Consensus Statements on the Use of Novel Formulations of Isotretinoin: A Modified Delphi Process.

Oral isotretinoin remains a mainstay of treatment for severe, recalcitrant nodular acne. Novel formulations of isotretinoin have been developed over the past decade, including lidose isotretinoin and micronized isotretinoin. It is important to understand the differences between isotretinoin formulations to help guide clinical decision-making and selection of isotretinoin therapy. This study aims to provide evidence-based consensus statements regarding the use of novel formulations of isotretinoin for the treatment of moderate-to-severe acne. The Expert Consensus Group consisted of dermatologists with expertise in the treatment of acne. Voting members met in person to conduct a modified Delphi process; a maximum of 2 rounds of voting were conducted for each consensus statement. A total of 5 statements were generated regarding the use of novel formulations of isotretinoin, addressing the efficacy, tolerability, and side effects of novel isotretinoin formulations. All 5 statements achieved agreement with high consensus. The Expert Consensus Group agrees that individualized selection of isotretinoin therapy is important to maximize efficacy and minimize side effects. Compared to generic isotretinoin, micronized isotretinoin may require lower doses to achieve sufficient plasma concentrations. With the increased bioavailability of micronized formulation, there is no need to calculate cumulative dose; instead, the general recommendation with micronized isotretinoin is to treat for at least 5 months, or longer if needed to achieve clearance. Micronized isotretinoin can be taken in the fed or fasted state and has an acceptable safety profile. J Drugs Dermatol. 2024;23(6):429-432.     doi:10.36849/JDD.7971.

Triple-Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Acne in Adult and Pediatric Participants.

BACKGROUND: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel (CAB) is the first fixed-dose triple-combination approved for the treatment of acne. This post hoc analysis investigated the efficacy and safety of CAB in pediatric (<18 years) and adult (greater than or equal to 18 years) participants. METHODS: In two multicenter, double-blind, phase 3 studies (NCT04214639 and NCT04214652), participants greater than or equal to 9 years of age with moderate-to-severe acne were randomized (2:1) to 12 weeks of once-daily treatment with CAB or vehicle gel. Pooled data were analyzed for pediatric and adult subpopulations. Assessments included treatment success (greater than or equal to 2-grade reduction from baseline in Evaluator's Global Severity Score and a score of 0 [clear] or 1 [almost clear], inflammatory/noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability. RESULTS: At week 12, treatment success rates for both pediatric and adult participants were significantly greater with CAB (52.7%; 45.9%) than with vehicle (24.0%; 23.5%; P<0.01, both). CAB-treated participants in both subgroups experienced greater reductions from baseline versus vehicle in inflammatory (pediatric: 78.6% vs 50.4%; adult: 76.6% vs 62.8%; P<0.001, both) and noninflammatory lesions (pediatric: 73.8% vs 41.1%; adult: 70.7% vs 52.2%; P<0.001, both). Acne-QoL improvements from baseline to week 12 were significantly greater with CAB than with a vehicle. Most TEAEs were of mild-to-moderate severity; no age-related trends for safety/tolerability were observed.  Conclusions: CAB gel demonstrated comparable efficacy, quality of life improvements, and safety in pediatric and adult participants with moderate-to-severe acne. As the first fixed-dose, triple-combination topical formulation, CAB represents an important new treatment option for patients with acne. J Drugs Dermatol. 2024;23(6):394-402.     doi:10.36849/JDD.8357.

Triple Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% for Acne: Efficacy and Safety from a Pooled Phase 3 Analysis.

INTRODUCTION: A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data. METHODS: In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated. RESULTS: At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P < 0.001). CAB resulted in > 70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P < 0.001, both). Most TEAEs were of mild-moderate severity, and < 3% of CAB-treated participants discontinued study/treatment because of AEs. Transient increases from baseline in scaling, erythema, itching, burning, and stinging were observed with CAB, but resolved back to or near baseline values by week 12. CONCLUSIONS: The innovative fixed-dose, triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel was efficacious and well tolerated in children, adolescents, and adults with moderate-to-severe acne. Half of participants achieved clear/almost clear skin by 12 weeks, rates not previously seen in clinical studies of other topical acne products. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04214639 and NCT04214652.

Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

Treatments for Moderate-to-Severe Acne Vulgaris: A Systematic Review and Network Meta-analysis.

BACKGROUND: Multiple treatment options exist for the management of moderate-to-severe acne. However, the comparative effectiveness (efficacy/safety) of moderate-to-severe acne treatments has not been systematically examined. METHODS: A systematic literature review (SLR) was conducted to identify randomized controlled trials of ≥4 weeks of treatment (topical, oral, physical, or combinations) for moderate-to-severe facial acne in patients aged ≥9 years. Efficacy outcomes included: percentage of patients achieving ≥2-grade reduction from baseline and “clear” or “almost clear” for global severity score (treatment success); absolute change in inflammatory (ILs reduction); and noninflammatory lesion counts (NILs reduction). A random-effects network meta-analysis (NMA) was conducted for the efficacy outcomes. Treatments were ranked with posterior rank plots and surface under cumulative ranking values.  Results: Eighty-five studies were included in the SLR/NMA. Topical triple-agent fixed-dose combination (FDC) gel (clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1%) and combinations of double-agent fixed-dose topical treatments with oral antibiotics (TOA3) consistently ranked in the top 3 treatments. Topical triple-agent FDC gel was numerically superior to TOA3 for treatment success (log-odds ratios: 1.84 [95% credible interval (CrI) 1.36 to 2.29]) and 1.69 (95% CrI: 1.01 to 2.32) vs placebo/vehicle). TOA3 was numerically superior to topical triple-agent FDC gel for reduction of ILs (mean difference: -8.21 [-10.33 to -6.13]) and -10.40 [-13.44 to -7.14] vs placebo/vehicle) and NILs (mean difference: -13.41 [-16.69 to -10.32] and -17.74 [-22.56 to -12.85] vs placebo/vehicle). CONCLUSIONS: Based on this SLR/NMA, topical triple-agent FDC gel was the most efficacious and safe treatment for moderate-to-severe acne. J Drugs Dermatol. 2024;23(4):     doi:10.36849/JDD.8148.

Early and Sustained Acne Lesion Reductions With Fixed-Dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel.

BACKGROUND: A once-daily, three-pronged approach using an antibiotic, antibacterial, and retinoid may provide faster acne improvement versus monotherapy or dual-combination products. This post hoc analysis compared threshold acne lesion reductions with clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel—the first FDA-approved triple-combination topical acne product—to its dyads and vehicle. METHODS: Phase 2 (N=741; NCT03170388) and phase 3 (N=183; N=180; NCT04214639; NCT04214652), double-blind, 12-week studies randomized participants aged ≥9 years with moderate-to-severe acne to once-daily CAB or vehicle gel; the phase 2 study included three additional dyad gel arms. The pooled percentage of participants achieving ≥33%, ≥50%, and ≥75% reduction in inflammatory and noninflammatory acne lesions was evaluated. RESULTS: As early as week 4 in the phase 2 study, ≥33% reduction in inflammatory lesions occurred in a significantly greater percentage of CAB gel-treated participants (82.7%) than with the 3 dyads and vehicle (61.1-69.8%; P<0.05, all). These early reductions were sustained throughout the study, with significantly (P<0.05) more CAB-treated participants achieving ≥50% reduction in inflammatory lesions versus dyads and vehicle from weeks 4-12. By week 12, CAB led to substantial reductions of ≥75% in significantly more participants than dyads and vehicle (65.8% vs 49.9-51.2% and 21.6%; P<0.05, all). Similar trends were observed for noninflammatory lesions in the phase 2 study and for inflammatory and noninflammatory lesions in the phase 3 studies. CONCLUSIONS: Lesion count reductions were significantly greater with CAB versus its dyads and vehicle gel as early as week 4, with substantial reductions observed after 12 weeks of treatment. This faster-acting and sustained efficacy of CAB gel—coupled with its optimized formulation, once-daily dosing, and tolerability—may positively impact treatment adherence. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7907.

INDIVIDUAL ARTICLE: Impact of Acne Vulgaris and Sarecycline on Social/Emotional Functioning and Daily Activities: PROSES Study.

BACKGROUND: Concise patient-reported outcome (PRO) instruments addressing the consequences of facial acne vulgaris (AV) on patients’ functioning and activities of daily living (ADL) are needed. METHODS: A 12-week, single-arm, prospective cohort study was conducted in patients ≥9 years old with moderate/severe non-nodular facial AV prescribed sarecycline as part of usual care. The primary endpoint included AV-specific patient- and caregiver-reported outcomes assessed with the expert panel questionnaire (EPQ, developed by 10 experts using a Delphi method) in patients (>12 years) and caregivers (for patients 9-11 years). Additional assessments included parental/caregiver perspectives on children’s AV. RESULTS: A total of 253 patients completed the study. Following 12-weeks of treatment, there were significant (P ≤.0001) changes from baseline in the proportion of patients responding that they never or rarely: felt angry (31.6%), worried about AV worsening (28.9%), had thoughts about AV (20.9%), had a certain level of worries about AV (38.7%), altered their social media/selfie activity (23.7%), had an impact on real-life plans due to AV (22.9%), made efforts to hide AV (21.3%), felt picked-on/judged due to AV (15.0%), were concerned about their ability to reach future goals due to AV (13.8%), or had sleep impacted due to AV (18.2%). No significant change from baseline was observed for parent/caregiver’s understanding of the child’s AV concerns, from both patient and parent/caregiver perspectives. CONCLUSIONS: Over 12 weeks of AV management with oral sarecycline, patients reported significant reductions in AV-related effects on emotional/social functioning and ADL as measured by the EPQ, a simple PRO with potential for use in clinical practice. J Drugs Dermatol. 2024;23:1(Suppl 1):s4-11.

INDIVIDUAL ARTICLE: Sarecycline Improves Acne Severity, Symptoms, and Psychosocial Burden in Non-nodular Acne Vulgaris: PROSES Study.

BACKGROUND: Patient-reported outcomes (PROs) are emerging as a fundamental component of disease impact assessment in acne vulgaris (AV), complementing clinician-reported outcomes. No data is available on PROs for patients with AV using sarecycline in real-world settings. METHODS: A single-arm, prospective cohort study that included patients ≥9 years old diagnosed with moderate or severe non-nodular AV was implemented as part of routine care in clinical practices (N=30). Patients received oral sarecycline (60 mg, 100 mg, or 150 mg) for 12 weeks, as part of usual care. The primary endpoint was Acne Symptom and Impact Scale (ASIS) responses from patients (≥12 years) and caregivers (for patients 9-11 years) at week 12 and change from baseline (CFB). Investigator’s Global Assessment (IGA) of AV severity and adverse events (AEs) were also recorded. RESULTS: A total of 253 patients with AV completed the study (adults: 60.1%, females: 77.6%). ASIS mean scores significantly decreased (P <.0001) at week 12 for: signs (mean CFB ± standard deviation [SD]: –0.8 ± 0.7), impact (–1.0 ± 1.0), emotional impact (–1.2 ± 1.1), and social impact (0.6 ± 1.1). Significant reductions in AV severity (P <.0001) were reported by patients and caregivers. The IGA success rate was 58.9% and physician satisfaction with treatment outcomes was 88.1%. A total of 31 (10.3%) patients reported ≥1 AE during the study. CONCLUSIONS: Patients with moderate-to-severe AV receiving acne management with an oral antibiotic for 12 weeks experienced a significant improvement in AV-related symptoms and psychosocial burden. J Drugs Dermatol. 2024;23:1(Suppl 1):s12-18.

Microencapsulated Benzoyl Peroxide for Rosacea in Context: A Review of the Current Treatment Landscape.

Rosacea, a chronic skin condition affecting millions of people in the USA, leads to significant social and professional stigmatization. Effective management strategies are crucial to alleviate symptoms and improve patients' quality of life. Encapsulated benzoyl peroxide 5% (E-BPO 5%) is a newly FDA-approved topical treatment for rosacea that shows promise in enhancing therapeutic response and minimizing skin irritation. This review aims to assess the role of recently FDA approved E-BPO 5% in the current treatment landscape for rosacea management, as it is not yet included in clinical guidelines that predominantly rely on older approved therapies. The review focuses on randomized controlled trials conducted in English-speaking adults. It evaluates the efficacy, safety, and tolerability of various US Food and Drug Administration (FDA)-approved agents used for rosacea treatment, including E-BPO cream, metronidazole gel, azelaic acid gel and foam, ivermectin cream, minocycline foam, oral doxycycline, brimonidine gel, and oxymetazoline HCl cream. Existing therapies have been effective in reducing papulopustular lesions and erythema associated with rosacea for many years. E-BPO 5% offers a promising addition to the treatment options due to its microencapsulation technology, which prolongs drug delivery time and aims to improve therapeutic response while minimizing skin irritation. Further research is necessary to determine the exact role of E-BPO 5% in the therapeutic landscape for rosacea. However, based on available evidence, E-BPO 5% shows potential as a valuable treatment option for managing inflammatory lesions of rosacea, and it may offer benefits to patients including: rapid onset of action, demonstrated efficacy by Week 2, excellent tolerability, and sustained long-term results for up to 52 weeks of treatment.

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.

Management of Truncal Acne With Oral Sarecycline: Pooled Results from Two Phase-3 Clinical Trials.

BACKGROUND: Acne vulgaris is a common skin disease that affects the face, chest, and back. While truncal acne is present in at least 50% of patients, clinical studies have focused predominantly on facial acne.1,2 Few treatments to date have been evaluated for truncal acne. Sarecycline is a narrow-spectrum, third-generation, tetracycline-class oral drug approved for the treatment of acne. Pivotal phase-3 studies show that sarecycline is safe, well-tolerated, and effective treatment for moderate to severe acne vulgaris. METHOD: Pooled analysis was performed for truncal acne results with sarecycline from the two phase 3 studies. Investigator Global Assessment (IGA) success was evaluated at weeks 3, 6, 9, and 12. RESULTS: Chest IGA success rate were significantly greater with sarecycline versus placebo at weeks 3 (11.84% vs 7.71%, respectively; P=0.0192), 6 (18.81% vs 14.03%, respectively; P=0.0390), and 12 (33.42% vs 20.77%, respectively; P<0.0001). Back IGA success rate was also significantly greater with sarecycline versus placebo group at weeks 3 (12.13% vs 7.04%, respectively; P=0.0023), 6 (18.42% vs 14.34%, respectively; P=0.0412), 9 (29.05% vs 19.88%, respectively; P=0.0004) and 12 (33.07% vs 21.91%, respectively; P<0.0001)Conclusion: Sarecycline efficacy for truncal acne was observed within 3 weeks after treatment, supporting sarecycline as an optimal choice for oral treatment of moderate to severe truncal acne. J Drugs Dermatol. 2021;20(6):634-640. doi:10.36849/JDD.6204.

Rationale for Use of Combination Therapy in Rosacea.

BACKGROUND: Rosacea is a chronic skin condition characterized by primary and secondary manifestations affecting the centrofacial skin. The primary diagnostic phenotypes for rosacea are fixed centrofacial erythema with periodic intensification, and phymatous changes. Major phenotypes, including papules and pustules, flushing, telangiectasia, and ocular manifestations, may occur concomitantly or independently with the diagnostic features. The phenotypes of rosacea patients may evolve between subtypes and may require multiple treatments concurrently to be effectively managed. We report the proceedings of a roundtable discussion among 3 dermatologists experienced in the treatment of rosacea and present examples of rosacea treatment strategies that target multiple rosacea symptoms presenting in individual patients. METHODS: Three hypothetical cases describing patients representative of those commonly seen by practicing dermatologists were developed. A roundtable discussion was held to discuss overall and specific strategies for treating rosacea based on the cases. RESULTS/DISCUSSION: With few exceptions, the dermatologists recommended combination therapy targeting each manifestation of rosacea for each case. These recommendations are in agreement with the current American Acne and Rosacea Society treatment guidelines for rosacea and are supported by several studies demonstrating beneficial results from combining rosacea treatments. CONCLUSIONS: Rosacea is an evolving condition; care should take into account all clinical signs and symptoms of rosacea that are present in an individual patient, understanding that symptoms may change over time, and utilize combination therapy when applicable to target all rosacea symptoms. J Drugs Dermatol. 2020;19(10): 929-934. doi:10.36849/JDD.2020.5367.

The Effects of Once-Daily Tretinoin 0.05% Lotion on Quality of Life in Patients with Moderate-to-Severe Acne Vulgaris.

BACKGROUND: In two phase III clinical trials of patients with moderate-to-severe acne (NCT02932306, NCT02965456), tretinoin 0.05% lotion reduced inflammatory and noninflammatory lesions relative to vehicle lotion, with low potential for cutaneous irritation. OBJECTIVE: Data from these studies were analyzed post hoc to investigate the effects of tretinoin 0.05% lotion on patient-reported quality of life, as assessed using the Acne-Specific Quality of Life Questionnaire (Acne-QoL). METHODS: Mean changes from baseline to week 12 in Acne-QoL scores were analyzed in the pooled intent-to-treat population and a subgroup with treatment success (≥ 2-grade improvement on the Evaluator's Global Severity Scale and rating of "clear" or "almost clear"). Pearson correlations were conducted in the pooled intent-to-treat population to assess the relationship between the Acne-QoL acne symptoms domain and each of the other three domains. RESULTS: In the pooled intent-to-treat population (n = 1640), greater mean improvements were found with tretinoin 0.05% lotion vs vehicle in all four domains: self-perception (mean change: 7.4 vs 6.7); role-emotional (6.8 vs 6.0); role-social (4.8 vs 4.6); acne symptoms (6.5 vs 5.6); all p < 0.05. Relative to the intent-to-treat population, participants who experienced treatment success with tretinoin 0.05% lotion had higher (better) mean Acne-QoL scores at week 12. Correlations between acne symptoms and the other three domains were found at baseline and week 12 (p < 0.05). CONCLUSIONS: Participants with moderate-to-severe acne reported better quality of life after 12 weeks of treatment with tretinoin 0.05% lotion. Clinical improvements in acne symptoms may have contributed to these outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02932306, NCT02965456.

Novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris: assessment of safety and tolerability in subgroups.

Background: Topical tretinoin's role in acne has been established through evidence-based guidelines. Cutaneous irritation and potential to cause or exacerbate postinflammatory hyperpigmentation (PIH) may limit use.Objective: Evaluate safety and tolerability of novel polymeric formulation of tretinoin 0.05% lotion in moderate-to-severe acne.Methods: One thousand six hundred and forty patients randomized to tretinoin 0.05% lotion or vehicle in two double-blind placebo-controlled 12-week studies. Investigator-evaluated cutaneous safety (erythema and scaling) and patient-reported tolerability (itching, burning/stinging) assessed using a scale of 0 (none) to 3 (severe). Hyper- and hypo-pigmentation evaluated at each study visit. A number of subpopulations were investigated.Results: Tretinoin 0.05% lotion was considered safe and very well tolerated. Only application site pain (3.1%), dryness (3.7%) and erythema (1.4%) were reported by >1% or patients. Treatment-related adverse events were particularly rare (≤2%) in Hispanic and male subpopulations, and lower in adult females. The severity of cutaneous safety and tolerability scores remained <0.5 (where 1 = mild) and were generally lower than baseline severity. Tretinoin 0.05% lotion did not appear to cause or exacerbate PIH.Conclusions: A novel polymeric formulation of tretinoin 0.05% lotion provides a highly favorable safety and tolerability profile, with an incidence of erythema, dryness, and skin burning lower than that previously reported with other formulations of tretinoin.

Efficacy and Tolerability of a Novel Tretinoin 0.05% Lotion for the Once-Daily Treatment of Moderate or Severe Acne Vulgaris in Adult Females

Background: A novel tretinoin 0.05% lotion formulation has been shown to be efficacious and well-tolerated, and especially effective in adult female acne patients. While it is perhaps counter-intuitive that patients with more severe disease would show clinically significant improvement with topical monotherapy, topical retinoids have been shown to offer realistic treatment options in these patients. Objective: To evaluate the safety and efficacy of once-daily tretinoin 0.05% lotion in adult females with moderate or severe acne. Methods: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies. Adult females (>=18 years of age) with moderate (N=551) and severe (N=55) acne were randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory/noninflammatory lesions, treatment success (at least 2-grade reduction in Evaluator's Global Severity Score [EGSS] and clear/almost clear) and quality of life (QoL) using the validated Acne-QoL questionnaire. Safety, adverse events (AEs), and cutaneous tolerability were evaluated throughout. Results: At week 12, efficacy in adult females with moderate acne (EGSS=3) treated with tretinoin 0.05% lotion was significantly greater than that reported with vehicle. Mean percent reduction in inflammatory and noninflammatory lesion counts was 58.5% and 55.5% respectively compared with 50.3% and 39.8% with vehicle (P=0.039 and P<0.001). Treatment success was achieved by 25.4% of subjects by week 12, compared with 15.4% with vehicle (P=0.006). Tretinoin 0.05% lotion was numerically more effective in adult females with severe acne (EGSS=4). Mean percent reduction in inflammatory and noninflammatory lesion counts was 59.0% and 58.8% respectively (compared with 53.5% and 45.5% with vehicle), and treatment success was achieved by 17.9% of subjects (compared with 4.5% with vehicle), with 46.6% of subjects achieving at least a 2-grade improvement in EGSS by week 12. Quality of life improvements with tretinoin 0.05% lotion were significant compared with vehicle in adult females with moderate acne (except role-social), but not in severe acne (probably due to the group size). The majority of AEs were mild and transient; more frequently reported in the moderate acne population where application site pain (2.9%), and application site dryness (5.0%) were the most common, compared with one report (4.5%) of application site pain and dryness in the severe acne population. Local cutaneous safety and tolerability assessments were generally mild-to-moderate and improved by week 12. Limitations: The number of severe subjects enrolled in the studies was considerably less than the number of subjects with moderate acne, and the studies were not powered to demonstrate a difference in efficacy based on acne severity. Conclusions: Tretinoin 0.05% lotion was significantly more effective than vehicle in achieving treatment success and reducing inflammatory and noninflammatory lesions in adult females with moderate acne, with notable improvements in treating adult females with severe acne. It was well-tolerated, and all treatment-related AEs were mild or moderate. J Drugs Dermatol. 2019;18(11):1147-1154.

Current Concepts in Acne Pathogenesis: Pathways to Inflammation.

Acne is a disease of pilosebaceous inflammation. Pivotal in pathogenesis are the roles of hormones (insulin, insulin-like growth factor-1, androgens), Propionibacterium acnes, lipogenesis, and a proinflammatory lipid profile. Innate immune responses are induced through interaction with toll-like receptors and inflammasome activation initially and subsequently through adaptive immune activation. These insights into pathogenic inflammatory pathways can translate into novel therapeutic approaches for acne. Semin Cutan Med Surg 37(supp3):S60-S62 ©2018 published by Frontline Medical Communication.

Advances in Acne and Rosacea Therapy.

New topical therapies have demonstrated efficacy in patients with moderate or severe acne who might otherwise have required therapy with systemic antibiotics or isotretinoin. Increasing knowledge about the pathogenesis of acne has facilitated the development of therapies with novel modes of action. New and investigational therapies also are available or in development for the treatment of both the papulopustular and erythematous manifestations of rosacea. Semin Cutan Med Surg 37(supp3):S63-S66 © 2018 published by Frontline Medical Communications.

Treating Acne in Adult Women.

Acne can persist into adulthood or erupt de novo at any point after adolescence. Adult acne is more common in women than in men. Considerations for treating acne in adult women include childbearing potential, pregnancy, lactation, and concomitant skin conditions. Semin Cutan Med Surg 37(supp3):S67-S70 © 2018 published by Frontline Medical Communications.