Martin A. Menter M.D.

Menter, A., Krueger, G.G., Paek, S.Y., Kivelevitch, D., Adamopoulos, I.E. and Langley, R.G. (2021). “Interleukin-17 and Interleukin-23: A Narrative Review of Mechanisms of Action in Psoriasis and Associated Comorbidities.” Dermatol Ther (Heidelb) 11(2): 385-400.

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Psoriasis is an immune-mediated inflammatory skin disease associated with numerous inflammatory comorbidities, including increased cardiovascular risk. The interleukin (IL)-23/IL-17 axis plays a central role in the immunopathogenesis of psoriasis and related comorbidities by acting to stimulate keratinocyte hyperproliferation and feed-forwarding circuits of perpetual T cell-mediated inflammation. IL-17 plays an important role in the downstream portion of the psoriatic inflammatory cascade. This review discusses the distinct mechanisms of action of IL-17 and IL-23 in the immunopathogenesis of psoriasis and related comorbidities plus the significant therapeutic benefits of selectively inhibiting these cytokines in patients with moderate to severe plaque psoriasis.

Menter, A., Krueger, G.G., Paek, S.Y., Kivelevitch, D., Adamopoulos, I.E. and Langley, R.G. (2021). “Interleukin-17 and Interleukin-23: A Narrative Review of Mechanisms of Action in Psoriasis and Associated Comorbidities.” Dermatol Ther (Heidelb) Jan 29. [Epub ahead of print].

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Psoriasis is an immune-mediated inflammatory skin disease associated with numerous inflammatory comorbidities, including increased cardiovascular risk. The interleukin (IL)-23/IL-17 axis plays a central role in the immunopathogenesis of psoriasis and related comorbidities by acting to stimulate keratinocyte hyperproliferation and feed-forwarding circuits of perpetual T cell-mediated inflammation. IL-17 plays an important role in the downstream portion of the psoriatic inflammatory cascade. This review discusses the distinct mechanisms of action of IL-17 and IL-23 in the immunopathogenesis of psoriasis and related comorbidities plus the significant therapeutic benefits of selectively inhibiting these cytokines in patients with moderate to severe plaque psoriasis.

Lebwohl, M.G., Leonardi, C.L., Mehta, N.N., Gottlieb, A.B., Mendelsohn, A.M., Parno, J., Rozzo, S.J. and Menter, M.A. (2020). “Tildrakizumab efficacy, drug survival, and safety are comparable in patients with psoriasis with and without metabolic syndrome: Long-term results from two phase 3 randomized controlled studies (reSURFACE 1 and reSURFACE 2).” J Am Acad Dermatol Sep 19;S0190-9622(20)32637-2. [Epub ahead of print.].
Menter1

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BACKGROUND: Data for the effect of metabolic syndrome (MetS) on efficacy and safety of biologic agents for psoriasis treatment are limited. OBJECTIVE: To evaluate long-term tildrakizumab efficacy, drug survival, and safety in patients with psoriasis by baseline MetS status. METHODS: Post hoc analyses of up to 3 years of efficacy data and 5 years of safety data from the phase 3, double-blind, randomized controlled reSURFACE 1 and 2 trial (NCT01722331; NCT01729754) base and extension studies were conducted for patients receiving continuous tildrakizumab 100 or 200 mg. RESULTS: Of 338 (n = 124/214) and 307 (n = 147/160) patients continuously receiving tildrakizumab 100 and 200 mg, respectively, throughout the studies, 26/44 (21%/21%) and 34/30 (23%/19%) met MetS criteria. Proportions of Psoriasis Area and Severity Index (PASI) 75 responders in reSURFACE 1/2 were generally comparable in patients with vs without MetS at week 52 (tildrakizumab 100 mg, 85%/86% vs 86%/94%; tildrakizumab 200 mg, 76%/87% vs 76%/87%) and through week 148. Results were similar for PASI 90/100 responders. Tildrakizumab’s safety profile did not vary by MetS status. LIMITATIONS: Small sample size and post hoc analysis limit interpretation. CONCLUSION: Long-term tildrakizumab efficacy and safety were comparable between patients with and without MetS.

Haque, E.K., Azhar, A., Corbett, J., Frieder, J., Wang, X. and Menter, A. (2020). “A Real-World Evaluation of the Long-Term Safety and Efficacy of Infliximab in the Treatment Moderate-to-Severe Psoriasis.” Dermatol Ther (Heidelb) 10(5): 1121-1135.

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INTRODUCTION: Psoriasis is a chronic immune-mediated inflammatory skin disease that occurs in 2.5-3.5% of the general population. Infliximab (INF), a TNF-α inhibitor biologic agent, is a long-standing efficacious treatment for psoriasis; however, not all patients sustain a long-term response (LTR) because of a number of factors including antibody production. There is a paucity of studies assessing infliximab efficacy over a period ≥ 5 years. METHODS: A retrospective cohort chart review of our clinic patients who had undergone ≥ 5 years of treatment with infliximab for chronic plaque psoriasis was performed. The following variables were recorded and analyzed with the Fisher exact test: age, sex, body mass index ([BMI]; normal weight [NW], overweight [OW], obese [OB]), changes in infliximab strength (dose or frequency), concomitant systemic therapy, and side effects. Clinical improvement was assessed by comparing the total body surface area (tBSA) affected by psoriasis before and after treatment. RESULTS: There was a significant difference in likelihood of achieving LTR between the NW, OW and OB groups (p = 0.044). Non-normal-weight patients (OW + OB) were significantly more likely to achieve and sustain LTR than NW patients (OR 9.07, p = 0.020). There were no other significant associations for the other evaluated variables. LIMITATIONS: Patients who began treatment with infliximab before 2009 (prior to the use of the clinic’s electronic medical record) were excluded. The Psoriasis Area and Severity Index (PASI) was not available for this study. CONCLUSION: Surprisingly, patients who are overweight or obese are more likely to obtain long-term clinical benefit in their psoriasis symptoms with infliximab therapy than patients who are normal weight.

Iversen, L., Kurvits, M., Snel-Prentø, A.M. and Menter, A. (2020). “Calcipotriol/Betamethasone Dipropionate Cutaneous Foam Treatment for Psoriasis in Patients With BSA 5-15% and PGA ≥ 3: Post-Hoc Analysis From Three Randomized Controlled Trials.” Dermatol Ther (Heidelb) 10(5): 1111-1120.

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INTRODUCTION: Psoriasis is a chronic, inflammatory disease, which ranges in severity from mild to severe. Although topical therapies are frequently used to treat mild disease, they are not routinely used to treat patients with moderate-to-severe disease who have a larger proportion of their body surface area (BSA) affected (≥ 5% BSA). Based on well-controlled trials in adults with mild-to-severe disease, fixed-dose combination calcipotriol 50 μg/g + betamethasone dipropionate 0.5 mg/g (Cal/BD) cutaneous foam has been approved (Enstilar®, LEO Pharma) in the USA and EU for the treatment of psoriasis vulgaris for up to 4 weeks in adults. In this post-hoc subgroup analysis, we used pooled data from phase II/III trials to investigate the efficacy and safety of Cal/BD cutaneous foam in patients with moderate-to-severe psoriasis. METHODS: Patients included in this analysis had psoriasis affecting 5-15% BSA and a physician’s global assessment (PGA) ≥ 3. Endpoints included: treatment success by PGA (rating: clear/almost clear), patient’s global assessment (PaGA) at week 4 (rating: clear/very mild) and safety. RESULTS: A total of 340 patients in the three randomized trials met the BSA/PGA inclusion criteria, of whom 254 were treated with Cal/BD foam and 86 with vehicle foam. Treatment success by PGA and PaGA at week 4 was achieved in 143 (58.1%) and 138 (56.1%) patients receiving Cal/BD foam, respectively, versus three (3.6%) and 14 (16.7%) patients receiving vehicle foam. Sixty-six adverse events (AEs) occurred in 47 (18.5%) patients receiving Cal/BD foam and 11 AEs occurred in 11 (12.8%) patients receiving vehicle foam. Three severe AEs and 15 non-serious treatment-related AEs occurred in patients receiving Cal/BD foam. CONCLUSION: The results from three clinical trials analyzed together show that topical Cal/BD foam is well tolerated and efficacious for treating patients with moderate-to-severe disease. Data support Cal/BD foam as a potential topical therapy for moderate-to-severe psoriasis.