Influence of Season on Efficacy and Tolerability of Tazarotene 0.045% Lotion for the Treatment of Acne.

Objective: The condition of the skin can vary due to weather fluctuations. Therefore, this post-hoc analysis evaluated efficacy and safety of tazarotene 0.045% lotion in warmer versus colder months. Methods: In two Phase III, double-blind, 12-week studies, participants aged nine years or older with moderate-to-severe acne were randomized 1:1 to once-daily tazarotene or vehicle lotion. The pooled population (N=1,614) was stratified by randomization date (warmer=May to September; colder=October to April). Evaluations included inflammatory/noninflammatory lesion counts, treatment success, adverse events, and safety/tolerability. Results: Tazarotene 0.045% lotion was similarly efficacious over colder and warmer months. Compared with vehicle, tazarotene demonstrated significantly greater least-squares mean absolute reductions from baseline to Week 12 in inflammatory (colder/warmer tazarotene vs. vehicle: -16.6/-15.8 vs. -13.2/-12.9) and noninflammatory lesions (-23.2/-22.6 vs. -17.5/-15.1); treatment success rates were also significantly higher (30.1/30.8% vs. 18.2/17.6%) (P<0.001, all). No strong seasonal trends in safety were observed, though tazarotene led to slightly more discontinuations (3.4% vs. 1.9%) and related adverse events (12.0% vs. 10.3%) in colder versus warmer months. Transient increases in scaling, erythema, and itching at Weeks 2 to 8 of tazarotene treatment were slightly higher in colder versus warmer months but returned to baseline/improved by Week 12. Limitations: Geographical variation across study sites can lead to varying temperatures and humidity within the same months. Conclusion: Tazarotene 0.045% lotion was efficacious and well tolerated for acne treatment, regardless of season. Year-round tolerability of tazarotene 0.045% lotion may be due to its lower tazarotene concentration and polymeric emulsion technology, which simultaneously delivers moisturizers/humectants/emollients to skin.

Improvements in acne and skin oiliness with tazarotene 0.045% lotion in patients with oily skin.

BACKGROUND: Excessive sebum production is a factor in acne development. Tazarotene 0.045% lotion has demonstrated reductions in acne lesions and acne-induced sequelae. OBJECTIVE: Evaluate efficacy, changes in skin oiliness, and safety with tazarotene 0.045% lotion in participants with moderate-to-severe acne and oily skin. METHODS: In two phase 3, double-blind, 12-week studies (NCT03168321; NCT03168334), participants aged ≥ 9 years with moderate-to-severe acne were randomized 1:1 to once-daily tazarotene 0.045% lotion or vehicle lotion (N = 1614). This pooled, post hoc analysis included only participants self-categorized with oily skin at baseline on the Acne-Specific Quality of Life questionnaire item 19 (scores: 0 [extremely oily] to 6 [not at all oily]). Inflammatory/noninflammatory lesion counts, treatment success, skin oiliness, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability were evaluated. RESULTS: In all participants with oily skin (n = 793), tazarotene provided greater reductions in inflammatory/noninflammatory lesions (p < 0.001, both) and greater treatment success rates versus vehicle (p < 0.01) at week 12. Over two-thirds of polymeric lotion-treated participants had subjective skin oiliness reductions by week 12, with around a third reporting 'low/not' oily skin. Tazarotene TEAE rates were similar to the overall population. CONCLUSIONS: Once-daily treatment with tazarotene 0.045% polymeric emulsion lotion may help improve patient-perceived skin oiliness in those with moderate-to-severe acne.

Efficacy and tolerability of three topical acne treatments by body mass index: post hoc analysis including overweight and obese patients.

BACKGROUND: Acne prevalence may be higher in overweight/obese individuals, potentially due to hormonal, inflammatory, and/or dietary factors. However, the effects of body mass index (BMI) on topical acne treatments are largely unknown. METHODS: Post hoc analyses of changes in inflammatory/noninflammatory lesions and treatment success were conducted using phase 3 data: clindamycin phosphate/benzoyl peroxide (CP/BPO) 1.2%/3.75% gel (NCT01701024); tretinoin 0.05% lotion (NCT02965456 and NCT02932306; pooled); and tazarotene 0.045% lotion (NCT03168321 and NCT03168334; pooled). Data were analyzed by BMI subgroups: <25kg/m2 (underweight-to-normal), 25-<30kg/m2 (overweight), and ≥30kg/m2 (obese). RESULTS: Among participants analyzed (CP/BPO = 495; tretinoin = 1,636; tazarotene = 1,612), ∼20-25% were overweight and 15-20% were obese. At week 12, mean percent changes from baseline in inflammatory lesions were: CP/BPO (overweight: -63.2%, obese: -56.0%); tretinoin (-57.6%, -53.1%); tazarotene (-59.9%, -56.8%). Mean changes in noninflammatory lesions were: CP/BPO (-54.2%, -50.8%); tretinoin (-51.6%, -44.9%); tazarotene (-56.7%, -54.6%). Treatment success rates with active treatment ranged from 16.2% to 33.5% across BMI groups. CONCLUSIONS: CP/BPO 1.2%/3.75% gel, tretinoin 0.05% lotion, and tazarotene 0.045% lotion were all effective in reducing acne lesions by ≥45% in overweight/obese patients with moderate-to-severe acne, comparable to the underweight-to-normal group. Efficacy of these topical acne treatments is not greatly impacted by BMI and may be affected more by the formulation.

Effects of Topical Retinoids on Acne and Post-inflammatory Hyperpigmentation in Patients with Skin of Color: A Clinical Review and Implications for Practice.

Acne is a common cause for post-inflammatory hyperpigmentation (PIH), particularly in patients with skin of color (SOC), and PIH is often more distressing to patients than the acne itself. Topical retinoids are approved for the treatment of acne and for pigmentation disorders such as melasma or mottled hyperpigmentation associated with photodamage; moreover, they have been shown to reduce hyperpigmentation in patients with SOC. Therefore, treatment with topical retinoids should be started as early as possible unless contraindicated. Use of novel formulations or application of commonly recommended moisturizers may help reduce irritation. Combining retinoids with other topical agents and procedures such as superficial chemical peels can help to improve hyperpigmentation. Primary acne lesions are likely to improve weeks before PIH resolves and helping patients manage their expectations may reduce frustration. Providing clinicians and researchers with more education about the presentation and management of dermatologic conditions in patients with SOC is also recommended.

50 Years of Topical Retinoids for Acne: Evolution of Treatment.

Since the US Food and Drug Administration (FDA) approved tretinoin in 1971, retinoids alone or combined with other agents have become the mainstay of acne treatment. Retinoids act through binding to retinoic acid receptors, altering expression levels of hundreds of cellular proteins affecting multiple pathways involved in acne pathogenesis. Retinoids have evolved from first-generation agents, such as tretinoin, through chemical modifications resulting in a second generation (etretinate and acitretin for psoriasis), a third generation (adapalene and tazarotene) and, most recently, a fourth (trifarotene). For all topical retinoids, local irritation has been associated with poor tolerability and suboptimal adherence. Efforts to improve tolerability have utilized novel delivery systems and/or novel agents. This qualitative literature review summarizes the evolution of the four topical single-agent retinoids available for the treatment of acne in the US today and their various formulations, presenting the rationale behind their development and data from key studies.

Tolerability of tretinoin lotion 0.05% for moderate to severe acne vulgaris: a post hoc analysis in a black population.

Acne vulgaris (acne) is the most common dermatologic disorder seen in black patients. However, data are lacking on the effects of treatments, such as topical retinoids. Acne in black patients is frequently associated with postinflammatory hyperpigmentation (PIH), which can be of greater concern than the patient's acne and often is the main reason these patients seek a dermatologist consultation. Retinoids can treat both acne and PIH. However, the potential for retinoids to induce an irritant contact dermatitis, which could lead to PIH, is a concern. A lotion formulation of tretinoin was developed to provide an important alternative option to treat acne in black patients who may be sensitive to the irritant effects of other tretinoin formulations or where PIH is a concern.

Halobetasol Propionate Lotion 0.01% for Moderate-to-Severe Plaque Psoriasis: Pooled Analysis in Male and Female Participants.

Introduction: Psoriasis is a chronic, immune-mediated skin disease that is associated with sex-related differences. Two double-blind, vehicle-controlled, phase 3 studies evaluated halobetasol propionate (HP) 0.01% lotion for the treatment of moderate-to-severe localized plaque psoriasis; pooled post hoc analyses investigated efficacy and safety in male and female subgroups. Methods: Participants were randomized (2:1) to once-daily HP or vehicle lotion for 8-weeks of double-blind treatment, with a 4-week posttreatment follow-up. Post hoc efficacy assessments in male (n=253) and female (n=177) subgroups included treatment success (≥2­grade improvement in Investigator's Global Assessment [IGA] score and score of 'clear' or 'almost clear'), treatment success in psoriasis signs (erythema, plaque elevation, and scaling) at the target lesion, and change in affected body surface area (BSA). Treatment-emergent adverse events (TEAEs) were evaluated. Results: At week 8, rates of IGA-rated treatment success were significantly greater for HP versus vehicle in males (34.0% vs 6.4%) and females (42.7% vs 14.6%; P<0.001 both). Treatment success in each psoriasis sign approached or exceeded 50% for HP-treated males and females, with all differences versus vehicle statistically significant (P<0.001). Percent reduction in affected BSA was significantly greater for HP versus vehicle in males (34.9% vs 6.7%) and females (35.6% vs 4.6%; P<0.001 both). Five HP treatment-related TEAEs (all application site-related) were reported through week 8. Conclusions: HP lotion was associated with significant reductions in disease severity in male and female participants with moderate-to-severe psoriasis, with good tolerability and safety over 8 weeks of once-daily use. In the overall pooled population, results were similar. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5250.

Novel Polymeric Tazarotene 0.045% Lotion for Moderate-to-Severe Acne: Pooled Phase 3 Analysis by Race/Ethnicity.

Background: Acne vulgaris and inflammation-associated sequelae are highly prevalent in black and Hispanic populations. In a phase 2 study, a novel polymeric emulsion formulation of tazarotene 0.045% lotion had relatively fewer adverse events than tazarotene 0.1% cream, but with comparable efficacy. The objective was to evaluate tazarotene 0.045% lotion by race and ethnicity in the pivotal trials. Methods: In two phase 3, double-blind, 12-week studies (NCT03168334; NCT03168321), participants with moderate-to-severe acne were randomized 1:1 to tazarotene 0.045% lotion or vehicle lotion (N=1,614). This pooled, post hoc analysis included subsets of participants that self-identified as white (n=1191) or black (n=262) and Hispanic (n=352) or non-Hispanic (n=1262). Coprimary endpoints were inflammatory/noninflammatory lesion counts and treatment success (defined as at least a 2-grade reduction from baseline in Evaluator's Global Severity Score and a score of 'clear' or 'almost clear'). Treatment-emergent adverse events (TEAEs) and cutaneous safety and tolerability were evaluated. Results: At week 12, tazarotene 0.045% lotion led to significantly greater percent reductions in inflammatory and noninflammatory lesions compared with vehicle in white, Hispanic, and non-Hispanic participants (P<0.05, all). Black participants had significantly greater reductions in noninflammatory lesions following treatment with tazarotene 0.045% versus vehicle (P<0.05). Treatment success rates in all subpopulations were higher with tazarotene 0.045% lotion (29.4-34.1%) versus vehicle (16.4-23.1%). TEAE rates were similar across tazarotene-treated groups and most were mild-to-moderate in severity. The incidence of hyperpigmentation decreased in black tazarotene-treated participants from baseline to week 12. Conclusions: Tazarotene 0.045% lotion demonstrated efficacy and was well tolerated across racial and ethnic subpopulations in this pooled analysis. J Drugs Dermatol. 2020;19(7) doi:10.36849/JDD.2020.5125.

Tazarotene 0.045% Lotion for the Once-Daily Treatment of Moderate-to-Severe Acne Vulgaris in Adult Males

BACKGROUND: There has been an increasing interest in gender differences both in the pathogenesis and treatment of acne vulgaris (acne). However, while acne prevalence among adolescents is comparable across sexes, acne is much more common in adult women than in adult men which has been largely ignored. Acne is likely less common in adult men because of the declining rate of sebum secretion observed with increasing age, and yet it can be more severe than in adult women. In addition, adherence to topical medications is especially poor in adult men where tactile and sensory perceptions are low. The first lotion formulation of tazarotene was developed using polymeric emulsion technology to provide an important alternative option to treat these acne patients, especially those who may be sensitive to the irritant effects of other tazarotene formulations. OBJECTIVE: To evaluate the efficacy and safety of a new tazarotene 0.045% lotion formulation based on polymeric emulsion technology in treating adult male subjects with moderate or severe acne, in comparison with adolescent males treated with the same tazarotene 0.045% lotion. METHODS: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies in moderate-or-severe acne. Subjects (aged 10 and older, N=1614) were randomized (1:1) to receive tazarotene 0.045% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator's Global Severity Score [EGSS] and clear or almost clear). Quality of Life was assessed using the validated Acne-QoL scale. Safety, adverse events (AEs) were evaluated throughout; cutaneous tolerability (using a 4-point scale where 0=none and 3=severe) at each study visit. RESULTS: A total of 268 male subjects (85≥18 years old and 183<18 years old) were treated with tazarotene 0.045% lotion once-daily for 12 weeks. At week 12, percent reductions in inflammatory and noninflammatory lesions with tazarotene 0.045% lotion were 62.3% and 59.5% in the adult male population, compared with 49.4% (P=0.001) and 49.5% (P=0.016) in the adolescent male population. Treatment success was achieved by 33.0% of adult male subjects treated with tazarotene 0.045% lotion, compared with 21.6% in the adolescent male population (P=0.059). Quality of life (as assessed by Acne-QoL domain scores) was better in adolescent males at baseline. Improvements in QoL domain scores were similar to those seen in the overall study population, with greater absolute change in domain scores in the adult males. Improvement in acne symptom scores was significantly greater in adult males (P=0.029). Tazarotene 0.045% lotion was well-tolerated. The number of subjects reporting any AE in the adult male population was 11 (13.6%) compared with 39 (21.4%) in the adolescent male population. There was only one (1.2%) treatment-related AE (application site pain) reported in the adult males compared with 11 (6.0%) in the adolescent males, where the most common treatment-related AEs were application site pain (3.3%), dryness (1.1%), and erythema (1.1%). Mean scores for hyper- and hypopigmentation were very low at baseline in both groups with no appreciable change with treatment. CONCLUSIONS: Tazarotene 0.045% lotion provides greater efficacy and better tolerability in adult males (above 18 years old) than the adolescent male population with moderate-to-severe acne patients. J Drugs Dermatol. 2020;19(1):78-85. doi:10.36849/JDD.2020.3979

Novel Tretinoin 0.05% Lotion for Once-Daily Treatment of Moderate-to-Severe Acne Vulgaris in a Hispanic Population

Background: Acne vulgaris (acne) is the most common dermatologic disease seen in a racially, geographically, politically, culturally, and socioeconomically diverse Hispanic population. Despite their growing demographics in the US, there are few studies evaluating acne treatment in this population. Potential for skin irritation and dryness, as well as pigmentary changes are key concerns. The first lotion formulation of tretinoin was developed using novel polymerized emulsion technology to provide an important alternative option to treat these acne patients who may be sensitive to the irritant effects of other tretinoin formulations. Objective: To determine the efficacy and safety of tretinoin 0.05% lotion in treating moderate-to-severe acne in a Hispanic population. Methods: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled Phase 3 studies in moderate or severe acne. Hispanic subjects (aged 11 to 50 years, N=766) were randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator's Global Severity Score [EGSS] and clear/almost clear). Safety, adverse events (AEs), and cutaneous tolerability were evaluated throughout using a 4-point scale where 0=none and 3=severe. Results: At week 12, mean percent reduction in inflammatory and noninflammatory lesion counts were 60.1% and 53.0%, respectively, compared with 51.1% and 38.7% with vehicle (P≤0.001) in the Hispanic population. Treatment success was achieved by 19.6% of subjects by week 12, compared with 12.7% on vehicle (P=0.015). The majority of AEs were mild and transient. There were four serious AEs (SAEs) reported (two each group) unrelated to treatment. Incidence of treatment-related AEs with tretinoin 0.05% lotion was lower than in the overall study population; the most frequently were application site pain (2.0%), dryness (1.4%), and erythema (1.2%). Local cutaneous safety and tolerability assessments were generally mild-to-moderate at baseline and improved by week 12. There were slight transient increases in scaling and burning over the first four weeks. Hyperpigmentation severity reduced progressively with treatment. Conclusions: Tretinoin 0.05% lotion was significantly more effective than its vehicle in achieving treatment success and reducing inflammatory and noninflammatory acne lesions in a Hispanic population. The new lotion formulation was well-tolerated, and all treatment-related AEs were both mild and transient in nature. J Drugs Dermatol. 2019;18(1):32-38.

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.

Efficacy, Safety, and Tolerability of Topical Dapsone Gel, 7.5% for Treatment of Acne Vulgaris by Fitzpatrick Skin Phototype.

BACKGROUND: Acne vulgaris (acne) is prevalent in individuals with skin of color, often with more frequent sequelae than in patients with lighter skin color. It is important to determine if there are also differences in response to medications. OBJECTIVE: This study evaluated the efficacy and tolerability of once-daily dapsone gel, 7.5% in patients with acne, stratified by Fitzpatrick skin phototype. METHODS: Data were pooled from 2 identically designed, phase 3, randomized, double-blind, vehicle-controlled studies in patients aged 12 years and older with moderate acne. Patients applied dapsone gel, 7.5% or vehicle once daily for 12 weeks. Efficacy was evaluated using the Global Acne Assessment Score (GAAS), lesion counts, and Acne Symptom and Impact Scale (ASIS); adverse events (AEs) and tolerability were also assessed. RESULTS: This analysis included 2216 patients with skin phototypes I-III and 2111 with types IV-VI. Dapsone gel, 7.5% significantly improved acne severity versus vehicle in both skin phototype subgroups, as determined by the percentage of patients with at least a 1-grade improvement in GAAS and mean change from baseline in GAAS (both, P less than .0001) at week 12 versus baseline. Dapsone gel, 7.5% significantly reduced inflammatory, comedonal, and total lesions in skin phototypes I-III (P less than .001) and IV-VI (P less than equal to .01) versus vehicle. Improvements in inflammatory lesions occurred first, with generally similar patterns of improvement seen over time in GAAS, comedonal lesions, and ASIS domains. The incidence of AEs was similar in both skin phototype subgroups and between study medications. Local scaling, erythema, stinging/burning, and dryness were rated "none" by most patients in both treatment groups and skin phototype subgroups. CONCLUSION: Once-daily dapsone gel, 7.5% was effective, safe, and well tolerated in patients with all skin phototypes who were treated for moderate acne. J Drugs Dermatol. 2018;17(2):160-167.

Pivotal Trial of the Efficacy and Safety of Oxymetazoline Cream 1.0% for the Treatment of Persistent Facial Erythema Associated With Rosacea: Findings from the First REVEAL Trial.

An unmet need exists for a safe, tolerable, effective treatment for moderate to severe persistent facial erythema in patients with rosacea. This pivotal phase 3, multicenter, double-blind study evaluated the efficacy and safety of topical oxymetazoline in patients with facial erythema associated with moderate to severe rosacea. Patients were randomly assigned to treatment with oxymetazoline hydrochloride cream 1.0% or vehicle applied once daily for 29 days, and were followed for 28 days posttreatment. The primary efficacy outcome was having at least a 2-grade decrease from baseline on both the Clinician Erythema Assessment (CEA) and the Subject Self-Assessment for rosacea facial redness (SSA) scales (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Safety assessments included treatment-emergent adverse events (TEAEs) and posttreatment worsening of erythema (composite CEA/SSA increase of 1-grade severity from baseline; rebound effect). A total of 440 patients (mean age, 49.5 years; 78.9% females) were randomized (oxymetazoline, n=222; vehicle, n=218); most had moderate erythema. On day 29, significantly greater proportions of oxymetazoline recipients achieved the primary efficacy outcome at each time point (P less than 0.02) and overall (P less than 0.001) compared with vehicle recipients. The incidence of discontinuation due to TEAEs was low in both groups (oxymetazoline group, 1.8%; vehicle group, 0.5%). The most common TEAEs reported during the entire study period were application-site dermatitis, application-site erythema, and headache in the oxymetazoline group (1.4% each), and headache (0.9%) in the vehicle group. Following cessation of treatment, low proportions of patients experienced rebound effect (oxymetazoline group, 2.2%; vehicle group, 1.1%). Oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in patients with moderate to severe persistent facial erythema of rosacea.

J Drugs Dermatol. 2018;17(1):97-105.

Adapalene/Benzoyl Peroxide Gel 0.3%/2.5%: A Safe and Effective Acne Therapy in All Skin Phototypes.

BACKGROUND: Acne affects individuals of all races and ethnicities; however, lighter and darker skin phototypes face different treatment challenges that may affect treatment response and tolerability. This analysis investigated possible differences in the efficacy and safety of the fixed dose combination of 0.3% adapalene with 2.5% benzoyl peroxide (A/BPO gel 0.3%/2.5%) in subjects with Fitzpatrick Skin Types (FST) I-VI.

METHODS: This was a post-hoc analysis of a Phase 3, multicenter, randomized, double-blind, parallel-group study of moderate to severe acne in subjects with FST I-VI. Subjects received A/BPO gel 0.3%/2.5%, A/BPO gel 0.1%/2.5% (benchmark), or vehicle, once daily for 12 weeks. Efficacy measurements included success rate (IGA of Clear or Almost Clear), change in inflammatory and noninflammatory lesions from baseline to week 12, safety, and tolerability. The intent to treat (ITT) and safety populations were analyzed. Demographics and disposition were analyzed with descriptive statistics; categorical variables by frequency and percentage; and continuous variables with means, medians, minimum, maximum, and standard deviations.

RESULTS: The A/BPO gel 0.3%/2.5% treatment group included 128 subjects with FST I-III, and 89 subjects with FST IV-VI. At week 12, A/BPO gel 0.3%/2.5% was safe, tolerable, and significantly superior to vehicle for all FST and severity groups in inflammatory and noninflammatory lesion reduction (P less than equal to .05). Compared to baseline, 32% of subjects with FST I-III were clear or almost clear, compared to 7% in the vehicle group (P=.001). In FST IV-VI, 28% of subjects were clear or almost clear, compared to 15% for vehicle (P=NS). In all treatment groups and skin phototypes, week 12 tolerability scores were similar to baseline scores, and tolerability scores for most subjects of all skin phototypes were "none" or "mild" for all measures.

SUMMARY: We report that the fixed dose combination of A/BPO gel 0.3%/2.5% is efficacious and safe in patients with FST I-VI with moderate and severe inflammatory acne.

Clinicaltrials.gov registry: NCT01880320

J Drugs Dermatol. 2017;16(6):574-581.

Efinaconazole solution 10% for treatment of toenail onychomycosis in Latino patients.

Onychomycosis is a common progressive fungal infection of the nail bed, matrix, or plate leading to destruction and deformity of the toenails and fingernails. The prevalence of onychomycosis is increasing in the United States, particularly in the growing population of Latino patients. In this study, we evaluated the efficacy and safety of efinaconazole solution 10% in Latino patients with onychomycosis. Once-daily application of efinaconazole solution 10% may be an effective topical option for treatment of onychomycosis in this patient population.

Emerging Issues in Adult Female Acne.

Acne vulgaris (acne) is a common affliction in adolescence and is a growing problem in adult women. Despite an increasing awareness of acne in the adult female population, there is a lack of good prospective studies assessing the severity, distribution, and differential response to treatment in this group. The long-held dogma that acne in adult women develops on the lower one-third of the face has been recently challenged, and here the authors critically review data from available literature. Moreover, while adult female acne has traditionally been defined as disease in women over age 25, it is the authors' experience that this group is subdivided into women ages 25 to 44 years, separate from perimenopausal patients, ages 45 years and up. While there is no data specifically comparing these two groups, the authors will review the existing data and provide practical recommendations based on our experience in treating these groups of patients. Finally, while there is a lack of data on this subject, it is the group's opinion that adherence to medication regimens is likely higher in women than men, which influences therapeutic outcomes.

Efficacy, Safety, and Dermal Tolerability of Dapsone Gel, 7.5% in Patients with Moderate Acne Vulgaris: A Pooled Analysis of Two Phase 3 Trials.

Objective: Assess efficacy and safety of once-daily topical dapsone gel, 7.5% compared with vehicle for treating acne vulgaris (acne). Design: A pooled analysis of data from two identically designed, randomized, double-blind, vehicle-controlled, multicenter, 12-week clinical trials. Setting: Study sites in the United States and Canada. Participants: overall, 4,340 patients were randomized 1:1 to dapsone and vehicle. Criteria included age 12 years or older with acne diagnosis, 20 to 50 facial inflammatory lesions (papules and pustules), 30 to 100 facial noninflammatory lesions (open and closed comedones), and acne grade of 3 (moderate) on the Global Acne Assessment Score scale. Measurements: Efficacy assessments included the Global Acne Assessment Score success rate (proportion of patients with Global Acne Assessment Score of 0 [none] or 1 [minimal]) and percentage change from baseline in inflammatory and noninflammatory lesions at Week 12. Results: Global Acne Assessment Score success rates were 29.8 percent and 21.1 percent for patients who received dapsone gel, 7.5% and vehicle, respectively (p<0.001). Patients receiving dapsone gel, 7.5% had greater percentage change in lesion counts than patients receiving vehicle (inflammatory lesions: -54.6% vs. -48.1%; p<0.001; -45.1 %; noninflammatory lesions: -39.4%; p<0.001). Most adverse events were mild to moderate in severity. Mean dermal tolerability scores for stinging/burning, dryness, scaling, and erythema were similarly low with dapsone gel, 7.5% and vehicle. Conclusion: Dapsone gel, 7.5%, with a 50-percent greater dapsone concentration than twice-daily dapsone gel, 5% formulation, is applied topically once daily for acne, is effective, safe, and well-tolerated over 12 weeks, and has local tolerability similar to that of vehicle. www.clinicaltrials.gov identifiers: NCT01974141 and NCT01974323.

Results of a Phase 2, Randomized,Vehicle-Controlled Study Evaluating the Efficacy,Tolerability, and Safety of Daily or Twice Daily SB204 for the Treatment of Acne Vulgaris.

OBJECTIVE: This randomized, double-blind, placebo-controlled, Phase 2 study compared efficacy, tolerability, and safety of SB204 once or twice daily to vehicle in the treatment of acne vulgaris. METHODS: Eligible subjects were to be between 12 and 40 years old, have facial acne vulgaris with 25 to 70 non-inflammatory lesions, 20 to 40 inflammatory lesions, no more than 2 nodules, and a baseline Investigator's Global Assessment (IGA) score of moderate or severe. The co-primary efficacy endpoints were the absolute change in inflammatory and non-inflammatory lesion counts and IGA success rate (baseline to week 12). Safety assessments included reported adverse events (AEs), physical examinations, and laboratory testing. Tolerability was evaluated by the investigators based on the occurrence and severity of erythema, scaling, dryness, pruritus, and burning/stinging. RESULTS: A total of 213 subjects were randomized: 27 subjects to vehicle once daily; 29 subjects to vehicle twice daily; 53 subjects to SB204 2% twice daily; 52 subjects to SB204 4% once daily; and 52 subjects to SB204 4% twice daily. When compared to vehicle, treatment with all 3 SB204 regimens significantly reduced the absolute inflammatory lesion count and SB204 4% once daily reduced the absolute non-inflammatory lesion count. Treatment with SB204 4% once daily demonstrated a significant reduction in percent inflammatory lesions by week 4. There were no significant differences in the IGA success rates between groups at the end of treatment. All treatment regimens of SB204 were found to be safe and well tolerated. CONCLUSIONS: When compared to vehicle, SB204 2% and SB204 4% significantly decreased the absolute inflammatory lesion count and SB204 4% once daily also significantly decreased the absolute non-inflammatory lesion count in subjects with acne vulgaris treated for 12 weeks. Treatment with SB204 2% and 4% was found to be safe and well tolerated. J Drugs Dermatol. 2016;15(12):1496-1502.

Efficacy and tolerability of a fixed combination of clindamycin phosphate (1.2%) and benzoyl peroxide (3.75%) aqueous gel in moderate or severe adolescent acne vulgaris.

BACKGROUND: Acne is commonplace in adolescents and can be difficult to manage. Providing an effective and well-tolerated treatment may lead to improved adherence, increased patient satisfaction, and improved clinical outcomes. METHODS: A post hoc analysis of efficacy and cutaneous tolerability in 289 adolescents (age range, 12 to <18 years) with moderate-to-severe acne who had been enrolled in a multicenter study and were randomized to receive either clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel or vehicle once daily for 12 weeks. RESULTS: Significantly superior reductions in lesion counts were observed in the clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel group compared to vehicle from Week 4, with mean percent reductions in inflammatory and noninflammatory lesions from baseline of 59.9 percent and 50.5 percent, respectively (both P<0.001 versus vehicle). One-third of patients treated with clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel achieved ≥2-grade improvement from baseline in their Evaluator's Global Severity Score (compared to 8.5% with vehicle, P<0.001) and 35 percent of patients reported clear or almost clear skin at Week 12 (compared to 12.8% with vehicle, P<0.001). Cutaneous tolerability was excellent with all mean scores ≤0.2 at Week 12 (where 1=mild). CONCLUSIONS: Clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel is an effective, safe, well-tolerated treatment for adolescents with moderate-to-severe acne.