Ustekinumab for the Treatment of Refractory Crohnʼs Disease

Khorrami, Sam; Ginard, Daniel; Marín-Jiménez, Ignacio; Chaparro, María; Sierra, Mónica; Aguas, Mariam; Sicilia, Beatriz; García–Sánchez, Valle; Suárez, Cristina Justo; Villòria, Albert; Taxonera, Carlos; Velasco-Guardado, Antonio; Martínez‐González, Javier; Gisbert, Javier P.

doi:10.1097/mib.0000000000000842

Cited by 154 publications

(68 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The open-label observational experience with ustekinumab prior to regulatory approval has been described in four studies (three published manuscripts and one abstract) from tertiary IBD centers in North America and Europe 42–45. The experience from the IBD Mayo Clinic in Rochester, Minnesota (January 2008–August 2013) included 18 refractory Crohn’s disease patients who had experienced failure of at least two TNF antagonists in 89% of patients, methotrexate in 83%, and thiopurines in 89%.…”

Section: Drug Developmentmentioning

confidence: 99%

“…The open-label experience across 42 Spanish tertiary IBD centers (March 2010 to December 2014) included 116 consecutive patients with Crohn’s disease who failed at least one immunomodulator and one TNF antagonist and received treatment with ustekinumab for at least 2 months 45. Clinical response (decrease in Harvey–Bradshaw index score by ≥3 points from the baseline) after induction dosing of ustekinumab was achieved in 84% of the patients.…”

Section: Drug Developmentmentioning

confidence: 99%

See 1 more Smart Citation

Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy

Deepak¹,

Loftus²

2016

DDDT

View full text Add to dashboard Cite

Crohn’s disease is characterized by a dysregulation of both innate and adaptive immunity responses. Interleukin-12/23 (IL-12/23) pathway has been found to be a major driver of inflammation in adaptive immune responses. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23 and prevents their interaction with their cell surface receptor and further cytokine activation. It is currently approved in the management of plaque psoriasis and psoriatic arthritis. Very promising data have emerged through phase II and phase III trials (UNITI-1, UNITI-2, and IM-UNITI) for both induction and maintenance of clinical response and remission in moderate-to-severe Crohn’s disease, resulting in approval by the Food and Drug Administration for this condition. This article reviews the immunology of the IL-12/23 pathway, available data regarding the initial designing of ustekinumab, drug development through clinical trials including pharmacokinetics, efficacy, and safety, and its potential place in the treatment of Crohn’s disease.

show abstract

Section: Drug Developmentmentioning

confidence: 99%

Section: Drug Developmentmentioning

confidence: 99%

Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy

Deepak¹,

Loftus²

2016

DDDT

View full text Add to dashboard Cite

show abstract

“…With respect to the TNF failure cohort of CD patients, retrospective data of real-world experience showed an initial clinical response to vedolizumab in about 60% and remission rates at week 54 between 21 and 25% [8]. A response to ustekinumab was demonstrated in 58% of patients [9]. The relevant group of nonresponding patients necessitates therapeutic alternatives for induction of remission in severe flares of the disease.…”

Section: Introductionmentioning

confidence: 99%

Cyclophosphamide Pulse Therapy in Severe Refractory Crohn's Disease: A Retrospective Multicenter Case Series

Bär

Krause²,

Stallmach

et al. 2017

Inflamm Intest Dis

View full text Add to dashboard Cite

Background and Aims: In Crohn's disease (CD) patients still remain refractory to current regimens, including biologicals. Previous data from small single-center studies indicated cyclophosphamide pulse therapy (CPT) to be effective for induction of remission at least in steroid-refractory cases. The aim of the present study was to study the efficacy and safety of CPT in mainly tumor necrosis factor (TNF)-refractory complicated CD patients. Methods: Patients with refractory CD undergoing CPT were identified in 13 centers of the German IBD Study Group and retrospectively registered. In total, 41 patients (12 male, 29 female, median age 36 years, range 18-72 years) were included for analysis. Seventy-eight percent of these had previously been treated with thiopurines and 90% had previously received anti-TNF antibodies. Former steroid treatment was found throughout the cohort. Results: Patients received a median number of 5 (1-13) pulses every 28 (13-54) days in a period of 120 (12-411) days. A median dose of 766 (600-1,200) mg and a median cumulative dose of 4,500 (750-9,750) mg was given. A clinical response (reduction in the Harvey-Bradshaw Index [HBI] ≥2 points) was found in 68% of the patients and clinical remission (HBI <5 points) in 32%. Steroids could be reduced from 31 to 12 mg per day over all patients. Side effects were recorded in 71% (n = 29) of the patients. Three patients terminated CPT due to side effects. No patient died. Conclusion: Our data point to CPT as a therapeutic alternative for induction of remission in patients with severe refractory courses of CD including TNF antagonists. CPT might serve as bridging for maintenance treatment.

show abstract

“…While up to 43% of patients in UNITI‐1 and 30% of patients in UNITI‐2 trials had perianal disease, the efficacy of ustekinumab in patients with perianal CD was not specifically addressed . Limited real‐world data have reported favorable efficacy, with a clinical improvement rate of 61–100% . It is possible that this cohort of patients may benefit from a higher ustekinumab trough level, but more data will be required …”

Section: Ustekinumabmentioning

confidence: 99%

A review of vedolizumab and ustekinumab for the treatment of inflammatory bowel diseases

et al. 2018

View full text Add to dashboard Cite

Recent advancement in the understanding of the pathophysiology of inflammatory bowel disease has seen an expansion in therapeutic options. Vedolizumab, a selective α4β7 inhibitor, and ustekinumab, an IL 12/23 p40 inhibitor, have provided the much‐awaited out‐of‐class alternatives for patients who have failed or who are intolerant to anti‐Tumor Necrosis Factor (TNF) therapy. However, questions remain as to how we may best use these novel therapeutic agents. We evaluate the evidence available from randomized controlled trials and postmarketing cohort studies and discuss their safety, efficacy, and limitations, in relation to anti‐TNF therapy, in optimizing the treatment outcomes.

show abstract

Ustekinumab for the Treatment of Refractory Crohnʼs Disease

Abstract: Subcutaneous ustekinumab is effective and safe in a high proportion of patients with CD that were resistant to conventional immunosuppressant and antitumor necrosis factor drugs.

Cited by 154 publications

References 28 publications

Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy

Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy

Cyclophosphamide Pulse Therapy in Severe Refractory Crohn's Disease: A Retrospective Multicenter Case Series

A review of vedolizumab and ustekinumab for the treatment of inflammatory bowel diseases

Contact Info

Product

Resources

About

Ustekinumab for the Treatment of Refractory Crohnʼs Disease

Abstract: Subcutaneous ustekinumab is effective and safe in a high proportion of patients with CD that were resistant to conventional immunosuppressant and antitumor necrosis factor drugs.

Cited by 154 publications

References 28 publications

Ustekinumab in treatment of Crohn&rsquo;s disease: design, development, and potential place in therapy

Ustekinumab in treatment of Crohn&rsquo;s disease: design, development, and potential place in therapy

Cyclophosphamide Pulse Therapy in Severe Refractory Crohn's Disease: A Retrospective Multicenter Case Series

A review of vedolizumab and ustekinumab for the treatment of inflammatory bowel diseases

Contact Info

Product

Resources

About

Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy

Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy