Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: a NORD-STAR study

Abstract

Objective: This report from the NORD-STAR (Nordic Rheumatic Diseases Strategy Trials and Registries) trial aimed to determine if obesity is associated with response to conventional and biological antirheumatic treatment in early rheumatoid arthritis (RA).

Methods: This report included 793 participants with untreated early RA from the randomised, longitudinal NORD-STAR trial, all of whom had their body mass index (BMI) assessed at baseline. Obesity was defined as BMI ≥30 kg/m². All participants were randomised 1:1:1:1 to one of four treatment arms: active conventional treatment, certolizumab-pegol, abatacept and tocilizumab. Clinical and laboratory measurements were performed at baseline and at 8, 12, 24 and 48-week follow-up. The primary endpoint for this report was response to treatment based on Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) remission and Disease Activity Score with 28 joints using C-reactive protein (DAS28-CRP) <2.6 stratified by BMI.

Results: Out of 793 people included in the present report, 161 (20%) had obesity at baseline. During follow-up, participants with baseline obesity had higher disease activity compared with those with lower BMI, despite having similar disease activity at baseline. In survival analyses, obesity was associated with a lower likelihood of achieving response to treatment during follow-up for up to 48 weeks (CDAI remission, HR 0.84, 95% CI 0.67 to 1.05; SDAI, HR 0.77, 95% CI 0.62 to 0.97; DAS28-CRP <2.6, HR 0.78, 95% CI 0.64 to 0.95). The effect of obesity on response to treatment was not influenced by the treatment arms.

Conclusion: In people with untreated early RA followed up for up to 48 weeks, obesity was associated with a lower likelihood of good treatment response, irrespective of the type of randomised treatment received.

Trial registration number: NCT01491815.

Keywords: Rheumatoid Arthritis; Risk Factors; Treatment.

Figure 1

Study design of the present report. Early termination because of abnormal laboratory results (which ruled out continuation of the study drug as determined by the investigator), lack of efficacy, death or other reasons. Arm 1—active conventional treatment (ACT); arm 2—methotrexate (MTX)+certolizumab; arm 3— MTX+abatacept; arm 4—MTX+tocilizumab. ADH, failure to adhere to the protocol; BMI, body mass index; ITT analysis, intention-to-treat analysis; PD, protocol deviation, PP analysis, per-protocol analysis; RA, rheumatoid arthritis.

Figure 2

Disease activity scores and response to treatment percentage over time stratified by BMI=30 kg/m². Mean values (A), level changes (B) and remission scores (C) for CDAI, SDAI and DAS28-CRP <2.6. Markers of disease activity are shown as mean values and SD. Relative delta changes in markers of disease activity are shown as mean and 95% CI. The relative delta changes between baseline and follow-up values were calculated as: (follow-up value – baseline value)/baseline value. Response to treatment is shown as % of participants who achieved response to treatment at certain time points during follow-up. P values for continuous variables have been calculated by linear regression analysis adjusted for sex, baseline age, current smoking, Patient Pain by VAS, DAS28-CRP, ACPA and treatment randomisation. P values for remission rates have been calculated by logistic regression analysis adjusted for sex, baseline age, current smoking, Patient Pain by VAS, DAS28-CRP, ACPA and treatment randomisation. *p<0.05, **p<0.01, ***p<0.001. ACPA, anti-cyclic citrullinated peptide; BMI, body mass index; CDAI, Clinical Disease Activity Index; DAS28-CRP, Disease Activity Score with 28 joints using C-reactive protein; SDAI, Simplified Disease Activity Index; VAS, Visual Analogue Scale (0–100 mm).

Figure 3

Disease activity markers over time in study participants stratified by BMI=30 kg/m². Mean values (A) and level changes (B) for SJC28, TJC28, CRP, Patient Global by VAS (0–100 mm), Physician Global by VAS (0–100 mm) and Patient Pain by VAS (0–100 mm). Markers of disease activity are shown as mean values and SD. Relative delta changes in markers of disease activity are shown as mean and 95% CI. The relative delta changes between baseline and follow-up values were calculated as: (follow-up value – baseline value)/baseline value. P values have been calculated by linear regression analysis adjusted for sex, baseline age, current smoking, Patient Pain by VAS, DAS28-CRP, ACPA and treatment randomisation. *p<0.05, **p<0.01, ***p<0.001. ACPA, anti-cyclic citrullinated peptide; BMI, body mass index; CRP, C-reactive protein; DAS28-CRP, Disease Activity Score with 28 joints using C-reactive protein; SJC, swollen joint count; TJC, tender joint count; VAS, Visual Analogue Scale of pain (0–100 mm).

Figure 4

Kaplan-Meier curves for response to treatment according to BMI=30 kg/m². CDAI remission (A); SDAI remission (B); DAS28-CRP <2.6 (C). Log-rank p values together with HRs and p values adjusted for sex, baseline age, current smoking, Patient Pain by VAS, DAS28-CRP, ACPA and treatment randomisation. ACPA, anti-cyclic citrullinated peptide; BMI, body mass index; CDAI, Clinical Disease Activity Index; DAS28-CRP, Disease Activity Score with 28 joints using C-reactive protein; SDAI, Simplified Disease Activity Index; VAS, Visual Analogue Scale of pain.

Figure 5

Kaplan-Meier curves for CDAI, SDAI remission, DAS28-CRP <2.6 stratified by treatment arms. Arm 1 —active conventional treatment (ACT; A); arm 2—methotrexate (MTX)+certolizumab (B); arm 3— MTX+abatacept (C); arm 4—MTX+tocilizumab (D). BMI, body mass index; CDAI, Clinical Disease Activity Index; DAS28-CRP, Disease Activity Score with 28 joints using C-reactive protein; SDAI, Simplified Disease Activity Index.