Ocrelizumab in the Treatment of Multiple Sclerosis – 10-Year Data

Ocrelizumab in MS Patients

Ocrelizumab is an anti-CD20 monoclonal antibody approved for the treatment of relapsing-remitting (RRMS) and primary progressive (PPMS) multiple sclerosis. Currently, more than 300,000 patients worldwide are treated with this drug, administered intravenously once every 6 months. In total, post-marketing surveillance provides experience and data from more than 750,000 patient-years of ocrelizumab exposure.

Significant findings are now available based on a 10-year analysis of long-term safety and efficacy from 2008 to 2020, including the original phase II randomized clinical trial and its open-label extension.

Confirmation of the Importance of Early Treatment Initiation

After 10 years of continuous ocrelizumab treatment, nearly 8 out of 10 RRMS patients and 1/3 of PPMS patients were progression-free as assessed by the EDSS scale. More than 90% of RRMS patients did not require walking aids, and more than 80% of PPMS patients did not need a wheelchair.

Early ocrelizumab treatment extended the progression-free period by almost 10 years in RRMS compared to less effective disease-modifying therapy (DMT). This impact on nearly a decade-long extension of the progression-free period emphasizes the importance of initiating treatment as early as possible across the MS spectrum.

Safety Profile

During the 10-year observation period, ocrelizumab demonstrated a stable and favorable safety profile. The incidence of adverse events (AEs) in the RRMS and PPMS populations remained stable and consistent with the incidence of AEs during the primary clinical trials.

The incidence of serious AEs remained low and stable in the RRMS and PPMS populations, regardless of Ig levels. Adverse effects leading to treatment discontinuation were rare and were not due to serious infections. The most frequent adverse event was an infusion-related reaction.

MRI and Laboratory Efficacy Parameters

Ocrelizumab treatment had a significant impact on brain MRI parameters. The average number of gadolinium-enhancing lesions decreased by 98–99% in the first 6 months of treatment compared to interferon β-1a and placebo and reached zero during the subsequent follow-up in the extension. Overall, the MRI profile across all other modalities remained at a very low activity level over the 10-year period.

After initiating ocrelizumab treatment, there was a rapid depletion of CD19⁺ cells, with a defined threshold for repopulation of these cells at 80/μl. The median time to repopulation to 80 CD19⁺ cells/μl was 72 weeks. The total number of T cells, including CD3⁺, CD3⁺CD4⁺, and CD3⁺CD8⁺ T cell subpopulations, remained unaffected by ocrelizumab treatment. Total Ig levels were reduced in all classes, most notably in the IgG class, and remained consistently low throughout the observation period.

Conclusion

In this longest follow-up of RS patients treated with ocrelizumab to date, no new adverse treatment effects were observed, and there were no signs of rebound phenomena upon treatment discontinuation. With sustained long-term efficacy, there can be discussions about the positive benefit-risk ratio of this treatment modality.

Prof. MUDr. Pavel Štourač, Ph.D.
MS Center, Neurological Clinic LF MU and FN Brno

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