Martin A. Menter M.D.

Thaçi, D., Strober, B., Gordon, K. B., Foley, P., Gooderham, M., Morita, A., Papp, K. A., Puig, L., Menter, M. A., Colombo, M. J., Elbez, Y., Kisa, R. M., Ye, J., Napoli, A. A., Wei, L., Banerjee, S., Merola, J. F. and Gottlieb, A. B. (2022). “Deucravacitinib in Moderate to Severe Psoriasis: Clinical and Quality-of-Life Outcomes in a Phase 2 Trial.” Dermatol Ther (Heidelb) 12(2): 495-510.

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INTRODUCTION: Deucravacitinib is an oral, selective tyrosine kinase 2 inhibitor that demonstrated therapeutic benefit in a Phase 2 clinical trial of adults with moderate to severe plaque psoriasis. This analysis was designed to evaluate the effect of deucravacitinib on additional clinical and quality-of-life (QoL) outcomes and assess the relationship between these outcomes in adults with psoriasis. METHODS: Post-hoc analysis of a 12-week Phase 2 trial was conducted for the three most efficacious dosage groups (3 mg twice daily, 6 mg twice daily, 12 mg once daily) and placebo. Investigator assessments for efficacy included Psoriasis Area and Severity Index (PASI), body surface area (BSA) involvement, and static Physician’s Global Assessment; QoL was assessed using the Dermatology Life Quality Index (DLQI). Treatment responses and their associations were evaluated over time. RESULTS: Deucravacitinib elicited improvement versus placebo as early as Week 4 for most efficacy measures (including changes in absolute PASI and BSA), with efficacy trends observed from Week 2 to Week 12. Improvements in QoL, assessed by achievement of a DLQI overall score of 0/1 (no effect at all on patient’s life), followed a pattern similar to deucravacitinib-related clinical outcomes over 12 weeks. Overall, patients with greater improvements in psoriasis-related clinical signs and symptoms also reported greater improvement in QoL. However, complete skin clearance was not required for achieving DLQI 0/1. CONCLUSION: Deucravacitinib treatment produced early response and similar trends in improvements across multiple efficacy assessments and QoL in moderate to severe plaque psoriasis. Deucravacitinib has the potential to become a promising new oral therapy for this condition. TRIAL REGISTRATION: ClinicalTrials.gov identifier; NCT02931838.

Reich, K., Mrowietz, U., Menter, A., Griffiths, C.E.M., Bagel, J., Strober, B., Nunez Gomez, N., Shi, R., Guerette, B. and Lebwohl, M. (2021). “Effect of baseline disease severity on achievement of treatment target with apremilast: results from a pooled analysis.” J Eur Acad Dermatol Venereol 35(12): 2409-2414.

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BACKGROUND: Treating to absolute treatment targets rather than relative measures such as Psoriasis Area and Severity Index (PASI)-75 is emerging as an important clinical concept included in psoriasis guidelines and clinical practice. Achieving treatment targets is associated with achievement of long-term outcomes. OBJECTIVE: To evaluate the relationship between psoriasis severity, disease characteristics and achievement of PASI ≤2 with apremilast in a pooled analysis of the phase 3 ESTEEM 1 and 2 (NCT01194219 and NCT01232283), phase 3b LIBERATE (NCT01690299) and phase 4 UNVEIL (NCT02425826) clinical trials. METHODS: Pooled data from patients with moderate-to-severe plaque psoriasis randomized to apremilast 30 mg BID were analysed by baseline PASI quartiles (Q1: 2.4-13.1; Q2: 13.2-15.9; Q3: 16.0-20.0; Q4: 20.1-57.8). Assessments included PASI, Dermatology Life Quality Index (DLQI), Scalp Physician’s Global Assessment (ScPGA; ScPGA ≥1) and target (worst) Nail Psoriasis Severity Index (NAPSI; NAPSI ≥1). RESULTS: Of 1062 patients, 963 had ScPGA ≥1 and 643 had NAPSI ≥1; 771 patients with baseline and Week 32 PASI assessments were included in analyses of Week 32 PASI target achievement. Rates of PASI ≤2 at Week 32 were greater in lower PASI quartiles (Q1: 43.5%; Q2: 31.2%; Q3: 26.8%; Q4: 18.4%). Most patients achieving PASI ≤2 target (83.6%) achieved DLQI ≤5 at Week 32; 59.3% of patients who did not achieve PASI ≤2 target achieved DLQI ≤5. At Week 32, mean improvements in ScPGA and NAPSI were similar with more moderate vs. more severe disease (ScPGA, range: 1.1-1.4; NAPSI, range: 1.6-2.5). In a subgroup analysis, achievement of PASI ≤2 target was higher in the lowest PASI quartile and with disease duration <5 years. CONCLUSIONS: Greater achievement of PASI ≤2 was observed in patients with more moderate vs. more severe skin disease. Apremilast may be particularly beneficial in more moderate disease early in the treatment paradigm.

Menter, A., A. S. Van Voorhees and S. Hsu (2021). “Pustular Psoriasis: A Narrative Review of Recent Developments in Pathophysiology and Therapeutic Options.” Dermatol Ther (Heidelb) Oct 9. [Epub ahead of print].

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Pustular psoriasis is an unusual form of psoriasis that frequently presents clinical challenges for dermatologists. The condition presents with pustules on an erythematous background and has two distinct subtypes: localized disease on the palms and soles, called palmoplantar pustulosis (PPP), and generalized pustular psoriasis (GPP). The involvement of the fingers, toes, and nails is defined as a separate localized variant, acrodermatitis continua of Hallopeau, and is now thought to be a subset of PPP. The rarity of pustular psoriasis frequently makes the correct diagnosis problematic. In addition, treatment is limited by a relative lack of evidence-based therapeutic options. Current management is often based on existing therapies for standard plaque psoriasis. However, there remains a need for treatments with high, sustained efficacy and a rapid onset of action in pustular psoriasis. Recent advances in understanding of the pathogenesis of pustular psoriasis have provided insights into potential therapies. Treatment of pustular psoriasis is generally determined by the extent and severity of disease, and recent years have seen an increasing use of newer agents, including biologic therapies. Current classes of biologic therapies with US Food and Drug Administration and European Medicines Agency approval for treatment of moderate-to-severe plaque psoriasis in the USA (and elsewhere) include tumor necrosis factor alpha inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab), interleukin (IL)-17 inhibitors (brodalumab, ixekizumab, secukinumab), an IL-12/23 inhibitor (ustekinumab), and IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab). Recently, specific inhibitors of the IL-36 pathway have been evaluated in GPP and PPP, including spesolimab, an IL-36 receptor inhibitor which has shown promising results in GPP. The emerging drugs for pustular psoriasis offer the possibility of rapid and effective treatment with lower toxicities than existing therapies. Further research into agents acting on the IL-36 pathway and other targeted therapies has the potential to transform the future treatment of patients with pustular psoriasis. This article reviews the clinical features of PPP and GPP, and current understanding of the genetics and immunopathology of these conditions; it also provides an update on emerging treatments.

Strober, B., D. Pariser, A. Deren-Lewis, T. J. Dickerson, M. Lebwohl and A. Menter (2021). “A Survey of Community Dermatologists Reveals the Unnecessary Impact of Trial-and-Error Behavior on the Psoriasis Biologic Treatment Paradigm.” Dermatol Ther (Heidelb) 11(5): 1851-1860.

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INTRODUCTION: In the USA, psoriasis affects approximately 3% of the population and costs more than $110 billion annually. The development of targeted biologics has revolutionized psoriasis management, but at an increasing cost. According to Joint AAD/NPF guidelines, an important need exists to identify biomarkers that can predict the appropriate biologic agent for patients. METHODS: A survey of community dermatologists was developed to address (1) significant factors influencing biologic therapy utilization in psoriasis; (2) the clinical utility of a test stratifying biologic response. RESULTS: Respondents confirmed that trial and error leads to frequent biologic switching. The survey indicated that 82% of dermatologists switch 10-30% of their patients in the first year and 98% switch intra-class for at least 50% of non-responding patients. The trial and error is due, in part, to formularies influencing the physician 77% of the time, with only 14% reporting that their first choice and the formulary alignment is greater than 75%. Compounding trial and error, 93% of the physicians report that they wait at least 12 weeks before determining non-response, in alignment with AAD/NPF guidelines. The lack of precision medicine and this trial-and-error approach result in unnecessary wasted spending and suboptimal patient outcomes. After being given an overview of Mind.Px, a dermal biomarker patch used to predict therapeutic response to a biologic class, survey participants expressed that: 93% would utilize Mind.Px results to determine first-line therapy even if this differed from initial clinical choice 100% would utilize Mind.Px if part of the prior authorization process 98% say Mind.Px would improve patient outcomes 81% reported Mind.Px would help with prior authorization process CONCLUSIONS: Surveyed dermatologists believe a test that predicts psoriasis treatment response to a class of biologic drugs would lessen trial and error, provide a tool for physicians to make more informed decisions about drug selection, improve patient outcomes, and significantly reduce wasted spending.

Lebwohl, M., Deodhar, A., Griffiths, C.E.M., Menter, M.A., Poddubnyy, D., Bao, W., Jehl, V., Marfo, K., Primatesta, P., Shete, A., Trivedi, V. and Mease, P.J. (2021). “The risk of malignancy in secukinumab-treated psoriasis, psoriatic arthritis and ankylosing spondylitis patients: analysis of up to five-year clinical trial and post-marketing surveillance data.” Br J Dermatol.

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BACKGROUND: Data on the use of biologic therapy and malignancy risk are inconsistent due to limited long-term robust studies. OBJECTIVE: To assess the malignancy risk in secukinumab-treated psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients. METHODS: This integrated safety analysis from both the secukinumab clinical trial program and post-marketing safety surveillance data included any patient receiving at least one approved dose of secukinumab with a maximum of five years follow-up. Safety analyses evaluated the rate of malignancy using exposure-adjusted incidence rates (EAIR; incidence rates/100-patient treatment-years [PTY]). Standardised incidence ratios (SIR) were reported using the Surveillance, Epidemiology, and End Results Program (SEER) database as a reference population. The crude incidence of malignancy was also reported using post-marketing surveillance data. RESULTS: Safety data from 10,685 psoriasis, 2,523 PsA and 1,311 AS secukinumab-treated patients from 49 clinical trials were included. Across indications over a five-year period, the EAIR of malignancy was 0.85/100 PTY (95% confidence intervals [CI]: 0.74, 0.98) in secukinumab-treated patients, corresponding to 204 patients/23,908 PTY. Overall, the observed vs. expected number of malignancies from secukinumab clinical trial data were comparable, as indicated by a SIR of 0.99 (95% CI: 0.82, 1.19) across indications. The estimated crude cumulative incidence reporting rate/100 PTY for malignancy was 0.27 in the post-marketing surveillance data across indications with a cumulative exposure of 285,811 PTY. CONCLUSIONS: In this large safety analysis, the risk of malignancy was low for up to five years of secukinumab treatment. These data support the long-term us of secukinumab in these indications.