Treatment-related improvement in physical function varies with duration of rheumatoid arthritis. A pooled analysis of clinical trial results

D Aletaha ^1*, V Strand ², J S Smolen ³ and M M Ward ⁴

¹ Medical University of Vienna, Austria
² Stanford University, United States
³ University of Vienna, Austria
⁴ National Institutes of Health, United States

^* To whom correspondence should be addressed. E-mail: daniel.aletaha{at}meduniwien.ac.at.

Accepted 21 June 2007

Abstract

Background: Physical function in rheumatoid arthritis (RA) has reversible and irreversible components, and is typically assessed by the Health Assessment Questionnaire Disability Index (HAQ). Since irreversible components are expected to increase with longer duration of RA and reduce the ability for improvement in physical function, we analyzed responsiveness of HAQ scores in patient populations with differing RA durations in randomized controlled trials (RCTs).

Methods: Data from all RCTs published between 1980 and 2005 that reported changes from baseline in HAQ at 6 and/or 12 months were analyzed. Treatments were grouped as "biologics", or "traditional" disease modifying antirheumatic drugs (DMARDs), and "placebo". We computed effect sizes of HAQ in each trial, and contrasted the association between these effects and duration of RA among treatment groups using regression models.

Results: We identified 42 RCTs with complete data for the statistical models. The models indicate that discrimination of functional improvement between active drug groups and placebo is reduced in patients with longer duration of RA (p=0.02 for the change in discrimination over time). The placebo-adjusted HAQ responses decreased on average by 0.37 per year of RA duration.

Conclusion: Responsiveness in HAQ scores is inversely associated with mean disease duration in RA. This impacts assessment of physical function, a key outcome measure in RCTs and practice, and impacts the ability to discriminate active treatment from placebo.

Keywords: discrimination of effects, function limitation, health assessment questionnaire, rheumatoid arthritis

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