Martin A. Menter M.D.

Elewski, B., A. Menter, J. Crowley, S. Tyring, Y. Zhao, S. Lowry, S. Rozzo, A. M. Mendelsohn, J. Parno and K. Gordon (2019). “Sustained and continuously improved efficacy of tildrakizumab in patients with moderate-to-severe plaque psoriasis.” J Dermatolog Treat Jul 22. [Epub ahead of print].

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Background: Tildrakizumab is a high-affinity, humanized, IgG1 kappa, anti-interleukin-23 monoclonal antibody approved for moderate-to-severe plaque psoriasis. Objectives: This analysis examined whether tildrakizumab’s week-28 efficacy can be sustained or improved to week 52. Methods: Psoriasis patients on the same-dose tildrakizumab (100 or 200 mg) in the first 52 weeks achieving week-28 PASI >/=50 were pooled from two phase-3 randomized controlled trials, and grouped into four mutually exclusive week-28 PASI response groups. Patients’ week-52 PASI responses were compared to their week-28 PASI responses. Results: Of 352 patients receiving 100-mg tildrakizumab, 10.5%, 25.3%, 38.4%, and 25.9% achieved PASI 50-74, 75-89, 90-99, and 100 at week 28, respectively. Among patients achieving PASI >/=90, >/=75, or >/=50 at week 28, 89.4%, 91.1%, or 97.4% maintained their week-28 PASI responses at week 52, respectively. Among patients achieving PASI 50-74, 75-89, or 90-99 at week 28, 64.8%, 33.7%, or 25.2% improved their week-28 PASI responses at week 52, respectively. Limitations: This post hoc analysis may be less robust than an a priori analysis. Conclusions: Most tildrakizumab-treated patients with week-28 PASI >/=75 maintained their week-28 PASI improvement at week 52. More than half of week-28 partial responders (PASI 50-74) improved their PASI responses to PASI >/=75 at week 52. Clinicaltrials.gov identifiers: NCT01722331, NCT01729754.

Reich, K., P. Rich, C. Maari, R. Bissonnette, C. Leonardi, A. Menter, A. Igarashi, P. Klekotka, D. Patel, J. Li, J. Tuttle, M. Morgan-Cox, E. Edson-Heredia, S. Friedrich and K. Papp (2019). “Efficacy and safety of mirikizumab (LY3074828) in the treatment of moderate-to-severe plaque psoriasis: results from a randomized phase II study.” Br J Dermatol 181(1): 88-95.

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BACKGROUND: Inhibiting interleukin (IL)-23 in patients with psoriasis has demonstrated high levels of skin clearance. OBJECTIVES: To investigate, in a phase II (AMAF; NCT02899988), multicentre, double-blind trial, the efficacy and safety of three doses of mirikizumab (LY3074828), a p19-directed IL-23 antibody, vs. placebo in patients with moderate-to-severe plaque psoriasis. METHODS: Adult patients were randomized 1 : 1 : 1 : 1 to receive placebo (n = 52), mirikizumab 30 mg (n = 51), mirikizumab 100 mg (n = 51) or mirikizumab 300 mg (n = 51) subcutaneously at weeks 0 and 8. The primary objective was to evaluate the superiority of mirikizumab over placebo in achieving a 90% improvement in the Psoriasis Area and Severity Index (PASI 90) response at week 16. Comparisons were done using logistic regression analysis with treatment, geographical region and previous biological therapy in the model. Missing data were imputed as nonresponses. RESULTS: Ninety-seven per cent of patients completed the first 16 weeks of the study. The primary end point was met for all mirikizumab dose groups vs. placebo, with PASI 90 response rates at week 16 of 0%, 29% (P = 0.009), 59% (P < 0.001) and 67% (P < 0.001) for patients receiving placebo, and mirikizumab 30 mg, 100 mg and 300 mg, respectively. There were two (1%) serious adverse events in mirikizumab-treated patients vs. one (2%) in a placebo-group patient. CONCLUSIONS: At week 16, 67% of patients treated with mirikizumab 300 mg at 8-week intervals achieved PASI 90. The percentage of patients reporting at least one treatment-emergent adverse event was similar among patients treated with placebo or mirikizumab.

Elewski, B., A. Menter, J. Crowley, S. Tyring, Y. Zhao, S. Lowry, S. Rozzo, A. M. Mendelsohn, J. Parno and K. Gordon (2019). “Sustained and Continuously Improved Efficacy of Tildrakizumab in Patients with Moderate-to-Severe Plaque Psoriasis.” J Dermatolog Treat Jul 3: 1-19. [Epub ahead of print].

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Background: Tildrakizumab is a high-affinity, humanized, IgG1 kappa, anti-interleukin-23 monoclonal antibody approved for moderate-to-severe plaque psoriasis. Objectives: This analysis examined whether tildrakizumab’s week-28 efficacy can be sustained or improved to week 52. Methods: Psoriasis patients on the same-dose tildrakizumab (100 or 200 mg) in the first 52 weeks achieving week-28 PASI >/=50 were pooled from two phase-3 randomized controlled trials, and grouped into four mutually exclusive week-28 PASI response groups. Patients’ week-52 PASI responses were compared to their week-28 PASI responses. Results: Of 352 patients receiving 100-mg tildrakizumab, 10.5%, 25.3%, 38.4%, and 25.9% achieved PASI 50-74, 75-89, 90-99, and 100 at week 28, respectively. Among patients achieving PASI >/=90, >/=75, or >/=50 at week 28, 89.4%, 91.1%, or 97.4% maintained their week-28 PASI responses at week 52, respectively. Among patients achieving PASI 50-74, 75-89, or 90-99 at week 28, 64.8%, 33.7%, or 25.2% improved their week-28 PASI responses at week 52, respectively. Limitations: This post-hoc analysis may be less robust than an a priori analysis. Conclusions: Most tildrakizumab-treated patients with week-28 PASI >/=75 maintained their week-28 PASI improvement at week 52. More than half of week-28 partial responders (PASI 50-74) improved their PASI responses to PASI >/=75 at week 52. Clinicaltrials.gov Identifiers: NCT01722331, NCT01729754.

Callewaert, C., T. Nakatsuji, R. Knight, T. Kosciolek, A. Vrbanac, P. Kotol, M. Ardeleanu, T. Hultsch, E. Guttman-Yassky, R. Bissonnette, J. I. Silverberg, J. Krueger, A. Menter, N. M. H. Graham, G. Pirozzi, J. D. Hamilton and R. L. Gallo (2019). “IL-4Ralpha Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis.” J Invest Dermatol Jun 25. [Epub ahead of print].

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Dupilumab is a fully human antibody to interleukin-4 receptor alpha that improves the signs and symptoms of moderate-to-severe atopic dermatitis. To determine the effects of dupilumab on Staphylococcus aureus colonization and microbial diversity on the skin, bacterial DNA was analyzed from swabs collected from lesional and nonlesional skin in a double-blind, placebo-controlled study of 54 patients with moderate-to-severe atopic dermatitis randomized (1:1) and treated with either dupilumab (200 mg weekly) or placebo for 16 weeks. Microbial diversity and relative abundance of Staphylococcus were assessed by DNA sequencing of 16S rRNA, and absolute S. aureus abundance was measured by quantitative PCR. Before treatment, lesional skin had lower microbial diversity and higher overall abundance of S. aureus than nonlesional skin. During dupilumab treatment, microbial diversity increased and the abundance of S. aureus decreased. Pronounced changes were seen in nonlesional and lesional skin. Decreased S. aureus abundance during dupilumab treatment correlated with clinical improvement of atopic dermatitis and biomarkers of type 2 immunity. We conclude that clinical improvement of atopic dermatitis that is mediated by interleukin-4 receptor alpha inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus. ClinicalTrials.gov identifier: NCT01979016.

Noe, M. H., M. T. Wan, D. B. Shin, A. W. Armstrong, K. C. Duffin, Z. C. Chiesa Fuxench, R. E. Kalb, A. Menter, E. L. Simpson, J. Takeshita, S. K. Tyring, A. S. Van Voorhees, N. N. Mehta and J. M. Gelfand (2019). “Patient-Reported Outcomes of Adalimumab, Phototherapy, and Placebo in the Vascular Inflammation in Psoriasis Trial: A Randomized Controlled Study.” J Am Acad Dermatol Jun 1. [Epub ahead of print].

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BACKGROUND: There is limited data about the impact of narrowband ultraviolet B phototherapy on patient-reported measures of health-related quality of life (HRQoL). OBJECTIVE: To evaluate the impact of adalimumab and phototherapy on HRQoL. METHODS: We examined patient-reported outcomes (PROs) from a multicenter, randomized placebo-controlled trial (NCT01553058). Dermatology Life Quality Index (DLQI) and EQ-5D-3L were evaluated every 4 weeks. RESULTS: We enrolled 97 patients: 30.9% female, mean (SD) age 43.5(14.0) years, median (interquartile range) PASI 16.7(13.9-21.6). At week 12, patients being treated with adalimumab (OR: 2.88, 95% CI:1.02, 8.17) and phototherapy (OR: 8.83, 95% CI:2.47, 31.57) were more likely to achieve the minimal clinically important difference (MCID) in DLQI compared to placebo. There were higher odds of achieving the MCID for the EQ-5D-3L Index score when comparing phototherapy versus placebo (OR: 9.78, 95% CI:2.99, 31.95) and phototherapy versus adalimumab (OR: 4.07, 95% CI:1.42, 11.70). LIMITATIONS: small sample size, secondary analysis, generalizability CONCLUSION: Phototherapy and adalimumab both improve skin-related quality of life and overall health related quality of life compared to placebo in patients with psoriasis, however, phototherapy treated patients achieved more improvement in overall health quality of life compared to patients treated with adalimumab.