Combination advanced therapy use and infection risks in immune-mediated inflammatory diseases

OBJECTIVE: To evaluate real-world evidence on combination advanced therapy (CAT) exposures and safety in patients with immune-mediated inflammatory diseases (IMIDs). METHODS: We conducted a retrospective new-user cohort study of individuals initiating advanced therapies between 2016 to 2023 using MarketScan® databases. We assessed for overlapping (≥30 days) exposures to different targeted synthetic or biologic disease-modifying antirheumatic drug (ts/bDMARD) classes (CAT episodes). We described baseline characteristics and calculated multivariate hazard ratios (HRs) for first CAT episode persistence. We estimated HRs for first serious infection (i.e. requiring hospitalization or intravenous antibiotics) comparing combined versus single advanced therapy, stratified by CAT regimens and IMIDs. RESULTS: A total of 270,198 individuals initiated 693,375 advanced therapy episodes, including 38,456 (14.2%) who started 52,212 CAT episodes. The most common IMIDs among CAT users were psoriasis, inflammatory bowel disease, rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis (AxSpA). Among CAT episodes, 51.2% involved TNFi exposure. Median duration of first CAT exposure was 42 days. CAT was associated with 5.2 serious infections per 100 person-years, yielding a HR of 1.61 (95% CI: 1.46-1.78) compared to monotherapy. Anti-adhesion agents combined with TNFi was associated with serious infection (HR 1.49, 95% CI 1.09-2.04) compared to other combinations. In IMID-stratified analysis, CAT (versus monotherapy) was associated with higher risk of serious infection across all diseases, except AxSpA. CONCLUSIONS: CAT was predominantly used within the spondyloarthritis umbrella of diseases. CAT exposure was associated with short duration and increased serious infection risk, although this risk varied by CAT regimen and underlying IMID.