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Original article
Effect of vedolizumab (anti-α4β7-integrin) therapy on histological healing and mucosal gene expression in patients with UC
  1. Ingrid Arijs1,2,3,
  2. Gert De Hertogh4,
  3. Bart Lemmens4,
  4. Leentje Van Lommel5,
  5. Magali de Bruyn1,6,
  6. Wiebe Vanhove1,
  7. Isabelle Cleynen1,7,
  8. Kathleen Machiels1,
  9. Marc Ferrante1,7,
  10. Frans Schuit5,
  11. Gert Van Assche1,8,
  12. Paul Rutgeerts1,8,
  13. Severine Vermeire1,8
  1. 1Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
  2. 2Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
  3. 3Jessa Hospital, Hasselt, Belgium
  4. 4Department of Imaging & Pathology, Translational Cell & Tissue Research, KU Leuven, Leuven, Belgium
  5. 5Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
  6. 6Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
  7. 7Department of Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium
  8. 8Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
  1. Correspondence to Dr Severine Vermeire, TARGID, KU Leuven, Herestraat 49, O&N1, mailbox 701, Leuven B-3000, Belgium; severine.vermeire{at}uzleuven.be

Abstract

Objective Lymphocyte recruitment to the inflamed gut is increased in UC. Inhibition of this cell trafficking by vedolizumab (VDZ) was successful in inducing and maintaining remission and in induction of endoscopic mucosal healing. There are no data on histological healing with VDZ. We studied histological changes following VDZ therapy and compared gene expression in patients with UC before and after therapy.

Design Forty-one patients with UC from GEMINI I and LTS were studied before and at three time points (weeks 6/12/52) following VDZ therapy. Colonic biopsies were scored using the Geboes index and correlated with Mayo endoscopic subscore. Gene expression was analysed using Affymetrix gene arrays.

Results Fifty-five per cent of patients achieving endoscopic healing (= Mayo endoscopic subscore 0–1) with VDZ at the studied time points also had histological healing (= Geboes grade 0–1). In most healers, some residual histological changes (eg, disturbed architecture and increased mononuclear cell infiltrate) were still observed, although this was less at week 52. VDZ restored expression of many inflammatory genes in patients with endoscopic healing only at week 52 and not before. In VDZ healers, the expression of many genes remained dysregulated at weeks 6/12/52 compared with controls.

Conclusions VDZ induces histological healing in >50% of patients with endoscopic healing, with maximal effect at week 52. VDZ also restored, although incompletely, the colonic expression of many immune-related genes in patients with UC achieving endoscopic healing at week 52. However, persistent histological and gene dysregulations did remain even in healers, suggesting that maintenance therapy will be necessary to control the intestinal inflammation.

Trial registration numbers: NCT00783718 and NCT00790933; post-results.

  • ULCERATIVE COLITIS
  • HISTOPATHOLOGY
  • MUCOSAL REPAIR
  • GENE EXPRESSION
  • CELL ADHESION
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Footnotes

  • Contributors IA and GDH contributed equally to the article. IA: study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, statistical analysis and technical support. GDH: study concept and design, analysis and interpretation of data and drafting of the manuscript. BL, LVL and WV: technical support. MdB and KM: critical revision of the manuscript for important intellectual content and technical support. IC, MF and GVA: critical revision of the manuscript for important intellectual content. FS: material support and critical revision of the manuscript for important intellectual content. PR: study concept and design, acquisition of data, analysis and interpretation of data, material support, critical revision of the manuscript for important intellectual content, obtained funding and study supervision. SV: study concept and design, acquisition of data, analysis and interpretation of data, material support, drafting of the manuscript, obtained funding and study supervision.

  • Funding This work was supported by grants from the Fund for Scientific Research-Flanders (FWO-Vlaanderen; no. G.0440.06 and no. G.0479.10), and from the Belgian Inflammatory bowel disease Research and Development (BIRD). MF, GVA and SV are senior clinical researchers of FWO. MdB is supported by a grant of the Agency for Innovation by Science and Technology in Flanders.

  • Competing interests GDH—consulting fees: Genentech, Centocor, Galapagos. MF—grant support: Takeda; lecture fees: Abbvie, Boehringer-Ingelheim, Chiesi, Falk, Ferring, Janssen, Mitsubishi Tanabe, MSD, Takeda, Tillotts, Zeria; consulting fees: Abbvie, Boehringer-Ingelheim, Ferring, Janssen, MSD. GVA—grant support: Abbvie, MSD; lecture fees: Abbvie, Ferring, MSD, Janssen, Takeda; consulting fees: Abbvie, MSD, Takeda. PR—grant support: Abbvie, Centocor, Merck, UCB; lecture fees: Centocor, Merck, Abbvie; consulting fees: Centocor, Merck, UCB, Abbvie, Millenium/Takeda, Genentech/Hoffman LaRoche, Merck/Serono, Bristol Myers Squibb, Robarts, Tillotts, Pfizer, Falk Pharma. SV—grant support from Abbvie, MSD; lecture fees: Abbvie, MSD, Takeda, Ferring, Falk Pharma, Hospira, Tillotts; grant support from Abbvie, MSD; consulting fees: Abbvie, MSD, Takeda, Ferring, Genentech/Roche, Shire, Pfizer, Galapagos, Mundipharma, Hospira, Celgene, Second Genome, Janssen.

  • Patient consent Obtained.

  • Ethics approval The ethics committee of the Leuven University Hospitals approved the study (B322201213950/S53684).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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