The efficacy of disease-modifying therapies in patients with clinically isolated syndrome: a systematic review and network meta-analysis

Clinically isolated syndrome (CIS) is the initial clinical presentation that may indicate the development of multiple sclerosis (MS). While significant advancements have been made in the treatment of MS, there remains no definitive consensus on the effective treatment of CIS. Our study aims to evaluate the outcomes of disease-modifying therapies (DMTs) in the progression of CIS to clinically definite multiple sclerosis (CDMS) and to assess their efficacy in the treatment of CIS. A literature search was conducted through March 2024, focusing on immunotherapies that can treat CIS. The control group consisted of patients who received a placebo. The primary outcomes were the number of patients who converted to CDMS over the course of the study and the progression of the severity of disability in patients with MS using the Expanded Disability Status Scale (EDSS). The secondary outcomes included improvement in CIS symptoms based on MRI lesions, including gadolinium-enhancing (GDE) and T2-weighted (T2W) lesions. A total of 9 studies (8 randomized controlled trials and 1 post hoc analysis) included 3,339 patients diagnosed with CIS who received immunotherapy. The patients had a mean age of 31.4 ± 7.8 years and were followed for a mean duration of 35.7 months. Cladribine showed the strongest evidence in lowering CDMS conversion (HR 0.37; 95% CrI 0.23-0.59; SUCRA 85.40 followed by GA (HR 0.50; 95% CrI 0.34-0.73; SUCRA 62.10), IFN beta-1b (HR 0.51; 95% CrI 0.35-0.74; SUCRA 60.60), teriflunomide (HR 0.59; 95% CrI 0.37-0.92; SUCRA 59.20), and IFN beta-1a (HR 0.62; 95% CrI 0.50-0.77; SUCRA 39.50), respectively. DMTs, including cladribine, teriflunomide, IFN beta-1a, IFN beta-1b, and GA, showed evidence of reducing conversion to CDMS compared with placebo. Cladribine and GA showed the strongest evidence for a high probability of reducing CDMS conversion.