Methods: The Brigham RA Sequential Study (BRASS) is a longitudinal cohort of RA patients followed in a hospital-based practice of 21 rheumatologists. The cohort began enrolling in 2003 and baseline data include demographics, joint examination, RF and CCP titers, and medications. DAS28-CRP scores are measured annually, and medication changes are recorded every 6 months. We analyzed trends in medication use over 24 months using McNemar’s test, and examined trends in DAS28-CRP over the same period using a mixed model.
Results: There are 961 subjects enrolled in BRASS (82% female, mean age of 57 years, mean disease duration of 14 years, and mean DAS28-CRP 4.1). Among 591 subjects with medication data at baseline and 24 months, there were significant declines in the use of steroids (p=0.003) and NSAIDs (p<0.001) and a significant increase in the use of TNF inhibitors (p<0.001). For example, while 51% of subjects were on NSAIDs at baseline, only 44% were on NSAIDs at 24 months. 39% of subjects were on TNF inhibitors at baseline, compared to 46% at 24 months.
In 686 subjects with laboratory data at 12 months, the mean DAS28-CRP was 3.5. In 394 subjects with data at 24 months, the mean DAS28-CRP remained stable at 3.5. After adjusting for age, sex, disease duration, and CCP, the trend toward improvement in DAS28-CRP is still observed between baseline and 24 months (p<0.001).
In our subset of subjects with available DAS28-CRP and medication use data at 12 months, 74 subjects who started TNF inhibitors demonstrated a mean reduction in DAS28-CRP of 1.12 over the first 12 months (p<0.001). Improvement in DAS28-CRP was also noted in subjects who were never on TNF inhibitors (n=378, mean reduction 0.53, p<0.001), as well as those who were on TNF inhibitors both at baseline and 12 months (n=247, mean reduction 0.50, p<0.001). The improvement noted in subjects who started TNF inhibitors was significantly greater than that noted in subjects who were never on TNF inhibitors (p<0.001). Subjects who stopped TNF inhibitors between baseline and 12 months had a non-significant increase in DAS28-CRP of 0.12 (n=28, p=0.59).
Conclusion: In this large practice-based clinical cohort, there was a significant trend toward a decrease in disease activity over the initial 24 months of follow-up. During this same time period, the use of TNF inhibitors increased and NSAID and steroid use decreased. While it is difficult to correlate these observations in a non-trial setting, the trends are compelling, and are consistent with findings in large clinical trials of biologic therapies.
K.L. Batra, None; J. Cui, Millennium Pharmaceuticals, 2; Biogen IDEC MA Inc., 2; R. Glass, Millennium Pharmaceuticals, 2; Bristol Myers Squibb Foundation, 2; Biogen IDEC MA Inc., 2; D.H. Solomon, Merck, 2; Pfizer, 2; Savient, 2; Proctor & Gamble, 2; Millennium Pharmaceuticals, 2; N.E. Maher, Millennium Pharmaceuticals, 2; Bristol Myers Squibb, 2; Biogen IDEC MA Inc., 2; M.E. Weinblatt, Millennium Pharmaceuticals, 2; Biogen, 2; Amgen, 2; Abbott, 2; Millennium Pharmaceuticals, 5; Biogen, 5; Amgen, 5; Abbott, 5; Wyeth, 5; Centocor, 5; UCB, 5; N.A. Shadick, Millennium Pharmaceuticals, 2; Biogen IDEC MA Inc., 2; Glaxo Smith Kline, 2; Dow Chemical Corporation, 2; Bristol Myers Squibb Foundation, 2.