A key lesson of both RABBIT and SABER is that much of the increased serious infection risk stems from comorbid conditions. The RABBIT investigators identified three additional risk factors: chronic lung disease, chronic kidney disease, and age older than 60 years. RA patients who had these three additional risk factors and were on at least 15 mg/day of prednisone had a serious infection rate of 45% per year if they were on an anti-TNF agent and 25% per year when on a conventional DMARD. If they had two additional risk factors rather than three, their serious infection risk dropped to less than 20% per year on anti-TNF therapy, and about half that on a conventional DMARD.
In contrast, patients with all three additional risk factors who were on less than 7.5 mg/day of prednisone or none at all had a serious infection rate below 10% per year if they were on a TNF inhibitor, and 5% if on a nonbiologic DMARD, Dr. Winthrop noted.
Similarly, SABER participants with chronic obstructive pulmonary disease at baseline had an absolute two- to threefold greater risk of serious infection on a TNF inhibitor or DMARD, compared with patients without COPD. Baseline diabetes mellitus also magnified the serious infection risk in SABER, although not in RABBIT, he continued.
The RABBIT investigators found that improvement in functional capacity resulting from effective treatment significantly reduced the risk of serious infections. Indeed, functional improvement had a greater impact on infection risk than did improvement in the DAS28 (disease activity score based upon a 28-joint count).
SABER was funded by the Food and Drug Administration, the Agency for Healthcare Research and Quality, and the Department of Health and Human Services.
Dr. Winthrop reported having received consultant fees from Abbott, Amgen, and Pfizer as well as research funding from Pfizer.