P569 Persistence and safety of upadacitinib in Crohn’s disease and ulcerative colitis in real life: results from a Spanish nationwide study
Authors: García M J , Brenes Y , Vicuña M , Bermejo F , Sierra-Ausín M , Polo Cuadro C , Arroyo M T , Martínez Montiel P , Villoria A , Pérez-Calle J L , Hernandez V , Piñero A , Carrillo-Palau M , Martín-Arranz M D , Miranda-Bautista J , Pajares R , Arranz Hernández L , Bejarano A , Guardiola J , Iyo E , Muñoz-Villafranca C , Talavera A , Alonso-Galán H , Barreiro-de Acosta M , Bosca-Watts M , Vázquez Rey T , Echarri A , Rodríguez-Grau M D C , Gutiérrez A , Huguet J M , López-Martín M C , Mesonero F , Pérez-Martínez I , Plaza R , Ramírez de la Piscina P , Gisbert J P , Chaparro M ,   *Equally contribution as senior authors
Published: January 2024

Abstract

Background
Upadacitinib (UPA) has demonstrated its efficacy in patients with inflammatory bowel disease (IBD) in clinical trials. However, these results may differ from those achieved in clinical practice. Thus, persistence and safety should be analysed in a real-world scenario. Main aim: to evaluate the persistence of UPA in real life, both in Crohn’s disease (CD) and ulcerative colitis (UC). Secondary aims: to assess the effectiveness and safety of UPA.

Methods
Multicentre, retrospective study of IBD patients who received UPA for IBD in clinical practice. Persistence was calculated from the date of the first dose to the date of the last dose of UPA. For effectiveness assessment, only patients with active IBD at baseline were considered. Active disease was defined as Harvey-Bradshaw index &gt;4 in CD, and partial Mayo score &gt;2 in UC. Negative imputation method was used to deal with missing data. Cox regression and logistic regression analyses were used to identify predictive factors of treatment persistence and effectiveness, respectively.

Results
One hundred patients from 34 centres were included, 68 with CD and 32 with UC. All patients had been previously exposed to biologics (median 4, IQR 3-4), and 26% to JAK inhibitors (78% in UC); 37% of them were on steroids at baseline. Regarding UPA survival, 81% of patients remained on UPA at month 6, and 66% at month 12 (figure 1). Loss of response was observed in 34% per patient-year of follow-up. Dose intensification was required in 18%, 72% of whom responded clinically. Finally, 23 patients interrupted UPA during the follow-up. Age below 40 at UPA start and CD were associated with higher risk of UPA withdrawal (HR 2.4; 95%CI:1.0-5.7 and HR 3.7; 95%CI:1.0-12.9, respectively). Seventy-eight patients had active disease at baseline and were considered for the effectiveness analysis. Short-term clinical remission was achieved in 51%, 59% and 64% at week 4, 8 and 12; focusing on the type of IBD, clinical remission was achieved in 79% of UC vs. 54% of CD (p=0.03) at week 12. In the long-term, 53% and 42% remained in clinical remission at months 6 and 12. Clinical remission in patients exposed to JAK inhibitors was achieved in 75% and 79% at week 8 and 12, respectively; and in the long-term, in 54% and 55% at months 6 and 12. A total of 41 patients (41%) presented at least one adverse event (Table 1).

Conclusion
In the largest real-life cohort of IBD patients treated with UPA, the proportion of patients maintaining UPA at 12 months seems relatively high, regardless of prior exposure to JAK inhibitors. UPA seems to be effective in inducing and maintaining clinical remission, both in CD and in UC. The safety profile was similar to that previously described.