Obesity Is a Predictor of Inferior Response to Anti-TNF Drugs

While it is already known that obesity, which affects 1 in 10 people in the world, may contribute to an increased risk developing some immune-mediated inflammatory diseases, as well as more severe disease activity and a higher burden of hospitalization, a new review found that obesity is also a predictor of inferior response to anti—tumor necrosis factor (anti-TNF) agents.

The systematic literature review, published in PLOS One, include phase 2 and phase 3 randomized controlled trials or observational cohort studies in patients with Crohn disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PsA), or spondyloarthropathy (SpA) who were treated with infliximab, adalimumab, certolizumab pegol, golimumab, or etanercept, and for which outcomes were stratified by baseline body mass index (BMI) or body weight. The primary outcome of interest was failure of biologic therapy. In total, the researchers identified 54 cohorts that reported on 19,372 patients.

Across the meta-analysis, the researchers found that obesity was associated with 60% higher odds of failure of anti-TNF therapy (OR, 1.60; 95% CI, 1.39-1.83), and each 1 kg/m² increase in BMI was associated with 6.5% higher odds of failing anti-TNF therapy. This effect was independent of the route of administration or dosing.

Obesity was also associated with inferior response to therapy in some of the indications studied; in 10 studies of patients with RA, patients with obesity had 80% higher odds of failing therapy, and patients with SpA, PsA, or psoriasis with co-occurring obesity had similar rates of inferior response to therapy. No significant association was observed between obesity and anti-TNF therapy response in those with CD or UC, however.

Finally, the effect of obesity was more pronounced in studies that used validated definitions of clinical remission or response versus studies that used pragmatic definitions of treatment modification.

According to the authors, obesity involves chronic low-grade inflammation and can also modify the pharmacokinetics of anti-TNF agents, leading to increased clearance of the drug, a shorter half-life, and lower serum trough drug concentrations. These facts may explain why patients with obesity have inferior response to therapy even on weight-based regimens.

The authors of the study called for further investigation of obesity and anti-TNF therapy, and write that, “If this effect is consistent, interventional studies targeting obesity should be explored for difficult-to-treat obese patients.”

Reference

Singh S, Facciorusso A, Sing AG, et al. Obesity and response to anti-tumor necrosis factor-α agents in patients with select immune-mediated inflammatory diseases: A systematic review and meta-analysis. [Published online May 17, 2018.] PLoS One. 10.1371/journal.pone.0195123.