Estimation of a numerical value for joint damage-related physical disability in rheumatoid arthritis clinical trials
- 1Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Austria
- 2Division of Rheumatology, University of Washington, Seattle, Washington, DC, USA
- Correspondence to Professor Josef S Smolen, Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna General Hospital, Waehringer Guertel 18–20, A-1090 Vienna, Austria;
Contributors JSS and DA designed the study, JG and TS recruited patients into the trial, JTS performed x-ray analyses, JSS and DA performed data analysis, JSS wrote the paper with major contributions from DA, as well as JG and TS.
- Accepted 17 August 2009
- Published Online First 27 August 2009
Background Joint damage is an important outcome in trials of rheumatoid arthritis (RA), usually assessed by Total Sharp Score (TSS). It is currently unknown how it translates numerically into disability by the Health Assessment Questionnaire (HAQ).
Objective To determine the units of HAQ score corresponding to one TSS unit.
Methods A short-term observational trial of glucocorticoids in RA (the ‘BEst LIfe with Rheumatoid Arthritis’ (BELIRA) trial) was evaluated, using randomised controlled clinical trial (RCT) data for confirmation. For each trial arm HAQ, TSS and the Simplified Disease Activity Index (SDAI) were assessed. Based on the hypothesis that short-term HAQ changes will mostly be due to changes of disease activity, activity HAQ (ACT-HAQ) at end point (EP) was determined and remaining disability defined as damage related (DAM-HAQ). Using TSS at EP, the HAQ units corresponding to a TSS unit were estimated.
Results In BELIRA, one TSS unit corresponded to a mean of 0.017 HAQ units; to account for other causes of irreversible disability, the 25th percentile was used: 0.011 HAQ units/TSS unit. In RCT trial arms, the HAQ/TSS were similar (0.013 and 0.015 in established and early RA, respectively; 25th percentile: 0.010). The correlation between DAM-HAQEP and TSS was r=0.829. Over 5 years, damage would amount to an increase of irreversible HAQ of 0.33 on placebo, 0.13 on disease-modifying antirheumatic drugs (DMARDs) and 0.03 on TNF inhibitors+methotrexate (MTX).
Conclusion An approach to estimate the numerical relationship between HAQ and damage as 0.01 HAQ points/TSS unit is presented, although the linear relationship may not be generally valid. This allows the assessment of functional correlates of radiographic changes in trials.
JTS is deceased.
Funding While we received data from the pharmaceutical industry, this study was not funded by any of the companies involved.
Competing interests JSS received honoraria and grant support from Abbott, Centocor, Schering-Plough, Wyeth and honoraria from Amgen and Sanofi-Aventis. DA received honoraria from Abbott, Schering-Plough, Sanofi-Aventis and Wyeth.
Ethics approval This study was conducted with the approval of the individual study centres and Medical University of Vienna.
Provenance and peer review Not commissioned; externally peer reviewed.