Dermatology

Ryan, C., A. Menter, L. Guenther, A. Blauvelt, R. Bissonnette, K. Meeuwis, J. Sullivan, J. C. Cather, G. Yosipovitch, A. B. Gottlieb, J. F. Merola, K. Callis Duffin, S. Fretzin, O. O. Osuntokun, R. Burge, A. N. Naegeli, F. E. Yang, C. Y. Lin, K. Todd and A. Potts Bleakman (2018). “Efficacy and Safety of Ixekizumab in a Randomized, Double-Blinded, Placebo-Controlled Phase 3b Study of Patients with Moderate-to-Severe Genital Psoriasis.” Br J Dermatol. May 10. [Epub ahead of print].

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BACKGROUND: Genital psoriasis (GenPs) is a common, debilitating, and difficult to treat manifestation of plaque psoriasis. However, few controlled, interventional studies of GenPs exist. OBJECTIVE: To determine the efficacy of ixekizumab versus placebo in patients with moderate-to-severe GenPs with BSA>/=1%. METHODS: Subjects with moderate-to-severe GenPs (defined as a baseline static Physician’s Global Assessment of Genitalia [sPGA-G] score of >/=3) with BSA>/=1% were randomized 1:1 to receive placebo (N=74) or the recommended dosing of ixekizumab (N=75). Major outcomes included the percentage of patients achieving 0 or 1 scores on the sPGA-G (primary endpoint), overall sPGA, GenPs Sexual Frequency Questionnaire (GenPs-SFQ) item 2, and a >/=3-point improvement from baseline on the GenPs itch numeric rating scale. RESULTS: At week 12, ixekizumab was superior to placebo on the sPGA-G 0/1 (73.3% versus 8.1%, p<0.001), overall sPGA 0/1 (73.3% versus 2.7%, p<0.001), GenPs-SFQ item 2 0/1 (78.4% versus 21.4%, p<0.001), and genital itch (59.7% versus 8.3%, p<0.001). No candidiasis was reported, no deaths occurred, and one (1.4%) serious adverse event was reported in a patient receiving placebo. CONCLUSIONS: Ixekizumab was superior to placebo for the treatment of moderate-to-severe GenPs with BSA>/=1%. The safety profile of ixekizumab was consistent with previous studies in moderate-to-severe plaque psoriasis.

Mehta, N. N., D. B. Shin, A. A. Joshi, A. K. Dey, A. W. Armstrong, K. C. Duffin, Z. C. Fuxench, C. L. Harrington, R. A. Hubbard, R. E. Kalb, A. Menter, D. J. Rader, M. P. Reilly, E. L. Simpson, J. Takeshita, D. A. Torigian, T. J. Werner, A. B. Troxel, S. K. Tyring, S. B. Vanderbeek, A. S. Van Voorhees, M. P. Playford, M. A. Ahlman, A. Alavi and J. M. Gelfand (2018). “Effect of 2 Psoriasis Treatments on Vascular Inflammation and Novel Inflammatory Cardiovascular Biomarkers: A Randomized Placebo-Controlled Trial.” Circ Cardiovasc Imaging 11(6): e007394.

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BACKGROUND: Psoriasis is a chronic inflammatory disease associated with dyslipidemia, cardiovascular events, and mortality. We aimed to assess and compare the effect of treatment of moderate-to-severe psoriasis with adalimumab or phototherapy on vascular inflammation and cardiovascular biomarkers. METHODS AND RESULTS: Randomized, double-blind, trial of adalimumab, phototherapy, and placebo (1:1:1) for 12 weeks, with crossover to adalimumab for 52 weeks total. Outcomes included vascular inflammation by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography and biomarkers of inflammation, insulin resistance, and lipoproteins. Ninety-seven patients were randomized, 92 completed the randomized controlled trial portion; 81 entered the adalimumab extension with 61 completing 52 weeks of adalimumab. There was no difference in change in vascular inflammation at week 12 in the adalimumab group (change compared with placebo, 0.64%; 95% confidence interval, -5.84% to 7.12%) or the phototherapy group (-1.60%; 95% confidence interval, -6.78% to 3.59%) or after 52-week adalimumab treatment (0.02% compared with initiation; 95% confidence interval, -2.85% to 2.90%). Both adalimumab and phototherapy decreased inflammation by serum CRP, interleukin-6. Only adalimumab reduced tumor necrosis factor and glycoprotein acetylation at 12 and 52 weeks. Neither had an impact on metabolic markers (insulin, adiponectin, and leptin). Only phototherapy increased high-density lipoprotein-p at 12 weeks. At 52-week of adalimumab cholesterol efflux and high-density lipoprotein-p were reduced. CONCLUSIONS: Adalimumab reduced key markers of inflammation including glycoprotein acetylation compared with phototherapy with no effect on glucose metabolism and vascular inflammation, and potential adverse effects on high-density lipoprotein. Glycoprotein acetylation improvement may partially explain the beneficial effects of adalimumab seen in observational studies. Larger studies with more detailed phenotyping of vascular disease should assess the comparative differences in the effects of adalimumab and phototherapy seen in our study. CLINICAL TRIAL REGISTRATION: NCT01866592 and NCT01553058.

Meeuwis, K. A. P., A. Potts Bleakman, P. C. M. van de Kerkhof, Y. Dutronc, C. Henneges, L. J. Kornberg and A. Menter (2018). “Prevalence of genital psoriasis in patients with psoriasis.” J Dermatolog Treat Mar 28. [Epub ahead of print].

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BACKGROUND: Psoriatic lesions in the genital area (GenPs) can cause considerable physical and emotional distress. To increase physician awareness, we estimated the GenPs prevalence among patients with psoriasis. METHODS: An English language literature search was performed. Articles reporting GenPs prevalence met the search criteria and were included. Because GenPs is rarely reported in demographics of prospective clinical trials, GenPs prevalence and baseline demographics of patients with and without GenPs in two prospective randomized phase 3b trials (NCT02561806 and NCT02634801) involving patients with moderate-to-severe psoriasis are reported. RESULTS: Overall, 600 references were screened. Eighteen articles met the search criteria. Patient populations were highly heterogeneous across articles. Broadly, the presence of GenPs was either physician-reported (physical examinations) or patient-reported (questionnaires). In the literature, GenPs prevalence at the time of reporting ranged from 7% to 42% and the prevalence of GenPs at any time during the course of psoriasis ranged from 33% to 63%. In the two prospective clinical trials, the prevalence of GenPs at the time of enrollment was 35-42%. CONCLUSION: A substantial proportion of patients experience genital lesions at some time during the course of psoriasis. Increased awareness of GenPs prevalence may drive improved assessment and treatment.

Kivelevitch, D., J. Frieder, I. Watson, S. Y. Paek and M. A. Menter (2018). “Pharmacotherapeutic approaches for treating psoriasis in difficult-to-treat areas.” Expert Opin Pharmacother 19(6): 561-575.

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INTRODUCTION: Despite great therapeutic advancements in psoriasis, four notable difficult-to-treat areas including the scalp, nails, intertriginous (including genitals), and palmoplantar regions, pose a challenge to both physicians and patients. Localized disease of these specific body regions inflicts a significant burden on patients’ quality of life and requires an adequate selection of treatments. Areas covered: This manuscript discusses appropriate therapies and important treatment considerations for these difficult-to-treat areas based on the available clinical data from the literature. Expert opinion: Clinical trials assessing therapies for the difficult-to-treat areas have been inadequate. With the first biological clinical trial for genital psoriasis pending publication, it is with hope that other biological agents will be evaluated for region-specific psoriasis. A greater understanding of the genetic and immunologic aspects of regional psoriasis, as well as identification of unique biomarkers, will further guide management decisions. For example, the recent discovery of the IL-36 receptor gene for generalized pustular psoriasis may prove valuable for other forms of psoriasis. Ultimately, identification of the most beneficial treatments for each psoriasis subtype and difficult-to-treat area will provide patients with maximal quality of life.

Michel, P., A. Menter and J. Griffin (2018). “A congenital naevus in a blaschkoid distribution.” Clin Exp Dermatol 43(2): 216-218.

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A 70-year-old man presented with a lesion on his lip of undetermined duration, which was considered to be nonmalignant. Total body skin examination revealed extensive areas of dilated follicular openings with hyperpigmented keratinous plugs within the follicles, extending from the lateral aspect of the patient’s right hip (Fig. 1) to the medial side of his ipsilateral thigh. Two areas with similar findings were found adjacent to the right gluteal cleft and the lateral aspect of the right shin. Discrete areas of atrophic scars were interspersed between the main lesions following the lines of Blaschko. On closer questioning, the patient stated that he was born with these lesions, which had remained relatively unchanged throughout his life. There was no associated family history. (Excerpt from text, p. 216; no abstract available.)