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Obesity and response to anti-tumor necrosis factor-α agents in patients with select immune-mediated inflammatory diseases: A systematic review and meta-analysis

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Singh S1,2, Facciorusso A3, Singh AG4, Casteele NV1, Zarrinpar A1,5,6, Prokop LJ7, Grunvald EL8, Curtis JR9, Sandborn WJ1. PLoS One. 2018 May 17;13(5):e0195123. doi: 10.1371/journal.pone.0195123. eCollection 2018.

Abstract

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1 Division of Gastroenterology, University of California San Diego, La Jolla, California, United States of America.

2 Division of Biomedical Informatics, University of California San Diego, La Jolla, California, United States of America.

3 Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy.

4 Division of Rheumatology, Allergy and Immunology, University of California San Diego, La Jolla, California, United States of America.

5 Institute for Diabetes and Metabolic Health, University of California, San Diego, La Jolla, California, United States of America.

6 VA San Diego Health Systems, La Jolla, California, United States of America.

7 Department of Library Services, Mayo Clinic, Rochester, Minnesota, United States of America.

8 Weight Management Program, Department of Medicine, University of California San Diego, La Jolla, California, United States of America.

9 Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.

Abstract

OBJECTIVES: We sought to evaluate the association between obesity and response to anti-tumor necrosis factor-α (TNF) agents, through a systematic review and meta-analysis.

METHODS: Through a systematic search through January 24, 2017, we identified randomized controlled trials (RCTs) or observational studies in adults with select immune-mediated inflammatory diseases-inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathies (SpA), psoriasis and psoriatic arthritis (PsA)-treated with anti-TNF agents, and reporting outcomes, stratified by body mass index (BMI) categories or weight. Primary outcome was failure to achieve clinical remission or response or treatment modification. We performed random effects meta-analysis and estimated odds ratios (OR) and 95% confidence interval (CI).

RESULTS: Based on 54 cohorts including 19,372 patients (23% obese), patients with obesity had 60% higher odds of failing therapy (OR,1.60; 95% CI,1.39-1.83;I2 = 71%). Dose-response relationship was observed (obese vs. normal BMI: OR,1.87 [1.39-2.52]; overweight vs. normal BMI: OR,1.38 [1.11-1.74],p = 0.11); a 1kg/m2 increase in BMI was associated with 6.5% higher odds of failure (OR,1.065 [1.043-1.087]). These effects were observed across patients with rheumatic diseases, but not observed in patients with IBD. Effect was consistent based on dosing regimen/route, study design, exposure definition, and outcome measures. Less than 10% eligible RCTs reported outcomes stratified by BMI.

CONCLUSIONS: Obesity is an under-reported predictor of inferior response to anti-TNF agents in patients with select immune-mediated inflammatory diseases. A thorough evaluation of obesity as an effect modifier in clinical trials is warranted, and intentional weight loss may serve as adjunctive treatment in patients with obesity failing anti-TNF therapy.