Dermatology

Fawaz, B., L. Dickson and A. Menter (2016). “Pustular psoriasis eruption with dabrafenib, a braf inhibitor.” J Dermatolog Treat Apr 14 [Epub ahead of print]

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Targeted BRAF inhibition with vemurafenib and dabrafenib has dramatically improved the survival rate in metastatic melanoma. These agents are now being tested for their efficacy against other tumors with BRAF mutations, including lung adenocarcinoma. While cutaneous adverse events are prevalent with BRAF inhibition, our patient, to our knowledge, is the first to develop a psoriatic eruption with BRAF inhibitors. We postulate that the elevation of tumor necrosis factor-alpha (TNF-alpha) and the paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway due to BRAF inhibition may be responsible for the eruption. More studies are needed to further elucidate the immunopathogenic mechanisms behind this adverse event. The response to MEK inhibitors and/or increased TNF-alpha inhibition may help support or debunk our hypothesis.

Campa, M., B. Mansouri, R. Warren and A. Menter (2016). “A review of biologic therapies targeting il-23 and il-17 for use in moderate-to-severe plaque psoriasis.” Dermatology and therapy 6(1): 1-12.

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The development of several highly effective biologic drugs in the past decade has revolutionized the treatment of moderate-to-severe plaque psoriasis. With increased understanding of the immunopathogenesis of psoriasis, the emphasis has turned toward more specific targets for psoriasis drugs. Although the complex immunological pathway of psoriasis is not yet completely understood, current models emphasize the significant importance of interleukin (IL)-23 and IL-17. Several biologic drugs targeting these cytokines are now in various stages of drug development. Drugs targeting IL-23 include BI-655066, briakinumab, guselkumab, tildrakizumab, and ustekinumab. Drugs targeting IL-17 include brodalumab, ixekizumab, and secukinumab. While many of these have shown safety and good efficacy in clinical trials of moderate-to-severe plaque psoriasis, long-term safety is still to be established.

Blome, C., A. Costanzo, E. Dauden, C. Ferrandiz, G. Girolomoni, R. Gniadecki, L. Iversen, A. Menter, K. Michaelis-Wittern, A. Morita, H. Nakagawa, K. Reich and M. Augustin (2016). “Patient-relevant needs and treatment goals in nail psoriasis.” Qual Life Res 25(5): 1179-1188.

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PURPOSE: Patient-centered health care implies that medical decisions are made jointly by physician and patient, based on patient needs. Aims were to (a) identify treatment goals for a new questionnaire on patient needs and benefits in nail psoriasis treatment; (b) analyze the importance of treatment goals in patients with nail psoriasis in general and in defined subgroups; and (c) determine the association between overall treatment goal importance and quality of life. METHODS: The study comprised the following steps: qualitative survey on needs and burdens in 120 patients; development of items by an interdisciplinary expert group; item testing in 55 patients in four countries; revision of the questionnaire and assessment in 203 patients in six countries (Germany, Denmark, Italy, Spain, USA, Japan). The percentage of patients rating the goals as ‘quite/very important’ was compared between various patient subgroups. RESULTS: Based on 692 free-text statements, 26 items were developed which were reduced to 24 items after pilot testing. Each of these treatment goals applied to the majority of patients in the multi-center study. Goal importance increased with severity of nail psoriasis, but not with age or disease duration. Manual dexterity and social interaction were of particular importance. Goal importance and quality of life were associated, but not redundant (r = 0.612, p < 0.001). CONCLUSIONS: Patients with nail psoriasis have manifold and specific treatment goals. Goal importance is a construct different from disease-specific quality of life and should be assessed separately. The new questionnaire can support goal setting in clinical practice.

Campa, M., B. Mansouri, B. Wilcox and J. R. Griffin (2016). “Radiation-induced localized bullous pemphigoid in a patient with breast carcinoma.” Dermatology online journal 22(1).

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Bullous pemphigoid (BP) is a common pemphigoid disorder, which is localized in approximately 16-29% of cases. A small subset of localized BP cases is associated with prior radiation therapy, most commonly for breast carcinoma. We present a patient with an unusual presentation of localized BP after receiving partial accelerated breast irradiation (a type of brachytherapy that has a decreased amount of radiation to the skin as compared to the more common external beam radiation therapy).

Menter, A., K. A. Papp, M. Gooderham, D. M. Pariser, M. Augustin, F. A. Kerdel, S. Fakharzadeh, K. Goyal, S. Calabro, W. Langholff, S. Chavers, D. Naessens, J. Sermon and G. G. Krueger (2016). “Drug survival of biologic therapy in a large, disease-based registry of patients with psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR).” J Eur Acad Dermatol Venereol. Mar 30. [Epub ahead of print]

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BACKGROUND: Drug survival is a marker for treatment sustainability in chronic diseases such as psoriasis. OBJECTIVE: The aim of these analyses was to assess survival of biologic treatments in the PSOriasis Longitudinal Assessment and Registry (PSOLAR). METHODS: PSOLAR is a large, prospective, international, disease-based registry of patients with psoriasis receiving (or eligible for) systemic therapy in a real-world setting. Drug survival is defined as the time from initiation to discontinuation (stop/switch) of biologic therapy on registry. The number of patients who discontinued each treatment and the duration of therapy were recorded. Using Kaplan-Meier survival curves and Cox-regression analyses [hazard ratios (HR) and 95% confidence intervals (CIs)], time to discontinuation was compared across cohorts undergoing first-, second- or third-line treatment with ustekinumab, infliximab, adalimumab or etanercept. RESULTS: As of the 2013 data cut, 12 095 patients with psoriasis were enrolled in PSOLAR. Of the 4000 patients initiating any new biologic therapy, approximately 3500 started a first-line, second-line or third-line biologic therapy during the registry. Lack of effectiveness was the most common reason for discontinuation across biologic therapies. Based on the multivariate analysis, significantly shorter times to discontinuation were observed for infliximab [HR (95%CI) = 2.73 (1.48-5.04), P = 0.0014]; adalimumab [4.16 (2.80-6.20), P < 0.0001]; and etanercept [4.91 (3.28-7.35) P < 0.0001] compared with ustekinumab [reference treatment]) for first-line biologic use; results were similar for treatment effects for second/third-line therapies. Although limited in power, analyses in patients with concurrent psoriatic arthritis confirmed by a rheumatologist reflect observations in the overall psoriasis population. CONCLUSION: Drug survival was superior for ustekinumab compared with infliximab, adalimumab and etanercept in patients with psoriasis.