P027  Factors Associated with Biologic Discontinuation in Patients with Inflammatory Bowel Disease in TARGET-IBD

P027  Factors Associated with Biologic Discontinuation in Patients with Inflammatory Bowel Disease in TARGET-IBD

 

Barnes Edward1, Ahmad Harris2, Zhuo Joe2, Sreih Antoine2, Canavan James3, Nguyen Joehl2, Gazis Derek4, Hildebrand Janet4, Crawford Julie4, Long Millie1, Hanson John5
1 University of North Carolina at Chapel-Hill, Chapel Hill, United States, 2 Bristol Myers Squibb, Princeton, United States, 3 Bristol-Myers Squibb, Princeton, United States, 4 Target RWE Health Evidence Solutions, Durham, United States, 5 Carolina Medical Center Atrium Health, Charlotte, United States

BACKGROUND: A substantial portion of patients who initiate biologic therapy for the treatment of ulcerative colitis (UC) and Crohn’s disease (CD) discontinue therapy within 6-12 months of induction. To better understand patterns of treatment discontinuation in the real-world management of patients with inflammatory bowel disease (IBD), we identified factors associated with treatment discontinuation among patients enrolled in TARGET-IBD, an observational registry of patients with IBD

METHODS: TARGET-IBD is a longitudinal cohort of patients receiving care at 34 community and academic practices in the United States. Patients with IBD enrolled between July 24, 2017 and August 17, 2020 were included in this analysis. To be included, patients were required to initiate a biologic drug of interest during the study period, with no biologic use in the 6 months prior to induction. If less than 10 participants were treated with a given therapy class, they were excluded from multivariable analyses. The primary outcome was calculated as time (continuous months) from biologic start date to the earliest of: discontinuation (event), total colectomy/proctocolectomy, death, or date of last clinical contact. Variables to include in the multivariable models were determined based on a manual stepwise approach. The primary outcome was assessed using Kaplan-Meier testing and Cox proportional hazards modeling. We also examined reasons for treatment discontinuation.

RESULTS: A total of 856 patients were included (39% UC, 61% CD). The median disease duration at therapy initiation was 4 years among patients with UC and 5 years among patients with CD; 92% of patients with UC were biologic naïve, as were 74% of patients with CD. Among all 856 patients, 268 (31%) discontinued therapy during the study period. The median time to discontinuation or censoring was 10.6 months (IQR 4.1– 18.6 months). In multivariable analysis among patients with UC, discontinuation was less likely in patients treated with an anti-integrin (Hazard Ratio [HR] 0.51, 95% CI 0.30 – 0.86) relative to anti-tumor necrosis factor alpha (anti-TNF), adjusting for disease duration, concomitant methotrexate/thiopurine use, and C-reactive protein. Patients with CD using anti-integrin or IL-12/IL-23 inhibitors were less likely to discontinue therapy compared to patients treated with anti-TNF (HR 0.66, 95% CI 0.43 – 1.02); this difference was not statistically significant after adjustment for sex, insurance, previous biologic exposure, age at disease onset, disease location, and history of perianal fistula. The most frequent reasons for treatment discontinuation were primary non-response/lack of efficacy (21%), secondary non-response/lack of efficacy (31%), and side effects of therapy (23%). Development of antibodies was specifically noted among 10% of participants as a cause of treatment discontinuation.

CONCLUSION(S): In a multicenter cohort of patients with IBD, nearly one-third discontinued biologic treatment. The most common reason for discontinuation was secondary loss of response followed by side effects, then primary non-response. Primary non-response and secondary loss of response remain concerns in the treatment of patients with CD and UC, and continued emphasis on proactive strategies to maintain durability of therapies should be considered.