Conference Coverage

Findings from the phase 3 ESOPEC trial demonstrate an overall survival advantage with a perioperative chemotherapy regimen known as FLOT, compared with a neoadjuvant chemoradiation approach, called CROSS, in patients with resectable, locally advanced esophageal adenocarcinoma.

The study results, presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO), help settle a long-standing debate about whether chemotherapy with FLOT — 5-florouracil, leucovorin, oxaliplatin, and docetaxel — before and after surgery, or neoadjuvant radiation plus CROSS — carboplatin and paclitaxel — followed by surgery is the best approach.

There has been “considerable disagreement as to whether giving all adjuvant therapy upfront versus ‘sandwich’ adjuvant therapy before and after surgery is the better standard of care for locally advanced resectable esophageal cancer,” Jennifer Tseng, MD, of Boston Medical Center, Boston, said in an ASCO press release. This randomized clinical trial shows the sandwich approach “provides better outcomes.”

The practice-changing ESOPEC findings will have an important effect on the management of patients with resectable esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, but local and distant failures remain a challenge in this population, explained invited discussant Karyn A. Goodman, MD.

Advances since the initiation of ESOPEC — such as immunotherapy options and personalized strategies — suggest the esophageal adenocarcinoma story is still evolving, said Dr. Goodman, professor and vice chair of research and quality in the Department of Radiation Oncology at Icahn School of Medicine at Mount Sinai, New York. 
 

The ESOPEC trial

Both the FLOT and CROSS regimens are established standards of care in resectable esophageal adenocarcinoma, and the choice of treatment has largely varied based on geographical location.

The current randomized, prospective, open-label ESOPEC trial, however, demonstrated that FLOT can prolong overall survival, first author Jens Hoeppner, MD, from the University of Bielefeld in Detmold, Germany, reported.

Overall, 438 patients with locally advanced, resectable esophageal adenocarcinoma recruited between February 2016 and April 2020 from 25 sites in Germany and randomized to either FLOT (n = 221) or CROSS (n = 217). The median age was 63 years, and most (89.3%) were men. Patients were followed until November 2023, and median follow-up was 55 months.

Patients in the FLOT arm received four cycles — one every 2 weeks for 8 weeks — followed by surgery 4-6 weeks later. FLOT cycles were reinitiated 4-6 weeks after surgery and given every 2 weeks for 8 weeks.

Those in the CROSS arm received one cycle per week of radiation therapy for 5 weeks plus carboplatin and paclitaxel followed by surgery 4-6 weeks after the last cycle.

Overall, 86% received both neoadjuvant therapy and surgery in the FLOT arm versus 82.9% in the CROSS group. Among these patients, 16.8% in the FLOT group achieved a pathological complete remission versus 10.0% in the CROSS arm.

In the intention-to-treat population, median overall survival was almost twice as long in the FLOT group — 66 months versus 37 months. At 3 years, those who received FLOT had a 30% lower risk of dying (hazard ratio [HR], 0.70), with 57.4% of patients alive at that point, compared with 50.7% patients in the CROSS arm.

The 5-year overall survival was 50.6% in the FLOT group versus 38.7% in the CROSS group.

Patients receiving FLOT also demonstrated improved progression-free survival (PFS), with a median PFS of 38 months versus 16 months. The 3-year PFS was 51.6% with FLOT versus 35.0% with CROSS (HR, 0.66). The exploratory subgroup analyses for sex, age, ECOG status, and clinical T and N stages also favored FLOT.

The 30-day postoperative mortality was 1.0% in the FLOT group and 1.7% in the CROSS group, and the 90-day postoperative mortality rate was 3.2% and 5.6%, respectively.

Based on these findings, perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with CROSS, Dr. Hoeppner concluded.

Dr. Goodman agreed, noting that, in the wake of ESOPEC, FLOT will likely be adopted as a more standard approach in the United States for patients who are fit. And, for patients who are not candidates for FLOT, CROSS is a reasonable option, she said.

But, she asked, does it really have to be an either/or situation?

Multiple studies, including Dr. Goodman’s 2021 Alliance/CALGB 80803 study, have demonstrated promising outcomes with combined modalities and adapting therapy based on treatment response. Several trials, for instance, are evaluating combining FLOT and CROSS, with some showing the approach is feasible and comes with manageable toxicity.

It’s also important to look outside of FLOT and CROSS. During ESOPEC, new approaches entered the treatment landscape, including the use of adjuvant immunotherapy following neoadjuvant chemoradiation and surgery for noncomplete response.

Take the CheckMate 577 study, which found that adjuvant nivolumab immunotherapy after preoperative CROSS and surgery significantly reduced metastatic recurrence and doubled disease-free survival in patients who did not achieve a complete response. This approach is now a standard of care for those patients.

FLOT plus neoadjuvant nivolumab may also be a viable option, Dr. Goodman noted, but we haven’t yet seen “any benefit in survival with the combo of chemotherapy and immunotherapy for resectable esophago-gastric cancer.”

Further studies are needed to evaluate the synergy of immunotherapy and radiotherapy. The next chapter of the esophageal adenocarcinoma story may feature a “best-of-both-worlds” approach that combines induction chemotherapy, followed by personalized chemoradiation, surgery, and potentially adjuvant immunotherapy, Dr. Goodman explained.

While the ESOPEC findings are impressive, the 5-year overall survival of only 50% is still suboptimal, she noted. “Given the poor prognosis with this disease, we need to continue to develop clinical trials to identify better targets, novel treatment combinations, and select patients that will respond best to specific treatment.”

ESOPEC was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation). Dr. Hoeppner reported receiving travel, accommodations, and expenses from Intuitive Surgical. Dr. Goodman reported a relationship with the National Cancer Institute and consulting or advisory roles for Novartis, Philips Healthcare, RenovoRX, and Roche/Genentech.

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

Findings from the phase 3 ESOPEC trial demonstrate an overall survival advantage with a perioperative chemotherapy regimen known as FLOT, compared with a neoadjuvant chemoradiation approach, called CROSS, in patients with resectable, locally advanced esophageal adenocarcinoma.

The study results, presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO), help settle a long-standing debate about whether chemotherapy with FLOT — 5-florouracil, leucovorin, oxaliplatin, and docetaxel — before and after surgery, or neoadjuvant radiation plus CROSS — carboplatin and paclitaxel — followed by surgery is the best approach.

There has been “considerable disagreement as to whether giving all adjuvant therapy upfront versus ‘sandwich’ adjuvant therapy before and after surgery is the better standard of care for locally advanced resectable esophageal cancer,” Jennifer Tseng, MD, of Boston Medical Center, Boston, said in an ASCO press release. This randomized clinical trial shows the sandwich approach “provides better outcomes.”

The practice-changing ESOPEC findings will have an important effect on the management of patients with resectable esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, but local and distant failures remain a challenge in this population, explained invited discussant Karyn A. Goodman, MD.

Advances since the initiation of ESOPEC — such as immunotherapy options and personalized strategies — suggest the esophageal adenocarcinoma story is still evolving, said Dr. Goodman, professor and vice chair of research and quality in the Department of Radiation Oncology at Icahn School of Medicine at Mount Sinai, New York. 
 

The ESOPEC trial

Both the FLOT and CROSS regimens are established standards of care in resectable esophageal adenocarcinoma, and the choice of treatment has largely varied based on geographical location.

The current randomized, prospective, open-label ESOPEC trial, however, demonstrated that FLOT can prolong overall survival, first author Jens Hoeppner, MD, from the University of Bielefeld in Detmold, Germany, reported.

Overall, 438 patients with locally advanced, resectable esophageal adenocarcinoma recruited between February 2016 and April 2020 from 25 sites in Germany and randomized to either FLOT (n = 221) or CROSS (n = 217). The median age was 63 years, and most (89.3%) were men. Patients were followed until November 2023, and median follow-up was 55 months.

Patients in the FLOT arm received four cycles — one every 2 weeks for 8 weeks — followed by surgery 4-6 weeks later. FLOT cycles were reinitiated 4-6 weeks after surgery and given every 2 weeks for 8 weeks.

Those in the CROSS arm received one cycle per week of radiation therapy for 5 weeks plus carboplatin and paclitaxel followed by surgery 4-6 weeks after the last cycle.

Overall, 86% received both neoadjuvant therapy and surgery in the FLOT arm versus 82.9% in the CROSS group. Among these patients, 16.8% in the FLOT group achieved a pathological complete remission versus 10.0% in the CROSS arm.

In the intention-to-treat population, median overall survival was almost twice as long in the FLOT group — 66 months versus 37 months. At 3 years, those who received FLOT had a 30% lower risk of dying (hazard ratio [HR], 0.70), with 57.4% of patients alive at that point, compared with 50.7% patients in the CROSS arm.

The 5-year overall survival was 50.6% in the FLOT group versus 38.7% in the CROSS group.

Patients receiving FLOT also demonstrated improved progression-free survival (PFS), with a median PFS of 38 months versus 16 months. The 3-year PFS was 51.6% with FLOT versus 35.0% with CROSS (HR, 0.66). The exploratory subgroup analyses for sex, age, ECOG status, and clinical T and N stages also favored FLOT.

The 30-day postoperative mortality was 1.0% in the FLOT group and 1.7% in the CROSS group, and the 90-day postoperative mortality rate was 3.2% and 5.6%, respectively.

Based on these findings, perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with CROSS, Dr. Hoeppner concluded.

Dr. Goodman agreed, noting that, in the wake of ESOPEC, FLOT will likely be adopted as a more standard approach in the United States for patients who are fit. And, for patients who are not candidates for FLOT, CROSS is a reasonable option, she said.

But, she asked, does it really have to be an either/or situation?

Multiple studies, including Dr. Goodman’s 2021 Alliance/CALGB 80803 study, have demonstrated promising outcomes with combined modalities and adapting therapy based on treatment response. Several trials, for instance, are evaluating combining FLOT and CROSS, with some showing the approach is feasible and comes with manageable toxicity.

It’s also important to look outside of FLOT and CROSS. During ESOPEC, new approaches entered the treatment landscape, including the use of adjuvant immunotherapy following neoadjuvant chemoradiation and surgery for noncomplete response.

Take the CheckMate 577 study, which found that adjuvant nivolumab immunotherapy after preoperative CROSS and surgery significantly reduced metastatic recurrence and doubled disease-free survival in patients who did not achieve a complete response. This approach is now a standard of care for those patients.

FLOT plus neoadjuvant nivolumab may also be a viable option, Dr. Goodman noted, but we haven’t yet seen “any benefit in survival with the combo of chemotherapy and immunotherapy for resectable esophago-gastric cancer.”

Further studies are needed to evaluate the synergy of immunotherapy and radiotherapy. The next chapter of the esophageal adenocarcinoma story may feature a “best-of-both-worlds” approach that combines induction chemotherapy, followed by personalized chemoradiation, surgery, and potentially adjuvant immunotherapy, Dr. Goodman explained.

While the ESOPEC findings are impressive, the 5-year overall survival of only 50% is still suboptimal, she noted. “Given the poor prognosis with this disease, we need to continue to develop clinical trials to identify better targets, novel treatment combinations, and select patients that will respond best to specific treatment.”

ESOPEC was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation). Dr. Hoeppner reported receiving travel, accommodations, and expenses from Intuitive Surgical. Dr. Goodman reported a relationship with the National Cancer Institute and consulting or advisory roles for Novartis, Philips Healthcare, RenovoRX, and Roche/Genentech.

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

Findings from the phase 3 ESOPEC trial demonstrate an overall survival advantage with a perioperative chemotherapy regimen known as FLOT, compared with a neoadjuvant chemoradiation approach, called CROSS, in patients with resectable, locally advanced esophageal adenocarcinoma.

The study results, presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO), help settle a long-standing debate about whether chemotherapy with FLOT — 5-florouracil, leucovorin, oxaliplatin, and docetaxel — before and after surgery, or neoadjuvant radiation plus CROSS — carboplatin and paclitaxel — followed by surgery is the best approach.

There has been “considerable disagreement as to whether giving all adjuvant therapy upfront versus ‘sandwich’ adjuvant therapy before and after surgery is the better standard of care for locally advanced resectable esophageal cancer,” Jennifer Tseng, MD, of Boston Medical Center, Boston, said in an ASCO press release. This randomized clinical trial shows the sandwich approach “provides better outcomes.”

The practice-changing ESOPEC findings will have an important effect on the management of patients with resectable esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, but local and distant failures remain a challenge in this population, explained invited discussant Karyn A. Goodman, MD.

Advances since the initiation of ESOPEC — such as immunotherapy options and personalized strategies — suggest the esophageal adenocarcinoma story is still evolving, said Dr. Goodman, professor and vice chair of research and quality in the Department of Radiation Oncology at Icahn School of Medicine at Mount Sinai, New York. 
 

The ESOPEC trial

Both the FLOT and CROSS regimens are established standards of care in resectable esophageal adenocarcinoma, and the choice of treatment has largely varied based on geographical location.

The current randomized, prospective, open-label ESOPEC trial, however, demonstrated that FLOT can prolong overall survival, first author Jens Hoeppner, MD, from the University of Bielefeld in Detmold, Germany, reported.

Overall, 438 patients with locally advanced, resectable esophageal adenocarcinoma recruited between February 2016 and April 2020 from 25 sites in Germany and randomized to either FLOT (n = 221) or CROSS (n = 217). The median age was 63 years, and most (89.3%) were men. Patients were followed until November 2023, and median follow-up was 55 months.

Patients in the FLOT arm received four cycles — one every 2 weeks for 8 weeks — followed by surgery 4-6 weeks later. FLOT cycles were reinitiated 4-6 weeks after surgery and given every 2 weeks for 8 weeks.

Those in the CROSS arm received one cycle per week of radiation therapy for 5 weeks plus carboplatin and paclitaxel followed by surgery 4-6 weeks after the last cycle.

Overall, 86% received both neoadjuvant therapy and surgery in the FLOT arm versus 82.9% in the CROSS group. Among these patients, 16.8% in the FLOT group achieved a pathological complete remission versus 10.0% in the CROSS arm.

In the intention-to-treat population, median overall survival was almost twice as long in the FLOT group — 66 months versus 37 months. At 3 years, those who received FLOT had a 30% lower risk of dying (hazard ratio [HR], 0.70), with 57.4% of patients alive at that point, compared with 50.7% patients in the CROSS arm.

The 5-year overall survival was 50.6% in the FLOT group versus 38.7% in the CROSS group.

Patients receiving FLOT also demonstrated improved progression-free survival (PFS), with a median PFS of 38 months versus 16 months. The 3-year PFS was 51.6% with FLOT versus 35.0% with CROSS (HR, 0.66). The exploratory subgroup analyses for sex, age, ECOG status, and clinical T and N stages also favored FLOT.

The 30-day postoperative mortality was 1.0% in the FLOT group and 1.7% in the CROSS group, and the 90-day postoperative mortality rate was 3.2% and 5.6%, respectively.

Based on these findings, perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with CROSS, Dr. Hoeppner concluded.

Dr. Goodman agreed, noting that, in the wake of ESOPEC, FLOT will likely be adopted as a more standard approach in the United States for patients who are fit. And, for patients who are not candidates for FLOT, CROSS is a reasonable option, she said.

But, she asked, does it really have to be an either/or situation?

Multiple studies, including Dr. Goodman’s 2021 Alliance/CALGB 80803 study, have demonstrated promising outcomes with combined modalities and adapting therapy based on treatment response. Several trials, for instance, are evaluating combining FLOT and CROSS, with some showing the approach is feasible and comes with manageable toxicity.

It’s also important to look outside of FLOT and CROSS. During ESOPEC, new approaches entered the treatment landscape, including the use of adjuvant immunotherapy following neoadjuvant chemoradiation and surgery for noncomplete response.

Take the CheckMate 577 study, which found that adjuvant nivolumab immunotherapy after preoperative CROSS and surgery significantly reduced metastatic recurrence and doubled disease-free survival in patients who did not achieve a complete response. This approach is now a standard of care for those patients.

FLOT plus neoadjuvant nivolumab may also be a viable option, Dr. Goodman noted, but we haven’t yet seen “any benefit in survival with the combo of chemotherapy and immunotherapy for resectable esophago-gastric cancer.”

Further studies are needed to evaluate the synergy of immunotherapy and radiotherapy. The next chapter of the esophageal adenocarcinoma story may feature a “best-of-both-worlds” approach that combines induction chemotherapy, followed by personalized chemoradiation, surgery, and potentially adjuvant immunotherapy, Dr. Goodman explained.

While the ESOPEC findings are impressive, the 5-year overall survival of only 50% is still suboptimal, she noted. “Given the poor prognosis with this disease, we need to continue to develop clinical trials to identify better targets, novel treatment combinations, and select patients that will respond best to specific treatment.”

ESOPEC was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation). Dr. Hoeppner reported receiving travel, accommodations, and expenses from Intuitive Surgical. Dr. Goodman reported a relationship with the National Cancer Institute and consulting or advisory roles for Novartis, Philips Healthcare, RenovoRX, and Roche/Genentech.

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 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.

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

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

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

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

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

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

At the recent American Diabetes Association (ADA) Scientific Sessions, researchers unveiled promising data on a novel antimicrobial peptide PL-5 spray. This innovative treatment shows significant promise for managing mild to moderate infected diabetic foot ulcers. 

Of the 1.6 million people with diabetes in the United States and the tens of millions of similar people worldwide, 50% will require antimicrobials at some time during their life cycle. Diabetic foot infections are difficult to treat because of their resistance to conventional therapies, often leading to severe complications, including amputations. 

To address this issue, the antimicrobial peptide PL-5 spray was developed with a novel mechanism of action to potentially improve treatment outcomes. The study aimed to assess the clinical efficacy and safety of the PL-5 spray combined with standard debridement procedures in treating mild to moderate diabetic foot ulcers.

This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in four hospitals across China. Participants with mild to moderate diabetic foot ulcers were randomly assigned in a 2:1 ratio to either the PL-5 group or the placebo group, both receiving standard debridement. The primary endpoint was clinical efficacy at day 1 after the end of treatment (EOT1). Secondary endpoints included clinical efficacy at day 7 (EOT7), microbiological efficacy, drug-resistant bacteria clearance rate, wound healing rate, and safety outcomes evaluated at both EOT1 and EOT7.

The study included 47 participants, with 32 in the PL-5 group and 15 in the placebo group. Both groups had statistically comparable demographic and clinical characteristics. The primary endpoint showed a higher clinical efficacy (cure/improvement ratio) in the PL-5 group, compared with the control group (1.33 vs 0.55; P =.0764), suggesting a positive trend but not reaching statistical significance in this population.

Among the secondary endpoints, clinical efficacy at EOT7 was significantly higher in the PL-5 group than in the control group (1.6 vs 0.86). Microbial eradication rates were notably better in the PL-5 group at both EOT1 (57.89% vs 33.33%) and EOT7 (64.71% vs 40.00%). The clearance rates of drug-resistant bacteria were also higher in the PL-5 group at EOT1 (71.43% vs 50%).

Of importance, safety parameters showed no significant differences between the two groups (24.24% vs 33.33%), highlighting the favorable safety profile of PL-5 spray.

The study presented at the ADA Scientific Sessions provides a glint of promising evidence supporting the potential efficacy and safety of PL-5 spray in treating mild to moderate diabetic foot infections. Despite the limited sample size, the results suggest that PL-5 spray may enhance the recovery speed of diabetic foot wounds, particularly in clearing drug-resistant bacterial infections. These findings justify further investigation with larger sample sizes to confirm or refute the efficacy and potentially establish PL-5 spray as a standard treatment option in diabetic foot care.

The novel antimicrobial peptide PL-5 spray shows potential in addressing the challenging issue of diabetic foot infections. This recent ADA presentation sparked significant interest and discussions about the future of diabetic foot ulcer treatments, emphasizing the importance of innovative approaches in managing complex diabetic complications.

Dr. Armstrong is a professor of surgery and director of limb preservation at the University of Southern California, Los Angeles. He reported no relevant conflicts of interest.

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

At the recent American Diabetes Association (ADA) Scientific Sessions, researchers unveiled promising data on a novel antimicrobial peptide PL-5 spray. This innovative treatment shows significant promise for managing mild to moderate infected diabetic foot ulcers. 

Of the 1.6 million people with diabetes in the United States and the tens of millions of similar people worldwide, 50% will require antimicrobials at some time during their life cycle. Diabetic foot infections are difficult to treat because of their resistance to conventional therapies, often leading to severe complications, including amputations. 

To address this issue, the antimicrobial peptide PL-5 spray was developed with a novel mechanism of action to potentially improve treatment outcomes. The study aimed to assess the clinical efficacy and safety of the PL-5 spray combined with standard debridement procedures in treating mild to moderate diabetic foot ulcers.

This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in four hospitals across China. Participants with mild to moderate diabetic foot ulcers were randomly assigned in a 2:1 ratio to either the PL-5 group or the placebo group, both receiving standard debridement. The primary endpoint was clinical efficacy at day 1 after the end of treatment (EOT1). Secondary endpoints included clinical efficacy at day 7 (EOT7), microbiological efficacy, drug-resistant bacteria clearance rate, wound healing rate, and safety outcomes evaluated at both EOT1 and EOT7.

The study included 47 participants, with 32 in the PL-5 group and 15 in the placebo group. Both groups had statistically comparable demographic and clinical characteristics. The primary endpoint showed a higher clinical efficacy (cure/improvement ratio) in the PL-5 group, compared with the control group (1.33 vs 0.55; P =.0764), suggesting a positive trend but not reaching statistical significance in this population.

Among the secondary endpoints, clinical efficacy at EOT7 was significantly higher in the PL-5 group than in the control group (1.6 vs 0.86). Microbial eradication rates were notably better in the PL-5 group at both EOT1 (57.89% vs 33.33%) and EOT7 (64.71% vs 40.00%). The clearance rates of drug-resistant bacteria were also higher in the PL-5 group at EOT1 (71.43% vs 50%).

Of importance, safety parameters showed no significant differences between the two groups (24.24% vs 33.33%), highlighting the favorable safety profile of PL-5 spray.

The study presented at the ADA Scientific Sessions provides a glint of promising evidence supporting the potential efficacy and safety of PL-5 spray in treating mild to moderate diabetic foot infections. Despite the limited sample size, the results suggest that PL-5 spray may enhance the recovery speed of diabetic foot wounds, particularly in clearing drug-resistant bacterial infections. These findings justify further investigation with larger sample sizes to confirm or refute the efficacy and potentially establish PL-5 spray as a standard treatment option in diabetic foot care.

The novel antimicrobial peptide PL-5 spray shows potential in addressing the challenging issue of diabetic foot infections. This recent ADA presentation sparked significant interest and discussions about the future of diabetic foot ulcer treatments, emphasizing the importance of innovative approaches in managing complex diabetic complications.

Dr. Armstrong is a professor of surgery and director of limb preservation at the University of Southern California, Los Angeles. He reported no relevant conflicts of interest.

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

At the recent American Diabetes Association (ADA) Scientific Sessions, researchers unveiled promising data on a novel antimicrobial peptide PL-5 spray. This innovative treatment shows significant promise for managing mild to moderate infected diabetic foot ulcers. 

Of the 1.6 million people with diabetes in the United States and the tens of millions of similar people worldwide, 50% will require antimicrobials at some time during their life cycle. Diabetic foot infections are difficult to treat because of their resistance to conventional therapies, often leading to severe complications, including amputations. 

To address this issue, the antimicrobial peptide PL-5 spray was developed with a novel mechanism of action to potentially improve treatment outcomes. The study aimed to assess the clinical efficacy and safety of the PL-5 spray combined with standard debridement procedures in treating mild to moderate diabetic foot ulcers.

This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in four hospitals across China. Participants with mild to moderate diabetic foot ulcers were randomly assigned in a 2:1 ratio to either the PL-5 group or the placebo group, both receiving standard debridement. The primary endpoint was clinical efficacy at day 1 after the end of treatment (EOT1). Secondary endpoints included clinical efficacy at day 7 (EOT7), microbiological efficacy, drug-resistant bacteria clearance rate, wound healing rate, and safety outcomes evaluated at both EOT1 and EOT7.

The study included 47 participants, with 32 in the PL-5 group and 15 in the placebo group. Both groups had statistically comparable demographic and clinical characteristics. The primary endpoint showed a higher clinical efficacy (cure/improvement ratio) in the PL-5 group, compared with the control group (1.33 vs 0.55; P =.0764), suggesting a positive trend but not reaching statistical significance in this population.

Among the secondary endpoints, clinical efficacy at EOT7 was significantly higher in the PL-5 group than in the control group (1.6 vs 0.86). Microbial eradication rates were notably better in the PL-5 group at both EOT1 (57.89% vs 33.33%) and EOT7 (64.71% vs 40.00%). The clearance rates of drug-resistant bacteria were also higher in the PL-5 group at EOT1 (71.43% vs 50%).

Of importance, safety parameters showed no significant differences between the two groups (24.24% vs 33.33%), highlighting the favorable safety profile of PL-5 spray.

The study presented at the ADA Scientific Sessions provides a glint of promising evidence supporting the potential efficacy and safety of PL-5 spray in treating mild to moderate diabetic foot infections. Despite the limited sample size, the results suggest that PL-5 spray may enhance the recovery speed of diabetic foot wounds, particularly in clearing drug-resistant bacterial infections. These findings justify further investigation with larger sample sizes to confirm or refute the efficacy and potentially establish PL-5 spray as a standard treatment option in diabetic foot care.

The novel antimicrobial peptide PL-5 spray shows potential in addressing the challenging issue of diabetic foot infections. This recent ADA presentation sparked significant interest and discussions about the future of diabetic foot ulcer treatments, emphasizing the importance of innovative approaches in managing complex diabetic complications.

Dr. Armstrong is a professor of surgery and director of limb preservation at the University of Southern California, Los Angeles. He reported no relevant conflicts of interest.

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

CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.

Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.

However, ctDNA’s role in guiding clinical decisions is still being defined. Australian investigators presented research showing that a negative ctDNA finding can be used to avoid unnecessary chemotherapy in postoperative stage II colon cancer patients without affecting survival outcomes, at the annual meeting of the American Society of Clinical Oncology (ASCO), in Chicago.

The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
 

DYNAMIC Trial Results

Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.

Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.

At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.

Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).

Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).

“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
 

DYNAMIC-Pancreas Study Results

In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.

At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.

Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.

In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.

“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”

The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.

“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”

But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.

Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”

Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.

Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”

Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.

Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.

CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.

Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.

However, ctDNA’s role in guiding clinical decisions is still being defined. Australian investigators presented research showing that a negative ctDNA finding can be used to avoid unnecessary chemotherapy in postoperative stage II colon cancer patients without affecting survival outcomes, at the annual meeting of the American Society of Clinical Oncology (ASCO), in Chicago.

The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
 

DYNAMIC Trial Results

Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.

Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.

At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.

Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).

Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).

“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
 

DYNAMIC-Pancreas Study Results

In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.

At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.

Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.

In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.

“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”

The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.

“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”

But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.

Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”

Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.

Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”

Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.

Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.

CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.

Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.

However, ctDNA’s role in guiding clinical decisions is still being defined. Australian investigators presented research showing that a negative ctDNA finding can be used to avoid unnecessary chemotherapy in postoperative stage II colon cancer patients without affecting survival outcomes, at the annual meeting of the American Society of Clinical Oncology (ASCO), in Chicago.

The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
 

DYNAMIC Trial Results

Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.

Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.

At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.

Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).

Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).

“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
 

DYNAMIC-Pancreas Study Results

In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.

At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.

Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.

In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.

“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”

The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.

“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”

But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.

Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”

Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.

Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”

Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.

Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.

WASHINGTON — In 2013, Vishal A. Patel, MD, was completing a fellowship in Mohs surgery and cutaneous oncology at Columbia University Irving Medical Center, New York City, when a study was published showing that most nonmelanoma skin cancers (NMSCs) were treated with surgery, regardless of the patient’s life expectancy. Life expectancy “should enter into treatment decisions,” the authors concluded.

“The article got a lot of pushback from the Mohs surgeons,” and the value of surgery in older adults and particularly those with limited life expectancy “became a hot topic,” Dr. Patel recalled at the ElderDerm conference hosted by the Department of Dermatology at George Washington University, Washington, DC, and described as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Christine Kilgore

Today, however, more than a decade later, guidelines still promote surgical therapy as the gold standard across the board, and questions raised by the study are still unaddressed, Dr. Patel, associate professor of dermatology and medicine/oncology at George Washington University, said at the meeting. These questions are becoming increasingly urgent as the incidence of skin cancer, especially NMSC, rises in the older adult population, especially in patients older than 85 years. “It’s a function of our training and our treatment guidelines that we reach for the most definitive treatment, which happens to be the most aggressive, in these patients,” added Dr. Patel, who is also director of the cutaneous oncology program at the GW Cancer Center.

“Sometimes we lose track of what ... we need to do” to provide care that reflects the best interests of the older patient, he continued. “Surgery may be the gold standard for treating the majority of NMSCs ... but is it the [best option] for what our older patients and patients with limited life expectancy need?”

Learning about what truly matters to the patient is a key element of the “age-friendly, whole-person care” that dermatologists must embrace as older adults become an increasingly large subset of their patient population, Christina Prather, MD, director and associate professor of geriatrics and palliative medicine at George Washington University, said at the meeting.

By 2040, projections are that the number of adults aged 85 years and older in the United States will be nearly quadruple the number in 2000, according to one estimate.

“We know that there are less than 6000 practicing geriatricians in the country ... [so the healthcare system] needs more of you who know how to bring an age-friendly approach to care,” Dr. Prather said. Dermatology is among the specialties that need to be “geriatricized.”
 

NMSC Increasing in the Older Population

The incidence of skin cancer is rising faster than that of any other cancer, Dr. Patel said. One window into the epidemiology, he said, comes from recently published data showing that an average of 6.1 million adults were treated each year for skin cancer during 2016-2018 (5.2 million of them for NMSC) — an increase from an average of 5.8 million annually in the 2012-2015 period. The data come from the Medical Expenditure Panel Survey (MEPS), which is conducted by the US Public Health Service through the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention.

As a frame of reference, the average number of adults treated each year for nonskin cancers during these periods rose from 10.8 to 11.9 million, according to the 2023 MEPS data. “Skin cancer is about one-third of all cancers combined,” Dr. Patel said.

Not only is the incidence of NMSC significantly higher than that of melanoma but it also shows a more prominent aging trend. This was documented recently in a long-term observational study from Japan, in which researchers looked at the change in the median age of patients with NMSC and melanoma, compared with cancers of other organs, from 1991 to 2020 and found that NMSC had by far the greatest rise in median age, to a median age of 80 years in 2021.

Even more notable, Dr. Patel said, was a particularly marked increase in the number of patients with skin cancer aged 90 years and older. In 2021, this group of older adults accounted for 17% of patients receiving treatment for skin cancer at the Japanese hospital where the data were collected.

The 2013 study that stirred Dr. Patel as a fellow was of 1536 consecutive patients diagnosed with NMSC at two dermatology clinics (a University of California San Francisco–based private clinic and a Veterans Affairs Medical Center clinic) and followed for 6 years. “What’s interesting and worth thinking about is that, regardless of patients’ life expectancy, NMSCs were treated aggressively and surgically, and the choice of surgery was not influenced by the patient’s poor prognosis in a multivariate model” adjusted for tumor and patient characteristics, he said at the meeting.

The researchers defined limited life expectancy as either 85 years or older or having a Charleston Comorbidity Index ≥ 3. Approximately half of the patients with limited life expectancy died within 5 years, none of NMSC. Most patients with limited life expectancy were not often bothered by their tumors, and approximately one in five reported a treatment complication within 2 years. The 5-year tumor recurrence rate was 3.7%.

A more recent study looked at 1181 patients older than 85 years with NMSC referred for Mohs surgery. Almost all patients in the multicenter, prospective cohort study (91.3%) were treated with Mohs.

Treated patients were more likely to have facial tumors and higher functional status than those not treated with Mohs surgery, and the most common reasons provided by surgeons for proceeding with the surgery were a patient desire for a high cure rate (66%), higher functional status for age (57%), and high-risk tumor type (40%). Almost 42% of the referred patients were 89 years or older.

“Granted, [the reasons] are justified indications for surgery,” Dr. Patel said. Yet the study brings up the question of “whether we need to do Mohs surgery this frequently in elderly patients?” In an email after the meeting, he added, “it’s a question we may need to reconsider as the elderly population continues to increase and median age of NMSC rises.”
 

Underutilized Management Options for NMSC

In his practice, discussions of treatment options are preceded by a thorough discussion of the disease itself. Many lesions are low risk, and helping patients understand risks, as well as understanding what is important to the patient — especially those with limited life expectancy — will guide shared decision-making to choose the best treatment, Dr. Patel said at the meeting.

The dermatologist’s risk assessment — both staging and stratifying risk as it relates to specific outcomes such as recurrence, metastases, or death — takes on added importance in the older patient, he emphasized. “I think we underutilize the risk assessment.”

Also underutilized is the option of shave removal for low-risk squamous cell carcinomas and basal cell carcinomas, Dr. Patel said, noting that, in the National Comprehensive Cancer Network guidelines, “there’s an option for shave removal and nothing more if you have clear margins.”

Alternatively, disc excision with the initial biopsy can often be considered. “Having that intent to treat at the time of biopsy may be all that needs to be done” in older patients with obvious or highly suspicious lesions, he said.

Systemic immunotherapy has joined the treatment armamentarium for advanced basal cell carcinoma and advanced cutaneous squamous cell carcinoma, and if early, ongoing research of intralesional programmed cell death protein 1 inhibitor treatment advances, this could be another option for older adults in the future, Dr. Patel said. Targeting drug delivery directly to the tumor would lower the total dose, decrease systemic exposure, and could be used to avoid surgery for some groups of patients, such as those with limited life expectancy.

A Personal Story, a Word on Melanoma

Dr. Prather recalled when her 97-year-old grandfather had a skin lesion on his forehead removed, and a conversation he had with her mother about whether he really needed to have the procedure because he had cognitive impairment and was on oral anticoagulants.

The clinician “said it absolutely had to go. ... I can’t tell you how much his doctors’ visits and wound care consumed my family’s life for the next few years — for this thing that never quite healed,” she said.

“Was it necessary? The more I’ve learned over time is that it wasn’t,” Dr. Prather added. “We have to take time [with our older patients] and think critically. What is feasible? What makes the most sense? What is the most important thing I need to know about the patient?”

Also important, Dr. Patel noted, is the big-picture consideration of skin cancer treatment costs. The MEPS survey data showing the rising prevalence of skin cancer treatment also documented the economic burden: A nearly 30% increase in the average annual cost of treating NMSC from $5 billion in 2012-2015 to $6.5 billion in 2016-2018. (The average annual costs of treating melanoma decreased slightly.) “Skin cancer is a big drain on our limited resources,” he said.

With melanoma as well, dermatologists must think critically and holistically about the individual patient — and not have “a single view lens of the disease and how we treat the disease,” said Dr. Patel, urging the audience to read a “Sounding Board” article published in The New England Journal of Medicine in 2021. The article argued that there is overdiagnosis of cutaneous melanoma stemming from increased screening, falling clinical thresholds for biopsy, and falling pathological thresholds for labeling morphologic changes as cancer.

“There’s a diagnostic disconnect and a problem of overdiagnosis ... because we’re afraid to miss or make a mistake,” he said. “It leads to the question, do all lesions denoted as skin cancers need aggressive treatment? What does it mean for the patient in front of you?”

Dr. Patel reported receiving honoraria from Regeneron, Almirall, Biofrontera, Sun Pharma, and SkylineDx and serving on the speaker bureau of Regeneron and Almirall. He is chief medical officer for Lazarus AI and is cofounder of the Skin Cancer Outcomes consortium. Dr. Prather disclosed relationships with the National Institutes of Health, AHRQ, The Washington Home Foundation, and the Alzheimer’s Association.

A version of this article appeared on Medscape.com.

WASHINGTON — In 2013, Vishal A. Patel, MD, was completing a fellowship in Mohs surgery and cutaneous oncology at Columbia University Irving Medical Center, New York City, when a study was published showing that most nonmelanoma skin cancers (NMSCs) were treated with surgery, regardless of the patient’s life expectancy. Life expectancy “should enter into treatment decisions,” the authors concluded.

“The article got a lot of pushback from the Mohs surgeons,” and the value of surgery in older adults and particularly those with limited life expectancy “became a hot topic,” Dr. Patel recalled at the ElderDerm conference hosted by the Department of Dermatology at George Washington University, Washington, DC, and described as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Christine Kilgore

Today, however, more than a decade later, guidelines still promote surgical therapy as the gold standard across the board, and questions raised by the study are still unaddressed, Dr. Patel, associate professor of dermatology and medicine/oncology at George Washington University, said at the meeting. These questions are becoming increasingly urgent as the incidence of skin cancer, especially NMSC, rises in the older adult population, especially in patients older than 85 years. “It’s a function of our training and our treatment guidelines that we reach for the most definitive treatment, which happens to be the most aggressive, in these patients,” added Dr. Patel, who is also director of the cutaneous oncology program at the GW Cancer Center.

“Sometimes we lose track of what ... we need to do” to provide care that reflects the best interests of the older patient, he continued. “Surgery may be the gold standard for treating the majority of NMSCs ... but is it the [best option] for what our older patients and patients with limited life expectancy need?”

Learning about what truly matters to the patient is a key element of the “age-friendly, whole-person care” that dermatologists must embrace as older adults become an increasingly large subset of their patient population, Christina Prather, MD, director and associate professor of geriatrics and palliative medicine at George Washington University, said at the meeting.

By 2040, projections are that the number of adults aged 85 years and older in the United States will be nearly quadruple the number in 2000, according to one estimate.

“We know that there are less than 6000 practicing geriatricians in the country ... [so the healthcare system] needs more of you who know how to bring an age-friendly approach to care,” Dr. Prather said. Dermatology is among the specialties that need to be “geriatricized.”
 

NMSC Increasing in the Older Population

The incidence of skin cancer is rising faster than that of any other cancer, Dr. Patel said. One window into the epidemiology, he said, comes from recently published data showing that an average of 6.1 million adults were treated each year for skin cancer during 2016-2018 (5.2 million of them for NMSC) — an increase from an average of 5.8 million annually in the 2012-2015 period. The data come from the Medical Expenditure Panel Survey (MEPS), which is conducted by the US Public Health Service through the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention.

As a frame of reference, the average number of adults treated each year for nonskin cancers during these periods rose from 10.8 to 11.9 million, according to the 2023 MEPS data. “Skin cancer is about one-third of all cancers combined,” Dr. Patel said.

Not only is the incidence of NMSC significantly higher than that of melanoma but it also shows a more prominent aging trend. This was documented recently in a long-term observational study from Japan, in which researchers looked at the change in the median age of patients with NMSC and melanoma, compared with cancers of other organs, from 1991 to 2020 and found that NMSC had by far the greatest rise in median age, to a median age of 80 years in 2021.

Even more notable, Dr. Patel said, was a particularly marked increase in the number of patients with skin cancer aged 90 years and older. In 2021, this group of older adults accounted for 17% of patients receiving treatment for skin cancer at the Japanese hospital where the data were collected.

The 2013 study that stirred Dr. Patel as a fellow was of 1536 consecutive patients diagnosed with NMSC at two dermatology clinics (a University of California San Francisco–based private clinic and a Veterans Affairs Medical Center clinic) and followed for 6 years. “What’s interesting and worth thinking about is that, regardless of patients’ life expectancy, NMSCs were treated aggressively and surgically, and the choice of surgery was not influenced by the patient’s poor prognosis in a multivariate model” adjusted for tumor and patient characteristics, he said at the meeting.

The researchers defined limited life expectancy as either 85 years or older or having a Charleston Comorbidity Index ≥ 3. Approximately half of the patients with limited life expectancy died within 5 years, none of NMSC. Most patients with limited life expectancy were not often bothered by their tumors, and approximately one in five reported a treatment complication within 2 years. The 5-year tumor recurrence rate was 3.7%.

A more recent study looked at 1181 patients older than 85 years with NMSC referred for Mohs surgery. Almost all patients in the multicenter, prospective cohort study (91.3%) were treated with Mohs.

Treated patients were more likely to have facial tumors and higher functional status than those not treated with Mohs surgery, and the most common reasons provided by surgeons for proceeding with the surgery were a patient desire for a high cure rate (66%), higher functional status for age (57%), and high-risk tumor type (40%). Almost 42% of the referred patients were 89 years or older.

“Granted, [the reasons] are justified indications for surgery,” Dr. Patel said. Yet the study brings up the question of “whether we need to do Mohs surgery this frequently in elderly patients?” In an email after the meeting, he added, “it’s a question we may need to reconsider as the elderly population continues to increase and median age of NMSC rises.”
 

Underutilized Management Options for NMSC

In his practice, discussions of treatment options are preceded by a thorough discussion of the disease itself. Many lesions are low risk, and helping patients understand risks, as well as understanding what is important to the patient — especially those with limited life expectancy — will guide shared decision-making to choose the best treatment, Dr. Patel said at the meeting.

The dermatologist’s risk assessment — both staging and stratifying risk as it relates to specific outcomes such as recurrence, metastases, or death — takes on added importance in the older patient, he emphasized. “I think we underutilize the risk assessment.”

Also underutilized is the option of shave removal for low-risk squamous cell carcinomas and basal cell carcinomas, Dr. Patel said, noting that, in the National Comprehensive Cancer Network guidelines, “there’s an option for shave removal and nothing more if you have clear margins.”

Alternatively, disc excision with the initial biopsy can often be considered. “Having that intent to treat at the time of biopsy may be all that needs to be done” in older patients with obvious or highly suspicious lesions, he said.

Systemic immunotherapy has joined the treatment armamentarium for advanced basal cell carcinoma and advanced cutaneous squamous cell carcinoma, and if early, ongoing research of intralesional programmed cell death protein 1 inhibitor treatment advances, this could be another option for older adults in the future, Dr. Patel said. Targeting drug delivery directly to the tumor would lower the total dose, decrease systemic exposure, and could be used to avoid surgery for some groups of patients, such as those with limited life expectancy.

A Personal Story, a Word on Melanoma

Dr. Prather recalled when her 97-year-old grandfather had a skin lesion on his forehead removed, and a conversation he had with her mother about whether he really needed to have the procedure because he had cognitive impairment and was on oral anticoagulants.

The clinician “said it absolutely had to go. ... I can’t tell you how much his doctors’ visits and wound care consumed my family’s life for the next few years — for this thing that never quite healed,” she said.

“Was it necessary? The more I’ve learned over time is that it wasn’t,” Dr. Prather added. “We have to take time [with our older patients] and think critically. What is feasible? What makes the most sense? What is the most important thing I need to know about the patient?”

Also important, Dr. Patel noted, is the big-picture consideration of skin cancer treatment costs. The MEPS survey data showing the rising prevalence of skin cancer treatment also documented the economic burden: A nearly 30% increase in the average annual cost of treating NMSC from $5 billion in 2012-2015 to $6.5 billion in 2016-2018. (The average annual costs of treating melanoma decreased slightly.) “Skin cancer is a big drain on our limited resources,” he said.

With melanoma as well, dermatologists must think critically and holistically about the individual patient — and not have “a single view lens of the disease and how we treat the disease,” said Dr. Patel, urging the audience to read a “Sounding Board” article published in The New England Journal of Medicine in 2021. The article argued that there is overdiagnosis of cutaneous melanoma stemming from increased screening, falling clinical thresholds for biopsy, and falling pathological thresholds for labeling morphologic changes as cancer.

“There’s a diagnostic disconnect and a problem of overdiagnosis ... because we’re afraid to miss or make a mistake,” he said. “It leads to the question, do all lesions denoted as skin cancers need aggressive treatment? What does it mean for the patient in front of you?”

Dr. Patel reported receiving honoraria from Regeneron, Almirall, Biofrontera, Sun Pharma, and SkylineDx and serving on the speaker bureau of Regeneron and Almirall. He is chief medical officer for Lazarus AI and is cofounder of the Skin Cancer Outcomes consortium. Dr. Prather disclosed relationships with the National Institutes of Health, AHRQ, The Washington Home Foundation, and the Alzheimer’s Association.

A version of this article appeared on Medscape.com.

WASHINGTON — In 2013, Vishal A. Patel, MD, was completing a fellowship in Mohs surgery and cutaneous oncology at Columbia University Irving Medical Center, New York City, when a study was published showing that most nonmelanoma skin cancers (NMSCs) were treated with surgery, regardless of the patient’s life expectancy. Life expectancy “should enter into treatment decisions,” the authors concluded.

“The article got a lot of pushback from the Mohs surgeons,” and the value of surgery in older adults and particularly those with limited life expectancy “became a hot topic,” Dr. Patel recalled at the ElderDerm conference hosted by the Department of Dermatology at George Washington University, Washington, DC, and described as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Christine Kilgore

Today, however, more than a decade later, guidelines still promote surgical therapy as the gold standard across the board, and questions raised by the study are still unaddressed, Dr. Patel, associate professor of dermatology and medicine/oncology at George Washington University, said at the meeting. These questions are becoming increasingly urgent as the incidence of skin cancer, especially NMSC, rises in the older adult population, especially in patients older than 85 years. “It’s a function of our training and our treatment guidelines that we reach for the most definitive treatment, which happens to be the most aggressive, in these patients,” added Dr. Patel, who is also director of the cutaneous oncology program at the GW Cancer Center.

“Sometimes we lose track of what ... we need to do” to provide care that reflects the best interests of the older patient, he continued. “Surgery may be the gold standard for treating the majority of NMSCs ... but is it the [best option] for what our older patients and patients with limited life expectancy need?”

Learning about what truly matters to the patient is a key element of the “age-friendly, whole-person care” that dermatologists must embrace as older adults become an increasingly large subset of their patient population, Christina Prather, MD, director and associate professor of geriatrics and palliative medicine at George Washington University, said at the meeting.

By 2040, projections are that the number of adults aged 85 years and older in the United States will be nearly quadruple the number in 2000, according to one estimate.

“We know that there are less than 6000 practicing geriatricians in the country ... [so the healthcare system] needs more of you who know how to bring an age-friendly approach to care,” Dr. Prather said. Dermatology is among the specialties that need to be “geriatricized.”
 

NMSC Increasing in the Older Population

The incidence of skin cancer is rising faster than that of any other cancer, Dr. Patel said. One window into the epidemiology, he said, comes from recently published data showing that an average of 6.1 million adults were treated each year for skin cancer during 2016-2018 (5.2 million of them for NMSC) — an increase from an average of 5.8 million annually in the 2012-2015 period. The data come from the Medical Expenditure Panel Survey (MEPS), which is conducted by the US Public Health Service through the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention.

As a frame of reference, the average number of adults treated each year for nonskin cancers during these periods rose from 10.8 to 11.9 million, according to the 2023 MEPS data. “Skin cancer is about one-third of all cancers combined,” Dr. Patel said.

Not only is the incidence of NMSC significantly higher than that of melanoma but it also shows a more prominent aging trend. This was documented recently in a long-term observational study from Japan, in which researchers looked at the change in the median age of patients with NMSC and melanoma, compared with cancers of other organs, from 1991 to 2020 and found that NMSC had by far the greatest rise in median age, to a median age of 80 years in 2021.

Even more notable, Dr. Patel said, was a particularly marked increase in the number of patients with skin cancer aged 90 years and older. In 2021, this group of older adults accounted for 17% of patients receiving treatment for skin cancer at the Japanese hospital where the data were collected.

The 2013 study that stirred Dr. Patel as a fellow was of 1536 consecutive patients diagnosed with NMSC at two dermatology clinics (a University of California San Francisco–based private clinic and a Veterans Affairs Medical Center clinic) and followed for 6 years. “What’s interesting and worth thinking about is that, regardless of patients’ life expectancy, NMSCs were treated aggressively and surgically, and the choice of surgery was not influenced by the patient’s poor prognosis in a multivariate model” adjusted for tumor and patient characteristics, he said at the meeting.

The researchers defined limited life expectancy as either 85 years or older or having a Charleston Comorbidity Index ≥ 3. Approximately half of the patients with limited life expectancy died within 5 years, none of NMSC. Most patients with limited life expectancy were not often bothered by their tumors, and approximately one in five reported a treatment complication within 2 years. The 5-year tumor recurrence rate was 3.7%.

A more recent study looked at 1181 patients older than 85 years with NMSC referred for Mohs surgery. Almost all patients in the multicenter, prospective cohort study (91.3%) were treated with Mohs.

Treated patients were more likely to have facial tumors and higher functional status than those not treated with Mohs surgery, and the most common reasons provided by surgeons for proceeding with the surgery were a patient desire for a high cure rate (66%), higher functional status for age (57%), and high-risk tumor type (40%). Almost 42% of the referred patients were 89 years or older.

“Granted, [the reasons] are justified indications for surgery,” Dr. Patel said. Yet the study brings up the question of “whether we need to do Mohs surgery this frequently in elderly patients?” In an email after the meeting, he added, “it’s a question we may need to reconsider as the elderly population continues to increase and median age of NMSC rises.”
 

Underutilized Management Options for NMSC

In his practice, discussions of treatment options are preceded by a thorough discussion of the disease itself. Many lesions are low risk, and helping patients understand risks, as well as understanding what is important to the patient — especially those with limited life expectancy — will guide shared decision-making to choose the best treatment, Dr. Patel said at the meeting.

The dermatologist’s risk assessment — both staging and stratifying risk as it relates to specific outcomes such as recurrence, metastases, or death — takes on added importance in the older patient, he emphasized. “I think we underutilize the risk assessment.”

Also underutilized is the option of shave removal for low-risk squamous cell carcinomas and basal cell carcinomas, Dr. Patel said, noting that, in the National Comprehensive Cancer Network guidelines, “there’s an option for shave removal and nothing more if you have clear margins.”

Alternatively, disc excision with the initial biopsy can often be considered. “Having that intent to treat at the time of biopsy may be all that needs to be done” in older patients with obvious or highly suspicious lesions, he said.

Systemic immunotherapy has joined the treatment armamentarium for advanced basal cell carcinoma and advanced cutaneous squamous cell carcinoma, and if early, ongoing research of intralesional programmed cell death protein 1 inhibitor treatment advances, this could be another option for older adults in the future, Dr. Patel said. Targeting drug delivery directly to the tumor would lower the total dose, decrease systemic exposure, and could be used to avoid surgery for some groups of patients, such as those with limited life expectancy.

A Personal Story, a Word on Melanoma

Dr. Prather recalled when her 97-year-old grandfather had a skin lesion on his forehead removed, and a conversation he had with her mother about whether he really needed to have the procedure because he had cognitive impairment and was on oral anticoagulants.

The clinician “said it absolutely had to go. ... I can’t tell you how much his doctors’ visits and wound care consumed my family’s life for the next few years — for this thing that never quite healed,” she said.

“Was it necessary? The more I’ve learned over time is that it wasn’t,” Dr. Prather added. “We have to take time [with our older patients] and think critically. What is feasible? What makes the most sense? What is the most important thing I need to know about the patient?”

Also important, Dr. Patel noted, is the big-picture consideration of skin cancer treatment costs. The MEPS survey data showing the rising prevalence of skin cancer treatment also documented the economic burden: A nearly 30% increase in the average annual cost of treating NMSC from $5 billion in 2012-2015 to $6.5 billion in 2016-2018. (The average annual costs of treating melanoma decreased slightly.) “Skin cancer is a big drain on our limited resources,” he said.

With melanoma as well, dermatologists must think critically and holistically about the individual patient — and not have “a single view lens of the disease and how we treat the disease,” said Dr. Patel, urging the audience to read a “Sounding Board” article published in The New England Journal of Medicine in 2021. The article argued that there is overdiagnosis of cutaneous melanoma stemming from increased screening, falling clinical thresholds for biopsy, and falling pathological thresholds for labeling morphologic changes as cancer.

“There’s a diagnostic disconnect and a problem of overdiagnosis ... because we’re afraid to miss or make a mistake,” he said. “It leads to the question, do all lesions denoted as skin cancers need aggressive treatment? What does it mean for the patient in front of you?”

Dr. Patel reported receiving honoraria from Regeneron, Almirall, Biofrontera, Sun Pharma, and SkylineDx and serving on the speaker bureau of Regeneron and Almirall. He is chief medical officer for Lazarus AI and is cofounder of the Skin Cancer Outcomes consortium. Dr. Prather disclosed relationships with the National Institutes of Health, AHRQ, The Washington Home Foundation, and the Alzheimer’s Association.

A version of this article appeared on Medscape.com.

VIENNA — To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.

“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.

The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.

The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.

“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.

A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.

Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.

Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.

At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.

At 2 years, the proportion of patients maintained at the target sUA was almost twice as great in the nurse-led arm (83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m² (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).

The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.

Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.

The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).

Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
 

Potential Advantages of Nurse-Led Care

Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.

“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.

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

VIENNA — To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.

“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.

The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.

The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.

“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.

A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.

Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.

Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.

At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.

At 2 years, the proportion of patients maintained at the target sUA was almost twice as great in the nurse-led arm (83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m² (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).

The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.

Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.

The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).

Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
 

Potential Advantages of Nurse-Led Care

Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.

“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.

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

VIENNA — To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.

“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.

The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.

The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.

“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.

A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.

Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.

Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.

At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.

At 2 years, the proportion of patients maintained at the target sUA was almost twice as great in the nurse-led arm (83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m² (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).

The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.

Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.

The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).

Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
 

Potential Advantages of Nurse-Led Care

Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.

“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

VIENNA — Ixekizumab (Taltz), an interleukin-17A inhibitor that’s already approved for the treatment of psoriatic arthritis and axial spondyloarthritis in adults appears likely to be granted the same corresponding indications for children, based on initial results from an open-label, phase 3 trial that employed adalimumab as a reference.

With a safety profile comparable with that seen in adult patients, ixekizumab “met the prespecified criterion for success at 16 weeks,” reported Athimalaipet V. Ramanan, MD, PhD, of Bristol Royal Hospital for Children and Translational Health Sciences, Bristol, England.

In this multicenter, randomized, open-label trial called COSPIRIT-JIA, which is still ongoing, investigators enrolled 101 children with active juvenile PsA (JPsA) or enthesitis-related arthritis (ERA), which is akin to spondyloarthritis in adults.

The efficacy and safety data at 16 weeks were presented as a late-breaking abstract at the annual European Congress of Rheumatology. Dr. Ramanan said that the open-label extension to 104 weeks is underway and further follow-up out to 264 weeks is planned.
 

Nearly 90% Achieve ACR30

The trial had an adaptive design in which the first 40 patients without biologics experience were randomized to ixekizumab or adalimumab, stratified by JPsA or ERA diagnosis, and the following 61 patients with either no biologic experience or an inadequate response or intolerance to biologics all received ixekizumab. The drugs were dosed according to weight. Dr. Ramanan explained that a placebo-controlled trial was considered unethical because of the strong evidence of benefit from biologics for JPsA and ERA.

The trial easily met its predefined threshold for success, which required ≥ 80% probability, based on Bayesian analysis, that ≥ 50% of patients would have 30% improvement in American College of Rheumatology response criteria (ACR30) at week 16. ACR30 was achieved in 88.9% of those treated with ixekizumab overall vs 95.0% of those treated with adalimumab, but the trial was not designed as a head-to-head comparison. Rather, adalimumab served as a reference.

When compared for the distinct diseases, the ACR30 rates were also numerically lower for ixekizumab relative to adalimumab for both ERA (88.9% vs 93.8%) and JPsA (88.9% vs 100%), but all of the adalimumab patients were naive to biologics. In comparison, about 75% of patients receiving ixekizumab were biologic-therapy naive.

Response rates to ixekizumab overall were numerically higher for patients without previous biologic experience than for those with experience (90.0% vs 85.7%), and this was also the case for patients with ERA (92.5% vs 78.6%). However, in the JPsA group, biologic-experienced patients had higher numerical response rates to ixekizumab (100% vs 85.0%).

An ACR30 is not a clinical goal that satisfies most patients and clinicians, Dr. Ramanan conceded, but he noted that ACR50 was reached with ixekizumab by 81.5% with ERA and 74.1% with JPsA, and ACR70 was reached by 68.5% and 55.6%, respectively. The highest responses of ACR90 (27.8% and 33.3%) and ACR100 (14.8% and 25.9%) were lower but still substantial in the ERA and JPsA groups, respectively.

Through week 16, 58.0% of those treated with ixekizumab had an adverse event considered treatment-related. Nearly half were of mild severity, and the remainder were moderate. Only 3.7% were considered serious. No patient discontinued study treatment because of an adverse event.

In this study, the presence of at least three active peripheral joints was an inclusion criterion. The median age was about 13 years in the biologic-naive adalimumab and ixekizumab groups and 14 years in the ixekizumab biologic-experienced group. The youngest patient in the study was aged 5 years, and the oldest was aged 18 years. Although about 40% of patients were women in the two biologic-naive subgroups, it was 60% in the biologic-experienced group.

On average, patients in the biologic-naive group were entered about 1 year after diagnosis. In the experienced patients, the average duration of disease at entry was nearly 4 years. About 45% of patients remained on conventional synthetic disease-modifying antirheumatic drugs while receiving ixekizumab. The proportion was 35% in the adalimumab reference arm.
 

Ixekizumab Might Fulfill Need for More Options

There are several biologics that have received regulatory approval or are already widely used for the treatment of JPsA or ERA, but more options are needed, according to Dr. Ramanan and the chair of the abstract session in which these data were reported. According to Caroline Ospelt, MD, PhD, a researcher at the Center for Experimental Rheumatology, University Hospital Zurich, Switzerland, regulatory approval of ixekizumab will depend on sustained efficacy and safety in longer follow-up from the COSPIRIT-JIA trial, but this trial supports continued development.

Despite a novel mechanism of action, “the data so far suggest a level of efficacy similar to that of anti-TNF [anti-tumor necrosis factor] biologics,” said Dr. Ospelt, who, in addition to moderating the late-breaking session, served as Scientific Program Chair of EULAR 2024.

While Dr. Ospelt emphasized that she is a researcher involved in translational rheumatology studies and not a clinician, she said there was consensus within the program committee to select this abstract from other high-quality latebreaker submissions on the basis of its potential clinical significance.

Dr. Ramanan reported financial relationships with AbbVie, AstraZeneca, Novartis, Pfizer, Roche, SOBI, UCB, and Eli Lilly, which provided funding for this study. Dr. Ospelt reported no potential conflicts of interest.
 

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

VIENNA — Ixekizumab (Taltz), an interleukin-17A inhibitor that’s already approved for the treatment of psoriatic arthritis and axial spondyloarthritis in adults appears likely to be granted the same corresponding indications for children, based on initial results from an open-label, phase 3 trial that employed adalimumab as a reference.

With a safety profile comparable with that seen in adult patients, ixekizumab “met the prespecified criterion for success at 16 weeks,” reported Athimalaipet V. Ramanan, MD, PhD, of Bristol Royal Hospital for Children and Translational Health Sciences, Bristol, England.

In this multicenter, randomized, open-label trial called COSPIRIT-JIA, which is still ongoing, investigators enrolled 101 children with active juvenile PsA (JPsA) or enthesitis-related arthritis (ERA), which is akin to spondyloarthritis in adults.

The efficacy and safety data at 16 weeks were presented as a late-breaking abstract at the annual European Congress of Rheumatology. Dr. Ramanan said that the open-label extension to 104 weeks is underway and further follow-up out to 264 weeks is planned.
 

Nearly 90% Achieve ACR30

The trial had an adaptive design in which the first 40 patients without biologics experience were randomized to ixekizumab or adalimumab, stratified by JPsA or ERA diagnosis, and the following 61 patients with either no biologic experience or an inadequate response or intolerance to biologics all received ixekizumab. The drugs were dosed according to weight. Dr. Ramanan explained that a placebo-controlled trial was considered unethical because of the strong evidence of benefit from biologics for JPsA and ERA.

The trial easily met its predefined threshold for success, which required ≥ 80% probability, based on Bayesian analysis, that ≥ 50% of patients would have 30% improvement in American College of Rheumatology response criteria (ACR30) at week 16. ACR30 was achieved in 88.9% of those treated with ixekizumab overall vs 95.0% of those treated with adalimumab, but the trial was not designed as a head-to-head comparison. Rather, adalimumab served as a reference.

When compared for the distinct diseases, the ACR30 rates were also numerically lower for ixekizumab relative to adalimumab for both ERA (88.9% vs 93.8%) and JPsA (88.9% vs 100%), but all of the adalimumab patients were naive to biologics. In comparison, about 75% of patients receiving ixekizumab were biologic-therapy naive.

Response rates to ixekizumab overall were numerically higher for patients without previous biologic experience than for those with experience (90.0% vs 85.7%), and this was also the case for patients with ERA (92.5% vs 78.6%). However, in the JPsA group, biologic-experienced patients had higher numerical response rates to ixekizumab (100% vs 85.0%).

An ACR30 is not a clinical goal that satisfies most patients and clinicians, Dr. Ramanan conceded, but he noted that ACR50 was reached with ixekizumab by 81.5% with ERA and 74.1% with JPsA, and ACR70 was reached by 68.5% and 55.6%, respectively. The highest responses of ACR90 (27.8% and 33.3%) and ACR100 (14.8% and 25.9%) were lower but still substantial in the ERA and JPsA groups, respectively.

Through week 16, 58.0% of those treated with ixekizumab had an adverse event considered treatment-related. Nearly half were of mild severity, and the remainder were moderate. Only 3.7% were considered serious. No patient discontinued study treatment because of an adverse event.

In this study, the presence of at least three active peripheral joints was an inclusion criterion. The median age was about 13 years in the biologic-naive adalimumab and ixekizumab groups and 14 years in the ixekizumab biologic-experienced group. The youngest patient in the study was aged 5 years, and the oldest was aged 18 years. Although about 40% of patients were women in the two biologic-naive subgroups, it was 60% in the biologic-experienced group.

On average, patients in the biologic-naive group were entered about 1 year after diagnosis. In the experienced patients, the average duration of disease at entry was nearly 4 years. About 45% of patients remained on conventional synthetic disease-modifying antirheumatic drugs while receiving ixekizumab. The proportion was 35% in the adalimumab reference arm.
 

Ixekizumab Might Fulfill Need for More Options

There are several biologics that have received regulatory approval or are already widely used for the treatment of JPsA or ERA, but more options are needed, according to Dr. Ramanan and the chair of the abstract session in which these data were reported. According to Caroline Ospelt, MD, PhD, a researcher at the Center for Experimental Rheumatology, University Hospital Zurich, Switzerland, regulatory approval of ixekizumab will depend on sustained efficacy and safety in longer follow-up from the COSPIRIT-JIA trial, but this trial supports continued development.

Despite a novel mechanism of action, “the data so far suggest a level of efficacy similar to that of anti-TNF [anti-tumor necrosis factor] biologics,” said Dr. Ospelt, who, in addition to moderating the late-breaking session, served as Scientific Program Chair of EULAR 2024.

While Dr. Ospelt emphasized that she is a researcher involved in translational rheumatology studies and not a clinician, she said there was consensus within the program committee to select this abstract from other high-quality latebreaker submissions on the basis of its potential clinical significance.

Dr. Ramanan reported financial relationships with AbbVie, AstraZeneca, Novartis, Pfizer, Roche, SOBI, UCB, and Eli Lilly, which provided funding for this study. Dr. Ospelt reported no potential conflicts of interest.
 

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

VIENNA — Ixekizumab (Taltz), an interleukin-17A inhibitor that’s already approved for the treatment of psoriatic arthritis and axial spondyloarthritis in adults appears likely to be granted the same corresponding indications for children, based on initial results from an open-label, phase 3 trial that employed adalimumab as a reference.

With a safety profile comparable with that seen in adult patients, ixekizumab “met the prespecified criterion for success at 16 weeks,” reported Athimalaipet V. Ramanan, MD, PhD, of Bristol Royal Hospital for Children and Translational Health Sciences, Bristol, England.

In this multicenter, randomized, open-label trial called COSPIRIT-JIA, which is still ongoing, investigators enrolled 101 children with active juvenile PsA (JPsA) or enthesitis-related arthritis (ERA), which is akin to spondyloarthritis in adults.

The efficacy and safety data at 16 weeks were presented as a late-breaking abstract at the annual European Congress of Rheumatology. Dr. Ramanan said that the open-label extension to 104 weeks is underway and further follow-up out to 264 weeks is planned.
 

Nearly 90% Achieve ACR30

The trial had an adaptive design in which the first 40 patients without biologics experience were randomized to ixekizumab or adalimumab, stratified by JPsA or ERA diagnosis, and the following 61 patients with either no biologic experience or an inadequate response or intolerance to biologics all received ixekizumab. The drugs were dosed according to weight. Dr. Ramanan explained that a placebo-controlled trial was considered unethical because of the strong evidence of benefit from biologics for JPsA and ERA.

The trial easily met its predefined threshold for success, which required ≥ 80% probability, based on Bayesian analysis, that ≥ 50% of patients would have 30% improvement in American College of Rheumatology response criteria (ACR30) at week 16. ACR30 was achieved in 88.9% of those treated with ixekizumab overall vs 95.0% of those treated with adalimumab, but the trial was not designed as a head-to-head comparison. Rather, adalimumab served as a reference.

When compared for the distinct diseases, the ACR30 rates were also numerically lower for ixekizumab relative to adalimumab for both ERA (88.9% vs 93.8%) and JPsA (88.9% vs 100%), but all of the adalimumab patients were naive to biologics. In comparison, about 75% of patients receiving ixekizumab were biologic-therapy naive.

Response rates to ixekizumab overall were numerically higher for patients without previous biologic experience than for those with experience (90.0% vs 85.7%), and this was also the case for patients with ERA (92.5% vs 78.6%). However, in the JPsA group, biologic-experienced patients had higher numerical response rates to ixekizumab (100% vs 85.0%).

An ACR30 is not a clinical goal that satisfies most patients and clinicians, Dr. Ramanan conceded, but he noted that ACR50 was reached with ixekizumab by 81.5% with ERA and 74.1% with JPsA, and ACR70 was reached by 68.5% and 55.6%, respectively. The highest responses of ACR90 (27.8% and 33.3%) and ACR100 (14.8% and 25.9%) were lower but still substantial in the ERA and JPsA groups, respectively.

Through week 16, 58.0% of those treated with ixekizumab had an adverse event considered treatment-related. Nearly half were of mild severity, and the remainder were moderate. Only 3.7% were considered serious. No patient discontinued study treatment because of an adverse event.

In this study, the presence of at least three active peripheral joints was an inclusion criterion. The median age was about 13 years in the biologic-naive adalimumab and ixekizumab groups and 14 years in the ixekizumab biologic-experienced group. The youngest patient in the study was aged 5 years, and the oldest was aged 18 years. Although about 40% of patients were women in the two biologic-naive subgroups, it was 60% in the biologic-experienced group.

On average, patients in the biologic-naive group were entered about 1 year after diagnosis. In the experienced patients, the average duration of disease at entry was nearly 4 years. About 45% of patients remained on conventional synthetic disease-modifying antirheumatic drugs while receiving ixekizumab. The proportion was 35% in the adalimumab reference arm.
 

Ixekizumab Might Fulfill Need for More Options

There are several biologics that have received regulatory approval or are already widely used for the treatment of JPsA or ERA, but more options are needed, according to Dr. Ramanan and the chair of the abstract session in which these data were reported. According to Caroline Ospelt, MD, PhD, a researcher at the Center for Experimental Rheumatology, University Hospital Zurich, Switzerland, regulatory approval of ixekizumab will depend on sustained efficacy and safety in longer follow-up from the COSPIRIT-JIA trial, but this trial supports continued development.

Despite a novel mechanism of action, “the data so far suggest a level of efficacy similar to that of anti-TNF [anti-tumor necrosis factor] biologics,” said Dr. Ospelt, who, in addition to moderating the late-breaking session, served as Scientific Program Chair of EULAR 2024.

While Dr. Ospelt emphasized that she is a researcher involved in translational rheumatology studies and not a clinician, she said there was consensus within the program committee to select this abstract from other high-quality latebreaker submissions on the basis of its potential clinical significance.

Dr. Ramanan reported financial relationships with AbbVie, AstraZeneca, Novartis, Pfizer, Roche, SOBI, UCB, and Eli Lilly, which provided funding for this study. Dr. Ospelt reported no potential conflicts of interest.
 

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