Abstract Background The concept of dual biologics therapy (DBT) in inflammatory bowel diseases (IBD) generates growing interest. Small-scale studies suggest its effectiveness, but data from unselected cohorts remain scarce. This nationwide study aimed to evaluate the effectiveness and durability of DBT in IBD. Methods We utilized data from the epi-IIRN cohort that includes data from all four health maintenance organizations (HMOs) in Israel, covering 98% of the population. Medication data are highly accurate since they are being dispensed and subsidized via the HMO. Patients with IBD who received concurrent biologic or small-molecule therapy in parallel for at least one month were included. We further evaluated the time to discontinuation of combination therapy and the time to initiation of corticosteroid treatment. Results Among 74,372 patients with IBD, 63 patients (0.08%) had documented DBT, including 65% with Crohn’s disease and 35% with ulcerative colitis with a median follow-up of 5.5 months since starting DBT IQR 3.85-12.5. While 57% of patients had pediatric-onset disease, most DBT (65%) were initiated during adulthood (mean age 31.9 years). The most commonly used agents were anti-TNF (n = 42) and vedolizumab (n = 38), with the most frequent combination being anti-TNF+vedolizumab (n = 23; 36.5%), followed by anti-TNF+ustekinumab (n = 14; 22%), ustekinumab+vedolizumab (n = 7; 11%), tofacitinib+vedolizumab (n = 6; 9.5%), and upadacitinib+ustekinumab (n = 5; 7.9%). Rapid decline in treatment durability was observed during the first six months, with a median DBT duration of 6.3 months (95% CI, 5.0-12.5). By the end of follow-up, 27% (17/63) of patients remained on DBT (none required corticosteroids); 47.6% (30/63) discontinued one biologic yet continued without steroid treatment, and 25.4% (16/63) discontinued one biologic and subsequently required systemic or locally active corticosteroids (Figure). No meaningful differences were observed between Crohn’s disease and ulcerative colitis; at 6 months, systemic and locally active steroid use was similar (8-9 percent for systemic and 9-16 percent for locally active; log-rank p 0.7). Conclusion In this nationwide study, DBT was infrequently used and typically discontinued within months. Nevertheless, the low rates of subsequent corticosteroid use might suggest that DBT discontinuation reflected disease improvement rather than treatment failure. Alternatively, the early discontinuation could, in part, reflect clinicians’ caution regarding the safety of combination therapy. These findings provide further real-world evidence supporting the potential role of short-term DBT in IBD management and highlight the need for further evaluation of both its efficacy and safety. Conflict of interest: Yuval Bar-Asher, Shira: No conflict of interest Sokolik, Menachem: No conflict of interest Ben-Tov, Amir: No conflict of interest Zacay, Galia: No conflict of interest Matz, Eran: No conflict of interest Zekaria, Shir: No conflict of interest Dotan, Iris: No conflict of interest Turner, Dan: No conflict of interest
Bar-Asher et al. (Thu,) studied this question.