Real-World Discontinuations of Ocrelizumab in MS Comparable to Pivotal Trials

Real-world discontinuation rates of ocrelizumab (Ocrevus) among patients receiving the treatment for their multiple sclerosis (MS) closely resembles data coming from pivotal trials of the drug, suggests a new analysis published in Neurology and Therapy.¹

The analysis of 30 studies on real-world use of the monoclonal antibody show that discontinuations of ocrelizumab are low, similar to that seen in the 3 pivotal trials of ocrelizumab: OPERA I (NCT01247324), OPERA II (NCT01412333), and ORATORIO (NCT01194570). Patients with relapsing remitting MS (RRMS) and primary progressive MS (PPMS) were included, showing discontinuation rates of 3.2%-4.1%.

Ocrelizumab is approved as an IV infusion for relapsing and primary progressive forms of MS and as a subcutaneous injection, given twice a year. | Image credit: Trsakaoe - stock.adobe.com

Ocrelizumab is approved as an intravenous (IV) infusion for relapsing and primary progressive forms of MS. In September 2024, the treatment gained FDA approval as a subcutaneous injection, given twice a year.^2,3

All but 1 of the studies included in the analysis showed comparable, if not lower, rates of discontinuation among patients with RRMS and PPMS.¹

“Only 1 study reported higher discontinuation rates due to adverse events compared with the clinical trials; mean disease duration in this study was higher than in the OPERA I and II clinical trials (12.5 years vs. 6.7 years), as was the mean age of the patients (49.8 vs. 37.1 and 37.2, respectively), which may be factors in the seemingly high discontinuation rate,” explained the researchers.

The group noted that the rate of discontinuation was 7% among patients aged 55 years or older, compared with the 4.7% discontinuation rate observed amongst the full patient population included in the study.

There were 7 studies of 18 to 439 patients that had no discontinuations reported over 6 to 18 months of follow-up, and in studies that reported on median time to discontinuation, discontinuation occurred after a median of 0.6 to 1.8 years. The researchers noted that the varying prevalence of discontinuations across studies is expected given patient differences across studies.

The studies included in the analysis reported on a variety of patients, with data coming from the United States, Europe, the Middle East, and South America. All 30 studies followed the Population, Intervention, Comparison, Outcomes, and Study criteria, though some were limited in available data, including in several conference abstracts.

Side effects were most commonly reported as the reason for treatment discontinuation, noted in 11 studies, following by concerns over efficacy reported in 8 studies, and pregnancy or family planning reported in 6 studies.

In a study comparing ocrelizumab with rituximab, significantly more patients discontinued ocrelizumab due to a side effects (9.3% vs 2.6%; P < .01), though the number of patients discontinuing due to a side effect was small (15 for ocrelizumab and 8 for rituximab). The researchers also noted that within the study, those receiving ocrelizumab had RRMS while those receiving rituximab had either RRMS or secondary progressive MS. Overall, there was no statistically significant difference in discontinuation within the first year of treatment with ocrelizumab or rituximab (15% and 10%, respectively; P = .11).

“Three additional studies were identified that reported comparative analysis of ocrelizumab discontinuation and adherence with other therapies, but these studies did not specify the MS patient population and therefore did not meet the inclusion criteria of this SLR,” wrote the researchers.“Nevertheless, 1 of these studies found that the risk of discontinuation was higher for other DMTs versus ocrelizumab, across all types of administration (oral, injectable, and infusion).”

Across the other 2 studies, ocrelizumab yielded higher adherence and lower discontinuations compared with other IV treatments, as well as injectable or oral treatments.

References

1. Petrie JL, Smith CA, Fountain D, Machnicki G. Real-world persistence with ocrelizumab in multiple sclerosis: a systematic review. Neurol Ther. 2024;13:1597-1605. doi:10.1007/s40120-024-00667-w
2. FDA approved Genentech’s OCREVUS (ocrelizumab) for relapsing and primary progressive forms of multiple sclerosis. News release. Genentech; March 28, 2017. https://www.gene.com/media/press-releases/14657/2017-03-28/fda-approves-genentechs-ocrevus-ocrelizu
3. FDA approves Ocrevus Zunovo as the first and only twice-a-year 10-minute subcutaneous injection for people with relapsing and progressive multiple sclerosis. News release. Genentech; September 13, 2024. https://www.gene.com/media/press-releases/15036/2024-09-13/fda-approves-ocrevus-zunovo-as-the-first