Association of joint space narrowing with impairment of physical function and work ability in patients with early rheumatoid arthritis: protection beyond disease control by adalimumab plus methotrexate

Abstract

Objectives: Tumour necrosis factor inhibition plus methotrexate is believed to inhibit radiographic progression independent of inflammation. This analysis assessed whether these protective effects are exerted on bone (joint erosion; JE) and/or cartilage (joint space narrowing; JSN), and what the independent effects of JE/JSN progression are on longer-term patient-reported outcomes.

Methods: PREMIER was a 2-year, randomised, controlled trial of adalimumab plus methotrexate (ADA+MTX) versus the monotherapies. The impact of treatment on the relationships between time-averaged disease activity (TA-DAS28(CRP)) and changes in JE/JSN and associations of JE/JSN with the disability index of the health assessment questionnaire (HAQ-DI) at baseline and weeks 52 and 104 were assessed through non-parametric approaches of analysis of variance and quantile regression. JE/JSN association with employment status was evaluated at baseline and weeks 52 and 104 through logistic regression.

Results: Increasing tertiles of TA-DAS28(CRP) were associated with JE and JSN progression in the monotherapy groups, a phenomenon largely absent in ADA+MTX-treated patients. Although JSN was not associated with HAQ-DI at baseline, it was at 52 and 104 weeks. In contrast, JE was not associated with HAQ-DI at any time point examined. Odds of being employed at baseline, 52 weeks and 104 weeks were significantly associated with lower JSN, but not JE, scores.

Conclusions: ADA+MTX inhibited both JE and JSN progression independently of disease activity. JSN played a more prominent role in patient-reported outcomes than JE. Preventing the onset or worsening of JSN probably represents a critical aspect of effective disease management of early rheumatoid arthritis patients.

Trial registration: ClinicalTrials.gov NCT00195663.

Figures

Figure 1

Changes in joint erosion (JE) by time-averaged 28-joint disease activity score (TA-DAS28(C-reactive protein (CRP))) tertiles. Changes in JE are shown over 52 weeks (A) and 104 weeks (B) by tertiles of TA-DAS28(CRP). *p<.0.05 for treatment group difference compared with methotrexate monotherapy figures show the median line mean and iqr ada adalimumab.>

Figure 2

Changes in joint space narrowing (JSN) by time-averaged 28-joint disease activity score (TA-DAS28(C-reactive protein (CRP))) tertiles. Changes in JSN are shown over 52 weeks (A) and 104 weeks (B) by tertiles of TA-DAS28(CRP). **p

Figure 3

Relationship between radiographic measures and employment status. (A) Logistic regression analysis of the relationship between joint erosion (JE) or joint space narrowing (JSN) and employment status at baseline, 52 weeks and 104 weeks. Percentages of patients who were employed at baseline within each baseline JE (A) or JSN (B) tertile.