BackgroundApremilast, an oral, small‐molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate‐to‐severe psoriasis.ObjectiveEvaluate efficacy and safety of apremilast vs. placebo in biologic‐naive patients with moderate‐to‐severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb, randomized, double‐blind, placebo‐controlled study (NCT01690299).MethodsTwo hundred and fifty patients were randomized to placebo (n = 84), apremilast 30 mg BID (n = 83) or etanercept 50 mg QW (n = 83) through Week 16; thereafter, all patients continued or switched to apremilast through Week 104. The primary efficacy endpoint was achievement of PASI‐75 at Week 16 with apremilast vs. placebo. Secondary endpoints included achievement of PASI‐75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16. Outcomes were assessed through Week 52. This study was not designed for apremilast vs. etanercept comparisons.ResultsAt Week 16, PASI‐75 achievement was greater with apremilast (39.8%) vs. placebo (11.9%; P < 0.0001); 48.2% of patients achieved PASI‐75 with etanercept (P < 0.0001 vs. placebo). PASI‐75 response was maintained in 47.3% (apremilast/apremilast), 49.4% (etanercept/apremilast) and 47.9% (placebo/apremilast) of patients at Week 52. Most common adverse events (≥5%) with apremilast, including nausea, diarrhoea, upper respiratory tract infection, nasopharyngitis, tension headache and headache, were mild or moderate in severity; diarrhoea and nausea generally resolved in the first month. No new safety or tolerability issues were observed through Week 52 with apremilast.ConclusionApremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic‐naive patients with psoriasis, which was sustained over 52 weeks, and demonstrated safety consistent with the known safety profile of apremilast. Switching from etanercept to apremilast did not result in any new or clinically significant safety findings, and efficacy was maintained with apremilast through Week 52.

No abstract

The role of vitamin D in psoriasis is complex and extensive. Oral and topical vitamin D therapies provide comparable efficacies to corticosteroids when used as monotherapy and may be superior when used in combination with a potent topical steroid. Additionally topical vitamin D analogs demonstrate a favorable safety profile with "steroid-sparing" effects. Thus, topical vitamin D derivatives should be considered an indispensable component of the current physician's arsenal in the treatment of psoriasis.

Background: Tapinarof is a topical therapeutic aryl hydrocarbon receptor modulating agent under investigation for atopic dermatitis (AD) and psoriasis treatment.Methods: A phase 2b, double-blind, vehicle-controlled study randomly assigned adolescents and adults with AD to receive tapinarof cream 0.5%, 1%, or vehicle, once or twice daily, for 12 weeks with a 4-week follow-up. Outcomes included Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI), body surface area affected, pruritus numeric rating scale scores, patients' impressions of AD and pruritus symptom severity, and Patient-Oriented Eczema Measure (POEM) scores.Results: Overall, 191 of 247 randomized patients completed the study. Week 12 IGA responses were higher in the tapinarof groups versus the vehicle group, reaching statistical significance with tapinarof 1% twice daily, $75%/90% improvement in EASI from baseline were significantly higher in the tapinarof groups (except 0.5% once daily and 0.5% twice daily), EASI scores were significantly improved in all tapinarof groups, and body surface area affected was significantly reduced in the tapinarof groups (except 0.5% twice daily). More patients reported AD and pruritus symptom severity as very/moderately improved in tapinarof groups, and POEM improvements were observed in all groups. Most adverse events were mild or moderate.Limitations: Larger prospective studies are required to confirm the reported analyses.

Targeted inhibition of Rho-associated kinase (ROCK)2 downregulates the proinflammatory T cell response while increasing the regulatory arm of the immune response in animals models of autoimmunity and Th17-skewing human cell culture in vitro. In this study, we report that oral administration of a selective ROCK2 inhibitor, KD025, reduces psoriasis area and severity index scores by 50% from baseline in 46% of patients with psoriasis vulgaris, and it decreases epidermal thickness as well as T cell infiltration in the skin. We observed significant reductions of IL-17 and IL-23, but not IL-6 and TNF-α, whereas IL-10 levels were increased in peripheral blood of clinical responders after 12 wk of treatment with KD025. Collectively, these data demonstrate that an orally available selective ROCK2 inhibitor downregulates the Th17-driven autoimmune response and improved clinical symptoms in psoriatic patients via a defined molecular mechanism that involves concurrent modulation of cytokines without deleterious impact on the rest of the immune system.