1. Patients with multiple sclerosis (MS) treated with ocrelizumab experienced lower annualized relapse rates compared to those treated with interferon beta-1a over a 96-month study.
2. Markers of MS disease progression such as clinical disability scores and identifiable brain lesions on MRI were lower in ocrelizumab treated patients.
Evidence Rating: 1 (Excellent)
Study Rundown: MS is thought to be influenced by B-cells modulating the progression of the disease via various pathological mechanisms. A potential treatment targeting B-cells involved in relapsing forms of MS is ocrelizumab. Ocrelizumab is an antibody that works to deplete B-cells which play a role in MS. This phase 3 study sought to compare MS relapse rates and indicators of disease progression between MS patients treated with ocrelizumab or interferon beta-1a.
Two associated randomized control trials included patients with relapsing MS and no baseline indication of neurologic worsening. Patients were treated with either ocrelizumab or interferon beta-1a for 96 months and followed to assess for clinical indicators of MS relapse and other indicators of disease progression or improvement. Those treated with ocrelizumab experienced significantly lower relapse rates, demonstrated lower rates of clinically assessed disease progression, and showed higher rates of disease improvement. The ocrelizumab group also had significantly fewer brain lesions found on MRI compared to the interferon beta-1a group.
Relevant Reading: Immunopathology of multiple sclerosis
In-Depth [randomized controlled trial]: From 2011 to 2013 two associated yet independent parallel randomized group trials were conducted at a total of 307 study sites. The first trial (OPERA I) included 821 (410 ocrelizumab, 411 interferon beta-1a) patients and the second trial (OPERA II) included 835 (417 ocrelizumab, 418 interferon beta-1a) patients. Results were assessed in both pooled and trial independent analysis. Patients included were 18-55 years old, had a diagnosis of MS, were not severely disabled, had recent episodes of disease relapse, and had not previously received B-cell targeted therapy. Clinical examiners of patients were independent of investigators treating the patients.
Patients were followed for 96 weeks to evaluate their MS state clinically, with MRI, and to identify adverse events. Intention-to-treat analysis showed MS relapse rates significantly lowered in the ocrelizumab groups compared to the interferon beta-1a groups (OPERA I, 0.16 vs 0.29, p < 0.001; OPERA II, 0.16 vs 0.29, p < 0.001). Pooled trial analysis indicated disease progression in the ocrelizumab group was significantly lower in patients at 12 weeks compared to the beta-1a group (9.1% vs 12.6%, HR 0.60, 95%CI 0.45 to 0.81; p < 0.001) Furthermore, disability improvement was greater at 12 weeks in the ocrelizumab group compared to the beta-1a group (20.7% vs 15.6%; p = 0.02). Total mean number of gadolinium-enhancing lesions on MRI were significantly lower in both OPERA I (0.02 vs 0.29, 94% lower number of lesions with ocrelizumab, p < 0.001) and OPERA II (0.02 vs 0.42, 95% lower number of lesions with ocrelizumab, p < 0.001) trials for ocrelizumab treated patients. Serious adverse events were reported in 6.9% and 7.0% of ocrelizumab treated patients and 7.8% and 9.6% of interferon beta-1a treated patients in the OPERA I and II trials, respectively. Rates of infection were 56.9% and 60.2% for ocrelizumab groups and 54.3% and 52.5% for interferon beta-1a groups in the OPERA I and II trials, respectively. More studies will be needed to evaluate whether limitation of disease progression seen in ocrelizumab treated patients can be observed over longer treatment periods.
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