Infection Risk Associated with Steroid-Sparing Therapies in GCA, PMR, and ANCA-Associated Vasculitis: A Systematic Review.

OBJECTIVE: Giant cell arteritis (GCA), polymyalgia rheumatica (PMR), and ANCA-associated vasculitis (AAV) often require prolonged glucocorticoid therapy. Steroid-sparing biologic and small molecule therapies reduce glucocorticoid exposure, but may increase infection risk, particularly in older adults. We evaluated infection risk associated with these therapies with concomitant glucocorticoid treatment, versus glucocorticoid treatment alone, in vasculitis/PMR clinical trials. METHODS: We searched PubMed, Embase, Cochrane, and ClinicalTrials.gov using terms related to GCA, PMR, AAV, biologics (tocilizumab, sarilumab), small molecule therapies (upadacitinib, avacopan), glucocorticoids, and infection outcomes. We included randomized controlled trials (RCTs) comparing biologics or small molecules plus glucocorticoid (active intervention) versus glucocorticoid monotherapy (comparator) reporting infection outcomes. We calculated the relative risk (RR) of infection and difference in glucocorticoid dose between the comparator and active intervention groups. RESULTS: We included 10 RCTs (1,487 patients total, enrolling adults averaged ≥50 years): 4 tocilizumab, 3 avacopan, 2 sarilumab, and 1 upadacitinib. When the active intervention had much lower glucocorticoid dosing than the comparator, the RR for infection was either close to 1 or <1. When the active intervention glucocorticoid dose was comparable to the comparator, the RR for infection was >1. CONCLUSION: Steroid-sparing therapies reduced glucocorticoid exposure with varying magnitudes but were not consistently associated with lower infection risk. These findings underscore the heightened risk of infection when these novel therapies are used in combination with glucocorticoids when the glucocorticoid dose cannot be adequately tapered, particularly in older adults.