RADIOGRAPHIC RESULTS FROM THE MINOCYCLINE IN RHEUMATOID-ARTHRITIS (MIRA) TRIAL

Objective. To assess radiographically determined disease progression i n patients in the Minocycline in Rheumatoid Arthritis (MIRA) Trial. Me thods. A double blind, randomized, multicenter, 48 week trial of oral minocycline (200 mg/day) or placebo in 6 clinical centers in the Unite d States. Patients include 219 adults with active RA previously receiv ing limited treatment with disease modifying drugs. Posteroanterior fi lms of the hands from baseline and finer visits, blinded for sequence, were read for erosions and joint space narrowing by trained observers . Outcomes included rate of disease progression (change/month) and per centage of patients with progression from baseline, newly involved joi nts, and newly erosive disease. Results. Using intent-to-treat analyse s, progression rates for erosions (0.11 +/- 0.42 minocycline, 0.17 +/- 0.41 placebo; p = 0.47) and joint space narrowing (0.16 +/- 0.55 mino cycline and 0.23 +/- 0.71 place bo; p = 0.14) were similar. (Power 43% to detect a 50% difference.) Newly erosive joints occurred more frequ ently in the placebo group (44 vs 32%; p = 0.08), not a statistically significant difference. Conclusion. Radiographic measurement of diseas e progression using 4 measures failed to show a significant difference between minocycline and placebo treatment, although for all methods t here was a trend toward treatment benefit, consistent with reported cl inical results. A one year trial duration, high measurement variabilit y, and slow rate of radiographic progression in this cohort may explai n the low power to detect a treatment effect. The measurement that den oted ''newly involved'' joints was most sensitive in detecting change. In future trials longer term assessment (minimum 2 years) of radiogra phic changes and further comparison of measures of disease progression are warranted.