Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of psoriasis in a randomized placebo-controlled phase IIa study

Ludbrook, Valerie J.; Hicks, Kirsty; Hanrott, Kate; Patel, Jatin; Binks, Michael; Wyres, Melody; Watson, Joanna; Wilson, Phebe; Simeoni, Monica; Schifano, Lorrie; Reich, Kristian; Griffiths, C.E.M.

doi:10.1111/bjd.14399

Cited by 71 publications

(70 citation statements)

References 22 publications

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“…There were no incidences of anaemia or thrombocytopenia during this study and the incidence of infections was low. Changes in lipid parameters were observed in this study, as has been reported in some studies with other JAK inhibitors . The most dramatic effects on HDL and LDL cholesterol were observed in subjects receiving PF‐04965842 BID.…”

Section: Discussionsupporting

confidence: 87%

Evaluation of a Janus kinase 1 inhibitor, PF‐04965842, in healthy subjects: A phase 1, randomized, placebo‐controlled, dose‐escalation study

Peeva

Hodge

Kieras

et al. 2018

Brit J Clinical Pharma

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Section: Discussionsupporting

confidence: 87%

Evaluation of a Janus kinase 1 inhibitor, PF‐04965842, in healthy subjects: A phase 1, randomized, placebo‐controlled, dose‐escalation study

Peeva

Hodge

Kieras

et al. 2018

Brit J Clinical Pharma

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“…Such clinical data may form an important foundation to support the evidence‐based care of psoriasis patients with itch symptoms. The following discussion reviews the itch effect of topical agents, systemics and biologics, and phototherapy, as revealed in recent studies (Table ) . Itch relief remains a significant gap in the treatment landscape for psoriasis, as not all patients are able to achieve control of this symptom, even with cleared or markedly improved skin.…”

Section: Management Of Itch In Psoriasismentioning

confidence: 99%

Itch: an under‐recognized problem in psoriasis

Elewski

Alexis

Lebwohl

et al. 2019

Acad Dermatol Venereol

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Psoriasis has historically been considered a nonpruritic dermatosis, in contrast with atopic dermatitis. Thus, itch has often been underappreciated and overlooked in psoriasis. However, increasing evidence over the past decade has shown that itch can be one of the most prevalent and burdensome symptoms associated with psoriasis, affecting almost every patient to some degree. Itch can involve the entire body, although it predominantly affects the legs, hands, back, body and especially the scalp. Uncontrolled itch can significantly impact all aspects of the well‐being and quality of life of the patient. While there has been some progress in trying to better understand the pathophysiology of itch in psoriasis, more research effort and interest are needed. This under‐recognition of itch in psoriasis is clearly reflected in the dearth of treatment options targeting itch despite significant advancement in treating the lesions themselves. Recently, however, clinical studies have begun to include itch as a study outcome. The resulting data have demonstrated concomitant antipruritic benefits and improved Psoriasis Area and Severity Index (PASI) scores with mainstay treatments for psoriasis, such as topical corticosteroids and vitamin D analogs, phototherapies, and various systemics and biologics. This article takes a closer look at this debilitating symptom, reviewing the available epidemiology data for psoriatic itch, presenting the current understanding of psoriatic itch pathophysiology and highlighting important clinical data for various treatment options for itch. Practical considerations for increasing the recognition of itch as well as improving its management in psoriasis are also provided.

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“…A new generation of JAK inhibitors, including both pan-JAK inhibitors (JAK1, JAK2, JAK3, and TYK2) and selective JAK inhibitors (i.e. JAK1 only or JAK3 only), are being developed 2,71–78 . The advent of JAK inhibitors in dermatology has been met with significant excitement.…”

Section: Discussionmentioning

confidence: 99%

JAK inhibitors in dermatology: The promise of a new drug class

Damsky

King

2017

Journal of the American Academy of Dermatology

382

286

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New molecularly targeted therapeutics are changing dermatologic therapy. JAK-STAT is an intracellular signaling pathway upon which many different pro-inflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators which rely on JAK-STAT signaling, and inhibition of this pathway using JAK inhibitors may be a useful therapeutic strategy for these diseases. There is growing evidence that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition may be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.

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Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of psoriasis in a randomized placebo-controlled phase IIa study

Abstract: Our study demonstrates that 12 weeks of treatment with GSK2586184 resulted in clinical improvement and was generally well tolerated in patients with moderate-to-severe plaque-type psoriasis.

Cited by 71 publications

References 22 publications

Evaluation of a Janus kinase 1 inhibitor, PF‐04965842, in healthy subjects: A phase 1, randomized, placebo‐controlled, dose‐escalation study

Evaluation of a Janus kinase 1 inhibitor, PF‐04965842, in healthy subjects: A phase 1, randomized, placebo‐controlled, dose‐escalation study

Itch: an under‐recognized problem in psoriasis

JAK inhibitors in dermatology: The promise of a new drug class

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