Abstract
BACKGROUND: Pediatric ulcerative colitis (UC) is typically more extensive and severe at diagnosis compared with adult disease. Tofacitinib, a Janus kinase inhibitor, has been used since 2018 to induce and maintain remission in UC. There are limited pediatric data regarding its use, either as a monotherapy or in combination with other treatments. OBJECTIVES: To determine the real-world experience and outcomes of tofacitinib therapy in the Irish national cohort with pediatric UC. METHODS: A retrospective study of tofacitinib outcomes was undertaken at Ireland's single national center for pediatric inflammatory bowel disease. All patients commenced on tofacitinib since its availability in 2019 were included. Baseline and follow-up clinical characteristics, phenotype, Pediatric Ulcerative Colitis Activity Index (PUCAI) scores, and treatments before and after tofacitinib commenced were recorded. The primary outcome was remission by 8 weeks, with other clinical outcomes being recorded to maximal available follow-up. RESULTS: Between November 1, 2019 and June 30, 2022, 15 children (M:F 1:2) were prescribed tofacitinib, 5 as monotherapy. Thirteen had baseline pancolitis at diagnosis and all patients had prior infliximab exposure. The mean time from diagnosis to starting tofacitinib was 381 days (±SD 265). Dual therapy included 5 with infliximab, 4 with vedolizumab, and 1 with adalimumab. The average length of treatment on tofacitinib was 232 days (±SD 170) with 2 patients transitioning to adult services while in remission on tofacitinib therapy. The mean PUCAI score was 48.7 (±SD 14.1) pre-tofacitinib, 16.7 (±SD 15.6) at week 8, and 22.5 (±SD 29.6) by week 16, with a significant reduction in PUCAI by week 16 (P = 0.0004). Eight patients (3 monotherapy) achieved clinical remission, with 4 of the 5 dual therapy patients on infliximab. There were no significant outcome differences between those on mono- or dual therapy. Three patients with combined vedolizumab therapy did not achieve remission, 2 of whom required colectomy by week 24. There were no malignancies, 1 patient developed shingles and another developed herpangina post-tofacitinib. Failure to achieve clinical remission by week 16 was seen in all children who progressed to colectomy (n = 4). CONCLUSION: Combining tofacitinib with other biologics is effective in select children with refractory UC. Early responders were more likely to achieve a sustained response at week 16. Failure to achieve remission by week 16 of tofacitinib therapy was strongly associated with progression to colectomy.