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

Deepak, Parakkal; Loftus, Edward V.

doi:10.2147/dddt.s102141

Cited by 41 publications

(29 citation statements)

References 79 publications

(93 reference statements)

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“…The pathogenesis and inflammation of CD are thought to be induced by interleukin‐12/23 receptor‐mediated stimulation of Th‐1 and Th‐17 cytokine pathways . UST is known to inhibit activation of Th‐1 cells and further activation of Th‐17 by preventing binding of IL‐12 and IL‐23 with IL‐12 receptor β1 . In clinical settings, UST is expected to induce sustained clinical remission in patients with moderate to severe active CD .…”

Section: Discussionmentioning

confidence: 99%

Combination Therapy With Intensive Granulocyte and Monocyte Adsorptive Apheresis Plus Ustekinumab in Patients With Refractory Crohn's Disease

et al. 2018

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Ustekinumab is applied to induce clinical remission in patients with Crohn's disease. Granulocyte and monocyte absorptive apheresis depletes activated myeloid lineage leukocytes and has been applied for active Crohn's disease. This study retrospectively examined the efficacy and safety of combining intensive granulocyte and monocyte absorptive apheresis and ustekinumab for remission induction therapy in refractory Crohn's disease. Between June and September 2017, three consecutive cases (two females) with refractory Crohn's disease were treated with intensive granulocyte and monocyte absorptive apheresis plus ustekinumab. Crohn's disease activity index, and simple endoscopic score for Crohn's disease at baseline and 10 weeks were applied as treatment efficacy outcomes. In all three cases, at week 10, clinical remission was achieved, while simple endoscopic score for Crohn's disease reflected no improvement. Thus, combination therapy with intensive granulocyte and monocyte absorptive apheresis plus ustekinumab appeared to represent a safe and effective intervention for inducing clinical remission.

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Section: Discussionmentioning

confidence: 99%

Combination Therapy With Intensive Granulocyte and Monocyte Adsorptive Apheresis Plus Ustekinumab in Patients With Refractory Crohn's Disease

et al. 2018

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“…Nevertheless, most clinical trials did not find an unexpected increase in cancer rates across approved indications. 49,50 In the palliative and refractory irAE setting, ustekinumab treatment may be a conceivable option in selected cases.…”

Section: Anti-il-23/12 Therapymentioning

confidence: 99%

New therapeutic perspectives to manage refractory immune checkpoint-related toxicities

Martins

Sykiotis

Maillard

et al. 2019

The Lancet Oncology

160

153

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Immune-checkpoint inhibitors (ICIs) are reshaping the prognosis of many cancer types and are progressively becoming a standard of care for many of them. Cancer immunotherapy has started a revolution in the oncology therapeutic landscape, bringing new hope to patients but also a whole new spectrum of toxicities for practitioners to manage. Oncologists and specialists involved in the pluridisciplinary management of immune-related adverse events (irAEs) are increasingly confronted with the therapeutic challenge of severe and/or refractory cases. In this personal view, we summarize the therapeutic strategies reported to manage them. Based on current knowledge of irAE pathogenesis and our immunological expertise, we also transpose the use of new biologic and non-biologic immunosuppressive agents, used to treat primary autoimmune disorders (AIDs), in the context of severe and/or steroid refractory irAE management. Depending on the immune-type predominant infiltrate, we propose a personalized treatment algorithm beyond corticosteroids. A shut-off strategy, intended to treat severe or steroid-refractory irAEs, based on the efficient inhibition of key inflammatory components involved in their pathophysiological processes, and limit potential adverse effects of drug immunosuppression on tumor response is proposed. This approach goes beyond current guidelines, challenging the step-by-step increase in drug immunosuppression proposed so far.

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“…Mixed results have also been reported in other inflammatory diseases. Ustekinumab, risankizumab and MEDI2070 (anti‐p19 monoclonal antibody) have demonstrated effectiveness for the treatment of Crohn's disease . Ustekinumab was not effective in treating symptoms of multiple sclerosis, although it was well tolerated …”

Section: Evidence For Role Of Il‐23 In Other Disease Statesmentioning

confidence: 99%

Shifting the focus – the primary role of IL‐23 in psoriasis and other inflammatory disorders

Gooderham

Papp

Lynde

2018

Acad Dermatol Venereol

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Insights into the pathophysiology of autoimmune inflammatory diseases including psoriasis have advanced considerably in recent years, and in parallel, so too have the available treatment options. Current clinical paradigms for the treatment of psoriasis have evolved to include targeted biologic therapies, starting with tumour necrosis factor‐alpha (TNF‐α) inhibitors and later, agents targeting interleukin (IL)‐12/23 and IL‐17. The most recent evidence suggests that IL‐23 might be an even more potent target for the effective treatment of psoriasis and other autoimmune inflammatory disorders. This review will describe recent developments leading to the current understanding of the key role of IL‐23 as a ‘master regulator’ of autoimmune inflammation and the clinical evidence for agents that specifically target this modulator in the context of treating psoriasis, spondyloarthropathy and inflammatory bowel disease.

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

Cited by 41 publications

References 79 publications

Combination Therapy With Intensive Granulocyte and Monocyte Adsorptive Apheresis Plus Ustekinumab in Patients With Refractory Crohn's Disease

Combination Therapy With Intensive Granulocyte and Monocyte Adsorptive Apheresis Plus Ustekinumab in Patients With Refractory Crohn's Disease

New therapeutic perspectives to manage refractory immune checkpoint-related toxicities

Shifting the focus – the primary role of IL‐23 in psoriasis and other inflammatory disorders

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