VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

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

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

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

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

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

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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

TOPLINE:

Over 80% of women with new-onset hypertensive disorders during pregnancy experienced persistent hypertension in the 6 weeks after delivery.

METHODOLOGY:

• Researchers analyzed data from 2705 women in the University of Pittsburgh Medical Center system who developed new-onset hypertensive disorders during pregnancy and participated in a remote blood pressure (BP) monitoring program after discharge from the hospital.
• Nurses showed patients how to monitor their pressure at home, and patients had access to a call center that focused on BP management.

TAKEAWAY:

• Persistent hypertension postpartum — defined as an at-home BP measurement of 140/90 mmHg or greater or treatment with an antihypertensive medication — occurred in 81.8% of the participants.
• A total of 14.1% developed severe hypertension (BP of 160/110 mmHg or greater); 22.6% started an antihypertensive medication after discharge.
• Hospital readmission occurred for 13.4% of the women with severe hypertension, 4% of the women with less serious hypertension, and 2.7% of those who did not have persistent high BP.

IN PRACTICE:

Many of the patients had met criteria to initiate antihypertensive treatment during the delivery admission based on guidance from the American College of Cardiology/American Heart Association (67.9%) and the American College of Obstetricians and Gynecologists (38.7%), “yet only 23.5% were discharged with antihypertensive medications,” Sadiya S. Khan, MD, MSc, of Northwestern University Feinberg School of Medicine, in Chicago, wrote in an editor’s note accompanying the study. “These data highlight several critical gaps in evidence-based recommendations for the monitoring and management of BP following a pregnancy complicated by” hypertensive disorders of pregnancy.

SOURCE:

The study was led by Alisse Hauspurg, MD, MS, of Magee-Womens Research Institute in Pittsburgh, and appeared online in JAMA Cardiology.

LIMITATIONS:

The study was limited to data from one center, and the researchers relied on self-reported BP measurements.

DISCLOSURES:

The study was supported by the National Institutes of Health and the American Heart Association. A coauthor disclosed consulting for Organon and being a cofounder of Naima Health.

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

TOPLINE:

Over 80% of women with new-onset hypertensive disorders during pregnancy experienced persistent hypertension in the 6 weeks after delivery.

METHODOLOGY:

• Researchers analyzed data from 2705 women in the University of Pittsburgh Medical Center system who developed new-onset hypertensive disorders during pregnancy and participated in a remote blood pressure (BP) monitoring program after discharge from the hospital.
• Nurses showed patients how to monitor their pressure at home, and patients had access to a call center that focused on BP management.

TAKEAWAY:

• Persistent hypertension postpartum — defined as an at-home BP measurement of 140/90 mmHg or greater or treatment with an antihypertensive medication — occurred in 81.8% of the participants.
• A total of 14.1% developed severe hypertension (BP of 160/110 mmHg or greater); 22.6% started an antihypertensive medication after discharge.
• Hospital readmission occurred for 13.4% of the women with severe hypertension, 4% of the women with less serious hypertension, and 2.7% of those who did not have persistent high BP.

IN PRACTICE:

Many of the patients had met criteria to initiate antihypertensive treatment during the delivery admission based on guidance from the American College of Cardiology/American Heart Association (67.9%) and the American College of Obstetricians and Gynecologists (38.7%), “yet only 23.5% were discharged with antihypertensive medications,” Sadiya S. Khan, MD, MSc, of Northwestern University Feinberg School of Medicine, in Chicago, wrote in an editor’s note accompanying the study. “These data highlight several critical gaps in evidence-based recommendations for the monitoring and management of BP following a pregnancy complicated by” hypertensive disorders of pregnancy.

SOURCE:

The study was led by Alisse Hauspurg, MD, MS, of Magee-Womens Research Institute in Pittsburgh, and appeared online in JAMA Cardiology.

LIMITATIONS:

The study was limited to data from one center, and the researchers relied on self-reported BP measurements.

DISCLOSURES:

The study was supported by the National Institutes of Health and the American Heart Association. A coauthor disclosed consulting for Organon and being a cofounder of Naima Health.

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

TOPLINE:

Over 80% of women with new-onset hypertensive disorders during pregnancy experienced persistent hypertension in the 6 weeks after delivery.

METHODOLOGY:

• Researchers analyzed data from 2705 women in the University of Pittsburgh Medical Center system who developed new-onset hypertensive disorders during pregnancy and participated in a remote blood pressure (BP) monitoring program after discharge from the hospital.
• Nurses showed patients how to monitor their pressure at home, and patients had access to a call center that focused on BP management.

TAKEAWAY:

• Persistent hypertension postpartum — defined as an at-home BP measurement of 140/90 mmHg or greater or treatment with an antihypertensive medication — occurred in 81.8% of the participants.
• A total of 14.1% developed severe hypertension (BP of 160/110 mmHg or greater); 22.6% started an antihypertensive medication after discharge.
• Hospital readmission occurred for 13.4% of the women with severe hypertension, 4% of the women with less serious hypertension, and 2.7% of those who did not have persistent high BP.

IN PRACTICE:

Many of the patients had met criteria to initiate antihypertensive treatment during the delivery admission based on guidance from the American College of Cardiology/American Heart Association (67.9%) and the American College of Obstetricians and Gynecologists (38.7%), “yet only 23.5% were discharged with antihypertensive medications,” Sadiya S. Khan, MD, MSc, of Northwestern University Feinberg School of Medicine, in Chicago, wrote in an editor’s note accompanying the study. “These data highlight several critical gaps in evidence-based recommendations for the monitoring and management of BP following a pregnancy complicated by” hypertensive disorders of pregnancy.

SOURCE:

The study was led by Alisse Hauspurg, MD, MS, of Magee-Womens Research Institute in Pittsburgh, and appeared online in JAMA Cardiology.

LIMITATIONS:

The study was limited to data from one center, and the researchers relied on self-reported BP measurements.

DISCLOSURES:

The study was supported by the National Institutes of Health and the American Heart Association. A coauthor disclosed consulting for Organon and being a cofounder of Naima Health.

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

TOPLINE:

Various surgical approaches to treat vaginal vault prolapse may be similarly safe and effective and can produce high rates of patient satisfaction.

METHODOLOGY:

• A randomized clinical trial at nine sites in the United States included 360 women with vaginal vault prolapse after hysterectomy (average age, 66 years).
• The women were randomly assigned to undergo native tissue repair (transvaginal repair using the sacrospinous or uterosacral ligament), sacrocolpopexy (mesh repair placed abdominally via open or minimally invasive surgery), or transvaginal mesh repair.

TAKEAWAY:

• At 36 months, a composite measure of treatment failure — based on the need for retreatment, the presence of symptoms, or prolapse beyond the hymen — had occurred in 28% of the women who received sacrocolpopexy, 29% who received transvaginal mesh, and 43% who underwent native tissue repair.
• Sacrocolpopexy was superior to native tissue repair for treatment success (adjusted hazard ratio, 0.57; P = .01), and transvaginal mesh was noninferior to sacrocolpopexy, the researchers found.
• All of the surgical approaches were associated with high rates of treatment satisfaction and improved quality of life and sexual function.
• Adverse events and mesh complications were uncommon.

IN PRACTICE:

“All approaches were associated with high treatment satisfaction; improved symptoms, quality of life, and sexual function; and low rates of regret,” the authors of the study wrote. “As such, clinicians counseling patients with prolapse can discuss the ramifications of each approach and engage in shared, individualized decision-making.”

SOURCE:

The study was led by Shawn A. Menefee, MD, Kaiser Permanente San Diego in San Diego, California. It was published online in JAMA Surgery.

LIMITATIONS:

The US Food and Drug Administration in April 2019 banned transvaginal mesh for pelvic organ prolapse because of concerns about complications such as exposure and erosion. Five trial participants who had been assigned to receive transvaginal mesh but had not yet received it at that time were rerandomized to one of the other surgical approaches.

DISCLOSURES:

The study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women’s Health. Researchers disclosed consulting for companies that market medical devices.

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

TOPLINE:

Various surgical approaches to treat vaginal vault prolapse may be similarly safe and effective and can produce high rates of patient satisfaction.

METHODOLOGY:

• A randomized clinical trial at nine sites in the United States included 360 women with vaginal vault prolapse after hysterectomy (average age, 66 years).
• The women were randomly assigned to undergo native tissue repair (transvaginal repair using the sacrospinous or uterosacral ligament), sacrocolpopexy (mesh repair placed abdominally via open or minimally invasive surgery), or transvaginal mesh repair.

TAKEAWAY:

• At 36 months, a composite measure of treatment failure — based on the need for retreatment, the presence of symptoms, or prolapse beyond the hymen — had occurred in 28% of the women who received sacrocolpopexy, 29% who received transvaginal mesh, and 43% who underwent native tissue repair.
• Sacrocolpopexy was superior to native tissue repair for treatment success (adjusted hazard ratio, 0.57; P = .01), and transvaginal mesh was noninferior to sacrocolpopexy, the researchers found.
• All of the surgical approaches were associated with high rates of treatment satisfaction and improved quality of life and sexual function.
• Adverse events and mesh complications were uncommon.

IN PRACTICE:

“All approaches were associated with high treatment satisfaction; improved symptoms, quality of life, and sexual function; and low rates of regret,” the authors of the study wrote. “As such, clinicians counseling patients with prolapse can discuss the ramifications of each approach and engage in shared, individualized decision-making.”

SOURCE:

The study was led by Shawn A. Menefee, MD, Kaiser Permanente San Diego in San Diego, California. It was published online in JAMA Surgery.

LIMITATIONS:

The US Food and Drug Administration in April 2019 banned transvaginal mesh for pelvic organ prolapse because of concerns about complications such as exposure and erosion. Five trial participants who had been assigned to receive transvaginal mesh but had not yet received it at that time were rerandomized to one of the other surgical approaches.

DISCLOSURES:

The study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women’s Health. Researchers disclosed consulting for companies that market medical devices.

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

TOPLINE:

Various surgical approaches to treat vaginal vault prolapse may be similarly safe and effective and can produce high rates of patient satisfaction.

METHODOLOGY:

• A randomized clinical trial at nine sites in the United States included 360 women with vaginal vault prolapse after hysterectomy (average age, 66 years).
• The women were randomly assigned to undergo native tissue repair (transvaginal repair using the sacrospinous or uterosacral ligament), sacrocolpopexy (mesh repair placed abdominally via open or minimally invasive surgery), or transvaginal mesh repair.

TAKEAWAY:

• At 36 months, a composite measure of treatment failure — based on the need for retreatment, the presence of symptoms, or prolapse beyond the hymen — had occurred in 28% of the women who received sacrocolpopexy, 29% who received transvaginal mesh, and 43% who underwent native tissue repair.
• Sacrocolpopexy was superior to native tissue repair for treatment success (adjusted hazard ratio, 0.57; P = .01), and transvaginal mesh was noninferior to sacrocolpopexy, the researchers found.
• All of the surgical approaches were associated with high rates of treatment satisfaction and improved quality of life and sexual function.
• Adverse events and mesh complications were uncommon.

IN PRACTICE:

“All approaches were associated with high treatment satisfaction; improved symptoms, quality of life, and sexual function; and low rates of regret,” the authors of the study wrote. “As such, clinicians counseling patients with prolapse can discuss the ramifications of each approach and engage in shared, individualized decision-making.”

SOURCE:

The study was led by Shawn A. Menefee, MD, Kaiser Permanente San Diego in San Diego, California. It was published online in JAMA Surgery.

LIMITATIONS:

The US Food and Drug Administration in April 2019 banned transvaginal mesh for pelvic organ prolapse because of concerns about complications such as exposure and erosion. Five trial participants who had been assigned to receive transvaginal mesh but had not yet received it at that time were rerandomized to one of the other surgical approaches.

DISCLOSURES:

The study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women’s Health. Researchers disclosed consulting for companies that market medical devices.

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

TOPLINE:

For patients with early multinodular hepatocellular carcinoma (HCC) who are ineligible for liver transplant, liver resection provides a survival advantage over percutaneous radiofrequency ablation and transarterial chemoembolization (TACE).

METHODOLOGY:

• The presentation of HCC is often multinodular — meaning patients have two or three nodules measuring ≤ 3 cm each. Although liver resection is considered the gold standard curative treatment for early-stage disease, experts debate its efficacy in multinodular HCC, researchers explained.
• Using two large Italian registries with data from multiple centers, researchers compared the efficacy of liver resection, percutaneous radiofrequency ablation, and TACE in 720 patients with early multinodular HCC. Overall, 296 patients underwent liver resection, 240 had percutaneous radiofrequency ablation, and 184 underwent TACE.
• To avoid crossovers between groups, the researchers considered liver resection, percutaneous radiofrequency ablation, and TACE the main treatments in each population in a hierarchical order. That meant, in the liver resection group, researchers excluded patients undergoing a superior treatment during the follow-up, such as liver transplant. In the ablation group, patients undergoing surgery to treat HCC recurrences were excluded.
• The primary outcome was overall survival at 1, 3, and 5 years. The researchers used a matching-adjusted indirect comparison (MAIC) to balance data and control for confounding factors between the three treatment groups.

TAKEAWAY:

• After MAIC adjustment, the survival rate at 1 year was slightly lower in the liver resection group — 89% vs 94% in the ablation group and 91% in the TACE group. However, at 3 and 5 years, survival rates were better in the liver resection group — 71% at 3 years and 56% at 5 years vs 65% and 40%, respectively, in the ablation group and 49% and 29%, respectively, in the TACE group.
• Median overall survival was 69 months with liver resection, 54 months with ablation, and 34 months with TACE. Multivariable Cox survival analysis confirmed a significantly higher mortality risk with ablation (hazard ratio [HR], 1.41; P = .01) and TACE (HR, 1.86; P = .001) than with liver resection.
• In competing risk analyses, patients who underwent liver resection had a lower risk for HCC-related death than peers who had ablation (HR, 1.38; P = .07) or TACE (HR, 1.91; P = .006).
• In a subgroup survival analysis of patients with Child-Pugh class B cirrhosis, liver resection provided significantly better overall survival than TACE (HR, 2.79; P = .001) and higher overall survival than ablation (HR, 1.44; P = .21), but these findings were not statistically significant.

IN PRACTICE:

“The main result of the current study is the indisputable superiority” of liver resection over percutaneous radiofrequency ablation and TACE in patients with multinodular HCC, the researchers concluded. “For patients with early multinodular HCC who are ineligible for transplant, LR [liver resection] should be prioritized as the primary therapeutic option,” followed by percutaneous radiofrequency ablation and TACE, when resection is not feasible.

The authors of an invited commentary said the analysis provides “convincing” data that liver resection leads to superior 3- and 5-year survival. “All of our local therapies are getting better. Making each available under different clinical circumstances and combining these when appropriate provides patients with the best chance at cure with the least invasiveness,” the editorialists added.
 

SOURCE:

The study, with first author Alessandro Vitale, MD, PhD, with the Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padua, Italy, and the accompanying commentary were published online last month in JAMA Surgery.

LIMITATIONS:

Selection bias cannot be ruled out due to potential hidden variables that were not collected in the centers’ databases. Not all patients included in the study were potentially treatable with all three proposed approaches. The study population was derived from Italian centers, which may have limited the generalizability of the results.

DISCLOSURES:

The study reported no specific funding. The authors reported various disclosures during the conduct of the study, including ties to AstraZeneca, AbbVie, Bayer, MSD, Roche, and Eisai. An editorialist reported ties to Medtronic, Theromics, Vergent Bioscience, Imugene, Sovato Health, XDemics, and Imugene.

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

TOPLINE:

For patients with early multinodular hepatocellular carcinoma (HCC) who are ineligible for liver transplant, liver resection provides a survival advantage over percutaneous radiofrequency ablation and transarterial chemoembolization (TACE).

METHODOLOGY:

• The presentation of HCC is often multinodular — meaning patients have two or three nodules measuring ≤ 3 cm each. Although liver resection is considered the gold standard curative treatment for early-stage disease, experts debate its efficacy in multinodular HCC, researchers explained.
• Using two large Italian registries with data from multiple centers, researchers compared the efficacy of liver resection, percutaneous radiofrequency ablation, and TACE in 720 patients with early multinodular HCC. Overall, 296 patients underwent liver resection, 240 had percutaneous radiofrequency ablation, and 184 underwent TACE.
• To avoid crossovers between groups, the researchers considered liver resection, percutaneous radiofrequency ablation, and TACE the main treatments in each population in a hierarchical order. That meant, in the liver resection group, researchers excluded patients undergoing a superior treatment during the follow-up, such as liver transplant. In the ablation group, patients undergoing surgery to treat HCC recurrences were excluded.
• The primary outcome was overall survival at 1, 3, and 5 years. The researchers used a matching-adjusted indirect comparison (MAIC) to balance data and control for confounding factors between the three treatment groups.

TAKEAWAY:

• After MAIC adjustment, the survival rate at 1 year was slightly lower in the liver resection group — 89% vs 94% in the ablation group and 91% in the TACE group. However, at 3 and 5 years, survival rates were better in the liver resection group — 71% at 3 years and 56% at 5 years vs 65% and 40%, respectively, in the ablation group and 49% and 29%, respectively, in the TACE group.
• Median overall survival was 69 months with liver resection, 54 months with ablation, and 34 months with TACE. Multivariable Cox survival analysis confirmed a significantly higher mortality risk with ablation (hazard ratio [HR], 1.41; P = .01) and TACE (HR, 1.86; P = .001) than with liver resection.
• In competing risk analyses, patients who underwent liver resection had a lower risk for HCC-related death than peers who had ablation (HR, 1.38; P = .07) or TACE (HR, 1.91; P = .006).
• In a subgroup survival analysis of patients with Child-Pugh class B cirrhosis, liver resection provided significantly better overall survival than TACE (HR, 2.79; P = .001) and higher overall survival than ablation (HR, 1.44; P = .21), but these findings were not statistically significant.

IN PRACTICE:

“The main result of the current study is the indisputable superiority” of liver resection over percutaneous radiofrequency ablation and TACE in patients with multinodular HCC, the researchers concluded. “For patients with early multinodular HCC who are ineligible for transplant, LR [liver resection] should be prioritized as the primary therapeutic option,” followed by percutaneous radiofrequency ablation and TACE, when resection is not feasible.

The authors of an invited commentary said the analysis provides “convincing” data that liver resection leads to superior 3- and 5-year survival. “All of our local therapies are getting better. Making each available under different clinical circumstances and combining these when appropriate provides patients with the best chance at cure with the least invasiveness,” the editorialists added.
 

SOURCE:

The study, with first author Alessandro Vitale, MD, PhD, with the Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padua, Italy, and the accompanying commentary were published online last month in JAMA Surgery.

LIMITATIONS:

Selection bias cannot be ruled out due to potential hidden variables that were not collected in the centers’ databases. Not all patients included in the study were potentially treatable with all three proposed approaches. The study population was derived from Italian centers, which may have limited the generalizability of the results.

DISCLOSURES:

The study reported no specific funding. The authors reported various disclosures during the conduct of the study, including ties to AstraZeneca, AbbVie, Bayer, MSD, Roche, and Eisai. An editorialist reported ties to Medtronic, Theromics, Vergent Bioscience, Imugene, Sovato Health, XDemics, and Imugene.

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

TOPLINE:

For patients with early multinodular hepatocellular carcinoma (HCC) who are ineligible for liver transplant, liver resection provides a survival advantage over percutaneous radiofrequency ablation and transarterial chemoembolization (TACE).

METHODOLOGY:

• The presentation of HCC is often multinodular — meaning patients have two or three nodules measuring ≤ 3 cm each. Although liver resection is considered the gold standard curative treatment for early-stage disease, experts debate its efficacy in multinodular HCC, researchers explained.
• Using two large Italian registries with data from multiple centers, researchers compared the efficacy of liver resection, percutaneous radiofrequency ablation, and TACE in 720 patients with early multinodular HCC. Overall, 296 patients underwent liver resection, 240 had percutaneous radiofrequency ablation, and 184 underwent TACE.
• To avoid crossovers between groups, the researchers considered liver resection, percutaneous radiofrequency ablation, and TACE the main treatments in each population in a hierarchical order. That meant, in the liver resection group, researchers excluded patients undergoing a superior treatment during the follow-up, such as liver transplant. In the ablation group, patients undergoing surgery to treat HCC recurrences were excluded.
• The primary outcome was overall survival at 1, 3, and 5 years. The researchers used a matching-adjusted indirect comparison (MAIC) to balance data and control for confounding factors between the three treatment groups.

TAKEAWAY:

• After MAIC adjustment, the survival rate at 1 year was slightly lower in the liver resection group — 89% vs 94% in the ablation group and 91% in the TACE group. However, at 3 and 5 years, survival rates were better in the liver resection group — 71% at 3 years and 56% at 5 years vs 65% and 40%, respectively, in the ablation group and 49% and 29%, respectively, in the TACE group.
• Median overall survival was 69 months with liver resection, 54 months with ablation, and 34 months with TACE. Multivariable Cox survival analysis confirmed a significantly higher mortality risk with ablation (hazard ratio [HR], 1.41; P = .01) and TACE (HR, 1.86; P = .001) than with liver resection.
• In competing risk analyses, patients who underwent liver resection had a lower risk for HCC-related death than peers who had ablation (HR, 1.38; P = .07) or TACE (HR, 1.91; P = .006).
• In a subgroup survival analysis of patients with Child-Pugh class B cirrhosis, liver resection provided significantly better overall survival than TACE (HR, 2.79; P = .001) and higher overall survival than ablation (HR, 1.44; P = .21), but these findings were not statistically significant.

IN PRACTICE:

“The main result of the current study is the indisputable superiority” of liver resection over percutaneous radiofrequency ablation and TACE in patients with multinodular HCC, the researchers concluded. “For patients with early multinodular HCC who are ineligible for transplant, LR [liver resection] should be prioritized as the primary therapeutic option,” followed by percutaneous radiofrequency ablation and TACE, when resection is not feasible.

The authors of an invited commentary said the analysis provides “convincing” data that liver resection leads to superior 3- and 5-year survival. “All of our local therapies are getting better. Making each available under different clinical circumstances and combining these when appropriate provides patients with the best chance at cure with the least invasiveness,” the editorialists added.
 

SOURCE:

The study, with first author Alessandro Vitale, MD, PhD, with the Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padua, Italy, and the accompanying commentary were published online last month in JAMA Surgery.

LIMITATIONS:

Selection bias cannot be ruled out due to potential hidden variables that were not collected in the centers’ databases. Not all patients included in the study were potentially treatable with all three proposed approaches. The study population was derived from Italian centers, which may have limited the generalizability of the results.

DISCLOSURES:

The study reported no specific funding. The authors reported various disclosures during the conduct of the study, including ties to AstraZeneca, AbbVie, Bayer, MSD, Roche, and Eisai. An editorialist reported ties to Medtronic, Theromics, Vergent Bioscience, Imugene, Sovato Health, XDemics, and Imugene.

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

To the Editor:

Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.^1-5

Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York^3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.⁷ Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.⁸ We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.

An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A_1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.

Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.

Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.

To the Editor:

Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.^1-5

Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York^3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.⁷ Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.⁸ We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.

An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A_1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.

Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.

Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.

To the Editor:

Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.^1-5

Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York^3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.⁷ Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.⁸ We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.

An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A_1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.

Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.

Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.

Several new studies in lung cancer have opened their doors recently. Is one of your patients eligible to participate?

Resected stage II, IIIA, or IIIB with nodal involvement non–small cell lung cancer (NSCLC). Adult patients with this type of cancer can join a randomized, controlled, phase 3 study assessing whether an investigational drug called V940 added to pembrolizumab (Keytruda) delays cancer recurrence better than pembrolizumab alone.

V940 is an individualized neoantigen therapy designed to generate T-cell antitumor responses targeted to a patient’s specific mutation profile.

V940 plus pembrolizumab showed a trend toward longer recurrence-free survival vs pembrolizumab alone in a recent phase 2 study in melanoma (hazard ratio, 0.561; P = .053).

In the current trial, one group of participants will receive intramuscular injections of V940 every 3 weeks plus intravenous (IV) pembrolizumab every 6 weeks for up to approximately 1 year or until disease recurrence or unacceptable toxicity, whichever happens first. The other people in the trial will be on the same schedule, with a placebo replacing V940.

Centers in Florida, Georgia, Kentucky, Montana, New Jersey, New York, North Dakota, and six other countries started recruiting for the trial’s 868 participants in December 2023. Disease-free survival is the primary endpoint. Overall survival over approximately 12 years and quality of life (QoL) are secondary endpoints. More details at clinicaltrials.gov.

Metastatic NSCLC with a programmed cell death ligand 1 (PD-L1)–tumor proportion score of > 50%. Adults in this clinical situation are eligible for a randomized, open-label, phase 3 trial to determine whether an experimental antibody-drug conjugate called MK-2870 added to standard pembrolizumab prolongs survival.

MK-2870 delivers a cytotoxin to cancer cells by binding to trophoblast cell-surface antigen 2, known to promote tumor cell growth and metastasis. For up to 2 years, half of participants will receive MK-2870 by IV every 2 weeks plus IV pembrolizumab every 6 weeks. The other group will receive only pembrolizumab.

In December 2023, study sites in Georgia, Minnesota, Mississippi, Nevada, Oregon, Australia, Denmark, Taiwan, and Turkey started seeking the trial’s 614 participants. Overall survival over approximately 4 years is the primary endpoint; QoL is a secondary endpoint. More details at clinicaltrials.gov.

Untreated locally advanced or metastatic NSCLC with KRAS G12C mutations. Individuals with this type of lung cancer may be interested in a randomized, controlled, phase 3 study examining whether an experimental oral KRAS G12C inhibitor called LY3537982 boosts the effectiveness of standard treatment and patients can tolerate the combination. Currently approved KRAS G12C inhibitors sotorasib (Lumakras, Lumykras) and adagrasib (Krazati) are indicated for second-line treatment; this trial may lead to a first-line approval for newcomer LY3537982.

The trial has three parts: dose optimization, safety, and efficacy. During dose optimization, each participant will take one of two oral doses of LY3537982 and receive IV pembrolizumab every 3 weeks. In the safety phase, all participants will receive oral LY3537982 at the chosen dose plus standard therapy of 3-times-weekly IV pembrolizumab, pemetrexed, and a platinum therapy (cisplatin or carboplatin). In the experimental phase, for up to about 1 year, participants will receive one of these four options: Pembrolizumab plus LY3537982, pembrolizumab plus a placebo, standard therapy plus LY3537982, or standard therapy plus a placebo.

The study, which is planning to recruit 1016 participants, opened across 16 US states and 12 countries worldwide in December 2023. Sites in 11 more US states, the District of Columbia, Brazil, Canada, China, India, and 11 more European countries are gearing up. Adverse events and progression-free survival are the primary endpoints. Overall survival over approximately 3 years and QoL are secondary endpoints. More details at clinicaltrials.gov.

Unresectable, untreated locally advanced or metastatic non-squamous NSCLC with human epidermal growth factor receptor 2 (HER2) mutations. People with this diagnosis who have HER2 mutations instead of KRAS G12C mutations can participate in a phase 3 study comparing an investigational oral first-line treatment with standard IV therapy. The drug in this study, zongertinib, is a HER2 tyrosine kinase inhibitor.

For up to approximately 4 years, one group of participants will take oral zongertinib only, and the other individuals will receive IV pembrolizumab, pemetrexed, and a platinum agent (cisplatin or carboplatin). Study sites in California, Missouri, South Carolina, Australia, China, Japan, South Korea, and Singapore opened in January ready to welcome 270 participants. Progression-free survival is the primary outcome. Overall survival over 53 months and QoL are secondary endpoints. More details at clinicaltrials.gov.

Completely resected stage IIB, IIIA, or select IIIB, PD-L1–positive NSCLC. Adults with this type of lung cancer who have received adjuvant platinum-based chemotherapy may be eligible for a randomized, controlled, phase 3 study to assess whether two immune checkpoint inhibitors are better than one at delaying cancer recurrence. In this trial, tiragolumab will be added to the approved PD-L1 inhibitor atezolizumab (Tecentriq).

A recent study, however, found that tiragolumab did not confer an additional benefit when added to atezolizumab, carboplatin, and etoposide in untreated extensive-stage small cell lung cancer.

In the current trial, one group of participants will receive IV atezolizumab and tiragolumab, while the other people will receive a placebo instead of tiragolumab. Centers in California, Georgia, Illinois, New Mexico, Australia, China, South Korea, and Taiwan started recruiting for the trial’s 1150 participants in March 2024. Disease-free survival is the primary endpoint. Overall survival over approximately 15 years and QoL are secondary outcomes. More details at clinicaltrials.gov.

Previously treated metastatic or non-operable non-squamous NSCLC. Adults in this position who have received no more than one platinum-based chemotherapy and one anti–PD-L1 drug are sought for a randomized, open-label, phase 3 trial comparing second-line standard docetaxel with experimental antibody-drug conjugate sigvotatug vedotin. Patients who have tumors with certain treatable genomic alterations must have received at least one drug targeted to that alteration, as well as a platinum-based agent.

Approximately half the participants will receive sigvotatug vedotin by IV every 2 weeks, and the other half will receive IV docetaxel every 3 weeks. The study opened in March across 13 US states, France, Hungary, Poland, and Spain seeking 600 people eligible to participate. The primary outcomes are overall survival over approximately 5 years and objective response rate. QoL is a secondary outcome. More details at clinicaltrials.gov.All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

Several new studies in lung cancer have opened their doors recently. Is one of your patients eligible to participate?

Resected stage II, IIIA, or IIIB with nodal involvement non–small cell lung cancer (NSCLC). Adult patients with this type of cancer can join a randomized, controlled, phase 3 study assessing whether an investigational drug called V940 added to pembrolizumab (Keytruda) delays cancer recurrence better than pembrolizumab alone.

V940 is an individualized neoantigen therapy designed to generate T-cell antitumor responses targeted to a patient’s specific mutation profile.

V940 plus pembrolizumab showed a trend toward longer recurrence-free survival vs pembrolizumab alone in a recent phase 2 study in melanoma (hazard ratio, 0.561; P = .053).

In the current trial, one group of participants will receive intramuscular injections of V940 every 3 weeks plus intravenous (IV) pembrolizumab every 6 weeks for up to approximately 1 year or until disease recurrence or unacceptable toxicity, whichever happens first. The other people in the trial will be on the same schedule, with a placebo replacing V940.

Centers in Florida, Georgia, Kentucky, Montana, New Jersey, New York, North Dakota, and six other countries started recruiting for the trial’s 868 participants in December 2023. Disease-free survival is the primary endpoint. Overall survival over approximately 12 years and quality of life (QoL) are secondary endpoints. More details at clinicaltrials.gov.

Metastatic NSCLC with a programmed cell death ligand 1 (PD-L1)–tumor proportion score of > 50%. Adults in this clinical situation are eligible for a randomized, open-label, phase 3 trial to determine whether an experimental antibody-drug conjugate called MK-2870 added to standard pembrolizumab prolongs survival.

MK-2870 delivers a cytotoxin to cancer cells by binding to trophoblast cell-surface antigen 2, known to promote tumor cell growth and metastasis. For up to 2 years, half of participants will receive MK-2870 by IV every 2 weeks plus IV pembrolizumab every 6 weeks. The other group will receive only pembrolizumab.

In December 2023, study sites in Georgia, Minnesota, Mississippi, Nevada, Oregon, Australia, Denmark, Taiwan, and Turkey started seeking the trial’s 614 participants. Overall survival over approximately 4 years is the primary endpoint; QoL is a secondary endpoint. More details at clinicaltrials.gov.

Untreated locally advanced or metastatic NSCLC with KRAS G12C mutations. Individuals with this type of lung cancer may be interested in a randomized, controlled, phase 3 study examining whether an experimental oral KRAS G12C inhibitor called LY3537982 boosts the effectiveness of standard treatment and patients can tolerate the combination. Currently approved KRAS G12C inhibitors sotorasib (Lumakras, Lumykras) and adagrasib (Krazati) are indicated for second-line treatment; this trial may lead to a first-line approval for newcomer LY3537982.

The trial has three parts: dose optimization, safety, and efficacy. During dose optimization, each participant will take one of two oral doses of LY3537982 and receive IV pembrolizumab every 3 weeks. In the safety phase, all participants will receive oral LY3537982 at the chosen dose plus standard therapy of 3-times-weekly IV pembrolizumab, pemetrexed, and a platinum therapy (cisplatin or carboplatin). In the experimental phase, for up to about 1 year, participants will receive one of these four options: Pembrolizumab plus LY3537982, pembrolizumab plus a placebo, standard therapy plus LY3537982, or standard therapy plus a placebo.

The study, which is planning to recruit 1016 participants, opened across 16 US states and 12 countries worldwide in December 2023. Sites in 11 more US states, the District of Columbia, Brazil, Canada, China, India, and 11 more European countries are gearing up. Adverse events and progression-free survival are the primary endpoints. Overall survival over approximately 3 years and QoL are secondary endpoints. More details at clinicaltrials.gov.

Unresectable, untreated locally advanced or metastatic non-squamous NSCLC with human epidermal growth factor receptor 2 (HER2) mutations. People with this diagnosis who have HER2 mutations instead of KRAS G12C mutations can participate in a phase 3 study comparing an investigational oral first-line treatment with standard IV therapy. The drug in this study, zongertinib, is a HER2 tyrosine kinase inhibitor.

For up to approximately 4 years, one group of participants will take oral zongertinib only, and the other individuals will receive IV pembrolizumab, pemetrexed, and a platinum agent (cisplatin or carboplatin). Study sites in California, Missouri, South Carolina, Australia, China, Japan, South Korea, and Singapore opened in January ready to welcome 270 participants. Progression-free survival is the primary outcome. Overall survival over 53 months and QoL are secondary endpoints. More details at clinicaltrials.gov.

Completely resected stage IIB, IIIA, or select IIIB, PD-L1–positive NSCLC. Adults with this type of lung cancer who have received adjuvant platinum-based chemotherapy may be eligible for a randomized, controlled, phase 3 study to assess whether two immune checkpoint inhibitors are better than one at delaying cancer recurrence. In this trial, tiragolumab will be added to the approved PD-L1 inhibitor atezolizumab (Tecentriq).

A recent study, however, found that tiragolumab did not confer an additional benefit when added to atezolizumab, carboplatin, and etoposide in untreated extensive-stage small cell lung cancer.

In the current trial, one group of participants will receive IV atezolizumab and tiragolumab, while the other people will receive a placebo instead of tiragolumab. Centers in California, Georgia, Illinois, New Mexico, Australia, China, South Korea, and Taiwan started recruiting for the trial’s 1150 participants in March 2024. Disease-free survival is the primary endpoint. Overall survival over approximately 15 years and QoL are secondary outcomes. More details at clinicaltrials.gov.

Previously treated metastatic or non-operable non-squamous NSCLC. Adults in this position who have received no more than one platinum-based chemotherapy and one anti–PD-L1 drug are sought for a randomized, open-label, phase 3 trial comparing second-line standard docetaxel with experimental antibody-drug conjugate sigvotatug vedotin. Patients who have tumors with certain treatable genomic alterations must have received at least one drug targeted to that alteration, as well as a platinum-based agent.

Approximately half the participants will receive sigvotatug vedotin by IV every 2 weeks, and the other half will receive IV docetaxel every 3 weeks. The study opened in March across 13 US states, France, Hungary, Poland, and Spain seeking 600 people eligible to participate. The primary outcomes are overall survival over approximately 5 years and objective response rate. QoL is a secondary outcome. More details at clinicaltrials.gov.All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

Several new studies in lung cancer have opened their doors recently. Is one of your patients eligible to participate?

Resected stage II, IIIA, or IIIB with nodal involvement non–small cell lung cancer (NSCLC). Adult patients with this type of cancer can join a randomized, controlled, phase 3 study assessing whether an investigational drug called V940 added to pembrolizumab (Keytruda) delays cancer recurrence better than pembrolizumab alone.

V940 is an individualized neoantigen therapy designed to generate T-cell antitumor responses targeted to a patient’s specific mutation profile.

V940 plus pembrolizumab showed a trend toward longer recurrence-free survival vs pembrolizumab alone in a recent phase 2 study in melanoma (hazard ratio, 0.561; P = .053).

In the current trial, one group of participants will receive intramuscular injections of V940 every 3 weeks plus intravenous (IV) pembrolizumab every 6 weeks for up to approximately 1 year or until disease recurrence or unacceptable toxicity, whichever happens first. The other people in the trial will be on the same schedule, with a placebo replacing V940.

Centers in Florida, Georgia, Kentucky, Montana, New Jersey, New York, North Dakota, and six other countries started recruiting for the trial’s 868 participants in December 2023. Disease-free survival is the primary endpoint. Overall survival over approximately 12 years and quality of life (QoL) are secondary endpoints. More details at clinicaltrials.gov.

Metastatic NSCLC with a programmed cell death ligand 1 (PD-L1)–tumor proportion score of > 50%. Adults in this clinical situation are eligible for a randomized, open-label, phase 3 trial to determine whether an experimental antibody-drug conjugate called MK-2870 added to standard pembrolizumab prolongs survival.

MK-2870 delivers a cytotoxin to cancer cells by binding to trophoblast cell-surface antigen 2, known to promote tumor cell growth and metastasis. For up to 2 years, half of participants will receive MK-2870 by IV every 2 weeks plus IV pembrolizumab every 6 weeks. The other group will receive only pembrolizumab.

In December 2023, study sites in Georgia, Minnesota, Mississippi, Nevada, Oregon, Australia, Denmark, Taiwan, and Turkey started seeking the trial’s 614 participants. Overall survival over approximately 4 years is the primary endpoint; QoL is a secondary endpoint. More details at clinicaltrials.gov.

Untreated locally advanced or metastatic NSCLC with KRAS G12C mutations. Individuals with this type of lung cancer may be interested in a randomized, controlled, phase 3 study examining whether an experimental oral KRAS G12C inhibitor called LY3537982 boosts the effectiveness of standard treatment and patients can tolerate the combination. Currently approved KRAS G12C inhibitors sotorasib (Lumakras, Lumykras) and adagrasib (Krazati) are indicated for second-line treatment; this trial may lead to a first-line approval for newcomer LY3537982.

The trial has three parts: dose optimization, safety, and efficacy. During dose optimization, each participant will take one of two oral doses of LY3537982 and receive IV pembrolizumab every 3 weeks. In the safety phase, all participants will receive oral LY3537982 at the chosen dose plus standard therapy of 3-times-weekly IV pembrolizumab, pemetrexed, and a platinum therapy (cisplatin or carboplatin). In the experimental phase, for up to about 1 year, participants will receive one of these four options: Pembrolizumab plus LY3537982, pembrolizumab plus a placebo, standard therapy plus LY3537982, or standard therapy plus a placebo.

The study, which is planning to recruit 1016 participants, opened across 16 US states and 12 countries worldwide in December 2023. Sites in 11 more US states, the District of Columbia, Brazil, Canada, China, India, and 11 more European countries are gearing up. Adverse events and progression-free survival are the primary endpoints. Overall survival over approximately 3 years and QoL are secondary endpoints. More details at clinicaltrials.gov.

Unresectable, untreated locally advanced or metastatic non-squamous NSCLC with human epidermal growth factor receptor 2 (HER2) mutations. People with this diagnosis who have HER2 mutations instead of KRAS G12C mutations can participate in a phase 3 study comparing an investigational oral first-line treatment with standard IV therapy. The drug in this study, zongertinib, is a HER2 tyrosine kinase inhibitor.

For up to approximately 4 years, one group of participants will take oral zongertinib only, and the other individuals will receive IV pembrolizumab, pemetrexed, and a platinum agent (cisplatin or carboplatin). Study sites in California, Missouri, South Carolina, Australia, China, Japan, South Korea, and Singapore opened in January ready to welcome 270 participants. Progression-free survival is the primary outcome. Overall survival over 53 months and QoL are secondary endpoints. More details at clinicaltrials.gov.

Completely resected stage IIB, IIIA, or select IIIB, PD-L1–positive NSCLC. Adults with this type of lung cancer who have received adjuvant platinum-based chemotherapy may be eligible for a randomized, controlled, phase 3 study to assess whether two immune checkpoint inhibitors are better than one at delaying cancer recurrence. In this trial, tiragolumab will be added to the approved PD-L1 inhibitor atezolizumab (Tecentriq).

A recent study, however, found that tiragolumab did not confer an additional benefit when added to atezolizumab, carboplatin, and etoposide in untreated extensive-stage small cell lung cancer.

In the current trial, one group of participants will receive IV atezolizumab and tiragolumab, while the other people will receive a placebo instead of tiragolumab. Centers in California, Georgia, Illinois, New Mexico, Australia, China, South Korea, and Taiwan started recruiting for the trial’s 1150 participants in March 2024. Disease-free survival is the primary endpoint. Overall survival over approximately 15 years and QoL are secondary outcomes. More details at clinicaltrials.gov.

Previously treated metastatic or non-operable non-squamous NSCLC. Adults in this position who have received no more than one platinum-based chemotherapy and one anti–PD-L1 drug are sought for a randomized, open-label, phase 3 trial comparing second-line standard docetaxel with experimental antibody-drug conjugate sigvotatug vedotin. Patients who have tumors with certain treatable genomic alterations must have received at least one drug targeted to that alteration, as well as a platinum-based agent.

Approximately half the participants will receive sigvotatug vedotin by IV every 2 weeks, and the other half will receive IV docetaxel every 3 weeks. The study opened in March across 13 US states, France, Hungary, Poland, and Spain seeking 600 people eligible to participate. The primary outcomes are overall survival over approximately 5 years and objective response rate. QoL is a secondary outcome. More details at clinicaltrials.gov.All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter. The Accelerated and Advance Payment program, which began in early March to assist hospitals and practices facing significant reimbursement delays, will stop accepting applications after July 12, 2024.

CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.

According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.

The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”

Ongoing Concerns from Health Care Organizations

Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.

“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.

In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.

Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.

“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”

Cyberattack Impact and Response

The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.

Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.

By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.

Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”

Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.

A version of this article appeared on Medscape.com.

The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter. The Accelerated and Advance Payment program, which began in early March to assist hospitals and practices facing significant reimbursement delays, will stop accepting applications after July 12, 2024.

CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.

According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.

The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”

Ongoing Concerns from Health Care Organizations

Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.

“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.

In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.

Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.

“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”

Cyberattack Impact and Response

The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.

Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.

By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.

Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”

Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.

A version of this article appeared on Medscape.com.

The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter. The Accelerated and Advance Payment program, which began in early March to assist hospitals and practices facing significant reimbursement delays, will stop accepting applications after July 12, 2024.

CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.

According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.

The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”

Ongoing Concerns from Health Care Organizations

Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.

“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.

In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.

Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.

“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”

Cyberattack Impact and Response

The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.

Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.

By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.

Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”

Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.

A version of this article appeared on Medscape.com.

An algorithm using two well-known tests has shown strong accuracy (91%) in predicting whether an older driver can pass an on-road driving evaluation according to a new study published in the Journal of the American Medical Directors Association .

The Fit2Drive algorithm combines the Mini-Mental State Exam (MMSE), a 30-point dementia screening tool that has been found in several studies to have an association with driving ability, and the Trails B test, which gauges cognitive flexibility and set-shifting (task switching), considered to be measures of executive functioning.
 

Algorithm Available for Providers

The algorithm is clinically available and providers can fill in patients’ information and results of the two tests at the Fit2Drive website. Results may help physicians with often-difficult conversations with older patients about driving when they present with cognitive concerns.

Families report it is one of the most difficult conversations they have with a loved one and doctors are often asked to be part of the conversation. This is particularly difficult when, often, little objective information is available. In the past, a clinical rule of thumb has been that people diagnosed with Alzheimer’s disease or related dementias (ADRD) will usually be able to drive for 3 years after diagnosis.

“[T]he anger, tears, and frustration on the part of the individual patient and the lack of objective data to guide provider recommendations are the driving forces behind our effort to develop a highly accurate, evidence-based predictor of the ability to pass an on-road driving test,” the authors write. They added that the goal of the study was to identify the smallest number of cognitive test results that could predict likelihood of passing an on-road driver evaluation.

A number of tests were evaluated for the algorithm, but the combination of Trails B in seconds and MMSE using the highest scores of the serial 7s (counting back from 100 by 7s) or WORLD spelled backward accounted for the highest correlation with passing the on-road driving test, according to the authors, led by Ruth Tappen, EdD, FN, with the Christine E. Lynn College of Nursing at Florida Atlantic University, in Boca Raton.

A receiver operator characteristic (ROC) analysis was conducted on the linear combination of the two assessments.

“Because an ROC of 0.70 is considered to be the minimal requirement [for predictive value], 0.80 is considered good, and higher than 0.90 is excellent, these findings [with 91% area under the curve] suggest excellent accuracy using these two cognitive tests in this population,” the authors write.

For this analysis, researchers included 412 older drivers (179 men and 233 women) with an average age of 80. T he study was conducted at the Florida Atlantic University’s Memory Center and Clinical Research Unit. Participants included those who received a driving evaluation at the Memory Center and agreed to have their results included in the Driving Repository, and community-based older drivers who volunteered to participate.
 

Limitations of the Study

There were marginal differences between sexes on the measures, but they were not significant. The sample was composed of relatively well-educated people, primarily of European American ethnic origin, which is a consideration in generalizing the results.

Among other limitations are that physical and sensory factors, in addition to cognitive issues, may affect an individual’s ability to drive safely and are not included in the algorithm. Sensory disabilities, including reduced visual acuity caused by binocular field vision loss, contrast sensitivity, glare sensitivity, and other conditions, may affect driving ability as well as the ability to fully rotate the head and neck. Medical conditions affecting the cardiovascular, neurological, and orthopedic systems can also influence driving ability.

“Future studies should involve more diverse samples and a greater variety of driving challenges, including school zones and multilane highways, which are not included in the study,” the authors write.

The study received grant support from the State of Florida Department of Health and the Ed and Ethel Moore Alzheimer’s Disease Research Program.

An algorithm using two well-known tests has shown strong accuracy (91%) in predicting whether an older driver can pass an on-road driving evaluation according to a new study published in the Journal of the American Medical Directors Association .

The Fit2Drive algorithm combines the Mini-Mental State Exam (MMSE), a 30-point dementia screening tool that has been found in several studies to have an association with driving ability, and the Trails B test, which gauges cognitive flexibility and set-shifting (task switching), considered to be measures of executive functioning.
 

Algorithm Available for Providers

The algorithm is clinically available and providers can fill in patients’ information and results of the two tests at the Fit2Drive website. Results may help physicians with often-difficult conversations with older patients about driving when they present with cognitive concerns.

Families report it is one of the most difficult conversations they have with a loved one and doctors are often asked to be part of the conversation. This is particularly difficult when, often, little objective information is available. In the past, a clinical rule of thumb has been that people diagnosed with Alzheimer’s disease or related dementias (ADRD) will usually be able to drive for 3 years after diagnosis.

“[T]he anger, tears, and frustration on the part of the individual patient and the lack of objective data to guide provider recommendations are the driving forces behind our effort to develop a highly accurate, evidence-based predictor of the ability to pass an on-road driving test,” the authors write. They added that the goal of the study was to identify the smallest number of cognitive test results that could predict likelihood of passing an on-road driver evaluation.

A number of tests were evaluated for the algorithm, but the combination of Trails B in seconds and MMSE using the highest scores of the serial 7s (counting back from 100 by 7s) or WORLD spelled backward accounted for the highest correlation with passing the on-road driving test, according to the authors, led by Ruth Tappen, EdD, FN, with the Christine E. Lynn College of Nursing at Florida Atlantic University, in Boca Raton.

A receiver operator characteristic (ROC) analysis was conducted on the linear combination of the two assessments.

“Because an ROC of 0.70 is considered to be the minimal requirement [for predictive value], 0.80 is considered good, and higher than 0.90 is excellent, these findings [with 91% area under the curve] suggest excellent accuracy using these two cognitive tests in this population,” the authors write.

For this analysis, researchers included 412 older drivers (179 men and 233 women) with an average age of 80. T he study was conducted at the Florida Atlantic University’s Memory Center and Clinical Research Unit. Participants included those who received a driving evaluation at the Memory Center and agreed to have their results included in the Driving Repository, and community-based older drivers who volunteered to participate.
 

Limitations of the Study

There were marginal differences between sexes on the measures, but they were not significant. The sample was composed of relatively well-educated people, primarily of European American ethnic origin, which is a consideration in generalizing the results.

Among other limitations are that physical and sensory factors, in addition to cognitive issues, may affect an individual’s ability to drive safely and are not included in the algorithm. Sensory disabilities, including reduced visual acuity caused by binocular field vision loss, contrast sensitivity, glare sensitivity, and other conditions, may affect driving ability as well as the ability to fully rotate the head and neck. Medical conditions affecting the cardiovascular, neurological, and orthopedic systems can also influence driving ability.

“Future studies should involve more diverse samples and a greater variety of driving challenges, including school zones and multilane highways, which are not included in the study,” the authors write.

The study received grant support from the State of Florida Department of Health and the Ed and Ethel Moore Alzheimer’s Disease Research Program.

An algorithm using two well-known tests has shown strong accuracy (91%) in predicting whether an older driver can pass an on-road driving evaluation according to a new study published in the Journal of the American Medical Directors Association .

The Fit2Drive algorithm combines the Mini-Mental State Exam (MMSE), a 30-point dementia screening tool that has been found in several studies to have an association with driving ability, and the Trails B test, which gauges cognitive flexibility and set-shifting (task switching), considered to be measures of executive functioning.
 

Algorithm Available for Providers

The algorithm is clinically available and providers can fill in patients’ information and results of the two tests at the Fit2Drive website. Results may help physicians with often-difficult conversations with older patients about driving when they present with cognitive concerns.

Families report it is one of the most difficult conversations they have with a loved one and doctors are often asked to be part of the conversation. This is particularly difficult when, often, little objective information is available. In the past, a clinical rule of thumb has been that people diagnosed with Alzheimer’s disease or related dementias (ADRD) will usually be able to drive for 3 years after diagnosis.

“[T]he anger, tears, and frustration on the part of the individual patient and the lack of objective data to guide provider recommendations are the driving forces behind our effort to develop a highly accurate, evidence-based predictor of the ability to pass an on-road driving test,” the authors write. They added that the goal of the study was to identify the smallest number of cognitive test results that could predict likelihood of passing an on-road driver evaluation.

A number of tests were evaluated for the algorithm, but the combination of Trails B in seconds and MMSE using the highest scores of the serial 7s (counting back from 100 by 7s) or WORLD spelled backward accounted for the highest correlation with passing the on-road driving test, according to the authors, led by Ruth Tappen, EdD, FN, with the Christine E. Lynn College of Nursing at Florida Atlantic University, in Boca Raton.

A receiver operator characteristic (ROC) analysis was conducted on the linear combination of the two assessments.

“Because an ROC of 0.70 is considered to be the minimal requirement [for predictive value], 0.80 is considered good, and higher than 0.90 is excellent, these findings [with 91% area under the curve] suggest excellent accuracy using these two cognitive tests in this population,” the authors write.

For this analysis, researchers included 412 older drivers (179 men and 233 women) with an average age of 80. T he study was conducted at the Florida Atlantic University’s Memory Center and Clinical Research Unit. Participants included those who received a driving evaluation at the Memory Center and agreed to have their results included in the Driving Repository, and community-based older drivers who volunteered to participate.
 

Limitations of the Study

There were marginal differences between sexes on the measures, but they were not significant. The sample was composed of relatively well-educated people, primarily of European American ethnic origin, which is a consideration in generalizing the results.

Among other limitations are that physical and sensory factors, in addition to cognitive issues, may affect an individual’s ability to drive safely and are not included in the algorithm. Sensory disabilities, including reduced visual acuity caused by binocular field vision loss, contrast sensitivity, glare sensitivity, and other conditions, may affect driving ability as well as the ability to fully rotate the head and neck. Medical conditions affecting the cardiovascular, neurological, and orthopedic systems can also influence driving ability.

“Future studies should involve more diverse samples and a greater variety of driving challenges, including school zones and multilane highways, which are not included in the study,” the authors write.

The study received grant support from the State of Florida Department of Health and the Ed and Ethel Moore Alzheimer’s Disease Research Program.

Glucagon-like peptide 1 (GLP-1) receptor agonists such as semaglutide (marketed as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for obesity) slow down digestion and curb hunger by working on the brain’s dopamine reward center. They are prescribed to promote weight loss, metabolic health in type 2 diabetes, and heart health in coronary artery disease.

Semaglutide can be prescribed in two forms: the brand-name version, which is approved and confirmed as safe and effective by the US Food and Drug Administration (FDA), and the versions that can be obtained from a compounding pharmacy. Compounding pharmacies are permitted by the FDA to produce what is “ essentially a copy” of approved medications when there’s an official shortage, which is currently the case with semaglutide and other GLP-1 receptor agonists.

Patients are often drawn to compounding pharmacies for pricing-related reasons. If semaglutide is prescribed for a clear indication like diabetes and is covered by insurance, the brand-name version is commonly dispensed. However, if it’s not covered, patients need to pay out of pocket for branded versions, which carry a monthly cost of $1000 or more. Alternatively, their doctors can prescribe compounded semaglutide, which some telehealth companies advertise at costs of approximately $150-$300 per month.
 

Potential Issues With Compounded Semaglutide 

Compounding pharmacies produce drugs from raw materials containing active pharmaceutical ingredients (APIs). Although compounders use many of the same ingredients found in brand-name medications, for drugs like semaglutide, they may opt for specific salts that are not identical to those involved in the production of the standard versions. These salts are typically reserved for research purposes and may not be suitable for general use.

In late 2023, the FDA issued a letter asking the public to exercise caution when using compounded products containing semaglutide or semaglutide salts. This was followed in January 2024 by an FDA communication citing adverse events reported with the use of compounded semaglutide and advising patients to avoid these versions if an approved form of the drug is available.
 

Compound Pharmacies: A Closer Look 

Compounding pharmacies have exploded in popularity in the past several decades. The compounding pharmacy market is expected to grow at 7.8% per year over the next decade. 

Historically, compounding pharmacies have filled a niche for specialty vitamins for intravenous administration as well as chemotherapy medications. They also offer controlled substances, such as ketamine lozenges and nasal sprays, which are unavailable or are in short supply from traditional manufacturers.

Compounding pharmacies fall into two categories. First are compounding pharmacies covered under Section 503A of the Federal Food, Drug and Cosmetic Act; these drugs are neither tested nor monitored. Such facilities do not have to report adverse events to the FDA. The second category is Section 503B outsourcing facilities. These pharmacies choose to be tested by, to be inspected by, and to report adverse events to the FDA. 
 

The FDA’s Latest Update on This Issue

This news organization contacted the FDA for an update on the adverse events reported about compounded semaglutide. From August 8, 2021, to March 31, 2024, they received more than 20,000 adverse events reports for FDA-approved semaglutide. Comparatively, there were 210 adverse events reported on compounded semaglutide products. 

The FDA went on to describe that many of the adverse events reported were consistent with known reactions in the labeling, like nausea, diarrhea, and headache. Yet, they added that, “the FDA is unable to determine how, or if, other factors may have contributed to these adverse events, such as differences in ingredients and formulation between FDA-approved and compounded semaglutide products.” They also noted there was variation in the data quality in the reports they have received, which came only from 503B compounding pharmacies.

In conclusion, given the concerns about compounded semaglutide, it is prudent for the prescribing physicians as well as the patients taking the medication to know that risks are “higher” according to the FDA. We eagerly await more specific information from the FDA to better understand reported adverse events. 
 

How to Help Patients Receive Safe Compounded Semaglutide 

For clinicians considering prescribing semaglutide from compounding pharmacies, there are several questions worth asking, according to the Alliance for Pharmacy Compounding. First, find out whether the pharmacy complies with United States Pharmacopeia compounding standards and whether they source their APIs from FDA-registered facilities, the latter being required by federal law. It’s also important to ensure that these facilities undergo periodic third-party testing to verify medication purity and dosing. 

Ask whether the pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation from the PCAB means that pharmacies have been assessed for processes related to continuous quality improvement. In addition, ask whether the pharmacy is designated as a 503B compounder and if not, why.

Finally, interviewing the pharmacist themselves can provide useful information about staffing, training, and their methods of preparing medications. For example, if they are preparing a sterile eye drop, it is important to ask about sterility testing.

Jesse M. Pines, MD, MBA, MSCE, is a clinical professor of emergency medicine at George Washington University in Washington, and a professor in the department of emergency medicine at Drexel University College of Medicine in Philadelphia, Pennsylvania. Dr. Pines is also the chief of clinical innovation at US Acute Care Solutions in Canton, Ohio. Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. Dr. Pines reported conflicts of interest with CSL Behring and Abbott Point-of-Care. Dr. Glatter reported no relevant conflicts of interest.
 

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

Glucagon-like peptide 1 (GLP-1) receptor agonists such as semaglutide (marketed as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for obesity) slow down digestion and curb hunger by working on the brain’s dopamine reward center. They are prescribed to promote weight loss, metabolic health in type 2 diabetes, and heart health in coronary artery disease.

Semaglutide can be prescribed in two forms: the brand-name version, which is approved and confirmed as safe and effective by the US Food and Drug Administration (FDA), and the versions that can be obtained from a compounding pharmacy. Compounding pharmacies are permitted by the FDA to produce what is “ essentially a copy” of approved medications when there’s an official shortage, which is currently the case with semaglutide and other GLP-1 receptor agonists.

Patients are often drawn to compounding pharmacies for pricing-related reasons. If semaglutide is prescribed for a clear indication like diabetes and is covered by insurance, the brand-name version is commonly dispensed. However, if it’s not covered, patients need to pay out of pocket for branded versions, which carry a monthly cost of $1000 or more. Alternatively, their doctors can prescribe compounded semaglutide, which some telehealth companies advertise at costs of approximately $150-$300 per month.
 

Potential Issues With Compounded Semaglutide 

Compounding pharmacies produce drugs from raw materials containing active pharmaceutical ingredients (APIs). Although compounders use many of the same ingredients found in brand-name medications, for drugs like semaglutide, they may opt for specific salts that are not identical to those involved in the production of the standard versions. These salts are typically reserved for research purposes and may not be suitable for general use.

In late 2023, the FDA issued a letter asking the public to exercise caution when using compounded products containing semaglutide or semaglutide salts. This was followed in January 2024 by an FDA communication citing adverse events reported with the use of compounded semaglutide and advising patients to avoid these versions if an approved form of the drug is available.
 

Compound Pharmacies: A Closer Look 

Compounding pharmacies have exploded in popularity in the past several decades. The compounding pharmacy market is expected to grow at 7.8% per year over the next decade. 

Historically, compounding pharmacies have filled a niche for specialty vitamins for intravenous administration as well as chemotherapy medications. They also offer controlled substances, such as ketamine lozenges and nasal sprays, which are unavailable or are in short supply from traditional manufacturers.

Compounding pharmacies fall into two categories. First are compounding pharmacies covered under Section 503A of the Federal Food, Drug and Cosmetic Act; these drugs are neither tested nor monitored. Such facilities do not have to report adverse events to the FDA. The second category is Section 503B outsourcing facilities. These pharmacies choose to be tested by, to be inspected by, and to report adverse events to the FDA. 
 

The FDA’s Latest Update on This Issue

This news organization contacted the FDA for an update on the adverse events reported about compounded semaglutide. From August 8, 2021, to March 31, 2024, they received more than 20,000 adverse events reports for FDA-approved semaglutide. Comparatively, there were 210 adverse events reported on compounded semaglutide products. 

The FDA went on to describe that many of the adverse events reported were consistent with known reactions in the labeling, like nausea, diarrhea, and headache. Yet, they added that, “the FDA is unable to determine how, or if, other factors may have contributed to these adverse events, such as differences in ingredients and formulation between FDA-approved and compounded semaglutide products.” They also noted there was variation in the data quality in the reports they have received, which came only from 503B compounding pharmacies.

In conclusion, given the concerns about compounded semaglutide, it is prudent for the prescribing physicians as well as the patients taking the medication to know that risks are “higher” according to the FDA. We eagerly await more specific information from the FDA to better understand reported adverse events. 
 

How to Help Patients Receive Safe Compounded Semaglutide 

For clinicians considering prescribing semaglutide from compounding pharmacies, there are several questions worth asking, according to the Alliance for Pharmacy Compounding. First, find out whether the pharmacy complies with United States Pharmacopeia compounding standards and whether they source their APIs from FDA-registered facilities, the latter being required by federal law. It’s also important to ensure that these facilities undergo periodic third-party testing to verify medication purity and dosing. 

Ask whether the pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation from the PCAB means that pharmacies have been assessed for processes related to continuous quality improvement. In addition, ask whether the pharmacy is designated as a 503B compounder and if not, why.

Finally, interviewing the pharmacist themselves can provide useful information about staffing, training, and their methods of preparing medications. For example, if they are preparing a sterile eye drop, it is important to ask about sterility testing.

Jesse M. Pines, MD, MBA, MSCE, is a clinical professor of emergency medicine at George Washington University in Washington, and a professor in the department of emergency medicine at Drexel University College of Medicine in Philadelphia, Pennsylvania. Dr. Pines is also the chief of clinical innovation at US Acute Care Solutions in Canton, Ohio. Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. Dr. Pines reported conflicts of interest with CSL Behring and Abbott Point-of-Care. Dr. Glatter reported no relevant conflicts of interest.
 

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

Glucagon-like peptide 1 (GLP-1) receptor agonists such as semaglutide (marketed as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for obesity) slow down digestion and curb hunger by working on the brain’s dopamine reward center. They are prescribed to promote weight loss, metabolic health in type 2 diabetes, and heart health in coronary artery disease.

Semaglutide can be prescribed in two forms: the brand-name version, which is approved and confirmed as safe and effective by the US Food and Drug Administration (FDA), and the versions that can be obtained from a compounding pharmacy. Compounding pharmacies are permitted by the FDA to produce what is “ essentially a copy” of approved medications when there’s an official shortage, which is currently the case with semaglutide and other GLP-1 receptor agonists.

Patients are often drawn to compounding pharmacies for pricing-related reasons. If semaglutide is prescribed for a clear indication like diabetes and is covered by insurance, the brand-name version is commonly dispensed. However, if it’s not covered, patients need to pay out of pocket for branded versions, which carry a monthly cost of $1000 or more. Alternatively, their doctors can prescribe compounded semaglutide, which some telehealth companies advertise at costs of approximately $150-$300 per month.
 

Potential Issues With Compounded Semaglutide 

Compounding pharmacies produce drugs from raw materials containing active pharmaceutical ingredients (APIs). Although compounders use many of the same ingredients found in brand-name medications, for drugs like semaglutide, they may opt for specific salts that are not identical to those involved in the production of the standard versions. These salts are typically reserved for research purposes and may not be suitable for general use.

In late 2023, the FDA issued a letter asking the public to exercise caution when using compounded products containing semaglutide or semaglutide salts. This was followed in January 2024 by an FDA communication citing adverse events reported with the use of compounded semaglutide and advising patients to avoid these versions if an approved form of the drug is available.
 

Compound Pharmacies: A Closer Look 

Compounding pharmacies have exploded in popularity in the past several decades. The compounding pharmacy market is expected to grow at 7.8% per year over the next decade. 

Historically, compounding pharmacies have filled a niche for specialty vitamins for intravenous administration as well as chemotherapy medications. They also offer controlled substances, such as ketamine lozenges and nasal sprays, which are unavailable or are in short supply from traditional manufacturers.

Compounding pharmacies fall into two categories. First are compounding pharmacies covered under Section 503A of the Federal Food, Drug and Cosmetic Act; these drugs are neither tested nor monitored. Such facilities do not have to report adverse events to the FDA. The second category is Section 503B outsourcing facilities. These pharmacies choose to be tested by, to be inspected by, and to report adverse events to the FDA. 
 

The FDA’s Latest Update on This Issue

This news organization contacted the FDA for an update on the adverse events reported about compounded semaglutide. From August 8, 2021, to March 31, 2024, they received more than 20,000 adverse events reports for FDA-approved semaglutide. Comparatively, there were 210 adverse events reported on compounded semaglutide products. 

The FDA went on to describe that many of the adverse events reported were consistent with known reactions in the labeling, like nausea, diarrhea, and headache. Yet, they added that, “the FDA is unable to determine how, or if, other factors may have contributed to these adverse events, such as differences in ingredients and formulation between FDA-approved and compounded semaglutide products.” They also noted there was variation in the data quality in the reports they have received, which came only from 503B compounding pharmacies.

In conclusion, given the concerns about compounded semaglutide, it is prudent for the prescribing physicians as well as the patients taking the medication to know that risks are “higher” according to the FDA. We eagerly await more specific information from the FDA to better understand reported adverse events. 
 

How to Help Patients Receive Safe Compounded Semaglutide 

For clinicians considering prescribing semaglutide from compounding pharmacies, there are several questions worth asking, according to the Alliance for Pharmacy Compounding. First, find out whether the pharmacy complies with United States Pharmacopeia compounding standards and whether they source their APIs from FDA-registered facilities, the latter being required by federal law. It’s also important to ensure that these facilities undergo periodic third-party testing to verify medication purity and dosing. 

Ask whether the pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation from the PCAB means that pharmacies have been assessed for processes related to continuous quality improvement. In addition, ask whether the pharmacy is designated as a 503B compounder and if not, why.

Finally, interviewing the pharmacist themselves can provide useful information about staffing, training, and their methods of preparing medications. For example, if they are preparing a sterile eye drop, it is important to ask about sterility testing.

Jesse M. Pines, MD, MBA, MSCE, is a clinical professor of emergency medicine at George Washington University in Washington, and a professor in the department of emergency medicine at Drexel University College of Medicine in Philadelphia, Pennsylvania. Dr. Pines is also the chief of clinical innovation at US Acute Care Solutions in Canton, Ohio. Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. Dr. Pines reported conflicts of interest with CSL Behring and Abbott Point-of-Care. Dr. Glatter reported no relevant conflicts of interest.
 

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