Eight years ago we suggested that anti-CD20 depleting antibodies may act for much longer than the dosing and suggested that it may be possible to use like alemtuzumab and cladribine and then we provided supportive evidence from the phase II study whereby efficacy was maintained for 18 months after stopping ocrelizumab which suggested that it may be possible to extend the interval between dosing. We couldnt get a trial off the ground as there was not equipoise in many places because they were extending the interval between doses because it was found to be effective during COVID-19. This is a study comparing 6 month and 12 month intervals between dosing with rituximab. After a year of treatment this was done and there was no real increase in failure. This allowed B cell recovery in more people. Will this change practise, I suspect not as some will say this is rituximab not ocrelizumab…however a trial is planned in the UK of extending dose intervals comparing 5 and 12 month dosing if it is the same they will drop to 9 month or increase to 15 month in an adaptive study…I guess you just need to read and say is 15 month too short… The question is how much breakthrough is acceptable as there is breakthrough even on 6 monthly dosing and I would ask if it allows anti-drug antibody responses to develop, as the repopulating B cells can make antibody…meaning you can get vaccine responses. The most significant element I think is that this should give some confidence to people on a treatment break during pregnancy
Langer-Gould A, Li BH, Smith JB, Nielsen AS, Beaber BE, Brara SM, Amirova S, Torres F, Xu S. Comparative Effectiveness of Rituximab Dosed Every 6 and 12 Months in Relapsing Multiple Sclerosis. Neurology. 2026; 106(2):e214473.
Background and objectives: Rituximab (RTX) dosed every 6 months is an affordable and highly effective treatment for relapsing multiple sclerosis (RMS). However, higher cumulative doses are associated with greater risks of infections. Whether extending dosing intervals at a low dose (500 mg) increases the risk of return of disease activity, particularly in those with only 1 year of stability or with significant return of B cells, is uncertain. Our objective was to compare whether extending RTX dosing to every 12 months (q12mo) vs continuing every 6 months (q6mo) dosing in patients with RMS increased the risk of return of disease activity.
Methods: We emulated a target trial comparing the effectiveness of RTX 500 mg q12mo to q6mo starting in year 2 (baseline) among patients with RMS who had active disease at RTX start and no evidence of disease activity (NEDA) during the first year on RTX. Eligible patients were identified from the retrospective cohort of patients with MS treated with RTX between 2008 and 2023 in Kaiser Permanente Southern California. The absence of relapses, MRI disease activity, and disability progression (NEDA-3) were analyzed by intention-to-treat (ITT) and per-protocol (PP) with inverse probability of treatment weighting of receiving q6mo or q12mo dosing.
Results: We identified 140 patients (mean age 40.4 years, 73.6% female) who received q12mo dosing and 468 patients (mean age 38.4, 70.9% female) on q6mo dosing after baseline with a median ITT follow-up of 2.6 (interquartile range [IQR] 1.9-3.3) and 3.9 years (IQR 2.4-4.8), respectively. Relapses and/or MRI disease activity (3.5%) and failing NEDA-3 (3.8%) up to 4 years later were uncommon. Extending dosing to q12mo was associated with significant B-cell repopulation (70.5% with ≥80 cells/μL PP, 75.7% ITT) compared with q6mo intervals (23.3% with ≥80 cells/μL PP, 60.2% ITT) but not with an increased risk of failing NEDA-3 up to 4 years after baseline in propensity score-adjusted ITT (hazard ratio [HR] 1.60, 95% CI 0.69-3.68) or PP analyses (HR 1.44, 95% CI 0.45-4.61).
Discussion: Extending low-dose RTX treatment intervals after 1 year of stability to q12mo was highly effective and did not result in an increased risk of disease activity despite high B-cell counts compared with continuing q6mo dosing over 2 or more years of follow-up.
This another anti-CD20 paper and supports efficacy seen in trials
Butzkueven H, Farr P, Ozakbas S, Boz C, Kalincik T, Taylor L, Van Der Walt A, Alroughani R, Buzzard K, Skibina O, Lechner-Scott J, Laureys G, Terzi M, Van Pesch V, Grand-Maison F, Barnett M, Kermode A, Menoyo JLS, Rojas J, Willekens B, Foschi M, Ramo-Tello C, Skromne E, Dirks P, Rouzic EM, Spelman T. Real-world effectiveness of ocrelizumab in relapsing multiple sclerosis: An MSBase registry sub-study. Mult Scler Relat Disord. 2025;106:106885. doi: 10.1016/j.msard.2025.106885. Epub ahead of print. PMID: 41421009.
Introduction: The MSOCR-R study evaluates the long-term effectiveness of ocrelizumab (OCR) in patients with relapsing multiple sclerosis (RMS) in real-world clinical settings.
Methods: MSOCR-R is an ongoing, prospective, longitudinal, observational cohort study of people with RMS newly treated with OCR, using data from the international MSBase registry. The study started in July 2018, and data collected up to October 2023 were analyzed. Outcomes were confirmed disability worsening (CDW), progression independent of relapses (PIRA), and no evidence of disease activity (NEDA-3: absence of relapse, 24-week CDW, or imaging activity).
Results: Overall, 1011 patients were enrolled (18.1% initiated OCR first-line therapy; 81.9% switched from previous treatment), with a median time of 3.4 years on OCR treatment. About 67% of patients were females. At OCR initiation, mean age was 41.9 years, median disease duration was 10.4 years, and median Expanded Disability Status Scale score was 3.0. The 4-year Kaplan-Meier probabilities of 24-week CDW or PIRA were 25.2% (95% CI 21.6-29.1) and 21.9% (95% CI 18.3-25.2), respectively. Annualized relapse rate substantially decreased from 0.58 (95% CI 0.53-0.63) before OCR to 0.05 (95% CI 0.04-0.06) after treatment initiation. NEDA-3 was assessed in 366 patients and the probability of achieving NEDA-3 was 39.7% (95% CI 36.0-43.5) at 4 years. Persistence on OCR was 88.0% (95% CI, 85.2-90.3) at 4 years. Better clinical outcomes were consistently observed among the first-line treatment cohort.
Conclusion: The MSOCR-R study provides strong real-world evidence of OCR effectiveness in people with RMS.
CoI. Multiple
Disclaimer. I am not a doctor and the advice is the summary of product characteristics of current anti-CD20 depleters is dose at one ofatumumab/6 monthly ublituximab/ocrelizumab
Source: multiple-sclerosis-research.org