Dermatology

Wu, J. J., J. F. Merola, S. R. Feldman, A. Menter and M. Lebwohl (2020). “Treatment of Psoriasis with Secukinumab in Challenging Patient Scenarios: A Review of the Available Evidence.” Dermatol Ther (Heidelb) Apr 2. [Epub ahead of print].

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Psoriasis (PsO) is a common, systemic, chronic, inflammatory disease characterized by key clinical symptoms, including itching, pain, and scaling. PsO is associated with a high prevalence of comorbidities, including other autoimmune diseases and malignancies. Furthermore, special populations, such as pregnant, pediatric, and elderly patients, and those with erythrodermic PsO, are challenging to treat and require tightly monitored disease and treatment management. Because certain populations have demographic or clinical characteristics that can affect the presentation of PsO and complicate treatment responses, these patient populations are largely excluded from clinical trials; therefore, most clinical evidence for the treatment of these patients is derived from case reports and series. Secukinumab, a fully human monoclonal interleukin-17A antibody, has been shown in several clinical trials to be effective and safe for the treatment of PsO; however, these studies offer only limited data on the use of secukinumab in patients with chronic illnesses or in special populations. This review explores the use of secukinumab for PsO in special populations, including pregnant women, children, elderly people, patients with erythrodermic PsO, and those with chronic illnesses, including latent tuberculosis, hepatitis B and C, HIV, multiple sclerosis, and malignancies.

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The authors would like to correct the error in Table 1.

Raoof, T. J., D. Hooper, A. Moore, M. Zaiac, T. Sullivan, L. Kircik, E. Lain, J. Jankicevic and I. Stuart (2020). “Efficacy and safety of a novel topical minocycline foam for the treatment of moderate to severe acne vulgaris: A phase 3 study.” J Am Acad Dermatol 82(4): 832-837.

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BACKGROUND: FMX101 4% topical minocycline foam has been shown to be an effective and safe treatment for acne vulgaris (AV). OBJECTIVE: To further evaluate the efficacy and safety of FMX101 4% in treating moderate to severe acne vulgaris. METHODS: A 12-week, multicenter, randomized (1:1), double-blind, vehicle-controlled study was conducted. Coprimary end points were the absolute change in inflammatory lesion count from baseline and the rate of treatment success (Investigator’s Global Assessment score of 0 or 1 with a >/=2-grade improvement). RESULTS: There were 1488 participants in the intent-to-treat population. The FMX101 4% group had significantly greater reductions in the number of inflammatory lesions from baseline (P < .0001) and a greater rate of treatment success based on Investigator's Global Assessment (P < .0001) versus the foam vehicle group at week 12. FMX101 4% was generally safe and well tolerated. LIMITATIONS: The efficacy and safety of FMX101 4% were not characterized in participants with mild AV. CONCLUSION: FMX101 4% topical minocycline.

Philipp, S., A. Menter, A. F. Nikkels, K. Barber, I. Landells, L. F. Eichenfield, M. Song, B. Randazzo, S. Li, M. C. Hsu, Y. Zhu, S. DePrimo and A. S. Paller (2020). “Ustekinumab for the treatment of moderate-to-severe plaque psoriasis in pediatric patients (>/=6 to <12 years of age): efficacy, safety, pharmacokinetic, and biomarker results from the open-label CADMUS Jr study." Br J Dermatol Mar 16. [Epub ahead of print].

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BACKGROUND: Limited options are available for treatment of pediatric psoriasis. OBJECTIVES: To evaluate the efficacy and safety of ustekinumab in pediatric psoriasis patients (>/=6 to <12 years of age). METHODS: CADMUS Junior (Jr), a phase 3, open-label, single-arm, multicenter study, evaluated ustekinumab in pediatric patients with moderate-to-severe plaque psoriasis. Patients received weight-based dosing of ustekinumab (<60kg: 0.75mg/kg; >/=60to100kg: 90mg) administered by subcutaneous injection at weeks 0/4, then every-12-weeks through week 40. Study endpoints (all at week 12) included the proportions of patients achieving a Physician’s Global Assessment score of cleared/minimal (PGA 0/1) and >/=75%/90% improvement in Psoriasis Area and Severity Index (PASI 75/90) and change in Children’s Dermatology Life Quality Index (CDLQI). Serum ustekinumab concentrations, anti-drug antibodies (ADA), and cytokine levels were measured through week 52. Safety was evaluated through week 56. RESULTS: A total of 44 patients (median age, 9.5 years) received at least one dose of ustekinumab. Three patients discontinued study agent through week 40. At week 12, 77.3% of patients achieved PGA 0/1, 84.1% achieved PASI 75, and 63.6% achieved PASI 90 response; mean change in CDLQI was -6.3. Trough serum ustekinumab concentrations reached steady state at weeks 28-52. The incidence of ADA was 9.5% (n=4). Mean serum concentrations of IL-17A/F and IL-22 were significantly reduced at weeks 12/52. Overall, 34 patients (77.3%) had at least one adverse event and 3 (6.8%) had a serious adverse event. CONCLUSIONS: Ustekinumab effectively treated moderate-to-severe psoriasis in pediatric patients, and no new safety concerns were identified.

Menter, A., J. M. Gelfand, C. Connor, A. W. Armstrong, K. M. Cordoro, D. M. R. Davis, B. E. Elewski, K. B. Gordon, A. B. Gottlieb, D. H. Kaplan, A. Kavanaugh, M. Kiselica, D. Kivelevitch, N. J. Korman, D. Kroshinsky, M. Lebwohl, C. L. Leonardi, J. Lichten, H. W. Lim, N. N. Mehta, A. S. Paller, S. L. Parra, A. L. Pathy, E. F. Prater, R. S. Rahimi, R. N. Rupani, M. Siegel, B. Stoff, B. E. Strober, E. B. Tapper, E. B. Wong, J. J. Wu, V. Hariharan and C. A. Elmets (2020). “Joint Aad-Npf Guidelines Of Care For The Management Of Psoriasis With Systemic Non-Biological Therapies.” J Am Acad Dermatol Feb 21. [Epub ahead of print].

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Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world’s population. In this guideline, we focus the discussion on systemic, non-biologic medications for the treatment of this disease. We provide a detailed discussion of efficacy and safety for the most commonly used medications-including methotrexate, cyclosporine, and acitretin-and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch upon a number of other medications, including fumaric acid esters (used outside the US) and therapies that are no longer widely used for the treatment of psoriasis, i.e. hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus.

Gelfand, J. M., D. B. Shin, K. C. Duffin, A. W. Armstrong, A. Blauvelt, S. K. Tyring, A. Menter, S. Gottlieb, B. N. Lockshin, E. L. Simpson, F. Kianifard, R. P. Sarkar, E. Muscianisi, J. Steadman, M. A. Ahlman, M. P. Playford, A. A. Joshi, A. K. Dey, T. J. Werner, A. Alavi and N. N. Mehta (2020). “A Randomized Placebo Controlled Trial of Secukinumab on Aortic Vascular Inflammation in Moderate to Severe Plaque Psoriasis (VIP-S).” J Invest Dermatol Feb 20. [Epub ahead of print].

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BACKGROUND: Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has demonstrated high efficacy with a favorable safety profile in various psoriatic disease manifestations. TRIAL DESIGN AND METHODS: Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, moderate-to-severe psoriasis patients received secukinumab for 40 weeks. Vascular inflammation using FDG-PET/CT imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. RESULTS: The difference in change in aortic inflammation from baseline to Week 12 for secukinumab (N=46) versus placebo (N=45) was -0.053 (95% CI: -0.169, 0.064; P=0.37). Small increases in total cholesterol, LDL, and LDL particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At Week 52, reductions in TNF-alpha (P=0.0063) and ferritin (P=0.0354), and an increase in fetuin A (P=0.0024), were observed with secukinumab treatment compared to baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared to baseline. CONCLUSION: Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment.