Effectiveness and safety of ustekinumab induction therapy for 103 patients with ulcerative colitis: a GETAID multicentre real-world cohort study.
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
10
01
2020
revised:
04
02
2020
accepted:
21
03
2020
pubmed:
16
4
2020
medline:
20
11
2020
entrez:
16
4
2020
Statut:
ppublish
Résumé
Phase III trials have demonstrated the efficacy and safety of ustekinumab in moderate-to-severe ulcerative colitis (UC), but few real-world data are currently available. To assess short-term effectiveness and safety of ustekinumab in patients with UC. From January to September 2019, all patients with UC treated with ustekinumab in 20 French GETAID centres were retrospectively included. The primary outcome was steroid-free clinical remission (partial Mayo Clinic score ≤2) at weeks 12-16 without a rectal bleeding subscore >1. Among the 103 patients included, 70% had been previously exposed to ≥2 anti-TNF agents and 85% to vedolizumab. At weeks 12-16, steroid-free clinical remission and clinical remission rates were 35.0% and 39.8% respectively; the absence of rectal bleeding with normal stool frequency was noted in 19.4% of patients. Two patients discontinued ustekinumab before the week 12-16 visit and underwent surgery. In multivariable analysis, a partial Mayo Clinic score >6 at inclusion (18.6% vs 46.7%, P = 0.003) and a history of both exposure to anti-TNF and vedolizumab therapies (27.3% vs 80.0%, P = 0.001) were negatively associated with steroid-free clinical remission at weeks 12-16. Adverse events occurred in 7.8% of patients and serious adverse events in 3.9% of patients. In a cohort of highly refractory patients with UC with multiple prior drug failures, ustekinumab provided steroid-free clinical remission in one-third of cases at weeks 12-16. Clinical severity and previous use of anti-TNF and vedolizumab therapies were associated with ustekinumab failure at weeks 12-16.
Sections du résumé
BACKGROUND
Phase III trials have demonstrated the efficacy and safety of ustekinumab in moderate-to-severe ulcerative colitis (UC), but few real-world data are currently available.
AIM
To assess short-term effectiveness and safety of ustekinumab in patients with UC.
METHODS
From January to September 2019, all patients with UC treated with ustekinumab in 20 French GETAID centres were retrospectively included. The primary outcome was steroid-free clinical remission (partial Mayo Clinic score ≤2) at weeks 12-16 without a rectal bleeding subscore >1.
RESULTS
Among the 103 patients included, 70% had been previously exposed to ≥2 anti-TNF agents and 85% to vedolizumab. At weeks 12-16, steroid-free clinical remission and clinical remission rates were 35.0% and 39.8% respectively; the absence of rectal bleeding with normal stool frequency was noted in 19.4% of patients. Two patients discontinued ustekinumab before the week 12-16 visit and underwent surgery. In multivariable analysis, a partial Mayo Clinic score >6 at inclusion (18.6% vs 46.7%, P = 0.003) and a history of both exposure to anti-TNF and vedolizumab therapies (27.3% vs 80.0%, P = 0.001) were negatively associated with steroid-free clinical remission at weeks 12-16. Adverse events occurred in 7.8% of patients and serious adverse events in 3.9% of patients.
CONCLUSION
In a cohort of highly refractory patients with UC with multiple prior drug failures, ustekinumab provided steroid-free clinical remission in one-third of cases at weeks 12-16. Clinical severity and previous use of anti-TNF and vedolizumab therapies were associated with ustekinumab failure at weeks 12-16.
Substances chimiques
Ustekinumab
FU77B4U5Z0
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1039-1046Investigateurs
Aurélien Amiot
(A)
Charlotte Gagnière
(C)
Jenny Tannoury
(J)
Jérôme Filippi
(J)
Xavier Hebuterne
(X)
Vered Abitbol
(V)
Guillaume Cadiot
(G)
Hedia Brixi
(H)
David Laharie
(D)
Pauline Rivière
(P)
Florian Poullenot
(F)
Melanie Serrero
(M)
Romain Altwegg
(R)
Guillaume Pineton de Chambrun
(G)
Yoram Bouhnik
(Y)
Xavier Treton
(X)
Carmen Stefanescu
(C)
Denis Diderot
(D)
Laurent Peyrin-Biroulet
(L)
Camille Zallot
(C)
Cyrielle Gilletta
(C)
Xavier Roblin
(X)
Lucine Vuitton
(L)
Anne Bourrier
(A)
Laurent Beaugerie
(L)
Philippe Seksik
(P)
Harry Sokol
(H)
Julien Kirchgesner
(J)
Stephane Nancey
(S)
Gilles Boschetti
(G)
Bernard Flourié
(B)
Claire Gay
(C)
Pauline Danion
(P)
Chloe Venturin
(C)
Jean-Marc Gornet
(JM)
Matthieu Allez
(M)
Clotilde Baudry
(C)
Stephane Nahon
(S)
Guillaume Bouguen
(G)
Stephanie Viennot
(S)
Benjamin Pariente
(B)
Maria Nachury
(M)
Pauline Wils
(P)
Mathurin Fumery
(M)
Franck Brazier
(F)
Clara Yzet
(C)
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2020 John Wiley & Sons Ltd.
Références
Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med. 2011;365:1713-1725.
Ungaro R, Mehandru S, Allen PB, et al. Ulcerative colitis. Lancet. 2017;389:1756-1770.
Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREATTM registry. Am J Gastroenterol. 2012;107:1409-1422.
Toruner M, Loftus EV Jr, Harmsen WS, et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology. 2008;134:929-936.
Pouillon L, Lamoureux A, Pineton de Chambrun G, et al. Dose de-escalation to adalimumab 40 mg every three weeks in patients with inflammatory bowel disease-A multicenter, retrospective, observational study. Dig Liver Dis Off J Ital Soc Gastroenterol Ital Assoc Study. Liver. 2019;51:236-241.
Singh S, Fumery M, Sandborn WJ, et al. Systematic review with network meta-analysis: first- and second-line pharmacotherapy for moderate-severe ulcerative colitis. Aliment Pharmacol Ther. 2018;47:162-175.
Peyrin-Biroulet L, Danese S, Argollo M, et al. Loss of response to vedolizumab and ability of dose intensification to restore response in patients with Crohn’s disease or ulcerative colitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2019;17:838-846. e2.
Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462-2476.
Ochsenkühn T, Tillack C, Szokodi D, et al. Clinical outcomes with ustekinumab as rescue treatment in therapy-refractory or therapy-intolerant ulcerative colitis. United Eur Gastroenterol J. 2019;8:91-98.
Amiot A, Grimaud J-C, Peyrin-Biroulet L, et al. Effectiveness and safety of vedolizumab induction therapy for patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2016;14:1593-1601. e2.
Amiot A, Serrero M, Peyrin-Biroulet L, et al. One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicenter cohort study. Aliment Pharmacol Ther. 2017. in press.
Amiot A, Serrero M, Peyrin-Biroulet L, et al. Three-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multi-centre cohort study. Aliment Pharmacol Ther. 2019;50:40-53.
Travis SPL, Schnell D, Krzeski P, et al. Reliability and initial validation of the ulcerative colitis endoscopic index of severity. Gastroenterology. 2013;145:987-995.
Sands BE, Sandborn WJ, Panaccione R, et al. Ustekinumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2019;381:1201-1214.
Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015;110:1324-1338.
Ma C, Fedorak RN, Kaplan GG, et al. Long-term maintenance of clinical, endoscopic, and radiographic response to ustekinumab in moderate-to-Severe Crohn’s disease: real-world experience from a multicenter cohort study. Inflamm Bowel Dis. 2017;23:833-839.
Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016;375:1946-1960.
Barré A, Colombel J-F, Ungaro R. Review article: predictors of response to vedolizumab and ustekinumab in inflammatory bowel disease. Aliment Pharmacol Ther. 2018;47:896-905.
Papp K, Gottlieb AB, Naldi L, et al. Safety surveillance for ustekinumab and other psoriasis treatments from the psoriasis longitudinal assessment and registry (PSOLAR). J Drugs Dermatol JDD. 2015;14:706-714.
Engel T, Yung DE, Ma C, et al. Effectiveness and safety of Ustekinumab for Crohn’s disease; systematic review and pooled analysis of real-world evidence. Dig Liver Dis. 2019;51:1232-1240.
López-Ferrer A, Laiz A, Puig L. The safety of ustekinumab for the treatment of psoriatic arthritis. Expert Opin Drug Saf. 2017;16:733-742.