Obesity is a strong predictor of worse clinical outcomes and treatment responses in early rheumatoid arthritis: results from the SWEFOT trial

Abstract

Objectives: The aim of this paper was to analyse the impact of obesity, in addition to known predictors, on disease outcome in early rheumatoid arthritis (RA).

Methods: Body mass index (BMI) was available in 260 patients from the Swedish pharmacotherapy trial (SWEFOT). Differences in disease activity (DAS28), functional impairment (HAQ), pain (Visual Analogue Scale, VAS-pain) and radiographic damage were evaluated over 24 months between BMI categories (obese BMI >30, n=43; overweight BMI=25-29.9, n=74; normal BMI <25, n=143) using non-parametric testing. Predictors of European League Against Rheumatism non-remission (DAS28 ≥2.6) at 24 months of follow-up were evaluated using binary univariate and multivariate logistic regression.

Results: Obesity at baseline was associated with worse continuous-scale clinical outcomes over 24 months (DAS28, HAQ and VAS-pain at last visit: obese vs normal: p<0.001; obese vs overweight: p<0.05). Furthermore, obese patients compared with non-obese patients had significantly greater odds of non-remission at 24 months (adjusted OR (aOR) 5.2; 95% CI 1.8 to 15.2). Other independent predictors were female sex (aOR 2.6; 95% CI 1.1 to 5.8), current smoking (aOR 2.6; 95% CI 1.1 to 6.3) and HAQ (per-unit increase, aOR 1.9; 95% CI 1.1 to 3.4). The pattern was similar among seropositive and seronegative patients; and in the subgroups of methotrexate responders and patients randomised at 3 months to add-on of sulfasalazine+hydroxychloroquine, although not significant with add-on of infliximab. Obesity had no independent association to radiographic progression.

Conclusions: In this early RA trial reflecting today's standard treatment, obesity, in addition to sex, smoking and functional impairment strongly lowered the chance of attaining good clinical outcomes, including remission, today's treatment goal. This highlights the importance of considering lifestyle modification as one of the cornerstones of RA care.

Trial registration number: NCT00764725; Post-results. WHO database at the Karolinska University Hospital: CT20080004.

Keywords: DMARDs (synthetic); anti-TNF; body mass index; disease activity; early rheumatoid arthritis; predictions and projections; treatment.

Conflict of interest statement

Competing interests: AL, KB, IH, KH, CL and SS have no conflicts of interest to disclose; RFvV has received grants/research support from AbbVie, BMS, GSK, Pfizer, Roche and UCB—and has received consultancy fees from AbbVie, Biotest, BMS, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer,Roche, UCB and Vertex outside the submitted work.

Figures

Figure 1

Changes in clinical outcome measures over 24 months on a continuous scale in the whole SWEFOT trial population with available baseline BMI categories. Mann-Whitney U tests were performed for all calculations. Medians and IQR are plotted for each BMI category. (A–D): DAS28, HAQ, VAS-pain and ESR, respectively, are plotted at BL; and at 3, 6, 9, 12, 18 and 24 months (m). BL, baseline; BMI, body mass index; SWEFOT, Swedish Pharmacotherapy Trial.

Figure 2

Changes in clinical disease activity over 24 months on a continuous scale in SWEFOT trial participants randomised to triple therapy or anti-TNF with available baseline BMI categories. Patients not achieving low disease activity (DAS28 A) is the combination of the two randomised groups, triple therapy (B), n=94 or anti-TNF (C), n=91. Responders to methotrexate (DAS28 ≤3.2) continued on monotherapy and are not included due to non-randomisation. Sample size (n) for normal weight, overweight and obese in (A): 103, 48, 32; (B): 52, 22, 20; and (C): 53, 26, 12, respectively. Obese versus normal weight: *p<0.05; **p≤0.002. BMI, body mass index; EULAR, European League Against Rheumatism; m, months; SWEFOT, Swedish Pharmacotherapy Trial; TNF, tumour necrosis factor.

Figure 3

Independent baseline predictors of non-remission at 24 months of follow-up in the SWEFOT trial population. (A) Adjusted ORs with 95% CIs for significant predictors in a binary logistic multivariate analysis of non-remission. Additional information can be found in table 2. (B) Risk matrices showing the likelihood (%) of non-remission with different combinations of predictors presented in (A). BMI and 24-month disease activity was available for 215 out of originally 403 SWEFOT trial participants. Of these, HAQ was available for 211 patients and smoking habits for 156 patients. Of those with HAQ and smoking habits (n=154), 26 were obese; 34, current smokers; 22, methotrexate responders; 65, randomised to triple therapy; 67, randomised to methotrexate+TNF inhibitor infliximab. HAQ, Health Assessment Questionnaire; NS, not significant; SWEFOT, Swedish Pharmacotherapy Trial; TNF, tumour necrosis factor.

Figure 4

Baseline BMI and disease activity over 24 months among SWEFOT trial participants: stratification by ACPA serostatus (A) ACPA-negative patients; (B) ACPA-positive patients. Normal weight, BMI<25 (A, n=43; B, 91); overweight, 25–29.9 (A, n=25; B, 45); obese, ≥30 (A, n=17; B, 23). Mann-Whitney U tests were performed for all calculations. Medians, IQR for each BMI category with DAS28 are plotted at BL; and at 3, 6, 9, 12, 18 and 24 months. ACPA, anticitrullinated protein antibody; BL, baseline; BMI, body mass index; m, months; SWEFOT, Swedish Pharmacotherapy Trial.