Ponesimod Compared With Teriflunomide in Patients With Relapsing Multiple Sclerosis in the Active-Comparator Phase 3 OPTIMUM Study: A Randomized Clinical Trial
| Autor: | Kappos, Ludwig, Fox, Robert J., Burcklen, Michel, Freedman, Mark S., Kubala Havrdova, Eva, Hennessy, Brian, Hohlfeld, Reinhard, Lublin, Fred, Montalban, Xavier, Pozzilli, Carlo, Scherz, Tatiana, D'Ambrosio, Daniele, Linscheid, Philippe, Vaclavkova, Andrea, Pirozek-Lawniczek, Magdalena, Kracker, Hilke, Sprenger, Till, Universitat Autònoma de Barcelona |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Toluidines Hydroxybutyrates law.invention 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Multiple Sclerosis Relapsing-Remitting Randomized controlled trial law Internal medicine Teriflunomide Nitriles medicine Clinical endpoint Humans Immunologic Factors 030212 general & internal medicine Original Investigation Expanded Disability Status Scale business.industry Multiple sclerosis McDonald criteria Middle Aged medicine.disease Magnetic Resonance Imaging Thiazoles chemistry Ponesimod Tolerability Crotonates Disease Progression Female Neurology (clinical) Neoplasm Recurrence Local business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | JAMA Neurol |
| Popis: | IMPORTANCE: To our knowledge, the Oral Ponesimod Versus Teriflunomide In Relapsing Multiple Sclerosis (OPTIMUM) trial is the first phase 3 study comparing 2 oral disease-modifying therapies for relapsing multiple sclerosis (RMS). OBJECTIVE: To compare the efficacy of ponesimod, a selective sphingosine-1-phosphate receptor 1 (S1P(1)) modulator with teriflunomide, a pyrimidine synthesis inhibitor, approved for the treatment of patients with RMS. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, double-blind, active-comparator, superiority randomized clinical trial enrolled patients from April 27, 2015, to May 16, 2019, who were aged 18 to 55 years and had been diagnosed with multiple sclerosis per 2010 McDonald criteria, with a relapsing course from the onset, Expanded Disability Status Scale (EDSS) scores of 0 to 5.5, and recent clinical or magnetic resonance imaging disease activity. INTERVENTIONS: Patients were randomized (1:1) to 20 mg of ponesimod or 14 mg of teriflunomide once daily and the placebo for 108 weeks, with a 14-day gradual up-titration of ponesimod starting at 2 mg to mitigate first-dose cardiac effects of S1P(1) modulators and a follow-up period of 30 days. MAIN OUTCOMES AND MEASURES: The primary end point was the annualized relapse rate. The secondary end points were the changes in symptom domain of Fatigue Symptom and Impact Questionnaire–Relapsing Multiple Sclerosis (FSIQ–RMS) at week 108, the number of combined unique active lesions per year on magnetic resonance imaging, and time to 12-week and 24-week confirmed disability accumulation. Safety and tolerability were assessed. Exploratory end points included the percentage change in brain volume and no evidence of disease activity (NEDA-3 and NEDA-4) status. RESULTS: For 1133 patients (567 receiving ponesimod and 566 receiving teriflunomide; median [range], 37.0 [18-55] years; 735 women [64.9%]), the relative rate reduction for ponesimod vs teriflunomide in the annualized relapse rate was 30.5% (0.202 vs 0.290; P |
| Databáze: | OpenAIRE |
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