Simulated treatment comparison of efficacy outcomes for ofatumumab in ASCLEPIOS I/II versus ocrelizumab in OPERA I/II for the treatment of patients with relapsing multiple sclerosis.

ABSTRACT

BACKGROUND: Ofatumumab is a subcutaneously administered anti-CD20 monoclonal antibody (MoAb) therapy that has been evaluated in two identically designed randomized controlled trials (RCTs), ASCLEPIOS I (NCT02792218) and ASCLEPIOS II (NCT02792231), in patients with relapsing multiple sclerosis (RMS). Ocrelizumab is another anti-CD20 MoAb therapy, administered intravenously, that has been evaluated in two identically designed RCTs, OPERA I (NCT01247324) and OPERA II (NCT01412333) in RMS. Given the absence of published RCTs with head-to-head comparisons between these MoAbs, this study assessed the indirect comparative efficacy of ofatumumab and ocrelizumab. METHODS: Given the availability of individual patient data for ASCLEPIOS I/II and summary-level data for OPERA I/II, simulated treatment comparisons were used to assess the comparative efficacy of ofatumumab versus ocrelizumab while adjusting for differences in baseline characteristics between trials. Comparative efficacy was estimated for the proportion of patients with 3- and 6-month confirmed disability progression (CDP) and for annualized relapse rate (ARR). Exploratory analyses were conducted for the outcome of no evidence of disease activity based on three parameters (NEDA-3) and magnetic resonance imaging (MRI) outcomes (proportion of patients with gadolinium-enhancing T1 lesions and brain volume change). RESULTS: Although comparative results were not significant for 3-month CDP (hazard ratio [HR] 0.90 [95% confidence interval [CI] 0.57-1.42]) or 6-month CDP (HR 0.84 [95% CI 0.47-1.49]), ofatumumab showed a significant improvement in ARR (rate ratio 0.60 [95% CI 0.43-0.84]) compared with ocrelizumab. Significantly favorable results were also associated with ofatumumab for NEDA-3 and MRI outcomes. CONCLUSION: Ofatumumab was associated with more favorable efficacy results compared with ocrelizumab for clinical, NEDA-3, and MRI outcomes.