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

Ann Rheum Dis. 2013 Jul;72(7):1156-62. doi: 10.1136/annrheumdis-2012-201620. Epub 2012 Aug 22.


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: NCT00195663.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / drug therapy*
  • Cartilage, Articular / diagnostic imaging
  • Disease Progression
  • Double-Blind Method
  • Drug Therapy, Combination
  • Employment / statistics & numerical data
  • Female
  • Foot Joints / diagnostic imaging
  • Hand Joints / diagnostic imaging
  • Humans
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Radiography
  • Treatment Outcome
  • Work Capacity Evaluation*


  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Adalimumab
  • Methotrexate

Associated data