Martin A. Menter M.D.

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) 6(4): 639-647.

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INTRODUCTION: 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.

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.

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.

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].

Full text of this article.

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.

Mansouri, B., D. Kivelevitch, B. Natarajan, A. A. Joshi, C. Ryan, K. Benjegerdes, J. M. Schussler, D. J. Rader, M. P. Reilly, A. Menter and N. N. Mehta (2016). “Comparison of coronary artery calcium scores between patients with psoriasis and type 2 diabetes.” JAMA Dermatol: 2016 Aug [Epub ahead of print].

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Psoriasis is associated with an increased risk of cardiovascular diseases. Subclinical atherosclerosis in patients with psoriasis has not been compared with other conditions associated with increased cardiovascular risk and more rigorous cardiovascular disease screening, such as type 2 diabetes. Objective: To assess the burden of asymptomatic coronary atherosclerosis measured by coronary artery calcium score in patients with moderate to severe psoriasis compared with patients with type 2 diabetes and healthy controls. Design, Setting, and Participants: Three single-center, cross-sectional studies were performed in patients recruited from specialty outpatient clinics with moderate to severe psoriasis without type 2 diabetes (recruited from November 1, 2013, through April 31, 2015), patients with type 2 diabetes without psoriasis or other inflammatory diseases (recruited from July 1, 2009, through June 20, 2011), and age- and sex-matched healthy controls without psoriasis, type 2 diabetes, or other inflammatory diseases (recruited from July 1, 2009, through June 20, 2011). Exposures: Psoriasis, type 2 diabetes, and healthy control effect on coronary artery calcium score. Main Outcomes and Measures: Coronary artery calcium measured by Agatston score. Results: A total of 387 individuals participated in the study. Mean (SD) age was 51 (7.7), 52 (8.0), and 52 (8.0) years in the psoriasis, type 2 diabetes, and healthy control cohorts, respectively. There were 64 men (49.6%) in each group, and most patients were white (119 [92.2%], 123 [95.3%], and 128 [99.2%] in the psoriasis, type 2 diabetes, and healthy control cohorts, respectively). Patients with psoriasis had low cardiovascular risk measured by the Framingham Risk Score but had a high prevalence of cardiovascular and cardiometabolic risk factors, similar to patients with type 2 diabetes. In a fully adjusted model, psoriasis was associated with coronary artery calcium (Tobit regression ratio, 0.89; P < .001) similar to the association in type 2 diabetes (Tobit regression ratio, 0.79; P = .04). Likelihood ratio testing revealed incremental value for psoriasis in a fully adjusted model (chi2 = 4.48, P = .03) in predicting coronary artery calcium. Psoriasis was independently associated with the presence of any coronary artery calcium (odds ratio, 2.35; 95% CI, 1.12-4.94) in fully adjusted models, whereas the association of coronary artery calcium with type 2 diabetes was no longer significant after adding body mass index to the model (odds ratio, 2.18; 95% CI, 0.75-6.35). Conclusions and Relevance: Patients with psoriasis have increased coronary artery calcium by mean total Agatston scores, similar to that of patients with type 2 diabetes, suggesting that patients with psoriasis harbor high rates of subclinical atherosclerosis beyond adjustment for body mass index. Major educational efforts for patients and physicians should be undertaken to reduce the burden of cardiovascular disease in patients with psoriasis.