Hepatic safety and efficacy of immunomodulatory drugs used in patients with autoimmune hepatitis

Benedetta Terziroli Beretta-Piccoli; Gustav Buescher; George Dalekos; Kalliopi Zachou; Anja Geerts; Nasser Semmo; Mirjam Kolev; Eleonora De Martin; Maciej K Janik; João Madaleno; Milica Lalosevic Stojkovic; Jérôme Dumortier; Thomas Vanwolleghem; Ida Schregel; Silja Steinmann; Florence Lacaille; Marcial Sebode

doi:10.1016/j.jaut.2023.103113

Hepatic safety and efficacy of immunomodulatory drugs used in patients with autoimmune hepatitis

J Autoimmun. 2023 Sep 14:140:103113. doi: 10.1016/j.jaut.2023.103113. Online ahead of print.

Authors

Benedetta Terziroli Beretta-Piccoli¹, Gustav Buescher², George Dalekos³, Kalliopi Zachou³, Anja Geerts⁴, Nasser Semmo⁵, Mirjam Kolev⁵, Eleonora De Martin⁶, Maciej K Janik⁷, João Madaleno⁸, Milica Lalosevic Stojkovic⁹, Jérôme Dumortier¹⁰, Thomas Vanwolleghem¹¹, Ida Schregel², Silja Steinmann², Florence Lacaille¹², Marcial Sebode²

Affiliations

¹ Epatocentro Ticino, Lugano, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany; MowatLabs, Faculty of Life Sciences & Medicine, King's College London, King's College Hospital, London, UK. Electronic address: benedetta.terziroli@usi.ch.
² European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany; I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
³ European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany; Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Centre in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.
⁴ European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany; Department of Gastroenterology and Hepatology, University Hospital of Ghent, Belgium.
⁵ Hepatology, University Clinic for Visceral Surgery and Medicine, Inselspital Bern, University of Bern, Bern, Switzerland.
⁶ European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany; Hépatologie et Transplantation Hépatique, Hôpital Paul Brousse, Villejuif, France.
⁷ European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany; . Department of Hepatology, Transplantology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
⁸ European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany; Liver Disease Unit, Internal Medicine Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
⁹ European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany; University Clinical Center of Serbia, Belgrade, Serbia.
¹⁰ European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany; Hôpital Edouard Herriot, Hospices Civils de Lyon and Université Claude Bernard Lyon 1, Lyon, France.
¹¹ European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany; Department of Gastroenterology and Hepatology Antwerp University Hospital, Antwerp, Belgium; Viral Hepatitis Research Group, Laboratory of Experimental Medicine and Pediatrics (LEMP), University of Antwerp, Antwerp, Belgium.
¹² European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany; Hôpital Necker-Enfants Malades, Paris, France.

PMID: 37716078
DOI: 10.1016/j.jaut.2023.103113

Abstract

Background and aims: There is little data on the hepatic efficacy and safety of immunomodulatory drugs used in patients with autoimmune hepatitis (AIH), despite their established use in dermatology, rheumatology and inflammatory bowel diseases (IBD). Our aim was to collect real-life data on the experience of expert centres in treating AIH patients with these drugs, considered unconventional for AIH management.

Methods: Online survey among hepatology centres being part of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER).

Results: 25 AIH patients have been reported. Ten were female, median age at diagnosis was 28 years; median follow-up was 17 months. All had initially received AIH-standard treatment. AIH-unconventional treatment was initiated for concomitant autoimmune diseases in 15 cases: nine for IBD (five vedolizumab and four ustekinumab), and one each for following diseases: autoinflammatory syndrome (tocilizumab), chronic urticaria (omalizumab), rheumatoid arthritis (abatacept), psoriasis (guselkumab), psoriatric arthritis (secukinumab, followed by ustekinumab) and alopecia (ruxolitinib). Three patients were treated with immunomodulatory drugs for side effects of previous treatments, including two patients with IBD treated with vedolizumab and ustekinumab, respectively, and one treated with belimumab. At the end of follow-up, 13 patients were in complete biochemical response, the patient on omalizumab had a relapse, and four patients with concomitant IBD had insufficient response. Seven patients were treated for lack of biochemical remission, of whom six with belimumab, all initially reaching complete biochemical response, but five relapsing during follow-up; and one with secukinumab, having concomitant rheumatoid arthritis and ankylosing spondylitis, reaching complete biochemical response. Only the patient on abatacept received unconventional treatment as monotherapy. Side effects were reported in two patients on belimumab: one recurrent soft tissue infections, one fatigue and arthralgia.

Conclusion: Among 25 AIH patients who were treated with immunomodulatory drugs for different reasons, the majority had a fovorable course, relapse was frequent in difficult-to-treat patients who received belimumab, and four with concomitant IBD had insufficient response.