Lynch KD¹, Chapman RW¹, Keshav S¹, Montano-Loza AJ², Mason AL², Kremer AE³, Vetter M³, de Krijger M⁴, Ponsioen CY⁴, Trivedi P⁵, Hirschfield G⁶, Schramm C⁷, Liu CH⁸, Bowlus CL⁸, Estes DJ⁹, Pratt D⁹, Hedin C¹⁰, Bergquist A¹¹, de Vries AC¹², Janneke van der Woude C¹², Yu L¹³, Assis DN¹⁴, Boyer J¹⁴, Ytting H¹⁵, Hallibasic E¹⁶, Trauner M¹⁶, Marschall HU¹⁷, Daretti LM¹⁸, Marzioni M¹⁸, Yimam KK¹⁹, Perin N²⁰, Floreani A¹⁰, Beretta-Piccoli BT²¹, Rogers JK²²; International Primary Sclerosing Cholangitis Study Group (IPSCSG)⁴, Levy C²³. Clin Gastroenterol Hepatol. 2019 May 14. pii: S1542-3565(19)30523-3. doi: 10.1016/j.cgh.2019.05.013. [Epub ahead of print]

Author information

1 Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

2 Division of Gastroenterology, University of Alberta, Edmonton, Canada.

3 Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.

4 Department of Gastroenterology and Hepatology, Amsterdam University Medical Centres, location AMC, Amsterdam, The Netherlands.

5 Centre for Liver and Gastroenterology Research, National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, UK; University Hospitals Birmingham, Birmingham, UK; Institute of Immunology and Immunotherapy, University of Birmingham, UK.

6 Centre for Liver and Gastroenterology Research, National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, UK; University Hospitals Birmingham, Birmingham, UK; Institute of Immunology and Immunotherapy, University of Birmingham, UK; Toronto Centre for Liver Disease, University Health Network and University of Toronto, Toronto, Canada.

7 First Department of Medicine and Martin Zeitz Centre for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

8 Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, California, USA.

9 Autoimmune and Cholestatic Liver Center, Massachusetts General Hospital, Boston, USA.

10 Patient Flow Gastrointestinal diseases, Patient Area Gastroenterology, Dermatovenerology and Rheumatology, Karolinska University Hospital, Karolinska Institute, Sweden.

11 Centre for Digestive Diseases, Division of Hepatology, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.

12 Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.

13 Liver Care & Transplantation Services, University of Washington Medical Center, Seattle, USA.

14 Yale Autoimmune and Cholestatic Liver Disease Program, Section of Digestive Diseases, Yale University School of Medicine, New Haven CT USA.

15 Department of Hepatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

16 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University if Vienna, Vienna, Austria.

17 Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

18 Clinic of Gastroenterology and Hepatology, Ospedali Riuniti University Hospital, Ancona, Italy.

19 Division of Hepatology and Liver Transplantation, California Pacific Medical Center, San Francisco, USA.

20 Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

21 Epatocentro Ticino, Lugano, Switzerland.

22 Department of Statistics, University of Oxford, Oxford, UK.

23 Division of Hepatology, University of Miami, Miami, Florida, USA. Electronic address: clevy@med.miami.edu.

Abstract

BACKGROUND & AIMS: Gut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD.

METHODS: We collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n=102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes.

RESULTS: In the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P=.018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P=.019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation.

CONCLUSIONS: In an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.