Long-Term Comparative Outcomes in Relapse Activity and Disability Progression Among Anti-CD20 Therapies in Relapsing Multiple Sclerosis: An Unanchored Matching-Adjusted Indirect Comparison

Multiple Sclerosis and Related Disorders, pp. 107953

Abstract

Background Anti-CD20 monoclonal antibodies are widely used in relapsing multiple sclerosis (RMS), but the absence of head-to-head randomized trials limits direct long-term comparisons between agents. Methods An unanchored matching-adjusted indirect comparison (MAIC) was conducted to explore five-year comparative outcomes in annualized relapse rate (ARR) and 24-week confirmed disability progression (CDP24) between ublituximab, ocrelizumab and ofatumumab. Individual patient data from the ULTIMATE I/II trials were reweighted to match published baseline characteristics from the OPERA I/II and ASCLEPIOS I/II trials. Long-term comparator outcomes were obtained from published follow-up data, with reconstruction of comparator patient-level data for time-to-event analyses where required. Sensitivity analyses included restricted mean survival time (RMST) for CDP24. Results MAIC-adjusted ublituximab ARR declined from 0.118 to 0.032 over five years versus ocrelizumab and from 0.116 to 0.030 versus ofatumumab. Ublituximab reduced the CDP24 hazard versus ocrelizumab (hazard ratio [HR] 0.560; 95% CI: 0.380–0.826) and ofatumumab (HR 0.509; 95% CI: 0.350–0.741), with 240-week RMST gains of 8 and 13 weeks, respectively. Conclusions These findings suggest directionally favorable long-term outcomes with ublituximab compared with the other two comparators. These findings should be interpreted carefully within the assumptions and inherent limitations of the unanchored MAIC approach.

Authors 14

1. Ralf Gold

   Ruhr University Bochum

   Affiliation as printed

   Ruhr-University Bochum, Department of Neurology, Bochum, Germany

2. Amir Ansaripour corresponding
   Affiliation as printed

   Optimax Access LTD, Rotterdam, The Netherlands

3. Klaus Schmierer

   Queen Mary University of London · Barts Health NHS Trust

   Affiliation as printed

   Barts Health NHS Trust, The Royal London Hospital, Clinical Board Medicine (Neuroscience), London, UK

   Queen Mary University of London, Faculty of Medicine & Dentistry, The Blizard Institute, Centre for Neuroscience, Surgery & Trauma, London, UK

4. Michael Barnett

   The University of Sydney · Royal Prince Alfred Hospital

   Affiliation as printed

   Royal Prince Alfred Hospital, Sydney, Australia

   University of Sydney, Brain and Mind Centre, Sydney, Australia

5. Hans Peter Hartung

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Heinrich-Heine-University, Düsseldorf, Germany

6. Yamout Bassem

   American University of Beirut Medical Center

   Affiliation as printed

   American University of Beirut Medical Center, Beirut, Lebanon

7. Jérôme de Seze

   Inserm · Université de Strasbourg · Hôpital Civil, Strasbourg

   Affiliation as printed

   CHU de Strasbourg and INSERM CIC-1434,Department of Neurology, Strasbourg, France

8. Krzysztof Selmaj

   University of Warmia and Mazury in Olsztyn

   Affiliation as printed

   University of Warmia and Mazury, Olsztyn, Center of Neurology, Lodz, Poland

9. Diego Centonze

   Istituto Neurologico Mediterraneo

   Affiliation as printed

   IRCCS Neurologico Mediterraneo Neuromed, Unit of Neurology, Pozzilli (IS), Italy

10. Nikolaos Grigoriadis

    Aristotle University of Thessaloniki · AHEPA University Hospital

    Affiliation as printed

    Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

11. Mehdi Javanbakht

    Optimat (United Kingdom)

    Affiliation as printed

    Optimax Access LTD, Southampton, United Kingdom

12. Hari Miskin

    CDG Therapeutics (United States)

    Affiliation as printed

    TG Therapeutics, USA

13. Andreas B. Schmitt Aachen

    Universitätsklinikum Aachen · Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

    Affiliation as printed

    University Hospital of Aachen, Aachen, Neuraxpharm GmbH, Duesseldorf, Germany

14. Gary Cutter corresponding

    University of Alabama at Birmingham

    Affiliation as printed

    University of Alabama, Department of Biostatistics, Birmingham, Alabama, United States