P1063 Impact of Upadacitinib in Crohn’s Disease in the Medium Term: Results from the UPITA-Crohn Registry in Clinical Practice
Authors: Caballero Mateos A M , Lázaro-Sáez M , Hernández-Martínez Á , Rodríguez-González F J , González-Parra A C , Martín-Rodríguez M D M , Agulleiro-Beraza I , Gijón-Villanova R , Saldaña L , Trapero-Martínez A M , Gómez-Delgado E , Benítez J M , Olmedo-Martín R V ,   GATEII
Published: January 2025

Abstract

Background
There is still insufficient evidence regarding the effectiveness and safety of Upadacitinib in real-world settings. This recently approved oral JAK inhibitor for moderate-to-severe Crohn’s disease is the focus of this study, which aims to evaluate them in this clinical context.

Methods
Clinical and biochemical data were retrospectively collected from 107 patients who initiated treatment with Upadacitinib across 10 hospitals in Andalusia. Clinical remission (CR) was defined as a Harvey-Bradshaw score of less than 5, clinical and biochemical remission (CBR) as a Harvey-Bradshaw score &lt;5, PCR &lt;5 mg/L, and Calprotectin &lt;250 μg/g, and remission without steroids (RWS) as a Harvey-Bradshaw score &lt;5 with no corticosteroid use since week 12. These and other variables were evaluated at week 12 and at 6 months. An intention-to-treat analysis was performed.

Results
The mean age of the 107 recruited patients was 41 years (range: 18–76), with 59% being female. Disease involvement was ileocolic in 52%, ileal in 33%, and colonic in 15%. Among these patients, 25% were smokers and 15% were ex-smokers. Extraintestinal manifestations were present in 45%. The mean disease duration was 13 years (range: 1–40), and 35% had previously undergone resective surgery. The mean number of failed advanced treatments was 3. At treatment initiation, 11% were on 5-ASA therapy, 10% on immunomodulators, and 33.6% on corticosteroids. Induction with 45 mg was administered for 8 weeks in 12.2% of patients, for 12 weeks in 75.5%, and for 16 weeks in 12.2% (Table 1a).
Clinical and biochemical efficacy data are shown in Table 1b. Among the patients who completed 12 weeks of treatment (84 patients), 54.6% achieved CR, and 18.5% achieved CBR. At 6 months (43 patients), 47.4% achieved CR, 22% achieved CBR, and 42.3% achieved SFR.
At the time of the study, 16 patients (14.9%) had discontinued treatment before the 6-month mark, primarily due to primary nonresponse (68%). One patient died from complications of the disease. Other reasons for discontinuation included popliteal thrombosis, pregnancy, fever, and a respiratory infection, each affecting one patient. Several mild and transient adverse effects were reported (5% of all patients), including 2 cases of acne, 2 of elevated liver transaminases, and 2 infections.

Conclusion
Upadacitinib is a favorable, effective, and safe treatment in the short to medium term for a cohort of patients with refractory Crohn’s disease.

References
-Clark JD, Flanagan ME, Telliez JB. Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases. J Med Chem 2014; 57: 5023–38.
-Padda IS, Bhatt R, Parmar M. Upadacitinib. 2023 Jun 3. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 34283454.
-Loftus EV Jr, Panés J, Lacerda AP, Peyrin-Biroulet L, D’Haens G, Panaccione R, Reinisch W, Louis E, Chen M, Nakase H, Begun J, Boland BS, Phillips C, Mohamed MF, Liu J, Geng Z, Feng T, Dubcenco E, Colombel JF. Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med. 2023 May 25;388(21):1966-1980. doi: 10.1056/NEJMoa2212728.