SINGLE CENTER EXPERIENCE WITH UPADACITINIB FOR REFRACTORY PEDIATRIC INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Upadactinib (UPA) was recently approved for ulcerative colitis (UC) for patients 18 and older, and there is promising data for its use in adult Crohn’s disease (CD). It is currently also approved for use in atopic dermatitis (AD) down to the age of 12, but doses used are lower than in inflammatory bowel disease (IBD). There is currently no data on its use for pediatric IBD; we present here a case series of patients ≤18 years on UPA. METHODS We identified ≤18yo patients who were started on UPA for the indication of IBD +/- AD and completed ≥58 days of therapy at a single, US center. Data, with relevant descriptive statistics, were gathered on demographics, disease subtype, Montreal classification, indication for UPA, time on UPA, number of biologic failures, tofacitinib use, concomitant biologic use, adverse events, and clinical and biomarker remission (8-16 week clinical remission: HBI <5, pMS <3; 2-6 month CRP normalization). RESULTS 12 patients (Median age at UPA start: 16.5y, Interquartile Range [IQR]: 4; 67% female) completed 8 or more weeks (Median [IQR] days: 118 [80]) of UPA (Table 1). Two-thirds of patients had CD. A quarter of patients (25%) had concomitant AD. All patients were diagnosed <17 years, with 67% patients diagnosed below or at the age of ten. The majority of patients (75%) had failed three or more biologics. UPA was used as monotherapy in 50% of patients. Four patients were exposed to and had a partial response to tofacitinib. The majority of patients (75%) had clinically active disease at UPA start. Most patients (83%) were induced with 45 mg, one patient was induced with 30mg, and one patient initiated 15mg as part of AD protocol, later increasing to 30mg. Out of the 12 total patients, 11/12 (92%) were in clinical remission between 8-16 weeks of therapy; in the subset of patients ≤17 years, 6/7 (86%) were in clinical remission. Nine patients had CRP levels measured 2-6 months after initiating UPA treatment; 8/9 (89%) of these patients achieved CRP normalization during this time. No serious adverse events occurred; one patient, who was on UPA monotherapy, developed recurrent styes that responded to hot compresses and antibiotic ointment. Joint involvement (sacroiliitis, arthritis, arthralgias) at the start of their treatment occurred in 3 patients; all of these patients had resolution of joint pain by 8 or more weeks. All patients had previously received vaccination for varicella; no patients were vaccinated for zoster, including the 5 who were 18 years of age. CONCLUSION No new safety signals were seen during induction dosing of UPA in teenage patients with IBD. In this very refractory group, nearly all patients achieved clinical & biomarker remission. Further study on the effectiveness and safety of UPA needs to be performed in pediatric patients.