Efficacy and safety of topical oxymetazoline cream 1.0% for the treatment of facial erythema associated with rosacea: Findings from the second of 2 pivotal trials

Introduction: A phase 3 pivotal trial examined the efficacy and safety of oxymetazoline, a specific α1A-adrenoceptor agonist, for treatment of moderate to severe persistent facial erythema associated with rosacea. Methods: In this multicenter double-blind trial, eligible patients were randomized 1:1 to receive vehicle or oxymetazoline hydrochloride cream 1.0% (oxymetazoline) applied topically to the face once daily for 29 days. The primary efficacy outcome was the proportion of patients with ≥2-grade decrease from baseline on Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA) at 3, 6, 9, and 12 hours postdose on day 29. Safety assessments included treatment-emergent adverse events (TEAEs), inflammatory lesions, dermal tolerability, and posttreatment rebound erythema (defined as composite CEA/SSA increase of 1-grade severity from baseline). Results: A total of 445 eligible patients (mean age: 50.3 years; 78.7% females) were randomized (oxymetazoline, n = 224; vehicle, n = 221). Most patients had moderate erythema (CEA: 84.0%; SSA: 91.5%). On day 29, the proportions of patients achieving ≥2-grade composite improvement in both CEA/SSA at 3, 6, 9, and 12 hours postdose were significantly greater with oxymetazoline vs vehicle at each time point ( P ≤ .03) and overall ( P = .001). Improvements in individual CEA and SEA components were also significantly greater with oxymetazoline vs vehicle on day 29 (overall P = .011). Incidences of TEAEs were low (oxymetazoline: 25.1%; placebo: 21.3%); most were mild or moderate in severity. The most common TEAEs with oxymetazoline and vehicle, respectively, were rosacea (3.1% [related to papules and/or pustules in all 7 patients] and 0.5% [inflammatory flare of rosacea in 1 patient]), application-site pruritus (1.8%, 1.8%), application-site dermatitis (1.8%, 0.0%), and headache (1.8%, 4.1%). Discontinuations due to TEAEs were low (oxymetazoline: 2.7%; vehicle: 0.5%). No clinically meaningful between-group differences were observed for worsening of inflammatory lesions or dermal tolerability. Following treatment cessation, low proportions of patients experienced rebound erythema (oxymetazoline: 1.2%; vehicle: 0.0%). Conclusion: Topical oxymetazoline was safe and effective in the treatment of moderate to severe persistent facial erythema associated with rosacea. There was no apparent rebound effect following cessation of oxymetazoline treatment compared with that experienced following cessation of vehicle treatment

Efficacy and safety of etrasimod, a sphingosine 1-phosphate receptor modulator, in adults with moderate-to-severe atopic dermatitis (ADVISE)

BACKGROUND: Etrasimod is an oral, selective, sphingosine 1-phosphate (S1P) receptor modulator in development for immune-mediated inflammatory disorders. Efficacy and safety of orally administered S1P receptor modulation in atopic dermatitis (AD) has not yet been examined. OBJECTIVE: To assess the efficacy and safety of etrasimod monotherapy in adults with moderate-to-severe AD. METHODS: In this phase 2, randomized, double-blind, placebo-controlled trial, participants (≥18 years) with moderate-to-severe AD defined as baseline validated Investigator\u27s Global Assessment (vIGA-AD) score ≥3, Eczema Area and Severity Index (EASI) score ≥16, and body surface area involvement ≥10% were randomized 1:1:1 to once-daily oral etrasimod 1 mg, 2 mg, or placebo for 12 weeks. The primary outcome was percent change in EASI score from baseline at week 12, assessed in the Full Analysis Set (all randomized participants). Key secondary outcomes were achievement of a vIGA-AD score of 0 or 1 with a ≥2-point improvement from baseline and EASI-75 response at week 12. Safety was assessed during the double-blind period. RESULTS: 140 participants were randomized to etrasimod 2 mg (n=47), 1 mg (n=47), or placebo (n=46). At week 12, percent change in EASI score was -57.2% in the etrasimod 2-mg group vs -48.4% in the placebo group (P=.18). A significantly greater proportion of participants receiving etrasimod 2 mg achieved vIGA-AD scores of 0 or 1 with a ≥2-point improvement at week 12 vs placebo (29.8% vs 13.0%; P=.045); however, EASI-75 response was not statistically significant vs placebo. Treatment-emergent adverse events occurred in 59.6%, 40.4%, and 47.8% of participants receiving etrasimod 2 mg, 1 mg, and placebo, respectively. There were no serious AEs or deaths. CONCLUSIONS: The primary outcome was not met, though efficacy was observed for etrasimod 2 mg on several clinician- and patient-assessed measures, and both 1-mg and 2-mg doses were well tolerated, warranting further clinical investigation in AD

Impact of adenosine on mechanisms sustaining persistent atrial fibrillation: Analysis of contact electrograms and non-invasive ECGI mapping data.

BackgroundWe evaluated the effect of adenosine upon mechanisms sustaining persistent AF through analysis of contact electrograms and ECGI mapping.MethodsPersistent AF patients undergoing catheter ablation were included. ECGI maps and cycle length (CL) measurements were recorded in the left and right atrial appendages and repeated following boluses of 18 mg of intravenous adenosine. Potential drivers (PDs) were defined as focal or rotational activations completing ≥ 1.5 revolutions. Distribution of PDs was assessed using an 18 segment biatrial model.Results46 patients were enrolled. Mean age was 63.4 ± 9.8 years with 33 (72%) being male. There was no significant difference in the number of PDs recorded at baseline compared to adenosine (42.1 ± 15.2 vs 40.4 ± 13.0; p = 0.417), nor in the number of segments harbouring PDs, (13 (11-14) vs 12 (10-14); p = 0.169). There was a significantly higher percentage of PDs that were focal in the adenosine maps (36.2 ± 15.2 vs 32.2 ± 14.4; p ConclusionAdenosine led to a small but significant shortening of CL which was more marked in the right than left atrium and may relate to shortening of refractory periods rather than an increase in driver burden or distribution. Registered on Clinicaltrials.gov: NCT03394404

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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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Development of the alopecia areata scale for clinical use: Results of an academic–industry collaborative effort

The current classification for alopecia areata (AA) does not provide a consistent assessment of disease severity. To develop an AA severity scale based on expert experience. A modified Delphi process was utilized. An advisory group of 22 AA clinical experts from the United States was formed to develop this AA scale. Representatives from the pharmaceutical industry provided feedback during its development. Survey responses were used to draft severity criteria, aspiring to develop a simple scale that may be easily applied in clinical practice. A consensus vote was held to determine the final AA severity statement, with all AA experts agreeing to adopt the proposed scale. The scale is a static assessment intended to be used in clinical practice and not clinical trials. The final AA disease severity scale, anchored in the extent of hair loss, captures key features commonly used by AA experts in clinical practice. This scale will better aid clinicians in appropriately assessing severity in patients with this common disease