Pathophysiology of psoriasis: Recent advances on IL-23 and Th17 cytokines

Fitch, Erin; Harper, Erin; Skorcheva, Iliyana; Kurtz, Stephen E.; Blauvelt, Andrew

doi:10.1007/s11926-007-0075-1

Cited by 338 publications

(283 citation statements)

References 59 publications

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“…[6][7][8] The interleukin (IL)-17 cytokine family plays an important role in psoriasis pathogenesis. 9,10 IL-23 induces expansion of T helper 17 cells and innate immune cells, which in turn produce IL-17A, IL-17C and IL-17F; these cytokines are elevated in psoriatic skin lesions. [11][12][13][14] Brodalumab, a fully human anti-IL-17 receptor A (IL-17RA) monoclonal antibody that blocks IL-17-mediated signalling, has demonstrated efficacy in the treatment of moderate-to-severe plaque psoriasis in a phase II clinical trial.…”

Section: Discussionmentioning

confidence: 99%

A prospective phase III, randomized, double‐blind, placebo‐controlled study of brodalumab in patients with moderate‐to‐severe plaque psoriasis

et al. 2016

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SummaryBackground The interleukin-17 cytokine family plays a central role in psoriasis pathogenesis. Objectives To evaluate the efficacy and safety of brodalumab, a human anti-interleukin-17 receptor antibody, in treating patients with moderate-to-severe plaque psoriasis. Methods In this phase III, double-blind, placebo-controlled study (NCT01708590; AMAGINE-1), adult patients in the U.S.A., Canada and Europe were randomized to brodalumab (140 or 210 mg) or placebo every 2 weeks (Q2W), with an additional dose at week 1, for a 12-week induction phase. At week 12, patients receiving brodalumab who achieved static Physician's Global Assessment 0 or 1 (sPGA success) were rerandomized to the placebo or induction dose. After week 16, patients with sPGA ≥ 3 were re-treated with the induction dose. After ≥ 12 weeks of retreatment, patients with sPGA 2 for ≥ 4 weeks or sPGA ≥ 3 were rescued with brodalumab 210 mg Q2W. At week 12, patients randomized to brodalumab with sPGA ≥ 2 or placebo received brodalumab 210 mg Q2W. Coprimary end points were the percentage of patients with ≥ 75% improvement in Psoriasis Area and Severity Index score (PASI 75) and sPGA success at week 12. Results There were 661 patients randomized: 220 placebo, 219 brodalumab 140 mg and 222 brodalumab 210 mg. At week 12, 60% (140 mg) and 83% (210 mg) vs. 3% (placebo) achieved PASI 75, and 54% (140 mg) and 76% (210 mg) vs. 1% (placebo) achieved sPGA success. The safety profile was considered acceptable. Conclusions Brodalumab therapy resulted in significant clinical benefit and an acceptable safety profile in patients with moderate-to-severe plaque psoriasis.

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Section: Discussionmentioning

confidence: 99%

A prospective phase III, randomized, double‐blind, placebo‐controlled study of brodalumab in patients with moderate‐to‐severe plaque psoriasis

et al. 2016

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“…Recent studies suggest that IL-23 has a critical role in the pathogenesis of psoriasis by inducing pathological T helper type 17 (Th17) cells that release IL-17 and IL-22 (Kikly et al, 2006;Fitch et al, 2007;Chiricozzi et al, 2014). However, it is not fully understood how the IL-23 pathway in psoriasis is regulated.…”

Section: Introductionmentioning

confidence: 99%

Circadian gene clock regulates psoriasis-like skin inflammation in mice

Ando

Nakamura

Aoki

et al. 2016

Journal of Dermatological Science

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There are several reports suggesting that the pathophysiology of psoriasis may be associated with aberrant circadian rhythms. However, the mechanistic link between psoriasis and the circadian time-keeping system, "the circadian clock," remains unclear. This study determined whether the core circadian gene, Clock, had a regulatory role in the development of psoriasis. For this purpose, we compared the development of psoriasis-like skin inflammation induced by the Toll-like receptor 7 ligand imiquimod (IMQ) between wild-type mice and mice with a loss-of-function mutation of Clock. We also compared the development of IMQ-induced dermatitis between wild-type mice and mice with a loss-of-function mutation of Period2 (Per2), another key circadian gene that inhibits CLOCK activity. We found that Clock mutation ameliorated IMQ-induced dermatitis, whereas the Per2 mutation exaggerated IMQ-induced dermatitis, when compared with wild-type mice associated with decreased or increased IL-23 receptor (IL-23R) expression in γ/δ + T cells, respectively. In addition, CLOCK directly bound to the promoter of IL-23R in γ/δ + T cells, and IL-23R expression in the mouse skin was under circadian control. These findings suggest that Clock is a novel regulator of psoriasis-like skin inflammation in mice via direct modulation of IL-23R expression in γ/δ + T cells, establishing a mechanistic link between psoriasis and the circadian clock.

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“…1 IL-17A blocking antibodies, such as secukinumab, are used to treat psoriasis 2 . However, only one case of a resulting mild clinical adverse cutaneous event has been reported.…”

Section: Recurrent Angular Cheilitis After Secukinumab Injectionsmentioning

confidence: 99%

“…In MNH, tumour cells are not naturally connected to the epidermis. 1,2 Thus, it is difficult to distinguish MNH de novo from cutaneous metastatic neoplasms. 2 Cutaneous metastasis from lung cancer is rare.…”

Section: Correspondence Lettermentioning

confidence: 99%