Background Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis. Objectives ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate‐to‐severe plaque psoriasis. Methods This phase III, double‐blind, placebo‐controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in Psoriasis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast. Results The modified intention‐to‐treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (28·8%), PASI 50 (55·5%) and static Physician's Global Assessment score of 0 or 1 (20·4%) vs. placebo (5·8%, 19·7%, 4·4%, respectively; P < 0·001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed significant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo (P < 0·001). The exposure‐adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection. Conclusions Apremilast was effective in the treatment of moderate‐to‐severe plaque psoriasis over 52 weeks.

Despite unmet need, 15 years have passed since a topical therapy with a new mechanism of action for atopic dermatitis (AD) has been approved. Janus kinase (JAK) inhibitor treatment effect via topical application in patients with AD is unknown. Tofacitinib, a small-molecule JAK inhibitor, was investigated for the topical treatment of AD. In this 4-week, phase IIa, randomized, double-blind, vehicle-controlled study (NCT02001181), 69 adults with mild-to-moderate AD were randomized 1:1 to 2% tofacitinib or vehicle ointment twice daily. Percentage change from baseline (CFB) in Eczema Area and Severity Index (EASI) score at week 4 was the primary end point. Secondary efficacy end points included percentage CFB in body surface area (BSA), CFB in EASI Clinical Signs Severity Sum Score, proportion of patients with Physician's Global Assessment (PGA) response and CFB in patient-reported pruritus. Safety, local tolerability and pharmacokinetics were monitored. The mean percentage CFB at week 4 in EASI score was significantly greater (P < 0·001) for tofacitinib (-81·7%) vs. vehicle (-29·9%). Patients treated with tofacitinib showed significant (P < 0·001) improvements vs. vehicle across all prespecified efficacy end points and for pruritus at week 4. Significant improvements in EASI, PGA and BSA were observed by week 1 and improvements in pruritus were observed by day 2. Safety/local tolerability were generally similar for both treatments, although more adverse events were observed for vehicle vs. tofacitinib. Tofacitinib ointment showed significantly greater efficacy vs. vehicle across end points, with early onset of effect and comparable safety/local tolerability to vehicle. JAK inhibition through topical delivery is potentially a promising therapeutic target for AD.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by intense pruritus and eczematous lesions.¹ The burden associated with the disease is substantial, encompassing physical, psychological, social, and economic costs.² Although emollients and topical anti-inflammatory agents are the cornerstone of AD treatment, they are often insufficient for individuals with moderate to severe disease.^3,4 Phototherapy and systemic corticosteroids are treatment options, but the former is limited by accessibility, and the latter is not recommended because of safety concerns.⁵ Systemic immunosuppressants may be prescribed but are off-label in many countries and are associated with considerable adverse effects that limit treatment duration.^3,5 Dupilumab was recently approved in several countries for treatment of moderate to severe AD.^6,7 Although this is an important addition to the treatment landscape, some patients do not respond adequately, and others are unwilling or unable to receive subcutaneous injections. Consequently, there remains a need for alternative therapies for AD.

Background: Drug survival is a marker for treatment sustainability in chronic diseases such as psoriasis.Objective: The aim of these analyses was to assess survival of biologic treatments in the PSOriasis Longitudinal Assessment and Registry (PSOLAR).Methods: PSOLAR is a large, prospective, international, disease‐based registry of patients with psoriasis receiving (or eligible for) systemic therapy in a real‐world setting. Drug survival is defined as the time from initiation to discontinuation (stop/switch) of biologic therapy on registry. The number of patients who discontinued each treatment and the duration of therapy were recorded. Using Kaplan–Meier survival curves and Cox‐regression analyses [hazard ratios (HR) and 95% confidence intervals (CIs)], time to discontinuation was compared across cohorts undergoing first‐, second‐ or third‐line treatment with ustekinumab, infliximab, adalimumab or etanercept.Results: As of the 2013 data cut, 12 095 patients with psoriasis were enrolled in PSOLAR. Of the 4000 patients initiating any new biologic therapy, approximately 3500 started a first‐line, second‐line or third‐line biologic therapy during the registry. Lack of effectiveness was the most common reason for discontinuation across biologic therapies. Based on the multivariate analysis, significantly shorter times to discontinuation were observed for infliximab [HR (95%CI) = 2.73 (1.48–5.04), P = 0.0014]; adalimumab [4.16 (2.80–6.20), P < 0.0001]; and etanercept [4.91 (3.28–7.35) P < 0.0001] compared with ustekinumab [reference treatment]) for first‐line biologic use; results were similar for treatment effects for second/third‐line therapies. Although limited in power, analyses in patients with concurrent psoriatic arthritis confirmed by a rheumatologist reflect observations in the overall psoriasis population.Conclusion: Drug survival was superior for ustekinumab compared with infliximab, adalimumab and etanercept in patients with psoriasis.

Introduction: Generalized pustular psoriasis (GPP) is a rare, severe relapsing/remitting, multisystem disease that can be difficult to treat. Recent clinical, histological, and genetic evidence suggests that GPP is a distinct clinical entity from plaque psoriasis and requires a separate diagnosis. The interleukin-36 pathway appears to be central to GPP pathogenesis. As no therapeutic agents have been approved for GPP to date in the United States or Europe, the introduction of anti-IL-36 therapies may change disease management. Areas covered: Using PubMed and Google Scholar, we reviewed the literature for articles related to GPP, psoriasis, and the genetics, pathogenesis, and treatment thereof. Expert opinion: New therapeutic options and updated guidelines for GPP treatment are needed. Ideal agents would have rapid onset of action and rapid time to achieve disease clearance, have the ability to prevent acute flares and avert recurrence, and possess a favorable safety profile. Such therapies should be readily accessible via approval or listing on formularies. Scoring systems to establish GPP disease burden and objective outcome measures could also help with further evaluation of therapies and treatment access issues. IL-36 remains a promising target, as supported by early phase data suggesting efficacy and safety for a novel anti-IL-36 therapy.