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Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy.

ABSTRACT: BACKGROUND:In Phase 3 studies of ustekinumab, a fully human monoclonal IL-12/23p40 antibody approved for moderate-to-severe Crohn's disease, patients entered a long-term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM-UNITI maintenance are reported. METHODS:UNITI-1 (TNF-antagonist failures) and UNITI-2 (conventional therapy failures) patients (N = 1281) entered IM-UNITI, including 397 ustekinumab intravenous induction responders randomised to subcutaneous ustekinumab 90 mg every 12 weeks, every 8 weeks, or placebo and 884 nonrandomised patients. Dose-adjustment to 90 mg every 8 weeks occurred in patients randomised to 90 mg every 12 weeks and placebo patients with loss of response (Weeks 8-32). All Week 44 completers could enter the long-term extension without further dose adjustment. Placebo patients discontinued following study unblinding. RESULTS:A total of 718 patients (all treated) entered the long-term extension (298 randomised and 420 not randomised). Overall, 86.5% (621/718) completed Week 96. The proportions of randomised patients in clinical remission were generally maintained from Week 44 through 92 in ustekinumab 90 mg every 12 weeks (77.4% to 72.6%), every 8 weeks (84.1% to 74.4%), and prior dose adjustment groups (63.4% to 53.5%). At Week 92, the proportions of patients in clinical remission were similar in the ustekinumab 90 mg every 12 weeks and every 8 weeks groups and lower in patients with prior dose adjustment. Proportions of patients in clinical remission at Week 92 for all treated every 8 weeks (64.4%) and every 12 weeks (64.3%) groups were lower than randomised every 8 weeks (74.4%) and every 12 weeks (72.6%) groups, but similarly maintained. Safety events (per hundred patient-years) were similar among all placebo and ustekinumab patients (Week 0-96), including adverse events (484.39 vs 447.76), serious adverse events (19.24 vs 18.82), and serious infections (4.09 vs 4.02). No dose effect was observed. CONCLUSIONS:Subcutaneous ustekinumab maintained clinical response and remission through Week 92. No new safety signals were observed. ClinicalTrials.gov number NCT01369355.

SUBMITTER: Sandborn WJ

PROVIDER: S-EPMC6032827 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy.

Sandborn W J WJ Rutgeerts P P Gasink C C Jacobstein D D Zou B B Johanns J J Sands B E BE Hanauer S B SB Targan S S Ghosh S S de Villiers W J S WJS Colombel J-F JF Feagan B G BG

Alimentary pharmacology & therapeutics 20180524 1

<h4>Background</h4>In Phase 3 studies of ustekinumab, a fully human monoclonal IL-12/23p40 antibody approved for moderate-to-severe Crohn's disease, patients entered a long-term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM-UNITI maintenance are reported.<h4>Methods</h4>UNITI-1 (TNF-antagonist failures) and UNITI-2 (conventional therapy failures) patients (N = 1281) entered IM-UNITI, including 39 ...[more]

PMID: 29797519

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Project description:The biologic agent ustekinumab is a human monoclonal antibody that binds to the p40 subunit shared by interleukins (ILs) 12 and 23. The antibody is able to prevent binding of cytokines to the IL-12R?1 cell surface receptor and therefore may prevent IL-23 driven activation of the IL-23/Th 17 axis of inflammation. The anti-inflammatory activity has been beneficial in adult psoriasis. Ustekinumab has been approved in the United States for the treatment of adults with psoriasis and psoriatic arthritis. Approval in children and adolescents has not been granted by the US Food and Drug Administration. Subcutaneous injections of ustekinumab are administered at baseline, week 4 and every 12 weeks thereafter, a regimen that is particularly appealing to young patients who do not like more frequent injections at home. The product is attractive because, although it works through an immune system mechanism, the selective activity is such that the drug has not been associated with many of the side effects attributed to other immunosuppressive medications. Case reports of ustekinumab for pediatric psoriasis have shown promising results, and the recent Phase III CADMUS trial tested the agent in adolescents aged 12-17 years with psoriasis, using standard dose 0.75 mg/kg (?60 kg), 45 mg (>60-?100 kg), and 90 mg (>100 kg) or half-standard dosing 0.375 mg/kg (?60 kg), 22.5 mg (>60-?100 kg), and 45 mg (>100 kg) with a loading dosage at week 0 and week 4. Psoriasis area and severity index-75 was achieved in more than three-quarters of patients in full and half dosing by 12 weeks, and psoriasis area and severity index-90 in 54.1% and 61.1% of half and full dosage by 12 weeks, respectively. Ustekinumab was generally well tolerated in adolescents, with some patients developing antibodies, and nasopharyngitis being the major adverse event. Ustekinumab is a promising agent in adolescent psoriasis that appears to be well tolerated. The best monitoring plan and usage in younger patients still remain to be defined.

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Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy.

Publications

Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy.

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