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DOP74 Effectiveness of dose escalation in Crohn’s disease patients with insufficient response to standard-dose subcutaneous ustekinumab maintenance therapy: A multicentre international cohort study

U. Kopylov1, J. Hanzel2, C. Liefferinckx3, D. De Marco4, N. Imperatore5, N. Plevris6, I. Baston-Rey7, R. Harris8, M. Truyens9, V. Domislovic10, S. Vavricka11, V. Biemans12,13, S. Myers14, S. Shaji14, S. Ben-Horin1, Y. González Lama15, C. Gilletta16, A. Bar-Gil Shitrit17, Z. Zelinkova18, R. Weishof19, D. Storan20, E. Zittan21, D. Franchimont3, A. Cremer3, W. Afif4, F. Castiglione5, C. Lees7, M. Barrero de Acosta7, T. Lobaton9, G. Doherty20, Z. Krznaric10, M. Pierik12, F. Hoentjen13, D. Drobne2

1Sheba Medical Center, Ramat Gan and Sackler Medical School, Tel Aviv, Israel, Department of Gastroenterology, Ramat Gan, Israel, 2Department of Gastroenterology, University Medical Centre Ljubljana, Ljubliana, Slovenia, 3Department of Gastroentrerology, Hôpital Erasme, ULB, Brussels, Belgium, Department of Gastroenterology, 4McGill University Health Center, Montreal, Canada, 5School of Medicine Federico II of Naples, Department of Clinical Medicine and Surgery, Department of Gastroenterology, Naples, Italy, 6Western General Hospital, Edinburgh IBD Unit, Edinburgh, UK, 7Servicio de Aparato Digestivo, Hospital Clínico Universitario de Santiago de Compostela, Unidad EII, Santiago de Compostela, Spain, 8University Hospital Southampton NHS Foundation Trust, Department of Gastroenterology, Southampton, UK, 9Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium, 10Department of Gastroenterology and Hepatology, University Hospital Centre Zagreb, Zagreb, Croatia, 11Center for Gastroenterology and Hepatology, Zurich, Switzerland, 12Division of Gastroenterology and Hepatology, Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands Antilles, 13Department of Gastroentrology, Radboud University Medical Center, Nijmegen, The Netherlands Antilles, 14IBD Unit, Hull University Teaching Hospitals NHS Trust, Hull, UK, 15Gastroenterology and Hepatology Department, Hospital Universitario Puerta de Hierro, IBD Unit, Madrid, Spain, 16CHU Toulouse Rangueil, Service de Gastroentérologie et Nutrition, Toulouse, France, 17Shaare Zedek Medical Center Affiliated with the Medical School, Hebrew University, IBD MOM Unit, Digestive Diseases Institute, Jerusalem, Israel, 18Department of Gastroenterology and Gastrointestinal Endoscopy, St Michael’s Hospital, Bratislava, Slovakia, 19Rambam Health Care Campus, Haifa, Israel, †Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Gastroenterology, Haifa, Israel, 20St. Vincent’s University Hospital and School of Medicine, University College Dublin, Centre for Colorectal Disease, Dublin, Ireland, 21Emek Medical Center, Ellen and Pinchas Mamber Institute of Gastroenterology and Liver Diseases, Afula, Israel

Background

Ustekinumab (UST) is an effective agent for induction and maintenance of response and remission in Crohn’s disease (CD). In addition to randomised controlled trials, an abundance of real-world evidence is available as well, suggesting that a substantial proportion of patients will not respond or lose response to UST therapy. To date, there is very little evidence to support the effectiveness of dose-optimisation strategy to manage primary or secondary non-response to ustekinumab.

Methods

This was a multicentre retrospective cohort study. The protocol was reviewed and approved by the Clinical Committee of ECCO. We included active (HBI≥5; CDAI ≥220) CD patients that received a standard-dose IV induction and at least one SC UST dose of 90 mg. Patients with ostomy were excluded. All patients received dose escalation by either shortening the interval between the doses to q4/6 weeks, intravenous reinduction or a combination of intravenous and subcutaneous escalation. The primary aim of the study was a clinical response (defined as Δ HBI≥3 or Δ CDAI ≥ 70 points) at week 16 after dose escalation. Clinical remission was defined as HBI<5 or CDAI <150.

Results

Of 140 patients, 83 (59.3%) were females, median age at treatment onset 36 (26–50) years, median duration of disease 9 (5–18) years from 21 centres in 13 countries (12 Europe, 1 Canada) were included. The patients were dose-escalated after a median treatment duration of 30 (20–45) weeks. Thirty-four (24,3%) were previously escalated from q12 to q8 maintenance regimen. Eighty-nine (63.5%) of the patients were escalated from q8 to q4 regimen, 20 (14.3%) – from q8 to q6, 15 (10.7%) received intravenous reinduction and 16 (11.4%) – a combination of intravenous reinduction and subcutaneous dose interval shortening. At week 16 from escalation, 83 (59.3%) responded to treatment, of them 21 (15%) were in clinical remission. Thirty-three (23.6%) of the patients were on systemic corticosteroids upon escalation; 7/33 (21.2%) achieved corticosteroid-free remission at week 16. One hundred and nine patients (77.8%) continued treatment beyond week 16. Follow-up data beyond week 16 were available for 75/150 (53.6%) of the patients (median duration of follow-up: 35 (32–54) weeks) from dose escalation. At the last follow-up, 53/75 (70.7%) continued to respond to treatment, including 42 (56%) in clinical remission; 25/75 (33%) discontinued treatment at last follow-up.

Conclusion

This large multicentre retrospective study demonstrates that intensification of ustekinumab maintenance dosage may be effective in up to 60% of the patients. This strategy should be considered in patients that are non-responsive to q8 ustekinumab maintenance dosing.

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