Abstract

Abstract Background Worldwide, >60% patients with rheumatoid arthritis (RA) are overweight/obese (body mass index, BMI≥25kg/m2). Studies demonstrate poorer disease outcomes and health-related quality of life in these patients. However, little is known about the effect of increased BMI on drug choice, dosing, or treatment response. Objective: To explore the effect of increased BMI on DMARD-prescribing, methotrexate (MTX)-dose, and disease activity over 12 months. Methods Participants registered on METEOR (international database of RA patients) were stratified into early (<1year post-diagnosis, eRA), and established RA (estRA). EULAR response and DAS28 remission (including components), and treatment regimens were recorded at baseline, 6, and 12 months. Increased BMI (defined overweight and obese) were explored in 1) eRA and 2) estRA, as predictors of good EULAR response, DAS28 remission, number of DMARDs prescribed, and MTX-dose. Logistic and linear regression models (controlling for age, gender, smoking, and baseline outcome values), subgroup analyses (by drug exposure), and sensitivity analyses, were performed. Results 1,313 patients (1056 female) were included, 582 eRA. In eRA, increased BMI was not significantly associated with remission outcomes. In estRA, obese patients on monotherapy were statistically significantly less likely to achieve good EULAR response [OR 0.4 (95%CI 0.23-0.7)] or DAS28 remission [OR 0.47 (95%CI 0.24-0.88)] at 6 months, compared to those of normal weight. A similar trend observed at 12 months did not reach significance. Obese estRA patients were more likely to be treated with combination conventional synthetic DMARDs (csDMARD) than monotherapy, compared with those of normal weight, significant at 6 months [OR 1.59 (95%CI 1.03-2.45)]. In early and established disease, no significant difference in remission outcomes was demonstrated for combination compared to monotherapy. However, overweight/obese individuals were less likely to achieve remission overall (non-significant). Regarding components of remission, tender joint count and ESR in estRA were higher in overweight/obese individuals at 6 months [β 1.05 (95%CI 0.05-2.06)] and 12 months [β 6.58 (95%CI 0.16-12.99)] respectively, compared to those of normal weight. Sensitivity analyses showed no difference in the above results. MTX-dose was available for 613 patients at sequential visits. Within this subgroup, overweight/obese patients with both eRA and estRA were exposed to higher doses of MTX (mono- and combination-therapy) at any time-point, compared to those of normal weight. eRA: overweight: β 5.33, 95%CI 3.10-7.56; obese: β 6.01, 95%CI 3.57-8.46. estRA: overweight: β 4.87, 95%CI 3.79-5.95; obese: β 2.69, 95%CI 1.56-3.83. An average weekly dose of 20mg was prescribed in overweight/obese patients, compared to 15mg in those of normal weight. Conclusion We observed that overweight/obese individuals require more intense csDMARD therapy to achieve the same treatment targets as those of normal weight. Awareness of this is particularly important given the increasing obesity prevalence in RA. Disclosures M. Dey None. S.S. Zhao None. E. Psarelli None. R.J. Moots None. R. Landewe Other; Member of METEOR board. N.J. Goodson None.

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