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

Abstract

ObjectivesThe aim of this paper was to analyse the impact of obesity, in addition to known predictors, on disease outcome in early rheumatoid arthritis (RA).MethodsBody 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.ResultsObesity 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.ConclusionsIn 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 numberNCT00764725; Post-results. WHO database at the Karolinska University Hospital: CT20080004.

A systematic review of the association of obesity with the outcomes of inflammatory rheumatic diseases

“…(67) IL-6 inhibitors, comprising the relatively new agent tocilizumab, inhibit IL-6mediated signalling and induce B-regulatory cells, decreasing pro-inflammatory cytokines. (68) We found that the studies involving TNF-α inhibitors were associated with different outcomes: four studies (2,10,16,17) were associated with positive outcomes, three studies (25,26,29) with neutral outcomes and ten studies (11,(32)(33)(34)40,55,56,61,62,65) with negative outcomes. Rituximab was associated with positive, (17) neutral (23) and negative (11,56) outcomes, while tocilizumab was similarly associated with positive, (15) neutral (22,27) and negative (11,56) outcomes.…”

Body Mass Index and Clinical Response to Tocilizumab in Patients With Rheumatoid Arthritis

“…Body mass index, a modifiable and easily recognized factor, has been reported to be associated with clinical response to IFX among RA patients in several studies. [6][7][8][9][10] A clinically important question is whether BMI at treatment initiation also influences treatment response to other bDMARDs other than IFX, thus we conducted this study to determine the relationship between baseline BMI and clinical response to TCZ among RA patients using our prospective cohort study data. Although multiple clinical response criteria and different comparison methods (quantitative and qualitative comparison) have been utilized, non-significant evidence was found and our results are in accordance with the findings of previous studies.…”

“…6 Subsequently, several studies have replicated the negative association of BMI at initial treatment with clinical response to IFX, RA patients with higher BMI having decreased likelihood to achieve favorable clinical response. [7][8][9][10] Intriguingly, one study performed by Gremese et al 7 consisting of 641 patients with longstanding RA patients treated by three types of TNF-a inhibitors (adalimumab, etanercept, and IFX) found that obese patients were less likely to achieve remission compared with non-obese patients when all these three types of TNF-a inhibitors were considered. When data were analyzed according to the type of TNF-a inhibitor separately, significant evidence was only found for IFX, and the results indicated that obesity was particularly associated with clinical response to IFX.…”

“…Based on the finding of RA patients with higher BMI being less likely to respond well to IFX, [6][7][8][9][10] it is natural to consider whether BMI affects the clinical response to bDMARDs other than IFX. As a consequence, the association between BMI and treatment response to abatacept (ABA, T-cell co-stimulation inhibitor), 13,[29][30][31][32] rituximab (B-cell depletion) 33 and TCZ 11,15,16 has been analyzed; however, non-significant evidence was found.…”

“…The available studies indicate that BMI might hold the potential to guide the personalized treatment for infliximab (IFX), a TNF-a inhibitor. [6][7][8][9][10] Whether BMI may also be used to guide the personalized treatment of other bDMARDs, particularly for TCZ, is of great interest, due to the relationship between IL-6 and obesity. It has been suggested that IL-6 could exert significant effect on weight status.…”