Phase 2 Trial of Topical Thykamine in Adults With Mild to Moderate Atopic Dermatitis.

BACKGROUND: Atopic dermatitis is a common skin disorder for which there remains an unmet need for topical pharmacotherapies that are safe and effective. This phase 2 study assessed the efficacy and safety of 3 dosages of PUR 0110 (Thykamine; Devonian Health Group Inc.) cream (0.05%, 0.1%, and 0.25%) compared to vehicle for treatment of adults with mild to moderate atopic dermatitis. The primary efficacy endpoint was the proportion of patients with an Investigator’s Global Assessment (IGA) of clear/almost clear and with a decrease from baseline score of at least 2 grades at day 29. Key secondary efficacy endpoints included change from baseline to day 29 in IGA, percent body surface area (%BSA) affected, Eczema Area and Severity Index (EASI) score, pruritus, and quality of life. Safety outcomes included the incidence of local and systemic adverse events. The primary efficacy endpoint was met with PUR 0110 cream 0.10% compared to vehicle (30.8% vs 6.7%, respectively, P=.014). Most secondary endpoints also favored PUR 0110 cream 0.10% vs vehicle, including change from baseline to day 29 in IGA score, %BSA affected, pruritus, and patient-reported quality of life. Adverse events occurred at a similar rate in all treatment groups; most were mild to moderate in intensity and were infrequently associated with study withdrawal. PUR 0110 cream 0.10% demonstrated rapid improvement in signs and symptoms of atopic dermatitis. This observation, along with its favorable safety and tolerability profile, could make it a useful therapeutic option for the treatment of atopic dermatitis. J Drugs Dermatol. 2022;21(10):1091-1097. doi:10.36849/JDD.6729.

Effect of Roflumilast Cream vs Vehicle Cream on Chronic Plaque Psoriasis: The DERMIS-1 and DERMIS-2 Randomized Clinical Trials.

Importance: Once-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis. Objective: To evaluate the efficacy of roflumilast cream, 0.3%, applied once daily for 8 weeks in 2 trials of patients with plaque psoriasis. Design, Setting, and Participants: Two phase 3, randomized, double-blind, controlled, multicenter trials (DERMIS-1 [trial 1; n = 439] and DERMIS-2 [trial 2; n = 442]) were conducted at 40 centers (trial 1) and 39 centers (trial 2) in the US and Canada between December 9, 2019, and November 16, 2020, and between December 9, 2019, and November 23, 2020, respectively. Patients aged 2 years or older with plaque psoriasis involving 2% to 20% of body surface area were enrolled. The dates of final follow-up were November 20, 2020, and November 23, 2020, for trial 1 and trial 2, respectively. Interventions: Patients were randomized 2:1 to receive roflumilast cream, 0.3% (trial 1: n = 286; trial 2: n = 290), or vehicle cream (trial 1: n = 153; trial 2: n = 152) once daily for 8 weeks. Main Outcomes and Measures: The primary efficacy end point was Investigator Global Assessment (IGA) success (clear or almost clear status plus ≥2-grade improvement from baseline [score range, 0-4]) at week 8, analyzed using a Cochran-Mantel-Haenszel test stratified by site, baseline IGA score, and intertriginous involvement. There were 9 secondary outcomes, including intertriginous IGA success, 75% reduction in Psoriasis Area and Severity Index (PASI) score, and Worst Itch Numeric Rating Scale score of 4 or higher at baseline achieving 4-point reduction (WI-NRS success) at week 8 (scale: 0 [no itch] to 10 [worst imaginable itch]; minimum clinically important difference, 4 points). Results: Among 881 participants (mean age, 47.5 years; 320 [36.3%] female), mean IGA scores in trial 1 were 2.9 [SD, 0.52] for roflumilast and 2.9 [SD, 0.45] for vehicle and in trial 2 were 2.9 [SD, 0.48] for roflumilast and 2.9 [SD, 0.47]) for vehicle. Statistically significantly greater percentages of roflumilast-treated patients than vehicle-treated patients had IGA success at week 8 (trial 1: 42.4% vs 6.1%; difference, 39.6% [95% CI, 32.3%-46.9%]; trial 2: 37.5% vs 6.9%; difference, 28.9% [95% CI, 20.8%-36.9%]; P < .001 for both). Of 9 secondary end points, statistically significant differences favoring roflumilast vs vehicle were observed for 8 in trial 1 and 9 in trial 2, including intertriginous IGA success (71.2% vs 13.8%; difference, 66.5% [95% CI, 47.1%-85.8%] and 68.1% vs 18.5%; difference, 51.6% [95% CI, 29.3%-73.8%]; P < .001 for both), 75% reduction in PASI score (41.6% vs 7.6%; difference, 36.1% [95% CI, 28.5%-43.8%] and 39.0% vs 5.3%; difference, 32.4% [95% CI, 24.9%-39.8%]; P < .001 for both), WI-NRS success (67.5% vs 26.8%; difference, 42.6% [95% CI, 31.3%-53.8%] and 69.4% vs 35.6%; difference, 30.2% [95% CI, 18.2%-42.2%]; P < .001 for both). The incidence of treatment-emergent adverse events was 25.2% with roflumilast vs 23.5% with vehicle in trial 1 and 25.9% with roflumilast vs 18.4% with vehicle in trial 2. The incidence of serious adverse events was 0.7% with roflumilast vs 0.7% with vehicle in trial 1 and 0% with roflumilast vs 0.7% with vehicle in trial 2. Conclusions and Relevance: Among patients with chronic plaque psoriasis, treatment with roflumilast cream, 0.3%, compared with vehicle cream resulted in better clinical status at 8 weeks. Further research is needed to assess efficacy compared with other active treatments and to assess longer-term efficacy and safety. Trial Registration: ClinicalTrials.gov Identifiers: NCT04211363, NCT04211389.

An Analysis of Patient-reported Outcomes in IXORA-S: Comparing Ixekizumab and Ustekinumab over 52 Weeks in Moderate-to-severe Psoriasis.

Patient-reported outcomes are valuable for assessing new psoriasis therapies. This study investigated patient-reported outcomes in patients with moderate-to-severe plaque psoriasis treated with ixekizumab or ustekinumab, dosed according to their respective labels, for 52 weeks (IXORA-S-NCT02561806). Patient-reported outcomes investigated included patient global assessment, pruritus, skin pain, health-related quality of life, and work productivity. Ixekizumab-treated patients reported greater improvements in patient-reported outcomes sooner after treatment compared with ustekinumab-treated patients, and maintained greater improvements in patient global assessment scores (ixekizumab 0.72, ustekinumab 1.19; p < 0.001), rates of Dermatology Life Quality Index (0, 1) (ixekizumab 71.3%, ustekinumab 56.6%, p < 0.01), and 36-item Short-form Health survey physical component summary score change from baseline (ixekizumab 5.53, ustekinumab 3.28; p < 0.05) at week 52. While clinically meaningful improvements in patient-reported outcomes resulted with either treatment, ixekizumab provided more rapid improvements in patient-reported outcomes and superior outcomes for some assessments through one year of treatment, while maintaining statistically superior improvements in skin severity, as assessed by either physicians or patients.

Greater cumulative benefits from ixekizumab versus ustekinumab treatment over 52 weeks for patients with moderate-to-severe psoriasis in a randomized, double-blinded phase 3b clinical trial.

Background: Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, has shown superiority to ustekinumab (UST) and etanercept in skin clearance from randomized clinical trials in patients with moderate-to-severe psoriasis.Objective: To compare cumulative benefits of IXE versus UST over 52 weeks of treatment.Methods: Cumulative clinical benefit of IXE and UST was assessed by evaluating the area under the curve (AUC) for responders of Psoriasis Area and Severity Index (PASI), itch numeric rating scale (Itch NRS), and Dermatology Life Quality Index (DLQI) outcomes over 52 weeks using data from IXORA-S trial comparing IXE (N = 136) and UST (N = 166). Normalized cumulative benefit was calculated to obtain the percentage of the maximum AUC for each outcome measure. Missing values were imputed using non-responder imputation.Results: Significantly greater cumulative benefits were obtained for IXE compared with UST. Normalized cumulative benefit with IXE versus UST for PASI 75/90/100, Itch NRS (0), and DLQI (0,1) were 83.1% and 67.6%; 68.9% and 46.5%; 41.1% and 23.4%; 40.4% and 30.9%; and 62.2% and 46.6%, respectively. Cumulative clinical benefit ratios for IXE:UST were 1.23 for PASI 75, 1.48 for PASI 90, and 1.76 for PASI 100, indicating an increase in the cumulative clinical benefit for IXE versus UST as the clearance levels increased.Conclusions: IXE showed greater cumulative clinical benefit than UST.

Results of patch testing in patients diagnosed with oral lichen planus.

BACKGROUND: Oral lichenoid lesions (OLLs) resemble oral lichen planus (OLP) but develop secondary to various underlying causes. The role of contact allergy in precipitating and/or perpetuating OLL is well documented but remains controversial. OBJECTIVE: To help elucidate the association of contact allergy and OLL, we reviewed patch-test readings in patients diagnosed with OLP-like lesions. METHODS: We retrospectively reviewed patients diagnosed with OLP-like lesions who had patch tests performed between January 1, 2006, and December 31, 2007. RESULTS: Patch tests were performed on 24 patients with a histopathologic and/or clinical diagnosis of OLP. Of these, 16 (67%) had positive patch-test readings. At least eight (50%) of these patients had clinically relevant reactions. Ten of the 16 patients (63%) had reactions to metals. In most of these patients, troublesome areas tended to localize adjacent to metallic dental restorations. Of the nine patients (56%) who had reactions to fragrances, flavorings, gallates, and/or diallyl disulfide, the majority improved after avoiding these allergens. CONCLUSION: Our findings support the notion that contact allergy may underlie the pathogenesis of OLL and that allergen avoidance may result in amelioration of disease.

A young man with fever and skin nodules.

BACKGROUND: There are two rare variants of cutaneous T-cell lymphoma (CTCL) that primarily involve the subcutis. These include subcutaneous panniculitis-like T-cell lymphoma (SPTL) and cutaneous gamma/delta T-cell lymphoma. OBJECTIVE: This case report describes the clinical presentation, diagnosis, and treatment of a young man with probable SPTL. A review of recent literature outlining the differences between SPTL and cutaneous gamma/delta T-cell lymphoma is discussed. CONCLUSION: The differential diagnosis in patients presenting with subcutaneous nodules and constitutional symptoms should include CTCL.

Priapism as a possible acute side effect of radical radiotherapy for prostate cancer.

We report a case of a 73 year-old male diagnosed with T1 N0 M0 prostate cancer, Gleason score 7, undergoing a course of radical radiotherapy using 7600 cGY delivered in 38 fractions. Several hours after receiving his 27th fraction, he reported experiencing a painful penile erection lasting more than 6 hours. A history and several investigations were conducted to determine the etiology of this adverse event. Although several possible etiologies were considered, the two most likely possibilities were direct prostate-irradiation and/or his use of alfuzosin, a novel alpha 1-adrenergic antagonist. A literature search revealed one case of priapism secondary to radiotherapy as well as reports of priapism associated with drugs similar to alfuzosin.