients with refractory cutaneous lupus.” While the therapy was approved for treating systemic lupus, it allows for off-label treatment of the cutaneous predominant form of the disease, he said.

Furthermore, the manufacturer of anifrolumab, AstraZeneca, is launching the LAVENDER clinical trial to assess the monoclonal antibody specifically for treating CLE. “This is a big deal because we may be able to prescribe anifrolumab for our cutaneous lupus patients who don’t have systemic lupus,” Dr. Fernandez said.

Phase 3 data supported use the of anifrolumab in systemic lupus, including the TULIP-2 trial, which demonstrated its superiority to placebo for reducing severity of systemic disease and lowering corticosteroid use. A study published in March 2023 of 11 patients showed that they had a “very fast response” to the agent, Dr. Fernandez said, with a 50% or greater improvement in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score reached by all participants at week 16. Improvements of 50% or more in this scoring system are considered clinically meaningful, he added.
 

Upcoming Dermatomyositis Treatments

Why highlight emerging therapies for CLE and dermatomyositis in the same ODAC presentation? Although distinct conditions, these autoimmune conditions are both mediated by type 1 IFN inflammation.

Dermatomyositis is a relatively rare immune-mediated disease that most commonly affects the skin and muscle. Doctors score disease presentation, activity, and clinical improvements on a scale similar to CLASI for cutaneous lupus, the CDASI or Cutaneous Dermatomyositis Disease Area and Severity Index. Among people with CDASI activity scores of at least 14, which is the threshold for moderate to severe disease, a 20% improvement is clinically meaningful, Dr. Fernandez said. In addition, a 40% or greater improvement correlates with significant improvements in quality of life.

There is now more evidence for the use of IVIG to treat dermatomyositis. “Among those of us who treat dermatomyositis on a regular basis, we believe IVIG is the most potent treatment. We’ve known that for a long time,” Dr. Fernandez said.

Despite this tenet, for years, there was only one placebo-controlled trial, published in 1993, that evaluated IVIG treatment for dermatomyositis, and it included only 15 participants. That was until October 2022, he said, when the New England Journal of Medicine published a study comparing a specific brand of IVIG (Octagam) with placebo in 95 people with dermatomyositis.

In the study, 79% of participants treated with IVIG had a total improvement score of at least 20 (minimal improvement), the primary endpoint, at 16 weeks, compared with 44% of those receiving a placebo. Those treated with IVIG also had significant improvements in the CDASI score, a secondary endpoint, compared with those on placebo, he said.

Based on results of this trial, the FDA approved Octagam 10% for dermatomyositis in adults. Dr. Fernandez noted the approval is restricted to the brand of IVIG in the trial, not all IVIG products. However, “the FDA approval is most important to us because it gives us ammunition to fight for insurers to approve IVIG when we feel our patients with dermatomyositis need it,” regardless of the brand.
 

The Potential of JAK1 Inhibitors

An open-label study of the JAK inhibitor tofacitinib, published in December 2020, showed that mean changes in CDASI activity scores at 12 weeks were statistically significant compared with baseline in 10 people with dermatomyositis. “The importance of this study is that it is proof of concept that JAK inhibition can be effective for treating dermatomyositis, especially with active skin disease,” Dr. Fernandez said.

In addition, two large phase 3 trials are evaluating JAK inhibitor safety and efficacy for treating dermatomyositis. One is the VALOR trial, currently recruiting people with recalcitrant dermatomyositis to evaluate treatment with brepocitinib. Researchers in France are looking at another JAK inhibitor, baricitinib, for treating relapsing or treatment-naive dermatomyositis. Recruitment for the BIRD clinical trial is ongoing.

Monoclonal Antibody Showing Promise

“When it comes to looking specifically at dermatomyositis cutaneous disease, it’s been found that the levels of IFN beta correlate best with not only lesional skin type 1 IFN inflammatory signatures but also overall clinical disease activity,” Dr. Fernandez said. This correlation is stronger than for any other IFN-1-type cytokine active in the disorder.

“Perhaps blocking IFN beta might be best way to get control of dermatomyositis activity,” he added.

With that in mind, a phase 2 trial of dazukibart presented at the American Academy of Dermatology 2023 annual meeting highlighted the promise of this agent that targets type 1 IFN beta.

The primary endpoint was improvement in CDASI at 12 weeks. “This medication has remarkable efficacy,” Dr. Fernandez said. “We were one of the sites for this trial. Despite being blinded, there was no question about who was receiving drug and who was receiving placebo.”

“A minimal clinical improvement in disease activity was seen in more than 90%, so almost every patient who received this medication had meaningful improvement,” he added.

Based on the results, the manufacturer, Pfizer, is recruiting participants for a phase 3 trial to further assess dazukibart in dermatomyositis and polymyositis. Dr. Fernandez said, “This is a story you should pay attention to if you treat any dermatomyositis patients at all.”

Regarding these emerging therapies for CLE and dermatomyositis, “This looks very much like the early days of psoriasis, in the early 2000s, when there was a lot of activity developing treatments,” Dr. Fernandez said. “I will predict that within 10 years, we will have multiple novel agents available that will probably work better than anything we have today.”

Dr. Fernandez reported receiving grant and/or research support from Alexion, Incyte, Mallinckrodt Pharmaceuticals, Novartis, Pfizer, and Priovant Therapeutics; acting as a consultant or advisory board member for AbbVie, Biogen, Mallinckrodt Pharmaceuticals; and being a member of the speaker bureau or receiving honoraria for non-CME from AbbVie, Kyowa Kirin, and Mallinckrodt Pharmaceuticals.

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — Advances in treating medical conditions rarely emerge in a straight line. Oftentimes, progress comes in fits and starts, and therapies to treat cutaneous lupus erythematosus (CLE) and dermatomyositis are no exception.

Beyond approved treatments that deserve more attention, like belimumab, approved by the Food and Drug Administration (FDA) for systemic lupus erythematosus (SLE) in 2011, and Octagam 10%, an intravenous immune globulin (IVIG) preparation approved for dermatomyositis in 2021, anticipation is growing for emerging therapies and their potential to provide relief to patients, Anthony Fernandez, MD, PhD, said at the ODAC Dermatology, Aesthetic & Surgical Conference. The tyrosine kinase 2 (TYK2) inhibitor deucravacitinib, Janus kinase (JAK) inhibitors brepocitinib and baricitinib, and the monoclonal antibody anifrolumab, he noted, are prime examples.

“There have been significant advances in the development of treatments for lupus erythematosus and dermatomyositis. In my opinion, this is the start of what will be the most exciting decade in the history of these two diseases,” said Dr. Fernandez, director of medical dermatology at the Cleveland Clinic.
 

Emerging Treatments for Cutaneous Lupus

Although SLE can involve many organ systems, the skin is one of the most affected. There are specific cutaneous lesions categorized as either acute cutaneous lupus, subacute cutaneous lupus, or chronic cutaneous lupus.

The oral TYK2 inhibitor deucravacitinib, for example, should be able to dampen interleukin responses in people with CLE, Dr. Fernandez said. Deucravacitinib was approved by the FDA to treat psoriasis in September 2022.

Cleveland Clinic Foundation

A phase 2 study published in 2023 focused on this agent for relief of systemic lupus. Improvements in cutaneous disease were a secondary endpoint. The trial demonstrated that the patients treated with deucravacitinib achieved a 56%-70% CLASI-50 response, depending on dosing, compared with a 17% response among those on placebo at week 48.

Based on the trial results, recruitment has begun for a phase 2 trial to evaluate deucravacitinib, compared with placebo, in patients with discoid and/or subacute cutaneous lupus. “This may be another medicine we have available to give to any of our patients with cutaneous lupus,” Dr. Fernandez said.
 

Anifrolumab Appears Promising

The FDA approval of anifrolumab, a type I interferon (IFN) receptor antagonist, for treating moderate to severe SLE in July 2021, for example, is good news for dermatologists and their patients, added Dr. Fernandez. “Almost immediately after approval, case studies showed marked improvement in patients with refractory cutaneous lupus.” While the therapy was approved for treating systemic lupus, it allows for off-label treatment of the cutaneous predominant form of the disease, he said.

Furthermore, the manufacturer of anifrolumab, AstraZeneca, is launching the LAVENDER clinical trial to assess the monoclonal antibody specifically for treating CLE. “This is a big deal because we may be able to prescribe anifrolumab for our cutaneous lupus patients who don’t have systemic lupus,” Dr. Fernandez said.

Phase 3 data supported use the of anifrolumab in systemic lupus, including the TULIP-2 trial, which demonstrated its superiority to placebo for reducing severity of systemic disease and lowering corticosteroid use. A study published in March 2023 of 11 patients showed that they had a “very fast response” to the agent, Dr. Fernandez said, with a 50% or greater improvement in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score reached by all participants at week 16. Improvements of 50% or more in this scoring system are considered clinically meaningful, he added.
 

Upcoming Dermatomyositis Treatments

Why highlight emerging therapies for CLE and dermatomyositis in the same ODAC presentation? Although distinct conditions, these autoimmune conditions are both mediated by type 1 IFN inflammation.

Dermatomyositis is a relatively rare immune-mediated disease that most commonly affects the skin and muscle. Doctors score disease presentation, activity, and clinical improvements on a scale similar to CLASI for cutaneous lupus, the CDASI or Cutaneous Dermatomyositis Disease Area and Severity Index. Among people with CDASI activity scores of at least 14, which is the threshold for moderate to severe disease, a 20% improvement is clinically meaningful, Dr. Fernandez said. In addition, a 40% or greater improvement correlates with significant improvements in quality of life.

There is now more evidence for the use of IVIG to treat dermatomyositis. “Among those of us who treat dermatomyositis on a regular basis, we believe IVIG is the most potent treatment. We’ve known that for a long time,” Dr. Fernandez said.

Despite this tenet, for years, there was only one placebo-controlled trial, published in 1993, that evaluated IVIG treatment for dermatomyositis, and it included only 15 participants. That was until October 2022, he said, when the New England Journal of Medicine published a study comparing a specific brand of IVIG (Octagam) with placebo in 95 people with dermatomyositis.

In the study, 79% of participants treated with IVIG had a total improvement score of at least 20 (minimal improvement), the primary endpoint, at 16 weeks, compared with 44% of those receiving a placebo. Those treated with IVIG also had significant improvements in the CDASI score, a secondary endpoint, compared with those on placebo, he said.

Based on results of this trial, the FDA approved Octagam 10% for dermatomyositis in adults. Dr. Fernandez noted the approval is restricted to the brand of IVIG in the trial, not all IVIG products. However, “the FDA approval is most important to us because it gives us ammunition to fight for insurers to approve IVIG when we feel our patients with dermatomyositis need it,” regardless of the brand.
 

The Potential of JAK1 Inhibitors

An open-label study of the JAK inhibitor tofacitinib, published in December 2020, showed that mean changes in CDASI activity scores at 12 weeks were statistically significant compared with baseline in 10 people with dermatomyositis. “The importance of this study is that it is proof of concept that JAK inhibition can be effective for treating dermatomyositis, especially with active skin disease,” Dr. Fernandez said.

In addition, two large phase 3 trials are evaluating JAK inhibitor safety and efficacy for treating dermatomyositis. One is the VALOR trial, currently recruiting people with recalcitrant dermatomyositis to evaluate treatment with brepocitinib. Researchers in France are looking at another JAK inhibitor, baricitinib, for treating relapsing or treatment-naive dermatomyositis. Recruitment for the BIRD clinical trial is ongoing.

Monoclonal Antibody Showing Promise

“When it comes to looking specifically at dermatomyositis cutaneous disease, it’s been found that the levels of IFN beta correlate best with not only lesional skin type 1 IFN inflammatory signatures but also overall clinical disease activity,” Dr. Fernandez said. This correlation is stronger than for any other IFN-1-type cytokine active in the disorder.

“Perhaps blocking IFN beta might be best way to get control of dermatomyositis activity,” he added.

With that in mind, a phase 2 trial of dazukibart presented at the American Academy of Dermatology 2023 annual meeting highlighted the promise of this agent that targets type 1 IFN beta.

The primary endpoint was improvement in CDASI at 12 weeks. “This medication has remarkable efficacy,” Dr. Fernandez said. “We were one of the sites for this trial. Despite being blinded, there was no question about who was receiving drug and who was receiving placebo.”

“A minimal clinical improvement in disease activity was seen in more than 90%, so almost every patient who received this medication had meaningful improvement,” he added.

Based on the results, the manufacturer, Pfizer, is recruiting participants for a phase 3 trial to further assess dazukibart in dermatomyositis and polymyositis. Dr. Fernandez said, “This is a story you should pay attention to if you treat any dermatomyositis patients at all.”

Regarding these emerging therapies for CLE and dermatomyositis, “This looks very much like the early days of psoriasis, in the early 2000s, when there was a lot of activity developing treatments,” Dr. Fernandez said. “I will predict that within 10 years, we will have multiple novel agents available that will probably work better than anything we have today.”

Dr. Fernandez reported receiving grant and/or research support from Alexion, Incyte, Mallinckrodt Pharmaceuticals, Novartis, Pfizer, and Priovant Therapeutics; acting as a consultant or advisory board member for AbbVie, Biogen, Mallinckrodt Pharmaceuticals; and being a member of the speaker bureau or receiving honoraria for non-CME from AbbVie, Kyowa Kirin, and Mallinckrodt Pharmaceuticals.

A version of this article appeared on Medscape.com.

Officials at Dana-Farber Cancer Institute are moving to retract at least six published research papers and correct 31 others amid allegations of data manipulation.

News of the investigation follows a blog post by British molecular biologist Sholto David, MD, who flagged almost 60 papers published between 1997 and 2017 that contained image manipulation and other errors. Some of the papers were published by Dana-Farber’s chief executive officer, Laurie Glimcher, MD, and chief operating officer, William Hahn, MD, on topics including multiple myeloma and immune cells.

Mr. David, who blogs about research integrity, highlighted numerous errors and irregularities, including copying and pasting images across multiple experiments to represent different days within the same experiment, sometimes rotating or stretching images.

In one case, Mr. David equated the manipulation with tactics used by “hapless Chinese papermills” and concluded that “a swathe of research coming out of [Dana-Farber] authored by the most senior researchers and managers appears to be hopelessly corrupt with errors that are obvious from just a cursory reading the papers.” 

“Imagine what mistakes might be found in the raw data if anyone was allowed to look!” he wrote.

Barrett Rollins, MD, PhD, Dana-Farber Cancer Institute’s research integrity officer, declined to comment on whether the errors represent scientific misconduct, according to STAT. Rollins told ScienceInsider that the “presence of image discrepancies in a paper is not evidence of an author’s intent to deceive.” 

Access to new artificial intelligence tools is making it easier for data sleuths, like Mr. David, to unearth data manipulation and errors. 

The current investigation closely follows two other investigations into the published work of Harvard University’s former president, Claudine Gay, and Stanford University’s former president, Marc Tessier-Lavigne, which led both to resign their posts. 

A version of this article appeared on Medscape.com.

Officials at Dana-Farber Cancer Institute are moving to retract at least six published research papers and correct 31 others amid allegations of data manipulation.

News of the investigation follows a blog post by British molecular biologist Sholto David, MD, who flagged almost 60 papers published between 1997 and 2017 that contained image manipulation and other errors. Some of the papers were published by Dana-Farber’s chief executive officer, Laurie Glimcher, MD, and chief operating officer, William Hahn, MD, on topics including multiple myeloma and immune cells.

Mr. David, who blogs about research integrity, highlighted numerous errors and irregularities, including copying and pasting images across multiple experiments to represent different days within the same experiment, sometimes rotating or stretching images.

In one case, Mr. David equated the manipulation with tactics used by “hapless Chinese papermills” and concluded that “a swathe of research coming out of [Dana-Farber] authored by the most senior researchers and managers appears to be hopelessly corrupt with errors that are obvious from just a cursory reading the papers.” 

“Imagine what mistakes might be found in the raw data if anyone was allowed to look!” he wrote.

Barrett Rollins, MD, PhD, Dana-Farber Cancer Institute’s research integrity officer, declined to comment on whether the errors represent scientific misconduct, according to STAT. Rollins told ScienceInsider that the “presence of image discrepancies in a paper is not evidence of an author’s intent to deceive.” 

Access to new artificial intelligence tools is making it easier for data sleuths, like Mr. David, to unearth data manipulation and errors. 

The current investigation closely follows two other investigations into the published work of Harvard University’s former president, Claudine Gay, and Stanford University’s former president, Marc Tessier-Lavigne, which led both to resign their posts. 

A version of this article appeared on Medscape.com.

Officials at Dana-Farber Cancer Institute are moving to retract at least six published research papers and correct 31 others amid allegations of data manipulation.

News of the investigation follows a blog post by British molecular biologist Sholto David, MD, who flagged almost 60 papers published between 1997 and 2017 that contained image manipulation and other errors. Some of the papers were published by Dana-Farber’s chief executive officer, Laurie Glimcher, MD, and chief operating officer, William Hahn, MD, on topics including multiple myeloma and immune cells.

Mr. David, who blogs about research integrity, highlighted numerous errors and irregularities, including copying and pasting images across multiple experiments to represent different days within the same experiment, sometimes rotating or stretching images.

In one case, Mr. David equated the manipulation with tactics used by “hapless Chinese papermills” and concluded that “a swathe of research coming out of [Dana-Farber] authored by the most senior researchers and managers appears to be hopelessly corrupt with errors that are obvious from just a cursory reading the papers.” 

“Imagine what mistakes might be found in the raw data if anyone was allowed to look!” he wrote.

Barrett Rollins, MD, PhD, Dana-Farber Cancer Institute’s research integrity officer, declined to comment on whether the errors represent scientific misconduct, according to STAT. Rollins told ScienceInsider that the “presence of image discrepancies in a paper is not evidence of an author’s intent to deceive.” 

Access to new artificial intelligence tools is making it easier for data sleuths, like Mr. David, to unearth data manipulation and errors. 

The current investigation closely follows two other investigations into the published work of Harvard University’s former president, Claudine Gay, and Stanford University’s former president, Marc Tessier-Lavigne, which led both to resign their posts. 

A version of this article appeared on Medscape.com.

TOPLINE:

Indicators of early bone loss were significantly higher in adults with severe obstructive sleep apnea (OSA) than in those with mild or moderate OSA and controls.

METHODOLOGY:

• The researchers enrolled 90 men aged 30-59 years who were patients at a single sleep and respiratory center between August 2017 and February 2019; the average age was 47.1 years, and the average body mass index was 25.7 kg/m².
• The study population included 25 individuals with mild OSA, 21 with moderate OSA, 34 with severe OSA, and 10 controls without OSA.
• Bone loss was assessed using high-resolution peripheral quantitative computed tomography and blood samples. The researchers collected information on metabolic and inflammatory bone turnover indicators, as well as bone geometric parameters, bone microstructure parameters, and measures of bone mineral density (BMD).

TAKEAWAY:

• Total volumetric bone mineral density was significantly lower in patients with OSA than in controls and significantly different among OSA groups, as were the meta trabecular volumetric BMD, trabecular thickness (Tb.Th), and cortical thickness (Ct.Th).
• Differences in bone microstructure between patients with OSA and controls were most evident in measures of Tb.Th and Ct.Th.
• No significant differences appeared in blood bone turnover indicators or inflammation indicators among the groups.

IN PRACTICE:

“A study with a larger sample is necessary to further assess the relationship and mechanisms between OSA and osteoporosis,” the researchers wrote. 

SOURCE:

The lead author on the study was Yixian Qiao, MD, of the Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. The study was published online in BMC Pulmonary Medicine.

LIMITATIONS:

The cross-sectional design, small sample size, and inability to control for several key confounders such as nutritional status and amount of exercise, as well as the exclusion of women and elderly individuals, limited the findings.

DISCLOSURES:

The study was supported by the National Key Research and Development Projects of China. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Indicators of early bone loss were significantly higher in adults with severe obstructive sleep apnea (OSA) than in those with mild or moderate OSA and controls.

METHODOLOGY:

• The researchers enrolled 90 men aged 30-59 years who were patients at a single sleep and respiratory center between August 2017 and February 2019; the average age was 47.1 years, and the average body mass index was 25.7 kg/m².
• The study population included 25 individuals with mild OSA, 21 with moderate OSA, 34 with severe OSA, and 10 controls without OSA.
• Bone loss was assessed using high-resolution peripheral quantitative computed tomography and blood samples. The researchers collected information on metabolic and inflammatory bone turnover indicators, as well as bone geometric parameters, bone microstructure parameters, and measures of bone mineral density (BMD).

TAKEAWAY:

• Total volumetric bone mineral density was significantly lower in patients with OSA than in controls and significantly different among OSA groups, as were the meta trabecular volumetric BMD, trabecular thickness (Tb.Th), and cortical thickness (Ct.Th).
• Differences in bone microstructure between patients with OSA and controls were most evident in measures of Tb.Th and Ct.Th.
• No significant differences appeared in blood bone turnover indicators or inflammation indicators among the groups.

IN PRACTICE:

“A study with a larger sample is necessary to further assess the relationship and mechanisms between OSA and osteoporosis,” the researchers wrote. 

SOURCE:

The lead author on the study was Yixian Qiao, MD, of the Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. The study was published online in BMC Pulmonary Medicine.

LIMITATIONS:

The cross-sectional design, small sample size, and inability to control for several key confounders such as nutritional status and amount of exercise, as well as the exclusion of women and elderly individuals, limited the findings.

DISCLOSURES:

The study was supported by the National Key Research and Development Projects of China. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Indicators of early bone loss were significantly higher in adults with severe obstructive sleep apnea (OSA) than in those with mild or moderate OSA and controls.

METHODOLOGY:

• The researchers enrolled 90 men aged 30-59 years who were patients at a single sleep and respiratory center between August 2017 and February 2019; the average age was 47.1 years, and the average body mass index was 25.7 kg/m².
• The study population included 25 individuals with mild OSA, 21 with moderate OSA, 34 with severe OSA, and 10 controls without OSA.
• Bone loss was assessed using high-resolution peripheral quantitative computed tomography and blood samples. The researchers collected information on metabolic and inflammatory bone turnover indicators, as well as bone geometric parameters, bone microstructure parameters, and measures of bone mineral density (BMD).

TAKEAWAY:

• Total volumetric bone mineral density was significantly lower in patients with OSA than in controls and significantly different among OSA groups, as were the meta trabecular volumetric BMD, trabecular thickness (Tb.Th), and cortical thickness (Ct.Th).
• Differences in bone microstructure between patients with OSA and controls were most evident in measures of Tb.Th and Ct.Th.
• No significant differences appeared in blood bone turnover indicators or inflammation indicators among the groups.

IN PRACTICE:

“A study with a larger sample is necessary to further assess the relationship and mechanisms between OSA and osteoporosis,” the researchers wrote. 

SOURCE:

The lead author on the study was Yixian Qiao, MD, of the Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. The study was published online in BMC Pulmonary Medicine.

LIMITATIONS:

The cross-sectional design, small sample size, and inability to control for several key confounders such as nutritional status and amount of exercise, as well as the exclusion of women and elderly individuals, limited the findings.

DISCLOSURES:

The study was supported by the National Key Research and Development Projects of China. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

A history of cancer is an independent predictor of major cardiovascular events in patients undergoing coronary angioplasty. Cancer should be considered a new cardiovascular risk factor in primary and secondary prevention, according to a study presented at the 2023 American Heart Association Congress in Philadelphia.

“We believe that this finding should, in the future, at least at the time of discharge or the end of oncologic treatment, [encourage] the pursuit of much more demanding cardiovascular primary prevention goals than in the general population, for example, equating it to the situation of a patient with diabetes or chronic renal failure,” said lead author Renzo Melchiori, MD, a cardiologist at the University Hospital Austral in Pilar, Argentina. 

The researchers also advocate for intensifying cardiovascular control measures in secondary prevention for these patients, reconsidering goals, and ensuring compliance with prescribed pharmacological regimens and healthy lifestyle habits.

“Previously, when a patient had oncological pathology, thinking about associated cardiovascular risk seemed somewhat superfluous. But today, oncological diseases are treated so effectively, increasing survival and life expectancy, that we begin to focus on what happens with the arteries of these patients after treatment,” said Dr. Melchiori.

Higher Incidence Density 

The retrospective analysis included 937 patients of both sexes aged 18 years and older who underwent coronary angioplasty for acute coronary syndrome between 2008 and 2022 at a university hospital. Of these participants, 89 (9.5%) had a history of cancer, with a median time since oncologic diagnosis of around 2 years for solid and hematologic tumors. Most participants had treated and resolved cancer.

Over a median follow-up of 45 months (range, 14-72 months), the cumulative incidence rates of a major cardiovascular event (nonfatal stroke, nonfatal acute myocardial infarction, cardiovascular death, or new angioplasty) were 22.2% (155/698) and 28.4% (25/88) in the groups without and with a history of cancer, respectively. The incidence density was significantly higher in the group with an oncologic history than in the group without such a history: 0.78 events/100 patients/month vs 0.48 events/100 patients/month (P = .01).

Kaplan-Meier analysis showed a higher probability of a major cardiovascular event in the group of patients with cancer or a history of cancer (P = .0086). In multivariate Cox regression analysis, cancer history was an independent predictor of major cardiovascular events adjusted for other risk factors such as age, hypertension, diabetes, smoking, sedentary lifestyle, and family history (hazard ratio, 1.66; P = .025).

Dr. Melchiori clarified that the increased incidence of cardiovascular events in patients with cancer or a history of cancer cannot be attributed to differences in percutaneous intervention or the indication or compliance of post-treatment pharmacological therapy.

In addition, the specialist acknowledged that due to the sample size, discrimination by cancer type, disease stage, or therapeutic strategies couldn’t be performed. A subanalysis, which has not been presented, indicated that the effect could not be explained solely by the application of radiotherapy or chemotherapy in the 90 days before angioplasty — two factors that cause arterial inflammation.

Intensifying Prevention Measures

Two independent experts told this news organization that the new study is "interesting" and reinforces the close connection between oncologic and cardiovascular pathology.

Andrés Daniele, MD, cardiologist and president of the Argentine Cardio-Oncology Association, a local chapter of the International Cardio-Oncology Society, emphasized that the study “reiterates an observation seen in other works: A higher rate of atherosclerotic pathology and cardiovascular events in patients with a history of cancer. And that has a reason to be: Both pathologies present common risk factors, and on the other hand, there is greater endothelial dysfunction secondary to the inflammatory syndrome and oncologic therapies.”

“There needs to be a continuum in the intensification of measures in primary and secondary cardiovascular prevention in cancer survivors, whether in remission or with chronic disease. We need to be very aggressive in managing risk factors and insist that patients who have had a cardiovascular event enter cardiovascular rehabilitation therapies,” said Dr. Daniele, who also heads the Cardio-Oncology Department at the centenary Roffo Institute of Oncology at the University of Buenos Aires, Argentina.

The study provides a valuable contribution because “we need to understand the epidemiology and natural history of patients with cancer at risk of developing cardiovascular complications to implement personalized cardiovascular prevention strategies,” said Teresa López Fernández, MD, cardiologist, coordinator of the Cardio-Oncology Program at La Paz University Hospital in Madrid, member of the Cardio-Oncology Working Group of the Spanish Society of Cardiology, member of the board of the International Cardio-Oncology Society, and cochair of the first clinical practice guidelines in cardio-oncology of the European Society of Cardiology.

“We have to be aware that perhaps we should not guide ourselves in these patients with the usual risk stratification scores as cancer or cardiotoxic treatment are not included as variables. However, they require our attention and effort to improve their quality and quantity of life, avoiding potentially preventable cardiovascular events that could negatively impact the survival achieved thanks to advances in cancer treatments,” said Dr. López Fernández.

Dr. Melchiori and Dr. Daniele declared no relevant economic conflicts of interest. Dr. López Fernández reported relationships with Daiichi Sankyo, Almirall España, Janssen-Cilag, Bayer, Roche, Philips, and Incyte. 

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

A history of cancer is an independent predictor of major cardiovascular events in patients undergoing coronary angioplasty. Cancer should be considered a new cardiovascular risk factor in primary and secondary prevention, according to a study presented at the 2023 American Heart Association Congress in Philadelphia.

“We believe that this finding should, in the future, at least at the time of discharge or the end of oncologic treatment, [encourage] the pursuit of much more demanding cardiovascular primary prevention goals than in the general population, for example, equating it to the situation of a patient with diabetes or chronic renal failure,” said lead author Renzo Melchiori, MD, a cardiologist at the University Hospital Austral in Pilar, Argentina. 

The researchers also advocate for intensifying cardiovascular control measures in secondary prevention for these patients, reconsidering goals, and ensuring compliance with prescribed pharmacological regimens and healthy lifestyle habits.

“Previously, when a patient had oncological pathology, thinking about associated cardiovascular risk seemed somewhat superfluous. But today, oncological diseases are treated so effectively, increasing survival and life expectancy, that we begin to focus on what happens with the arteries of these patients after treatment,” said Dr. Melchiori.

Higher Incidence Density 

The retrospective analysis included 937 patients of both sexes aged 18 years and older who underwent coronary angioplasty for acute coronary syndrome between 2008 and 2022 at a university hospital. Of these participants, 89 (9.5%) had a history of cancer, with a median time since oncologic diagnosis of around 2 years for solid and hematologic tumors. Most participants had treated and resolved cancer.

Over a median follow-up of 45 months (range, 14-72 months), the cumulative incidence rates of a major cardiovascular event (nonfatal stroke, nonfatal acute myocardial infarction, cardiovascular death, or new angioplasty) were 22.2% (155/698) and 28.4% (25/88) in the groups without and with a history of cancer, respectively. The incidence density was significantly higher in the group with an oncologic history than in the group without such a history: 0.78 events/100 patients/month vs 0.48 events/100 patients/month (P = .01).

Kaplan-Meier analysis showed a higher probability of a major cardiovascular event in the group of patients with cancer or a history of cancer (P = .0086). In multivariate Cox regression analysis, cancer history was an independent predictor of major cardiovascular events adjusted for other risk factors such as age, hypertension, diabetes, smoking, sedentary lifestyle, and family history (hazard ratio, 1.66; P = .025).

Dr. Melchiori clarified that the increased incidence of cardiovascular events in patients with cancer or a history of cancer cannot be attributed to differences in percutaneous intervention or the indication or compliance of post-treatment pharmacological therapy.

In addition, the specialist acknowledged that due to the sample size, discrimination by cancer type, disease stage, or therapeutic strategies couldn’t be performed. A subanalysis, which has not been presented, indicated that the effect could not be explained solely by the application of radiotherapy or chemotherapy in the 90 days before angioplasty — two factors that cause arterial inflammation.

Intensifying Prevention Measures

Two independent experts told this news organization that the new study is "interesting" and reinforces the close connection between oncologic and cardiovascular pathology.

Andrés Daniele, MD, cardiologist and president of the Argentine Cardio-Oncology Association, a local chapter of the International Cardio-Oncology Society, emphasized that the study “reiterates an observation seen in other works: A higher rate of atherosclerotic pathology and cardiovascular events in patients with a history of cancer. And that has a reason to be: Both pathologies present common risk factors, and on the other hand, there is greater endothelial dysfunction secondary to the inflammatory syndrome and oncologic therapies.”

“There needs to be a continuum in the intensification of measures in primary and secondary cardiovascular prevention in cancer survivors, whether in remission or with chronic disease. We need to be very aggressive in managing risk factors and insist that patients who have had a cardiovascular event enter cardiovascular rehabilitation therapies,” said Dr. Daniele, who also heads the Cardio-Oncology Department at the centenary Roffo Institute of Oncology at the University of Buenos Aires, Argentina.

The study provides a valuable contribution because “we need to understand the epidemiology and natural history of patients with cancer at risk of developing cardiovascular complications to implement personalized cardiovascular prevention strategies,” said Teresa López Fernández, MD, cardiologist, coordinator of the Cardio-Oncology Program at La Paz University Hospital in Madrid, member of the Cardio-Oncology Working Group of the Spanish Society of Cardiology, member of the board of the International Cardio-Oncology Society, and cochair of the first clinical practice guidelines in cardio-oncology of the European Society of Cardiology.

“We have to be aware that perhaps we should not guide ourselves in these patients with the usual risk stratification scores as cancer or cardiotoxic treatment are not included as variables. However, they require our attention and effort to improve their quality and quantity of life, avoiding potentially preventable cardiovascular events that could negatively impact the survival achieved thanks to advances in cancer treatments,” said Dr. López Fernández.

Dr. Melchiori and Dr. Daniele declared no relevant economic conflicts of interest. Dr. López Fernández reported relationships with Daiichi Sankyo, Almirall España, Janssen-Cilag, Bayer, Roche, Philips, and Incyte. 

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

A history of cancer is an independent predictor of major cardiovascular events in patients undergoing coronary angioplasty. Cancer should be considered a new cardiovascular risk factor in primary and secondary prevention, according to a study presented at the 2023 American Heart Association Congress in Philadelphia.

“We believe that this finding should, in the future, at least at the time of discharge or the end of oncologic treatment, [encourage] the pursuit of much more demanding cardiovascular primary prevention goals than in the general population, for example, equating it to the situation of a patient with diabetes or chronic renal failure,” said lead author Renzo Melchiori, MD, a cardiologist at the University Hospital Austral in Pilar, Argentina. 

The researchers also advocate for intensifying cardiovascular control measures in secondary prevention for these patients, reconsidering goals, and ensuring compliance with prescribed pharmacological regimens and healthy lifestyle habits.

“Previously, when a patient had oncological pathology, thinking about associated cardiovascular risk seemed somewhat superfluous. But today, oncological diseases are treated so effectively, increasing survival and life expectancy, that we begin to focus on what happens with the arteries of these patients after treatment,” said Dr. Melchiori.

Higher Incidence Density 

The retrospective analysis included 937 patients of both sexes aged 18 years and older who underwent coronary angioplasty for acute coronary syndrome between 2008 and 2022 at a university hospital. Of these participants, 89 (9.5%) had a history of cancer, with a median time since oncologic diagnosis of around 2 years for solid and hematologic tumors. Most participants had treated and resolved cancer.

Over a median follow-up of 45 months (range, 14-72 months), the cumulative incidence rates of a major cardiovascular event (nonfatal stroke, nonfatal acute myocardial infarction, cardiovascular death, or new angioplasty) were 22.2% (155/698) and 28.4% (25/88) in the groups without and with a history of cancer, respectively. The incidence density was significantly higher in the group with an oncologic history than in the group without such a history: 0.78 events/100 patients/month vs 0.48 events/100 patients/month (P = .01).

Kaplan-Meier analysis showed a higher probability of a major cardiovascular event in the group of patients with cancer or a history of cancer (P = .0086). In multivariate Cox regression analysis, cancer history was an independent predictor of major cardiovascular events adjusted for other risk factors such as age, hypertension, diabetes, smoking, sedentary lifestyle, and family history (hazard ratio, 1.66; P = .025).

Dr. Melchiori clarified that the increased incidence of cardiovascular events in patients with cancer or a history of cancer cannot be attributed to differences in percutaneous intervention or the indication or compliance of post-treatment pharmacological therapy.

In addition, the specialist acknowledged that due to the sample size, discrimination by cancer type, disease stage, or therapeutic strategies couldn’t be performed. A subanalysis, which has not been presented, indicated that the effect could not be explained solely by the application of radiotherapy or chemotherapy in the 90 days before angioplasty — two factors that cause arterial inflammation.

Intensifying Prevention Measures

Two independent experts told this news organization that the new study is "interesting" and reinforces the close connection between oncologic and cardiovascular pathology.

Andrés Daniele, MD, cardiologist and president of the Argentine Cardio-Oncology Association, a local chapter of the International Cardio-Oncology Society, emphasized that the study “reiterates an observation seen in other works: A higher rate of atherosclerotic pathology and cardiovascular events in patients with a history of cancer. And that has a reason to be: Both pathologies present common risk factors, and on the other hand, there is greater endothelial dysfunction secondary to the inflammatory syndrome and oncologic therapies.”

“There needs to be a continuum in the intensification of measures in primary and secondary cardiovascular prevention in cancer survivors, whether in remission or with chronic disease. We need to be very aggressive in managing risk factors and insist that patients who have had a cardiovascular event enter cardiovascular rehabilitation therapies,” said Dr. Daniele, who also heads the Cardio-Oncology Department at the centenary Roffo Institute of Oncology at the University of Buenos Aires, Argentina.

The study provides a valuable contribution because “we need to understand the epidemiology and natural history of patients with cancer at risk of developing cardiovascular complications to implement personalized cardiovascular prevention strategies,” said Teresa López Fernández, MD, cardiologist, coordinator of the Cardio-Oncology Program at La Paz University Hospital in Madrid, member of the Cardio-Oncology Working Group of the Spanish Society of Cardiology, member of the board of the International Cardio-Oncology Society, and cochair of the first clinical practice guidelines in cardio-oncology of the European Society of Cardiology.

“We have to be aware that perhaps we should not guide ourselves in these patients with the usual risk stratification scores as cancer or cardiotoxic treatment are not included as variables. However, they require our attention and effort to improve their quality and quantity of life, avoiding potentially preventable cardiovascular events that could negatively impact the survival achieved thanks to advances in cancer treatments,” said Dr. López Fernández.

Dr. Melchiori and Dr. Daniele declared no relevant economic conflicts of interest. Dr. López Fernández reported relationships with Daiichi Sankyo, Almirall España, Janssen-Cilag, Bayer, Roche, Philips, and Incyte. 

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

Foreign-trained doctors can supplement the nation’s waning physician workforce and bring diverse perspectives to patient care, but a new study finds that most never enter comparable roles after immigration, raising questions about the feasibility of educational and licensing pathways for international medical graduates (IMGs). 

Conducted by the Federal Reserve Bank of Minneapolis and the nonprofit Upwardly Global, the study analyzed the data of 300 physicians who immigrated to the United States between 2004 and 2022. 

Although 85% of IMGs found employment, only 1 in 3 became a medical resident or doctor. 

Despite the study’s small sample size, it highlights the hurdles IMGs face, the authors noted. Even though they have a medical degree and potentially years of clinical experience in another country, they typically must start all over again in the US — passing the United States Medical Licensing Examination (USMLE), obtaining clinical experience, and securing a residency spot. 

If unable to complete these steps, IMGs may pursue other healthcare jobs for which they’re overqualified and underpaid, given their experience. The study found that 23% of IMGs who were not on track to become physicians worked as medical assistants. Others became clinical researchers, medical interpreters, and case managers. 

Russian ob/gyn Maxim Nikolaevskiy moved to the US in 2018 and understands why some IMGs switch career paths. His wife, who also trained as a physician in Russia, opted to enroll in a respiratory therapy program after they immigrated to Minnesota, whereas he found work as a research coordinator. The pressure to find housing, enroll their kids in school, and establish new routines took much of their focus. 

Dr. Nikolaevskiy told this news organization that IMGs often struggle to find a residency program willing to consider their unique career trajectory, which looks markedly different from that of someone trained in the US. 

“Multiple residency programs refuse IMGs’ applications, saying they graduated too long ago, without understanding they worked as a physician before,” he said. Immigrant doctors accepting nonphysician jobs once in the US, often out of financial necessity, only adds to this confusion. 

New federal and state legislation aim to reduce practice barriers for IMGs and shore up physician shortages and access for some of the nation›s most vulnerable counties. 

The Conrad State 30 and Physician Access Reauthorization Act, supported by the American Medical Association, would revamp the J-1 visa waiver program to permit more immigrant physicians to work in medically underserved areas instead of returning to their home countries. 

Last year, Alabama streamlined rules to allow IMGs to practice earlier. Effective July 1, those residing in Tennessee may skip residency requirements and receive a temporary medical license once they pass the state medical board and prove they have completed a 3-year postgraduate training program in their licensing country or recently fulfilled physician duties outside the US. 

Washington state now issues 2-year medical licenses to foreign-trained doctors, no residency required, with the possibility of renewal. Doctors must meet other requirements, including passing all steps of the USMLE and establishing a practice agreement with a supervising physician. Illinois recently passed a similar law that will take effect in January 2025. 

Beyond laws, communities can embrace IMGs and offer career guidance and clinical opportunities. Daniel Weber, MD, founded the International Healthcare Professionals Program in Lancaster, Pennsylvania, to provide this critical support. 

“It is daunting to master a new language and pass medical licensing and English proficiency exams while working full time to support themselves and their families,” Dr. Weber said. 

Some participants have entered US residency training programs, but Weber told this news organization that many others have earned nursing degrees and are on track to become nurse practitioners. 

More than 5 years after leaving Russia, Dr. Nikolaevskiy is inching closer to practicing medicine again. 

He recently completed the Bridge to Residency for Immigrant International Doctor Graduates (BRIIDGE) program at the University of Minnesota Medical School. The 9-month program offers clinical experiences in community settings, outpatient primary care, and inpatient general medicine and pediatrics, clearing the way for him to apply for family medicine residency and possibly match in this cycle. 

“If not for the BRIIDGE program, I would still be [doing] medical monitoring in clinical trials or pharmacovigilance jobs. I’m grateful for the clinical experience and the people and institutions ready to give me a second chance,” he said.

A version of this article appeared on Medscape.com.

Foreign-trained doctors can supplement the nation’s waning physician workforce and bring diverse perspectives to patient care, but a new study finds that most never enter comparable roles after immigration, raising questions about the feasibility of educational and licensing pathways for international medical graduates (IMGs). 

Conducted by the Federal Reserve Bank of Minneapolis and the nonprofit Upwardly Global, the study analyzed the data of 300 physicians who immigrated to the United States between 2004 and 2022. 

Although 85% of IMGs found employment, only 1 in 3 became a medical resident or doctor. 

Despite the study’s small sample size, it highlights the hurdles IMGs face, the authors noted. Even though they have a medical degree and potentially years of clinical experience in another country, they typically must start all over again in the US — passing the United States Medical Licensing Examination (USMLE), obtaining clinical experience, and securing a residency spot. 

If unable to complete these steps, IMGs may pursue other healthcare jobs for which they’re overqualified and underpaid, given their experience. The study found that 23% of IMGs who were not on track to become physicians worked as medical assistants. Others became clinical researchers, medical interpreters, and case managers. 

Russian ob/gyn Maxim Nikolaevskiy moved to the US in 2018 and understands why some IMGs switch career paths. His wife, who also trained as a physician in Russia, opted to enroll in a respiratory therapy program after they immigrated to Minnesota, whereas he found work as a research coordinator. The pressure to find housing, enroll their kids in school, and establish new routines took much of their focus. 

Dr. Nikolaevskiy told this news organization that IMGs often struggle to find a residency program willing to consider their unique career trajectory, which looks markedly different from that of someone trained in the US. 

“Multiple residency programs refuse IMGs’ applications, saying they graduated too long ago, without understanding they worked as a physician before,” he said. Immigrant doctors accepting nonphysician jobs once in the US, often out of financial necessity, only adds to this confusion. 

New federal and state legislation aim to reduce practice barriers for IMGs and shore up physician shortages and access for some of the nation›s most vulnerable counties. 

The Conrad State 30 and Physician Access Reauthorization Act, supported by the American Medical Association, would revamp the J-1 visa waiver program to permit more immigrant physicians to work in medically underserved areas instead of returning to their home countries. 

Last year, Alabama streamlined rules to allow IMGs to practice earlier. Effective July 1, those residing in Tennessee may skip residency requirements and receive a temporary medical license once they pass the state medical board and prove they have completed a 3-year postgraduate training program in their licensing country or recently fulfilled physician duties outside the US. 

Washington state now issues 2-year medical licenses to foreign-trained doctors, no residency required, with the possibility of renewal. Doctors must meet other requirements, including passing all steps of the USMLE and establishing a practice agreement with a supervising physician. Illinois recently passed a similar law that will take effect in January 2025. 

Beyond laws, communities can embrace IMGs and offer career guidance and clinical opportunities. Daniel Weber, MD, founded the International Healthcare Professionals Program in Lancaster, Pennsylvania, to provide this critical support. 

“It is daunting to master a new language and pass medical licensing and English proficiency exams while working full time to support themselves and their families,” Dr. Weber said. 

Some participants have entered US residency training programs, but Weber told this news organization that many others have earned nursing degrees and are on track to become nurse practitioners. 

More than 5 years after leaving Russia, Dr. Nikolaevskiy is inching closer to practicing medicine again. 

He recently completed the Bridge to Residency for Immigrant International Doctor Graduates (BRIIDGE) program at the University of Minnesota Medical School. The 9-month program offers clinical experiences in community settings, outpatient primary care, and inpatient general medicine and pediatrics, clearing the way for him to apply for family medicine residency and possibly match in this cycle. 

“If not for the BRIIDGE program, I would still be [doing] medical monitoring in clinical trials or pharmacovigilance jobs. I’m grateful for the clinical experience and the people and institutions ready to give me a second chance,” he said.

A version of this article appeared on Medscape.com.

Foreign-trained doctors can supplement the nation’s waning physician workforce and bring diverse perspectives to patient care, but a new study finds that most never enter comparable roles after immigration, raising questions about the feasibility of educational and licensing pathways for international medical graduates (IMGs). 

Conducted by the Federal Reserve Bank of Minneapolis and the nonprofit Upwardly Global, the study analyzed the data of 300 physicians who immigrated to the United States between 2004 and 2022. 

Although 85% of IMGs found employment, only 1 in 3 became a medical resident or doctor. 

Despite the study’s small sample size, it highlights the hurdles IMGs face, the authors noted. Even though they have a medical degree and potentially years of clinical experience in another country, they typically must start all over again in the US — passing the United States Medical Licensing Examination (USMLE), obtaining clinical experience, and securing a residency spot. 

If unable to complete these steps, IMGs may pursue other healthcare jobs for which they’re overqualified and underpaid, given their experience. The study found that 23% of IMGs who were not on track to become physicians worked as medical assistants. Others became clinical researchers, medical interpreters, and case managers. 

Russian ob/gyn Maxim Nikolaevskiy moved to the US in 2018 and understands why some IMGs switch career paths. His wife, who also trained as a physician in Russia, opted to enroll in a respiratory therapy program after they immigrated to Minnesota, whereas he found work as a research coordinator. The pressure to find housing, enroll their kids in school, and establish new routines took much of their focus. 

Dr. Nikolaevskiy told this news organization that IMGs often struggle to find a residency program willing to consider their unique career trajectory, which looks markedly different from that of someone trained in the US. 

“Multiple residency programs refuse IMGs’ applications, saying they graduated too long ago, without understanding they worked as a physician before,” he said. Immigrant doctors accepting nonphysician jobs once in the US, often out of financial necessity, only adds to this confusion. 

New federal and state legislation aim to reduce practice barriers for IMGs and shore up physician shortages and access for some of the nation›s most vulnerable counties. 

The Conrad State 30 and Physician Access Reauthorization Act, supported by the American Medical Association, would revamp the J-1 visa waiver program to permit more immigrant physicians to work in medically underserved areas instead of returning to their home countries. 

Last year, Alabama streamlined rules to allow IMGs to practice earlier. Effective July 1, those residing in Tennessee may skip residency requirements and receive a temporary medical license once they pass the state medical board and prove they have completed a 3-year postgraduate training program in their licensing country or recently fulfilled physician duties outside the US. 

Washington state now issues 2-year medical licenses to foreign-trained doctors, no residency required, with the possibility of renewal. Doctors must meet other requirements, including passing all steps of the USMLE and establishing a practice agreement with a supervising physician. Illinois recently passed a similar law that will take effect in January 2025. 

Beyond laws, communities can embrace IMGs and offer career guidance and clinical opportunities. Daniel Weber, MD, founded the International Healthcare Professionals Program in Lancaster, Pennsylvania, to provide this critical support. 

“It is daunting to master a new language and pass medical licensing and English proficiency exams while working full time to support themselves and their families,” Dr. Weber said. 

Some participants have entered US residency training programs, but Weber told this news organization that many others have earned nursing degrees and are on track to become nurse practitioners. 

More than 5 years after leaving Russia, Dr. Nikolaevskiy is inching closer to practicing medicine again. 

He recently completed the Bridge to Residency for Immigrant International Doctor Graduates (BRIIDGE) program at the University of Minnesota Medical School. The 9-month program offers clinical experiences in community settings, outpatient primary care, and inpatient general medicine and pediatrics, clearing the way for him to apply for family medicine residency and possibly match in this cycle. 

“If not for the BRIIDGE program, I would still be [doing] medical monitoring in clinical trials or pharmacovigilance jobs. I’m grateful for the clinical experience and the people and institutions ready to give me a second chance,” he said.

A version of this article appeared on Medscape.com.