Query: Ustekinumab crohn's disease

title: Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease.
abstract: 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.  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)  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.  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

title: Ustekinumab is associated with superior effectiveness outcomes compared to vedolizumab in Crohn's disease patients with prior failure to anti TNF treatment
abstract: 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.

title: The effectiveness of either ustekinumab or vedolizumab in 239 patients with Crohn's disease refractory to anti tumour necrosis factor
abstract: 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)

title: Ustekinumab induction and maintenance therapy in refractory Crohn's disease.
abstract: In patients with Crohn's disease, the efficacy of ustekinumab, a human monoclonal antibody against interleukin 12 and interleukin 23, is unknown.  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.  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.  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.

title: 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
abstract: s of the 13th Congress of ECCO European Crohn's and Colitis Organisation S243

title: Ustekinumab for Crohn's Disease: Results of the ICC Registry, a Nationwide Prospective Observational Cohort Study
abstract: 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.  We prospectively enrolled CD patients initiating ustekinumab in regular care between December 2016 and January 2019.  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.  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.  Ustekinumab is a relatively safe and effective treatment option for CD patients with prior failure of anti TNF and anti integrin therapies.

title: Effectiveness of ustekinumab dose escalation in Crohn's disease patients with insufficient response to standard dose subcutaneous maintenance therapy
abstract: 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.

title: Effectiveness of Ustekinumab Dose Escalation in Patients with Crohn's Disease.
abstract: 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.  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%  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.  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.

title: High Immunogenicity to Influenza Vaccination in Crohn's Disease Patients Treated with Ustekinumab
abstract: 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.

title: Comparative effectiveness of ustekinumab or vedolizumab after one year in 130 patients with anti TNF refractory Crohn's disease
abstract: 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.