Tofacitinib, a selective small molecule Janus Kinase (JAK) inhibitor, is well known in treatment of rheumatoid diseases and in recent years became increasingly important in managing adults with Inflammatory Bowel disease (IBD). In the paediatric population, data is scarce, however has proven to show rapid response of symptoms in moderate to severe Ulcerative Colitis (UC) after biologic treatment failure and/or prior to undergoing surgery.^1–3 Here we describe a potent treatment of a 13-year-old with newly diagnosed unclassified IBD (IBD-U) and severe colitis with Tofacitinib.

The previously healthy male adolescent was diagnosed with IBD-U with a high Paediatric Ulcerative Colitis Activity Index (PUCAI) of 85 and severe colitis macroscopically and histopathologically. Initial OGD and colonoscopy showed macroscopical and histological chronic duodenitis, severe left sided chronic active colitis. Acute inflammation in the transverse, descending and sigmoid colon in the ultrasound was confirmed, the MR enterography showed additional 2 cm focal narrowing in the Terminal Ileum. On day 7 of high dose intravenous steroids and on azathioprine, he presented with a persistent PUCAI above 60, weight loss of 2kg within two weeks of admission and ongoing rectal bleeding, therefore first line biologic treatment with intensified Infliximab regime, together with IV antibiotics were added and parenteral nutrition (PN) for gut rest was started. On endoscopical re-assessment on day 20 of steroid treatment ongoing chronic active colitis was seen. Because PUCAI stayed above 45 despite medical escalation and gut rest, potential need for colectomy was discussed. Following a multidisciplinary team discussion, trial of Tofacitinib for colonic salvage was initiated.

There was a rapid and dramatic response to oral Tofacitinib 10 mg twice daily. PN was able to be stopped after 10 days since on Tofacitinib and within 28 days he gained 4.1kg of weight, PUCAI dropped from 45 to 0, ESR and CRP normalised (maximum 22 to 6mm/hr and maximum 9 to below 5 mg/L, respectively), albumin normalised (lowest 31g/L, latest result 48 g/L) and significant improvement of faecal calprotectin (>10.000ug/g to 934 ug/g). After weaning off steroid completely, currently on Prednisolone 5 mg once daily and Tofacitinib 5 mg twice daily, long-term plan is to bridge him to Vedolizumab.

In this case Tofacitinib supports previous data of prompt and effective results. JAK inhibitors are beneficial as rescue therapy for steroid non-responder and primary anti-TNFα non-responder and therefore can avoid major surgical intervention.

References

1. Dolinger MT, Rolfes P, Phan BL, Dubinsky MC. Letter: tofacitinib use for biologic-refractory paediatric inflammatory bowel disease. Aliment Pharmacol Ther 2019;50(8):966–967. https://doi.org/10.1111/apt.15496

2. Moore H, Dubes L, Fusillo S, Baldassano R, Stein R. Tofacitinib therapy in children and young adults with pediatric-onset medically refractory inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2021;73(3):e57-e62. https://doi.org/10.1097/MPG.0000000000003190

3. Sandborn WJ, Armuzzi A, Liguori G, Irving PM, Sharara AI, Mundayat R, Lawendy N, Woolcott JC, Danese S. Predictors of sustained response with tofacitinib therapy in patients with ulcerative colitis. Inflamm Bowel Dis 2022;28(9):1338–1347. https://doi.org/10.1093/ibd/izab278