patient care perspectives

Impact of Obesity and Comorbidity on Biologic Therapy Effectiveness

by Jeffrey R. Curtis, MD, MS, MPH

Overview

There is a clear link between obesity in rheumatoid arthritis (RA) and greater disease activity and less robust responses to disease-modifying therapies. This link has several treatment implications.

Expert Commentary

Jeffrey R. Curtis, MD, MS, MPH

Marguerite Jones Harbert-Gene V. Ball, MD Professor of Medicine
Co-Director, UAB Pharmacoepidemiology and Pharmacoeconomics Research (PEER) Unit
Division of Clinical Immunology and Rheumatology
University of Alabama at Birmingham
Birmingham, AL

Rheumatologists can educate their patients about the link between obesity and disease activity, highlighting the opportunity for improved response to anti-RA therapy with weight loss.

Jeffrey R. Curtis, MD, MS, MPH

In individuals with obesity, adipose tissue is pro-inflammatory and is associated with increased levels of cytokines that are involved in the pathogenesis of RA, including tumor necrosis factor α (TNF-α) and interleukins 1 and 6. Chronic inflammation also contributes to the risk of cardiometabolic disease. Other comorbidities such as osteoarthritis in weight-bearing joints may develop and interact with the RA. Determining whether obesity and RA are intrinsically interlinked or whether they simply co-occur in a somewhat negative and synergistic way likely enters the minds of most clinicians as we treat these patients. Individuals who are obese tend to have worse disease activity scores, greater disability, more self-reported pain, and worse patient global assessment scores.

As many as one-half to two-thirds of patients with RA meet obesity criteria by body mass index—a practical, yet inaccurate, measurement. We currently lack an everyday gold standard for assessing obesity outside of the context of research. Adipokines (eg, leptin, resistin, adiponectin) can be measured, and leptin is featured prominently in the assessment of disease activity in RA by the multi-biomarker disease activity score.

Patients with obesity are only approximately half as likely to achieve low disease activity or clinical remission compared with similar nonobese patients with RA. Curiously, they seem to have a similar prevalence of synovitis based on several studies that included a magnetic resonance imaging component. These individuals also have a lower risk for radiographic progression, which may relate to a protective effect from adipokines. Further, obesity can affect anti-RA treatment response, with data from meta-analyses suggesting that therapy with anti-TNF agents is less effective in patients with obesity. A 2019 meta-analysis by Shan and Zhang again showed a diminution of response to anti-TNF therapy in patients with obesity, also finding that those receiving newer biologics including abatacept and tocilizumab may have a slightly less diminished response. The clinical significance of these findings is uncertain.

In our practice, we would recommend a comprehensive wellness program that includes weight loss. The role of bariatric surgery is better delineated for comorbidities such as type 2 diabetes; however, data from small observational studies suggest that weight loss with bariatric surgery may improve RA disease activity. Reduction in doses of systemic corticosteroids would also be advisable in such patients. Rheumatologists can educate their patients about the link between obesity and disease activity, highlighting the opportunity for improved response to anti-RA therapy with weight loss. I like to frame the issue in terms of goal setting by identifying specific goals that the patient would like to achieve, such as being able to get down on the floor to play with grandchildren. We then discuss how the achievement of weight loss will help them to realize those goals.

References

Ayhan FF, Ataman S, Rezvani A, et al. Obesity associated with active, but preserved joints in rheumatoid arthritis: results from our national registry. Arch Rheumatol. 2016;31(3):272-280.

Curtis JR, Flake DD II, Weinblatt ME, et al. Adjustment of the multi-biomarker disease activity score to account for age, sex and adiposity in patients with rheumatoid arthritis. Rheumatology (Oxford). 2018 Dec 24. doi: 10.1093/rheumatology/key367. [Epub ahead of print]

Liu Y, Hazelwood GS, Kaplan GG, Eksteen B, Barnabe C. Impact of obesity on remission and disease activity in rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2017;69(2):157-165.

Schulman E, Bartlett SJ, Schieir O, et al; CATCH Investigators. Overweight, obesity, and the likelihood of achieving sustained remission in early rheumatoid arthritis: results from a multicenter prospective cohort study. Arthritis Care Res (Hoboken). 2018;70(8):1185-1191.

Shan J, Zhang J. Impact of obesity on the efficacy of different biologic agents in inflammatory diseases: a systematic review and meta-analysis. Joint Bone Spine. 2019;86(2):173-183.

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