Ustekinumab crohn's disease
10545520
Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease.
BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin 12 and interleukin 23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI 1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI 2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn's Disease Activity Index [CDAI] score of =100 points or a CDAI score <150) The primary end point for the maintenance trial was remission at week 44 (CDAI score <150) RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI 1, 34.3% 33.7% and 21.5% respectively, with P<=0.003 for both comparisons with placebo; in UNITI 2, 51.7% 55.5% and 28.7% respectively, with P<0.001 for both doses) In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8% respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P=0.005 and P=0.04, respectively) Within each trial, adverse event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn's disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329 NCT01369342 and NCT01369355
The New England journal of medicine
Brian G Feagan William J Sandborn Christopher R Gasink Douglas A Jacobstein Yinghua Lang Joshua R Friedman Marion A Blank Jewel Johanns Long-Long Gao Ye Miao Omoniyi J Adedokun Bruce E Sands Stephen Hanauer Severine Vermeire Stephan A Targan Subrata Ghosh Willem JS de Villiers J F Colombel Zsolt Tulassay Ursula E Seidler Bruce A Salzberg Pierre Desreumaux Scott D Lee Edward V Loftus Levinus Albert Dieleman Seymour Katz Paul J Rutgeerts
218831544
Ustekinumab is associated with superior effectiveness outcomes compared to vedolizumab in Crohn's disease patients with prior failure to anti TNF treatment
Both vedolizumab and ustekinumab can be considered for the treatment of Crohn's disease (CD) when anti TNF treatment fails. However, head to head trials are currently not available or planned.
Alimentary pharmacology therapeutics
Vince B C Biemans C Janneke van der Woude Gerard Dijkstra Andrea E van der Meulen-de Jong Mark Lowenberg Nanne K H de Boer Bas Oldenburg Nidhi Srivastava Jeroen M Jansen A G L Bodelier Rachel L West Annemarie C de Vries Jeoffrey J L Haans Dirk J de Jong Frank Hoentjen Marie J Pierik
214810751
The effectiveness of either ustekinumab or vedolizumab in 239 patients with Crohn's disease refractory to anti tumour necrosis factor
There is no head to head trial comparing ustekinumab and vedolizumab in patients with Crohn's disease (CD) refractory to anti tumour necrosis factor (anti TNF)
Alimentary pharmacology therapeutics
Hadrien Alric Aurelien Amiot Julien Kirchgesner Xavier Treton Mathieu Allez Yoram Bouhnik Laurent Beaugerie Franck Carbonnel Antoine Meyer
205094495
Ustekinumab induction and maintenance therapy in refractory Crohn's disease.
BACKGROUND In patients with Crohn's disease, the efficacy of ustekinumab, a human monoclonal antibody against interleukin 12 and interleukin 23, is unknown. METHODS We evaluated ustekinumab in adults with moderate to severe Crohn's disease that was resistant to anti tumor necrosis factor (TNF) treatment. During induction, 526 patients were randomly assigned to receive intravenous ustekinumab (at a dose of 1, 3, or 6 mg per kilogram of body weight) or placebo at week 0. During the maintenance phase, 145 patients who had a response to ustekinumab at 6 weeks underwent a second randomization to receive subcutaneous injections of ustekinumab (90 mg) or placebo at weeks 8 and 16. The primary end point was a clinical response at 6 weeks. RESULTS The proportions of patients who reached the primary end point were 36.6% 34.1% and 39.7% for 1, 3, and 6 mg of ustekinumab per kilogram, respectively, as compared with 23.5% for placebo (P=0.005 for the comparison with the 6 mg group) The rate of clinical remission with the 6 mg dose did not differ significantly from the rate with placebo at 6 weeks. Maintenance therapy with ustekinumab, as compared with placebo, resulted in significantly increased rates of clinical remission (41.7% vs. 27.4% P=0.03) and response (69.4% vs. 42.5% P<0.001) at 22 weeks. Serious infections occurred in 7 patients (6 receiving ustekinumab) during induction and 11 patients (4 receiving ustekinumab) during maintenance. Basal cell carcinoma developed in 1 patient receiving ustekinumab. CONCLUSIONS Patients with moderate to severe Crohn's disease that was resistant to TNF antagonists had an increased rate of response to induction with ustekinumab, as compared with placebo. Patients with an initial response to ustekinumab had significantly increased rates of response and remission with ustekinumab as maintenance therapy. (Funded by Janssen Research and Development; CERTIFI ClinicalTrials.gov number, NCT00771667.
The New England journal of medicine
William J Sandborn Christopher R Gasink Long-Long Gao Marion A Blank Jewel Johanns Cynthia A Guzzo Bruce E Sands Stephen Hanauer Stephan R Targan Paul J Rutgeerts Subrata Ghosh Willem JS de Villiers Remo Panaccione Gordon R Greenberg Stefan Schreiber Simon Lichtiger Brian G Feagan
79537495
P281 Combined clinical and biological response (concomitant CRP and faecal calprotectin reductions) in induction and maintenance from the phase 3 ustekinumab Crohn's disease studies
s of the 13th Congress of ECCO European Crohn's and Colitis Organisation S243
J F Colombel Christopher R Gasink Alessandra Oortwijn Roger van Kruchten Sheldon Sloan Victor Laliman Paul J Rutgeerts Subrata Ghosh William J Sandborn Brian G Feagan Bruce E Sands
195190970
Ustekinumab for Crohn's Disease: Results of the ICC Registry, a Nationwide Prospective Observational Cohort Study
Abstract Background and Aims Ustekinumab is approved for the treatment of Crohn's disease [CD] Systematically registered prospective real world data are scarce. We therefore aimed to study the effectiveness, safety and usage of ustekinumab for CD in everyday practice. Methods We prospectively enrolled CD patients initiating ustekinumab in regular care between December 2016 and January 2019. Clinical (Harvey Bradshaw Index [HBI] biochemical (C reactive protein [CRP] and faecal calprotectin [FCP] extra intestinal manifestations and, peri anal fistula activity, ustekinumab dosage, concomitant medication use, and adverse events were documented at weeks 0, 12, 24, and 52. The primary outcome was corticosteroid free clinical remission. Results In total, 221 CD patients were included (98.6% anti tumour necrosis factor [TNF] and 46.6% vedolizumab exposed) with a median follow up of 52.0 weeks [interquartile range 49.3 58.4] Corticosteroid free clinical remission rates at weeks 24 and 52 were 38.2% and 37.1% respectively. An initial dosing schedule of 8 weeks, compared to 12 weeks, correlated with a lower discontinuation rate [20.0% vs 42.6% p 0.01] but comparable corticosteroid free clinical remission at week 52 (46.3% [q8w] vs 34.6% [q12w] p 0.20) There was no clinical benefit of combination therapy after 52 weeks when compared to ustekinumab monotherapy [combi 40.6% vs mono 36.0% p 0.64] At baseline, 28 patients had active peri anal fistula, of whom 35.7% showed complete clinical resolution after 24 weeks. During follow up we encountered six severe infections [3.5 per 100 patient years] with all patients being on concomitant immunosuppressant therapies. Ustekinumab treatment discontinuation was observed in 75 [33.9% patients mainly due to lack of response. Conclusion Ustekinumab is a relatively safe and effective treatment option for CD patients with prior failure of anti TNF and anti integrin therapies.
Journal of Crohn's colitis
Vince B C Biemans Andrea E van der Meulen - de Jong Christine J van der Woude Mark Lowenberg Gerard Dijkstra Bas Oldenburg Nanne K H de Boer Sander van der Marel A G L Bodelier Jeroen M Jansen Jeoffrey J L Haans Rosaline Theeuwen Dirk J de Jong Marie J Pierik Frank Hoentjen
218646522
Effectiveness of ustekinumab dose escalation in Crohn's disease patients with insufficient response to standard dose subcutaneous maintenance therapy
Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose optimisation for ustekinumab nonresponse is limited.
Alimentary pharmacology therapeutics
Uri Kopylov Jurij Hanzel Claire Liefferinckx D de Marco Nicola Imperatore Nikolas Plevris Iria Baston-Rey Richard James Harris Marie Truyens Viktor Domislovic Stephan R Vavricka Vince B C Biemans Sally Myers Shaji Sebastian Shomron Ben-Horin Yago Gonzalez Lama Cyrielle Gilletta Bar-Gil Shitrit Ariella Zuzana Zelinkova Roni Weishof Darragh Storan Eran Zittan Klaudia Farkas Tamas Molnar Denis Franchimont Anneline Cremer Waqqas Afif Fabiana Castiglione Charlie W Lees Manuel Barreiro-de Acosta Triana Lobaton Glen A Doherty Zeljko Krznaric Marie J Pierik Frank Hoentjen David Drobne
211564586
Effectiveness of Ustekinumab Dose Escalation in Patients with Crohn's Disease.
BACKGROUND AIMS A subset of patients with Crohn's disease (CD) do not respond to ustekinumab at the standard dose of 90 mg every 8 weeks. Little is known about the efficacy of shortening the interval between doses. METHODS We performed a retrospective study to determine the effectiveness of ustekinumab dose interval shortening, collecting data from 506 patients with CD who received subcutaneous ustekinumab 90 mg every 8 weeks at a single center. We obtained data from 110 patients who initially received subcutaneous ustekinumab 90 mg every 8 weeks and then had their interval shortened to every 4 weeks. Harvey Bradshaw Index (HBI) scores before and after the dose interval shortening was available for 78 patients in the cohort (71% levels of C reactive protein (CRP) for 60 patients (55% and levels of fecal calprotectin for 8 patients (7% RESULTS Following dose interval shortening, the patients' median HBI decreased from 4.5 to 3 (P=.002) the median level of CRP decreased from 8 mg/l to 3 mg/l (P=.031) and median level of fecal calprotectin decreased from 378 mg/g to 157 mg/g (P=.57) Among patients who had an HBI >4, a level of CRP =5mg/dl, a level of fecal calprotectin >250ug/g, or endoscopic evidence for disease activity before dose interval shortening, after the dose interval was shortened, 28% achieved clinical remission (an HBI score =4) 22% had a normal level of CRP <5 mg/dl) 50% had reduced levels of fecal calprotectin, and 36% achieved endoscopic remission. CONCLUSIONS Shortening the ustekinumab 90 mg dose interval to 4 weeks for patients with CD who did not respond to doses every 8 weeks improved clinical and biological indices of disease activity. Patients who lose response to the standard dose of ustekinumab might benefit from dose interval shortening, which was effective and safe.
Clinical gastroenterology and hepatology the official clinical practice journal of the American Gastroenterological Association
Jacob E Ollech Inessa Normatov Noam Peleg Jingzhou Wang Shivani A Patel Victoria Rai Yangtian Yi Jorie Singer Sushila Dalal Atsushi Sakuraba Russell D Cohen David T Rubin Joel Pekow
221237566
High Immunogenicity to Influenza Vaccination in Crohn's Disease Patients Treated with Ustekinumab
Influenza vaccination can be less effective in patients treated with immunosuppressive therapy. However, little is known about the effects of ustekinumab; an anti IL 12/23 agent used to treat Crohn's disease (CD) on vaccination response. In this prospective study, we assessed immune responses to seasonal influenza vaccination in CD patients treated with ustekinumab compared to CD patients treated with anti TNFa therapy (adalimumab) and healthy controls. Humoral responses were assessed with hemagglutinin inhibition (HI) assays. Influenza specific total CD3+ CD3+CD4+ and CD3+CD8+ T cell responses were measured with flow cytometry. Fifteen patients treated with ustekinumab; 12 with adalimumab and 20 healthy controls were vaccinated for seasonal influenza in September 2018. Seroprotection rates against all vaccine strains in the ustekinumab group were high and comparable to healthy controls. Seroconversion rates were comparable, and for A/H3N2 highest in the ustekinumab group. HI titers were significantly higher in the ustekinumab group and healthy controls than in the adalimumab group for the B/Victoria strain. Post vaccination T cell responses in the ustekinumab group were similar to healthy controls. One month post vaccination proliferation of CD3+CD8+ T cells was highest in the ustekinumab group. In conclusion, ustekinumab does not impair immune responses to inactivated influenza vaccination. Therefore, CD patients treated with ustekinumab can be effectively vaccinated for seasonal influenza.
Vaccines
Laura Doornekamp Rogier L Goetgebuer Katharina S Schmitz Marco Goeijenbier C Janneke van der Woude Ron A M Fouchier Eric C M van Gorp Annemarie C de Vries
221812042
Comparative effectiveness of ustekinumab or vedolizumab after one year in 130 patients with anti TNF refractory Crohn's disease
Anti tumour necrosis factor (TNF) agents are effective in Crohn's disease but some patients lose response and require alternative biologic therapy. There are few data on comparative effectiveness of vedolizumab and ustekinumab in this setting.
Alimentary pharmacology therapeutics
Tristan Townsend Violeta Razanskaite Susanna Dodd Daniel Storey Stephanie Michail James Morgan Michael Davies Douglas Penman Christopher Watters Mirashini Swaminathan Joseph Sabine Adam Chapman Paul K Flanagan Ian Reilly Keith Bodger Sreedhar Subramanian