Effects of IL-6 Signaling Pathway Inhibition on Weight and BMI: A Systematic Review and Meta-Analysis

Abstract

Inhibitors of the IL-6 signaling pathway, such as tocilizumab, are frequently administered for the treatment of immune diseases, e.g., rheumatoid arthritis and multicentric Castleman's disease. The aim of this systematic review and meta-analysis was to ascertain the effects of IL-6 pathway inhibitors on weight and body mass index (BMI). Using PRISMA guidelines, we systematically reviewed relevant articles from three databases (PubMed, OVID, EMBASE). A random effects model was used to estimate standardized mean change (SMCC). Ten studies with a total of 1531 patients were included in the meta-analysis for weight and ten studies with a total of 1537 patients were included in the BMI meta-analysis. The most commonly administered IL-6 pathway inhibitor was tocilizumab. IL-6 pathway inhibitors were associated with increases in weight (SMCC = 0.09, p = 0.016, 95% CI [0.03, 0.14]) and BMI (SMCC = 0.10, p = 0.0001, 95% CI [0.05, 0.15]). These findings suggest that the IL-6 pathway is involved in weight regulation. Modulating IL-6 signaling may be a potential future therapeutic avenue used as an adjunct for the treatment of disorders associated with weight changes, such as cancer cachexia and anorexia nervosa.

Keywords: BMI; IL-6; obesity; rheumatoid arthritis; siltuximab; spondyloarthritis; tocilizumab; weight.

Figure 1

Forest plot of standardized mean change in body weight from nine datasets (n = 1531). Zero indicates no effect, whereas points to the right indicate an increase in weight when comparing baseline with follow-up values post-treatment with an IL-6 signaling pathway inhibitor.

Figure 2

Forest plot of standardized mean change in body mass index (BMI) from nine datasets (n = 1537). Zero indicates no effect, whereas points to the right indicate an increase in weight when comparing values at baseline and after treatment with an IL-6 signaling pathway inhibitor.

Figure 3

PRISMA flow diagram.