Martin A. Menter M.D.

Gelfand, J. M., D. B. Shin, K. C. Duffin, A. W. Armstrong, A. Blauvelt, S. K. Tyring, A. Menter, S. Gottlieb, B. N. Lockshin, E. L. Simpson, F. Kianifard, R. P. Sarkar, E. Muscianisi, J. Steadman, M. A. Ahlman, M. P. Playford, A. A. Joshi, A. K. Dey, T. J. Werner, A. Alavi and N. N. Mehta (2020). “A Randomized Placebo Controlled Trial of Secukinumab on Aortic Vascular Inflammation in Moderate to Severe Plaque Psoriasis (VIP-S).” J Invest Dermatol Feb 20. [Epub ahead of print].

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BACKGROUND: Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has demonstrated high efficacy with a favorable safety profile in various psoriatic disease manifestations. TRIAL DESIGN AND METHODS: Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, moderate-to-severe psoriasis patients received secukinumab for 40 weeks. Vascular inflammation using FDG-PET/CT imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. RESULTS: The difference in change in aortic inflammation from baseline to Week 12 for secukinumab (N=46) versus placebo (N=45) was -0.053 (95% CI: -0.169, 0.064; P=0.37). Small increases in total cholesterol, LDL, and LDL particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At Week 52, reductions in TNF-alpha (P=0.0063) and ferritin (P=0.0354), and an increase in fetuin A (P=0.0024), were observed with secukinumab treatment compared to baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared to baseline. CONCLUSION: Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment.

Silfvast-Kaiser, A. and M. A. Menter (2020). “How can we manage the safety concerns associated with the increase in biologics for psoriasis?” Expert Opin Drug Saf Jan 31. [Epub ahead of print].

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Psoriasis is a chronic, systemic, inflammatory disease affecting 2–3% of the worldwide population. It is associated with multiple comorbidities including cardiovascular disease, metabolic syndrome, diabetes, obesity, arthritis, and negative psychosocial issues. Often, the choice of appropriate biologic therapy is driven by an individual’s comorbidities and conditions. The spectrum of biologic therapies for the treatment of moderate-to-severe plaque psoriasis (MTSPP) has expanded significantly over the past decade, exhibiting increasing efficacy and safety. Currently, eleven biologics are available for the treatment of MTSPP. These include 4 tumor necrosis factor-alpha (TNF-α) inhibitors, a single molecule targeting IL-12/IL-23 combination, 3 IL-17 agents, and 3 IL-23 agents. Each novel therapy exhibits its own benefit/risk profile and generally, less adverse effects than those of the older systemic non-biologic agents. Data suggest that most patients are likely to maintain effective and safe long-term treatment on these medications. Despite this, both patients and providers have important safety concerns . . . The field of biologic therapy continues to expand as our understanding of psoriasis and its immunopathogenesis increases. We fully expect therapies to continue becoming increasingly effective and specific. As the specificity of biologic therapies develops, biologic medications will become increasingly safe with less potential for adverse effect. Novel biologic therapies already show considerable promise in the treatment of psoriasis with clearance in up to 90% of patients. With more long-term data and newer agents, we can potentially effect improvement on the multiple systemic co-morbidities associated with psoriasis as well. Biomarker research could help clinicians individualize their approach to treating psoriasis in the future, allowing for even more optimization of treatment, safety, and efficacy in each individual patient. As the biologic armamentarium expands, the expectation is rising for clinicians to better understand the safety and efficacy of these medications. The future of biologics for psoriasis continues to be extremely bright. (Excerpts from text, n.p.; no abstract available.)

Lebwohl, M. G., C. L. Leonardi, N. N. Mehta, A. B. Gottlieb, A. M. Mendelsohn, J. Parno, S. J. Rozzo and A. Menter (2020). “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 82(2): 519-522.

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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 and reSURFACE 2. Patients with vs without MetS had higher prevalence of pre-existing cardiovascular disease and diabetes and higher median baseline weight and body mass index. Six patients (4.1%) with MetS (n = 5 tildrakizumab 100 mg; n = 1 tildrakizumab 200 mg) and 25 patients (4.5%) 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 Psoriasis 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 after tildrakizumab 100 mg and injury/procedural complications and nervous system disorders after 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. Incidence was similar in patients with and without MetS receiving tildrakizumab 100 mg and numerically higher in patients with and without MetS receiving tildrakizumab 200 mg. The 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 treatment-emergent AEs 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 cofactors. Although abdominal obesity is more highly correlated with MetS risk factors relative to body mass index, 2 the latter was used because 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 a body mass index of <30 kg/m 2 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. (Excerpts from text, p. 519-521; no abstract available; full text contains links to supplemental data.)

Hinkley, S. B., S. C. Holub and A. Menter (2020). “The Validity of Cutaneous Body Image as a Construct and as a Mediator of the Relationship Between Cutaneous Disease and Mental Health.” Dermatol Ther (Heidelb) 10(1): 203-211.

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INTRODUCTION: Cutaneous body image (CBI) is a construct encompassing how individuals perceive their hair, skin, and nails. Negative CBI has been related to negative psychological outcomes and body image concerns. The first aim of our study was to further validate CBI as a construct. Second, as individuals with dermatologic conditions are at an increased risk for anxiety and depression, the study examined CBI as a mediator of the relationships between having a skin condition and anxiety and depression. METHODS: A convenience sample of clinical participants with dermatologist-validated diagnoses of psoriasis, atopic dermatitis, or acne who were currently taking systemic medication (n = 128) were matched to a sample of comparison participants without skin conditions (n = 128) on self-reported gender, ethnicity, developmental stage, and weight status (body mass index). All participants reported on their CBI, self-esteem (global, appearance-related, and weight-related), body dissatisfaction, drive for thinness, dietary restraint, anxiety, depression, and demographic characteristics. RESULTS: Cutaneous body image was more negative in those respondents with skin conditions (regression analysis B = – 0.61, standard error 0.23, p = 0.008), demonstrating the criterion-related validity of the measure. CBI was significantly correlated with global (r = 0.39, p < 0.001) and appearance-related self-esteem (r = 0.50, p < 0.001), which establishes convergent validity. CBI was not significantly related to a drive for thinness (r = - 0.12, p = 0.06) or to dietary restraint (r = - 0.05, p = 0.39), supporting discriminant validity. CBI mediated the relationships between having a dermatologic condition and anxiety [point estimate of indirect effect 0.07, 95% confidence interval (CI) 0.02, 0.15] and depression (point estimate of indirect effect 0.04, 95% CI 0.01, 0.08). CONCLUSIONS: The measure of CBI has been further validated. Dermatologists must be aware that various dermatoses may impact patient mental health via the mechanism of negative CBI.

Grace, E., O. Goldblum, L. Renda, N. Agada, K. See, C. Leonardi and A. Menter (2020). “Injection Site Reactions in the Federal Adverse Event Reporting System (FAERS) Post-Marketing Database Vary Among Biologics Approved to Treat Moderate-To-Severe Psoriasis.” Dermatol Ther (Heidelb) 10(1): 99-106.

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INTRODUCTION: Biologics used to treat moderate-to-severe plaque psoriasis may cause injection site reactions (ISRs) characterized by erythema, edema, itch, and sometimes pain. The Federal Adverse Event Reporting System (FAERS) is a repository of spontaneous post-marketing reports of adverse events (AEs) that are reported to the US Food and Drug Administration (FDA). Our objective was to perform a pharmacovigilance analysis of FAERS reports of ISRs associated with the use of subcutaneously administered biologic products approved to treat moderate-to-severe plaque psoriasis. METHODS: The products included in our assessment were adalimumab, etanercept, ixekizumab, secukinumab, and ustekinumab. Reports from the date of US approval for each biologic as treatment for plaque psoriasis through 2 years were included using the search term “injection site.” RESULTS: The results show that the FAERS database contained reports of ISRs for all of the included biologics during the 2 years following FDA approval. The most common reports on ISRs were on pain, irritation, and erythema for adalimumab; reaction, pain, and erythema for etanercept; erythema, pain, and reaction for ixekizumab; bruising, pain, hemorrhage for secukinumab; and pain, induration, and swelling for ustekinumab. FAERS does not include data on total patient exposure; therefore, ISR rates could not be calculated. CONCLUSIONS: Specific ISRs varied among the biologic therapies assessed. The findings presented could be helpful when patients consider switching therapies due to ISRs. FUNDING: Eli Lilly and Company.