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

Imtiaz A Samjoo; Luisa Klotz; Gavin Giovannoni; Christopher Drudge; Anja Haltner; Evelyn Worthington; Melody Zhao; Róisín Brennan; Dieter A Häring; Chris Cameron; Nicholas Adlard

doi:10.1016/j.msard.2022.104031

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

Mult Scler Relat Disord. 2022 Oct:66:104031. doi: 10.1016/j.msard.2022.104031. Epub 2022 Jul 4.

Authors

Affiliations

¹ EVERSANA™, Burlington, Ontario, Canada.
² Department of Neurology, University Hospital Münster, Münster, Germany.
³ Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁴ EVERSANA™, Sydney, Nova Scotia, Canada.
⁵ Novartis Ireland, Dublin, Ireland.
⁶ Novartis Pharma AG, Basel 4002, Switzerland.
⁷ Novartis Pharma AG, Basel 4002, Switzerland. Electronic address: nicholas.adlard@novartis.com.

PMID: 35841716
DOI: 10.1016/j.msard.2022.104031

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.

Keywords: Indirect treatment comparison; Ocrelizumab; Ofatumumab; Relapsing multiple sclerosis; Simulated treatment comparison.

MeSH terms

Antibodies, Monoclonal, Humanized* / therapeutic use
Gadolinium / therapeutic use
Humans
Immunologic Factors / therapeutic use
Multiple Sclerosis, Relapsing-Remitting* / drug therapy
Randomized Controlled Trials as Topic

Substances

Antibodies, Monoclonal, Humanized
Gadolinium
Immunologic Factors
ocrelizumab
ofatumumab