Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients With Moderate to Severe Crohn’s Disease: A Phase 2a Study

Sands, Bruce E.; Chen, Jingjing; Feagan, Brian G.; Penney, Mark; Rees, William; Danese, Silvio; Higgins, Peter; Newbold, Paul; Faggioni, Raffaella; Patra, Kaushik; Li, Jing; Klekotka, Paul; Morehouse, Chris; Pulkstenis, Erik; Drappa, Jörn; Merwe, René van der; Gasser, Robert A.

doi:10.1053/j.gastro.2017.03.049

Cited by 227 publications

(166 citation statements)

References 25 publications

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“…Numerous pipeline‐specific anti‐IL‐23 agents, like brazikumab, risankizumab, mirikizumab, tildrakizumab, and guselkumab, seem to be much more promising as a new approach for the management of these situations and might surpass ustekinumab in terms of efficacy and safety profile, as side effects dependent on the Th1 pathway inhibition are notably absent . Last year, guselkumab was approved for psoriasis, and risankizumab is currently undergoing trial for its use in IBD . It is expected that more studies will follow this route, and new indications for the management of psoriasiform lesions in IBD patients with anti‐IL‐23 agents will arise in the near future.…”

Section: Discussionmentioning

confidence: 99%

Clinical management of Anti‐TNF‐alpha‐induced psoriasis or psoriasiform lesions in inflammatory bowel disease patients: a systematic review

Melo

Magina

2018

Int J Dermatology

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Tumor necrosis factor alpha inhibitors (anti-TNF-α) completely revolutionized the treatment of inflammatory bowel disease (IBD). However, anti-TNF-α-induced cutaneous side effects have been increasingly reported in the literature. Particularly, psoriasis and the recently recognized psoriasiform lesions are of particular concern, as anti-TNF-α agents are also used in the treatment of psoriasis, seemingly reflecting an immunological paradox. The clinical management of these cutaneous lesions is particularly challenging, owing to the potential need of anti-TNF-α discontinuation and scarcity of other therapeutic options. Therefore, optimization of current topical and systemic therapies and incorporation of new therapeutic agents is of great interest. Our aim is to review data in the literature regarding the clinical management of these cutaneous lesions and provide a therapeutic algorithm, supported by our experience as a tertiary referral center for IBD. Although in older reports no distinction was made, anti-TNF-α-induced psoriasiform lesions are not only more prevalent but also bear notable differences from classical psoriasis, possibly reflecting a different nosological entity. Onset of lesions has been related to periods of IBD remission, as supported by low levels of fecal calprotectin. Psoriasiform lesions can be adequately managed either by topical (glucocorticoids, calcineurin inhibitors, and antibiotics) or systemic (phototherapy, acitretin, glucocorticoids, and antibiotics) therapies and/or switch to other anti-TNF-α agents. Data referring to patients who were able to continue on the same IBD therapy ranged from 30.7 to 100%, reinforcing the importance of an adequate control of these lesions. The recently approved ustekinumab offers another step in the management of anti-TNF-α-intolerant patients.

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Section: Discussionmentioning

confidence: 99%

Clinical management of Anti‐TNF‐alpha‐induced psoriasis or psoriasiform lesions in inflammatory bowel disease patients: a systematic review

Melo

Magina

2018

Int J Dermatology

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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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“…125 In this trial, higher baseline serum concentrations of IL-22, which is induced by IL-23, were associated with greater likelihood of response to brazikumab.…”

Section: What Is On the Horizonmentioning

confidence: 68%

“…Given the potential issues with IL-12 blockade, perhaps of greater interest and potential are the new monoclonal antibodies that specifically bind the p19 subunit and are thus specific for IL-23 only. Brazikumab 125 and risankizumab 126 are such IL-23-specific antagonists that have shown efficacy in phase 2 trials in CD.…”

Section: What Is On the Horizonmentioning

confidence: 99%

The current state of the art for biological therapies and new small molecules in inflammatory bowel disease

et al. 2018

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The emergence of biologic therapies is arguably the greatest therapeutic advance in the care of inflammatory bowel disease (IBD) to date, allowing directed treatments targeted at highly specific molecules shown to play critical roles in disease pathogenesis, with advantages in potency and selectivity. Furthermore, a large number of new biologic and small-molecule therapies in IBD targeting a variety of pathways are at various stages of development that should soon lead to a dramatic expansion in our therapeutic armamentarium. Additionally, since the initial introduction of biologics, there have been substantial advances in our understanding as to how biologics work, the practical realities of their administration, and how to enhance their efficacy and safety in the clinical setting. In this review, we will summarize the current state of the art for biological therapies in IBD, both in terms of agents available and their optimal use, as well as preview future advances in biologics and highly targeted small molecules in the IBD field.

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Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients With Moderate to Severe Crohn’s Disease: A Phase 2a Study

Abstract: In a phase 2a trial of patients with moderate to severe Crohn's disease who had failed treatment with tumor necrosis factor antagonists, 8 and 24 weeks of treatment with MEDI2070 were associated with clinical improvement. ClinicalTrials.gov ID: NCT01714726.

Cited by 227 publications

References 25 publications

Clinical management of Anti‐TNF‐alpha‐induced psoriasis or psoriasiform lesions in inflammatory bowel disease patients: a systematic review

Clinical management of Anti‐TNF‐alpha‐induced psoriasis or psoriasiform lesions in inflammatory bowel disease patients: a systematic review

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

The current state of the art for biological therapies and new small molecules in inflammatory bowel disease

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