There has been a continued research effort to quantify the effect that clinical obesity has on treatment response to anti-tumor necrosis factor-alpha (anti-TNF -alpha) treatment for rheumatoid arthritis (RA). Although the reasons why blockade of TNF-alpha would be less effective in obese RA patients have yet to be completely investigated, it is postulated that persistent inflammation of visceral fat produces an overproduction of proinflammatory cytokines that overwhelms the effects of TNF-alpha blockade.1 Current literature reports reduced clinical response to anti-TNF-alpha  in obese as compared to normal-weight patients with RA. 2 Patients with high body mass index (BMI) and obesity have been shown to have less response to treatment with infliximab dosed according to weight, as well as etanercept and adalimumab administered at a fixed-dose regimen.3,4

In a study published in Clinical Rheumatology, Gardette and colleagues evaluated the effects of BMI on clinical response to tocilizumab (TCZ) in patients with.5 A total of 115 patients with RA treated with TCZ were included in a multicenter retrospective study in which BMI was calculated at baseline. Changes in Disease Activity Score 28 (DAS28), pain as measured by the visual analog scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and tenderness of joints were analyzed.  A decrease in DAS 28 ≥ 1.2 was identified as the primary end point in assessing efficacy of treatment.  Median BMI did not differ between TCZ responders and nonresponders for DAS28 decrease ≥ 1.2 (25.7 [22.1-29.9] vs 24.9 [22.0-27.1], P = .38), European League Against Rheumatism (EULAR) good response (25.9 [22.8-30.0] vs 25.4 [22.0-28.4], P = .61), and remission (25.1 [22.5-28.6] vs 25.4 [22.0-28.9], P = .76). These results suggested that BMI did not have an effect on response to TCZ for the treatment of RA.

Summary and Clinical Applicability


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Previous studies have shown that a subset of obese patients with RA demonstrate poor response to anti-TNF-alpha agents. It had been suggested that the overexpression of inflammatory cytokines by adipose tissue or alterations in pharmacokinetics due to fat “sink” component could be contributing factors.  However, the findings reported herein suggest that RA in obese patients is not always refractory to TCZ treatment and thus these patients remain candidates for treatment if other agents fail.  Future clinical studies to elucidate the pharmacokinetics of specific anti-TNF-alpha agents in relation to BMI should provide further clinical guidance.

References

1. Ajeganova S, Andersson ML, Hafström I.  Association of obesity with worse disease severity in rheumatoid arthritis as well as with comorbidities: a long-term follow-up from disease onset. Arthritis Care Res. 2013;65(1):78-87. doi: 10.1002/acr.21710.

2. Sandberg ME, Bengtsson C, Källberg H, et al. Overweight decreases the chance of achieving good response and low disease activity in early rheumatoid arthritis. Ann Rheum Dis. 2014;73(11):2029-2033. doi: 10.1136/annrheumdis-2013-205094.

3. Klaasen R, Wijbrandts CA, Gerlag DM, Tak PP. Body mass index and clinical response to infliximab in rheumatoid arthritis. Arthritis Rheum. 2011;63(2):359-364. doi: 10.1002/art.30136.

4. Gremese E, Carletto A, Padovan M, et al; for the Gruppo Italiano di Studio sulle Early Arthritis (GISEA). Obesity and reduction of the response rate to anti-tumor necrosis factor-α in rheumatoid arthritis: an approach to a personalized medicine. Arthritis Care Res . 2013;65(1):94-100. doi: 10.1002/acr.21768.

5.  Gardetta A, Ottaviani S, Berenbaum F, et al. Body mass index and response to tocilizumab in rheumatoid arthritis: a real life study. Clin Rheumatol. 2016; Jan 22. [Epub ahead of print]