Dermatology

Frieder, J., D. Kivelevitch, I. Haugh, I. Watson and A. Menter (2017). “Anti-il-23 and anti-il-17 biologic agents for the treatment of immune-mediated inflammatory conditions.” Clin Pharmacol Ther: 2017 Sep [Epub ahead of print].

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Advancements in the immunopathogenesis of psoriasis have identified interleukin (IL)-23 and IL-17 as fundamental contributors in the immune pathways of the disease. Leveraging these promising therapeutic targets has led to the emergence of a number of anti-IL-23 and -17 biologic agents with the potential to treat multiple conditions with common underlying pathology. The unprecedented clinical efficacy of these agents in the treatment of psoriasis has paved way for their evaluation in diseases such as psoriatic arthritis, Crohn’s disease, rheumatoid arthritis, in addition to other immune-mediated conditions. Here, we will review the IL-23/IL-17 immune pathways and discuss the key clinical and safety data of the anti-IL-23 and anti-IL-17 biologic agents in psoriasis and other immune-mediated diseases.

Bagel, J., K. C. Duffin, A. Moore, L. K. Ferris, K. Siu, J. Steadman, F. Kianifard, J. Nyirady and M. Lebwohl (2017). “The effect of secukinumab on moderate-to-severe scalp psoriasis: Results of a 24-week, randomized, double-blind, placebo-controlled phase 3b study.” J Am Acad Dermatol 77(4): 667-674.

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BACKGROUND: Moderate-to-severe scalp psoriasis has not been evaluated in prospective trials of patients without moderate-to-severe body psoriasis. OBJECTIVE: Evaluate the efficacy and safety of secukinumab in moderate-to-severe scalp psoriasis. METHODS: In this 24-week, double-blind, phase 3b study, 102 patients were randomized 1:1 to subcutaneous secukinumab 300 mg or placebo at baseline, weeks 1, 2, and 3, and then every 4 weeks from week 4 to 20. The primary efficacy variable was 90% improvement of Psoriasis Scalp Severity Index (PSSI 90) score from baseline to week 12. RESULTS: At week 12, PSSI 90 (secukinumab 300 mg vs placebo, 52.9% vs 2.0%) and Investigator’s Global Assessment modified 2011 scalp responses of 0 or 1 (secukinumab 300 mg vs placebo, 56.9% vs 5.9%) were significantly greater with secukinumab 300 mg than placebo (P < .001 for both). In addition, significantly more patients achieved complete clearance of scalp psoriasis at week 12 with secukinumab 300 mg than placebo (35.3% vs 0%; P < .001). The median time to 50% reduction in PSSI score was 3.29 weeks with secukinumab 300 mg. The safety profile of secukinumab was consistent with previous phase 3 studies. LIMITATIONS: There was no active comparator arm. CONCLUSION: Secukinumab is efficacious and well-tolerated for patients with extensive moderate-to-severe scalp psoriasis.

Menter, A., D. Thaci, J. J. Wu, W. Abramovits, F. Kerdel, D. Arikan, D. Guo, A. Ganguli, M. Bereswill, A. Camez and W. C. Valdecantos (2017). “Long-term safety and effectiveness of adalimumab for moderate to severe psoriasis: Results from 7-year interim analysis of the esprit registry.” Dermatol Ther (Heidelb): 2017 Aug [Epub ahead of print].

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INTRODUCTION: ESPRIT (NCT00799877) is an ongoing 10-year international prospective observational registry evaluating the long-term safety and effectiveness of originator adalimumab in routine clinical practice for adult patients with chronic plaque psoriasis. Herein, we report the long-term safety, effectiveness, and patient-reported outcomes (PROs) following adalimumab treatment over the first 7 years of the ESPRIT registry. METHODS: All treatment-emergent (All-TE) adverse events (AE) since the initial (first ever) dose of adalimumab were assessed. Physician Global Assessment (PGA) and PROs (PROs for US patients only) were evaluated during registry participation. RESULTS: As of 30 November 2015, 6051 patients in the ESPRIT registry were analyzed, representing 23,660.1 patient-years (PY) of overall adalimumab exposure. The incidence rates for All-TE serious AEs, serious infections, and malignancies were 4.4, 1.0, and 1.0 events per 100 PY (E/100PY), respectively. The standardized mortality ratio for TE deaths in the registry was 0.27 (95% CI 0.18-0.38). During the registry’s first 7 years, PGA “clear” or “minimal” was achieved by >50% of patients at each annual visit, and among US patients, the mean improvement from baseline in different PROs was maintained. CONCLUSION: No new safety signals were identified during the first 7 years of the registry, and safety was consistent with the known safety profile of adalimumab. The number of TE deaths was below the expected rate. During the registry’s first 7 years, most of the patients remained free of All-TE cardiovascular events, serious infections, and malignancy. As-observed effectiveness of adalimumab and improvements from baseline in PROs were maintained through 7 years of registry participation.

Kivelevitch, D., J. M. Schussler and A. Menter (2017). “Coronary plaque characterization in psoriasis.” Circulation 136(3): 277-280.

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Psoriasis is strongly associated with multiple comorbidities, including obesity, tobacco smoking, diabetes mellitus, dyslipidemia, hypertension, and psychiatric, autoimmune, renal, and cardiovascular diseases, among others.5 Multiple publications have confirmed the association between psoriasis and vascular disease.5–8 Patients with psoriasis, especially those <50 years old and with more severe disease, are at higher risk of developing coronary artery disease (CAD).9 Furthermore, patients with moderate to severe psoriasis have a reduced life expectancy of ≈4 to 5 years relating to cardiovascular disease (CVD). Traditional risk assessment tools such as the Framingham risk score do not appropriately estimate this CAD risk. Recent studies that used both noninvasive and invasive coronary artery studies of patients with psoriasis and have shown a higher prevalence of CAD in patients with psoriasis compared with healthy individuals.10–13 Our recent coronary artery calcium score study of 129 patients with psoriasis with moderate to severe disease revealed a risk similar to that of patients with type II diabetes mellitus and significantly higher than that of healthy patients.10 One of the major areas of research and interest in the therapy of moderate to severe psoriasis is the potential benefit of systemic therapies such as methotrexate and biological therapies, especially tumor necrosis factor-α antagonist agents, on CAD.14

Bagel, J., K. C. Duffin, A. Moore, L. K. Ferris, K. Siu, J. Steadman, F. Kianifard, J. Nyirady and M. Lebwohl (2017). “The effect of secukinumab on moderate-to-severe scalp psoriasis: Results of a 24-week, randomized, double-blind, placebo-controlled phase 3b study.” J Am Acad Dermatol: 2017 Aug [Epub ahead of print].

Full text of this article.

BACKGROUND: Moderate-to-severe scalp psoriasis has not been evaluated in prospective trials of patients without moderate-to-severe body psoriasis. OBJECTIVE: Evaluate the efficacy and safety of secukinumab in moderate-to-severe scalp psoriasis. METHODS: In this 24-week, double-blind, phase 3b study, 102 patients were randomized 1:1 to subcutaneous secukinumab 300 mg or placebo at baseline, weeks 1, 2, and 3, and then every 4 weeks from week 4 to 20. The primary efficacy variable was 90% improvement of Psoriasis Scalp Severity Index (PSSI 90) score from baseline to week 12. RESULTS: At week 12, PSSI 90 (secukinumab 300 mg vs placebo, 52.9% vs 2.0%) and Investigator’s Global Assessment modified 2011 scalp responses of 0 or 1 (secukinumab 300 mg vs placebo, 56.9% vs 5.9%) were significantly greater with secukinumab 300 mg than placebo (P < .001 for both). In addition, significantly more patients achieved complete clearance of scalp psoriasis at week 12 with secukinumab 300 mg than placebo (35.3% vs 0%; P < .001). The median time to 50% reduction in PSSI score was 3.29 weeks with secukinumab 300 mg. The safety profile of secukinumab was consistent with previous phase 3 studies. LIMITATIONS: There was no active comparator arm. CONCLUSION: Secukinumab is efficacious and well-tolerated for patients with extensive moderate-to-severe scalp psoriasis.