SPECIAL REPORT
Use in pediatric-onset MS (POMS)
Efficacy and safety in an adult population
Safety during pregnancy
Management of older MS patients
The widespread adoption of anti-CD20 therapies for the treatment of multiple sclerosis has sparked interest in the use of these agents throughout the clinical course. This was one of the key areas of research highlighted at the recent European Committee for Treatment and Research in MS (ECTRIMS) congress, held September 24-26, 2025, in Barcelona, Spain. The following summarizes some of the studies reported for the anti-CD20 agent ocrelizumab.
Use in pediatric-onset MS (POMS)
The OPERETTA program is currently investigating the use of ocrelizumab in POMS. OPERETTA 1 was a 24-week pharmacodynamic study in patients aged 10-17 years (N=23) and reported earlier this year that a body weight-adjusted dose (300 mg for < 35 kg, 600 mg for >35 kg q24wk) was optimal (Mar et al. J Neurol 2025;272:137). A cut-off of 40 kg was used in the 24-week extension. Results at 96 weeks are now available (Waubant et al. ECTRIMS 2025;O106). Treatment was generally well-tolerated and the side effect profile was similar to what is seen in adults. The most common adverse effects (non-COVID-19-related) were infusion reactions (about 80%), which mainly occurred with the first dose, headache and upper respiratory tract infections. Six patients experienced serious adverse effects including two with serious infections. No relapses were recorded and EDSS scores were stable.
OPERETTA 2 was a phase III non-inferiority study (N=187) that compared ocrelizumab 300 mg or 600 mg q24wk with fingolimod 0.25 mg or 0.5 mg/day (Banwell et al. ECTRIMS 2025;O130). Median age was 15 years; median EDSS was 1.5; median time from diagnosis was 8-9 months. Median time on treatment was 76.7 weeks for the ocrelizumab arms and 73.9 weeks for the fingolimod arms. The annualized relapse rate (ARR) was 0.07 with ocrelizumab versus 0.14 with fingolimod; risk reduction was 48%. Ocrelizumab was associated with a significant 48% reduction in new/enlarging T2 lesions during the course of the study. Ocrelizumab was also superior to fingolimod (87% reduction) in the number of Gd+ lesions at week 12 (gadolinium was not administered past week 12 due to safety concerns). The rates of serious adverse events (6.5% vs. 8.7%) and serious infections (3.2% vs. 3.3%) were comparable with ocrelizumab and fingolimod.
Efficacy and safety in an adult population
A retrospective study (N=102) compared the effect of higher-efficacy versus lower-efficacy DMTs on disability worsening and progression independent of relapse activity (PIRA) in patients with non-active RMS (Diras et al. ECTRIMS 2025;P842). The largest proportion of patients in the high-efficacy group received ocrelizumab. Overall, 5.9% in the higher-efficacy group experienced a PIRA event compared to 21.6% in the lower-efficacy group. The rates of EDSS progression were 0.01 vs. 0.42, respectively.
A real-world study (N=241) of older patients (mean age 52.6 years) reported that ocrelizumab-treated patients remained clinically stable with minimal change in EDSS score (from 5.23 to 5.40) over a five-year period (Ozakbas et al. ECTRIMS 2025;P806). Interestingly, cognitive performance showed significant improvement in the domains of verbal and visuospatial memory. The authors concluded that ocrelizumab may contribute to cognitive resilience in older MS patients.
The German CONFIDENCE study (N=2263) evaluated the impact of ocrelizumab on work productivity and activity impairment (Buttmann et al. ECTRIMS 2025;P864). Over a 24-month period, ocrelizumab-treated patients demonstrated a reduction in work impairment and absenteeism, and an improvement in managing activities of daily living.
Safety during pregnancy
The MINORE study (N=35) recently reported that there was minimal placental transfer of ocrelizumab during pregnancy in women receiving ocrelizumab <6 months before their last menstrual period (Hellwig et al. ACTRIMS Forum 2025;P106). (See ACTRIMS Forum 2025 Highlights – Update on Ocrelizumab, NeuroSens, March 24, 2025.) There was also minimal drug transfer in breast milk when ocrelizumab was re-initiated 2-24 weeks postpartum in the SOPRANINO study (N=13) (Hellwig et al. ACTRIMS Forum 2025;P101). At one-year follow-up of the two studies, B cell levels were within normal range in all infants (Bove et al. ECTRIMS 2025;O102). Infant growth was within the normal range for head circumference, weight and height/length. All infants were vaccinated and were able to mount a seroprotective humoral response to measles (96-100%), mumps (78-85%), rubella (96-100%), diphtheria (100%), tetanus (100%), pneumococcus (85-100%), and Haemophilus influenzae (80-83%).
An analysis of the Ocrelizumab Pregnancy Registry (N=226) of ocrelizumab exposure during pregnancy reported that >90% of pregnancies resulted in live births (Hellwig et al. ECTRIMS 2025;P084). The rate of spontaneous abortions was higher in the ocrelizumab group versus a comparator group of patients receiving glatiramer acetate or no treatment (6.5% vs. 1.8%); the rate of spontaneous abortions in the general population is typically 10-12%. The frequency of major congenital malformations was lower in the ocrelizumab-exposed group versus the comparator group (1.8% vs. 4.9%). The MAGGIORE study plans to evaluate the long-term outcomes of ocrelizumab-exposed infants.
The frequency of peripartum relapses was examined in a retrospective analysis of patients treated at the BARLO MS Centre, Toronto (McIsaac et al. ECTRIMS 2025;P584). Birth outcomes were similar in untreated patients and those treated with a lower-efficacy injectable versus those receiving a higher-efficacy DMT prior to pregnancy. The relapse rate was lowest in those who had received prior ocrelizumab or oral cladribine.
Management of older MS patients
A potential concern is the increasing risk of infection among older MS patients on treatment for an extended period. A retrospective study at the Massachusetts General Hospital examined the infection risk with ocrelizumab in patients aged >55 years (N=533); 26% of the cohort were aged >70 years (Lee et al. ECTRIMS 2025;P348). The median duration of treatment with ocrelizumab was 3.2 years. Overall, there were 33.5 infections/1000 person-months of drug exposure (excluding COVID-19). The most common infections were UTIs and upper respiratory tract infections; 83.3% of infections did not require hospitalization.
MANUSCRIPT is a long-term surveillance study of RMS and PPMS patients in the real-world setting using information from the BigMS data network (N=52,219) (Butzkueven et al. ECTRIMS 2025;P295). The risk of serious infections was not significantly different when comparing the cohort treated with ocrelizumab versus other DMTs (hazard ratio 1.38). The pooled hazard ratio showed no increased risk of malignancies with ocrelizumab versus other DMTs (HR 1.04).
Also noteworthy was a French Registry study that examined the safety of discontinuing ocrelizumab or rituximab in patients aged >50 years (N=224 matched patients) (Kerbrat et al. ECTRIMS 2025;O005). Mean age was 57.4 years; median EDSS was 5.4; mean disease duration was 19.4 years. There was no significant difference between the discontinuation versus continuation groups in time to first relapse, time to first inflammatory activity or time to first confirmed disability event after a median follow-up of 2.9 years. The risk of relapse was associated with patient age, with relapse risk decreasing 11% per year after discontinuation. The authors concluded that anti-CD20 agents can be safely discontinued in older patients without the need for de-escalation to another DMT.