DOP029 Ustekinumab efficacy and safety in Crohn's disease patients refractory to conventional and anti-TNF therapy: a multicenter retrospective experience.
P. Wils*1, Y. Bouhnik2, B. Flourie3, H. Brixi4, J. Cosnes5, M. Allez6, B. Duclos7, P. Michetti8, J.-C. Grimaud9, G. Bommelaer10, A. Amiot11, M. Fumery12, J. Filippi13, V. Abitbol14, B. Coffin15, M. Simon16, D. Laharie17, B. Pariente1
1CHU de Lille, Department of Gastroenterology, Lille, France, 2Beaujon Hospital, Gastroenterology Unit, Clichy, France, 3Centre Hospitalier Lyon-Sud, Service d'Hépato-gastro-entérologie, Lyon, France, 4CHU de Reims, Gastroenterologie, Reims, France, 5University Hospital of Saint Antoine, APHP, Gastroenterology, Paris, France, 6APHP, Hopital Saint Louis, Department of Gastroenterology, Paris, France, 7Université de Strasbourg, Gastroenterology, Strasbourg, France, 8University Hospital Lausanne, Division of Gastroenterology & Hepatology,, Lausanne, Switzerland, 9Hôpital Nord, Gastroenterology Unit, Marseille, France, 10CHU de Clermont-Ferrand, Department of Gastroenterology, Clermont-Ferrand, France, 11Hospital Henri-Mondor, Department of Gastroenterology, Creteil, France, 12Amiens University Hospital, Gastroenterology, Amiens, France, 13CHU de Nice, Department of Gastroenterology, Nice, France, 14Cochin University Hospital, Gastroenterology, Paris, France, 15Hopital Louis-Mourier, Gastroenterologie, Colombes, France, 16Institut Mutualiste Montsouris , Gastroenterology , Paris, France, 17CHU de Bordeaux, Gastroenterology, Pessac, France
Ustekinumab is a human monoclonal antibody against the p40 subunit of interleukin-12 and interleukin-23. It has been shown to be effective in Crohn's disease (CD) patients refractory to anti-TNF in a phase II trial (Sandborn WJ et al N Engl J Med. 2012). The aim of the present study was to assess subcutaneous ustekinumab benefits and safety, and to identify predictive factors of clinical response in a multicenter cohort of anti-TNF refractory CD patients.
A retrospective observational study was conducted in French tertiary centers from the GETAID, including all consecutive patients who received subcutaneous ustekinumab for refractory CD to conventional and anti-TNF therapy and having a follow-up of more than 3 months. The primary objective was ustekinumab clinical benefit at 3 months, defined by a significant improvement as judged by the physician leading to continue the treatment with complete steroids weaning if given at inclusion. Ustekinumab safety and clinical benefit at 6, 12 months and end of follow-up were also recorded.
Ninety-seven CD patients (27 males, mean age 35.1 ± 11.6 years) received at least one subcutaneous ustekinumab injection in 16 centers. At baseline, median (IQR) disease duration was 11.9 (7.3-16.2) years; 97 (100%) patients experienced previous failure or intolerance to thiopurines or methotrexate and to at least one anti-TNF agent (infliximab or adalimumab, with 85 (87%) who received both anti-TNFs) and 59 (61%) patients underwent prior intestinal resection. Ustekinumab was given for luminal CD in 88 (91%) patients and for perianal disease in 9 (9%). Median follow-up duration was 39.2 ± 32.8 weeks. Mean cumulative dose of ustekinumab given for induction from week 0 to 4 was 148.5 ± 65 mg (range: 45-396 mg). At inclusion, 15 patients received corticosteroids and 12 patients concomitant immunosuppressant (IS). Clinical benefit at 3 months was observed in 69 (71%) patients in the whole population and in 8/9 of patients with perianal CD. Among the primary ustekinumab responders, 78% and 86% experienced clinical benefit at 6 and 12 months, respectively. Concomitant IS and absence of corticosteroids at time of ustekinumab introduction were associated, but non-significantly, with clinical response to ustekinumab at 3 months (p=0.09). No serious adverse effects related to ustekinumab were reported.
In patients with highly refractory CD, a clinical benefit to subcutaneous ustekinumab was observed in 71% at 3 months and was maintained in the majority of patients for up to 12 months. Along this, ustekinumab could be considered as a rescue therapy in CD patients who experienced prior failure or intolerance to conventional IS and to anti-TNF agents.