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Review
. 2022 Nov;146(5):403-409.
doi: 10.1111/ane.13697. Epub 2022 Sep 2.

Is there a role for off-label high-efficacy disease-modifying drugs in progressive multiple sclerosis? A network meta-analysis

Guilherme Diogo Silva  1 , Bruno Batitucci Castrillo  1   2 , Samira Luísa Apóstolos-Pereira  1 , Dagoberto Callegaro  1
Affiliations
Review

Is there a role for off-label high-efficacy disease-modifying drugs in progressive multiple sclerosis? A network meta-analysis

Guilherme Diogo Silva et al. Acta Neurol Scand. 2022 Nov.

Abstract

Ocrelizumab and siponimod are the two on-label drugs used for progressive forms of multiple sclerosis (PMS). However, many patients with PMS do not have access to these high-efficacy disease-modifying drugs (DMDs). Off-label prescription of other high-efficacy DMDs (fingolimod, rituximab and natalizumab) may be a strategy to improve access to immunotherapy for these patients. We aim to compare on-label and off-label high-efficacy drugs for their effect on disability progression in PMS. In December 2021, we searched MEDLINE (PubMed), Embase, Cochrane Central and Scopus databases for randomized clinical trials involving patients with PMS. High-efficacy drugs were considered as intervention and placebos as comparison. The outcome contemplated was risk of Expanded Disability Severity Scale (EDSS) progression at 2 years. A network meta-analysis was performed to compare the relative risk of EDSS progression at 2 years compared with placebo in on-label and off-label drugs. We included five studies with 4526 patients. The median EDSS progression at 2 years in patients that received any immunotherapy was 30%, compared with 35% in placebo groups. Overall, the risk of bias of individual studies was low. Network analysis revealed overlapping confidence intervals in off-label drugs (CI95% 0.51-2.16) versus ocrelizumab (reference) and off-label drugs (CI 95% 0.53-1.96) versus siponimod (reference), suggesting similar efficacy. The same result was found even after excluding studies with the risk of publication bias. Off-label high efficacy immunotherapy in PMS has biological plausibility and presented similar effectiveness to on-label DMDs in this network meta-analysis. The use of fingolimod, rituximab or natalizumab may be a strategy that reduces costs and improves access to immunotherapy for patients with PMS.

Keywords: immunotherapy; meta-analysis; progressive multiple sclerosis.

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References

REFERENCES

    1. Laurson-Doube J, Rijke N, Helme A, et al. Ethical use of off-label disease-modifying therapies for multiple sclerosis. Mult Scler. 2021;27(9):1403-1410. doi:10.1177/13524585211030207
    1. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209-220. doi:10.1056/NEJMoa1606468
    1. Kappos L, Bar-Or A, Cree BAC, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018;391(10127):1263-1273. [Published correction appears in Lancet. 2018 Nov 17;392(10160):2170]. doi:10.1016/S0140-6736(18)30475-6
    1. Giovannoni G, Hawkes CH, Lechner-Scott J, Levy M, Yeh EA. Multiple sclerosis is one disease. Mult Scler Relat Disord. 2022;63:103961. doi:10.1016/j.msard.2022.103961
    1. Capanna M, Signori A, Sormani MP. Is the effect of drugs in progressive MS only due to an effect on inflammation? A subgroup meta-analysis of randomised trials. Mult Scler. 2022. [Published online ahead of print, 2022 May 17]. doi:10.1177/13524585221094944

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