Efficacy classification of modern therapies in multiple sclerosis
Publication: Journal of Comparative Effectiveness Research
Abstract
Background: The Association of British Neurologists (ABN) 2015 guidelines suggested classifying multiple sclerosis therapies according to their average relapse reduction. We sought to classify newer therapies (cladribine, ocrelizumab, ofatumumab, ozanimod) based on these guidelines. Materials & methods: Therapies were classified by using direct comparative trial results as per ABN guidelines and generating classification probabilities for each therapy based on comparisons versus placebo in a network meta-analysis for annualized relapse rate. Results: For both approaches, cladribine and ofatumumab were classified as high efficacy. Ocrelizumab and ozanimod (1.0 mg) were classified as moderate or high efficacy depending on the approach used. Conclusion: Cladribine and ofatumumab have an efficacy comparable with therapies classified in the ABN guidelines as high efficacy.
Formats available
You can view the full content in the following formats:
Supplementary Material
File (supplementary materials.docx)
- Download
- 240.91 KB
References
Papers of special note have been highlighted as: • of interest; •• of considerable interest
1.
Compston A, Coles A. Multiple sclerosis. Lancet 372(9648), 1502–1517 (2008).
2.
Lublin FD, Reingold SC, Cohen JA et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 83(3), 278–286 (2014).
3.
European Medicines Agency. Clinical investigation of medicinal products for the treatment of multiple sclerosis. (2015). https://www.ema.europa.eu/en/clinical-investigation-medicinal-products-treatment-multiple-sclerosis
4.
Gajofatto A, Benedetti M. Treatment strategies for multiple sclerosis: when to start, when to change, when to stop? World J. Clin. Cases 3(7), 545–555 (2015).
5.
Rae-Grant A, Day GS, Marrie RA et al. Practice guideline recommendations summary: disease-modifying therapies for adults with multiple sclerosis. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 90(17), 777–788 (2018).
6.
Scolding N, Barnes D, Cader S et al. Association of British Neurologists: revised (2015) guidelines for prescribing disease-modifying treatments in multiple sclerosis. Pract. Neurol. 15(4), 273–279 (2015).
•• Multiple sclerosis (MS) treatment guidelines from the Association of British Neurologists, which provided the basis for this study.
7.
Marques VD, Passos GRD, Mendes MF et al. Brazilian consensus for the treatment of multiple sclerosis: Brazilian Academy of Neurology and Brazilian Committee on Treatment and Research in Multiple Sclerosis. Arq. Neuropsiquiatr. 76, 539–554 (2018).
8.
Montalban X, Gold R, Thompson AJ et al. ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis. Multiple Scler. J. 24(2), 96–120 (2018).
9.
Giovannoni G, Comi G, Cook S et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N. Engl. J. Med. 362(5), 416–426 (2010).
• The CLARITY trial was a pivotal Phase III cladribine trial investigating cladribine (3.5 or 5.25 mg/kg cumulative dose) versus placebo in patients with relapsing–remitting MS.
10.
Hauser SL, Bar-Or A, Comi G et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N. Engl. J. Med. 376(3), 221–234 (2017).
• The OPERA I and II trials were pivotal Phase III ocrelizumab trials investigating ocrelizumab versus IFN-β-1a in patients with relapsing MS.
11.
Hauser SL, Bar-Or A, Cohen J et al. Efficacy and safety of ofatumumab versus teriflunomide in relapsing multiple sclerosis: results of the phase 3 ASCLEPIOS I and II trials. Presented at: ECTRIMS 2019. Stockholm, Sweden (2019).
• The ASCLEPIOS I and II trials were pivotal Phase III ofatumumab trials investigating ofatumumab versus teriflunomide in patients with relapsing MS.
12.
Cohen JA, Comi G, Selmaj KW et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, Phase III trial. Lancet Neurol. 18(11), 1021–1033 (2019).
• The RADIANCE trial was a pivotal Phase III ozanimod trial investigating ozanimod (0.5 or 1.0 mg dose) versus IFN-β-1a in patients with relapsing MS.
13.
Comi G, Kappos L, Selmaj KW et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, Phase III trial. Lancet Neurol. 18(11), 1009–1020 (2019).
• The SUNBEAM trial was a pivotal Phase III ozanimod trial investigating ozanimod (0.5 or 1.0 mg dose) versus IFN-β-1a in patients with relapsing MS.
14.
Merkel B, Butzkueven H, Traboulsee AL, Havrdova E, Kalincik T. Timing of high-efficacy therapy in relapsing–remitting multiple sclerosis: a systematic review. Autoimmun. Rev. 16(6), 658–665 (2017).
15.
Rotstein DL, Healy BC, Malik MT, Chitnis T, Weiner HL. Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort. JAMA Neurol. 72(2), 152–158 (2015).
16.
Utz KS, Hoog J, Wentrup A et al. Patient preferences for disease-modifying drugs in multiple sclerosis therapy: a choice-based conjoint analysis. Ther. Adv. Neurol. Disord. 7(6), 263–275 (2014).
17.
National Institute for Health and Care Excellence. Single technology appraisal: user guide for company evidence submission template. (2017). https://www.nice.org.uk/process/pmg24/chapter/instructions-for-companies
18.
Moher D, Liberati A, Tetzlaff J, Altman DG. Group ATP. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann. Intern. Med. 151(4), 264–269 (2009).
19.
Samjoo IA, Worthington E, Drudge C et al. Comparison of ofatumumab and other disease-modifying therapies for relapsing multiple sclerosis: a network meta-analysis. J. Comp. Eff. Res. 9(18), 1255–1274 (2020).
20.
Hoaglin DC, Hawkins N, Jansen JP et al. Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2. Value Health 14(4), 429–437 (2011).
21.
Jansen JP, Fleurence R, Devine B et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1. Value Health 14(4), 417–428 (2011).
22.
Jansen JP, Naci H. Is network meta-analysis as valid as standard pairwise meta-analysis? It all depends on the distribution of effect modifiers. BMC Med. 11(1), 159 (2013).
23.
Institute for Clinical and Economic Review. Disease-modifying therapies for relapsing–remitting and primary-progressive multiple sclerosis: effectiveness and value. (2017).
24.
Lucchetta RC, Tonin FS, Borba HHL et al. Disease-modifying therapies for relapsing–remitting multiple sclerosis: a network meta-analysis. CNS Drugs 32(9), 813–826 (2018).
25.
McCool R, Wilson K, Arber M et al. Systematic review and network meta-analysis comparing ocrelizumab with other treatments for relapsing multiple sclerosis. Multiple Scler. Relat. Disord. 29, 55–61 (2019).
26.
Siddiqui MK, Khurana IS, Budhia S, Hettle R, Harty G, Wong SL. Systematic literature review and network meta-analysis of cladribine tablets versus alternative disease-modifying treatments for relapsing–remitting multiple sclerosis. Curr. Med. Res. Opin. 34(8), 1361–1371 (2018).
27.
Dias S, Sutton AJ, Ades A, Welton NJ. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med. Decis. Making 33(5), 607–617 (2013).
28.
Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res. Synth. Meth. 1(2), 97–111 (2010).
29.
Spiegelhalter D, Thomas A, Best N. WinBUGS User Manual. MRC Biostat Unit, Cambridge, UK (2004). https://www.mrc-bsu.cam.ac.uk/wp-content/uploads/manual14.pdf
30.
Cree BaC, Corboy J, Singer B et al. Efficacy and safety of fingolimod versus glatiramer acetate in patients with relapsing–remitting multiple sclerosis in the ASSESS study. Presented at: 2019 Consortium of Multiple Sclerosis Centers Annual Meeting. Seattle, WA, USA (2019).
31.
Calabresi PA, Kieseier BC, Arnold DL et al. Pegylated interferon beta-1a for relapsing–remitting multiple sclerosis (ADVANCE): a randomised, Phase III, double-blind study. Lancet Neurol. 13(7), 657–665 (2014).
32.
Durelli L, Verdun E, Barbero P et al. Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN). Lancet 359(9316), 1453–1460 (2002).
33.
National Institute for Health and Care Excellence. Technology appraisal guidance TA533: ocrelizumab for treating relapsing–remitting multiple sclerosis. (2018). https://www.nice.org.uk/guidance/ta533
34.
Vartanian T. An examination of the results of the EVIDENCE, INCOMIN, and Phase III studies of interferon beta products in the treatment of multiple sclerosis. Clin. Ther. 25(1), 105–118 (2003).
35.
Boiko AN, Lashch NY, Sharanova SN et al. A comparative placebo-controlled clinical trial of the efficacy and safety of glatiramer acetate 20 mg in patients with remitting multiple sclerosis: first-year study results. Neurosci. Behav. Physiol. 48(3), 351–357 (2018).
36.
CAMMS223 Trial Investigators. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N. Engl. J. Med. 359(17), 1786–1801 (2008).
37.
Cohen JA, Coles AJ, Arnold DL et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing–remitting multiple sclerosis: a randomised controlled Phase III trial. Lancet 380(9856), 1819–1828 (2012).
38.
Coles AJ, Twyman CL, Arnold DL et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled Phase III trial. Lancet 380(9856), 1829–1839 (2012).
39.
Fox RJ, Miller DH, Phillips JT et al. Placebo-controlled Phase III study of oral BG-12 or glatiramer in multiple sclerosis. N. Engl. J. Med. 367(12), 1087–1097 (2012).
40.
Gold R, Kappos L, Arnold DL et al. Placebo-controlled Phase III study of oral BG-12 for relapsing multiple sclerosis. N. Engl. J. Med. 367(12), 1098–1107 (2012).
41.
Kappos L, Radue E-W, O'Connor P et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N. Engl. J. Med. 362(5), 387–401 (2010).
42.
Calabresi PA, Radue E-W, Goodin D et al. Safety and efficacy of fingolimod in patients with relapsing–remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, Phase III trial. Lancet Neurol. 13(6), 545–556 (2014).
43.
Cohen JA, Barkhof F, Comi G et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N. Engl. J. Med. 362(5), 402–415 (2010).
44.
O'Connor P, Filippi M, Arnason B et al. 250 microg or microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing–remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol. 8(10), 889–897 (2009).
45.
Bornstein MB, Miller A, Slagle S et al. A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis. N. Engl. J. Med. 317(7), 408–414 (1987).
46.
Calabrese M, Bernardi V, Atzori M et al. Effect of disease-modifying drugs on cortical lesions and atrophy in relapsing–remitting multiple sclerosis. Multiple Scler. J. 18(4), 418–424 (2012).
47.
Lublin FD, Cofield SS, Cutter GR et al. Randomized study combining interferon and glatiramer acetate in multiple sclerosis. Ann. Neurol. 73(3), 327–340 (2013).
48.
Johnson KP, Brooks BR, Cohen JA et al. Copolymer 1 reduces relapse rate and improves disability in relapsing–remitting multiple sclerosis: results of a Phase III multicenter, double-blind, placebo-controlled trial. Neurology 45(7), 1268–1276 (1995).
49.
Mikol DD, Barkhof F, Chang P et al. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurol. 7(10), 903–914 (2008).
50.
Khan O, Rieckmann P, Boyko A, Selmaj K, Zivadinov R. GALA Study Group. Three times weekly glatiramer acetate in relapsing–remitting multiple sclerosis. Ann. Neurol. 73(6), 705–713 (2013).
51.
Vollmer TL, Sorensen PS, Selmaj K et al. A randomized placebo-controlled Phase III trial of oral laquinimod for multiple sclerosis. J. Neurol. 261(4), 773–783 (2014).
52.
Jacobs LD, Cookfair DL, Rudick RA et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann. Neurol. 39(3), 285–294 (1996).
53.
Stępień A, Chalimoniuk M, Lubina-Dąbrowska N, Chrapusta SJ, Galbo H, Langfort J. Effects of interferon beta-1a and interferon beta-1b monotherapies on selected serum cytokines and nitrite levels in patients with relapsing–remitting multiple sclerosis: a 3-year longitudinal study. Neuroimmunomodulation 20(4), 213–222 (2013).
54.
Ebers GC. PRISMS Study Group. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet 352(9139), 1498–1504 (1998).
55.
Panitch H, Goodin DS, Francis G et al. Randomized, comparative study of interferon beta-1a treatment regimens in MS: the EVIDENCE trial. Neurology 59(10), 1496–1506 (2002).
56.
IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing–remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43(4), 655–655 (1993).
57.
Polman CH, O'Connor PW, Havrdova E et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. 354(9), 899–910 (2006).
58.
O'Connor P, Wolinsky JS, Confavreux C et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N. Engl. J. Med. 365(14), 1293–1303 (2011).
59.
Vermersch P, Czlonkowska A, Grimaldi LM et al. Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled Phase III trial. Multiple Scler. J. 20(6), 705–716 (2014).
60.
Confavreux C, O'Connor P, Comi G et al. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, Phase III trial. Lancet Neurol. 13(3), 247–256 (2014).
Information & Authors
Information
Published In
Pages: 495 - 507
PubMed: 33620251
Copyright
© 2021 Chris Cameron. This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License
History
Received: 1 December 2020
Accepted: 5 February 2021
Published online: 23 February 2021
Keywords:
Topics
Authors
Funding Information
Novartis
Metrics & Citations
Metrics
Article Usage
Article usage data only available from February 2023. Historical article usage data, showing the number of article downloads, is available upon request.
Citations
How to Cite
Efficacy classification of modern therapies in multiple sclerosis. (2021) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2020-0267
Export citation
Select the citation format you wish to export for this article or chapter.
Citing Literature
- Alessia Cipriani, Matteo Polsinelli, Giuseppe Placidi, AI and radiomics for improving the medical workflow for Multiple Sclerosis, Computer Methods and Programs in Biomedicine, 10.1016/j.cmpb.2026.109475, 285, (109475), (2026).
- Mitra Pourseirafi, Seyed Reza Mousavi, Anoosha Niazmand, Neda Hosseini, Nasimeh Vatandoost, Mansoor Salehi, Uncovering the role of microRNAs in response to interferon-beta therapy among multiple sclerosis patients: A systematic review, Multiple Sclerosis and Related Disorders, 10.1016/j.msard.2026.107265, 111, (107265), (2026).
- Jasmin Wich, Tatjana Beppler, Michelle Dreiling, André Scherag, Matthias Schwab, Florian Rakers, Real-world effectiveness of high-efficacy therapies in multiple sclerosis: a propensity score-matched cohort study, Frontiers in Neurology, 10.3389/fneur.2026.1773074, 17, (2026).
- Yanisa Chumpangern, Yanika Seawsirikul, Panisara Keatbundit, Leeyaporn Thongtem, Ekdanai Uawithya, Roongnapa Khampang, Tatchaporn Ongphichetmetha, Sasitorn Siritho, Naraporn Prayoonwiwat, Jiraporn Jitprapaikulsan, The efficacy of disease-modifying therapies in patients with clinically isolated syndrome: a systematic review and network meta-analysis, Scientific Reports, 10.1038/s41598-026-43240-1, 16, 1, (2026).
- Xiang Wang, Fei-li Zhao, David Newby, Shuchuen Li, Evaluating use of disease-modifying therapies for multiple sclerosis using claims data, Frontiers in Health Services, 10.3389/frhs.2026.1714922, 6, (2026).
- Pedro César de Souza, Thaynara Paula Warren Bezerra, Moacyr Jesus Barreto de Melo Rêgo, Michelle Melgarejo da Rosa, Advances in neurological therapies: A review of clinical trials in Alzheimer’s, Parkinson’s, and multiple sclerosis, The American Journal of Medicine, 10.1016/j.amjmed.2025.11.025, 139, 3, (264-275), (2026).
- Alessandro Miscioscia, Constantina A Treaba, Elena Barbuti, Valeria T Barletta, Jacob A Sloane, Eric C Klawiter, Julien Cohen-Adad, Paolo Gallo, Patrizia Pantano, Caterina Mainero, Spinal cord versus brain imaging biomarkers of multiple sclerosis trajectory combining 7T and 3T MRI, Brain Communications, 10.1093/braincomms/fcag059, 8, 2, (2026).
- Simone Marcheselli, Federica Galota, Patrizia Natali, Francesco Corrado, Alessia Fiore, Francesca Vitetta, Krzysztof Smolik, Giulia De Napoli, Martina Cardi, Diana Ferraro, Kappa Index predicts disease activity and transition to high-efficacy therapies in multiple sclerosis, Clinical Chemistry and Laboratory Medicine (CCLM), 10.1515/cclm-2025-1339, 64, 5, (1093-1101), (2025).
- Daria D. Eliseeva, Ekaterina V. Baydina, Taras O. Simaniv, Lola Sh. Askarova, Julia E. Korzhova, Inessa V. Zakroyshchikova, Ivan A. Kochergin, Oksana E. Panova, Ekaterina O. Chekanova, Denis V. Shevchuk, Aleksandra O. Kozlova, Dmitry A. Ganin, Kirill V. Sapozhnikov, Mariya N. Zakharova, Targeted therapy of multiple sclerosis: real-world experience with divozilimab, Annals of Clinical and Experimental Neurology, 10.17816/ACEN.1426, 19, 4, (51-61), (2025).
- Ryan Kammeyer, Stefan Sillau, Kimberly Chapman, Jennifer J. Lindwall, Christa Hutaff-Lee, Teri Schreiner, Self-reported quality of life related to cognitive function and fatigue in adults with multiple sclerosis, Multiple Sclerosis and Related Disorders, 10.1016/j.msard.2025.106809, 104, (106809), (2025).
- See more