MEANINGFUL IMPROVEMENT CRITERIA SETS IN A RHEUMATOID-ARTHRITIS CLINICAL-TRIAL

Objective. To compare 3 sets of criteria for meaningful improvement in a rheumatoid arthritis (RA) clinical trial, and to evaluate the impli cations of these criteria sets for RA trial design. Methods. Data were obtained from the Minocycline in Rheumatoid Arthritis (MIRA) trial (p rimary outcome measures: 50% improvement in joint tenderness and 50% i mprovement in joint swelling, based on joint scores), These MIRA data were evaluated against 1) the Paulus criteria (20% improvement in 4 of 6 measures: joint tenderness scores, joint swelling scores, physician 's and patient's global assessments, erythrocyte sedimentation rate [E SR], and morning stiffness); and 2) the American College of Rheumatolo gy (ACR) criteria (20% improvement in joint tenderness and joint swell ing counts, and in 3 of 5 other measures: physician's and patient's gl obal assessments, ESR, modified Health Assessment Questionnaire, and p atient's pain assessment), The ACR criteria were modified using 3 of 4 remaining measures, since baseline pain assessment data were not avai lable. Results. Percentages of minocycline-treated patients versus pla cebo-treated patients showing meaningful improvement were as follows: by MIRA criteria, for joint tenderness, 56% versus 41% (P = 0.021), an d for joint swelling, 54% versus 39% (P = 0.023); by Paulus criteria, 41% versus 28% (P = 0.040); and by ACR criteria, 44% versus 26% (P = 0 .004), Both the modified ACR criteria and the Paulus criteria demonstr ated a reduced placebo response rate, Compared with the MIRA criteria, the ACR criteria increased, and the Paulus criteria decreased, absolu te between-group differences in improvement; however, both criteria se ts increased relative percentages of patients showing improvement in t he minocycline group versus the placebo group, Study design considerat ions indicated that application of the ACR criteria would reduce the r equired sample size. Conclusion. Different placebo response rates and treatment group differences were found using the 3 RA improvement crit eria sets, These findings support the use of the ACR criteria for defi ning improvement in RA clinical trials.