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 350 publications

(289 citation statements)

References 59 publications

Supporting

Mentioning

266

Contrasting

Unclassified

Order By: Relevance

“…[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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…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%