Safety and Efficacy of IL-6 Inhibitors in the Treatment of Neuromyelitis Optica Spectrum Disorders. A Meta-analysis

Abstract

BackgroundInterleukin-6 (IL-6) inhibitors like Tocilizumab and Satralizumab are showing promising results in the treatment of Neuromyelitis Optica spectrum disorder (NMOSD). We aimed to investigate the efficacy and safety of various IL-6 inhibitors in the management of NMO/NMOSD.MethodsPubMed, Embase, and The Cochrane Library were systematically searched for suitable studies. Change in Annualized Relapse Ratio (ARR), Change in Extended Disability Status Scale (EDSS) s, the proportion of relapse-free patients, on trial relapse risk, and proportion of patients with adverse events, including serious adverse events and mortality were the parameters considered for the meta-analysis. Mean difference (MD) with 95% CI was used to quantify the change in ARR and change in EDSS-before and after treatment. While pooled risk ratio between the intervention group and placebo group was used in Randomized Controlled Trial (RCTs). A forest plot was prepared to indicate the efficacy outcomes.Results A total of nine studies with 202 patients were included in our meta-analysis. IL-6 inhibitors found a good proportion (75%,95% CI: 0.62–0.89; p<0.001) of relapse free patients at follow up. It also significantly reduced mean ARR (mean difference: -2.6 95% CI: -2.71 to -1.68; p<0.001) and on trial relapse risk (RR: 0.46; 95% CI: 0.32‐0.66; P< 0.001) but did not show significant difference in change in EDSS score (mean difference=-0.79, 95% CI: -1.89 to -0.31; p=0.16). Also, the toxicity profile of IL-6 inhibitors was acceptable considering the proportions of patients with adverse events (72%, 95% C.I.;0.59-0.84, I2=85.29%, p<0.001), proportions of patients with serious adverse events (18%;95% C.I.; -3.68 to 4.04, I2=0%, p=0.93) and zero treatment related deaths. In subgroup analysis, we found subcutaneous administration to be superior (81%;95% CI:0.74-0.82) than intravenous route (67%; 95% CI:0.67-0.89) in relapse free maintenance.ConclusionIL-6 inhibitor therapy showed significant benefits in reducing mean ARR, relapse risk and increasing the number of relapse-free patients with acceptable adverse events profile.