Early Ocrelizumab Intervention in RRMS: Real-World Data Reinforces a Shift in Strategy

Emerging real-world evidence continues to challenge longstanding treatment hierarchies in multiple sclerosis (MS) care. A retrospective, monocentric study by Kvartskhava et al. brings momentum to a growing movement favoring early, high-efficacy therapy—specifically using ocrelizumab—as first-line intervention in patients with highly active relapsing-remitting multiple sclerosis (RRMS). With a dramatic 97% reduction in annualized relapse rates (ARR), the results underscore the potential of ocrelizumab to reshape therapeutic timing and strategy.

The analysis focused on 33 treatment-naïve RRMS patients drawn from an academic MS outpatient clinic in Germany. All participants had highly active disease as defined by at least two relapses in one year or the presence of numerous or symptomatic MRI lesions. Many patients initiated ocrelizumab within 12 months of diagnosis and were followed for a mean duration of 27.7 months.

Treatment adhered to standard protocols: two initial 300 mg infusions, given two weeks apart, followed by 600 mg infusions every six months. MRI and Expanded Disability Status Scale (EDSS) scores were tracked throughout. Subgroup analyses stratified patients by age, gender, baseline EDSS, and timing of therapy initiation.

Efficacy Anchored in Clinical and Radiological Stability

The study reports a sharp drop in ARR from 2.24 to 0.058 (p < 0.0001) sustained over multiple years with no subgroup variation, representing a 97% reduction in relapse rate. These relapse suppression levels compare favorably not only with the pivotal OPERA trials (ARR 0.16 after two years) but also with their nine-year open-label extension (ARR 0.05), lending further weight to the authors’ position.

Radiological findings reinforced the clinical picture. MRI scans revealed a 90% reduction in new FLAIR lesions and a 94% reduction in gadolinium-enhancing lesions (p < 0.0001 for both) with particularly robust suppression in infratentorial and spinal regions. This radiological quiescence is especially important for patients at risk of rapid neurological decline.

While the median EDSS for the full cohort declined modestly from 2.5 to 2.0, this change did not reach statistical significance. However, patients with baseline EDSS scores <3.0 exhibited a significant reduction in disability over three years (p = 0.03), and those who began therapy within 12 months of symptom onset showed better EDSS trajectories than those with delayed initiation. Although the latter group did not experience statistically significant EDSS worsening, they started with higher disability levels and did not improve, highlighting the narrowing window for maximal functional preservation.

Interestingly, gender and age influenced baseline EDSS, with males and patients over 35 showing higher initial scores, but had no discernible effect on treatment efficacy.

Safety and Tolerability

Adverse events were in line with known ocrelizumab safety profiles. Infusion-related reactions (IRRs) occurred in 55% of infusions—most commonly fatigue (24.6%) and headaches (8.5%). Infections were reported in 21% of patients, all of which were mild. Only one patient discontinued treatment due to recurrent infections, reflecting a discontinuation rate (3%) comparable to clinical trials.

This study contributes a confident, real-world endorsement for initiating ocrelizumab early in highly active RRMS. The modest sample size tempers the generalizability, but the findings echo a broader reevaluation of escalation therapy in favor of upfront high-efficacy interventions. Perhaps most importantly, the data spotlight the value of early EDSS stability and radiological quiescence—both harbingers of long-term functional preservation.

Reference

Kvartskhava T, Freudenstein D, Sarmiento N, Angstwurm K, Linker R, Lee DH. Ocrelizumab as first-line therapy in highly active relapsing-remitting multiple sclerosis. J Neurol Sci. 2025;475:123577. doi:10.1016/j.jns.2025.123577