Ustekinumab in Crohn’s disease: evidence to date and place in therapy

Engel, Tal; Kopylov, Uri

doi:10.1177/2040622316653306

Cited by 25 publications

(17 citation statements)

References 44 publications

(77 reference statements)

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“…Ustekinumab is the most recently approved drug for the treatment of Crohn's disease (CD). 1,2 Interleukin (IL) 12 and IL23, increased in CD, are heterodimers composed of a unique subunit bound to a shared subunit, P40. 3,4 Ustekinumab is a fully human monoclonal immunoglobulin G 1 kappa (IgG1k) antibody that acts against the P40 subunit, thus inhibiting their binding to the receptors on CD4+ T lymphocytes, natural killer (NK) cells, and antigen-presenting cells (APC).…”

Section: Introductionmentioning

confidence: 99%

Real‐world long‐term effectiveness of ustekinumab in Crohn's disease: results from the ENEIDA registry

Iborra¹,

Beltrán²,

Fernández-Clotet³

et al. 2020

Aliment Pharmacol Ther

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Summary Background Data on the long‐term administration of ustekinumab in recommended doses are limited. Aim To assess the real‐world, long‐term effectiveness of ustekinumab in refractory Crohn's disease (CD). Methods Multi‐centre study of CD patients starting ustekinumab at the recommended dose, followed for 1 year. Values for the Harvey‐Bradshaw Index (HBI), endoscopic activity, C‐reactive protein (CRP), and faecal calprotectin (FC) were recorded at baseline and at weeks 26 and 52. Demographic and clinical data, previous treatments, adverse events (AEs) and hospitalisations were documented. Potential predictors of remission were examined. Results A total of 407 patients were analysed. The initial maintenance dose of 90 mg SC was administered every 12, 8 and 4 weeks in 56 (14%), 347 (85%) and 4 (1%) patients, respectively. After 52 weeks, treatment was discontinued in 112 patients (27.5%). At baseline, 295 (72%) had an HBI >4 points. Of these, 169 (57%) and 190 (64%) achieved clinical remission at weeks 26 and 52, respectively. FC levels returned to normal in 44% and 54% of patients at weeks 26 and 52, and CRP returned to normal in 36% and 37% of patients at weeks 26 and 52, respectively. AEs were recorded in 60 patients. The use of fewer previous anti‐TNFα agents and ileal localisation were associated with clinical remission, and endoscopic severity was associated with poor response. No factors correlated with endoscopic remission. Conclusion After 52 weeks, ustekinumab demonstrated effectiveness in inducing clinical and endoscopic remission in patients with refractory CD.

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Section: Introductionmentioning

confidence: 99%

Real‐world long‐term effectiveness of ustekinumab in Crohn's disease: results from the ENEIDA registry

Iborra¹,

Beltrán²,

Fernández-Clotet³

et al. 2020

Aliment Pharmacol Ther

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“…243 244 Safety data from the Crohn's disease clinical trials and the psoriasis literature are also promising, suggesting that ustekinumab may have a place as a first line therapy for Crohn's disease alongside anti-TNF agents. 245 However, it is still early days, and much has to be learnt about the real world application of ustekinumab with regard to optimal dosing, treatment of specific phenotypes (eg, patients with perianal disease), and long term safety before it can be routinely recommended ahead of anti-TNF therapy.…”

Section: Malignancy and Infectionmentioning

confidence: 99%

Update on anti-tumor necrosis factor agents and other new drugs for inflammatory bowel disease

Cohen

Sachar

2017

BMJ

113

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The treatment of inflammatory bowel disease (IBD)-ulcerative colitis (UC) and Crohn's disease (CD)-has evolved beyond surgery with the introduction of biologic agents, primarily antibodies against mediators of inflammation and cell attraction. Anti-tumor necrosis factor (TNF) agents have been the first line treatment for moderate to severe ulcerative colitis and Crohn's disease for more than 15 years. During that time much has been learnt about how best to use these agents. This review will assess the evidence on how to optimize the use of anti-TNF agents; when and how to start treatment; how to monitor treatment and when to de-escalate it; and the potential adverse effects of these drugs. New and emerging treatments such as anti-attractants, anti-interleukins, and Janus kinase (JAK) inhibitors will also be discussed.

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“…The pro-inflammatory cytokine IL-12 family, which includes IL-22, IL-23, IL-25 and IL-27, is responsible for the differentiation of T helper (Th) cells into Th1 cells and has been recently linked to the pathophysiology of CD as well as other immune-mediated disorders [ 40 ]. IL-12 and IL-23 are heterodimeric proteins composed of a unique subunit linked to a shared p40 subunit and studies have shown that patients with CD have an elevation of these subunits [ 41 , 42 ].…”

Section: Targeting the Adaptive Immune Systemmentioning

confidence: 99%

The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease

Holleran

Lopetuso

Petito

et al. 2017

IJMS

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Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date.

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Ustekinumab in Crohn’s disease: evidence to date and place in therapy

Cited by 25 publications

References 44 publications

Real‐world long‐term effectiveness of ustekinumab in Crohn's disease: results from the ENEIDA registry

Real‐world long‐term effectiveness of ustekinumab in Crohn's disease: results from the ENEIDA registry

Update on anti-tumor necrosis factor agents and other new drugs for inflammatory bowel disease

The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease

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