Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2025 Aug;62(4):430-439.
doi: 10.1111/apt.70199. Epub 2025 May 22.

Effectiveness and Safety of a Second JAK Inhibitor in Ulcerative Colitis: The J2J Multicentre Study

Mathilde Osty  1 , Romain Altwegg  2 , Mélanie Serrero  3 , Alban Benezech  4 , Albane Lecomte  5 , Guillaume Cadiot  6 , Lucine Vuitton  7 , Anne Wampach  8 , Stéphane Nancey  9 , Anthony Buisson  10 , Catherine le Berre  11 , Clea Rouillon  12 , Cyrielle Gilletta  13 , Felix Goutorbe  14 , Mathurin Fumery  15 , Nassim Hammoudi  16 , Ludovic Caillo  17 , Mathias Vidon  18 , Nadia Arab  19 , Gaelle Sickersen  20 , Maryan Cavicchi  21 , Sophie Vieujean  22 , Maeva Charkaoui  23 , Nicolas Richard  24 , Pauline Wils  25 , Bénédicte Caron  26 , Aurélien Amiot  27 , Alexandre Nuzzo  28 , David Laharie  29 , Julien Kirchgesner  30 , Mathieu Uzzan  1 ; GETAID‐J2J group
Collaborators, Affiliations
Observational Study

Effectiveness and Safety of a Second JAK Inhibitor in Ulcerative Colitis: The J2J Multicentre Study

Mathilde Osty et al. Aliment Pharmacol Ther. 2025 Aug.

Abstract

Background: While three Janus kinase inhibitors (JAKi) have demonstrated efficacy in ulcerative colitis (UC), scarce data exist regarding JAKi intraclass switching.

Aim: To evaluate the effectiveness and safety of a second JAK inhibitor in UC.

Methods: This was a multicentre, retrospective, observational cohort including patients with moderate to severe UC who received a second-line of JAKi after failure or intolerance of a first. The primary outcome was steroid-free clinical remission (SFCR) at Weeks 8-14, defined as a partial Mayo score of 2 or less with no individual sub-score above 1.

Results: Among the 169 patients from 28 participating centres, 105 received upadacitinib, 54 filgotinib and 10 tofacitinib as a second-line of JAKi. Overall, 81/169 achieved SFCR at Weeks 8-14: 58/105 with upadacitinib, 18/54 with filgotinib and 5/10 with tofacitinib (p = 0.03). In the multivariate analysis, upadacitinib was independently associated with higher odds of SFCR than filgotinib (OR = 3.15, 95% CI [1.52-6.79]). With a median follow-up duration of 96 days, drug persistence at 6 months was 72.8% with upadacitinib, 57.2% with filgotinib and 66.7% with tofacitinib (p = 0.099). 24.3% of patients (41/169) experienced at least one adverse event leading to treatment withdrawal in 9 patients (5%). No cases of death, cancer, or major acute cardiovascular events were reported.

Conclusion: A second-line of JAKi provided clinical remission in about half of patients after induction, and was well tolerated.

Keywords: biologics (IBD); disease‐based; topics; ulcerative colitis.

PubMed Disclaimer

Conflict of interest statement

M.U. declares counselling, boards or fees for AbbVie, Amgen, Celltrion, Janssen, Lilly and Takeda. R.A. declares counselling, boards or fees for AbbVie, Alphasigma, Amgen, Biogen, Celltrion, Ferring, Janssen, Lilly, MSD, Pfizer, Sandoz and Takeda. M.S. declares boarding or lecture fees for Abbvie, Alfasigma, Amgen, Biogen, Celltrion, Ferring, Janssen, MSD, Pfizer and Takeda. A.B. declares boards or fees for AbbVie, Amgen, Janssen and Takeda. G.C. declares boards for Johnson and Johnson, Lilly; and lectures for Abbvie, Takeda. C.R. has received lecture/consultant fees from Abbvie, Lilly, Janssen, Biogen, Amgen, Takeda and Galapagos. M.F. received lecture and/or consulting fees from Sandoz, Biogen, Amgen, Alfasigma, Galapagos, Ferring, Tillots, Nordic‐Pharma, Celltrion, Janssen, Amgen, Lilly, Pfizer, Janssen, Abbvie, Takeda, Lilly and Gilead. N.H. has served as a consultant/advisory board member to Abbvie, Celltrion, Fresenius Kabi, Janssen and Lilly and as a speaker for Abbvie, Galapagos and Takeda. L.C. declares counselling, boards or fees for AbbVie, Amgen, Celltrion, Johnson & Johnson, Lilly, Pfizer and Takeda. M.C. declares counselling and boards for AbbVie, Janssen, Lilly, Pfizer, MSD and lecture fees for Ferring, Alfasigma, Takeda, Pfizer, Amgen, Lilly, Tillotts and Abbvie. N.R. declares counselling, boards or fees for AbbVie, Amgen, Celltrion, Ferring, Janssen and Takeda. S.V. received lecture and/or consulting fees from AbbVie, Alfasigma, Celltrion, Ferring, Janssen, Lilly and Takeda. P.W. declares lecture fees from Abbvie, Ferring, Takeda, Amgen, Biogen and Janssen. B.C. received lecture and/or consulting fees from AbbVie, Amgen, Celltrion, Ferring, Galapagos, Janssen, Lilly, Nordic Pharma, Pfizer and Takeda. A.A. received consulting fees from Abbvie, Pfizer, Takeda, Adacyte, Sandoz, Tillotts Pharma, Janssen and Sandoz as well as lecture fees and travel accommodations from Abbvie, Janssen, Pfizer, Takeda, Biogen, Fresenius Kabi, Amgen, Adacyte, Ferrin, Biogen and Celltrion. A.N. has received lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Janssen, Alfasigma, Lilly and a grant from MSD‐Avenir. D.L. declares counselling, boards, transports, or fees from Abbvie, Alfasigma, Amgen, Celltrion, Ferring, Janssen, Lilly, Medac, MSD, Pfizer, Sandoz and Takeda. J.K. received lecture fees from Janssen and Lilly, and consulting fees from Roche, Pfizer, Janssen, Abbvie, Takeda, Lilly and Gilead. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Clinical remission and response rated at Weeks 8–14. (A) Steroids‐free clinical remission. (B) Clinical remission. (C) Steroids‐free clinical response. (D) Clinical response.
FIGURE 2
FIGURE 2
Survival without second‐JAK inhibitor discontinuation. Survival was estimated within the Kaplan–Meier analysis for the overall cohort (A) or according to type of second‐line JAKi (B).
See this image and copyright information in PMC

References

    1. Danese S., Argollo M., Le Berre C., and Peyrin‐Biroulet L., “JAK Selectivity for Inflammatory Bowel Disease Treatment: Does It Clinically Matter?,” Gut 68, no. 10 (2019): 1893–1899, 10.1136/gutjnl-2019-318448. - DOI - PubMed
    1. Sandborn W. J., Su C., Sands B. E., et al., “Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis,” New England Journal of Medicine 376, no. 18 (2017): 1723–1736, 10.1056/nejmoa1606910. - DOI - PubMed
    1. Loftus E. V., Panés J., Lacerda A. P., et al., “Upadacitinib Induction and Maintenance Therapy for Crohn's Disease,” New England Journal of Medicine 388, no. 21 (2023): 1966–1980, 10.1056/NEJMoa2212728. - DOI - PubMed
    1. Feagan B. G., Danese S., Loftus E. V., et al., “Filgotinib as Induction and Maintenance Therapy for Ulcerative Colitis (SELECTION): A Phase 2b/3 Double‐Blind, Randomised, Placebo‐Controlled Trial,” Lancet 397, no. 10292 (2021): 2372–2384, 10.1016/S0140-6736(21)00666-8. - DOI - PubMed
    1. Akiyama S., Shimizu H., Tamura A., et al., “Comparative Efficacy and Safety of Three Janus Kinase Inhibitors in Ulcerative Colitis: A Real‐World Multicentre Study in Japan,” Alimentary Pharmacology & Therapeutics 61, no. 3 (2024), 10.1111/apt.18406. - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources