Dermatology

Campa, M. and A. Menter (2016). “A review of emerging il-17 inhibitors in the treatment of psoriasis focusing on preclinical through phase ii studies.” Expert Opin Investig Drugs 25(11): 1337-1344.

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INTRODUCTION: Interleukin-17 has recently been identified as a key player in the pathogenesis of psoriasis. As such, several drugs targeting IL-17 are in various stages of clinical development. Areas covered: In this review, the authors describe several emerging therapies and drug candidates targeting IL-17. The authors detail many biologic injectable drug candidates as well as numerous potential oral and topical small molecule drug candidates. Expert opinion: Approval of IL-17 inhibitors has significantly improved the treatment options for psoriasis patients. Secukinumab and ixekizumab are approved in both Europe and the USA, and brodalumab is likely facing approval by the end of 2016. Numerous additional biologic and small molecule drug candidates are in the pipeline, and once deemed safe and effective will likely offer significant benefit to our psoriasis population.

Gupta, A. K., J. Carviel and W. Abramovits (2016). “Treating alopecia areata: Current practices versus new directions.” Am J Clin Dermatol: 2016 Oct [Epub ahead of print].

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Alopecia areata (AA) is non-scarring hair loss resulting from an autoimmune disorder. Severity varies from patchy hair loss that often spontaneously resolves to severe and chronic cases that can progress to total loss of scalp and body hair. Many treatments are available; however, the efficacy of these treatments has not been confirmed, especially in severe cases, and relapse rates are high. First-line treatment often includes corticosteroids such as intralesional or topical steroids for mild cases and systemic steroids or topical immunotherapy with diphenylcyclopropenone or squaric acid dibutylester in severe cases. Minoxidil and bimatoprost may also be recommended, usually in combination with another treatment. Ongoing research and new insights into mechanisms have led to proposals of innovative therapies. New directions include biologics targeting immune response as well as lasers and autologous platelet-rich plasma therapy. Preliminary data are encouraging, and it is hoped this research will translate into new options for the treatment of AA in the near future.

Campa, M. and A. Menter (2016). “A review of emerging il-17 inhibitors in the treatment of psoriasis focusing on preclinical through phase ii studies.” Expert Opin Investig Drugs: 2016 Sep [Epub ahead of print].

Full text of this article.

INTRODUCTION: Interleukin-17 has recently been identified as a key player in the pathogenesis of psoriasis. As such, several drugs targeting IL-17 are in various stages of clinical development. AREAS COVERED: In this review, the authors describe several emerging therapies and drug candidates targeting IL-17. The authors detail many biologic injectable drug candidates as well as numerous potential oral and topical small molecule drug candidates. EXPERT OPINION: Approval of IL-17 inhibitors has significantly improved the treatment options for psoriasis patients. Secukinumab and ixekizumab are approved in both Europe and the USA, and brodalumab is likely facing approval by the end of 2016. Numerous additional biologic and small molecule drug candidates are in the pipeline, and once deemed safe and effective will likely offer significant benefit to our psoriasis population.

Frieder, J. and C. Ryan (2016). “Psoriasis and cardiovascular disorders.” G Ital Dermatol Venereol: 2016 Sep [Epub ahead of print].

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Psoriasis is associated with an increased risk of cardiovascular disease and related comorbidities such as diabetes mellitus, metabolic syndrome, dyslipidemia, and obesity. The precise mechanistic links underlying the association between psoriasis and cardiovascular disease remain unknown, however, multiple pathologic mechanisms have been proposed. Shared inflammatory pathways between psoriasis and atherosclerosis are likely involved. Other possible mechanisms include endothelial dysfunction, cytokine dysregulation, platelet upregulation, and dyslipidemia. Additional studies are needed to more clearly define the association between psoriasis and cardiovascular disease. Current, but limited, data suggests that psoriasis treatments targeting inflammation may be able to reduce the cardiovascular risks in this patient population. As new therapies become available, long-term prospective studies will be required to determine their potential effects on cardiovascular risk. This review summarizes the current literature on proposed pathogenic links between psoriasis and cardiovascular disease, the epidemiology of psoriasis and associated cardiovascular and cardiometabolic diseases, and the impact of anti-psoriatic treatments on cardiovascular risk profile. In addition, we provide a brief discussion of risk factor management strategies in patients with psoriasis.

Menter, A., J. C. Cather, M. Jarratt, X. Meng, A. Guana and J. Nyirady (2016). “Efficacy of secukinumab on moderate-to-severe plaque psoriasis affecting different body regions: A pooled analysis of four phase 3 studies.” Dermatol Ther (Heidelb): 2016 Aug [Epub ahead of print].

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The impact of psoriasis varies with the body region affected. In addition, patients have different perceptions of disease improvement and treatment satisfaction based on the location of skin clearance with treatment. The monoclonal antibody secukinumab selectively targets interleukin-17A-a central cytokine of psoriasis-and provides rapid and sustained clearance for moderate-to-severe psoriasis affecting all body regions. The objective of this study was to evaluate the efficacy of secukinumab on moderate-to-severe psoriasis affecting the trunk, upper limbs, and lower limbs. METHODS: Data were pooled from four phase 3 studies. To be included in the analysis for each body region, patients were required to have a Psoriasis Area and Severity Index (PASI) score >/=12 for that body region and psoriasis covering >/=10% of the surface area of that region. Secukinumab was administered at Baseline, Weeks 1, 2 and 3, and then every 4 weeks from Week 4 to 48. RESULTS: Across the trunk, upper limbs, and lower limbs, initial PASI subscore responses were sustained to Week 52. At Week 52, trunk (T) PASI 90/100 responses were achieved by 78.4%/71.1% of patients receiving secukinumab 300 mg, respectively, and by 66.3%/56.9% of patients receiving secukinumab 150 mg, respectively. At Week 52, upper limb (UL) PASI 90/100 responses were achieved by 67.3%/59.1% of patients receiving secukinumab 300 mg, respectively, and by 50.3%/43.3% of patients receiving secukinumab 150 mg, respectively. At Week 52, lower limb (LL) PASI 90/100 responses were achieved by 63.9%/55.3% of patients receiving secukinumab 300 mg, respectively, and by 45.1%/36.4% of patients receiving secukinumab 150 mg, respectively. A 50% reduction in mean PASI subscore occurred after 2.8, 2.9, and 3.4 weeks with secukinumab 300 mg on the trunk, upper limbs, and lower limbs, respectively. CONCLUSION: Secukinumab provided robust and sustained efficacy for moderate-to-severe psoriasis affecting the trunk, upper limbs, and lower limbs.