Upadacitinib is a selective Janus kinase 1 inhibitor approved for the treatment of patients 18 years and older with the diagnosis of Crohn’s disease and ulcerative colitis (Napolitano, M et al, 2022, Ma, C et al, 2019). Although there is promising data for its use in adult inflammatory bowel disease (IBD), limited data are currently available on its use in paediatric IBD (Collen, LV et al, 2023, Spencer, EA et al, 2023). We present our experience in this case series of patients ≤ 18 years on Upadacitinib.

We identified patients under the age of ≤ 18 years, started on Upadacitinib for the indication of IBD. Data on demographics, disease subtype, duration on Upadacitinib, number of biologic failures, tofacitinib use, concomitant biologic use, adverse events and clinical remission were gathered.

12 patients with paediatric IBD (median age at Upadacitinib start 15.5 years, range 13.9 to 17.8 years, 8 (67%) males, were identified. 7 patients had Crohn’s disease, 3 patients had ulcerative colitis and 2 patients had IBD unclassified. 4 patients (33%) were diagnosed under the age of 6 years with early onset IBD (EOIBD), 1 was 3.5 years old, 1 was 4 years old and 2 were 5 years old. 11/12 (92%) patients had failed 3 or more biologics. Upadacitinib was used as monotherapy in all patients and previous biologic treatments were stopped. 1 patient with a partial response to tofacitinib was switched to Upadacitinib. All patients had active disease at commencement of Upadacitinib. All 12 (100%) patients were started on 45 mg of Upadacitinib. 8/12 (67%) patients have been followed up for at least 8 weeks. Out of the 8 patients, 5/8 (63%) patients were in clinical remission between 8–16 weeks of therapy, 2/8 (25%) had partial response and 1/8 (13%) has been refractory to treatment. Relapse of symptoms was noted in 1 patient after dose was dropped to 30 mg; this patient had achieved remission on 45 mg. No serious adverse events occurred; 2 patients noted to have increased triglycerides (max 5.75mmol/L; range 0.38–1.58mmol/L). 1 of them had previous exposure to tofacitinib and the triglycerides were already raised prior to starting Upadacitinib. 1 patient developed headaches, as a result, Upadacitinib dose was decreased. There were no incidences of shingles or other serious infections (table 1).

The patients in this case series, started on Upadacitinib, are a heterogeneous group with refractory disease. In these paediatric and adolescent patients Upadacitinib seemed safe and efficacious with a low side effect profile. Further national and international collaborative studies are needed to confirm our findings.

References

1. Napolitano M, D’Amico F, Ragaini E, et al. Evaluating upadacitinib in the treatment of moderate-to-severe active ulcerative colitis: design, development, and potential position in therapy. Drug Des Devel Ther. 2022 Jun 17;16:1897–1913.

2. Ma C, Jairath V, Vande Casteele N. Pharmacology, efficacy and safety of JAK inhibitors in Crohn’s disease. Best Pract Res Clin Gastroenterol. 2019 Feb-Apr;38–39:101606.

3. Collen LV. Rapid clinical remission with upadacitinib in a pediatric patient with refractory Crohn’s disease. Inflamm Bowel Dis. 2023 Jul 5;29(7):1175–1176.