Abstract

Background:A number of previous reports suggested that obesity is one of the baseline factors indicates refractory to biologic disease-modifying antirheumatic drugs (bDMARDs). However, difference of the significant responses appears on obesity patients depending on each kind of drug is yet unclear. However, it is yet unclear how the significant responses on obesity patients vary on each kind of drug.Objectives:To assess whether obesity affects clinical outcome in rheumatoid arthritis (RA) treated with each molecular-targeted agent including bDMARDs and tofacitinib.Methods:In Kansai consortium for well-being of rheumatic disease patients (ANSWER) cohort, which was the real-world retrospective cohort of clinical database for rheumatic diseases, RA patients who initiated biological / targeted disease modifying anti-rheumatic drugs were included and consecutively followed. Obesity was defined as BMI over than 25, and patients were divided between obese (“Ob”) and non-obese (“non-Ob”) patients. SDAI (simplified disease activity index) was compared between non-Ob and Ob at month 0, 3, 6, 9, 12 after the indicated drugs were administered. Using logistic regression analysis, odds ratio (OR) and their corresponding 95% confidence intervals (95% CIs) were further calculated to estimate achievement rate of SDAI remission defined as lower than 3.3 by obesity and other relevant clinical parameters. Once after the drugs were discontinued by any unfavorable reason, disease activities were no more scored and the Last Observation Carried Forward (LOCF) imputation method was used for SDAI at month 3 and thereafter.Results:A total of 1936 patients met in the inclusion criteria were under the analysis. In each drug, SDAI remission rate (non-Ob, Ob, p-value by Chi-square test) at month 12 was as follows; Infliximab (IFX, n=135): 43%, 38%, NS (not significant); Etanercept (ETN, n=188): 44%, 19%, p=0.0122; Adalimumab (ADA, n=169): 50%, 56%, NS; Golimumab (GLM, n=315): 36%, 30%, NS; Certolizumab pegol (CZP, n=131): 33%, 56%, p=0.0287; Tocilizumab (TCZ, n=423): 41%, 29%, p=0.0456; Abatacept (ABT, n=144): 26%, 23%, NS; Tofacitinib (TOF, n=69): 27%, 23%, NS. In multivariate analysis to predict SDAI remission at month 12, obesity was an independent protective factor in CZP (OR: 0.29, 95% CIs: 0.10 – 0.83), but was an independent risk factor in TCZ (OR: 1.9, 95% CIs: 1.01 – 3.61) irrespective of age, sex, disease duration, SDAI at month 0 or number of previous bDMARDs. Any other drug including ETN did not show significant result between non -Ob and Ob in the multivariate analysis.Conclusion:Obese patients were more resistant to TCZ but more effective in CZP than non-obese patients.

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