Treatment of Psoriasis With Biologics and Apremilast in Patients With a History of Malignancy: A Retrospective Chart Review

Introduction: Biologics have transformed the management of moderate-to-severe psoriasis. The risk of developing a malignancy during treatment is an important consideration, and many studies have been conducted to determine the magnitude of this risk. However, there is little research on the use of biologic treatment in psoriasis patients with a history of established malignancy. Methods: We preformed a retrospective chart review of patients with psoriasis and a history of malignancy that were treated with biologics or apremilast. A list was created containing the 690 patients with psoriasis who were treated in our clinic with biologics or apremilast between January 1st, 2012 and May 31, 2018. The charts were examined, and 16 patients were found to have a history of malignancy excluding non-melanoma skin cancer. Results: Sixteen patients met criteria to be included in this review. The average time from cancer diagnosis to initiation of biologics or apremilast was 4.7 years, and 9 patients (56%) started treatment within five years. Three patients (19%) received concurrent cancer therapy during biologic treatment. None of the 16 patients had recurrence or progression of their cancer noted clinically or radiographically during biologic or apremilast treatment. Most patients had improvement of their psoriasis. Discussion: The data reviewed here show successful treatment on biologics despite concurrent malignancy, though confirmatory research is needed. J Drugs Dermatol. 2019;18(4):387-390.

Systemic Treatment of Recalcitrant Pediatric Psoriasis: A Case Series and Literature Review.

BACKGROUND/PURPOSE: No systemic drugs are approved by the Food and Drug Administration to treat pediatric psoriasis due to a lack of supporting data. The purpose of this study is to present cases demonstrating the use of systemic drugs in pediatric psoriasis. METHODS: In this case series, data were collected on patients ≤ 18 years old with moderate-to-severe psoriasis treated with systemic medications (traditional systemic drugs or biologics) from 2008 through 2014. Efficacy was measured using the validated simple measure for assessing psoriasis activity (S-MAPA), and the product of the body surface area and Physician Global Assessment. RESULTS: Twenty-seven patients aged 5 to 18 years were eligible, and 56 treatment courses were analyzed. Methotrexate (MTX) was the most frequently prescribed systemic (70%), followed by etanercept (59%). Clearance rates were highest on biologic medications (67% for etanercept and adalimumab, 33% for ustekinumab). Phototherapy, cyclosporine, and MTX were less effective in clearing psoriasis, although they were successful in improving S-MAPA ≥ 50% from baseline 100%, 67%, and 36% of the time, respectively. The most common adverse events were sunburn for patients on narrowband ultraviolet B phototherapy (14%), gastrointestinal intolerance and minor infections for patients on MTX (16% each), and minor infections for patients on etanercept (25%) and adalimumab (33%). The most common reasons for discontinuation were secondary failure (38% for etanercept, 33% for adalimumab) or lack of response (37% for MTX, 33% for cyclosporine). CONCLUSION: Although phototherapy, MTX, and cyclosporine are effective for controlling resistant pediatric psoriasis, concerns about long-term safety or inconvenience have led people to consider biologics in their place. However, there is a lack of literature on the use of biologics in pediatric psoriasis. These cases attest to the safety and efficacy of etanercept, adalimumab, and ustekinumab in pediatric psoriasis, expanding the treatment repertoire and guiding dermatologists in better managing recalcitrant pediatric psoriasis.

CCL20 and IL22 Messenger RNA Expression After Adalimumab vs Methotrexate Treatment of Psoriasis: A Randomized Clinical Trial.

IMPORTANCE: Methotrexate is a first-line systemic agent for treating of psoriasis, although its onset of effects is slower and overall it is less effective than tumor necrosis factor blockers. OBJECTIVE: To differentiate the response of psoriatic disease to adalimumab and methotrexate sodium. DESIGN, SETTING, AND PARTICIPANTS: Single-center, randomized, assessor-blind, 2-arm clinical trial of 30 patients from the outpatient dermatology center of Tufts Medical Center, enrolled from August 18, 2009, to October 11, 2011. Patients aged 18 to 85 years with chronic plaque-type psoriasis, a minimum Physician Global Assessment score of 3 (higher scores indicate more severe disease), and a psoriatic plaque of at least 2 cm were randomized in a 1:1 fashion to receive subcutaneous adalimumab or oral methotrexate. Skin biopsy specimens obtained at baseline and weeks 1, 2, 4, and 16 were given a histologic grade by blinded assessors to evaluate treatment response. Analyses were conducted from April 16, 2013, to January 5, 2015. INTERVENTIONS: A 16-week course of subcutaneous adalimumab (40 mg every 2 weeks after a loading dose) or low-dosage oral methotrexate sodium (7.5-25 mg/wk). MAIN OUTCOMES AND MEASURES: Changes in genomic, immunohistochemical, and messenger RNA (mRNA) profiles. RESULTS: Methotrexate responders experienced significant downregulation of helper T-cell-related (T(H)1, T(H)17, and T(H)22) mRNA expression compared with methotrexate nonresponders. Comparisons among adalimumab-treated patients were limited by the number of nonresponders (n = 1). Between adalimumab and methotrexate responders, we found no significant differences in gene expression at any study point or in the expression of T-cell-related mRNA at week 16. Adalimumab responders demonstrated early downregulation of chemokine (C-C motif) ligand 20 (CCL20) mRNA (mean [SE] at week 2, -1.83 [0.52], P < .001; week 16, -3.55 [0.54], P < .001) compared with late downregulation for methotrexate responders (week 2, 0.02 [0.51], P = .96; week 16, -2.96 [0.51], P < .001). Similar differences were observed with interleukin 22 (IL22) mRNA showing early downregulation for adalimumab responders (week 2, -3.17 [1.00], P < .001; week 16, -3.58 [1.00], P < .001) compared with late downregulation for methotrexate responders (week 2, -0.44 [0.68], P = .64; week 16, -5.14 [0.68], P < .001). Analysis of variance findings for key mRNA and immunohistochemical marker expression over the study course were significant only for CCL20 (P = .03) and IL22 (P = .006) mRNA comparing adalimumab and methotrexate responders. CONCLUSIONS AND RELEVANCE: Methotrexate is an immunomodulator with effects on helper T-cell signaling in psoriasis. Similar genomic and immunohistochemical response signatures and levels of mRNA downregulation at study completion among adalimumab and methotrexate responders suggest a disease-driven instead of therapeutic-driven pathway regulation. Adalimumab and methotrexate responses are differentiated by patterns of normalization of CCL20 and IL22 mRNA expression and may explain the varied onset and degree of clinical responses by each treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00932113.

A randomized, prospective, sham-controlled study of localized narrow-band UVB phototherapy in the treatment of plaque psoriasis.

IMPORTANCE: UV phototherapy remains a useful and frequently employed treatment for chronic plaque psoriasis. In those patients with plaque body surface area less than 10%, targeted treatment is the safest and most effective modality. OBJECTIVE: We aimed to evaluate the efficacy of the Levia® localized NB-UVB phototherapy machine in the treatment of patients with symmetrical psoriatic lesions. DESIGN: We performed a prospective, double-blinded, sham-treatment controlled study of this device beginning March 2012 through April 2014. SETTING: a comprehensive dermatology clinic in the northeastern United States. PARTICIPANTS: 21 subjects with chronic plaque psoriasis. INTERVENTIONS: Each patient had one lesion randomized to receive the Levia treatment and one lesion (the control) treated with visible light. Treatment was administered three times a week for twelve weeks. Target lesion score (TLS), a rating of 0-4 each of erythema, scaling, and thickness, was measured biweekly by a blinded assessor, and visual analogue scale of pruritus was recorded by subjects. MAIN OUTCOMES AND MEASURES: The primary outcome, formulated prior to study initiation, was the percentage of lesions achieving clear or almost clear TLS after 12 weeks of treatment. Secondary endpoints included changes in target lesion pruritus VAS, percentage improvement in TLS, and the percentage of subjects achieving 50% improvement in TLS (TLS-50). RESULTS: The primary endpoint, TLS of three or less, was not achieved (P=0.118), but the secondary endpoints of percentage improvement in TLS (P=0.043) and TLS-50 (P=0.0195) were significantly superior in treated compared to sham-treated lesions. Percentage improvement in pruritus VAS was not significant (P=0.0565). CONCLUSIONS AND RELEVANCE: This device was found to be efficacious, though not necessarily to the point of clearance, in the treatment of psoriasis over a 12-week period. TRIAL REGISTRATION: www.clinicaltrials.gov, identifier: NCT02107482, http://clinicaltrials.gov/show/NCT02107482

Prevalence of the metabolic syndrome in children with psoriatic disease.

Adults with psoriasis have a greater risk of developing metabolic syndrome (MetS) and cardiovascular disease (CVD), but few studies have investigated the prevalence of MetS and other risk factors for CVD in children with psoriasis. In an assessor-blinded study, 20 children ages 9-17 years with a current or previously documented history of psoriasis involving 5% or more of their body surface area or psoriatic arthritis were compared with a cohort of age- and sex-matched controls with benign nevi, warts, or acne. MetS, our primary endpoint, was defined by the presence of abnormal values in at least three of the following measures: triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), waist circumference, and blood pressure. Secondary endpoints included high-sensitivity C-reactive protein (hs-CRP), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Thirty percent (6/20) of children with psoriasis met the criteria for MetS, compared with 5% (1/20) of the control group (p < 0.05). Subjects with psoriasis had higher mean FBG (91.1 mg/dL) than the control group (82.9 mg/dL) (p = 0.01). There were no statistically significant differences in the other four components of MetS, BMI, BMI percentile, hs-CRP, TC, or LDL-C. The results of this trial demonstrate that children with psoriasis have higher rates of MetS than age- and sex-matched controls. It may therefore be important to evaluate children with psoriasis for components of MetS to prevent future CVD morbidity and mortality.

Assessor-blinded study of the metabolic syndrome and surrogate markers of increased cardiovascular risk in children with moderate-to-severe psoriasis compared with age-matched population of children with warts.

Adult patients with psoriasis have an increased prevalence of the metabolic syndrome (MetS) and cardiovascular disease (CVD) risk factors due to elevations of Tumor Necrosis Factor and other inflammatory cytokines.1,2 Recently, higher rates of hyperlipidemia, obesity, hypertension, and diabetes mellitus were seen in patients with juvenile psoriasis.3 Here, we report the interim results of an ongoing study of MetS and CVD risk factors in pediatric psoriasis patients.