Tofacitinib Therapy in Children and Young Adults With Pediatric-onset Medically Refractory Inflammatory Bowel Disease

Abstract

Objectives: Tofacitinib, a selective Janus kinase inhibitor, effectively induces and maintains remission in adults with inflammatory bowel disease (IBD), but data are limited in children. This study aimed to evaluate the efficacy and safety of tofacitinib for medically refractory pediatric-onset IBD. Methods: This single-center retrospective study included subjects ages 21 years and younger who started tofacitinib for medically refractory IBD. Clinical activity indices, clinical response, steroid-free remission, biochemical response, and adverse events (AEs) were evaluated over 52 weeks.Results: Twenty-one subjects, 18 with ulcerative colitis or indeterminate IBD, received tofacitinib. At the end of the 12-week induction period, 9 out of 21 (42.9%) subjects showed clinical response and 7 out of 21 (33.3%) were in steroid-free remission. Of evaluable subjects at 52 weeks, 7 out of 17 (41.2%) showed clinical response and were in steroid-free remission. Of those remaining on tofacitinib at 1 year, none required concomitant systemic corticosteroids. Tofacitinib was discontinued in 8 subjects because of refractory disease, including 8 who ultimately underwent colectomy, and in 1 subject who developed a sterile intra-abdominal abscess. There were no instances of thrombi, zoster reactivation, or clinically significant hyperlipidemia, all of which were AEs of interest. Conclusions: There is limited experience with tofacitinib in pediatric IBD. In this cohort, tofacitinib induced rapid clinical response with sustained efficacy in nearly half of subjects. This study provides encouraging evidence for the efficacy and safety of tofacitinib as part of the treatment paradigm for young individuals with moderate-to-severe IBD. Larger, well-powered, prospective studies are warranted.

Japanese pediatric patient with refractory steroid-resistant ulcerative colitis successfully treated with Tofacitinib: A case report

“…This study provided encouraging evidence on the efficacy and safety of tofacitinib as part of the treatment paradigm for young patients with moderate-to-severe inflammatory bowel disease. [ 6 ] The present case showed its efficacy on a Japanese pediatric patient with refractory steroid-resistant UC, which was refractory to 3 biologics, namely, vedolizumab, golimumab, and ustekinumab. UC morbidity differs with race, [ 13 ] and 1 of the possible reasons is the effect of UC-related genes and human leukocyte antigen.…”

“…[5] However, the efficacy of tofacitinib in pediatric patients with UC is limited. [6] In March 2013, tofacitinib was approved in Japan as a new treatment drug for rheumatoid arthritis in adults and permitted for use in adults with UC in May 2018. To our knowledge, there are no reports of Japanese children with UC who received longterm tofacitinib therapy.…”

Tofacitinib to Treat Severe Acute Refractory Colitis in a Teenager: Case Report and Review of the Literature

“…Only 1 patient had a severe adverse event: septic arthritis and deep vein thrombosis on vedolizumab/tofacitinib and 30 mg prednisone daily, but after specific treatment, he achieved complete mucosal healing and steroid-free remission ( 34 ). More recently, Moore et al ( 35 ) published a retrospective study including 21 patients aged 21 years and younger who started tofacitinib for medically refractory IBD (18 UC/IBD-U, 3 CD). At the end of the 12-week induction period, 9 of 21(42.9%) subjects showed clinical response, 7 of 21(33.3%) were in steroid-free remission, and 4 of 21 underwent colectomy before completing induction.…”

Pharmacologic Management of Monogenic and Very Early Onset Inflammatory Bowel Diseases

“…They are available in oral form and do not require drug level monitoring. Tofacitinib is approved for use in adults with ulcerative colitis; off-label use in pediatric UC also shows promise [ 119 ]. In a single-center, retrospective study, Tofacitinib induced clinical remission in nearly 50% of tested patients after the 12-week induction period (N = 9/21).…”

“…In a single-center, retrospective study, Tofacitinib induced clinical remission in nearly 50% of tested patients after the 12-week induction period (N = 9/21). After 52 weeks, approximately 40% of subjects achieved steroid free remission (N = 7/17) [ 119 ]. Of note, 67% of patients included in this study had ulcerative colitis, 14% had Crohn’s disease, and 19% had indeterminant IBD.…”