Disease-modifying therapy in progressive multiple sclerosis: a systematic review and network meta-analysis of randomized controlled trials

Xin Wu; Shixin Wang; Tao Xue; Xin Tan; Jiaxuan Li; Zhouqing Chen; Zhong Wang

doi:10.3389/fneur.2024.1295770

Disease-modifying therapy in progressive multiple sclerosis: a systematic review and network meta-analysis of randomized controlled trials

Front Neurol. 2024 Mar 11:15:1295770. doi: 10.3389/fneur.2024.1295770. eCollection 2024.

Authors

Xin Wu^#¹, Shixin Wang^#¹, Tao Xue^#², Xin Tan³, Jiaxuan Li¹, Zhouqing Chen¹, Zhong Wang¹

Affiliations

¹ Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
² Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
³ Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, China.

^# Contributed equally.

Abstract

Background: Currently, disease-modifying therapies (DMTs) for progressive multiple sclerosis (PMS) are widely used in clinical practice. At the same time, there are a variety of drug options for DMTs, but the effect of the drugs that can better relieve symptoms and improve the prognosis are still inconclusive.

Objectives: This systematic review aimed to evaluate the efficacy and safety of DMTs for PMS and to identify the best among these drugs.

Methods: MEDLINE, EMBASE, the Cochrane Library, and clinicaltrials.gov were systematically searched to identify relevant studies published before 30 January, 2023. We assessed the certainty of the evidence using the confidence in the network meta-analysis (CINeMA) framework. We estimated the summary risk ratio (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes with 95% credible intervals (CrIs).

Results: We included 18 randomized controlled trials (RCTs) involving 9,234 patients in the study. DMT can effectively control the disease progression of MS. Among them, mitoxantrone, siponimod, and ocrelizumab are superior to other drug options in delaying disease progression (high certainty). Mitoxantrone was the best (with high certainty) for mitigating deterioration (progression of disability). Ocrelizumab performed best on the pre- and post-treatment Timed 25-Foot Walk test (T25FW; low certainty), as did all other agents (RR range: 1.12-1.05). In the 9-Hole Peg Test (9HPT), natalizumab performed the best (high certainty), as did all other agents (RR range: 1.59-1.09). In terms of imaging, IFN-beta-1b performed better on the new T2 hypointense lesion on contrast, before and after treatment (high certainty), while siponimod performed best on the change from baseline in the total volume of lesions on T2-weighted image contrast before and after treatment (high certainty), and sWASO had the highest area under the curve (SUCRA) value (100%). In terms of adverse events (AEs), rituximab (RR 1.01), and laquinimod (RR 1.02) were more effective than the placebo (high certainty). In terms of serious adverse events (SAEs), natalizumab (RR 1.09), and ocrelizumab (RR 1.07) were safer than placebo (high certainty).

Conclusion: DMTs can effectively control disease progression and reduce disease deterioration during the treatment of PMS.

Systematic review registration: https://inplasy.com/?s=202320071, identifier: 202320071.

Keywords: disease-modifying therapy; multiple sclerosis; natalizumab; ocrelizumab; randomized controlled; rituximab.

Publication types

Systematic Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (No. 81971171), the Suzhou Science and Technology Project (No. SLT201906), and the Suzhou Health Talents Training Project (No. GSWS2019002).