Martin A. Menter M.D.

Simpson, E., R. Bissonnette, L. F. Eichenfield, E. Guttman, B. King, J. I. Silverberg, L. A. Beck, T. Bieber, K. Reich, K. Kabashima, M. Seyger, E. Siegfried, G. Stingl, S. R. Feldman, A. Menter, P. van de Kerkhof, G. Yosipovitch, C. Paul, P. Martel, A. Dubost-Brama, J. Armstrong, R. Chavda, S. Frey, Y. Joubert, M. Milutinovic, A. Parneix, H. D. Teixeira, C. Y. Lin, L. Sun, P. Klekotka, B. Nickoloff, Y. Dutronc, L. Mallbris, J. M. Janes, A. M. DeLozier, F. Nunes and A. S. Paller (2020). “The validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): The development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis.” J Am Acad Dermatol Apr 25. pii: S0190-9622(20)30720-9. [Epub ahead of print].

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BACKGROUND: An Investigator Global Assessment (IGA) is recommended by health agencies for drug registration in atopic dermatitis (AD). Current IGA scales lack standardization. OBJECTIVES: To develop an IGA scale, training module, and clinical certification exam for use in AD trials, and establish content validity and assess reliability. METHODS: Expert dermatologists participated in the development of the validated IGA for AD (vIGA-AD). Reliability (inter-rater and intra-rater) was assessed by 2 web-based surveys. Clinical certification for investigators consisted of a training module and exam. RESULTS: Expert consensus was achieved around a 5-point IGA scale including morphological descriptions, and content validity was established. Survey 1 showed strong inter-rater reliability (Kendall’s coefficient of concordance W [Kendall’s W] = 0.809, intra-class correlation [ICC] = 0.817) and excellent agreement (weighted Kappa = 0.857). Survey 2, completed 5 months after training of dermatologists, showed improvements in scale reliability (Kendall’s W = 0.819, ICC = 0.852, weighted Kappa = 0.889). In this study 627 investigators completed vIGA-AD training and certification. LIMITATIONS: Ratings were assessed on photographs. CONCLUSION: A validated IGA scale and training module were developed with the intent of harmonizing assessment of disease severity in AD trials. Strong reliability and excellent agreement between assessments were observed.

Papp, K., A. Menter, C. Leonardi, J. Soung, S. Weiss, R. Pillai and A. Jacobson (2020). “Long-term efficacy and safety of brodalumab in psoriasis through 120 weeks and after withdrawal and retreatment: subgroup analysis of a randomised phase 3 trial (AMAGINE-1).” Br J Dermatol Apr 14. [Epub ahead of print].

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BACKGROUND: Brodalumab is efficacious for the treatment of moderate-to-severe plaque psoriasis through 52 weeks. OBJECTIVE: To evaluate the efficacy and safety of brodalumab through 120 weeks, including following withdrawal and retreatment. METHODS: At baseline, patients were randomized to brodalumab (n=222) or placebo (n=220). At week 12, patients achieving static physician’s global assessment score of 0 or 1 (sPGA 0/1) with brodalumab were re-randomized to brodalumab (n=83) or placebo (n=84; later re-treated with brodalumab if sPGA >/=3 occurred), and patients receiving placebo switched to brodalumab (n=208). Safety was assessed by treatment-emergent adverse events. RESULTS: Among those who achieved sPGA 0/1 at week 12 and were re-randomized to brodalumab, 95.7% and 79.5% using observed data, respectively, and 73.9% and 61.4% using nonresponder imputation, respectively, achieved 75% improvement in psoriasis area and severity index (PASI 75) and PASI 100 at week 120. Following withdrawal from brodalumab, return of disease occurred after a mean (standard deviation) of 74.7 (50.5) days. Among those who switched from brodalumab to placebo at week 12, PASI 75 rates using observed data and nonresponder imputation were 55.1% and 51.2% at week 20, respectively, and 94.0% and 75.0% at week 120, respectively; PASI 100 rates at week 120 were 74.6% and 59.5%, respectively. Efficacy was maintained through week 120 in those receiving brodalumab after placebo. No new safety signals were observed. CONCLUSIONS: These findings indicate that brodalumab is efficacious and safe for continuous long-term treatment of psoriasis and support potential for response after discontinuation and retreatment.

Wu, J. J., J. F. Merola, S. R. Feldman, A. Menter and M. Lebwohl (2020). “Treatment of Psoriasis with Secukinumab in Challenging Patient Scenarios: A Review of the Available Evidence.” Dermatol Ther (Heidelb) Apr 2. [Epub ahead of print].

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Psoriasis (PsO) is a common, systemic, chronic, inflammatory disease characterized by key clinical symptoms, including itching, pain, and scaling. PsO is associated with a high prevalence of comorbidities, including other autoimmune diseases and malignancies. Furthermore, special populations, such as pregnant, pediatric, and elderly patients, and those with erythrodermic PsO, are challenging to treat and require tightly monitored disease and treatment management. Because certain populations have demographic or clinical characteristics that can affect the presentation of PsO and complicate treatment responses, these patient populations are largely excluded from clinical trials; therefore, most clinical evidence for the treatment of these patients is derived from case reports and series. Secukinumab, a fully human monoclonal interleukin-17A antibody, has been shown in several clinical trials to be effective and safe for the treatment of PsO; however, these studies offer only limited data on the use of secukinumab in patients with chronic illnesses or in special populations. This review explores the use of secukinumab for PsO in special populations, including pregnant women, children, elderly people, patients with erythrodermic PsO, and those with chronic illnesses, including latent tuberculosis, hepatitis B and C, HIV, multiple sclerosis, and malignancies.

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The authors would like to correct the error in Table 1.

Philipp, S., A. Menter, A. F. Nikkels, K. Barber, I. Landells, L. F. Eichenfield, M. Song, B. Randazzo, S. Li, M. C. Hsu, Y. Zhu, S. DePrimo and A. S. Paller (2020). “Ustekinumab for the treatment of moderate-to-severe plaque psoriasis in pediatric patients (>/=6 to <12 years of age): efficacy, safety, pharmacokinetic, and biomarker results from the open-label CADMUS Jr study." Br J Dermatol Mar 16. [Epub ahead of print].

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BACKGROUND: Limited options are available for treatment of pediatric psoriasis. OBJECTIVES: To evaluate the efficacy and safety of ustekinumab in pediatric psoriasis patients (>/=6 to <12 years of age). METHODS: CADMUS Junior (Jr), a phase 3, open-label, single-arm, multicenter study, evaluated ustekinumab in pediatric patients with moderate-to-severe plaque psoriasis. Patients received weight-based dosing of ustekinumab (<60kg: 0.75mg/kg; >/=60to100kg: 90mg) administered by subcutaneous injection at weeks 0/4, then every-12-weeks through week 40. Study endpoints (all at week 12) included the proportions of patients achieving a Physician’s Global Assessment score of cleared/minimal (PGA 0/1) and >/=75%/90% improvement in Psoriasis Area and Severity Index (PASI 75/90) and change in Children’s Dermatology Life Quality Index (CDLQI). Serum ustekinumab concentrations, anti-drug antibodies (ADA), and cytokine levels were measured through week 52. Safety was evaluated through week 56. RESULTS: A total of 44 patients (median age, 9.5 years) received at least one dose of ustekinumab. Three patients discontinued study agent through week 40. At week 12, 77.3% of patients achieved PGA 0/1, 84.1% achieved PASI 75, and 63.6% achieved PASI 90 response; mean change in CDLQI was -6.3. Trough serum ustekinumab concentrations reached steady state at weeks 28-52. The incidence of ADA was 9.5% (n=4). Mean serum concentrations of IL-17A/F and IL-22 were significantly reduced at weeks 12/52. Overall, 34 patients (77.3%) had at least one adverse event and 3 (6.8%) had a serious adverse event. CONCLUSIONS: Ustekinumab effectively treated moderate-to-severe psoriasis in pediatric patients, and no new safety concerns were identified.

Menter, A., J. M. Gelfand, C. Connor, A. W. Armstrong, K. M. Cordoro, D. M. R. Davis, B. E. Elewski, K. B. Gordon, A. B. Gottlieb, D. H. Kaplan, A. Kavanaugh, M. Kiselica, D. Kivelevitch, N. J. Korman, D. Kroshinsky, M. Lebwohl, C. L. Leonardi, J. Lichten, H. W. Lim, N. N. Mehta, A. S. Paller, S. L. Parra, A. L. Pathy, E. F. Prater, R. S. Rahimi, R. N. Rupani, M. Siegel, B. Stoff, B. E. Strober, E. B. Tapper, E. B. Wong, J. J. Wu, V. Hariharan and C. A. Elmets (2020). “Joint Aad-Npf Guidelines Of Care For The Management Of Psoriasis With Systemic Non-Biological Therapies.” J Am Acad Dermatol Feb 21. [Epub ahead of print].

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Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world’s population. In this guideline, we focus the discussion on systemic, non-biologic medications for the treatment of this disease. We provide a detailed discussion of efficacy and safety for the most commonly used medications-including methotrexate, cyclosporine, and acitretin-and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch upon a number of other medications, including fumaric acid esters (used outside the US) and therapies that are no longer widely used for the treatment of psoriasis, i.e. hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus.