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.
Highlights
Interleukin (IL)-6 is a small signaling molecule involved in inflammatory processes, initiating fever and mediating the acute phase response
IL-6 has been implicated in inflammatory and auto-immune processes related to a wide range of diseases such as diabetes [1], atherosclerosis [2], depression [3], rheumatoid arthritis [4] and Castleman’s disease [5], as well as several cancers [6,7,8] and cancer cachexia [9,10]
Our results show a small but significant increase in weight and body mass index (BMI) following treatment with an IL-6 pathway inhibitor
Summary
Interleukin (IL)-6 is a small signaling molecule involved in inflammatory processes, initiating fever and mediating the acute phase response It is a pleiotropic cytokine secreted by a range of cells, such as T cells, B cells, macrophages, osteoblasts, smooth muscle cells and several tumor cells. Inhibiting the action of IL-6 can be achieved either by targeting the soluble IL-6 molecule or by blocking the cell surface receptor (IL-6R) on which IL-6 attaches The latter are known as IL-6 receptor antagonists, and the first FDA-approved medication targeting IL-6 signaling, tocilizumab, belongs to this class. Siltuximab directly targets the IL-6 soluble molecule and there are several other agents (olokizumab, elsilimomab, sirukumab) in this class that are currently being tested and are at various phases of clinical trials Even though these agents inhibit the IL-6 signaling pathway via different mechanisms, we have included all IL-6 pathway inhibitors in this review and meta-analysis
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