Effect of Ocrelizumab on Humoral Immunity Markers in the Phase III, Double-Blind, Double-Dummy, IFNß-1a–Controlled OPERA I and OPERA II Studies
Objectives: To assess the effect of OCR on specific humoral immunity in 2 identical Phase III, randomized, double-blind, double-dummy, IFN-beta-1a (IFNβ-1a)-controlled trials in relapsing multiple sclerosis (OPERA I and OPERA II).
Methods: In OPERA I and OPERA II, patients were randomized 1:1 to receive OCR 600 mg via intravenous infusion every 24 weeks or subcutaneous IFNβ-1a 44 μg three-times weekly over the 96-week study treatment period. Prior to study enrollment, physicians were advised to review patient immunization status and follow local guidance for vaccination; immunizations were to be completed ≥ 6 weeks prior to treatment. Measurements of antibody (Ab) titers against mumps, rubella, varicella, and Streptococcus pneumoniaewere taken at baseline and at Weeks 12, 24, 48, 72, and 96. The proportion of patients with Ab levels that could be considered protective was assessed for each treatment group over time.
Results: The pooled safety analysis of the OPERA I and OPERA II studies included 826 IFNβ-1a–treated and 825 OCR-treated patients. At baseline, 94.1% and 93.6% of the IFNβ-1a and OCR groups, respectively, had positive levels of mumps Ab; this proportion ranged (min–max) 92.7–94.8% and 91.8–93.5% over the 6 measurements taken during the 96-week study treatment period. Positive rubella Ab levels were seen among 87.9% and 89.0% of the IFNβ-1a and OCR groups, respectively, at baseline and ranged 89.8–90.8% and 88.7–89.4% over the treatment period. Positive varicella Ab levels were seen in 95.5% of both treatment groups at baseline and ranged 96.2–97.5% and 94.8–95.6% over the treatment period in the IFNβ-1a and OCR groups, respectively. Among the evaluable patients, the mean (standard deviation) level of S. pneumoniaeAb was 53.67 (54.13) mg/L and 55.35 (67.00) mg/L at baseline; at 96 weeks, the mean change from baseline was −1.13 (40.25) mg/L and −1.99 (59.60) mg/L in the IFNβ-1a and OCR groups, respectively.
Conclusions: In OPERA I and OPERA II, Ab titers against common viral and bacterial antigens were similar between the IFNβ-1a and OCR groups at baseline and were maintained during the 96-week study treatment period. Treatment with OCR does not appear to affect preexisting humoral immunity.
Supported by F. Hoffmann-La Roche Ltd.