Dermatology

Moore, A. Y., J. E. M. Charles and S. Moore (2019). “Sarecycline: a narrow spectrum tetracycline for the treatment of moderate-to-severe acne vulgaris.” Future Microbiol Sep 2. [Epub ahead of print].

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Sarecycline is a novel, narrow-spectrum, once-daily tetracycline-derived oral antibiotic that is FDA-approved in the US to be taken with or without food for moderate-to-severe acne vulgaris for ages 9 years of age and older. Sarecycline possesses anti-inflammatory properties and potent activity against Gram-positive bacteria, including activity against multiple strains of Cutibacterium acnes, while exhibiting minimal activity against enteric aerobic Gram-negative bacteria. Unlike many acne studies, sarecycline was investigated for chest and back acne. Significant reduction in inflammatory lesions was seen at week 12 at 1.5 mg/kg/day of sarecycline, with statistically significant improvement seen as early as week 3. No reports of phototoxicity, dizziness, pseudotumor cerebri or lupus but 1.2% nausea and 1.2% vaginal candidiasis was reported in the pivotal Phase III studies.

Elmets, C. A., H. W. Lim, B. Stoff, C. Connor, K. M. Cordoro, M. Lebwohl, A. W. Armstrong, D. M. R. Davis, B. E. Elewski, J. M. Gelfand, K. B. Gordon, A. B. Gottlieb, D. H. Kaplan, A. Kavanaugh, M. Kiselica, D. Kivelevitch, N. J. Korman, D. Kroshinsky, C. L. Leonardi, J. Lichten, N. N. Mehta, A. S. Paller, S. L. Parra, A. L. Pathy, E. A. Farley Prater, R. N. Rupani, M. Siegel, B. E. Strober, E. B. Wong, J. J. Wu, V. Hariharan and A. Menter (2019). “Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis with phototherapy.” J Am Acad Dermatol 81(3): 775-804.

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Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world’s population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light-based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments.

Bissonnette, R., P. Fernandez-Penas, L. Puig, A. M. Mendelsohn, S. J. Rozzo and A. Menter (2019). “Incidence of cardiovascular events among tildrakizumab-treated patients with moderate-to-severe plaque psoriasis: pooled data from three large randomised clinical trials.” J Eur Acad Dermatol Venereol Aug 12. [Epub ahead of print].

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Psoriasis is an independent risk factor for incidence of major adverse cardiovascular (CV) events (MACE), a composite endpoint including myocardial infarction, stroke and death. While many biologics, including tumour necrosis factor inhibitors, interleukin (IL)‐17 inhibitors, and IL‐12/23 inhibitors are approved for the treatment of psoriasis, evidence is limited on the impact of biologics on CV outcomes in patients with psoriasis. In a phase 2b (P05495, NCT01225731) and 2 phase 3 (reSURFACE 1, NCT01722331; and reSURFACE 2, NCT01729754) trials conducted in patients with moderate‐to‐severe chronic plaque psoriasis, tildrakizumab—a high‐affinity, humanised, immunoglobulin G1κ, anti–IL‐23p19 antibody—was well tolerated, with low frequencies of serious adverse events and discontinuations due to adverse events. Here, we evaluated incidence of CV events using pooled safety data obtained from the full trial periods and year 1 of the phase 3 extension studies. (Excerpt from text of authors’ commentary on the article, Papp K, Thaci D, Reich K et al. Tildrakizumab (MK‐3222), an anti‐interleukin‐23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo‐controlled trial. Br J Dermatol 2015; 173: 930– 939, and related studies.)

Elewski, B., A. Menter, J. Crowley, S. Tyring, Y. Zhao, S. Lowry, S. Rozzo, A. M. Mendelsohn, J. Parno and K. Gordon (2019). “Sustained and continuously improved efficacy of tildrakizumab in patients with moderate-to-severe plaque psoriasis.” J Dermatolog Treat Jul 22. [Epub ahead of print].

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Background: Tildrakizumab is a high-affinity, humanized, IgG1 kappa, anti-interleukin-23 monoclonal antibody approved for moderate-to-severe plaque psoriasis. Objectives: This analysis examined whether tildrakizumab’s week-28 efficacy can be sustained or improved to week 52. Methods: Psoriasis patients on the same-dose tildrakizumab (100 or 200 mg) in the first 52 weeks achieving week-28 PASI >/=50 were pooled from two phase-3 randomized controlled trials, and grouped into four mutually exclusive week-28 PASI response groups. Patients’ week-52 PASI responses were compared to their week-28 PASI responses. Results: Of 352 patients receiving 100-mg tildrakizumab, 10.5%, 25.3%, 38.4%, and 25.9% achieved PASI 50-74, 75-89, 90-99, and 100 at week 28, respectively. Among patients achieving PASI >/=90, >/=75, or >/=50 at week 28, 89.4%, 91.1%, or 97.4% maintained their week-28 PASI responses at week 52, respectively. Among patients achieving PASI 50-74, 75-89, or 90-99 at week 28, 64.8%, 33.7%, or 25.2% improved their week-28 PASI responses at week 52, respectively. Limitations: This post hoc analysis may be less robust than an a priori analysis. Conclusions: Most tildrakizumab-treated patients with week-28 PASI >/=75 maintained their week-28 PASI improvement at week 52. More than half of week-28 partial responders (PASI 50-74) improved their PASI responses to PASI >/=75 at week 52. Clinicaltrials.gov identifiers: NCT01722331, NCT01729754.

Reich, K., P. Rich, C. Maari, R. Bissonnette, C. Leonardi, A. Menter, A. Igarashi, P. Klekotka, D. Patel, J. Li, J. Tuttle, M. Morgan-Cox, E. Edson-Heredia, S. Friedrich and K. Papp (2019). “Efficacy and safety of mirikizumab (LY3074828) in the treatment of moderate-to-severe plaque psoriasis: results from a randomized phase II study.” Br J Dermatol 181(1): 88-95.

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BACKGROUND: Inhibiting interleukin (IL)-23 in patients with psoriasis has demonstrated high levels of skin clearance. OBJECTIVES: To investigate, in a phase II (AMAF; NCT02899988), multicentre, double-blind trial, the efficacy and safety of three doses of mirikizumab (LY3074828), a p19-directed IL-23 antibody, vs. placebo in patients with moderate-to-severe plaque psoriasis. METHODS: Adult patients were randomized 1 : 1 : 1 : 1 to receive placebo (n = 52), mirikizumab 30 mg (n = 51), mirikizumab 100 mg (n = 51) or mirikizumab 300 mg (n = 51) subcutaneously at weeks 0 and 8. The primary objective was to evaluate the superiority of mirikizumab over placebo in achieving a 90% improvement in the Psoriasis Area and Severity Index (PASI 90) response at week 16. Comparisons were done using logistic regression analysis with treatment, geographical region and previous biological therapy in the model. Missing data were imputed as nonresponses. RESULTS: Ninety-seven per cent of patients completed the first 16 weeks of the study. The primary end point was met for all mirikizumab dose groups vs. placebo, with PASI 90 response rates at week 16 of 0%, 29% (P = 0.009), 59% (P < 0.001) and 67% (P < 0.001) for patients receiving placebo, and mirikizumab 30 mg, 100 mg and 300 mg, respectively. There were two (1%) serious adverse events in mirikizumab-treated patients vs. one (2%) in a placebo-group patient. CONCLUSIONS: At week 16, 67% of patients treated with mirikizumab 300 mg at 8-week intervals achieved PASI 90. The percentage of patients reporting at least one treatment-emergent adverse event was similar among patients treated with placebo or mirikizumab.