SPECIAL REPORT
First-line use of ocrelizumab
CONSONANCE study in progressive MS
Safety in pregnancy
Treatment effects in the CNS
The use of the anti-CD20 agent ocrelizumab as a first-line agent in the treatment or multiple sclerosis and its safety in pregnancy were among the issues addressed at the recent Americas Committee on Treatment and Research in MS (ACTRIMS) Forum, held February 27-March 1, 2025 in West Palm Beach, Florida. The following summarizes key ocrelizumab data presented at the congress.
First-line use of ocrelizumab
Two studies at the ACTRIMS Forum 2025 reported on the efficacy and safety of ocrelizumab as a first-line agent. The MSBase group’s ongoing OCR-R study evaluated 183 patients with MS; mean age was 37.3 years, median time since diagnosis was three months, and median EDSS was 2.0 at study start (Craveiro et al. ACTRIMS Forum 2025;P417). The annualized relapse rate (ARR) was 0.04, with 91.7% relapse-free at four years. A total of 83.4% were free of disability worsening at year 4. The overall rates of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) were 1.1% and 8.2%, respectively. The probabilities of remaining free of RAW and PIRA at four years were 98.3% and 85.2%, respectively.
A separate analysis looked at long-term outcomes in the treatment-naive subgroup (n=757) in the OPERA I/II trials of ocrelizumab versus interferon-beta (Cerqueira et al. ACTRIMS Forum 2025;P071). Mean time from symptom onset was three years. Median time on treatment was 10.6 years for the continuous ocrelizumab group. A total of 82.4% receiving continuous ocrelizumab were free of 48-week confirmed disability progression (CDP) compared to 81.6% in the interferon-beta/ocrelizumab switch group at 11 years. ARR over 11 years was significantly lower in the continuous ocrelizumab versus IFN/OCR group (0.054 vs. 0.076). There was also a significant difference in the mean percentage brain loss (-3.35% vs. -3.71%) during the observation period, indicating that earlier treatment with ocrelizumab is associated with greater preservation of brain tissue. Brain atrophy rates were comparable to those seen with normal aging.
CONSONANCE study in progressive MS
The phase IIIb CONSONANCE study is the first to examine the efficacy of ocrelizumab in patients with SPMS and PPMS (N=629) (McGinley et al. ACTRIMS Forum 2025;P105). Patients were adults with PMS with evidence of PIRA in the two years prior to entry. Mean age was 48.5 years; median EDSS 6.0 for SPMS and 5.0 for PPMS. A total of 21.3% of the SPMS group and 11.1% of the PPMS group had Gd+ lesions at baseline. There was no 24-week EDSS progression in 71.4% of SPMS patients and 58.1% of PPMS patients at four years. About one-third showed no progression on any measure (EDSS, T25FW, 9HPT). Cognitive function on the Symbol Digit Modalities Test (SDMT) was stable or improved in 88.4% of the SPMS group and 82.4% of the PPMS group; cognitive function improved in 22.5% overall. In addition, disability improvement on at least one outcome measure was seen in 32.5% of SPMS patients and 25.0% of PPMS patients.
Safety in pregnancy
Two studies examined the impact of ocrelizumab exposure during pregnancy and postpartum. Preliminary results were presented at ECTRIMS 2024 (Hellwig et al. P087, and Bove et al. O039). The phase IV MINORE study (N=35) examined placental transfer of ocrelizumab during pregnancy and the potential impact on the infant’s B cell levels (Hellwig et al. ACTRIMS Forum 2025;P106). All subjects had their last ocrelizumab infusion <6 months after their last menstrual period; this included three women who were treated during pregnancy (median 1.9 months after the last menstrual period). The median time from infusion to last menstrual period was 3.2 months. All pregnancies resulted in full-term live births. Ocrelizumab was undetectable in 94.3% of cord blood samples at birth and 97.0% of serum samples at week 6. B cell levels were above the age-specific lower limit of normal in all newborns at week 6. The median time to restarting ocrelizumab was week 5.4 postpartum. Moreover, median antibody titres to immunization in pregnant women were above seroprotective levels; most patients had a positive humoral response to relevant pathogens. The researchers concluded that women should be advised to follow local recommendations for vaccine use during pregnancy.
Transfer of ocrelizumab in breast milk was examined in the SOPRANINO study (N=13) (Hellwig et al. ACTRIMS Forum 2025;P101). All patients started/re-started ocrelizumab at 2-24 weeks postpartum. The median age of infants at the time of treatment start was 2.0 months. The level of ocrelizumab in breast milk was near to the lower limit of quantification. The median average daily infant dose was 45.1 µg (range 0-191.8 µg). Infant serum levels of ocrelizumab were undetectable. B cell levels were within the normal range in all infants. One case of severe infection (Grade 3 bronchiolitis) was reported. No effects on infant growth or development were evident. An analysis of infant humoral response to vaccination is planned.
Treatment effects in the CNS
Novel imaging and computing techniques have enabled the analysis or re-examination of datasets to determine the treatment effects on regions of interest. A post-hoc study combined conventional T1/T2 and FLAIR images from the ORATORIO trial of ocrelizumab in PPMS to generate imaging modalities (e.g. FLAIR2, artificial intelligence double inversion recovery) that could visualize cortical lesions (Dwyer et al. ACTRIMS Forum 2025;CE2.2). The mean cortical lesion number at baseline was 15.11 in the ocrelizumab group compared to 12.9 in the placebo group; cortical lesion volume was 755.99 and 634.15 mm3, respectively. Ocrelizumab was associated with a significant 74.8% reduction in the number of new/enlarging cortical lesions per scan versus placebo over 120 weeks. Cortical lesion volume increased 13.4 mm3 in the ocrelizumab group and 100.1 mm3 in the placebo group.
Quantitative susceptibility mapping (QSM), which measures magnetic sources in tissue such as iron and myelin, can be used to detect paramagnetic rim lesions (PRL), a type of chronic active lesion characterized by iron-laden microglia. Both iron deposition (QSM positive) and myelin loss (QSM negative) significantly contribute to the QSM value in white matter, so source separation algorithms are used to distinguish iron from myelin in voxels. These techniques were used in an analysis of 29 MS patients (mean age 40.5 years pre-treatment) with at least one PRL (Markowitz et al. ACTRIMS Forum 2025;CE1.3). Patients were followed for a median of 4.2 years pre-treatment and 4.09 years after ocrelizumab initiation. There were 97 PRLs at baseline (median three/patient). The slope of QSM positive values (indicating iron) substantially declined (from -0.457 ppb/year to -1.041 ppb/year) within the first six months of ocrelizumab initiation. Treatment was also associated with an increase in myelin in PRL and non-PRL lesions. The authors concluded that these findings suggest that treatment is associated with a reduction in pro-inflammatory activity in the CNS and increased remyelination.