A phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of atopic dermatitis

Peppers, Johnny; Paller, Amy S.; Maeda-Chubachi, Tomoko; Wu, Sterling; Robbins, K. Thomas; Gallagher, Kelly; Kraus, John E.

doi:10.1016/j.jaad.2018.06.047

Cited by 127 publications

(109 citation statements)

References 16 publications

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“…The anti-inflammatory effects of coal tar extracts, which have been used topically for AD for decades, may also result from activation of AhR/nuclear factor, erythroid 2 like 2 [61]. A double-blind, vehicle-controlled, randomized trial was performed in patients aged 12-65 years, with body surface area involvement of at least 5%-35% and an IGA score of 3 or 4 at baseline [33]. Primary end points included an IGA score of clear or almost clear and a minimum 2-grade improvement (treatment success) at week 12.…”

Section: Tapinarof: Ahr Modulatormentioning

confidence: 99%

Novel topical and systemic therapies in atopic dermatitis

Suga

Sato

2019

Immunological Medicine

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Atopic dermatitis (AD) is the most common inflammatory skin disease driven by both terminal keratinocyte differentiation defects and type 2 immune responses, and this condition causes psychological and social morbidity. Although patients with severe AD require systemic immunotherapy, conventional agents including ciclosporin could not be used for several years due to side effects such as nephrotoxicity, hypertension and long-term risks of malignancy. It is well known that dupilumab, which blocks receptor binding of both IL-4 and IL-13, is remarkably efficacious in the treatment of AD. We have entered a new era when many novel topical and systemic agents that may have great potential in AD treatment are emerging through clinical trials. The purpose of this article is to summarize the efficacy and safety of the current topical and systemic therapies in AD by reviewing recently published papers regarding phase II/III clinical trials. It is revealed that topical phosphodiesterase 4 inhibitors and Janus kinase (JAK) inhibitors are promising treatments for AD. Moreover, systemic therapies such as biologics targeting IL-13 and oral JAK inhibitors show strong efficacy in AD.

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Section: Tapinarof: Ahr Modulatormentioning

confidence: 99%

Novel topical and systemic therapies in atopic dermatitis

Suga

Sato

2019

Immunological Medicine

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“…In a recent phase 2 randomized study of 2 concentrations and 2 frequencies of tapinarof cream vs vehicle in 247 randomized patients aged 12 to 65 years with moderate to severe disease, tapinarof demonstrated greater success with both concentrations than vehicle at all visits beyond week 2. 25 Additionally, in patients treated with tapinarof cream 1%, nearly 50% reached an IGA score of clear to almost clear with at least a 2-grade improvement. More than 50% of patients achieved EASI-75 improvement at 12 weeks of treatment with tapinarof cream 1% used daily.…”

Section: Evolving Topical Therapiesmentioning

confidence: 95%

Update on Pediatric Atopic Dermatitis

Tracy¹,

Bhatti²,

Eichenfield³

2020

Cutis

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WWW.MDEDGE.COM/DERMATOLOGY CLINICAL REVIEW Recent studies have led to new insights into atopic dermatitis (AD) pathogenesis and epidemiology as well as its impact on the quality of life of affected children and adolescents. In addition, there are several novel topical and systemic agents recently approved and in late-stage clinical development programs. Epidemiologic insights include relative prevalence rates in different countries and studies of subsets of pediatric patients with different disease longevity and persistence. Studies on quality of life have shown tremendous impact on sleep, not only in affected individuals but in their parents/guardians. The impact of bathing regimens is discussed. Newer topical therapies are reviewed, including topical crisaborole, with a new indication for infants as young as 3 months of age. Topical Janus kinase (JAK) inhibitors are being developed, with some studies including adolescents and children. Other novel therapies include the topical aryl hydrocarbon receptor agonist tapinarof and oral JAK inhibitors; adolescents are being included in the initial clinical trials for several of these therapies. Dupilumab, the first biologic agent approved for AD, has now been well studied in patients aged 6 years and older, with expanded indication down to 6 years of age.

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“…IPS is also a natural agonist of the aryl hydrocarbon receptor (AhR) and has been shown to resolve skin inflammation in mice and humans [97]. Under the trade name Tapinarof, IPS has recently successfully completed phase 2 clinical trials for the treatment of psoriasis and atopic dermatitis [98,99].…”

Section: Ij Recovery and Inter-kingdom Signallingmentioning

confidence: 99%

Photorhabdus: a tale of contrasting interactions

Clarke

2020

Microbiology

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Different model systems have, over the years, contributed to our current understanding of the molecular mechanisms underpinning the various types of interaction between bacteria and their animal hosts. The genus Photorhabdus comprises Gram-negative insect pathogenic bacteria that are normally found as symbionts that colonize the gut of the infective juvenile stage of soil-dwelling nematodes from the family Heterorhabditis. The nematodes infect susceptible insects and release the bacteria into the insect haemolymph where the bacteria grow, resulting in the death of the insect. At this stage the nematodes feed on the bacterial biomass and, following several rounds of reproduction, the nematodes develop into infective juveniles that leave the insect cadaver in search of new hosts. Therefore Photorhabdus has three distinct and obligate roles to play during this life-cycle: (1) Photorhabdus must kill the insect host; (2) Photorhabdus must be capable of supporting nematode growth and development; and (3) Photorhabdus must be able to colonize the gut of the next generation of infective juveniles before they leave the insect cadaver. In this review I will discuss how genetic analysis has identified key genes involved in mediating, and regulating, the interaction between Photorhabdus and each of its invertebrate hosts. These studies have resulted in the characterization of several new families of toxins and a novel inter-kingdom signalling molecule and have also uncovered an important role for phase variation in the regulation of these different roles.

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A phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of atopic dermatitis

Cited by 127 publications

References 16 publications

Novel topical and systemic therapies in atopic dermatitis

Novel topical and systemic therapies in atopic dermatitis

Update on Pediatric Atopic Dermatitis

Photorhabdus: a tale of contrasting interactions

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