Estimation of a numerical value for joint damage-related physical disability in rheumatoid arthritis clinical trials.
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-HAQ(EP) 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).


CONCLUSIONS
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.
Smolen
Josef S
JS
Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria. josef.smolen@wienkav.at
Aletaha
Daniel
D
Grisar
Johannes C
JC
Stamm
Tanja A
TA
Sharp
John T
JT
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D004185:Disability Evaluation; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D018501:Antirheumatic Agents; D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D008775:Methylprednisolone