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Medscape
a day ago
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- Medscape
‘Enormous Burden' Cataloged in Relapsing Polychondritis
A large multicenter prospective cohort study has expanded 'the understanding of the range of manifestations of disease in patients with relapsing polychondritis [RP]' — particularly involving the ear, nose, throat, and musculoskeletal systems — as well as a high prevalence of organ damage, near-universal use of glucocorticoids, and frequent use of additional nonbiologic or biologic immunomodulatory therapies. METHODOLOGY: Researchers conducted a multicenter cohort study between 2017 and 2023 to evaluate clinical manifestations, treatment approaches, and the association between them in 195 patients with RP (median age, 48 years; 85.6% women). A diagnosis of RP was confirmed using comprehensive laboratory, radiographic, and other tests; all participants tested negative for proteinase 3 and myeloperoxidase. Data on clinical manifestations, organ damage, and medication history were collected at baseline study visits using standardized case report forms. Patients were grouped by treatment: Group 1 received glucocorticoids or no drugs, group 2 received nonbiologic immunosuppressive drugs (excluding JAK inhibitors) with or without glucocorticoids, and group 3 received JAK inhibitors or biologic drugs with or without nonbiologic immunosuppressives or glucocorticoids. TAKEAWAY: All patients presented with at least three clinical manifestations of RP, with a median of 11 manifestations per patient; all showed ear, nose, or airway involvement, and 83% had musculoskeletal manifestations. A substantial portion of patients (41%) developed organ damage, including sensorineural hearing loss (25%), auricular and saddle nose deformities (12% each), and subglottic stenosis (9%); among those who underwent dynamic CT of the chest, 31% had tracheomalacia, and 20% had bronchomalacia. Treatment groups 1, 2, and 3 comprised 19%, 28%, and 53% of patients, respectively; most patients (95%) received glucocorticoids, and a substantial proportion (81%) received additional immunomodulatory treatments. Patients in treatment group 3 had the highest rate of organ damage (62% vs 22% in group 2 and 15% in group 1) and were more likely to have arthritis and stenosis, whereas those in group 1 were less likely to experience nose pain. IN PRACTICE: 'Standardized assessment of disease activity is warranted for patients with RP for early detection and timely initiation of treatment. These findings also highlight the absence of a consensus approach to treatment for patients with RP and underscore the need for clinical trials and treatment guidelines in this disease to help reduce the enormous burden of disease for patients,' the authors wrote. SOURCE: This study was led by Roger Yang, MD, University of Pennsylvania, Philadelphia, and University of Montreal, Montreal, Quebec, Canada. It was published online on May 20, 2025, in ACR Open Rheumatology . LIMITATIONS: This study did not capture data on dose and duration of immunomodulatory medications or clinical features at treatment decisions. Treatment choices were made independently by clinicians and may have been influenced by factors such as drug availability or insurance, introducing variability. Moreover, the academic referral setting may have contributed to selection bias. DISCLOSURES: Two authors reported receiving support from the Vasculitis Clinical Research Consortium, Association des médecins rhumatologues du Québec, Institute for Translational Medicine and Therapeutics, and other sources. This research was also supported by the Relapsing Polychondritis Foundation and other generous donors to the Penn Relapsing Polychondritis Program.
Medscape
27-05-2025
- Business
- Medscape
Etrasimod Shows Promise in Eosinophilic Esophagitis
Etrasimod, a once-daily oral selective sphingosine-1-phosphate receptor modulator, is well tolerated and effective in treating eosinophilic esophagitis (EoE), demonstrating sustained histologic and endoscopic improvements over 52 weeks. METHODOLOGY: Etrasimod, currently approved in adults with moderate to severe ulcerative colitis, blocks lymphocyte trafficking to inflamed mucosal tissues and may offer a promising option for treating EoE. Researchers conducted an international phase 2 multicenter trial to assess the efficacy and safety of etrasimod vs placebo in patients (age, 18-65 years) with previously diagnosed and histologically active EoE. Patients were randomized to receive oral 1 mg etrasimod, 2 mg etrasimod, or placebo once daily for 24 weeks, with stratification according by history of dilation and concurrent proton pump inhibitor therapy. Patients who completed the initial treatment phase entered a 28-week extension period, during which they either continued their etrasimod dose or were randomly switched from placebo to 1 or 2 mg etrasimod. The primary endpoint was a percentage change in the esophageal peak eosinophil count from baseline to week 16; safety was assessed through week 52. TAKEAWAY: Researchers randomized 108 patients: 41 to receive 2 mg etrasimod, 39 to receive 1 mg etrasimod, and 28 to receive placebo; 85 patients completed the double-blind period and entered the extension period. At week 16, only etrasimod 2 mg significantly reduced peak eosinophil count from baseline vs placebo ( P = .010); however, at week 24, both 1 and 2 mg doses showed significant reductions ( P = .0022 and P < .0001, respectively). = .010); however, at week 24, both 1 and 2 mg doses showed significant reductions ( = .0022 and < .0001, respectively). Endoscopic and histologic severity scores improved with 2 mg etrasimod and both doses, respectively, at week 24, with benefits sustained through week 52. Significant improvements in Dysphagia Symptom Questionnaire scores were noted at week 24 in patients without prior endoscopic dilation compared with patients receiving placebo. Gastrointestinal disorders were the most common treatment-emergent adverse events, occurring in 27% (2 mg), 33% (1 mg), and 50% (placebo). Three cases of mild or moderate bradycardia were reported. IN PRACTICE: 'Etrasimod offers a promising new therapeutic approach for eosinophilic oesophagitis, addressing the complexities of [type 2 helper T cells]–driven inflammation and the challenges posed by preexisting fibrotic changes,' an expert wrote in an accompanying editorial. 'Etrasimod's simple administration, independent of meals, could potentially increase patient compliance.' SOURCE: The study was led by Evan S. Dellon, MD, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine in Chapel Hill. It was published online in The Lancet Gastroenterology & Hepatology . LIMITATIONS: This study was not powered to assess dysphagia symptoms. It included a high proportion of patients with stenosis and prior dilation and few with atopic conditions, relative to other reported EoE studies. The extension phase involved a limited number of patients. DISCLOSURES: This study was funded by Pfizer. Nine authors declared being current or former employees of Pfizer and holding stock or stock options. Several others reported receiving grants, honoraria, fees, or travel support from, holding stocks of, or having other ties with Pfizer and other pharmaceutical companies.
Medscape
23-05-2025
- Health
- Medscape
Can Nivolumab Maintain AML Remission?
In a randomized phase 2 study of 79 patients with acute myeloid leukemia (AML) in first complete remission, nivolumab maintenance therapy did not improve progression-free survival (13.2 vs 10.9 months) or overall survival (53.9 vs 30.9 months) compared with observation. Adverse events were more frequent in the nivolumab arm, with 71% experiencing grade ≥ 3 events vs 12% in the observation arm. METHODOLOGY: A multicenter, open-label, randomized phase 2 trial enrolled 79 patients with AML in first complete remission or complete remission with incomplete hematologic recovery who were not candidates for stem cell transplant. Participants were randomized to either observation or nivolumab arm (3 mg/kg intravenously every 2 weeks for 46 doses), with a median follow-up duration of 24 months. Primary endpoint was progression-free survival, defined as time to disease relapse or death, while secondary endpoints included overall survival and evaluation of adverse events. Analysis included measurement of measurable residual disease (MRD) through ultrasensitive duplex DNA sequencing in 55 patients and targeted RNA sequencing in two patients before randomization. TAKEAWAY: Median progression-free survival duration was 13.2 months (95% CI, 8.5-21.8) in the nivolumab arm vs 10.9 months (95% CI, 5.4-14.9) in the observation arm (hazard ratio [HR], 0.92; 95% CI, 0.54-1.56; P = .38). = .38). Overall survival analysis showed median survival duration of 53.9 months (95% CI, 23.4 to not estimable) in the nivolumab arm vs 30.9 months (95% CI, 14.4 to not estimable) in the observation arm (HR, 0.78; 95% CI, 0.40-1.51; P = .23). = .23). Adverse events of grade ≥ 3 occurred in 71% of nivolumab-treated patients compared with 12% of patients in the observation arm ( P < .001), with fatigue (42%), hypertension (37%), and diarrhea (34%) being most common. < .001), with fatigue (42%), hypertension (37%), and diarrhea (34%) being most common. MRD positive patients showed significantly higher relapse rates at 2 years (74% vs 37%; P = .046) and decreased progression-free survival (21% vs 63%; P = .032) than MRD negative patients. IN PRACTICE: 'With negative results using checkpoint inhibitors alone (or in combination with HMA [hypomethylating agent]), now in both the MRD setting and in the front line, the utility of targeting the PD1-PDL1 [programmed cell death 1–programmed death ligand 1] pathway in unselected AML appears limited…. It remains possible that further correlatives studies might identify a subset of patients with AML who may responses to immune checkpoint inhibition,' wrote the authors of the study. SOURCE: The study was led by Athalia Pyzer and Hongtao Liu, The University of Chicago in Chicago. It was published online on May 13 in Blood Advances . LIMITATIONS: According to the authors, subgroup analysis in the cohort of MRD positive patients did not demonstrate any effect of nivolumab on clinical outcomes, but these comparisons were underpowered. The researchers noted that other immune escape mechanisms, even beyond checkpoint pathways, likely contribute to the persistence of this disease. DISCLOSURES: The study was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, a University of Chicago Comprehensive Cancer Center pilot grant, the Ullman Scholar Award, and the Elsa U. Pardee Foundation. Additional disclosures are noted in the original article.
Medscape
14-05-2025
- Health
- Medscape
Adult Sugammadex Dosing Safe, Effective in Kids Aged < 2
Sugammadex doses of 2 and 4 mg/kg, recommended for adults and children aged 2 years or older, were safe and effective for reversing neuromuscular blockade (NMB) in neonates and infants younger than 2 years. The 2-mg/kg dose of sugammadex reversed moderate NMB faster than neostigmine plus glycopyrrolate or atropine (neostigmine), whereas the 4-mg/kg dose led to a rapid reversal of deep NMB. METHODOLOGY: Researchers conducted a phase 4, multicenter clinical trial (July 2019-September 2023) to assess the tolerability and efficacy of sugammadex in reversing NMB in children younger than 2 years. Overall, 138 children (mean age, 164 days; 66.7% boys) received NMB induced by rocuronium or vecuronium for surgeries such as repair of a cleft lip or an inguinal hernia, and orchidopexy. The first part of the trial was open label and involved pharmacokinetic assessments of 2- and 4-mg/kg doses of sugammadex to determine if dose adjustment was necessary based on age. The second part was double blind, with patients randomly assigned to receive a 2-mg/kg dose of sugammadex for reversing moderate NMB (defined as return of second twitch), neostigmine for reversing moderate NMB, or a 4-mg/kg dose of sugammadex for reversing deep NMB (defined as a post-tetanic count of 1 or 2). The primary efficacy endpoint was time to neuromuscular recovery. TAKEAWAY: Doses of sugammadex of 2 and 4 mg/kg were found appropriate for reversing moderate and deep NMB in children younger than 2 years, according to pharmacokinetic assessments performed in the first part of the trial. In moderate NMB, time to neuromuscular recovery was significantly faster with the 2-mg/kg dose of sugammadex than with neostigmine (hazard ratio, 2.40; P = .0002). = .0002). A rapid neuromuscular recovery for deep NMB was achieved over a median of 1.1 minutes with the 4-mg/kg dose of sugammadex. Procedural pain and vomiting were the most frequently reported adverse events, with no significant differences observed between the sugammadex and neostigmine groups. No deaths or drug-related serious adverse events were reported with either doses of sugammadex. IN PRACTICE: 'These results support the use of sugammadex doses of 2 mg/kg and 4 mg/kg, the same doses as recommended for children > 2 years old and adults, for reversing rocuronium- or vecuronium-induced moderate and deep NMB in the youngest pediatric population from birth to < 2 years of age,' the researchers reported. SOURCE: This study was led by Edith Mensah-Osman, MD, PhD, and Yuki Mukai, MD, from Merck & Co., Inc., Rahway, New Jersey. It was published online on May 5, 2025, in Anesthesiology . LIMITATIONS: The pharmacokinetic analyses in the first part of the trial involved a relatively small number of participants, particularly for the cohort of infants aged 1 month or younger. The study was not designed as a dose-ranging trial but rather to confirm established doses from older age groups. The potential influence of the total dose of NMB agents was not evaluated. DISCLOSURES: This study received funding from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. Nine authors reported being employed by and owing stocks in the funding agency, and two authors reported receiving research grants from the same organization.
