Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis.
Adult
Anti-Inflammatory Agents
/ administration & dosage
Colitis, Ulcerative
/ drug therapy
Dose-Response Relationship, Drug
Double-Blind Method
Female
Humans
Induction Chemotherapy
Infusions, Intravenous
Injections, Subcutaneous
Maintenance Chemotherapy
Male
Patient Acuity
Remission Induction
/ methods
Ustekinumab
/ administration & dosage
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
26 09 2019
26 09 2019
Historique:
entrez:
26
9
2019
pubmed:
26
9
2019
medline:
3
10
2019
Statut:
ppublish
Résumé
The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown. We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range-based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P<0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P = 0.002 and P<0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo. Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis. (Funded by Janssen Research and Development; UNIFI ClinicalTrials.gov number, NCT02407236.).
Sections du résumé
BACKGROUND
The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown.
METHODS
We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range-based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components).
RESULTS
The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P<0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P = 0.002 and P<0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo.
CONCLUSIONS
Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis. (Funded by Janssen Research and Development; UNIFI ClinicalTrials.gov number, NCT02407236.).
Identifiants
pubmed: 31553833
doi: 10.1056/NEJMoa1900750
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Ustekinumab
FU77B4U5Z0
Banques de données
ClinicalTrials.gov
['NCT02407236']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1201-1214Investigateurs
Steven Brown
(S)
Susan Connor
(S)
Peter De Cruz
(P)
Nick John Ding
(NJ)
Tim Florin
(T)
Peter Hendy
(P)
Rupert Leong
(R)
Gregory Moore
(G)
Paul Pavli
(P)
Miles Sparrow
(M)
Sonja Gassner
(S)
Harald Vogelsang
(H)
Filip Baert
(F)
Arnaud Colard
(A)
Martine De Vos
(M)
Francois D'heygere
(F)
Marc Ferrante
(M)
Edouard Louis
(E)
Dirk Staessen
(D)
Temenuzhka Berova
(T)
Jordan Churchev
(J)
Raina Draganova
(R)
Diana Gancheva
(D)
Neli Ivanova
(N)
Ivanka Marinova
(I)
Mario Markov
(M)
Rossen Nikolov
(R)
Nikolay Tsonev
(N)
Galina Vassileva
(G)
Waqqas Afif
(W)
Charles Berstein
(C)
Brian Bressler
(B)
Vipul Jairath
(V)
Jean-Rene Lachance
(JR)
Ranjit Singh
(R)
Kim Tilbe
(K)
Victor Komarek
(V)
Jana Kozeluhova
(J)
Milan Lukas
(M)
Miroslava Volfova
(M)
Jens Dahlerup
(J)
Romain Altwegg
(R)
Sylvain Beorchia
(S)
Guillaume Bouguen
(G)
Guillaume Cadiot
(G)
Jean-Louis Dupas
(JL)
Pierre Desreumaux
(P)
Bernard Flourie
(B)
Jean-Charles Grimaud
(JC)
Olivier Guillaud
(O)
Jacques Moreau
(J)
Xavier Roblin
(X)
Frank Zerbib
(F)
Daniel Baumgart
(D)
Susanne Beckebaum
(S)
Bernd Bokemeyer
(B)
Matthias Ebert
(M)
Peter Hasselblatt
(P)
Andreas Lügering
(A)
Christian Maaser
(C)
Inglof Schiefke
(I)
Stefan Schreiber
(S)
Ursula Seidler
(U)
Istvan Altorjay
(I)
Gyula G Kiss
(GG)
Botond Literati-Nagy
(B)
Arpád Patai
(A)
Gyula Pecsi
(G)
Agnes Salamon
(A)
Robert Schnabel
(R)
Andras Székely
(A)
Zsolt Tulassay
(Z)
Marta Varga
(M)
Alexander Fich
(A)
Sigal Fishman
(S)
Fred Konikoff
(F)
Lev Lichtenstein
(L)
Tova Rainis
(T)
Wisam Sbeit
(W)
Doron Schwartz
(D)
Vito Annese
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Livia Biancone
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Rocco Costintino
(R)
Silvio Danese
(S)
Walter Fries
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(A)
Luisa Guidi
(L)
Anna Kohn
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Giovanni Maconi
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Rodolfo Rocca
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Francesca Rogai
(F)
Erica Villa
(E)
Giorgio Zoli
(G)
Hirotada Akiho
(H)
Nobuo Aoyama
(N)
Tomiyasu Arisawa
(T)
Hisamitsu Hidaka
(H)
Tadakazu Hisamatsu
(T)
Noriyuki Horiki
(N)
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