Noninflammatory Lesion Counts Research Articles

Efficacy of a new generation topical retinoid in the treatment of patients with moderate to severe acne on the face and trunk

Rationale. The extreme prevalence of acne, long-term course and multifactorial pathogenesis necessitate the development of new drugs and treatment methods aimed at increasing efficiency and achieving clinical effects in the shortest possible time. This article presents data from two international clinical studies to determine the effectiveness and safety of trifarotene 50 µg/g (0.005%) cream in the treatment of patients with moderate acne on the face and trunk. The purpose of the study. To evaluate the safety and effectiveness of trifarotene cream, 0.005%, a new topical retinoid, for moderate acne of the face and trunk. Material and research methods. Two international, double-blind, randomized, placebo (vehicle) controlled, 12-week phase III studies screened 2817 and randomized 2420 patients 9 years of age and over. The effectiveness of the drug was assessed based on the registration of the number of patients who achieved the effect of “clear” or “almost clear” skin condition and an improvement of ≥ 2 points in terms of IGA on the facial skin and PGA on the truncal skin during 12 weeks of treatment, as well as by calculating the change in absolute number of inflammatory and non-inflammatory acne elements relatively to the initial level. The safety of therapy was assessed based on the registration of adverse events, local tolerability (the formation and severity of retinoic dermatitis), abnormalities in vital signs and the results of standard laboratory tests. Results. The onset of effect of trifarotene versus that of its vehicle was rapid, with significant reductions in both inflammatory and noninflammatory lesion counts seen as early as 1 week after treatment on the face and as early as 2 weeks after treatment on the trunk. In both studies, at week 12 the facial success rates according to IGA and PGA and change in inflammatory and noninflammatory lesion counts (both absolute and percentage) were all highly significant (P0.001) in favor of trifarotene when compared with the vehicle and the formation of the “almost clear” and “clean” effect was registered in the vast majority of patients, who used cream with 0.005% trifarotene. Conclusion. The results of the study demonstrated the pronounced clinical effectiveness of trifarotene cream 0.005% in the treatment of patients with moderate acne on the skin of the face and trunk.

A dermocosmetic regimen is effective and safe for mild to moderate acne in subjects of all skin phototypes

AbstractBackgroundAcne vulgaris is a chronic inflammatory skin condition with a multifactorial pathogenesis. The clinical appearance of acne and its sequelae may differ according to phototypes. Data regarding the potential benefit of dermocosmetics (DC) regardless of phototype are lacking and assessing acne improvement can be difficult, given the lack of visual support in people with skin of colour. A DC regimen, combining a cleanser and a cream, both containing thermal spring water, has been developed for the management of mild‐to‐moderate acne, for all skin phototypes studied.ObjectivesTo assess the efficacy and local tolerance of a DC routine in mild‐to‐moderate acne and to visualize the clinical improvement in all skin phototypes.MethodsIn an open‐labelled, multicentre clinical study, subjects of any phototype aged above 11 years and above with mild (N = 48, 55.2%) or moderate (N = 39, 44.8%) facial acne applied the DC twice daily for 56 days. No other acne care was allowed. Acne severity, as well as inflammatory and noninflammatory lesion counts, were assessed at baseline, Days 28 and 56. Photographs were taken using a novel imaging tool based on multimodal acquisition, to show clinical improvement over time.ResultsEighty‐seven subjects, 41 adults and 46 adolescents, were included; 59.8% were female and were aged between 11 and 44 years. The total acne lesion count decreased by 34%, the noninflammatory lesion count by 28%, and the inflammatory lesion count by 52% at Day 56. All % changes were statistically significant (p < 0.05). The GEA score decreased, with 25% of subjects showing at least a one‐grade improvement at Day 28 and 59% at Day 56. Local tolerance was excellent.ConclusionsThe tested DC care is beneficial for the improvement of acne and is very well tolerated in all skin phototypes studied.

Comparison of the Efficacy of Clascoterone, Trifarotene, and Tazarotene for the Treatment of Acne: A Systematic Literature Review and Meta-Analysis.

Acne vulgaris, a chronic inflammatory condition, is associated with significant physical and psychosocial burden. Since 2019, three new topical agents for acne vulgaris have been approved in the USA and Canada. We performed a systematic review and meta-analysis to compare the efficacy between twice-daily clascoterone cream 1%, once-daily trifarotene 0.005% cream, and once-daily tazarotene 0.045% lotion for acne treatment. Randomized controlled trials (RCTs) comparing clascoterone, trifarotene, or tazarotene with vehicle in patients with moderate-to-severe acne were identified from a systematic literature review and included in a meta-analysis. Primary outcomes were percentage reduction in inflammatory and noninflammatory lesion count (ILC and NILC, respectively) and treatment success rate (≥ 2-grade improvement in Investigator's Global Assessment or Evaluator's Global Severity Score and a rating of clear or almost clear) at week 12. DerSimonian and Laird random-effects models with the inverse variance method were used to calculate the mean difference (MD) for percentage reduction in ILC and NILC, and odds ratios (ORs) for the rate of treatment success. Six Phase 3 RCTs were included in the meta-analysis. The analyses showed robust differences favoring the interventions for ILC (MD: - 11.5; 95% confidence interval [CI]: - 14.39, - 8.62), NILC (MD: - 12.25; 95% CI: - 15.21, - 9.29), and treatment success rate (OR: 2.14; 95% CI: 1.81, 2.53). No differences were observed between clascoterone, trifarotene, and tazarotene for ILC (MD: - 12.8, - 11.2, and - 10.1, respectively), NILC (MD: - 11.6, - 13.9, and - 12.8, respectively), or treatment success rate (OR: 2.9, 1.9, and 2.1, respectively (all P > 0.05). No significant differences in efficacy were observed between clascoterone, trifarotene, and tazarotene after 12weeks of treatment in patients with moderate-to-severe acne. Differences in application frequency and safety profile should also be taken into consideration when making treatment decisions.

Efficacy and Safety of Micronized Isotretinoin Administered Once Daily Without Food in Patients With Recalcitrant Nodular Acne.

Micronized isotretinoin 0.4 to 0.8 mg/kg/day administered in 2 divided doses with or without meals is approved for the treatment of severe nodular acne in patients aged 12 years or older. Although practitioners may suggest once-daily dosing to increase patient compliance, supporting data are limited. In this pilot study, patients aged 12 years or older with severe nodular acne (Investigator's Global Assessment [IGA] =>4 and >5 facial nodules) received once-daily micronized isotretinoin 0.4 to 0.8 mg/kg/day without food for 20 weeks. The coprimary efficacy endpoints were changes from baseline in nodular lesion count (NLC) and percentage of patients with a =>90% reduction in NLC at week 24. Secondary endpoints included percentage of patients achieving IGA 0/1; reductions in inflammatory lesion count (ILC) and noninflammatory lesion count (NILC); adverse events (AEs); and severity of erythema, dryness, peeling, oiliness, burning, and pruritus. Analyses included all enrolled patients with the last observation carried forward. Twenty-two of 24 patients completed the study. From baseline to week 24, NLC decreased by a median (quartile [Q]1, Q3) of 6 (5, 7), all patients experienced complete clearance of nodules, 23/24 (96%) patients achieved IGA 0/1, and ILC and NILC decreased by a mean +/- standard deviation of 97.8% +/- 5.7% and 98.4% +/- 6.2%, respectively (all P<0.0001). There were small, significant, early increases in the severity of erythema, dryness, and peeling; 2 patients experienced 3 AEs considered unrelated to treatment. Once-daily micronized isotretinoin administered without food was efficacious and well tolerated in patients with severe nodular acne.  J Drugs Dermatol. 2024;23(6):423-428.     doi:10.36849/JDD.7863.

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

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. 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). 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.

Efficacy of Low-Level Laser Versus Topical Erythromycin 2% in the Treatment of Inflammatory Acne Vulgaris.

Acne vulgaris is a skin problem affecting many people of different ages. Despite many options that are available for treatment of acne vulgaris, many patients still respond inadequately to treatment. Phototherapy is one of the best acne treatment options. It was to compare the efficacy of low-level laser therapy in treatment of inflammatory acne versus topical erythromycin 2% cream. This study included 40 patients (18 males, 22 females) with different clinical severities of acne vulgaris. All the participants underwent split-face treatment: one side with 8 treatments (twice per week) of a low-level continuous infrared diode laser (808 nm) wavelength and (500 Hz) frequency and the other side with topical erythromycin 2% twice daily (aknemycin cream 2%). Evaluation was done at start of sessions, 2 weeks after the end of sessions and 3 months after stoppage of treatment depending on: photographs, global evaluation of acne scale, and Indian acne association grading. There was improvement of acne lesions on laser side and antibiotic side (assessed as non-inflammatory and inflammatory lesion counts). Laser side showed better results than antibiotic side. Patients were more satisfied with laser treatment due to minimal side effects and less relapse. A series of 8 treatments using low level continuous infrared diode laser represents a cheap, safe and effective non-invasive therapeutic option for acne vulgaris.

Efficacy and Safety of Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel in Females with Moderate to Severe Acne: Post Hoc Analysis by Age

Introduction: While acne is common in adolescents, the overall prevalence in adults is increasing, especially among females. In addition, acne in older females is associated with greater negative impacts on quality of life. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% (CAB) gel—the first fixed-dose, triple-combination topical product approved for acne—has demonstrated good efficacy, safety, and tolerability in participants with moderate-to-severe acne. The objective of this analysis is to assess the impact of age on efficacy, safety, and tolerability in females with moderate-to-severe acne.
 Methods: In one phase 2 (N=741; NCT03170388) and two identically designed phase 3 (N=183; N=180; NCT04214639; NCT04214652), double-blind, randomized, 12-week studies, participants aged ≥9 years with moderate-to-severe acne were randomized to receive once-daily CAB or vehicle gel; the phase 2 study included three additional dyad randomization arms (data not shown). Coprimary endpoints comprised inflammatory and noninflammatory lesion counts and treatment success (≥2-grade reduction from baseline in Evaluator’s Global Severity Score and score of ‘clear’ or ‘almost clear’). Treatment-emergent adverse events (TEAEs) and cutaneous safety and tolerability were also assessed. Pooled data from these studies were analyzed post hoc from female participants categorized by age: 9-24 years (n=274) and ≥25 years (n=121).
 Results: At week 12 in both age groups, least-squares mean percent reductions from baseline were >70% in CAB-treated females versus vehicle gel for inflammatory (9-24 y: 77.8% vs 53.8%; ≥25 y: 77.8% vs 60.5%; P<0.01, both) and noninflammatory lesions (9-24 y: 72.8% vs 44.5%; ≥25 y: 73.7% vs 55.2%; P<0.001, both). Half of CAB-treated females in both age groups achieved treatment success at week 12 versus less than one-quarter with vehicle (9-24 y: 54.1% vs 15.6%; ≥25 y: 50.1% vs 22.5%; P<0.01, both). Most TEAEs were mild-to-moderate in severity, with rates similar to the overall pooled phase 2 and 3 populations. Although there were transient increases in the severity of cutaneous safety/tolerability assessments with CAB, scores generally returned to or near baseline levels for most assessments by week 12 in younger and older females. No notable age-related trends in safety were observed.
 Conclusions: With greater than 70% lesion reductions and half of participants achieving treatment success by week 12, the innovative, fixed-dose triple combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel demonstrated good efficacy, safety, and tolerability in both younger and older females with moderate-to-severe acne.
 Funding: Ortho Dermatologics

Efficacy and Safety of Fixed-Dose Triple-Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Moderate-to-Severe Acne Vulgaris in Children and Adolescents

Background: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the first fixed-dose triple-combination formulation approved for acne vulgaris and is indicated for use in patients aged 12 years and older. As topical acne treatment in pediatric patients may be complicated by tolerability issues and/or a perceived lack of efficacy, the objective of this post hoc analysis was to investigate the efficacy and safety of CAB in children and adolescents.
 Methods: Data were pooled from two phase 3 double-blind, randomized, 12-week studies (NCT04214639; NCT04214652). Eligible participants ≥9 years of age with moderate-to-severe acne were randomized (2:1) to once-daily CAB or vehicle gel. This analysis evaluated adolescents aged 12-17 years (CAB: n=123; vehicle: n=50). Endpoints included ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin (treatment success), least-squares mean percent change from baseline in inflammatory/noninflammatory lesions, and treatment-emergent adverse events (TEAEs). Descriptive efficacy and safety data for five children aged 10-11 years enrolled in the study are also summarized (CAB: n=3; vehicle: n=2).
 Results: At week 12, 51.5% of CAB–treated participants aged ≥12 years achieved treatment success vs 24.9% with vehicle gel (P<0.01). CAB treatment resulted in significant reductions of >70% in inflammatory and noninflammatory lesion counts in adolescents (78.3% and 73.7%, respectively) vs vehicle (50.5% and 42.9%; P<0.001, both). Most TEAEs were of mild-to-moderate severity, and the most common (>3% in any treatment) treatment-related TEAE was application site pain. Less than 2.5% of participants withdrew due to AEs. For the 5 children aged <12 years, all 3 treated with CAB achieved treatment success, with reductions in inflammatory/noninflammatory lesions ranging from 76%-100%; neither vehicle-treated participant achieved treatment success. Only one CAB–treated younger participant experienced TEAEs (application site pain/dryness, and erythema [all mild/moderate]) and none discontinued the study.
 Conclusions: In two pooled phase 3 studies, once-daily CAB gel—the first approved fixed-dose, triple-combination topical formulation for acne vulgaris—was well tolerated and efficacious in pediatric participants with moderate-to-severe acne, with over half achieving treatment success at week 12.
 Funding: Ortho Dermatologics

Twelve Week Study Evaluating the Efficacy of a Novel Standardized Nutraceutical to Improve Acne and Skin Health

INTRODUCTION
 Although acne is generally viewed as the result of a localized immune response at the pilosebaceous unit, it is a condition with multifactorial etiology. While conventional treatments have focused primarily on the four major pathogenic factors, nutraceuticals offer an alternative or complementary approach to address more systemic, intertwined mechanisms involved in acne pathogenesis. These include stress, diet and metabolism, skin and gut microbiome, hormonal fluctuations, oxidative stress, and immune function. Therapies which target these underlying mechanisms have gone largely unexplored as ways to address acne. Here, we present the results of a novel nutraceutical addressing these root causes in patients with non-cystic acne. 
 DESIGN
 This was a 12-week single-arm prospective study for adults aged 18-50 with facial non-cystic acne ranging from mild to severe. Subjects discontinued all acne medications and topicals prior to the start of the study. Clinical assessments at baseline, week 4, 8 and 12 included IGA, inflammatory and non-inflammatory lesion counts, clinical grading of PIH/PIE, and texture. Bioinstrumentation included corneometer, tewameter and sebumeter measurements. Questionnaires on perception of efficacy were also completed.
 RESULTS
 Fifty-one subjects were recruited with 39 subjects completing the study. The majority were female (67%); racial/ethnic background was comprised of white/caucasian (41%), black (41%) and Asian (13%). Reasons for discontinuation were: lost to follow up/withdrawal (n=7), non-compliance (n=1) and adverse events (n=4). Significant and progressive improvements were seen starting at week 4 in IGA with 85% of subjects showing significant improvements for acne severity at week 12. All lesion counts decreased over the duration of the study with a significant proportion of subjects seeing improvements in inflammatory lesion counts (69%) and non-inflammatory lesion counts (87%). Overall, clinical grading of skin quality parameters progressively improved throughout the duration of the study. Notably PIH/PIE parameters significantly improved in nearly 80% of subjects by week 12. Sebumeter measurements improved significantly with a decrease of 25% as early as week 4 and remained lower than baseline throughout the duration of the study. Skin hydration as measured by the corneometer improved as well. Subjective impressions of improvement as measured by the questionnaire at 12 weeks showed subjects had ‘less breakouts’ (77%), ‘less oily skin’ (74%) and that their ‘acne had improved’ (87%).
 CONCLUSION
 The paucity of scientific evidence and lack of clinical data on the efficacy of CAM, including nutraceuticals, have limited their recommendation for use in acne. This proof-of-concept study showed improvements in acne and skin parameters. Although more studies are needed, these results offer insight into the potential benefits of nutraceuticals addressing underlying mechanisms that up to now, have gone largely unexplored. Addressing root causes that contribute to a generalized inflammatory response leading to the development of acne may prove to be an important step in expanding our toolbox in providing more options for patients and improving skin health.

The efficacy of Topical Clascoterone versus systematic spironolactone for treatment of acne vulgaris: A systematic review and network meta-analysis.

This study aimed to evaluate the effectiveness of topical clascoterone (TC) compared to oral spironolactone for acne vulgaris treatment. A computerized search through PubMed/MEDLINE, SCOPUS, and the Cochrane Library was conducted to find relevant papers. We used the "netmeta" and "meta" packages for network meta-analysis (NMA) in RStudio 1.2.5019 (2009-2019 RStudio, Inc.) to conduct all of our statistical tests. Seven articles (n = 2,006 patients) were included. The fixed-effect size showed that TC 1% bis in die (BID) showed potential effectiveness in reducing the inflammatory and non-inflammatory lesion count compared to placebo (Standardized mean difference, SMD = -0.27, 95% CI: -0.36 to -0.17) and (SMD = -0.31, 95% CI: -0.41 to -0.22), respectively. The random-effect size showed that TC 1% BID was significantly associated with a 12-week treatment success compared to placebo (Odds ratio, OR = 2.44, 95% CI: 1.12 to 5.30). Spironolactone 200 mg was associated with a significant reduction in total lesion count (SMD = -4.46, 95% CI: -5.60 to -3.32). TC appears to reduce both inflammatory and non-inflammatory lesion count and may lead to treatment success. Spironolactone at 200 mg showed potential effectiveness in terms of total lesion count reduction. These results suggest that both TC and Spironolactone could be beneficial in treating patients with acne vulgaris.

A Systematic Literature Review and Network Meta-Analysis of Comparative Efficacy of Topical Fixed-Dose Combination Treatments for Moderate to Severe Acne Vulgaris

INTRODUCTION: Several topical and oral monotherapies/combination treatments are available for treating patients with moderate to severe acne vulgaris and a few are currently under review with the United States (US) Food and Drug Administration (FDA). Among these treatments, topical fixed-dose combinations (FDCs) are widely used in the US. No study has assessed the comparative efficacy of topical FDCs based on the treatment success endpoint of the proportion of patients achieving ≥2 grade reduction AND "Clear" or "Almost clear” status by week 12 on an Investigator's Global Assessment (IGA) or equivalent scales. The objective of this study was to conduct a systematic literature review (SLR) and network meta-analysis (NMA) to compare the efficacy of topical FDCs for the treatment of moderate to severe acne.
 STUDY DESCRIPTION: An SLR was conducted for identifying randomized controlled trials (RCTs), that included at least one topical FDC (currently approved/under review with FDA) arm, in academic (MEDLINE, Embase, Cochrane CENTRAL, PEDE, and NHS EED) and non-academic databases (HTA databases, conference abstracts databases, and trial registries). The search was conducted in May 2022, based on a pre-specified inclusion/exclusion criterion. RCTs included in the analysis evaluated acne severity using IGA or equivalent (Evaluator's Global Severity Score, Investigator’s Static Global Assessment) scales. A Bayesian network meta-regression was conducted, using the proportion of patients with moderate acne, inflammatory and non-inflammatory lesion counts at baseline as covariates to account for acne severity.
 RESULTS: Twelve Phase II/III/IV RCTs were identified from 5,159 citations comprising 8,349 patients across 8 treatment groups. The odds ratio for treatment success with topical FDC of clindamycin phosphate 1.2%, adapalene 0.15%, and benzoyl peroxide 3.1% (first triple agent FDC) gel was estimated to be 7.61 (95% Credible Interval: 4.44 –13.20) in comparison to Vehicle gel. Comparative effectiveness ranking demonstrated that the topical triple agent FDC gel was the most effective treatment with surface under cumulative ranking of 100%.
 CONCLUSION: Based on this SLR/NMA, the topical triple agent FDC of clindamycin phosphate 1.2%, adapalene 0.15%, and benzoyl peroxide 3.1% gel, which is currently under FDA review (PDUFA date 10/20/2023), was clinically superior to all other topical FDC treatments for moderate to severe acne vulgaris.

ANTIHISTAMINE AS AN ADJUNCTIVE TREATMENT IN ACNE VULGARIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Approximately one-tenth of the global population suffer from acne vulgaris, which is a skin disease with considerable psychological impact. Recently, antihistamines have been used in the treatment of acne. However, their overall treatment effects for this indication remain unclear. This systematic review and meta-analysis aim to evaluate the clinical efficacy and safety of the antihistamines in the treatment of acne vulgaris. The following databases were searched: PubMed, Scopus, Embase, Cochrane Central Register of Controlled Clinical Trials, and Google Scholar. We included the randomized controlled trials on acne vulgaris patients which compared any H1- antihistamine drug in combination with other medications to placebo, no treatment, or other medications, with acne lesion (non-inflammatory and inflammatory) counts, acne severity score, patient satisfaction, acne flare, or adverse events as an outcome of interest. Six studies contributing to 388 patients were included, involving two H1 antihistamines (i.e., levocetrizine and desloratadine), isotretinoin, azithromycin, and topical azelaic acid cream. From the network meta–analysis, levocetirizine+isotretinoin was better than the isotretinoin alone in the inflammatory lesion count, but not in the non-inflammatory lesion count. The desloratadine+isotretinoin retained the best balance in terms of non-inflammatory lesion count, inflammatory lesion count, acne flare, and mucocutaneous adverse events. The desloratadine+isotretinoin and levocetirizine+isotretinoin were considered safe.

Post-Hoc Exploratory Pooled Analysis of the Impact of IDP-126 Gel on QoL in Moderate-to-Severe Acne.

Acne has psychosocial effects on patient's quality of life (QoL). This post hoc exploratory analysis of pooled phase 3 data assessed the impact of investigational IDP-126 gel (for moderate to severe acne) on the Acne-Specific Quality of Life Questionnaire (Acne-QoL; exploratory endpoint in the trials).  Methods: A post hoc exploratory analysis using pooled data (N=309; age ≥13 years) was conducted to assess if 1) changes from baseline to week 12 in Acne-QoL domain scores significantly differ by treatment; 2) differences were clinically meaningful, and 3) relative importance of acne severity as measured by the Evaluator's Global Severity Score (EGSS) or lesion counts explains the changes in QoL (Acne-QoL).  Results: Acne-QoL domain scores significantly (P<0.001, each) improved for patients treated with IDP-126 Gel vs vehicle in all four domains (role-emotional [least squares mean difference {LSMean} 4.1], self-perception [LSMean 3.8], acne symptoms [LSMean 2.6], and role-social [LSMean 2.0]). The proportion of responders was significantly higher (P<0.05, each) in the IDP-126 Gel group vs vehicle across Acne-QoL domains, self-perception (odds ratio [OR]: 4.32), acne symptoms (OR: 3.90), role-social (OR: 3.59), and role-emotional (OR: 2.50). Across all Acne QoL domains, the improvement on the EGSS endpoint (53.8-63.3%) was more likely to influence QoL improvements than the inflammatory (20.1-33.4%) and non-inflammatory lesion (9.5-18.7%) counts.  Conclusions: This post hoc exploratory analysis of pooled phase 3 data (moderate to severe acne) suggests that treatment with IDP 126 Gel led to statistically significant and clinically meaningful improvements in QoL and improvement in QoL was primarily influenced by EGSS.J Drugs Dermatol. 2023;22(10):1033-1039      doi:10.36849/JDD.7812.

Correlating the Gut Microbiota and Circulating Hormones with Acne Lesion Counts and Skin Biophysical Features.

Acne vulgaris is a common inflammatory condition that is multi-factorial and impacted by both intrinsic and extrinsic features. Several previous studies have assessed for correlations between factors such as circulating hormones, stress, or the microbiome. However, there have not been any correlations specifically against lesion counts or differentiating correlations between inflammatory and non-inflammatory lesion counts. Here, we correlate several factors against acne lesions. Twenty men and women with mild to moderate acne were recruited, and their hormonal levels and their gut microbiome were collected and correlated against their inflammatory and non-inflammatory lesions of acne. Facial non-inflammatory lesions were weakly correlated to sebum excretion rate and weakly inversely correlated to forehead and cheek hydration. We examined stress through the use of a normalized peak-to-trough ratio (higher numbers indicated less stress), which correlated with skin hydration and inversely correlated with sebum excretion rate. Sebum excretion rate was weakly correlated to testosterone levels, and facial hydration correlated with estradiol levels. Correlations with the gut microbiome showed differential correlations with inflammatory and non-inflammatory lesions, with Clostridium sp AF 23-8 correlating to inflammatory lesion counts, while Actinomyces naeslundii str Howell 279 correlated to non-inflammatory lesions. Overall, measures of stress and circulating hormones correlate to skin biophysical properties and acne lesion counts. Also, different gut bacteria correlate with either inflammatory or non-inflammatory lesion counts. We hope that our findings stimulate further work on the gut-mind-stress-skin axis within acne.

Efficacy and safety of microencapsulated benzoyl peroxide and microencapsulated tretinoin for the treatment of acne vulgaris: Results from two phase 3 double-blind, randomized, vehicle-controlled studies

Benzoyl peroxide and tretinoin are commonly prescribed acne treatments. Historically, they have been difficult to combine in a single formulation due to chemical instability, and both medications are potentially irritating. Microencapsulation helps overcome these challenges. Examine efficacy, safety, and tolerability of encapsulated BPO/encapsulated tretinoin (E-BPO/T) cream, 3%/0.1%. Subjects ≥9 years old with moderate to severe acne were enrolled in 2 multicenter, double-blind, vehicle-controlled, parallel trials and randomized (2:1) to 12weeks of once-daily E-BPO/T (n=571) or vehicle cream (n=287). E-BPO/T was significantly superior to vehicle in both studies, with more subjects achieving IGA success with E-BPO/T (38.5%/25.4%) versus vehicle (11.5%/14.7%; P<.001/P=.017). The change from baseline in inflammatory lesion count for E-BPO/T was -21.6 versus -14.8 for vehicle (P<.001) in study 1 and -16.2 versus -14.1 (P=.018) in study 2. The changes from baseline in noninflammatory lesions for E-BPO/T were -29.7 versus -19.8 for vehicle (P<.001) and -24.2 and -17.4 (P<.001) in studies 1 and 2, respectively. E-BPO/T was well tolerated in both studies. Long-term data are not available. E-BPO/T provided statistically significant and clinically relevant improvements in IGA and inflammatory and noninflammatory lesion counts and was well tolerated in subjects with moderate to severe acne.

DMT310, a novel once-weekly topical treatment for patients with moderate-to-severe acne vulgaris: Results of a phase 2b randomized, double-blind, placebo-controlled trial

Poor patient adherence with antiacne medications is a common clinical challenge. DMT310, a natural, topical product with a once-weekly application schedule, may alleviate this obstacle. Evaluate the safety, tolerability, and efficacy of DMT310 in treating moderate-to-severe acne. This 12-week, randomized, double-blind, placebo-controlled, multicenter clinical trial enrolled participants 12years and older with moderate-to-severe acne. The intent-to-treat population included a total of 181 participants (DMT310, N=91; placebo, N=90). Participants who received DMT310 vs participants treated with placebo demonstrated a statistically significant greater reduction in the number of inflammatory and noninflammatory lesions at all time points: inflammatory lesion counts at week 12 (-15.64 vs -10.84, P<.001); noninflammatory lesion counts at week 12 (-18.26 vs -12.41, P<.001). DMT310-treated participants also had higher rates of Investigator's Global Assessment treatment success than participants in the placebo group at all time points: Investigator's Global Assessment at week 12 (44.40% vs 17.78%; P<.001). No serious treatment related adverse events occurred. DMT310 once-weekly topical treatment significantly reduced both inflammatory and noninflammatory lesions and yielded a greater proportion of Investigator's Global Assessment treatment success at all time points in participants with moderate-to-severe acne.

A Novel, Hand-Held, and Low-Level Light Therapy Device for the Treatment of Acne Vulgaris: A Single-Arm, Prospective Clinical Study

There is an increasing demand for low-level light therapy devices for the treatment of dermatologic conditions, such as acne, hair loss, undesirable body hair, and skin aging. This study evaluated the safety and effectiveness of a novel hand-held low-level light therapy device with a 680 nm red laser diode and a 450 nm blue light-emitting diode for the treatment of mild-to-moderate acne. A prospective clinical study was conducted on 57 patients with mild-to-moderate acne and Fitzpatrick skin types II–IV. Treatments were self-administered by the patients at home daily for 4 weeks. Conventional treatment was restricted during the study period. The number of inflammatory and noninflammatory lesion counts, Investigator’s Global Assessment grade, patients’ self-assessment, and adverse events were measured every two weeks, and follow-ups were performed until four weeks after the final treatment. Moreover, we evaluated the bactericidal effect of low-level light therapy on Cutibacterium acnes, a causative agent of acne vulgaris, in vitro. The mean number of inflammatory acne lesions decreased statistically at weeks 4 ( ∗ ∗ ∗ p &lt; 0.001 ) and 8 ( ∗ ∗ ∗ p &lt; 0.001 ). The proportion of Investigator’s Global Assessment grade 3, indicating moderate acne severity, decreased significantly at the final visit. No severe adverse reactions were reported. Furthermore, there was a significant reduction in the viability of Cutibacterium acnes following low-level light therapy exposure in vitro. The results of this study demonstrate that this novel, hand-held, and low-level light therapy device are safe and effective for the treatment of inflammatory acne, with good adherence.

Safety and efficacy of nadifloxacin versus clindamycin observed in a tertiary care teaching hospital of Deccan Plateau

Acne vulgaris is characterised by excess sebum production and inflammatory reaction in sebaceous glands. As propionibacterium is involved in aggravation of acne, antimicrobials like nadifloxacin and clindamycin were found to be effective in treatment.Comparison of nadifloxacin with clindamycin in terms of inflammatory and non-inflammatory lesion count and global improvement rating, when given in combination with benzoyl peroxide in patients in acne vulgarisNadifloxacin 1%, benzoyl peroxide 2.5% and clindamycin 1% were used as topical treatment option. Study cohort was randomly divided into two groups: Nadifloxacin group and Clindamycin group. All subjects who were included in the study were instructed to apply a thin layer of medication over acne lesions; benzoyl peroxide 2.5% gel once daily at bedtime and clindamycin 1% gel or Nadifloxacin 1% gel twice daily. Efficacy is analysed by comparing changes in total, inflammatory and non-inflammatory lesion counts, In addition, global improvement was rated by patients using a six-point scale (worsening, no improvement, slight improvement, moderate improvement, good improvement, clearance) at end of treatment.There is progressive decline in number of inflammatory and non-inflammatory lesions in both groups. Analysis of lesion counts not showed any significant difference in between two groups. In global improvement rating scale, more number of patients using nadifloxacin with benzoyl peroxide reported good improvement compared to patients using Clindamycin with benzoyl peroxide. No patient in any group reported worsening of lesions. None of patients in study groups reported clearance. Two adverse events were reported during study, they were, burning sensation and dryness. There was no significant difference in incidence of adverse events in both treatment groups.Topical Nadifloxacin, a new fluoroquinolone is effective, tolerable and safe for mild or moderate facial acne. Its clinical effectiveness is equivalent to clindamycin when used as add-on therapy to benzoyl peroxide.

Prospective Placebo-Controlled Assessment of Spore-Based Probiotic Supplementation on Sebum Production, Skin Barrier Function, and Acne.

Probiotic supplementation has been shown to modulate the gut-skin axis. The goal of this study was to investigate whether oral spore-based probiotic ingestion modulates the gut microbiome, plasma short-chain fatty acids (SCFAs), and skin biophysical properties. This was a single-blinded, 8-week study (NCT03605108) in which 25 participants, 7 with noncystic acne, were assigned to take placebo capsules for the first 4 weeks, followed by 4 weeks of probiotic supplementation. Blood and stool collection, facial photography, sebum production, transepidermal water loss (TEWL), skin hydration measurements, and acne assessments were performed at baseline, 4, and 8 weeks. Probiotic supplementation resulted in a decreasing trend for the facial sebum excretion rate and increased TEWL overall. Subanalysis of the participants with acne showed improvement in total, noninflammatory, and inflammatory lesion counts, along with improvements in markers of gut permeability. The gut microbiome of the nonacne population had an increase in the relative abundance of Akkermansia, while the subpopulation of those with acne had an increase in the relative abundance of Lachnospiraceae and Ruminococcus gnavus. Probiotic supplementation augmented the circulating acetate/propionate ratio. There is preliminary evidence for the use of spore-based probiotic supplementation to shift the gut microbiome and augment short-chain fatty acids in those with and without acne. Further spore-based supplementation studies in those with noncystic acne are warranted.

Montelukast as an effective adjuvant in the treatment of moderate acne vulgaris.

Although antibiotics are among the most commonly used treatments of acne, there are refractory cases, or they can cause some complications. Recently, leukotriene B4 has been found to play a major role in inflammatory acne lesions. This double blind, randomized clinical trial was conducted on 108 patients with acne who needed systemic therapy and referred to dermatology clinics affiliated to Shiraz University of Medical Sciences. One group (53 patients) received 100 mg doxycycline daily plus placebo and the other group (55 patients) received 100 mg daily doxycycline plus 10mg daily montelukast. Both groups also received topical benzoyl peroxide 5% every other night. The study period was 3 months and the patients were investigated by lesion count, investigator global assessment (IGA), global acne grading system (GAGS), and Cardiff acne disability index (CADI) scoring systems. Total lesion count, inflammatory lesion count, and non-inflammatory lesion count as well as IGA and GAGS decreased in both treatment groups. At the end of the study, however, the inflammatory lesion count and IGA score reduced more significantly in the montelukast group (p=0.018 and 0.045, respectively). In addition, the two groups were significantly different with regard to the percentage of decrease in the total lesion count, inflammatory lesions, and IGA (p=0.033, 0.003, and 0.044, respectively). Thus, montelukast can be used as an adjuvant therapy besides other treatments of acne, especially for inflammatory lesions.