Drug persistence of first- and advanced-line therapy for chronic inflammatory pouch disorders: A prospective cohort...

Chronic inflammation of the pouch may affect a significant proportion of patients following ileal pouch-anal anastomosis (IPAA), increasingly treated by advanced therapies. Persistence of such agents or evidence to guide sequencing is scarce. This study aims to quantify first- and advanced-line drug persistence and identify factors associated with discontinuation.

This single-center prospective cohort enrolled adults with IPAA (1986-2021) who initiated biologic/small-molecule therapy between 2001-2024. Persistence was defined as treatment continuation at the last follow-up. Kaplan-Meier and Cox models estimated persistence and its predictors.

Of 186 patients, 38 (20.4 %) initiated advanced therapy. Overall follow-up was 16.8y. Agents included: adalimumab 21 (32 %), infliximab 17 (26 %), ustekinumab 16 (25 %), vedolizumab 5 (7.7 %), upadacitinib 3 (4.6 %), risankizumab 1 (1.5 %), certolizumab 1 (1.5 %), and golimumab 1 (1.5 %). Advanced treatment commenced at a median of 10.7y after ileostomy closure. Advanced treatments (≥2nd line) were prescribed for 15 patients (40 %). Each additional treatment line doubled the discontinuation risk (HR 2.48, 95 % CI 1.26-4.90). Ustekinumab retained the highest persistence post-failure of a previous advanced therapy.

In inflammatory pouch disorders, biologic/small-molecule persistence falls steeply after first-line failure, underscoring the importance of early drug selection and avoidance of recycled pre-IPAA agents. Ustekinumab shows superior persistence both as first- and second-line therapy.