AIM:Given the chronic nature of acne, two 6-month studies were conducted to evaluate the long-term efficacy and tolerability of clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB)-the only approved triple-combination acne topical-and its effects on scarring/dyspigmentation in participants with moderate to severe acne. MATERIALS AND METHODS:Data were pooled from 2 identical, open-label, single-center studies conducted in participants (N = 50) aged ≥12 years with Investigator's Global Assessment (IGA) score of 3/4. Endpoints included change from baseline in IGA score, inflammatory/noninflammatory lesions, skin appearance (dryness, postinflammatory hyperpigmentation [PIH], postinflammatory erythema [PIE]), and scarring. Adverse events and tolerability (itching, burning, redness, swelling) were assessed. RESULTS:At week 24, 67% of participants achieved treatment success, and significant reductions from baseline in inflammatory (88%) and noninflammatory (68%) lesions were observed (p < 0.001, both). Significant reductions in scarring (33%), investigator- and participant-assessed PIH (71%; 78%, respectively), and PIE (77%; 77%, respectively) were demonstrated (p < 0.001, all). Most participants (>70%) reported no tolerability issues throughout the studies. Seven adverse events occurred; 4 were related to CAB, and 3 led to study discontinuation (BPO allergy [n = 2], irritant contact dermatitis to BPO [n = 1]). CONCLUSIONS:These findings suggest that CAB is an appropriate and effective topical option for the long-term treatment of acne vulgaris.

Introduction Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel—the only approved triple-combination acne topical—was efficacious and well tolerated in 12-week clinical trials and in 24-week studies. Acne presentation and sequelae vary by skin type, requiring long-term management strategies to account for differences in skin pigmentation. This post hoc analysis assessed long-term efficacy and tolerability of acne treatment with CAB gel in participants with Fitzpatrick skin phototypes IV-VI. Methods Data were pooled from 2 identical, postmarketing, 24-week, single-center, open-label studies of once-daily CAB gel in 50 participants ≥12 years with moderate to severe acne (Investigator’s Global Assessment [IGA] score=3 or 4). Endpoints included changes from baseline in IGA score and inflammatory/noninflammatory lesions at week 24. Scarring (assessed using the Goodman Qualitative Scar Scale), skin appearance (dryness, postinflammatory hyperpigmentation [PIH], postinflammatory erythema [PIE]), tolerability (itching, burning, redness, swelling), and adverse events (AEs) were evaluated. Results Of 24 participants with Fitzpatrick skin types IV-VI, 22 completed the studies. Participants were a mean age of 26.6 years and 86.4% were female. At week 24, 73% of participants achieved treatment success (≥2-grade reduction from baseline in IGA score and clear/almost clear skin), with reductions in inflammatory and noninflammatory lesions of 90% and 66%, respectively. PIH, PIE, and scarring improved from baseline by 71%, 87%, and 32%, respectively. No participants reported tolerability issues at week 24 and all had skin dryness scores of 0 (none). One participant experienced an AE (bronchitis), which was deemed unrelated to study product. Conclusions In participants with darker skin phototypes, 6 months of once-daily CAB gel use led to 73% treatment success and inflammatory lesion reductions of 90%. These improvements are higher than those seen at week 12 in the pivotal trials and support the long-term use of CAB gel in patients with darker skin phototypes.

Background: Topical treatment of acne—particularly with retinoids—often incurs a transient period of dermal irritation characterized by erythema, scaling, and other dermal changes that may reflect the same mechanisms of action by which acne pathophysiology is addressed. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel demonstrated efficacy in the treatment of acne, with a safety/tolerability profile typical of topical acne treatment. The objective of this post-hoc analysis is to determine whether CAB efficacy was related to occurrence of cutaneous safety/tolerability events. Methods: Data were pooled from 4 double-blind, 12-week studies of participants with moderate-to-severe acne. Efficacy endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of 0 or 1 [clear/almost clear]) and reductions from baseline in inflammatory (IL) and noninflammatory lesions (NIL). Cutaneous safety/tolerability assessments of erythema and scaling (investigator-assessed) and itching, burning, and stinging (participant-assessed) were graded on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe). To determine if CAB efficacy was associated with cutaneous events, efficacy endpoints at week 12 were compared for CAB-treated participants who experienced no increase versus ≥1-grade (any) increase in any safety/tolerability score at weeks 2, 4, or 8. Results: At week 12, CAB-treated participants experiencing any safety/tolerability event (n=411) had significantly greater rates of treatment success and IL reductions, and numerically greater NIL reductions, than those without events (n=188; treatment success: 55.0% vs 43.0%; P<0.01; IL reductions: 79.1% vs 72.3%; P<0.001; NIL reductions: 73.1% vs 68.1%). At weeks 2, 4, and 8, IL/NIL reductions were significantly greater among participants experiencing any cutaneous event than those without events (P<0.05, all). Overall, improved efficacy appeared to be driven by events of scaling, itching, and burning. Conclusions: Across four clinical studies, CAB-treated participants who experienced safety/tolerability events at weeks 2, 4, or 8 also experienced greater lesion reductions across 12 weeks of treatment and greater rates of treatment success at week 12. These findings are consistent with the theory that early instances of cutaneous irritation during topical acne treatment may reflect therapeutic mechanisms of action. Setting patient expectations regarding the potential for transient irritation during treatment may contribute to greater adherence and efficacy with CAB gel. Funding: Ortho Dermatologics

We describe a 1726 nm laser system for treating inflammatory acne, key to which is a real-time skin temperature monitoring subsystem. This capability allows us to use a closed-loop, "treat-to-temperature" approach rather than the conventional "treat-to-power" (or fluence) approach used in most dermatological lasers. The goal of our acne treatment is to raise sebaceous gland (SG) temperature high enough to damage the gland while sparing the surrounding dermal tissue. Unfortunately, even at 1726 nm, where there is a small window of selectivity between sebum and water, the contrast in absorption coefficient is small, similar to 2:1. The result is that the target temperature window for safe and efficacious acne treatment is also small, approximately 5 degrees C at the skin surface. The open-loop, treat-to-power approach, wherein the clinician selects a suggested good laser power or fluence, does not work well for acne as the variability in skin response, as well as variability in system heating and cooling, results in treatment temperature variations of 6-8 degrees C or more. Additionally, there is no consistent clinical endpoint to indicate to the clinician that the treatment was safe and effective. To overcome this challenge, we employ a compact thermal imaging camera into the treatment handpiece to enable the accurate, real-time measurement of skin temperature. Real-time temperature feedback allows software to control laser power to reach a target skin surface treatment temperature while ensuring that the epidermal and dermal tissues do not overheat. Our thermal camera monitors the entire treatment area by sensing thermal radiation in the 7-14 micron band at 60 frames per second. To ensure measurement accuracy, which is key, we added a temperature-controlled reference source in the field-of-view of the camera. As an added safety feature, these measurements allow software to detect skin overheating or over-cooling conditions and stops the treatment and shuts off the laser and/or air cooling, if needed.

Background: Triple-combination therapies for acne including an antibiotic, topical retinoid, and benzoyl peroxide (BPO) are more effective than dual combinations or topical monotherapy. In clinical studies of participants with moderate to severe acne, clindamycin phosphate (CLIN) 1.2%/adapalene (ADAP) 0.15%/BPO 3.1% (CAB) gel demonstrated superior efficacy to vehicle and component dyads, with good safety and tolerability. Because acne pathogenesis and presentation can vary by skin type and ethnicity, it is important to assess treatment outcomes for specific populations. This post hoc analysis assessed efficacy and safety of CAB gel in Caucasian participants. Methods: Data were pooled from two phase 2 and two phase 3 double-blind, 12-week studies of participants with moderate to severe acne (N=1787). The pooled population included 1283 self-identified Caucasian participants, randomized to 6 treatment arms: once-daily CAB gel (n=446), ADAP 0.15%/BPO 3.1% gel (n=109), CLIN 1.2%/BPO 3.1% gel (n=101), CLIN 1.2%/ADAP 0.15% gel (n=109), branded ADAP 0.3%/BPO 2.5% gel (n=165), and vehicle (n=353). Endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of 0 or 1 [clear/almost clear]) and reductions from baseline in inflammatory/noninflammatory lesions. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were also assessed. Results: At week 12, a significantly greater percentage of Caucasian participants achieved treatment success with CAB gel (51.5%) than dyads (range, 31.7%-34.3%), randed ADAP 0.3%/BPO 2.5% gel (33.5%), or vehicle (17.9%; P<0.01, all). CAB yielded significantly greater reductions from baseline in inflammatory and noninflammatory lesions (76.8% and 73.0%, respectively) than dyads (62.7%-70.2% and 60.9%-63.4%, P<0.01, all), randed ADAP 0.3%/BPO 2.5% gel (72.6% and 65.7%, P<0.05, both) and vehicle (52.3% and 44.8%, P<0.001, both). Most TEAEs were of mild to moderate severity; the most common treatment-related TEAEs were application site pain, dryness, dermatitis, and erythema. Transient increases in cutaneous safety/tolerability scores beginning at week 2 resolved back to or near baseline by week 12; all scores were <1 (mild) at all post-baseline assessments. Conclusions: In Caucasian participants with moderate to severe acne across 4 clinical studies, triple-combination CAB gel demonstrated significantly greater efficacy without worsening tolerability vs dyad gels, randed ADAP 0.3%/BPO 2.5% gel, or vehicle. Funding: Ortho Dermatologics

BACKGROUND:Hyperkeratotic psoriatic plaques, characterized by considerable elevation and scaling, present treatment challenges with topical therapy. This post hoc analysis of two phase 3 trials evaluated the efficacy and tolerability of fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ; indicated for the topical treatment of plaque psoriasis in adults) in treating hyperkeratotic plaques. METHODS:Participants received HP/TAZ or vehicle daily for 8 weeks, with a 4-week posttreatment follow-up. Multiple subpopulations represented patients with hyperkeratotic plaques. Analysis 1 included a subgroup with severe plaque elevation and a second subgroup with severe scaling. Analysis 2 included a subgroup with either an investigator's global assessment (IGA) of 3 with moderate-to-severe plaque elevation or an IGA of 4. Endpoints included plaque elevation and/or scaling success (greater than or equal to 2-grade improvement for either) and safety assessments. RESULTS:At week 8, the severe plaque elevation subgroup and severe scaling subgroup achieved plaque elevation and scaling success, respectively, at significantly greater rates with HP/TAZ versus vehicle (P&lt;0.05 for all; Analysis 1). Analysis 2 participants achieved significantly greater rates of plaque elevation and scaling success with HP/TAZ versus vehicle at week 8 (P less than or equal to 0.001 for all). Tolerability improved from baseline by &gt;46% for all subgroups. Adverse events were similar between treatment groups. CONCLUSION:HP/TAZ was efficacious and well tolerated for treating hyperkeratotic plaques. CITATION:Tanghetti E, Stein Gold L, Lain E, Jacobson A. Clinical profile of halobetasol propionate 0.01%/tazarotene 0.045% lotion in patients with hyperkeratotic plaque psoriasis. J Drugs Dermatol. 2025;24(6):590-598. doi:10.36849/JDD.8720R1.

Background: Acne treatment can take weeks to result in noticeable improvements, which may diminish patients’ perception of treatment effectiveness and negatively affect treatment adherence. Acne treatments that deliver early visible improvements may encourage treatment adherence and bolster overall treatment effectiveness. Combination topical treatments that target multiple acne pathophysiological pathways are more efficacious than monotherapies and simplifying the treatment regimen by delivering multiple active ingredients as fixed combinations may improve adherence. Objective: To evaluate early acne improvements in clinical trials of fixed-combination acne topicals. Methods: Week 4 efficacy data for fixed-combination topical treatments were gathered from US Food and Drug Administration medical reviews, prescribing information, and/or publications of pivotal phase 2 and phase 3 clinical trials of 7 acne topicals, comprising fixed combinations of adapalene (ADAP), benzoyl peroxide (BPO), clindamycin phosphate (CLIN), and tretinoin. For the triple-combination formulation (CLIN 1.2%/ADAP 0.15%/BPO 3.1% gel), data from a nonpivotal phase 2 study with dyad combination treatment arms were also included. Outcomes included reductions from baseline in inflammatory lesions (ILs) and noninflammatory lesions (NILs) and treatment success (≥2-grade reduction in global acne severity score and clear/almost clear skin). Results: At week 4, IL reductions from baseline ranged from 32-54% while NIL reductions ranged from 25-45%. Rates of treatment success ranged from 3-12%. Overall, efficacy was greatest with triple-combination CLIN 1.2%/ADAP 0.15%/BPO 3.1% gel (IL: 54-55%; NIL: 43-45%; treatment success: 8-12%), followed by combinations of ADAP/BPO (IL: ~42-48%; NIL: ~38%; treatment success: 4-~7%). None of the branded topical products were evaluated in a head-to-head study. Conclusions: In pivotal clinical trials of topical fixed-combination formulations for acne, triple-combination CLIN 1.2%/ADAP 0.15%/BPO 3.1% gel yielded greater lesion reductions and rates of treatment success after 4 weeks of treatment than dyad formulations. Even greater differences may be expected with real-world world use, as early improvements may foster better long-term outcomes by increasing patients’ confidence in and adherence to the treatment. Funding: Ortho Dermatologics

ABSTRACTObjectivesThis work highlights the methods used to develop a multi‐pulse 1726 nm laser system combined with bulk air‐cooling for selective sebaceous gland (SG) photothermolysis using thermal imaging and software algorithms. This approach enables treating to a desired tissue temperature and depth to provide a safe, effective, reproducible, and durable treatment of acne.MethodsWe designed and built a 1726 nm laser system with a 40 W maximum power output, a highly controlled air‐cooling device, and a thermal camera in the handpiece, which permits real‐time temperature monitoring of the epidermis. IRB‐approved safety and efficacy trials demonstrated SG damage at depth, resulting in safe, efficacious, and durable clinical outcomes. Bioheat transfer and light transport modeling confirmed that the pulsing protocols could produce therapeutic temperatures at various SG depths, while protecting the epidermis and dermis with bulk air‐cooling. Similarly, we employed clinical observations and photothermal modeling to identify pain mitigation opportunities while maintaining therapeutic efficacy. Biopsies were subsequently taken for histological evaluation.ResultsClinical and histological data, confirmed with modeling, demonstrated that multi‐pulse laser delivery with bulk air‐cooling selectively increased SG temperature compared to surrounding dermis and at depths unachievable by a single pulse. Subjects showed an average 71% ILC reduction at 3 months posttreatment. We identified two different pulsing protocols with similar selective photothermolysis (SP) of the SG with very different pain responses. Thus, changing the pulsing protocols allowed for pain mitigation and eliminated the need for injectable anesthetic. Histology confirmed the selective damaging of the SG at depth and the preservation of the surrounding dermis and the epidermis.ConclusionsThe multi‐pulse 1726 nm laser with bulk air‐cooling, thermal monitoring, treat‐to‐temperature (and depth) control, and a unique pulsing protocol, is capable of selectively damaging SGs at depth without damage to the surrounding dermis or the epidermis. The system offers two different protocols that were developed with different levels of discomfort allowing for two different methods for pain mitigation (injectable vs. topical anesthesia).

ImportanceInconsistent 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.ObjectiveTo 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 ReviewA 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.FindingsThe 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 RelevanceThis 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.

Background: As acne can cause inflammation-associated sequelae (eg, post-inflammatory hyperpigmentation) in individuals with melanin-rich skin, effective and rapid management must be balanced with minimization of skin irritation. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (IDP-126) polymeric mesh gel is the first fixed-dose, triple-combination topical acne product in development. In clinical studies, over half of participants achieved treatment success with IDP-126 gel after 12 weeks. The objective of this pooled, post hoc analysis was to evaluate safety and tolerability of IDP-126 gel in Black participants. Methods: In two identical phase 3, double-blind, randomized, 12-week studies (NCT04214639; NCT04214652), participants aged ≥9 years with moderate-to-severe acne were randomized (2:1) to receive once-daily IDP-126 or vehicle gel. Assessments included treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability (hyperpigmentation, hypopigmentation, erythema, scaling, itching, burning, and stinging; graded from 0 [none] to 3 [severe]). Post hoc analyses were based on participants’ self-identification of race as ‘Black or African American’ (hereafter referred to as Black). Results: Of 363 randomized participants, 54 (14.9%) self-identified as Black. No serious TEAEs were reported and no TEAEs led to discontinuation. Treatment-related TEAEs were reported in 7 (17.5%) IDP-126-treated Black participants; the most common were application site pain (n=5 [12.5%]) and application site pruritus (n=2 [5.0%]). No vehicle-treated participants reported treatment-related TEAEs. TEAEs in Black participants were generally similar to the overall population. Mean severity scores for all cutaneous safety/tolerability assessments following IDP-126 treatment were <0.55 at all study visits (1=mild). Rates of hyperpigmentation remained relatively unchanged throughout the study while erythema decreased by over 10% from baseline to week 12 with IDP-126 treatment. Rates of all other cutaneous safety/tolerability assessments were low (<9%) at both baseline and week 12. Conclusions: Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (IDP-126) gel was safe and well tolerated in Black participants with moderate-to-severe acne over 12 weeks, with no discontinuations or serious TEAEs. Additionally, IDP-126 treatment led to improved erythema in Black participants and no substantial increases in hyperpigmentation. These post hoc analyses add valuable information to the limited literature describing treatment effects and tolerability of novel acne therapeutics in Black individuals. Support: Ortho Dermatologics.

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

Background: Hyperkeratotic psoriasis produces plaques with extensive elevation and scaling and may be challenging to treat. Tazarotene-induced gene modulation may normalize the keratinocyte differentiation observed in psoriasis. This post hoc analysis of two phase 3 trials of fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) reports skin clearance as measured by the product of the Investigator's Global Assessment and affected body surface area (IGA×BSA) in participants with moderate-to-severe scaling or plaque elevation.

Introduction: Acne vulgaris and related sequelae negatively impact quality of life and are associated with increased rates of anxiety and depression. However, treatment of acne can be difficult due to its long time course, chronicity, and low patient adherence. While national acne guidelines have been recently updated, there is a need for practical, easy-to-use guidance for healthcare practitioners who treat patients with acne. Methods: A roundtable discussion with a panel of eight clinicians and dermatologists was held to provide recommendations for the diagnosis and treatment of acne, including appropriate pharmaceutical treatments based on clinical presentation and patient population, patient discussion points, and advice for clinicians regarding acne treatment. Results: The consensus was that successful acne treatment is contingent upon meeting three core goals: 1) correct diagnosis; 2) proper treatment regimen; and 3) patient adherence and education. 1: Acne should be diagnosed using both quantitative and qualitative assessments, taking into consideration the patient’s lived experience with acne. Quantitative assessments include acne duration; lesion type and location; inflammation; acne-related sequelae; and family history of scarring. Qualitative assessments determine how bothersome acne and/or sequelae are to patients and how much they impact quality of life. Differential diagnoses should be performed to rule out acneiform lesions, genetic disorders, infections, and certain types of medications. 2: For most patients, a combination topical treatment containing benzoyl peroxide and a retinoid and/or an antibiotic is recommended to address the multiple acne pathological processes, though sequelae and patient characteristics should be considered (eg, post-inflammatory hyperpigmentation in patients with skin of color). Fixed-dose combinations are preferred to ensure proper skin coverage, simplify treatment complexity, and improve adherence. 3: For optimal outcomes, patients should be educated about their treatments and consequences of non-adherence; realistic treatment goals should be established to manage patient expectations. A patient handout on skin care best practices can be used to detail their overall skin care regimen, treatments, and subsequent visits. Conclusions: This practical guidance aims to assist clinicians in the successful diagnosis and treatment of acne as well as patient management/education.

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

The vehicles used for topical dermatological treatments can significantly contribute to treatment effects while also delivering ingredients to maintain skin barrier function and reduce irritation. Tazarotene 0.045% lotion was developed using proprietary polymeric emulsion technology to provide uniform and efficient delivery of the active ingredient as well as improved safety and tolerability compared to higher-dose tazarotene formulations. The lotion vehicle additionally provides rapid and sustained improvements in moisturization and skin barrier function with patient-friendly application and cosmetic properties. Compared with trifarotene 0.005% cream, tazarotene 0.045% lotion demonstrated ∼30% greater spreadability and a lower potential for irritation. In clinical trials and investigator-initiated studies, tazarotene 0.045% lotion demonstrated efficacy in the treatment of facial and truncal acne and improved skin oiliness. Facial acne improvements were similar among study participants grouped by sex, race, ethnicity, or age. In a head-to-head study, efficacy was comparable to tazarotene 0.1% cream with approximately half the rate of treatment-emergent adverse events. Tazarotene 0.045% lotion is a beneficial acne treatment option for patients of varying ages, races, ethnicities, and skin types, delivered in a formulation that can be easily used on the face, back, and chest.

Background: Triple-combination therapies for acne including an antibiotic, topical retinoid, and benzoyl peroxide (BPO) are among the most effective, with meta-analyses demonstrating greater efficacy with triple-combinations than dual-combinations or topical monotherapy. However, this benefit may be offset by reduced adherence to a complicated treatment regimen. Here, the clinical efficacy of fixed-dose clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% (CAB) gel is reviewed, and the ease of CAB application is compared with the layered application of its individual active ingredients. Methods: In a phase 2 (N=741) and two phase 3 (N=183; N=180), double-blind, randomized, 12-week studies, participants aged ≥9 years with moderate-to-severe acne were randomized to receive once-daily CAB or vehicle; the phase 2 study also included treatment arms containing dyad gels (BPO/adapalene; clindamycin phosphate/BPO; clindamycin phosphate/adapalene). Efficacy endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin) and reductions from baseline in inflammatory (IL) and noninflammatory lesions (NIL). In a split-face study of adults with acne-prone skin (N=25), participant-application of CAB (0.3 cc) was compared to sequential, layered application of benzoyl peroxide cream, adapalene gel, and clindamycin gel (0.1 cc each). IDP-126 and clindamycin gels were compounded with pyranine, which fluoresces under blue light; photos were taken under blue light to assess evenness of product application. Results: In all three clinical studies at week 12, half of CAB-treated participants achieved treatment success (range: 49.6%-52.5%), significantly greater than with vehicle (8.1%-24.9%; P<0.01, all) or dyads (phase 2 study only; 27.8%-30.5%; P≤0.001, all). Reductions from baseline in both IL and NIL were also significantly greater for CAB vs vehicle (range, IL: 75.7%-80.1% vs 50.4%-59.6%; NIL: 71.0%-73.3% vs 45.8%-49.0%; P<0.001, all) and dyads (IL: 64.0%-69.2%; NIL: 58.7%-61.1%; P<0.01, all vs IDP-126). In the split-face study, 100% of Investigator and participant assessments of evenness of application favored CAB over the three layered products. In addition, all participants rated CAB as both easier and faster to apply, and most (96%) preferred CAB for use at home. Conclusions: Fixed-dose CAB gel applied more evenly than separate application of its three active ingredients, and demonstrated significantly greater efficacy in the treatment of moderate-to-severe acne than dyad gels or vehicle. By addressing three of the main acne pathogenic pathways in a single, easy-to-apply formulation, CAB may improve efficacy of and adherence to acne treatment. Funding: Ortho Dermatologics

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.

BACKGROUND:Using a three-pronged acne treatment approach-combining an antibiotic, antimicrobial agent, and retinoid-may provide greater efficacy than monad or dyad treatments. Herein are the dermal sensitization, irritation, safety, and tolerability results from phase 1 and 2 studies of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) polymeric mesh gel. METHODS:Two phases 1, single-blind, vehicle-controlled dermal safety studies were conducted in healthy participants aged ≥18 years. One phase 2 (NCT03170388) double-blind, randomized, parallel-group, and vehicle-controlled study was conducted over 12 weeks in participants aged ≥9 years with moderate-to-severe acne. RESULTS:A total of 1,020 participants (IDP-126 gel, vehicle, or 1 of the 3 dyad gels [phase 2 only]) were included across the 3 studies (safety populations: n = 1,004). In the phase 1 studies, IDP-126 had no confirmed sensitization or contact dermatitis. IDP-126 (deemed "moderately irritating") was significantly less irritating than commercially available BPO 2.5%/adapalene 0.3% gel. CONCLUSIONS:The results from these three studies show that the triple-combination IDP-126 had a positive safety profile and was well tolerated in healthy participants and those with moderate-to-severe acne.

Introduction: Post-inflammatory hyperpigmentation (PIH) that results from acne in patients with skin of color may be more distressing than the acne itself, and likely impacts patients with higher skin phototypes more greatly than those with lower skin phototypes. Topical retinoids, a mainstay of acne treatment, can also reduce hyperpigmentation. For example, significant PIH improvements with a cream formulation of the retinoid tazarotene (0.1%) were observed following 16 weeks of treatment in patients with acne. However, skin irritation and other skin reactions may limit use of some tazarotene gel and cream formulations. A hydrating, lower-dose tazarotene 0.045% lotion formulation utilizes polymeric emulsion technology to allow for more efficient delivery of tazarotene into dermal layers while reducing potential for skin irritation. This pooled, post hoc analysis evaluates safety of tazarotene 0.045% lotion and its effect on hyperpigmentation in Black individuals with acne. Methods: In two identical phase 3 randomized, double-blind, vehicle-controlled, studies (NCT03168321; NCT03168334), participants aged ≥9 years with moderate-to-severe acne (Evaluator's Global Severity Score of 3/4) were randomized (1:1) to once-daily tazarotene 0.045% or vehicle lotion for 12 weeks. Safety evaluations included adverse events (AEs) reports and investigator-assessed hyperpigmentation (4-point scale: 0 [none] to 3 [severe]). Post hoc analyses were based on participants’ self-identification of race, including ‘Black or African American’ (herein referred to as Black). Results: Of 1,614 participants randomized in the two phase 3 studies, 262 (16%) self-identified as Black. The safety population comprised 253 Black participants. The most common TEAEs with tazarotene 0.045% lotion were at the application site: pain (6.6%), exfoliation (5.0%), and dryness (3.3%). No Black participants reported application site irritation or dermatitis with tazarotene lotion. Hyperpigmentation rates in Black participants, which were high at baseline, decreased by week 12 with tazarotene treatment (40.5% to 31.4%) compared to vehicle (37.9% to 37.2%). Conclusions: Acne regimens that maximize efficacy while mitigating irritation is key to managing acne in patients with skin of color, given the higher pigmentary alteration risk in melanin-rich skin. Tazarotene 0.045% lotion was safe and well tolerated in Black participants, with no application-site irritation or dermatitis after 12 weeks of once-daily treatment. Tazarotene also led to improvements in hyperpigmentation, an inflammation-associated sequala of acne. As PIH can take longer than 12 weeks to resolve with treatment, additional improvements in hyperpigmentation may be expected with continued tazarotene 0.045% lotion use. Support: Ortho Dermatologics.