Martin A. Menter M.D.

Lebwohl, M. G., C. L. Leonardi, N. N. Mehta, A. B. Gottlieb, A. M. Mendelsohn, J. Parno, S. J. Rozzo and A. Menter (2019). “Tildrakizumab Efficacy and Safety Are Not Altered by Metabolic Syndrome Status in Patients with Psoriasis: Post Hoc Analysis of 2 Phase 3 Randomized Controlled Studies (Resurface 1 and Resurface 2).” J Am Acad Dermatol Sep 26. [Epub ahead of print].

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This post hoc analysis evaluated tildrakizumab efficacy, durability of response, and safety in patients with moderate to severe chronic psoriasis with vs without metabolic syndrome (MetS) using pooled data from 2 phase 3, double-blind, randomized, placebo-controlled studies (reSURFACE 1 [NCT01722331] and 2 [NCT01729754]). Patients with vs without MetS had higher prevalence of pre-existing cardiovascular disease and diabetes and higher median baseline weight and body mass index (BMI). Six (4.1%) patients with MetS (n=5 tildrakizumab 100 mg; n=1 tildrakizumab 200 mg) and 25 (4.5%) patients without MetS (n=12 tildrakizumab 100 mg; n=13 tildrakizumab 200 mg) did not complete the study. Percentages of patients with ≥75% improvement on the Psorasis Area and Severity Index (PASI 75 responders) at weeks 12 and 52 were comparable between patients with and without MetS for both tildrakizumab doses. Percentages of PASI 90 and PASI 100 responders through week 52 were similar regardless of MetS status for both tildrakizumab doses. Tildrakizumab efficacy through week 52 was maintained comparably in patients with and without MetS. Reductions in mean PASI from baseline were similar regardless of MetS status for both tildrakizumab doses. Percentages of patients with ≥1 serious adverse event (AE) and those with ≥1 serious infection were similar in patients with and without MetS. The most common serious AEs for patients with vs without MetS were gastrointestinal and cardiac disorders following tildrakizumab 100 mg and injury / procedural complications and nervous system disorders following tildrakizumab 200 mg. Fatal AEs occurred in 2 patients with MetS (both tildrakizumab 100 mg) and 2 patients without MetS (1 per tildrakizumab dose). Infection was the most commonly reported treatment-emergent AE (TEAE). Incidence was similar in patients with and without MetS receiving tildrakizumab 100 mg and numerically higher in patients with vs without MetS receiving tildrakizumab 200 mg. Incidence of cardiovascular events did not vary by MetS status, and there were no reports of diabetes worsening after treatment. Weight increases through week 28 were limited (~1 kg on average) in patients with and without MetS across both tildrakizumab doses. Exposure-adjusted rates of tier 1 TEAEs were comparable across doses regardless of MetS status. These post hoc analyses were not powered for statistical analyses based on MetS status, and populations were not matched for smoking history and other potential co-factors. Although abdominal obesity is more highly correlated with MetS risk factors relative to BMI, the latter was used as abdominal obesity data were not collected. Sample sizes for patients with MetS were relatively small; further evaluation of the effect of weight only on treatment efficacy and safety was not feasible because only 25 patients with BMI <30 kg/m2 met ≥3 criteria for MetS. Despite limitations, these results suggest efficacy, safety, and drug survival of tildrakizumab are comparable in patients with psoriasis regardless of MetS status. (Excerpt from text of this article-in-press.)

Lebwohl, M. G., A. Blauvelt, A. Menter, K. A. Papp, S. Guenthner, R. Pillai, R. J. Israel and A. Jacobson (2019). “Efficacy, Safety, and Patient-Reported Outcomes in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Brodalumab for 5 Years in a Long-Term, Open-Label, Phase Ii Study.” Am J Clin Dermatol Sep 6. [Epub ahead of print].

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BACKGROUND: Chronic inflammatory diseases such as psoriasis require treatment options that maintain efficacy and tolerability during extended treatment. OBJECTIVE: The aim of the study was to assess the long-term efficacy and safety of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. METHODS: Patients who completed a 12-week, phase II, dose-ranging clinical trial received brodalumab 210 mg every 2 weeks in an open-label extension study. Efficacy was assessed by static physician’s global assessment (sPGA) and psoriasis area and severity index (PASI). Quality of life, assessed by dermatology life quality index (DLQI), and safety were also evaluated. RESULTS: Overall, 181 patients received brodalumab for a median of 264 weeks. Brodalumab treatment resulted in rapid improvements in sPGA, PASI, and DLQI that were maintained through week 264. Achieving PASI 90 to < 100 or PASI 100 at weeks 12, 240, and 264 was associated with greater likelihood for DLQI 0 or 1 compared with achieving PASI 75 to < 90. Over 5 years, one adverse event of suicidal ideation was reported, no suicides occurred, and no new safety signals emerged. CONCLUSIONS: Brodalumab demonstrated skin clearance and improved quality of life, with an acceptable safety profile, throughout 5 years of treatment. ClinicalTrials.gov/NCT01101100.

Crow, L. D., A. Jambusaria-Pahlajani, C. L. Chung, D. A. Baran, S. E. Lowenstein, M. Abdelmalek, R. L. Ahmed, M. J. Anadkat, S. M. Arcasoy, D. Berg, K. P. Bibee, E. Billingsley, W. H. Black, T. W. Blalock, M. Bleicher, D. C. Brennan, D. G. Brodland, M. R. Brown, B. T. Carroll, J. A. Carucci, T. W. Chang, G. Chaux, C. A. Cusack, D. F. Dilling, A. Doyle, A. M. Emtiazjoo, N. H. Ferguson, S. W. Fosko, M. C. Fox, S. Goral, A. L. Gray, J. R. Griffin, R. R. Hachem, S. A. Hall [. . .] A. Menter [. . .] S. Y. Paek [. . .] and S. T. Arron (2019). “Initial Skin Cancer Screening for Solid Organ Transplant Recipients in the United States: Delphi Method Development of Expert Consensus Guidelines.” Transpl Int. Sep 10. [Epub ahead of print].

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Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.

Elmets, C. A., H. W. Lim, B. Stoff, C. Connor, K. M. Cordoro, M. Lebwohl, A. W. Armstrong, D. M. R. Davis, B. E. Elewski, J. M. Gelfand, K. B. Gordon, A. B. Gottlieb, D. H. Kaplan, A. Kavanaugh, M. Kiselica, D. Kivelevitch, N. J. Korman, D. Kroshinsky, C. L. Leonardi, J. Lichten, N. N. Mehta, A. S. Paller, S. L. Parra, A. L. Pathy, E. A. Farley Prater, R. N. Rupani, M. Siegel, B. E. Strober, E. B. Wong, J. J. Wu, V. Hariharan and A. Menter (2019). “Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis with phototherapy.” J Am Acad Dermatol 81(3): 775-804.

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Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world’s population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light-based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments.

Bissonnette, R., P. Fernandez-Penas, L. Puig, A. M. Mendelsohn, S. J. Rozzo and A. Menter (2019). “Incidence of cardiovascular events among tildrakizumab-treated patients with moderate-to-severe plaque psoriasis: pooled data from three large randomised clinical trials.” J Eur Acad Dermatol Venereol Aug 12. [Epub ahead of print].

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Psoriasis is an independent risk factor for incidence of major adverse cardiovascular (CV) events (MACE), a composite endpoint including myocardial infarction, stroke and death. While many biologics, including tumour necrosis factor inhibitors, interleukin (IL)‐17 inhibitors, and IL‐12/23 inhibitors are approved for the treatment of psoriasis, evidence is limited on the impact of biologics on CV outcomes in patients with psoriasis. In a phase 2b (P05495, NCT01225731) and 2 phase 3 (reSURFACE 1, NCT01722331; and reSURFACE 2, NCT01729754) trials conducted in patients with moderate‐to‐severe chronic plaque psoriasis, tildrakizumab—a high‐affinity, humanised, immunoglobulin G1κ, anti–IL‐23p19 antibody—was well tolerated, with low frequencies of serious adverse events and discontinuations due to adverse events. Here, we evaluated incidence of CV events using pooled safety data obtained from the full trial periods and year 1 of the phase 3 extension studies. (Excerpt from text of authors’ commentary on the article, Papp K, Thaci D, Reich K et al. Tildrakizumab (MK‐3222), an anti‐interleukin‐23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo‐controlled trial. Br J Dermatol 2015; 173: 930– 939, and related studies.)