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Abstract Introduction Lebrikizumab is a novel monoclonal antibody with established efficacy in patients with moderate-to-severe atopic dermatitis (AD) in multiple Phase 3 trials. One of the ultimate treatment goals for patients with moderate-to-severe AD is to achieve stable disease control without concern for planning future life events. Methods In ADvocate1 and ADvocate2, lebrikizumab-treated patients meeting the protocol-defined response criteria at Week 16 were re-randomized 2:2:1 to receive lebrikizumab every 2 weeks (Q2W), lebrikizumab every 4 weeks (Q4W), or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. In this post hoc analysis, we evaluated the proportions of patients with no or minimal fluctuations of efficacy during the 36-week maintenance period and plotted individual patient trajectories. We defined no or minimal fluctuations as achieving and maintaining the defined endpoint (≥ 75% improvement in the Eczema Area and Severity Index [EASI 75], ≥ 90% improvement in EASI, Pruritus Numeric Rating Scale [NRS] ≥ 4-point improvement, or Pruritus NRS ≥ 3-point improvement) for ≥ 80% of the study visits. If patients used rescue medication, discontinued treatment, or transferred to the escape arm, data collected at or after the event were imputed as non-response. Results The proportions of lebrikizumab responders who maintained EASI 75 with no or minimal fluctuations were 70.8% (lebrikizumab Q2W), 71.2% (lebrikizumab Q4W), and 60.0% (lebrikizumab withdrawal). Of the patients with baseline Pruritus NRS ≥ 4 and who achieved ≥ 4-point improvement at Week 16, 66.1% (lebrikizumab Q2W), 62.7% (lebrikizumab Q4W), and 55.2% (lebrikizumab withdrawal) maintained ≥ 4-point Pruritus NRS improvement with no or minimal fluctuations. Conclusions Patients who met the response criteria at Week 16 and continued treatment with lebrikizumab Q2W or Q4W demonstrated a stable response with no or minimal fluctuations of efficacy in measures of skin and itch up to Week 52. Clinical Trial Registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).

Abstract 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 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

Background The decision to initiate advanced systemics in patients with atopic dermatitis (AD) is complex.Objectives To explore disease burden and clinical characteristics of patients with moderate-to-severe AD and identify characteristics associated with initiating new systemics.Methods Data from prospective, longitudinal, non-interventional CorEvitas AD Registry were evaluated. Differences in demographic and clinical characteristics, comorbidities, disease severity (vIGA-AD™; body surface area (BSA); Eczema Area and Severity Index (EASI); SCORing AD [SCORAD]), and patient-reported outcomes (PROs) were assessed between systemic and non-systemic therapy groups.Results Of 883 patients, 673 were newly prescribed systemics and 210 were not. Non-systemic therapy group had higher than expected rates of severe disease at enrollment based on vIGA-AD = 4 (39%), mean BSA involvement (31%), and mean EASI (19). PROs for non-systemic therapy group indicated elevated burden from AD on quality of life and poor disease control. SCORAD, peak pruritus in the past 24 h, history of biologics, and facial pallor, were significantly associated with initiation of systemics at enrollment.Conclusion While disease burden likely influences the initiation of systemic therapy, many patients with significant burden are not treated with systemics for unclear reasons. Further research is needed to identify other factors, beyond disease severity, that influence this decision.

AbstractPurpose: Topical clindamycin, a lincosamide antibiotic, is commonly combined with benzoyl peroxide or a retinoid for acne vulgaris (AV) treatment. While oral and topical clindamycin carry warnings/contraindications regarding gastrointestinal (GI) adverse events (AEs), real-world incidence of GI AEs with topical clindamycin is unknown. This review provides background information and an overview of safety data of topical clindamycin for treating AV.Materials and Methods: Available safety data from published literature, previously unpublished worldwide pharmacovigilance data, and two retrospective cohort studies were reviewed.Results and Conclusions: According to pharmacovigilance data, the rate of GI adverse drug reactions with topical clindamycin-containing products was 0.000045% (64/141,084,533). Results from two retrospective medical record studies of patients with AV indicated that physicians prescribe topical clindamycin equally to patients with or without inflammatory bowel disease history, and that rates of pseudomembranous colitis in these patients were low. In 8 published pivotal clinical trials of topical clindamycin for AV, GI AEs were reported in 1.4% of participants. Limitations include under/inaccurate reporting of AEs or prescription data and limited generalizability. This review of published case reports, worldwide pharmacovigilance data, retrospective US prescription data, and clinical trials safety data demonstrates that the incidence of colitis in patients exposed to topical clindamycin is extremely low.

Abstract Tapinarof cream 1% (VTAMA®; Dermavant Sciences, Inc.) is a non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration (FDA) to treat plaque psoriasis in adults and under investigation for the treatment of psoriasis in children down to 2 years of age, and for atopic dermatitis in adults and children down to 2 years of age. The PSOARING phase 3 clinical trial program evaluated tapinarof cream 1% once daily (QD) in adults with mild to severe plaque psoriasis for up to 52 weeks (NCT03956355, NCT03983980, NCT04053387). Here we present case photography documenting outcomes in the PSOARING trials. Cases illustrate various outcomes across different body areas, including responses meeting the formal FDA-mandated regulatory endpoint of a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear) and a decrease of at least 2 points from baseline at week 12, meaningful clinical improvement not meeting this formal endpoint, patient-reported outcomes, and pre-specified adverse events of special interest (AESIs). Tapinarof cream 1% QD demonstrated rapid and highly statistically significant efficacy, with improvements in disease activity and quality of life. In addition, a high rate (40.9%; n = 312/763) of complete disease clearance (PGA = 0) was achieved, and improvements exceeding National Psoriasis Foundation treatment goals were demonstrated. After first achieving complete disease clearance (PGA = 0), patients treated with tapinarof experienced an approximately 4-month remittive effect off therapy. Incidence and severity of folliculitis and contact dermatitis AESIs were generally mild or moderate, localized to the site of application, and associated with low discontinuation rates. Medical images are of importance in trials of dermatologic therapies to inform clinical decision-making and enhance patient assessment. Tapinarof cream 1% QD is efficacious and well tolerated in patients with mild to severe plaque psoriasis, with clinically relevant improvements seen early in the course of treatment. Clinicaltrials.gov numbers: NCT03956355, NCT03983980, NCT04053387.

Background: Acne, a commonly treated skin disease, requires patient-centered management due to its varying presentations, chronicity, and impact on health-related quality of life. Despite this, evidence-based clinical guidelines focus primarily on clinical severity of facial acne, omitting important patient- and disease-related factors, including ongoing management. Objectives: To generate recommendations to support patient-centered acne management, which incorporate priority and prognostic factors beyond conventional clinical severity, traditionally defined by grading the appearance and extent of visible lesions. Methods: The Personalizing Acne: Consensus of Experts consisted of 17 dermatologists who used a modified Delphi approach to reach consensus on statements regarding patient- and treatment-related factors pertaining to patient-centered acne management. Consensus was defined as ≥75% voting “agree” or “strongly agree.” Results: Recommendations based on factors such as acne sequelae, location of acne, high burden of disease, and individual patient features were generated and incorporated into the Personalized Acne Treatment Tool. Limitations: Recommendations are based on expert opinion, which may differ from patients’ perspectives. Regional variations in healthcare systems may not be represented. Conclusions: The Personalizing Acne: Consensus of Experts panel provided practical recommendations to facilitate individualized management of acne, based on patient features, which can be implemented to improve treatment outcomes, adherence, and patient satisfaction.

Abstract Introduction Psoriasis ranges from mild to severe with the majority of patients having mild disease. Mild to moderate disease is often treated with topical therapies while photo-, oral, and biologic therapies are generally reserved for moderate-to-severe disease. There is a strong scientific rationale for the combination of calcipotriene (CAL) and betamethasone dipropionate (BDP) with respect to mode of action, efficacy, and safety and CAL/BDP has shown an inhibitory effect on key pathogenic cytokines in psoriasis including tumor necrosis factor-α, interleukin (IL)-17, and IL-23. Methods The objective of this pooled post hoc analysis is to investigate the efficacy of CAL/BDP polyaphron dispersion (PAD)-cream in subgroups of patients with moderate-to-severe psoriasis from two completed phase 3 studies conducted in the USA and Europe. Results The proportion of patients achieving Physician Global Assessment (PGA) treatment success as well as a modified Psoriasis Area and Severity Index (mPASI)75 response was higher in the subgroup with a body surface area > 10% and mPASI > 10 and Dermatology Life Quality Index > 10 at baseline compared to the overall patient population. Furthermore, the numerical difference in treatment efficacy between CAL/BDP PAD-cream and CAL/BDP topical suspension/gel increased in patient subgroups with higher baseline severity. Similar patterns were shown for the patient-reported outcomes. Conclusion In this subgroup analysis, patients who had higher disease severity at baseline achieved greater efficacy than the total patient population when treated with 8 weeks of CAL/BDP PAD-cream as compared to a currently marketed active comparator. Additionally, as indicated by this analysis, CAL/BDP PAD-cream treatment may also be more convenient and less greasy, which may reduce the burden of daily treatment and improve adherence to therapy. Trial Registration NCT03308799 and NCT03802344.

Background Excessive sebum production is a factor in acne development. Tazarotene 0.045% lotion has demonstrated reductions in acne lesions and acne-induced sequelae. Objective Evaluate efficacy, changes in skin oiliness, and safety with tazarotene 0.045% lotion in participants with moderate-to-severe acne and oily skin. Methods In two phase 3, double-blind, 12-week studies (NCT03168321; NCT03168334), participants aged ≥ 9 years with moderate-to-severe acne were randomized 1:1 to once-daily tazarotene 0.045% lotion or vehicle lotion (N = 1614). This pooled, post hoc analysis included only participants self-categorized with oily skin at baseline on the Acne-Specific Quality of Life questionnaire item 19 (scores: 0 [extremely oily] to 6 [not at all oily]). Inflammatory/noninflammatory lesion counts, treatment success, skin oiliness, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability were evaluated. Results In all participants with oily skin (n = 793), tazarotene provided greater reductions in inflammatory/noninflammatory lesions (p

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

Abstract Introduction The Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) survey study was conducted globally in 2020 to understand how disease perceptions, including disease severity, treatment goals, and quality of life (QoL), have evolved recently, especially for mild-to-moderate psoriatic disease. Here, key findings from the UPLIFT survey based on respondents located in the US are presented. Leveraging results from the UPLIFT survey could lead to more effective interactions between patients and physicians and greater patient satisfaction. Methods UPLIFT was a multinational web-based survey of dermatologists, rheumatologists, and patients who self-reported a healthcare provider diagnosis of psoriasis (PsO) and/or psoriatic arthritis (PsA) conducted from March 2, 2020, to June 3, 2020. Results US respondents included 1006 patients (26.4% of global population; PsO only, n = 535; PsA only, n = 72; PsO and PsA, n = 399) and 216 physicians (dermatologists, n = 115; rheumatologists, n = 101). Most patients (66.4%) reported a body surface area (BSA; assessed by number of palms) of ≤ 3; of these, 56.2% rated their disease as moderate or severe. Most patients with PsO felt they were somewhat (40.1%) or very (49.3%) closely aligned with their dermatologists regarding treatment goals. Alternately, most patients with PsA felt that they were not too closely (32.1%) or not at all (59.3%) aligned with their rheumatologists. Most patients reported either a moderate (PsO, 35.5%; PsA, 31.8%) or strong (PsO, 47.7%; PsA, 53.9%) need for better treatments. Across BSA subgroups, most patients (60.8% to 86.1%) had a Dermatology Life Quality Index score ≥ 6, indicating at least a moderately impacted QoL. Conclusions Despite more treatment options, management of psoriatic disease remains suboptimal, with many patients reporting moderate-to-severe disease and impaired QoL, even with limited skin involvement. Results further suggest an unmet need for alignment between patients and physicians in the US to optimize the management of PsO and PsA. Graphical Abstract

Background: The physical sequelae of acne include erythema, hyperpigmentation, and scarring, which are highly burdensome for patients. Early, effective treatment can potentially limit and prevent sequelae development, but there is a need for guidance for and evidence of prevention-oriented management to improve patient outcomes. Objective: To identify unmet needs of acne sequelae and generate expert recommendations to address gaps in clinical guidance. Methods: The Personalizing Acne: Consensus of Experts panel of 13 dermatologists used a modified Delphi approach to achieve a consensus on the clinical aspects of acne sequelae. A consensus was defined as ≥75% of the dermatologists voting “agree” or “strongly agree.” All voting was electronic and blinded. Results: The panel identified gaps in current guidance and made recommendations related to acne sequelae. These included identification and classification of sequelae, pertinent points to consider for patient consultations, and management aimed at reducing the development of sequelae. Limitations: The recommendations are based on expert opinion and made in the absence of high-quality evidence. Conclusions: The identified gaps should help inform future research and guideline development for acne sequelae. The consensus-based recommendations should also support the process of consultations throughout the patient journey, helping to reduce the development and burden of acne sequelae through improved risk factor recognition, early discussion, and appropriate management.

Background: Truncal acne is common and burdensome for patients; however, there is paucity of evidence and guidance for the management of truncal acne. Currently, clinical practice guidelines provide very little guidance on the assessment or management of truncal acne. Objectives: To identify unmet needs in truncal acne and make recommendations to address clinical and management gaps using an international consensus. Methods: The Personalising Acne: Consensus of Experts panel consisted of 13 dermatologists, who used a modified Delphi approach to reach a consensus on statements related to clinically relevant aspects of truncal acne evaluation and management. A consensus was defined as ≥75% of the panelists voting “agree” or “strongly agree.” The voting was electronic and blinded. Results: The panel identified gaps and made recommendations related to truncal acne identification, assessment, and grading; the evaluation of the impact on patients; and treatment goals and factors to be considered for its management. Limitations: The recommendations are based on expert opinion, in the absence of high-quality evidence. Conclusions: We highlighted addressing not just facial acne but also truncal acne during patient consultations. The recommendations made herein may help facilitate the care of patients who present with truncal acne, with or without facial acne.

Background: Acne is a chronic disease with a varying presentation that requires long-term management. Despite this, the clinical guidelines for acne offer limited guidance to facilitate personalized or longitudinal management of patients. Objectives: To generate recommendations to support comprehensive, personalized, long-term patient management that address all presentations of acne and its current and potential future burden. Methods: The Personalising Acne: Consensus of Experts panel consisted of 13 dermatologists who used a modified Delphi approach to reach consensus on statements related to longitudinal acne management. The consensus was defined as ≥75% voting “agree” or “strongly agree.” All voting was electronic and blinded. Results: Key management domains, consisting of distinct considerations, points to discuss with patients, and “pivot points” were identified and incorporated into the Personalised Acne Care Pathway. Long-term treatment goals and expectations and risk of (or fears about) sequelae are highlighted as particularly important to discuss frequently with patients. Limitations: Recommendations are based on expert opinion, which could potentially differ from patients' perspectives. Regional variations in health care systems may not have been captured. Conclusions: The Personalised Acne Care Pathway provides practical recommendations to facilitate the longitudinal management of acne, which can be used by health care professionals to optimize and personalize care throughout the patient journey.

BackgroundVestibular side effects such as dizziness and vertigo can be a limitation for some antibiotics commonly used to treat acne, rosacea, and other dermatology indications.ObjectiveUnlike minocycline, which is a second-generation tetracycline, sarecycline, a narrow-spectrum third-generation tetracycline-class agent approved to treat acne vulgaris, has demonstrated low rates of vestibular-related adverse events in clinical trials. In this work, we evaluate the brain-penetrative and lipophilic attributes of sarecycline in 2 non-clinical studies and discuss potential associations with vestibular adverse events.MethodsRats received either intravenous sarecycline or minocycline (1.0 mg/kg). Blood-brain penetrance was measured at 1, 3, and 6 h postdosing. In another analysis, the lipophilicity of sarecycline, minocycline, and doxycycline was measured via octanol/water and chloroform/water distribution coefficients (logD) at pH 3.5, 5.5, and 7.4.ResultsUnlike minocycline, sarecycline was not detected in brain samples postdosing. In the octanol/water solvent system, sarecycline had a numerically lower lipophilicity profile than minocycline and doxycycline at pH 5.5 and 7.4.ConclusionThe reduced blood-brain penetrance and lipophilicity of sarecycline compared with other tetracyclines may explain low rates of vestibular-related adverse events seen in clinical trials.

AbstractBackground Lebrikizumab improved itch, interference of itch on sleep, and quality of life (QoL) in patients with moderate-to-severe atopic dermatitis (AD), in two Phase 3 trials at 16 weeks compared to placebo.Objectives We assess improvements in itch and sleep interference due to itch and their impact on QoL measurements after treatment.Methods Data were analyzed from ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) in patients with moderate-to-severe AD. QoL was evaluated using Dermatology Life Quality Index (DLQI) at Week 16 in patients (>16 years of age) who were itch responders/non-responders (defined as ≥4-point improvement in Pruritus Numeric Rating Scale) or Sleep-Loss Scale responders/non-responders (defined as ≥2-point improvement in itch interference on sleep).Results In ADvocate1 and ADvocate2, significantly greater proportions of itch responders had a clinically meaningful improvement in measures related to QoL (DLQI scores (0/1), ≤5 DLQI total score and ≥4-point DLQI improvement) compared to itch non-responders. In both studies, a significantly greater proportion of Sleep-Loss Scale responders, reported a DLQI score of (0/1), DLQI total score of ≤5 and DLQI improvement of ≥4 points compared to Sleep-Loss Scale non-responders.Conclusions Improvement in itch and sleep interference due to itch is associated with improvement in the QoL of patients after treatment with lebrikizumab for moderate-to-severe AD.ClinicalTrials.gov registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).