Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis

Abstract

Background Different therapeutic strategies are available for the treatment of people with relapsing‐remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biological agents. Although each one of these therapies reduces relapse frequency and slows disability accumulation compared to no treatment, their relative benefit remains unclear. This is an update of a Cochrane review published in 2015. Objectives To compare the efficacy and safety, through network meta‐analysis, of interferon beta‐1b, interferon beta‐1a, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta‐1a, daclizumab, laquinimod, azathioprine, immunoglobulins, cladribine, cyclophosphamide, diroximel fumarate, fludarabine, interferon beta 1‐a and beta 1‐b, leflunomide, methotrexate, minocycline, mycophenolate mofetil, ofatumumab, ozanimod, ponesimod, rituximab, siponimod and steroids for the treatment of people with RRMS. Search methods CENTRAL, MEDLINE, Embase, and two trials registers were searched on 21 September 2021 together with reference checking, citation searching and contact with study authors to identify additional studies. A top‐up search was conducted on 8 August 2022. Selection criteria Randomised controlled trials (RCTs) that studied one or more of the available immunomodulators and immunosuppressants as monotherapy in comparison to placebo or to another active agent, in adults with RRMS. Data collection and analysis Two authors independently selected studies and extracted data. We considered both direct and indirect evidence and performed data synthesis by pairwise and network meta‐analysis. Certainty of the evidence was assessed by the GRADE approach. Main results We included 50 studies involving 36,541 participants (68.6% female and 31.4% male). Median treatment duration was 24 months, and 25 (50%) studies were placebo‐controlled. Considering the risk of bias, the most frequent concern was related to the role of the sponsor in the authorship of the study report or in data management and analysis, for which we judged 68% of the studies were at high risk of other bias. The other frequent concerns were performance bias (34% judged as having high risk) and attrition bias (32% judged as having high risk). Placebo was used as the common comparator for network analysis. Relapses over 12 months: data were provided in 18 studies (9310 participants). Natalizumab results in a large reduction of people with relapses at 12 months (RR 0.52, 95% CI 0.43 to 0.63; high‐certainty evidence). Fingolimod (RR 0.48, 95% CI 0.39 to 0.57; moderate‐certainty evidence), daclizumab (RR 0.55, 95% CI 0.42 to 0.73; moderate‐certainty evidence), and immunoglobulins (RR 0.60, 95% CI 0.47 to 0.79; moderate‐certainty...

Editorial: New drugs, approaches and strategies for multiple sclerosis treatment

“…In fact, nerve disfunction and demyelination become more crucial processes in the progressive phase than the inflammatory mechanisms. Approved drugs for MS treatment do not change the course of the disease and to date, the most important challenge is the developing of new therapeutic strategies against this multifactorial disease (Gonzalez-Lorenzo et al, 2024 ). For this reason, new diagnostic tools and drugs must be urgently developed to efficiently fight the disease and to reduce the deleterious important side-effects promoted by the MS current treatments (e.g., cancer, leukopenia, hepatotoxicity), increasing the quality of life and decreasing the sequelae of patients suffering from MS (Mercadante, 2024 ).…”