The FDA has approved ocrelizumab for treating relapsing forms of multiple sclerosis and primary progressive multiple sclerosis.
It is estimated that about 10% to 15% of patients with multiple sclerosis (MS) have the primary progressive type (PPMS), characterized by a gradual decline in function from symptom onset without remission.
This March, FDA approved the monoclonal antibody ocrelizumab (Ocrevus) for adult patients with relapsing forms of MS and PPMS. To date, it is the only medication that is FDA approved for the treatment of PPMS.1
The efficacy of ocrelizumab was demonstrated in two identical randomized double-blind double-dummy active-comparator-controlled clinical trials known as OPERA I and OPERA II. A total of 1656 patients were randomized in a 1:1 ratio to receive either ocrelizumab every 24 weeks or the active comparator of interferon beta-1a (Rebif) three times a week for a total treatment duration of 96 weeks. Each group also received a corresponding placebo.2
The primary efficacy endpoint was the annualized relapse rate (ARR) at 96 weeks, which reflects the number of relapses meeting the prespecified criteria that were observed per person-year of follow-up. There was a 46% and 47% lower ARR in the ocrelizumab group compared to the interferon beta-1a group in the OPERA I and OPERA II trials, respectively (P<0.001).2
Additionally, the percentage of patients with disability progression confirmed at 12 weeks and 24 weeks was significantly lower with ocrelizumab than with interferon beta-1a (9.1% vs. 13.6%; 95% confidence interval [CI], 0.45 to 0.81; P<0.001) and (6.9% vs. 10.5%; 95% CI, 0.43 to 0.84; P=0.003), respectively. Patients receiving ocrelizumab also showed a significant reduction in gadolinium-enhancing lesions on MRI scans in both trials (94% reduction and 95% reduction, respectively).
Finally, the MS functional composite score significantly favored the ocrelizumab group in OPERA 2 although there was no difference in groups in OPERA 1.2
The most common adverse effects in clinical trials were upper respiratory tract infections (40% to 49%) and infusion reactions (34% to 40%).3
Ocrelizumab carries warnings for increased risk of herpes, hepatitis B reactivation, and progressive multifocal leukoencephalopathy. It should not be used in patients with active hepatitis B infection. Other adverse events seen in trials include skin or lower respiratory tract infections, cough, diarrhea, peripheral edema, and back pain.3
The first dose of ocrelizumab is administered as two intravenous infusions of 300 mg separated by 2 weeks. All subsequent doses are administered as a single 600-mg infusion every 6 months. The rate of the infusion should start at 30 ml/hr and can be titrated by 30 ml/hr every 30 minutes as tolerated, to a maximum rate of 180 ml/hr.
Patients should be observed for at least one hour after the completion of the infusion to ensure there are no infusion reactions. If a scheduled infusion is missed, the patient should receive the drug as soon as possible rather than waiting for the next scheduled infusion. The dosing schedule can then be reset to make sure that there are at least five months separating doses.3
1. U.S. Food and Drug Administration. FDA Approves New Drug to Treat Multiple Sclerosis. ; 2017 March 29. Accessed June 6, 2017 June6. Available at http://bit.ly/2qWxl52.
2. Hauser SL, Bar-Or A, Comi G, et al. OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017. Jan 19;376(3):221-234
3. Ocrevus [package insert]. South San Francisco, CA: Genentech, Inc; 2017.