Abstract

Background:BMI appears to be associated with treatment response on TNFi(nhibitors) in rheumatoid arthritis (RA), but large heterogeneity between studies exists. More extreme BMI categories are rarely studied and it is unclear if differences exist between various TNFi.1Table 1Characteristics of RA patientsFemale, n (%)935 (79.8)Age, years*51.0 ±13.7Current smokers, n (%)256 (23.2)RF Positivity, n (%)404 (55.6)Anti-CCP Positivity, n (%)430 (58.2)X-ray Erosion, n (%)317 (61.9)ESR, mm/h*31.2±21.9CRP, mg/L*17.2±3.9DAS 28-CRP*3.8±1.6VAS global*46.6±28.6HAQ*0.9±0.7First TNFi Etanercept, n (%)525 (38.7) Adalimumab, n (%)379 (27.9) Infliximab, n (%)118 (8.7) Certolizumab, n (%)188 (13.8) Golimumab, n (%)147 (10.9)* mean ±S.DRF, Rheumatoid factor; Anti-CCP, Anti- cyclic citrullinated peptid; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; DAS28–CRP, Disease Activity Score using 28 joints–CRP; VAS, Visual analog scale; HAQ, Health Assessment QuestionnaireObjectives:To study whether there is an association between BMI category and drug survival in RA patients starting treatment with various TNFi in a real life longitudinal international registry.Methods:Data from 5230 RA patients starting a TNFi were included from the METEOR registry. Timing of follow-up visits was daily practice based. Follow-up was censored at 5000 days (±13.5 years). Patients were divided into 6 BMI categories (WHO definition): underweight BMI <18.5, normal weight BMI 18.5-25, pre-obesity BMI 25-30, obesity class I BMI 30-35, class II BMI 35-40, and class III BMI >40. Missing data were imputed using chained equations. The association between BMI category and time on treatment was investigated using Kaplan-Meier (KM) curves and Cox regression analyses, for time on first TNFi and for the first prescribed course of adalimumab (ADA), etanercept (ETA) and infliximab (IFX) separately. All analyses were adjusted for the potential confounders age, gender, smoking, baseline DAS28, concomitant glucocorticoid use and country. Potential effect modification by reported pain was tested by adding an interaction term between BMI category and baseline pain category (VAS pain 0-25, 25-50, 50-75 and 75-100).Results:Most patients had a normal weight (46%) or pre-obesity (32%). 4% of patients were underweight, 10% had obesity class I, 3% obesity class II and 1% obesity class III. N=2936 patients ever started ETA, n=2069 ADA, n=1390 IFX, n=263 certolizumab and n=84 golimumab. The KM curve in fig 1A shows TNFi survival in patient starting their first TNFi per BMI category. Patients with normal weight and pre-obesity had longest drug survival and patients with obesity class II and especially patients with obesity class III had shortest drug survival. The adjusted Cox regression support these findings, with statistically significantly shorter drug survival for patients with obesity class III [HR (95% CI) 1.67 (1.29; 2.18)] and class II [1.28 (1.06; 1.54)], but also for underweight patients [1.3 (1.07; 1.58)], compared to normal weight patients. KM curves for individual TNFi showed shorter drug survival on ADA for patients with obesity class II and III (fig 1B), on ETA for patients with obesity, especially in class III (fig 1C) and on IFX, for patients with obesity class II and III and underweight patients (fig 1D). After adjustment in Cox regression, statistical significant BMI-drug survival associations remained for patients with pre-obesity starting ADA [HR (95% CI) 0.86 (0.75; 0.99)], for patients starting ETA with obesity class II [HR (95% CI) 1.27 (0.98; 1.65) or class III [1.79 (1.25; 2.55)] and for patients on IFX who were underweight [HR (95% CI) 1.82 (1.20; 2.76)] or in obesity class II [1.49 (0.98; 2.26)]. No effect modification was found for reported pain.Conclusion:Both underweight (as identified in IFX treated patients) and overweight patients (in ADA, ETA and IFX treated patients) discontinued a first TNFi treatment earlier than normal weight patients. Reported pain was not the main determinant. It remains uncertain what determines TNFi survival in individual patients.

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