Introduction
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, durability and safety should be analysed in a real-world scenario. Main aim: to evaluate the durability 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
Aims & Methods
Multicentre, retrospective study of IBD patients who received UPA in clinical practice. Durability was calculated from the date of the first dose to the date of the last dose of UPA. Active disease was defined as Harvey-Bradshaw index >4 in CD, and partial Mayo score >2 in UC. For effectiveness assessment, only patients with active IBD at baseline were considered. Negative imputation method was used to impute missing data. Cox regression models, and logistic regression analyses were used to identify predictive factors of treatment durability and effectiveness
Results
Fifty-one patients from 21 centres have been included so far, 36 with CD and 15 with UC. All patients have been previously exposed to biologics (median 3, IQR 2-4), and 27% to JAK inhibitors (86% in UC); 33% of them were on steroids at baseline. Regarding UPA survival, 91% of patients remained on UPA at month 6, and 51% at month 12. The induction dose of 45 mg q.d. was prescribed in 94% of patients while the dosage during the maintenance phase was 30 mg q.d. in 43% and 45 mg q.d. in 40%. Loss of response was observed in 21%. Intensification was required in 55% of patients, 83% of whom responded clinically. Finally, 10 patients (20%) interrupted UPA during the follow-up, mainly due to primary non-response (n=4) and secondary loss of response (n=3). Younger age (<40 years) at UPA start was the only variable significantly associated with a higher UPA durability in the multivariate analysis (HR 5.6, 95%CI:1.2-28).
Forty-one patients had active disease at baseline and were considered for the effectiveness analysis. Clinical remission in the short-term was achieved in 54%, 53% and 59% at week 4, 8 and 12; in the long-term, 46% and 37% remained in clinical remission at months 6 and 12. Clinical response (including remission) in the short-term was reached in 68%, 78% and 76% at week 4, 8 and 12 respectively; and in the long-term, in 53% and 37% at months 6 and 12. In multivariate analysis, UC (vs. CD) (OR 7; 95%CI:1.1-43) and mild clinical activity (vs. moderate-severe) (OR 22; 95%CI:3-152) were associated with clinical remission at week 12. Focusing on the type of IBD, clinical remission was achieved in 69% of UC vs. 44% of CD (p=0.1) at week 8.
A total of 24 patients (47%) presented at least one adverse event. The most frequently reported were infections (14%), followed by hypercholesterolemia (12%) and anaemia (8%). According to investigator criteria, 19 adverse events (36%) were related to UPA. Serious adverse events were described in 4 patients (8%), all of them requiring hospital admission: Campylobacter jejuni infection, severe flare-up of CD, acute pancreatitis, and creatinine kinase elevation. Three patients (6%) suffered an adverse event leading to UPA discontinuation
Conclusion
In the largest cohort providing real world evidence about UPA in IBD patients, the proportion of patients maintaining the drug at 12 months seems relatively high, considering that it was a highly refractory population. 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
Disclosure
MJ García has received financial support for travelling and educational activities from Janssen, Pfizer, Takeda, Fae Farma and Ferring. M. Barreiro-de Acosta has served as a speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gillead, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte and Vifor Pharma. A. Gutiérrez has served as a speaker, a consultant and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Tillotts Pharma, Chiesi and Otsuka Pharmaceutical. J.M.Huguet has received founding for educational activities research projects scientific meetings or advisory boards sponsored by MSD, Ferring, Abbvie. M Bosca-Watts declares educational activities, research projects, scientific meetings and advisory boards sponsored by MSD, Ferring, Abbvie, Janssen, Biogen and Takeda. H. Alonso-Galán has received financial support for travelling and educational activities from or has served as an advisory board member to Janssen, MSD, Abbvie, Takeda, Ferring, Pfizer and Falk Pharma. M.D. Martín-Arranz has received fees as a speaker, consultant and advisory member for or has received funding from MSD, AbbVie, Hospira, Pfizer, Takeda, Janssen, Shire Pharmaceuticals, Tillots Pharma, and Faes Pharma. J. P. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene, Gilead, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, and Vifor Pharma. M. Chaparro has served as a speaker, as consultant or has received research or education funding from MSD, AbbVie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Biogen, Gilead and Lilly.![]()