Berdazimer gel for molluscum contagiosum: An integrated analysis of 3 randomized controlled trials.

BACKGROUND: An out-of-office therapeutic agent indicated for molluscum contagiosum is needed. OBJECTIVE: To assess the efficacy and safety of berdazimer gel, 10.3% (a topical, antiviral, nitric oxide-releasing medication) versus vehicle. METHODS: Berdazimer gel, 10.3% or vehicle was applied once daily to all molluscum contagiosum lesions for 12 weeks in patients ≥6 months with 3-70 mollusca. Efficacy assessment: complete lesion clearance and partial clearance at week 12. Safety and tolerability assessment: adverse events through week 24 and local skin reactions through week 12. RESULTS: There were 1598 patients enrolled (n = 917 berdazimer, n = 681 vehicle). Berdazimer was superior to vehicle at week 12 in complete clearance rates, 30.0% versus 19.8% (odds ratio, 1.75; 95% CI, 1.38-2.23, P < .001). Subgroup analyses of primary efficacy showed consistent favorable efficacy for berdazimer across most subgroups, including age, sex, baseline lesion count, and disease duration. Berdazimer provided favorable outcome for partial clearance. Application-site pain (18.7% vs 4.8% in berdazimer vs vehicle) and erythema (11.7% vs 1.3%), mostly mild to moderate, were the most common local skin reactions. LIMITATIONS: Berdazimer sodium in molluscum patients with lesions (B-SIMPLE) trials enrolled only US patients; no efficacy assessments beyond week 12. CONCLUSIONS: Berdazimer gel, 10.3% showed favorable efficacy and safety across subgroups.

Vaccination recommendations for adults receiving biologics and oral therapies for psoriasis and psoriatic arthritis: Delphi consensus from the medical board of the National Psoriasis Foundation.

BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.

Berdazimer gel for molluscum contagiosum in patients with atopic dermatitis.

OBJECTIVE: Controlling molluscum contagiosum (MC) infections is critical in atopic dermatitis (AD) management. This post hoc analysis assessed the efficacy and safety of berdazimer gel, 10.3% (topical, antiviral, nitric oxide-releasing medication) versus vehicle in MC patients with or without AD. METHODS: Three Phase 3, multicenter, randomized, double-blind, vehicle-controlled, parallel-group trials (B-SIMPLE[berdazimer sodium in molluscum patients with lesions]1, -2, -4) enrolled patients 6 months and older with 3-70 mollusca. Berdazimer or vehicle was applied once daily to all MC lesions for 12 weeks. Data from three Phase 3 studies were integrated for subgroup efficacy and safety assessments using several weighted meta-analysis approaches. Patients with concurrent AD or a history of AD/eczema were categorized as AD+ subgroup (AD- when absent). Primary efficacy endpoint: complete lesion clearance at Week 12. Safety endpoints included adverse events (AEs) through Week 24 and local skin reactions through Week 12. RESULTS: Of 1598 enrolled patients, 209 (13.1%) were AD+. Baseline mean lesion counts were greater in AD+ (26.4) than AD- (19.3). Complete clearance rates were higher at Week 12 for berdazimer compared with vehicle in AD+ (n = 209; 35.0% vs. 27.4%; odds ratio [OR], 1.3; 95% CI, 0.7-2.5) and AD- (n = 1389; 29.1% vs. 18.9%; OR 1.8; 95% CI 1.4-2.4) subgroups. AEs in AD+ were application-site pain (21.6% with berdazimer vs. 11.9% with vehicle), dermatitis (12.8% vs. 2.4%), and erythema (9.6% vs. 7.1%). CONCLUSIONS: Berdazimer gel showed favorable efficacy regardless of AD status. Berdazimer-induced erythema may be indistinguishable from AD symptoms or with inflammatory response upon resolution of molluscum.

A novel, fixed-dose calcipotriol and betamethasone dipropionate cream for the topical treatment of plaque psoriasis: Direct and indirect evidence from phase 3 trials discussed at the 30th EADV Congress 2021.

Four posters about the novel, fixed-dose calcipotriol and betamethasone dipropionate cream (CAL/BDP cream) based on Poly-Aphron Dispersion (PAD) Technology were presented at the 30th European Academy of Dermatology and Venereology (EADV) Congress 2021 and are summarized here. CAL/BDP cream was compared in two randomized, phase 3 trials to vehicle and active comparator (CAL/BDP gel/topical suspension [TS]) in adults with plaque psoriasis (NCT03802344 and NCT03308799). Pooled data from both trials demonstrated significant greater efficacy in favour of CAL/BDP cream for all efficacy endpoints, including PGA treatment success, mPASI, and mPASI75 compared to CAL/BDP gel/TS. CAL/BDP cream was well tolerated and comparable to CAL/BDP gel/TS with no adverse drug reactions with a frequency >1%. In the NCT03308799 study, CAL/BDP cream demonstrated a substantial improvement in the proportion of participants achieving a minimum 4-point improvement on the peak pruritus numeric rating scale (NRS) score compared with vehicle at Weeks 1, 4 and 8. CAL/BDP cream also improved quality of life (QoL), as assessed through the Dermatology Life Quality Index (DLQI), and the EQ-VAS at Week 8 compared with active comparator. Treatment convenience of CAL/BDP cream, as measured by the Psoriasis Treatment Convenience Scale, was superior to CAL/BDP gel/TS at all studied timepoints, including questions addressing formulation's greasiness and overall treatment satisfaction. Finally, an indirect comparison following the Bucher's method of adjusted indirect comparison and the difference-in-differences method was conducted to compare CAL/BDP cream and CAL/BDP foam, as both therapies have been compared to CAL/BDP gel/TS. Indirect evidence showed that treatment with CAL/BDP cream was associated with a trend for greater QoL improvement than CAL/BDP foam when DLQI improvement was assessed at the recommended treatment duration of 8 weeks for CAL/BDP cream and 4 weeks for CAL/BDP foam. CAL/BDP cream was statistically superior versus CAL/BDP foam in four out of five treatment satisfaction domains.

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.

Prior Botulinum Toxin Treatment Does Not Impact Efficacy or Safety in Clinical Trials: Analysis of DaxibotulinumtoxinA for Injection in the SAKURA Program.

BACKGROUND: Pivotal studies of approved botulinum toxin type A (BoNTA) formulations for treatment of glabellar lines have mostly included treatment-naive participants, and the impact of prior BoNTA treatment on efficacy and safety is not well documented. OBJECTIVE: To evaluate whether prior BoNTA treatment affects efficacy, duration of response, and tolerability for treatment of glabellar lines. METHODS: Adults with moderate or severe glabellar lines treated with DaxibotulinumtoxinA for Injection (DAXI) or placebo from the randomized, double-blind SAKURA 1/2 trials and the open-label SAKURA 3 safety study were analyzed by prior BoNTA treatment status. Efficacy was evaluated using investigator and participant assessments. RESULTS: In this analysis, 609 participants (52.2% BoNTA-experienced) from the SAKURA 1/2 trials and 2,380 (38.0% BoNTA-experienced) from the SAKURA 3 study were evaluated. Proportion of participants with none or mild glabellar lines and duration of response were similar between the BoNTA-naive and BoNTA-experienced cohorts in both the DAXI and placebo groups. The incidence of adverse events was also comparable regardless of prior BoNTA treatment status. CONCLUSION: Efficacy and tolerability were similar with DAXI and placebo regardless of prior BoNTA treatment. Assuming an appropriate washout is observed, future BoNTA trials should enroll both treatment-experienced and treatment-naive participants to reflect clinical practice.

DaxibotulinumtoxinA for Injection for the Treatment of Glabellar Lines: Efficacy Results From SAKURA 3, a Large, Open-Label, Phase 3 Safety Study.

BACKGROUND: DaxibotulinumtoxinA for Injection (DAXI) is botulinum toxin Type A formulated with a novel peptide excipient. Two pivotal, single-treatment, placebo-controlled trials demonstrated efficacy and safety for moderate or severe glabellar lines. OBJECTIVE: To further evaluate DAXI in a large, open-label, repeat-treatment study. METHODS: Subjects (n = 2,691) were enrolled from the preceding pivotal trials or de novo and received 40U DAXI. Those who received repeat treatments could be retreated when they returned to baseline on the Investigator Global Assessment-Frown Wrinkle Severity (IGA-FWS) and Patient FWS (PFWS) scales at/after 12 weeks and up to 36 weeks after treatment. RESULTS: High (>96%) response rates (none or mild severity) on the IGA-FWS scale were seen after each of the 3 treatments, with peak response between Weeks 2 to 4. At Week 24, ≥32% had a response of none or mild severity. Peak response rates of ≥92% were observed at Weeks 2 to 4 on the PFWS scale. The median duration for return to moderate or severe severity was 24 weeks. The safety profile was favorable and consistent with previous trials. CONCLUSION: DaxibotulinumtoxinA for Injection efficacy was highly consistent across treatment cycles. These results confirm the previously observed efficacy rates and duration of response.

Tazarotene 0.045% Lotion for Moderate-to-Severe Acne Patients: Pooled Phase 3 Analysis by Age and Sex.

BACKGROUND: Two identical phase 3 trials (NCT03168321 and NCT03168334) and pooled post hoc analyses have established efficacy and safety of a polymeric tazarotene 0.045% lotion formulation in patients with moderate-to-severe acne. Presented here are post hoc analyses that further examine efficacy and safety of tazarotene 0.045% lotion by age and sex. METHODS: Patients aged ≥ 9 years with moderate-to-severe acne (score 3 or 4 on the Evaluator's Global Severity Score [EGSS]) were equally randomized to once-daily tazarotene 0.045% lotion or vehicle lotion for 12 weeks. Efficacy outcomes included inflammatory/noninflammatory lesion counts and treatment success (proportion of participants achieving ≥ 2-grade reduction from baseline in EGSS and score of 0 [clear] or 1 [almost clear]). Adolescent and adult females (n=1,013) and males (n=529) were subdivided into 3 age groups: 13­19, 20­29, and ≥30 years. RESULTS: At week 12, large least-squares mean percent reductions in inflammatory and noninflammatory lesions were observed across all 3 tazarotene-treated age groups in males and females (range, -50.2% to -64.8%). Treatment success rates ranged from 23.6% to 38.4%. Across all efficacy assessments, significant differences between tazarotene and vehicle (P<0.05) were generally observed in the younger male and female participants (13­19 and 20­29). No notable age-related patterns were found for safety outcomes, though tazarotene-treated males of all age groups reported fewer adverse events than females. CONCLUSIONS: Tazarotene 0.045% lotion is efficacious and well tolerated in female and male adolescents and adults with moderate-to-severe acne. J Drugs Dermatol. 2021;20(6):608-615. doi:10.36849/JDD.6070.

A Phase 3, Randomized Trial Demonstrating the Improved Efficacy and Patient Acceptability of Fixed Dose Calcipotriene and Betamethasone Dipropionate Cream.

BACKGROUND: The fixed dose combination of calcipotriene and betamethasone dipropionate (CAL/BDP) is a well-established, efficacious, and safe topical treatment of psoriasis. METHOD: A Phase 3, multicenter, randomized, investigator-blind, active, and vehicle-controlled trial enrolling 796 patients with moderate to severe psoriasis according to the Physician Global Assessment (PGA) scale. Products were applied once daily for 8 weeks. RESULTS: The proportion of patients achieving PGA treatment success after 8 weeks was statistically significantly greater for CAL/BDP cream (37.4%) compared to CAL/BDP TS (22.8%, P<0.0001), and vehicle (3.7%, P<0.0001). A similar statistically significant difference in favor of CAL/BDP cream at week 8 was demonstrated for the percentage change in mPASI from baseline and the proportion of patients obtaining mPASI75. Patient reported treatment convenience for CAL/BDP cream was rated superior to CAL/BDP TS. Safety assessments during the trial demonstrated that CAL/BDP cream was well-tolerated with no adverse reactions with a frequency greater than 1%. CONCLUSION: CAL/BDP cream is a novel topical treatment of psoriasis, which in a single product, offers a unique combination of high efficacy combined with favorable safety and excellent treatment convenience. For these reasons, CAL/BDP cream offers a distinctive advantage for the topical treatment of plaque psoriasis. ClinicalTrials.gov: NCT03308799J Drugs Dermatol. 20(4):420-425. doi:10.36849/JDD.5653.

Improvements in Submental Contour up to 3 Years After ATX-101: Efficacy and Safety Follow-Up of the Phase 3 REFINE Trials.

BACKGROUND: ATX-101 (deoxycholic acid) significantly reduced submental fat (SMF) severity in two 24-week Phase 3 studies (REFINE-1 and REFINE-2). OBJECTIVES: The aim of this study was to evaluate the durability of effect and long-term safety of ATX-101. METHODS: REFINE study patients who maintained ≥1-grade improvement on the Clinician-Reported SMF Rating Scale (CR-1 responders) 12 weeks after their last REFINE treatment were eligible for enrollment in this multicenter, double-blind, nontreatment, long-term, follow-up study (NCT02163902). The primary endpoint was CR-1 response at Years 1, 2, and 3. Patient-reported satisfaction, psychological impact, and adverse events were monitored. RESULTS: In total, 224 patients (ATX-101, n = 113; placebo, n = 111) were enrolled. Maintenance of CR-1 response was significantly better in the ATX-101 group than in the placebo group at Year 1 (86.4% vs 56.8%; P < 0.001), Year 2 (90.6% vs 73.8%; P = 0.014), and Year 3 (82.4% vs 65.0%; P = 0.03). Most (74%) ATX-101‒treated patients satisfied at 12 weeks remained satisfied at Year 3. Significant reductions from baseline in psychological impact scores were sustained through Year 3 (P < 0.001). No new treatment-related adverse events were reported. CONCLUSIONS: Improvements in submental contour achieved with ATX-101 are maintained for 3 years in most patients. No new safety signals emerged.

Comparison of the Safety and Efficacy of Tumor Necrosis Factor Inhibitors and Interleukin-17 Inhibitors in Patients With Psoriasis

Psoriasis (PsO) is a common, systemic, chronic inflammatory disease characterized by key clinical symptoms, including itching, pain, and scaling, and is associated with substantial physical, psychosocial, and economic health burdens. Currently, there is no cure for PsO; however, the introduction of biologic therapies has revolutionized the clinical management of patients with PsO by expanding treatment options to include multiple therapies with different mechanisms of action targeting cytokines, including tumor necrosis factor inhibitors (TNFis), interleukin (IL)-17A inhibitors, an IL-12/23 inhibitor, and IL-23 inhibitors. TNFis are historically considered the first-line biologic treatment and the first-generation biologics; however, increased understanding of TNF-α and IL-17 synergistic functions have recently led to evidence that specifically targeting IL-17 may be more likely to improve disease activity than a more general, nonspecific therapy target, such as TNF-α. This review highlights currently available evidence and demonstrates the differences between TNFis and IL-17A inhibitors in patients with PsO with regard to efficacy and safety.

Efficacy of a Once-Daily Fixed Combination Halobetasol (0.01%) and Tazarotene (0.045%) Lotion in the Treatment of Localized Moderate-to-Severe Plaque Psoriasis

Recently, clinical data on 8 weeks' once-daily treatment of localized moderate-to-severe psoriasis with a novel fixed combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion were published.1,2 HP/TAZ lotion was significantly more effective than individual active ingredients or vehicle, based on improvements in Investigator's Global Assessment (IGA), body surface area (BSA) involvement, and signs and symptoms of psoriasis (erythema, plaque elevation, and scaling) at the target lesion as well as a synergistic benefit over individual active ingredients, and good tolerability.

Efficacy of Topical Botanical Treatment of Children With Mild to Moderate Atopic Dermatitis

Objective: The study was conducted to determine the efficacy of the botanical combination incorporated in Kamedis Eczema Therapy Cream (the test product) for children with mild to moderate atopic dermatitis. Design: The study was designed as an interventional, multi-center, double-blind, randomized, controlled study. Setting: Children subjects were a sub-population of the 108 combined population of adults and children evenly randomly divided into three treatment groups: test product, vehicle, and comparator. The vehicle used was the identical test product without the botanical combination while the comparator was a leading OTC brand in the US market. All three groups used the same Kamedis body wash followed by one of the three randomized treatment creams for the affected areas. Participants: Thirty-nine (39) children subjects with uncomplicated, stable, mild to moderate atopic dermatitis were recruited and qualified for the study, 24 female and 15 male, ages varying between 3 and 18. Measurements: Investigators assessed the severity of each subject using the Investigator Global Assessment (IGA), affected Body Surface Area (BSA) extent evaluated parameters at each of the visit days 0, 7, 14, and 28. Subjective symptoms of pruritus and insomnia were evaluated by the patient or their legal guardian. The SCORAD and EASI indexes were calculated based on the collected parameters. Results: The test product demonstrated an improvement in all evaluated and calculated clinical parameters over the vehicle at the end of the treatment duration, proving the validation that the test product is much more effective and beneficial than the vehicle. The test product reached 40% of 'clear' IGA subjects out of the enrolled subjects and 60% out of the 'clear' and 'almost clear' IGA subjects comparing to 8% and 38%, respectively, with the vehicle, presenting a clear advantage over the vehicle. The BSA improvement comparison analysis of the test product over the vehicle yielded P value of less than 0.05, which is statistically significant. The SCORAD and EASI indexes also showed an advantage of the test product versus the vehicle at week 4. Conclusion: The study results validate that the botanical combination is the key factor for the efficacy and improvement of the AD symptoms within this population of children. J Drugs Dermatol. 2019;18(10):1038-1045.

A Phase 2, Multicenter, Double-Blind, Randomized, Vehicle-Controlled Clinical Study to Compare the Safety and Efficacy of a Novel Tazarotene 0.045% Lotion and Tazarotene 0.1% Cream in the Treatment of Moderate-to-Severe Acne Vulgaris

Background: Tazarotene has been extensively studied in clinical trials and is widely used to treat acne vulgaris (acne). Irritation potential has limited its use. Objective: To compare efficacy, safety, and tolerability of a novel formulation tazarotene 0.045% lotion based on polymeric emulsion technology, and tazarotene 0.1% cream in patients with moderate-to-severe acne. Methods: A total of 210 patients, 12 years and older were randomized to receive tazarotene 0.045% lotion, tazarotene 0.1% cream, or respective vehicle in double-blind, randomized, vehicle-controlled, 12-week study evaluating safety and efficacy (inflammatory and noninflammatory lesion counts and using Evaluator Global Severity Scores [EGSS]). In addition, patients completed a patient satisfaction survey (PSS), and acne-specific quality of life (QoL) questionnaire. Safety and cutaneous tolerability were assessed throughout. Results: A novel tazarotene 0.045% lotion demonstrated statistically significant superiority to vehicle in reducing inflammatory and noninflammatory lesion counts (P=.006 and P<.001) and clearly more effective in treatment success at week 12. In addition, at less than half the concentration, tazarotene 0.045% lotion was numerically more effective than tazarotene 0.1% cream. Mean percent reductions in inflammatory and noninflammatory lesions were 63.8% and 56.9%, compared with 60.0% and 54.1% with tazarotene 0.1% cream at week 12. Treatment success assessed by the investigator or patients' self-assessment was also numerically greater with tazarotene 0.045% lotion. There were no significant differences in patient satisfaction or QoL between the two active treatments. Both were well-tolerated, however, there were more treatment-related adverse events with tazarotene 0.1% cream (5.6% versus 2.9%); most common being application site pain. Limitations: This study was primarily designed to direct the phase 3 program and some of the results are post hoc analyses. Conclusions: A novel tazarotene 0.045% lotion provides statistically significant greater efficacy than vehicle in terms of lesion reduction, and numerically better treatment success than tazarotene 0.1% cream; with a highly favorable safety and tolerability profile in moderate-to-severe acne patients. J Drugs Dermatol. 2019;18(6):542-548.

Validation of Botanical Treatment Efficiency for Adults and Children Suffering from Mild to Moderate Atopic Dermatitis

Objective: The study was conducted to determine the efficiency of the botanicals combination incorporated in the Kamedis Eczema Therapy Cream (the tested product) for adults and children suffering from mild to moderate Atopic Dermatitis. Design: The study designed as an interventional, multi-center, double-blind, randomized, controlled study. Setting: Subjects were evenly randomly divided into three treatment groups: tested product, vehicle, and comparator. The vehicle used was the identical tested product without the botanical combination while the comparator was a leading OTC brand in the US market. All three above groups used a similar Kamedis wash for the body and face following by one of the three randomized treatment creams for the affected areas on the face and body. Participants: One hundred and eight (108) subjects with uncomplicated, stable, mild to moderate atopic dermatitis recruited and qualified for the study; 71 females and 37 males, age 3 to 73. Measurements: The investigator assessed the severity of each subject using the Investigator Global Assessment (IGA) and affected body surface area (BSA) at each of the visit days 0, 7, 14, and 28. Results: The tested product demonstrated an improvement in IGA and BSA over the vehicle at every visit across treatment time, proving the validation that the botanical product is much more effective and beneficial than the same product without the botanicals. The tested product as well as the comparator reached exactly the same percentage, 34%, of 'clear' IGA subjects of the enrolled subjects, presenting advantage over the vehicle. The BSA improvement comparison analysis of the tested product over the vehicle yielded statistically significant P value of 0.0369. Conclusion: The study results approve and validate that the botanical combination is the key factor for the efficacy and improvement of the AD symptoms within this study population. J Drugs Dermatol. 2019;18(6):557-561.

Halobetasol 0.01%/Tazarotene 0.045% Lotion in the Treatment of Moderate-to-Severe Plaque Psoriasis: Maintenance of Therapeutic Effect After Cessation of Therapy.

BACKGROUND: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Topical corticosteroids (TCS) are the mainstay of treatment. Long-term safety remains a concern, limiting use, and posttreatment flare is common. Tazarotene has also been shown to be effective in psoriasis, with efficacy maintained several weeks posttreatment. Fixed combination therapy with TCS and tazarotene may improve psoriasis signs and minimize posttreatment flare or rebound. OBJECTIVE: To investigate the maintenance of effect posttreatment with a once-daily application of halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in comparison with its active ingredients and vehicle in patients with moderate-to-severe plaque psoriasis. METHODS: Multicenter, randomized, double-blind, vehicle-controlled Phase 2 study in moderate or severe psoriasis (N=212). Patients randomized (2:2:2:1 ratio) to receive HP/TAZ, individual active ingredients, or vehicle, once-daily for 8 weeks with a 4-week posttreatment follow-up. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline in the IGA score, and 'clear' or 'almost clear'), and impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion. RESULTS: At the end of the 4-week posttreatment period, 38.2% of patients who had been treated with HP/TAZ were treatment successes; compared with 21.0%, 12.8% and 6.9% of patients who had been treated with HP (P=0.042), TAZ (P=0.004), or vehicle (P=0.002). HP/TAZ lotion was also superior in maintaining reductions in psoriasis signs of erythema, plaque elevation, and scaling at the target lesion. At the end of the 4-week posttreatment period, 49.1%, 54.5%, and 54.5% of patients, respectively, were treatment successes: compared with 38.7% (P=0.26), 48.4% (P=0.51), and 48.4% (P=0.51) of patients who had been treated with HP; 29.8% (P=0.049), 31.9% (P=0.022), and 23.4% (P=0.001) who had been treated with TAZ; and 13.8% (P=0.002), 20.7% (P=0.003), and 20.7% (P=0.003) who had been treated with vehicle. Side effects were minimal and tended to resolve during the posttreatment period. CONCLUSIONS: In conclusion, HP 0.01%/TAZ 0.045% lotion provides synergistic efficacy following 8 weeks' therapy that is sustained after a 4-week posttreatment period. J Drugs Dermatol. 2018;17(7):723-726.

Safety and Efficacy of a Once-Daily Halobetasol Propionate 0.01% Lotion in the Treatment of Moderate-to-Severe Plaque Psoriasis: Results of Two Phase 3 Randomized Controlled Trials.

BACKGROUND: Topical corticosteroids (TCS) are the mainstay of psoriasis treatment; long-term safety concerns limiting consecutive use of potent TCS to 2-4 weeks. OBJECTIVE: Investigate safety and efficacy of halobetasol propionate 0.01% lotion in moderate-to-severe plaque psoriasis. METHODS: Two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies (N=430). Subjects randomized (2:1) to halobetasol propionate 0.01% lotion or vehicle once-daily for 8 weeks, 4-week posttreatment follow-up. Primary efficacy assessment: treatment success (at least a 2-grade improvement from baseline in Investigator Global Assessment [IGA] score and 'clear' or 'almost clear') at week 8. Safety and treatment emergent adverse events (AEs) evaluated throughout. RESULTS: Halobetasol propionate 0.01% lotion demonstrated statistically significant superiority over vehicle as early as week 2. By week 8, 36.5% (Study 1) and 38.4% (Study 2) of subjects were treatment successes compared with 8.1% and 12.0% on vehicle (P less than 0.001). Halobetasol propionate 0.01% lotion was also superior in reducing psoriasis signs and symptoms, body surface area (BSA), and improving quality of life. Halobetasol propionate 0.01% lotion was well-tolerated with no treatment-related AEs greater than 1%. LIMITATIONS: Study did not include subjects with BSA greater than 12. CONCLUSIONS: Halobetasol propionate 0.01% lotion was associated with significant reductions in the severity of the clinical signs of psoriasis, without the safety concerns of a longer treatment course. J Drugs Dermatol. 2018;17(10):1062-1069.

Once-Daily Oral Sarecycline 1.5 mg/kg/day Is Effective for Moderate to Severe Acne Vulgaris: Results from Two Identically Designed, Phase 3, Randomized, Double-Blind Clinical Trials.

BACKGROUND: Side effects may limit the use of current tetracycline-class antibiotics for acne. OBJECTIVE: Evaluate the efficacy and safety of once-daily sarecycline, a novel, narrow-spectrum tetracycline-class antibiotic, in moderate to severe acne. METHODS: Patients 9-45 years with moderate to severe facial acne (Investigator's Global Assessment [IGA] score ≥ 3, 20-50 inflammatory and ≤ 100 noninflammatory lesions, and ≤ 2 nodules) were randomized 1:1 to sarecycline 1.5 mg/kg/day or placebo for 12 weeks in identically designed phase 3 studies (SC1401 and SC1402). RESULTS: In SC1401 (sarecycline n=483, placebo n=485) and SC1402 (sarecycline n=519, placebo n=515), at week 12, IGA success (≥ 2-grade improvement and score 0 [clear] or 1 [almost clear]) rates were 21.9% and 22.6% (sarecycline), respectively, versus 10.5% and 15.3% (placebo; P less than 0.0001 and P equals 0.0038). Onset of efficacy in inflammatory lesions occurred by the first visit (week 3), with mean percentage reduction in inflammatory lesions at week 12 in SC1401 and SC1402 of -51.8% and -49.9% (sarecycline), respectively, versus -35.1% and -35.4% (placebo; P less than 0.0001). Onset of efficacy for absolute reduction of noninflammatory lesion count occurred at week 6 in SC1401 (P less than 0.05) and week 9 in SC1402 (P less than 0.01). In SC1401, the most common TEAEs (in ≥ 2% of either sarecycline or placebo group) were nausea (4.6% [sarecycline]; 2.5% [placebo]), nasopharyngitis (3.1%; 1.7%), headache (2.7%; 2.7%), and vomiting (2.1%; 1.4%) and, in SC1402, nasopharyngitis (2.5%; 2.9%) and headache (2.9%; 4.9%). Most were not considered treatment-related. Vestibular (dizziness, tinnitus, vertigo) and phototoxic (sunburn, photosensitivity) TEAEs both occurred in ≤ 1% of sarecycline patients. Gastrointestinal TEAE rates for sarecycline were low. Among females, vulvovaginal candidiasis (SC1401: 1.1% [sarecycline] and 0 [placebo]; SC1402: 0.3% and 0) and mycotic infection (0.7% and 0; 1.0% and 0) rates were low. CONCLUSION: The narrow-spectrum antibiotic sarecycline was safe, well tolerated, and effective for moderate to severe acne, with low rates of side effects common with tetracycline antibiotics. J Drugs Dermatol. 2018;17(9):987-996.