Martin A. Menter M.D.

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 29(8): 754-760.

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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.

Haugh, I. M., A. K. Preston, D. N. Kivelevitch and A. M. Menter (2018). “Risankizumab: an anti-IL-23 antibody for the treatment of psoriasis.” Drug Des Devel Ther 12: 3879-3883.

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Risankizumab, a fully human IgG monoclonal antibody inhibitor of IL-23, is a therapeutic agent currently in late stage development for use in the treatment of moderate-to-severe plaque psoriasis. It is a biologic agent similar to guselkumab and tildrakizumab which targets IL-23 specifically, and has been primarily developed for use in moderate-to-severe psoriasis. USA-based pharmaceutical company Abbvie submitted it for a Biologics License Application to the US Food and Drug Administration (FDA) in April 2018. Risankizumab is the result of a collaboration between the German company Boehringer Ingelheim and Abbvie, which together are leading the future development and commercialization of risankizumab globally. The results from Phase I to Phase III clinical trials of risankizumab show it is highly effective and its FDA-approval in 2018 is likely. In this article we provide an independent expert opinion on the efficacy and safety of risankizumab in psoriasis based on a full review of the literature.

Strober, B., J. Crowley, R. G. Langley, K. Gordon, A. Menter, C. Leonardi, D. Arikan and W. C. Valdecantos (2018). “Systematic review of the real-world evidence of adalimumab safety in psoriasis registries.” J Eur Acad Dermatol Venereol Aug 1. [Epub ahead of print].

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Long-term safety of adalimumab in psoriasis clinical studies has been established. The objective of this research was to review real-world evidence of adalimumab safety from registries of adult patients with psoriasis treated in clinical practise. Databases (BIOSIS Previews, Current Contents Search, Derwent Drug File, Embase, Embase Alert, EMCare, MEDLINE, SciSearch) were searched for psoriasis registries with adalimumab safety data. Eligible papers were English language manuscripts (conference abstracts excluded) from psoriasis registries presenting safety data for adult patients with psoriasis receiving adalimumab. The incidence and rate (events/100 patient-years [PY]) of adverse events (AEs), serious AEs (SAEs), and AEs of special interest are reported. Abstracts of 425 publications were screened, and 401 publications excluded (208 conference abstracts; 193 papers). Remaining manuscripts were fully screened; 14 were excluded (no adalimumab data, n=10; no safety data, n=2; no on-treatment data, n=1; not English, n=1), and 10 selected. Overall rates of AEs (4273 [22.2/100PY]) and SAEs (827 [4.3/100PY]) were reported in the ESPRIT registry (N=6059). Rates of infections (7.7-14.7/100PY) and serious infections (<0.6-2.0/100PY) were reported in 4 studies. Cardiovascular-related events were reported in 3 studies:

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.