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Multiple sclerosis
Original research
Comparing ocrelizumab to interferon/glatiramer acetate in people with multiple sclerosis over age 60
  1. Yi Chao Foong1,2,3,
  2. Daniel Merlo1,4,
  3. Melissa Gresle1,2,5,
  4. Katherine Buzzard4,6,
  5. Michael Zhong1,2,
  6. Wei Zhen Yeh1,2,
  7. Vilija Jokubaitis1,2,
  8. Mastura Monif1,2,
  9. Olga Skibina2,4,
  10. Serkan Ozakbas,7,
  11. Francesco Patti8,9,
  12. Pierre Grammond10,
  13. Maria Pia Amato11,
  14. Tomas Kalincik6,12,
  15. Dana Horakova13,
  16. Eva Kubala Havrdova13,
  17. Bianca Weinstock-Guttman14,
  18. Jeanette Lechner Scott15,16,
  19. Cavit Boz17,
  20. Maria Jose Sa18,19,
  21. Helmut Butzkueven1,2,
  22. Anneke van der Walt1,2,
  23. Chao Zhu1
  24. on behalf of MSBASE study group
    1. 1 Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia
    2. 2 Alfred Health, Melbourne, Victoria, Australia
    3. 3 Department of Neurology, Tasmanian Health Service, Hobart, Tasmania, Australia
    4. 4 Eastern Health, Box Hill, Victoria, Australia
    5. 5 Melbourne Health, Melbourne, Victoria, Australia
    6. 6 Department of Neurology, The Royal Melbourne Hospital, Parkville, Victoria, Australia
    7. 7 Medical Point Hospital, Izmir, Turkey
    8. 8 Neuroscience, University of Catania Department of Surgical and Medical Sciences and Advanced Technologies 'G.F. Ingrassia', Catania, Italy
    9. 9 University of Catania, Catania, Italy
    10. 10 Hotel-Dieu de Levis, Levis, Quebec, Canada
    11. 11 Department of Neurological Siences, University of Florence, Florence, Italy
    12. 12 CORe, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
    13. 13 Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic
    14. 14 Neurology, Jacobs Comprehensive MS Treatment and Research Center, Buffalo, New York, USA
    15. 15 Hunter New England Health, New Lambton, New South Wales, Australia
    16. 16 The University of Newcastle, Newcastle, New South Wales, Australia
    17. 17 Karadeniz Technical University, Trabzon, Turkey
    18. 18 Neurology, Centro Hospitalar de São João, Porto, Portugal
    19. 19 Faculty of Health Sciences University Fernando Pessoa, Porto, Portugal
    1. Correspondence to Dr Anneke van der Walt; anneke.vanderwalt{at}monash.edu

    Abstract

    Background Ongoing controversy exists regarding optimal management of disease modifying therapy (DMT) in older people with multiple sclerosis (pwMS). There is concern that the lower relapse rate, combined with a higher risk of DMT-related infections and side effects, may alter the risk-benefit balance in older pwMS. Given the lack of pwMS above age 60 in randomised controlled trials, the comparative efficacy of high-efficacy DMTs such as ocrelizumab has not been shown in older pwMS. We aimed to evaluate the comparative effectiveness of ocrelizumab, a high-efficacy DMT, versus interferon/glatiramer acetate (IFN/GA) in pwMS over the age of 60.

    Methods Using data from MSBase registry, this multicentre cohort study included pwMS above 60 who switched to or started on ocrelizumab or IFN/GA. We analysed relapse and disability outcomes after balancing covariates using an inverse probability treatment weighting (IPTW) method. Propensity scores were obtained based on age, country, disease duration, sex, baseline Expanded Disability Status Scale, prior relapses (all-time, 12 months and 24 months) and prior DMT exposure (overall number and high-efficacy DMTs). After weighting, all covariates were balanced. Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP) and confirmed disability improvement (CDI).

    Results A total of 248 participants received ocrelizumab, while 427 received IFN/GA. The IPTW-weighted ARR for ocrelizumab was 0.01 and 0.08 for IFN/GA. The IPTW-weighted ARR ratio was 0.15 (95% CI 0.06 to 0.33, p<0.001) for ocrelizumab compared with IFN/GA. On IPTW-weighted Cox regression models, HR for time to first relapse was 0.13 (95% CI 0.05 to 0.26, p<0.001). The hazard of first relapse was significantly reduced in ocrelizumab users after 5 months compared with IFN/GA users. However, the two groups did not differ in CDP or CDI over 3.57 years.

    Conclusion In older pwMS, ocrelizumab effectively reduced relapses compared with IFN/GA. Overall relapse activity was low. This study adds valuable real-world data for informed DMT decision making with older pwMS. Our study also confirms that there is a treatment benefit in older people with MS, given the existence of a clear differential treatment effect between ocrelizumab and IFN/GA in the over 60 age group.

    • MULTIPLE SCLEROSIS
    • STATISTICS
    • NEUROEPIDEMIOLOGY
    • GERIATRICS

    Data availability statement

    Data are available upon reasonable request. In principle, patient-level data sharing is possible. However, permission from each contributing data controller is required.

    https://doi.org/10.1136/jnnp-2023-332883

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      Data availability statement

      Data are available upon reasonable request. In principle, patient-level data sharing is possible. However, permission from each contributing data controller is required.

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      Footnotes

      • HB, AvdW and CZ are joint senior authors.

      • X @foongahh

      • Collaborators MSBASE study group.

      • Contributors YCF performed the statistical analyses, interpreted the results, drafted, revised the manuscript and acts as the study guarantor. HB, CZ and AvdW contributed to study design, data collection, designed the statistical analyses, interpreted the results, edited and reviewed the manuscript. MG, CZ and DM contributed to the study design, interpreted the results and edited and reviewed the manuscript. KB, MZ, WZY, VJ, MM, OS, SO, FP, PG, MPA, TK, DH, EKH, BW-G, JLS, CB and MJS contributed data, interpreted the results and edited and reviewed the manuscript.

      • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

      • Competing interests YCF received travel compensation from Biogen, National Health and Medical Research Council, Multiple Sclerosis Research Australia and Australian and New Zealand Association of Neurologists. MG is currently working on observational studies funded by Biogen and Roche. DM has received honoraria from Novartis. CZ has nothing to disclose. KB has received honoraria for presentations and/or educational support from Biogen, Sanofi Genzyme, Merck, Roche, Alexion and Teva and serves on medical advisory boards for Merck and Biogen. MZ has received conference travel support from Novartis and Roche, and research support from the Australian Government Research Training Program and MS Research Australia. WZY: received honoraria from Merck and Novartis. VJ receives research grant support form F.Hoffmann La-Roche, MS Research Australia and the National Health and Medical Research Council of Australia (NHMRC 1156519). MM has received research support from National Health and Medical Research Council, Medical Research Future Fund, Brain Foundation, Charles and Sylvia Viertel Foundation, MS Research Australia, Merck and Ku Leuven University, served on advisory board for Merck, has received speaker honoraria from Merck and Biogen. OS received honoraria and consulting fees from Bayer Schering, Novartis, Merck, Biogen and Genzyme. SO has nothing to disclose. FP received personal compensation for serving on advisory board by Almirall, Alexion, Biogen, Bristol, Merck, Novartis and Roche and received research grant by Biogen, Merck and Roche and by FISM, Reload Association (Onlus), Italian Health Minister, University of Catania. PG has served in advisory boards for Novartis, EMD Serono, Roche, Biogen idec, Sanofi Genzyme, Pendopharm and has received grant support from Genzyme and Roche, has received research grants for his institution from Biogen idec, Sanofi Genzyme, EMD Serono. MPA received honoraria as consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck, Teva and Sanofi-Aventis and has received research grants by Biogen, Bayer-Schering, Merck, Teva and Novartis. TK served on scientific advisory boards for MS International Federation and WHO, BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. DH supported by the Charles University: Cooperatio Programme in Neuroscience, by the project National Institute for Neurological Research (Programme EXCELES, ID Project No. LX22NPO5107)—funded by the European Union – Next Generation EU, General University Hospital in Prague project MH CZ-DRO-VFN64165 and received compensation for travel, speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche, and Teva, as well as support for research activities from Biogen Inc. EKH received honoraria/research support from Biogen, Merck Serono, Novars, Roche, and Teva; has been member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novars, and Sanofi Genzyme; received honoraria/research support from Biogen, Merck Serono, Novars, Roche, and Teva; has been member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novars and Sanofi Genzyme; and has been supported by the Czech Ministry of Education—project Cooperatio LF1, research area Neuroscience, and the project National Institute for Neurological Research (Programme EXCELES, ID project No LX22NPO5107)—funded by the European Union-Next Generation EU. BW-G participated in speaker’s bureaus and/or served as a consultant and received grants from Biogen, EMD Serono, Novartis, Genentech, Celgene/Bristol Meyers Squibb, Sanofi Genzyme, Bayer, Janssen and Horizon; she also serves in the editorial board for BMJ Neurology, Children, CNS Drugs, MS International and Frontiers Epidemiology. JLS received travel compensation from Novartis, Biogen, Roche and Merck and her institution receives the honoraria for talks and advisory board commitment as well as research grants from Biogen, Merck, Roche, TEVA and Novartis. CB received conference travel support from Biogen, Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis. MJS: Received consulting fees, speaker honoraria, and/or travel expenses for scientific meetings from Alexion, Bayer Healthcare, Biogen, Bristol Myers Squibb, Celgene, Janssen, Merck-Serono, Novartis, Roche, Sanofi and Teva. AvdW served on advisory boards for Novartis, Biogen, Merck and Roche and NervGen, received research grants from National Health and Medical Research Council of Australia, MS Research Australia, Novartis, Biogen, Merck and Roche, received speaker’s honoraria and travel support from Novartis, Roche, Biogen and Merck and is currently a coprincipal investigator on a cosponsored observational study with Roche. HB’s Institution has received compensation for advisory boards or lecture fees from Novartis, Biogen, Merck, UCB Pharma and Roche and receives research funding from Novartis, Biogen, Merck, Roche, The National Health and Medical Research Council of Australia, The Medical Research Future Fund (Australia), Monash Partners, the Trish MS Foundation, The Pennycook Foundation, and MS Australia; he also receives personal compensation as the Managing Director of the MSBase Foundation and from the Oxford Health Policy Forum Brain Health Initiative.

      • Provenance and peer review Not commissioned; externally peer reviewed.