Subcutaneous Ustekinumab Provides Clinical Benefit for Two-Thirds of Patients With Crohn’s Disease Refractory to Anti–Tumor Necrosis Factor Agents

Wils, Pauline; Bouhnik, Yoram; Michetti, Pierre; Flourié, Bernard; Brixi, Hédia; Bourrier, Anne; Allez, Matthieu; Duclos, Bernard; Grimaud, Jean–Charles; Buisson, Anthony; Amiot, Aurélien; Fuméry, Mathurin; Roblin, Xavier; Peyrin–Biroulet, Laurent; Filippi, Jérôme; Bouguen, Guillaume; Abitbol, Véred; Coffin, Benoït; Simon, M.; Laharie, David; Pariente, Benjamin

doi:10.1016/j.cgh.2015.09.018

Cited by 160 publications

(161 citation statements)

References 25 publications

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“…In addition, the initial response to ustekinumab and the use of two or more immunosuppressants were found to predict a good response, while previous bowel resection predicted long-term failure with ustekinumab [69]. Another observational study demonstrated that almost two-thirds of patients with CD refractory to at least one anti-TNF agent receiving ustekinumab were able to be free from steroids for up to 12 months [71].…”

Section: Interleukin Inhibitor Ustekinumabmentioning

confidence: 98%

Emerging biologics in inflammatory bowel disease

Chan

2016

J Gastroenterol

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Early biologic therapy is recommended in patients with inflammatory bowel disease and poor prognostic factors and in those refractory to conventional medications. Anti-tumor necrosis factor (anti-TNF) agents are the most commonly used biologic agents. However, some patients may not have an initial response to anti-TNF therapy, and one-third will develop loss of response over time. Anti-TNF drugs can also be associated with side effects. In addition, the use of biologics is currently limited by their cost, especially in developing countries. A number of new therapeutic targets, including novel small molecules, and cellular therapy are available or under investigation. These novel molecules include oral Janus kinase (JAK) inhibitor (tofacitinib), interleukin inhibitor (ustekinumab), oral SMAD7 antisense oligonucleotide (mongersen), and anti-integrin inhibitors (vedolizumab). Here, we review the mechanisms of action, the efficacy, and the safety data of these novel agents. Biological products that are highly similar to reference biologic products whose patents have expired-also known as ''biosimilars''-can be produced at lower cost with similar efficacy, and are also available for the treatment of IBD. We review the efficacy data for such agents as well.

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Section: Interleukin Inhibitor Ustekinumabmentioning

confidence: 98%

Emerging biologics in inflammatory bowel disease

Chan

2016

J Gastroenterol

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“…Forty-three patients had a clear non-response at 3 months. Out of the 79 patients with a clinical benefit at 3 months, the majority had luminal CD [66] . Only a minority had perianal disease.…”

Section: Anti Il-23 Strategies In Ibdmentioning

confidence: 99%

“…Remission at week 6, however, showed no significant difference between the treatment groups and placebo. As Ustekinumab has been approved as Stelara ® for the treatment for psoriasis, there was a small GETAID study published by Wils et al [66] from Lille about the efficacy and safety of subcutaneous Ustekinumab in refractory CD patients. This was a multicenter retrospective study on off-label use of Ustekinumab in patients with desperate situations [66] .…”

Section: Anti Il-23 Strategies In Ibdmentioning

confidence: 99%

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Anti-Cytokine Strategies beyond Anti-Tumour Necrosis Factor-α Therapy: Pathophysiology and Clinical Implications

Rogler

Biedermann

Scharl

2017

Dig Dis

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Cytokines are small proteins produced by a broad range of cells important in cell signaling. They include interleukins, but also chemokines, interferons, and tumor necrosis factors (TNF). They play an important role for communication between cells of the innate and adaptive immune system. The cytokine network is complex and, therefore, therapeutic interventions are difficult. The first anti-cytokine strategy successfully introduced into IBD therapy was the neutralization of TNF by antibodies. Beyond targeting this cytokine anti-IL-23 strategies were demonstrated to be of therapeutic benefit in IBD. Anti-IL-6 strategies seem to have clinical potential but also cause some risk for the patient due to the lack of CRP increase upon severe inflammation. JAK inhibitors target the intracellular signaling of several cytokine receptors and represent a promising class of broader and somewhat unspecific anti-cytokine strategies. Many other anti-cytokine approaches have failed due to the redundant nature of the cytokine network. Whether further anti-cytokines strategies have potential for IBD treatment may be evaluated in future studies.

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“…Therapy with Infliximab (IFX), Adalimumab (ADA) or Certolizumab Pegol (CZP), are antibodies against TNF-α, have demonstrated that it is effective in terms of induction and maintained responses [11][12][13]. Unfortunately, approximately 20-40% of CD patients do not respond to anti-TNF-α therapy and 40% of patients who initially respond lose response [14]. Those who do not respond to the first anti-TNF-α have lower response rates to the second or third with this kind of therapy.…”

Section: Introductionmentioning

confidence: 99%

Crohn’s Disease Biologic Therapies Advances: A current review

Serra¹,

Teixeira²,

Balteiro³

et al. 2017

Biomed Res Rev

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Crohn's Disease (CD) is an intestinal chronic inflammatory disease included in the group of inflammatory bowel disease. It is associated with an inflammatory process and may affect any part of the gastrointestinal tract. The pathogenesis of CD has become better understood owing to advances in genetic and immunologic technology. Studies suggest that the origin of the inflammation may be due to an exacerbated response of the immune system. The elevated production of inflammatory cytokines, such as tumor necrosis factor-alpha, in CD patients were described. The new therapeutic with biological agents were developed for CD patients who not respond to conventional therapy. These novel biologics has been shown frequently to decrease the inflammatory activity in the gut, with the goal to achieve remission with mucosal healing. The Infliximab therapy is one of more used in these patients. However, there are many patients who do not respond or lose response. Who do not respond to these therapeutics have other biologic therapeutics such as Certolizumab Pegol, Natalizumab, Vedolizumab, Ustekinumab and Secukinumab. It is necessary to analyse the effectiveness and safety of these treatments to see which is most effective.

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Subcutaneous Ustekinumab Provides Clinical Benefit for Two-Thirds of Patients With Crohn’s Disease Refractory to Anti–Tumor Necrosis Factor Agents

Abstract: Almost two-thirds of patients with CD refractory to at least 1 anti-TNF agent receive clinical benefit from ustekinumab therapy, not requiring steroids for up to 12 months afterward. While awaiting results from ongoing trials, ustekinumab can be considered for use in these patients.

Cited by 160 publications

References 25 publications

Emerging biologics in inflammatory bowel disease

Emerging biologics in inflammatory bowel disease

Anti-Cytokine Strategies beyond Anti-Tumour Necrosis Factor-α Therapy: Pathophysiology and Clinical Implications

Crohn’s Disease Biologic Therapies Advances: A current review

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