ORCID
- Ashwin Dhanda: 0000-0002-0523-0193
Abstract
Background and Aims: Short-term mortality in alcohol-related hepatitis (AH) is high, and no current therapy results in durable benefit. A role for interleukin (IL)-1β has been demonstrated in the pathogenesis of alcohol-induced steatohepatitis. This study explored the safety and efficacy of canakinumab (CAN), a monoclonal antibody targeting IL-1β, in the treatment of patients with AH. Methods: Participants with biopsy-confirmed AH and discriminant function ≥32 but Model for End-Stage Liver Disease ≤27 were randomly allocated 1:1 to receive either CAN 3 mg/kg or placebo (PBO). Liver biopsies were taken before and 28 days after treatment. The primary endpoint was the overall histological improvement in inflammation analyzed by the modified intention-to-treat principle. Results: Fifty-seven participants were randomized: 29 to CAN and 28 to PBO. Two participants had histology that did not corroborate the clinical diagnosis. Of the remaining 55 participants, paired histology data were evaluable from 48 participants. In CAN-treated participants, 14 (58%) of 24 demonstrated histological improvement compared with 10 (42%) of 24 in the PBO group (P = .25). There was no improvement in prognostic scores of liver function. Four (7%) of the 55 participants died within 90 days, 2 in each group. The number of serious adverse events was similar between CAN vs PBO. In post hoc exploratory analyses after adjustment for baseline prognostic factors, CAN therapy was associated with overall histological improvement (P = .04). Conclusions: CAN therapy in severe AH participants with Model for End-Stage Liver Disease ≤27 did not alter biochemical or clinical outcomes compared with PBO. Nonsignificant histological improvements did not translate into clinical benefit. EudraCT, Number: 2017-003724-79; ClinicalTrials.gov, Number: NCT03775109.
DOI Link
Publication Date
2025-01-01
Publication Title
Clinical Gastroenterology and Hepatology
Volume
23
Issue
5
ISSN
1542-3565
Acceptance Date
2024-01-01
Deposit Date
2026-01-12
Additional Links
Keywords
Alcohol-Related Hepatitis, Interleukin-1b, MELD, Model for End-Stage Liver Disease
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Vergis, N., Patel, V., Bogdanowicz, K., Czyzewska-Khan, J., Keshinro, R., Fiorentino, F., Day, E., Middleton, P., Atkinson, S., Tranah, T., Cross, M., Babalis, D., Foster, N., Lord, E., Quaglia, A., Lloyd, J., Goldin, R., Rosenberg, W., Parker, R., Richardson, P., Masson, S., Whitehouse, G., Sieberhagan, C., Patch, D., Naoumov, N., Dhanda, A., Forrest, E., & Thursz, M. (2025) 'IL-1 Signal Inhibition in Alcohol-Related Hepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial of Canakinumab', Clinical Gastroenterology and Hepatology, 23(5). Available at: 10.1016/j.cgh.2024.07.025
