Open AccessContinuous indices of core data set measures in rheumatoid arthritis clinical trials: Lower responses to placebo than seen with categorical responses with the American College of Rheumatology 20% criteria
Author(s) -
Pincus Theodore,
Amara Ingrid,
Koch Gary G.
Publication year - 2005
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.20995
Subject(s) - medicine , rheumatoid arthritis , rheumatology , placebo , leflunomide , methotrexate , categorical variable , erythrocyte sedimentation rate , physical therapy , clinical trial , surgery , statistics , mathematics , alternative medicine , pathology
Objective To describe indices that are continuous counterparts of categorical responses to the American College of Rheumatology 20% improvement criteria (ACR20), ACR50, and ACR70, which extend rheumatoid arthritis (RA) clinical trial results and recognize clinical worsening (as well as improvement) with active and placebo treatments. Methods Data from a clinical trial of leflunomide, methotrexate, and placebo treatment over 1 year were reanalyzed. Percent change was computed for each of the 7 components of the ACR core set of outcome measures. Four continuous indices were computed: 1) ACR‐N (lowest of 3 values: number of swollen joints, number of tender joints, and median of the other 5 measures); 2) composite (median of all 7 measures [3 patient and 3 assessor measures plus erythrocyte sedimentation rate]); 3) patient‐only (median of physical function, pain, and global status); and 4) assessor‐only (median of number of swollen joints, number of tender joints, and global status). Means, medians, categorical 20%, 50%, and 70% responses, and continuous probability plots were computed according to each index for the 3 treatment groups and were compared with one another and with standard ACR20, ACR50, and ACR70 responses. Results Mean levels of improvement calculated using the different methods, in patients taking leflunomide, placebo, and methotrexate, respectively, were as follows: ACR‐N 20%, −12%, and 13%; composite 43%, 9%, and 33%; patient‐only 36%, 0%, and 26%; assessor‐only 50%, 20%, and 44%; and ACR20 52%, 26%, and 46%. Differences between leflunomide and placebo were 30–36%, and differences between methotrexate and placebo were 24–26%. Conclusion Continuous indices may be an informative addition to categorical ACR 20%, 50%, or 70% responses to compare efficacies of various treatments in RA, and to describe lower responses to placebo by recognizing worsening as well as improvement.