Bimekizumab: a dual IL-17A and IL-17F inhibitor for the treatment of psoriasis and psoriatic arthritis

Ali, Zara; Matthews, R. L.; Al‐Janabi, Ali; Warren, Richard B.

doi:10.1080/1744666x.2021.1967748

Cited by 8 publications

(6 citation statements)

References 44 publications

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“…Secukinumab and ixekizumab are currently FDA-approved to treat PsA [ 38 ]. Brodalumab has completed phase III trials and bimekizumab has been studied in phase II/III trials for PsA [ 85 , 86 ].…”

Section: Resultsmentioning

confidence: 99%

The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications

Singh

Koppu

Perche

et al. 2021

IJMS

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Psoriasis is the result of uncontrolled keratinocyte proliferation, and its pathogenesis involves the dysregulation of the immune system. The interplay among cytokines released by dendritic, Th1, Th2, and Th17 cells leads to the phenotypical manifestations seen in psoriasis. Biological therapies target the cytokine-mediated pathogenesis of psoriasis and have improved patient quality of life. This review will describe the underlying molecular pathophysiology and biologics used to treat psoriasis. A review of the literature was conducted using the PubMed and Google Scholar repositories to investigate the molecular pathogenesis, clinical presentation, and current therapeutics in psoriasis. Plaque psoriasis’, the most prevalent subtype of psoriasis, pathogenesis primarily involves cytokines TNF-α, IL-17, and IL-23. Pustular psoriasis’, an uncommon variant, pathogenesis involves a mutation in IL-36RN. Currently, biological therapeutics targeted at TNF-α, IL-12/IL-23, IL-17, and IL-23/IL-39 are approved for the treatment of moderate to severe psoriasis. More studies need to be performed to elucidate the precise molecular pathology and assess efficacy between biological therapies for psoriasis. Psoriasis is a heterogenous, chronic, systemic inflammatory disease that presents in the skin with multiple types. Recognizing and understanding the underlying molecular pathways and biological therapeutics to treat psoriasis is important in treating this common disease.

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Section: Resultsmentioning

confidence: 99%

The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications

Singh

Koppu

Perche

et al. 2021

IJMS

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“…Together with recently published similar pooled safety analyses for other IL-17-targeting biologics, including secukinumab and ixekizumab ( 22 , 23 ), this integrated analysis of brodalumab clinical trials provides important context for providers considering optimal treatment for patients with psoriasis. As there are now multiple IL-17 targeting biologics – with 3 distinct mechanisms of action (MOA): anti-IL17A, anti-IL-17RA, anti-IL-17A/F ( 24 , 25 ) available for the treatment of psoriasis, it will become increasingly important for prescribers to understand specific differences in the efficacy and safety profiles within the class of IL-17-inhibiting drugs. This is particularly relevant in light of potentially class-related safety events, such as Candida infections and IBD exacerbation, which may differ between different members of this class, based on their different MOA.…”

Section: Discussionmentioning

confidence: 99%

Safety of Brodalumab in Plaque Psoriasis: Integrated Pooled Data from Five Clinical Trials

Reich

Thaçi²,

Stingl³

et al. 2022

Acta Derm Venereol

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Brodalumab is approved for treatment of moderate-to-severe plaque psoriasis. Here, we assess the safety profile of brodalumab using pooled safety data from five Phase II/III trials of brodalumab 140 mg or 210 mg. In total, 4,464 patients received brodalumab, representing 8,891.6 patient-years of exposure. During the placebo-controlled 12-week induction period, rates of serious adverse events per 100 patient-years were 10.8 and 9.6 (brodalumab 140 mg and 210 mg, respectively) versus 4.3 and 6.5 (ustekinumab and placebo, respectively); infections were the most frequent serious adverse event. Rates of serious adverse events during the comparator-controlled 52-week period were 14.4, 10.2 and 8.3 per 100 patient-years for brodalumab 210 mg, brodalumab 140 mg, and ustekinumab, respectively. Brodalumab was not associated with increased risks of malignancy, major adverse cardiac events, suicidal ideation and behaviour, or fatal events. Overall, brodalumab demonstrated an acceptable safety profile in short- and long-term treatment.

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“…Consistently, Neurath et al demonstrated that blockage both IL-17A and IL-17F relieves the colitis development, and proposed that combination of anti-IL-17A and anti-IL-17F might be developed as therapeutics for chronic colitis 42 . In Th17-cell related inflammatory diseases, including psoriasis and psoriatic arthritis (PsA), dual blocking of IL-17A and IL-17 F has been shown to be more effective than IL-17 A blockade alone 43 . In support, our findings demonstrated that blocking of both IL-17A and IL-17F had the most prominent effect on alleviation of colitis development, even though interfering either one also showed beneficial outcome.…”

Section: Discussionmentioning

confidence: 99%

Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis

et al. 2023

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T helper 17 (Th17) cells are a subset of CD4+ T helper cells involved in the inflammatory response in autoimmunity. Th17 cells secrete Th17 specific cytokines, such as IL-17A and IL17-F, which are governed by the master transcription factor RoRγt. However, the epigenetic mechanism regulating Th17 cell function is still not fully understood. Here, we reveal that deletion of RNA 5-methylcytosine (m5C) methyltransferase Nsun2 in mouse CD4+ T cells specifically inhibits Th17 cell differentiation and alleviates Th17 cell-induced colitis pathogenesis. Mechanistically, RoRγt can recruit Nsun2 to chromatin regions of their targets, including Il17a and Il17f, leading to the transcription-coupled m5C formation and consequently enhanced mRNA stability. Our study demonstrates a m5C mediated cell intrinsic function in Th17 cells and suggests Nsun2 as a potential therapeutic target for autoimmune disease.

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Bimekizumab: a dual IL-17A and IL-17F inhibitor for the treatment of psoriasis and psoriatic arthritis

Cited by 8 publications

References 44 publications

The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications

The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications

Safety of Brodalumab in Plaque Psoriasis: Integrated Pooled Data from Five Clinical Trials

Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis

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