52 Week Outcomes of Upadacitinib in Pediatric Ibd: A Single-Center Experience

BACKGROUND Upadacitinib (UPA) is a selective JAK1 inhibitor approved for use in adult IBD, including CD and UC. Off-label use in pediatric IBD is common, but long-term outcomes data with respect to efficacy and safety are lacking. METHODS This was a single-center, retrospective study of pediatric patients with IBD, who initiated UPA at < 18 years. Primary outcome was corticosteroid-free clinical remission (CFCR) at 52 ± 16 weeks, defined by PUCAI < 10 (UC), PCDAI ≤10 (CD), or PGA = 0 (where PUCAI or PCDAI unavailable). Secondary outcomes were durability, normalization of CRP, endoscopic remission, and adverse events (AEs). Endoscopic remission was defined as Mayo score 0 (UC) or SES-CD score 0-2 (CD). RESULTS Forty-eight patients, including 22 (46%) with CD and 26 (54%) with UC were included. Patients were diagnosed at mean age 10.9 ± 4.0 years and started UPA at mean age 14.1 ± 2.9 years. Prior advanced therapy failures included anti-TNF (98%), ustekinumab (56%), vedolizumab (46%), tofacitinib (15%), and risankizumab (6%). For those with CD, 18/22 (82%) had ileocolonic disease and 9/22 (41%) had perianal disease. For those with UC, 20/26 (77%) had pancolitis and 21/26 (81%) had S1 ever-severe disease. Twenty-nine patients (60%) had CRP elevations at UPA initiation and all (100%) had active disease endoscopically. More than half of patients in our cohort (25/48, 52%) had extra-intestinal manifestations (EIMs), with psoriasis (n = 7, 15%), atopic dermatitis (n = 5, 10%), and cutaneous CD (n = 4, 8%) most common. At 52-week follow-up, 39/48 (81%) remained on UPA, including 17/22 (77%) with CD and 22/26 (85%) UC, and of these, 8/17 (47%) with CD and 16/22 (73%) with UC were in CFCR. Of the 7 tofacitinib-experienced patients, 6/7 (86%, 3 CD, 3 UC) continued on UPA at 52 weeks, and 4/7 (57%, 2 CD, 2 UC) achieved CFCR at 52 weeks. Maintenance dosing at 52 weeks was 30 mg (46%), 15 mg (17%), 45 mg (15%), and 12 mg (2%). In terms of biomarker outcomes, 27/37 (73%) had normal CRP values at 52 weeks, including 12/17 (71%) with CD and 15/20 (75%) with UC. Twenty-eight patients had endoscopic re-staging at 52 weeks, and of these, 13 (46%) had confirmed endoscopic remission, including 5/12 (42%) with CD and 8/16 (50%) with UC. AEs were documented in 23/48 (48%), with acne (n = 9, 19%) and abnormal cholesterol (n = 7, 15%) most common. Two patients (4.2%) discontinued UPA due to AEs, including leukopenia (n = 1) and drug reaction (n = 1). There was one reported serious infection occurring on UPA (MRSA cellulitis); there were no thrombotic events, malignancies, or deaths. CONCLUSIONS In this single-center cohort of pediatric IBD patients using UPA, we report high durability and high rates of CFCR at 52 weeks, especially in UC. Most patients used 30 mg or higher maintenance dosing. AEs were common, but AEs leading to medication discontinuation were rare.