In early rheumatoid arthritis, comorbidities do not explain the increased risk of failure to reach remission in patients with obesity

Abstract

Objective: To examine whether obesity and/or overweight are independently associated with an increased risk of remission failure in patients with early rheumatoid arthritis (RA), treated with methotrexate as first disease-modifying antirheumatic drug, or if the previously reported associations could be explained by underlying comorbidities and lifestyle factors.

Methods: For patients included in the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study 2006-2018 initiating methotrexate monotherapy (n=1285), we captured data on body mass index, comorbidities and disease activity from EIRA and through linkage to nationwide Swedish clinical and quality registers. The primary outcome was failure to reach 28-joint Disease Activity Score (DAS28) remission at 3 and 6 months. Secondary outcomes included Boolean, Simplified Disease Activity Index and Clinical Disease Activity Index remission and their individual components. We estimated the relative risk (RR) of remission failure in patients with obesity and overweight compared with normal weight using modified Poisson regression, adjusting for potential confounders.

Results: After 6 months, 64% (n=98/153) of patients with obesity, 52% (n=171/326) with overweight and 48% (n=210/433) with normal weight failed to reach DAS28 remission, with an RR of 1.33 (95% CI 1.14 to 1.55) for patients with obesity after adjustment for age and sex. The increased risk of remission failure in patients with obesity remained after further adjustment for seropositivity, educational level, smoking, alcohol use, physical activity, calendar period, glucocorticoid treatment and comorbidities (RR=1.27, 95% CI 1.08 to 1.50). No significant association was observed for patients with overweight. The results were similar for the secondary outcomes and after 3 months.

Conclusion: Obesity is a risk factor for remission failure in early RA, independent of comorbid conditions.

Keywords: Arthritis, Rheumatoid; Epidemiology; Methotrexate; Sweden.

Figure 1. Flow chart showing selection of study population. EIRA, Epidemiological Investigation of Rheumatoid Arthritis; RA, rheumatoid arthritis; SRQ, Swedish Rheumatology Quality Register.

Figure 2. Relative risk of patients with overweight and obesity and early rheumatoid arthritis (RA) of not reaching remission compared with patients with normal weight, estimated by modified Poisson regression. (A) At 3 months after RA diagnosis. (B) At 6 months after RA diagnosis. Normal weight: BMI 18.5–24.9 kg/m² (reference), overweight: BMI 25–29.9 kg/m², obese: BMI≥30 kg/m². Crude: adjusted for sex and age. Adjusted: adjusted for serological status, glucocorticoid treatment at methotrexate initiation (yes/no), educational level, smoking, alcohol use, physical activity and calendar period of methotrexate start. Fully adjusted: adjusted+the individual comorbidity categories. Numbers are shown in online supplemental tables S7 and S10. BMI, body mass index; CDAI, Clinical Disease Activity Index; DAS28, 28-joint Disease Activity Score; SDAI, Simplified Disease Activity Index.

Figure 3. Relative risk of patients with overweight and obesity and early rheumatoid arthritis (RA) of scoring over the cut-off of the 28-joint Disease Activity Score (DAS28) components and visual analogue scale (VAS) pain compared with patients with normal weight, estimated by modified Poisson regression. (A) At 3 months after RA diagnosis. (B) At 6 months after RA diagnosis. Normal weight: BMI 18.5–24.9 kg/m² (reference), overweight: BMI 25–29.9 kg/m², obese: BMI≥30 kg/m². Results from the fully adjusted model are shown in the figure: adjusted for serological status, glucocorticoid treatment at methotrexate initiation, educational level, smoking, alcohol use, physical activity, calendar period of methotrexate start and the individual comorbidity categories. All models and numbers are shown in online supplemental table S11. BMI, body mass index; CRP, C reactive protein (mg/L); ESR, erythrocyte sedimentation rate (mm) (ESR>20 mm/hour for women/>15 mm/hour for men); PGA, Patient Global Assessment in VAS; SJC, swollen joint count (28 joints); TJC, tender joint count (28 joints).