BackgroundEarly high-efficacy treatment for people with relapsing multiple sclerosis (pwRMS) may provide better long-term outcomes compared with the escalation strategy. In this study, we present an analysis of treatment success and safety from the CONFIDENCE study in a real-world cohort of pwRMS treated with ocrelizumab in different treatment lines for up to 5.5 years.MethodsThe ongoing German non-interventional post-authorization safety study, CONFIDENCE (ML39632, EUPAS22951), evaluates the long-term safety and effectiveness of therapy in pwMS newly treated with ocrelizumab or other disease-modifying therapies for up to 10 years. This analysis presents CONFIDENCE treatment success (proportion of people with no clinical disease activity measured by relapse or disease progression and no treatment discontinuation due to adverse event [AE] or lack of therapeutic effectiveness), confirmed disability progression (CDP), annualized relapse rates, and safety in pwRMS stratified by the number of previous MS therapies (PMSTs).ResultsAt the data cutoff (11 October 2023), the full analysis set included 2,261 pwRMS treated with ≥1 dose of ocrelizumab. At baseline, the mean age (SD) of the participants was 41.16 (11.39) years (treatment-naïve, 39.19 [12.95] years; ≥3 PMSTs, 42.80 [10.08] years), and the mean Expanded Disability Status Scale (EDSS) score was 3.08 (1.86) (treatment-naïve, 2.37 [1.54]; ≥3 PMSTs, 3.57 [1.90]). Overall, 58.4% of pwRMS with continuous treatment achieved CONFIDENCE treatment success from baseline until year 5 (74.0 and 50.3% of pwRMS with 0 and ≥3 PMSTs). The main reasons for not achieving CONFIDENCE treatment success were relapse and CDP, while treatment discontinuation due to AEs or lack of effectiveness played a minor role. The proportion of pwRMS with AEs did not increase with longer treatment duration and tended to be higher with more PMSTs. The spectrum of AEs was similar across treatment lines, and no new or unexpected AEs were observed.ConclusionCONFIDENCE treatment success remained high over 5 years of ocrelizumab treatment, even among people with RMS (pwRMS) with a higher number of PMSTs. Only a small proportion of pwRMS discontinued treatment due to AEs. These results support early intervention with high-efficacy ocrelizumab treatment to optimize long-term outcomes for pwRMS.Trial registrationhttps://catalogues.ema.europa.eu/node/3142/administrative-details, identifiers ML39632 and EUPAS22951.

Background: Ozanimod, a sphingosine 1-phosphate receptor 1 and 5 modulator, was approved as a disease-modifying therapy for active relapsing-remitting multiple sclerosis (RRMS) in 2020 and for active ulcerative colitis in 2021. Long-term, real-world studies in a nonselective population are needed. OzEAN is an ongoing study to assess the real-world persistent use, effectiveness, and safety of ozanimod and its impact on quality of life (QoL) in patients with RRMS over a 5-year period. Methods This prospective, noninterventional, postmarketing authorization study will enroll ~1,300 patients (≥18 years of age) with active RRMS. The decision to initiate ozanimod must have been made before and independent from study participation. Enrollment began in March 2021. Recruitment is ongoing and will last for 36 months across 140 sites in Germany. Treatment-naive patients or those having prior experience with a disease-modifying therapy receive oral ozanimod 0.92 mg/day after an initial dose escalation, per the summary of product characteristics recommendations, for up to 60 months. Persistence with ozanimod treatment (primary endpoint) is assessed at month 60. Secondary endpoints include additional physician-reported outcomes [persistence at earlier time points, annualized relapse rate, Expanded Disability Status Scale score, cognition (Symbol Digit Modalities Test), and incidence of adverse events], and patient-reported outcomes assessing patient satisfaction, adherence, and treatment modalities (Treatment Satisfaction Questionnaire for Medication, v1.4), disability (United Kingdom Neurological Disability Rating Scale), QoL (MSQOL-54 questionnaire), fatigue (Fatigue Scale for Motor and Cognitive Functions), and health economics [Work Productivity and Activity Impairment Questionnaire for Multiple Sclerosis (German v2.1); Multiple Sclerosis Health Resource Survey, v3.0]. A Multiple Sclerosis Documentation System with an internet-based e-health portal allows patients to view files and complete questionnaires. A safety follow-up will occur 3–8 months after the last ozanimod dose for patients who discontinue treatment early. Long-term results are anticipated after study completion in 2029. Yearly interim analyses are planned after enrollment has reached 25%. Conclusion This is the first long-term, real-world study of ozanimod in patients with RRMS and, to our knowledge, the first noninterventional study utilizing a patient portal. These data will add to the safety/efficacy profile of ozanimod demonstrated in phase 3 trials. Clinical Trial Registration Clinicaltrials.gov, identifier: NCT05335031.

Background Real-world relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS) populations may be more diverse than in clinical trials. Here, we present a first analysis of safety, adherence and persistence data from a real-world cohort of patients newly treated with ocrelizumab. Methods CONFIDENCE (ML39632, EUPAS22951) is an ongoing multicenter, non-interventional post authorization safety study assessing patients with RMS or PPMS newly treated with ocrelizumab or other disease-modifying therapies for up to 10 years. For this analysis, patients newly treated with ocrelizumab were analyzed in subgroups by MS phenotype and age over a mean ~1 year of exposure totaling 2,329 patient years [PY]). Results At data cutoff (14 October 2020), 1,702 patients with RMS and 398 patients with PPMS were treated with ≥1 dose of ocrelizumab. At baseline, the mean ages (SD) of patients with RMS and PPMS were 41.59 (11.24) and 50.95 (9.88) years and the mean EDSS (Expanded Disability Status Scale) was 3.18 (1.87) and 4.41 (1.59), respectively. The most common adverse events (AEs) and serious AEs across both phenotypes were infections and infestations, with infection SAE rates of 2.8 events/100 PY and 1.5 events/100 PY in patients with RMS and PPMS, respectively. Across all phenotypes, ocrelizumab persistence was 92% at 24 months; median time between doses was ~6 months. Conclusions The ocrelizumab safety profile observed in the CONFIDENCE real-world MS population was consistent to the one observed in pivotal clinical trials. High treatment persistence and adherence were observed. Trial Registration ML39632, EUPAS22951