Martin A. Menter M.D.

Frieder, J., D. Kivelevitch and A. Menter (2017). “Calcipotriene betamethasone dipropionate aerosol foam in the treatment of plaque psoriasis: A review of the literature.” Ther Deliv: 2017 Jun [Epub ahead of print].

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Psoriasis is a common chronic immune-mediated skin disease which has a significant impact on patients’ quality of life, and is associated with numerous comorbidities (i.e., psoriatic arthritis, Crohn’s disease and cardiovascular disease). A greater understanding of its immunopathogenesis has guided the development of novel, more targeted therapies. Nonetheless, traditional treatment with topical agents, phototherapy and systemic medications is used in the management of the majority of psoriasis patients. Mainstay topical treatments include corticosteroids and vitamin D derivatives. Calcipotriene/betamethasone dipropionate aerosol foam is a novel single product combination, which seeks to provide superior therapeutic efficacy in addition to enhanced cosmetic properties. This article reviews the literature on the pharmacology and clinical data in terms of safety, efficacy and patient satisfaction of this topical medication.

Shear, N. H., R. Alhusayen, A. Fernandez-Obregon, A. B. Kimball, A. Menter, J. J. Wu, K. Goyal, H. Patel, R. Lin and A. W. Armstrong (2017). “Observations from our evaluation of body weight changes after initiation of a biologic therapy in psolar.” J Eur Acad Dermatol Venereol: 2017 Jun [Epub ahead of print].

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PSOLAR is a global, prospective, observational study designed to evaluate long-term safety and clinical outcomes for over 12,000 psoriasis patients who are receiving, or are eligible to receive, biologic and/or conventional systemic agents. Data from the registry may also be used to test hypotheses for topics of interest to dermatologists.1 While PSOLAR has produced many viable analyses of safety and efficacy outcomes, including overall safety, serious infections, comparative effectiveness, and persistence of treatment,2-5 a recently tested hypothesis related to treatment effect on body weight did not generate interpretable results. Our observations may be relevant for future research in this area.

Paul, C., C. Leonardi, A. Menter, K. Reich, L. S. Gold, R. B. Warren, A. Moller and M. Lebwohl (2017). “Calcipotriol plus betamethasone dipropionate aerosol foam in patients with moderate-to-severe psoriasis: Sub-group analysis of the pso-able study.” Am J Clin Dermatol 18(3): 405-411.

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BACKGROUND: Fixed-combination calcipotriol 50 mug/g plus betamethasone 0.5 mg/g (Cal/BD) aerosol foam is a new topical treatment for psoriasis. Although moderate-to-severe psoriasis is typically treated with systemic/biologic therapies, a topical treatment that is efficacious in these patients may be a significant cost-saving alternative to systemic therapy. OBJECTIVE: The objective of this study was to assess the response to Cal/BD foam and gel in patients with moderate-to-severe psoriasis enrolled in the phase III, 12-week PSO-ABLE study. METHODS: Patients eligible for this analysis had moderate-to-severe psoriasis, defined by the ‘Rule of Tens’: body surface area >/=10% or Psoriasis Area and Severity Index (PASI) [excluding head; modified PASI (mPASI)] >10 or Dermatology Life-Quality Index >10. Endpoints included: proportion of patients achieving mPASI75 or mPASI90; change in body surface area; proportion of patients clear/almost clear with a >/=2 grade improvement (i.e., treatment success); change in Dermatology Life-Quality Index. RESULTS: Seventy-seven Cal/BD foam patients and 82 gel patients had moderate-to-severe psoriasis. A greater proportion achieved mPASI75 and mPASI90 with Cal/BD foam than gel at weeks 4, 8, and 12 (57.1 vs. 35.4%; p = 0.006 and 15.6 vs. 12.2% at week 12, respectively); overall reduction in mPASI from baseline to week 12 was 64% with the foam vs. 51% with the gel. Overall reduction in body surface area at week 12 was 50% with the foam and 39% with the gel. Treatment success rates were higher with the Cal/BD foam than the gel at weeks 1, 2, 4, 8 (p = 0.0089), and 12, and a greater proportion of foam patients achieved a Dermatology Life-Quality Index score of 0/1 at weeks 4 (p = 0.004), 8, and 12 (p = 0.001). CONCLUSION: Cal/BD foam can be considered as a treatment option in some patients with moderate-to-severe psoriasis who are potential candidates for systemic therapy.

Papp, K. A., A. Blauvelt, M. Bukhalo, M. Gooderham, J. G. Krueger, J. P. Lacour, A. Menter, S. Philipp, H. Sofen, S. Tyring, B. R. Berner, S. Visvanathan, C. Pamulapati, N. Bennett, M. Flack, P. Scholl and S. J. Padula (2017). “Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis.” N Engl J Med 376(16): 1551-1560.

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BACKGROUND: Interleukin-23 is thought to be critical to the pathogenesis of psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically targeting the p19 subunit and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, in patients with moderate-to-severe plaque psoriasis. METHODS: We randomly assigned a total of 166 patients to receive subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to body weight, at weeks 0, 4, and 16). The primary end point was a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12. RESULTS: At week 12, the percentage of patients with a 90% or greater reduction in the PASI score was 77% (64 of 83 patients) for risankizumab (90-mg and 180-mg groups, pooled), as compared with 40% (16 of 40 patients) for ustekinumab (P<0.001); the percentage of patients with a 100% reduction in the PASI score was 45% in the pooled 90-mg and 180-mg risankizumab groups, as compared with 18% in the ustekinumab group. Efficacy was generally maintained up to 20 weeks after the final dose of 90 or 180 mg of risankizumab. In the 18-mg and 90-mg risankizumab groups and the ustekinumab group, 5 patients (12%), 6 patients (15%), and 3 patients (8%), respectively, had serious adverse events, including two basal-cell carcinomas and one major cardiovascular adverse event; there were no serious adverse events in the 180-mg risankizumab group. CONCLUSIONS: In this phase 2 trial, selective blockade of interleukin-23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab. This trial was not large enough or of long enough duration to draw conclusions about safety.

Menter, A., R. B. Warren, R. G. Langley, J. F. Merola, L. N. Kerr, E. B. Dennehy, D. Shrom, D. Amato, Y. Okubo and K. Reich (2017). “Efficacy of ixekizumab compared to etanercept and placebo in patients with moderate to severe plaque psoriasis and non-pustular palmoplantar involvement: results from three phase 3 trials (UNCOVER-1, -2, and -3).” J Eur Acad Dermatol Venereol: 2017 Mar [Epub ahead of print].

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BACKGROUND: Palmoplantar psoriasis has significant physical and emotional impact on patients and can be difficult to treat. OBJECTIVE: To evaluate the efficacy of ixekizumab in the treatment of patients with moderate-to-severe non-pustular palmoplantar involvement and moderate-to-severe plaque psoriasis. METHODS: In three phase 3, double-blind, placebo-controlled trials, patients with moderate-to-severe non-pustular plaque psoriasis (UNCOVER-1 (N=1296), UNCOVER-2 (N=1224), UNCOVER-3 (N=1346)) were randomised to subcutaneous 80 mg ixekizumab every 2 or 4 weeks (Q2W, Q4W), after a 160 mg starting dose, or placebo through week 12. Additional UNCOVER-2 and -3 cohorts were randomised to 50 mg etanercept bi-weekly. Patients entering the open-label long-term extension (UNCOVER-3) received ixekizumab Q4W weeks 12-60. Moderate-to-severe palmoplantar involvement was defined as Palmoplantar Psoriasis Area and Severity Index (PPASI) >/=8. RESULTS: Twenty-eight percent of UNCOVER-1,-2,-3 patients had baseline palmoplantar involvement (PPASI>/=0, n=1092) and 9.1% (n=350) had moderate-to-severe involvement, with mean baseline PPASI ~20, PASI ~24, and most (>60%) had static Physician’s Global Assessment >/=4. Higher percentages of patients treated with ixekizumab versus placebo or etanercept achieved PPASI 50 (approximately 80% versus 32.9%, 67.8%; ixekizumab, placebo, etanercept, respectively) and PPASI 75 (approximately 70% versus 18.8%, 44.1%; ixekizumab, placebo, etanercept, respectively) at week 12 (all P<0.05). PPASI 100 was achieved by higher percentages of ixekizumab-treated patients versus placebo (approximately 50% versus 8.2%, P<0.001) and ixekizumab Q2W-treated patients versus etanercept (51.8% versus 32.2%, P<0.05). Outcomes were maintained or improved in patients continuing on ixekizumab Q4W through week 60. Differences between ixekizumab and placebo or etanercept were statistically significant as early as week 1. CONCLUSION: In a subpopulation analysis of patients from phase 3 trials with moderate-to-severe non-pustular palmoplantar involvement and moderate-to-severe plaque psoriasis, ixekizumab treatment resulted in greater and more rapid improvements than placebo and etanercept at week 12; improvements were sustained with continued treatment.