Leon Kircik

Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis

BACKGROUND Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis. METHODS In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physicians global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100% reduction in PASI score (PASI 100). RESULTS At week 12, the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P<0.001); the rates of sPGA scores of 0 or 1 were also higher with brodalumab (P<0.001). The week 12 PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab (44% vs. 22% [AMAGINE-2] and 37% vs. 19% [AMAGINE-3], P<0.001). The PASI 100 response rates with 140 mg of brodalumab were 26% in AMAGINE-2 (P=0.08 for the comparison with ustekinumab) and 27% in AMAGINE-3 (P=0.007). Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo. Mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo. Through week 52, the rates of serious infectious episodes were 1.0 (AMAGINE-2) and 1.3 (AMAGINE-3) per 100 patient-years of exposure to brodalumab. CONCLUSIONS Brodalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.).

Use of etanercept for psoriatic arthritis in the dermatology clinic: The Experience Diagnosing, Understanding Care, and Treatment with Etanercept (EDUCATE) study

Objective: To assess the efficacy and tolerability of etanercept to treat psoriatic arthritis. Materials and methods: A total of 1122 patients who had active psoriatic arthritis were enrolled in a Phase 4, non‐randomized, open‐label, single‐arm, 24‐week study. These patients had clinically stable, plaque psoriasis involving ⩾10% body surface area and joint disease (either ⩾two swollen and ⩾two tender/painful joints for ⩾3 months, or ⩾one joint with sacroiliitis or spondylitis). They received etanercept therapy 50 mg subcutaneously once weekly for 24 weeks. Results: After 24 weeks of treatment, 865 patients (77.1%; 95% CI: 74.64–79.55%) achieved a ‘mild or better’ score on the physician global assessment of psoriasis and were improved from baseline. Mean improvement in body surface area involvement was 16.9 percentage points (15.89–17.91). Patient global assessment of psoriasis, joint pain, and joint disease scores were improved by means of 2.2 (2.15–2.34), 2.7 (2.53–2.84), and 1.5 (1.39–1.55), respectively. Thirty‐five patients (3.1%) experienced at least one serious adverse event. No patient died during the study. Conclusions: These results support the effectiveness and tolerability of etanercept treatment in patients with psoriatic arthritis being treated at dermatology clinics.

A review of delivery systems in cosmetics

Physicians and patients have come to expect that our prescription topicals not only be efficacious but also minimally irritating and cosmetically pleasing. Much research and development effort are being spent to identify new vehicles to achieve these goals. Consumers are also demanding nonprescription products that give them noticeable results. The cosmeceutical industry, which accounts for multibillion dollars a year in sells, is on the forefront of the research. We reviewed the literature to identify and discuss some of those delivery systems used in consumer health products.

A randomized study to evaluate the efficacy and safety of adding topical therapy to etanercept in patients with moderate to severe plaque psoriasis

BACKGROUND Few clinical trials have evaluated the combination of topical corticosteroids plus systemic therapies for psoriasis. OBJECTIVE We sought to evaluate efficacy and safety of etanercept plus topical clobetasol propionate (CP) foam versus etanercept monotherapy for treatment of moderate to severe plaque psoriasis. METHODS Adults with Psoriasis Area and Severity Index (PASI) score greater than or equal to 10 and psoriasis-affected body surface area greater than or equal to 10% were randomized to etanercept with CP as needed to clear (2 up-to-2-week courses, weeks 11-12 and 23-24) or etanercept alone (each arm at 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks). RESULTS A total of 592 patients enrolled (295 etanercept + CP arm; 297 etanercept arm). At week 12, significant differences were observed for response of 75% improvement in PASI score (primary end point, 65.2% vs 48.3% in the etanercept + CP vs etanercept arms, respectively; P < .001), response of 90% improvement in PASI score (29.7% vs 19.4%; P = .009), percentage PASI score improvement (76.5% vs 68.2%; P < .001), static physician global assessment of clear/almost clear (63.1% vs 47.3%; P < .001), and patient satisfaction with treatment (P = .006). Response of 75% improvement in PASI score and static physician global assessment of clear/almost clear were not significantly different between arms at week 24. Patient satisfaction with treatment (P = .001) and percentage improvement in PASI score (P = .031) were also greater in the etanercept + CP arm compared with etanercept only at week 24. Comparable numbers of adverse events occurred in each arm. LIMITATIONS No placebo for CP foam was provided in the etanercept arm. CONCLUSIONS Addition of CP to etanercept yielded increased efficacy compared with etanercept alone at week 12 without an increase in treatment-related adverse events.

Pediatric Contact Dermatitis Registry Inaugural Case Data

BackgroundLittle is known about the epidemiology of allergic contact dermatitis (ACD) in US children. More widespread diagnostic confirmation through epicutaneous patch testing is needed. ObjectiveThe aim was to quantify patch test results from providers evaluating US children. MethodsThe study is a retrospective analysis of deidentified patch test results of children aged 18 years or younger, entered by participating providers in the Pediatric Contact Dermatitis Registry, during the first year of data collection (2015–2016). ResultsOne thousand one hundred forty-two cases from 34 US states, entered by 84 providers, were analyzed. Sixty-five percent of cases had one or more positive patch test (PPT), with 48% of cases having 1 or more relevant positive patch test (RPPT). The most common PPT allergens were nickel (22%), fragrance mix I (11%), cobalt (9.1%), balsam of Peru (8.4%), neomycin (7.2%), propylene glycol (6.8%), cocamidopropyl betaine (6.4%), bacitracin (6.2%), formaldehyde (5.7%), and gold (5.7%). ConclusionsThis US database provides multidisciplinary information on pediatric ACD, rates of PPT, and relevant RPPT reactions, validating the high rates of pediatric ACD previously reported in the literature. The registry database is the largest comprehensive collection of US-only pediatric patch test cases on which future research can be built. Continued collaboration between patients, health care providers, manufacturers, and policy makers is needed to decrease the most common allergens in pediatric consumer products.

Effect of tofacitinib withdrawal and re‐treatment on patient‐reported outcomes: results from a Phase 3 study in patients with moderate to severe chronic plaque psoriasis

Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. A Phase 3 withdrawal/re‐treatment study (NCT01186744; OPT Retreatment) showed tofacitinib re‐treatment was effective in patients with chronic plaque psoriasis.

An open-label, single-center pilot study to determine the antifungal activity of a new nonsteroidal cream (Promiseb Topical Cream) after 7 days of use in healthy volunteers

Topical corticosteroids are effective for the treatment of seborrheic dermatitis. The duration of treatment with mid- to high-potency formulations is limited by the well-known side effects associated with their long-term use; further, topical corticosteroids treat only the inflammation associated with the disease. This study assessed the antifungal activity of a new corticosteroid-free cream against Malassezia spp, which may be an important pathogenic factor in seborrheic dermatitis. This was a single-center, bilateral, open-label pilot study in 10 healthy volunteers. The nonsteroidal cream was applied twice daily to a designated target area on the chest for 7 days, and the number of colony-forming units of Malassezia spp taken by tape stripping after 7 days was compared with baseline. The percentage reduction from baseline to day 7 in the number of colony-forming units of Malassezia spp was 94% on the treated side versus 49% on the untreated side (P = .03). This pilot study shows the nonsteroidal topical cream has antifungal activities. Further exploration into its potential as a therapeutic alternative for seborrheic dermatitis is warranted.

Differences in psoriasis signs and symptom severity between patients with clear and almost clear skin in clinical practice.

Abstract Introduction: In psoriasis clinical trials, treatment success is often defined as achieving a static Physician Global Assessment (sPGA) score of 0 (clear) or 1 (almost clear). Patients with clear versus almost clear skin may experience psoriasis differently. This study assessed whether aggregating these patients underestimates subjective improvements associated with total skin clearance. Methods: Patients with plaque psoriasis with stable sPGA 0 or 1 currently treated with adalimumab, etanercept, infliximab, or ustekinumab reported Psoriasis Symptom Inventory (PSI) scores for seven days and Dermatology Life Quality Index (DLQI) scores on day 8. The PSI measures psoriasis signs and symptom severity; the DLQI measures the impact of skin disease on quality of life. This analysis compared PSI and DLQI outcomes between patients with sPGA 0 and 1. Results: This study assessed 230 patients: 79 sPGA 0 and 151 sPGA 1. A greater percentage with sPGA 0 than sPGA 1 achieved a total PSI score of 0 (“best”; 61% vs. 5%, p < 0.0001) and DLQI 0 (“no effect”; 79% vs. 24%, p < 0.001). Patients with sPGA 0 reported better scores than sPGA 1 on all other PSI and DLQI assessments. Conclusions: Achieving total skin clearance, compared with almost clear skin, provides clinically meaningful improvements in psoriasis.

Improvement in itch and other psoriasis symptoms with brodalumab in phase 3 randomized controlled trials

Patients with psoriasis have lesional symptoms, including itch, which can reduce quality of life. The efficacy and safety of brodalumab, an interleukin‐17 receptor A antagonist, in treating moderate‐to‐severe psoriasis have been reported in three randomized, controlled, phase 3 trials (AMAGINE‐1/‐2/‐3).

WITHDRAWN: Efficacy and safety of topical oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea: findings from the 2 phase 3, 29-day, randomized, controlled REVEAL trials

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