Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn's Disease.

Humans Crohn Disease / drug therapy Ustekinumab / therapeutic use Male Female Adult Middle Aged Antibodies, Monoclonal / therapeutic use Remission Induction Severity of Illness Index Intention to Treat Analysis Young Adult

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:
18 Jul 2024

Historique:

medline: 17 7 2024

pubmed: 17 7 2024

entrez: 17 7 2024

Statut: ppublish

Résumé

The efficacy and safety of risankizumab as compared with ustekinumab in patients with Crohn's disease are unknown. In this phase 3b, multicenter, open-label, randomized, controlled trial with blinded assessment of end points, patients with moderate-to-severe Crohn's disease who had had an inadequate response to anti-tumor necrosis factor (TNF) therapy or unacceptable side effects with such therapy were randomly assigned to receive risankizumab or ustekinumab at standard doses for 48 weeks. The two primary end points, which were tested sequentially, were clinical remission at week 24 (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]), which was analyzed in the first 50% of patients to complete the week 24 visit, with a noninferiority margin of 10 percentage points; and endoscopic remission at week 48 (defined as a score of ≤4, a decrease of ≥2 points from baseline, and no subscore >1 in any individual variable on the Simple Endoscopic Score for Crohn's Disease [range, 0 to 56, with higher scores indicating more severe disease]), which was analyzed for superiority in 100% of the patients. Safety was assessed in all patients who received at least one dose of risankizumab or ustekinumab. In the full intention-to-treat population for the efficacy analysis, 230 of 255 patients (90.2%) who received risankizumab and 193 of 265 patients (72.8%) who received ustekinumab completed all the assigned treatments. Both primary end points were met; risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 (58.6% vs. 39.5%; adjusted difference, 18.4 percentage points; 95% confidence interval [CI], 6.6 to 30.3) and superior to ustekinumab with respect to endoscopic remission at week 48 (31.8% vs. 16.2%; adjusted difference, 15.6 percentage points; 95% CI, 8.4 to 22.9; P<0.001). The incidence of adverse events appeared to be similar in the two groups. In this head-to-head clinical trial of risankizumab and ustekinumab involving patients with moderate-to-severe Crohn's disease who had had unacceptable side effects with anti-TNF therapy or an inadequate response to such therapy, risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 and superior with respect to endoscopic remission at week 48. (Funded by AbbVie; ClinicalTrials.gov number, NCT04524611.).

Sections du résumé

BACKGROUND BACKGROUND

The efficacy and safety of risankizumab as compared with ustekinumab in patients with Crohn's disease are unknown.

METHODS METHODS

In this phase 3b, multicenter, open-label, randomized, controlled trial with blinded assessment of end points, patients with moderate-to-severe Crohn's disease who had had an inadequate response to anti-tumor necrosis factor (TNF) therapy or unacceptable side effects with such therapy were randomly assigned to receive risankizumab or ustekinumab at standard doses for 48 weeks. The two primary end points, which were tested sequentially, were clinical remission at week 24 (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]), which was analyzed in the first 50% of patients to complete the week 24 visit, with a noninferiority margin of 10 percentage points; and endoscopic remission at week 48 (defined as a score of ≤4, a decrease of ≥2 points from baseline, and no subscore >1 in any individual variable on the Simple Endoscopic Score for Crohn's Disease [range, 0 to 56, with higher scores indicating more severe disease]), which was analyzed for superiority in 100% of the patients. Safety was assessed in all patients who received at least one dose of risankizumab or ustekinumab.

RESULTS RESULTS

In the full intention-to-treat population for the efficacy analysis, 230 of 255 patients (90.2%) who received risankizumab and 193 of 265 patients (72.8%) who received ustekinumab completed all the assigned treatments. Both primary end points were met; risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 (58.6% vs. 39.5%; adjusted difference, 18.4 percentage points; 95% confidence interval [CI], 6.6 to 30.3) and superior to ustekinumab with respect to endoscopic remission at week 48 (31.8% vs. 16.2%; adjusted difference, 15.6 percentage points; 95% CI, 8.4 to 22.9; P<0.001). The incidence of adverse events appeared to be similar in the two groups.

CONCLUSIONS CONCLUSIONS

In this head-to-head clinical trial of risankizumab and ustekinumab involving patients with moderate-to-severe Crohn's disease who had had unacceptable side effects with anti-TNF therapy or an inadequate response to such therapy, risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 and superior with respect to endoscopic remission at week 48. (Funded by AbbVie; ClinicalTrials.gov number, NCT04524611.).

Identifiants

DOI: 10.1056/NEJMoa2314585 PMID: 39018531

pubmed: 39018531

doi: 10.1056/NEJMoa2314585

doi:

Substances chimiques

Ustekinumab FU77B4U5Z0

risankizumab 90ZX3Q3FR7

Antibodies, Monoclonal 0

Banques de données

ClinicalTrials.gov

['NCT04524611']

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Clinical Trial, Phase III Comparative Study Equivalence Trial

Langues

eng

Sous-ensembles de citation

Pagination

213-223

Investigateurs

Domingo Balderramo (D)

Juan De Paula (J)

Silvina Goncalves (S)

Raquel Analia Gonzalez (RA)

Juan Lasa (J)

Abel Novillo (A)

Ignacio Zubiaurre (I)

Jakob Begun (J)

Gregory Moore (G)

Claudia Rogge (C)

Dheeraj Shukla (D)

Derrick Tee (D)

Andreas Maieron (A)

Peter Piringer (P)

Walter Reinisch (W)

Didier Baert (D)

Filip Baert (F)

Arnaud Colard (A)

Olivier Dewit (O)

Joris Dutré (J)

Marc Ferrante (M)

Denis Franchimont (D)

Jeroen Geldof (J)

Tom Holvoet (T)

Edouard Louis (E)

Jean-Francois Rahier (JF)

Adriana Catapani (A)

Roberto Kaiser Junior (R)

Rogerio Parra (R)

Ligia Sassaki (L)

Petko Karagyozov (P)

Plamen Penchev (P)

Desislav Stanchev (D)

Nikolay Tsonev (N)

Kenneth Atkinson (K)

Jeﬀrey Axler (J)

Melanie Beaton (M)

Talat Bessissow (T)

Allen Lim (A)

Dustin Loomes (D)

Remo Panaccione (R)

Joannie Ruel (J)

Scot Shulman (S)

Jesse Siﬄedeen (J)

Hillary Steinhart (H)

Michael Stewart (M)

Felix Trottier Tellier (F)

Andrew Wisniewski (A)

Ignacio Alfaro (I)

Carlos Valenzuela (C)

Gustavo Walsen (G)

Ping An (P)

Qian Cao (Q)

Yan Chen (Y)

Youxiang Chen (Y)

Baisui Feng (B)

Xiang Gao (X)

Hong Guo (H)

Xiaohua Hou (X)

Yan Li (Y)

Mei Liu (M)

Wenjia Liu (W)

Zhihua Ran (Z)

Ding Shigang (D)

Lin Wang (L)

Xiaoyan Wang (X)

Xinying Wang (X)

Xuehong Wang (X)

Yufang Wang (Y)

Qiang Zhan (Q)

Kaiguang Zhang (K)

Xiaoping Zou (X)

Martin Bortlik (M)

Milan Lukas (M)

Jan Matous (J)

Tomas Vanasek (T)

Michal Voska (M)

Petr Vyhnalek (P)

Lore Billiauws (L)

Lucile Boivineau (L)

Arnaud Bourreille (A)

Anthony Buisson (A)

Guillaume Cadiot (G)

Mathurin Flamant (M)

Cyrielle Gilleta de Saint Joseph (C)

Florent Gonzalez (F)

Xavier Hebuterne (X)

David Laharie (D)

Nicolas Mathieu (N)

Maria Nachury (M)

Laurent Peyrin-Biroulet (L)

Xavier Roblin (X)

Melanie Serrero (M)

Xavier Treton (X)

Raja Atreya (R)

Irina Blumenstein (I)

Carsten Buening (C)

Axel Dignass (A)

Andreas Fischer (A)

Peter Hasselblat (P)

Arne Kandulski (A)

Jochen Klaus (J)

Torsten Kucharzik (T)

Sebastian Kuepper (S)

Wolfgang Mohl (W)

Michael Mross (M)

Axel Naumann (A)

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Stefan Schreiber (S)

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