Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis.

BACKGROUND: Tapinarof cream is a topical aryl hydrocarbon receptor-modulating agent under investigation for the treatment of psoriasis. Tapinarof modulates the expression of interleukin-17 and the skin-barrier proteins filaggrin and loricrin. METHODS: We conducted two identical phase 3 randomized trials of tapinarof in patients with mild-to-severe plaque psoriasis. Adults with a baseline Physician's Global Assessment (PGA) score of 2 (mild) to 4 (severe) (on a scale from 0 to 4, with higher scores indicating more severe psoriasis) and a percent of total body-surface area affected of 3 to 20% were randomly assigned in a 2:1 ratio to use tapinarof 1% cream or vehicle cream once daily for 12 weeks. The primary end point, PGA response, was a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points at week 12. Secondary efficacy end points at week 12 were a reduction of at least 75% in the Psoriasis Area and Severity Index (PASI) score, a PGA score of 0 or 1, the mean change from baseline in the percent of body-surface area affected, and a reduction of at least 90% in the PASI score. Patient-reported outcomes were the mean changes from baseline to week 12 in the proportion of patients who had a decrease of at least 4 points in the Peak Pruritus Numeric Rating Scale (PP-NRS) score (range, 0 [no itch] to 10 [worst imaginable itch]), the PP-NRS total score, the Dermatology Life Quality Index total score, and the Psoriasis Symptom Diary score. RESULTS: In trials 1 and 2, a total of 692 and 674 patients, respectively, were screened, with 510 and 515 patients being enrolled. A PGA response occurred in 35.4% of the patients in the tapinarof group and in 6.0% of those in the vehicle group in trial 1 and in 40.2% and 6.3%, respectively, in trial 2 (P<0.001 for both comparisons). Results for secondary end points and patient-reported outcomes were generally in the same direction as those for the primary end point. Adverse events with tapinarof cream included folliculitis, nasopharyngitis, contact dermatitis, headache, upper respiratory tract infection, and pruritus. CONCLUSIONS: Tapinarof 1% cream once daily was superior to vehicle control in reducing the severity of plaque psoriasis over a period of 12 weeks but was associated with local adverse events and headache. Larger and longer trials are needed to evaluate the efficacy and safety of tapinarof cream as compared with existing treatments for psoriasis. (Funded by Dermavant Sciences; PSOARING 1 and 2 ClinicalTrials.gov numbers, NCT03956355 and NCT03983980, respectively.).

Long-term safety and effectiveness of roflumilast cream 0.3% in adults with chronic plaque psoriasis: A 52-week, phase 2, open-label trial.

BACKGROUND: Efficacy and/or safety profiles limit topical psoriasis treatments. OBJECTIVE: Evaluate long-term effects of once-daily roflumilast cream 0.3% in patients with psoriasis. METHODS: In this open-label phase 2 trial, adult patients (N = 332) with psoriasis who completed the phase 2b parent trial or were newly enrolled applied roflumilast once-daily for 52 weeks. Safety and effectiveness were assessed. RESULTS: Overall, 244 patients (73.5%) completed the trial; 13 patients (3.9%) discontinued due to adverse events (AEs) and 3 (0.9%) due to lack of efficacy. Twelve patients (3.6%) reported treatment-related AEs; none were serious. ≥97% of patients had no irritation. No tachyphylaxis was observed with 44.8% of the patients achieving Investigator Global Assessment (IGA) Clear or Almost Clear at Week 52. LIMITATIONS: Intertriginous-IGA and Psoriasis Area and Severity Index (PASI) were not evaluated in all patients. CONCLUSIONS: In this long-term trial, once-daily roflumilast cream was well-tolerated and efficacious up to 64 weeks in patients in the earlier trial, suggesting it is suitable for chronic treatment, including the face and intertriginous areas.

Tapinarof cream 1% once daily: Significant efficacy in the treatment of moderate to severe atopic dermatitis in adults and children down to 2 years of age in the pivotal phase 3 ADORING trials.

BACKGROUND: Tapinarof cream 1% once daily (QD), a topical aryl hydrocarbon receptor agonist, downregulates pro-inflammatory Th2 cytokines, upregulates skin-barrier components, and reduces oxidative stress. OBJECTIVE: To assess tapinarof efficacy and safety in adults and children down to 2 years of age with atopic dermatitis (AD). METHODS: Eight hundred and thirteen patients were randomized to tapinarof or vehicle QD in two 8-week phase 3 trials. RESULTS: The primary efficacy endpoint, Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and ≥2-grade improvement from baseline at Week 8, was met with statistical significance in both trials: 45.4% versus 13.9% and 46.4% versus 18.0% (tapinarof vs vehicle; both P < .0001). Significantly superior Eczema Area and Severity Index 75 (EASI75) responses were also observed with tapinarof versus vehicle at Week 8: 55.8% versus 22.9% and 59.1% versus 21.2% (both P < .0001). Rapid improvements in patient-reported pruritus were also significant with tapinarof versus vehicle. Common adverse events (≥5%) of folliculitis, headache, and nasopharyngitis were mostly mild or moderate, with lower discontinuations due to adverse events in the tapinarof groups than with vehicle. LIMITATIONS: Long-term efficacy was not assessed. CONCLUSION: Tapinarof demonstrated highly significant efficacy and favorable safety and tolerability in a diverse population of patients with AD down to 2 years of age.

Full Guidelines-From the Medical Board of the National Psoriasis Foundation: Perioperative management of systemic immunomodulatory agents in patients with psoriasis and psoriatic arthritis.

BACKGROUND: Systemic immunomodulatory agents are indicated in the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. Perioperative use of these medications may increase the risk of surgical site infection (SSI) and complication. OBJECTIVE: To evaluate the risk of SSI and complication in patients with chronic autoimmune inflammatory disease receiving immunomodulatory agents (tumor necrosis factor-alfa [TNF-α] inhibitors, interleukin [IL] 12/23 inhibitor, IL-17 inhibitors, IL-23 inhibitors, cytotoxic T-lymphocyte-associated antigen-4 costimulator, phosphodiesterase-4 inhibitor, Janus kinase inhibitors, tyrosine kinase 2 inhibitor, cyclosporine (CsA), and methotrexate [MTX]) undergoing surgery. METHODS: We performed a search of the MEDLINE PubMed database of patients with chronic autoimmune inflammatory disease on immune therapy undergoing surgery. RESULTS: We examined 48 new or previously unreviewed studies; the majority were retrospective studies in patients with rheumatoid arthritis and inflammatory bowel disease. CONCLUSION: For low-risk procedures, TNF-α inhibitors, IL-17 inhibitors, IL-23 inhibitors, ustekinumab, abatacept, MTX, CsA, and apremilast can safely be continued. For intermediate- and high-risk surgery, MTX, CsA, apremilast, abatacept, IL-17 inhibitors, IL-23 inhibitors, and ustekinumab are likely safe to continue; however, a case-by-case approach is advised. Acitretin can be continued for any surgery. There is insufficient evidence to make firm recommendations on tofacitinib, upadacitinib, and deucravacitinib.

Vaccination recommendations for adults receiving biologics and oral therapies for psoriasis and psoriatic arthritis: Delphi consensus from the medical board of the National Psoriasis Foundation.

BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.

Halobetasol Propionate 0.01% and Tazarotene 0.045% Lotion With a Ceramide-Containing Moisturizer in Adults With Psoriasis.

INTRODUCTION: Moisturizers are often used as adjuvant therapy for psoriasis to assist with rehydration and skin barrier restoration. Fixed-combination halobetasol propionate 0.01% and tazarotene 0.045% lotion (HP/TAZ) is indicated for the topical treatment of plaque psoriasis in adults, with a demonstrated clinical profile in two phase 3 trials. However, the effect of application order with HP/TAZ has yet to be explored. This study evaluated the clinical profile of HP/TAZ applied before versus after a ceramide-containing moisturizer in adults with mild-to-moderate plaque psoriasis. METHODS: Sixteen participants were randomized to apply HP/TAZ followed by moisturizer on one side and moisturizer followed by HP/TAZ on the other side once daily for 12 weeks. Tolerability, safety, efficacy, and quality of life endpoints were assessed.  Results: Significant Investigator's Global Assessment improvement was observed across all time points (P≤0.003) regardless of application order. Total Dermatology Life Quality Index scores significantly improved at all time points (P≤0.003), and visual analog scale for itch significantly improved at weeks 4, 8, and 12 (P<0.008). Four moderate adverse events were experienced by 3 participants. Two participants reported itching/irritation, which was worse when HP/TAZ was applied first. CONCLUSIONS: The application order of moisturizer did not decrease therapeutic efficacy of HP/TAZ. Moisturizer application before HP/TAZ may reduce incidence of application site adverse events, ultimately increasing tolerability and supporting the real-world recommendation that applying a ceramide-containing moisturizer before HP/TAZ, versus after, results in a safe and effective therapeutic option for plaque psoriasis. J Drugs Dermatol. 2024;23(2):50-53.     doi:10.36849/JDD.7928.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

INDIVIDUAL ARTICLE: Antibiotic Stewardship in Acne: 2023 Update.

Antibiotics, topical and oral, are a cornerstone in the treatment of acnes vulgaris specifically by targeting the skin bacterium Cutibacterium acnes. Billions of individuals have received antibiotics as part of their treatment resulting in a worldwide pandemic of antibiotic resistance not only for C. acnes but also many other pathogens. With the increasing prevalence of acne and exponentially increasing utilization of antibiotics, prescribers must urgently embrace the notion of antibiotic stewardship to maintain the efficacy of acne treatments while attenuating the rise of resistance. This paper serves as an update on C. acnes resistance to antibiotics commonly employed in the treatment of acne and the necessity of implementing benzoyl peroxide in the treatment regimen as monotherapy or combination antibiotic therapies for overcoming and preventing resistance. J Drugs Dermatol. 2024;23:1(Suppl 2):s4-10.

COVID-19 Protection Strategies: Lessons Learned About Epidermal Barrier Function and the Significance of Optimized Skin Care.

Initially categorized as primarily a respiratory disease, COVID-19 can involve other organ systems and may have direct skin manifestations, including exanthems, morbilliform eruption, generalized urticaria, or pseudo-chilblains —commonly called “COVID Toes.” Frequent handwashing and prolonged wearing of face masks and shields in efforts to minimize transmission of SARS-CoV-2, the novel coronavirus that causes COVID, has given rise to indirect skin manifestations of COVID. “Maskne” and handwashing dermatitis are particularly common among healthcare workers. Characterized by skin inflammation, dryness, pruritus, and other symptoms, these conditions are fundamentally disorders of skin barrier dysfunction. This dysfunction may result from the combination of mechanical skin damage, changes in skin pH, reductions in skin lipids attributable to protection measures, and local alterations in the cutaneous microbiome. Strategies to manage these conditions focus on reversing and repairing skin barrier damage with preventative general measures, optimized skin care with the selection of proper products, eliminating irritant exposures, and avoiding certain medications, such as topical corticosteroids, that may further impair barrier function despite temporary improvement in signs and symptoms. J Drugs Dermatol. 2024;23(4):  doi:10.36849/JDD.7862.

INDIVIDUAL ARTICLE: Update on Combined Topical Products for Treating Acne: Leaping From Dyads.

Antibiotic resistance and treatment adherence remain significant challenges for acne treatment. Advances in topical formulations have ushered in an era of fixed combination topical therapeutics that are well-tolerated and more efficacious. In addition, their once-daily application leads to increased treatment adherence. This article discusses formulation strategies that allow for the coadministration of active drugs and reviews all commercially available fixed-combination topical acne treatments.  J Drugs Dermatol. 2024;23:4(Suppl 2):s4-10.

Selective Tyrosine Kinase 2 (TYK2) Inhibition in Plaque Psoriasis.

Members of the Janus kinase (JAK) superfamily, comprising tyrosine kinase 2 (TYK2) and JAK1, JAK2, and JAK3, mediate signaling by cytokines (eg, interleukin [IL]-23) involved in psoriasis pathogenesis. Binding of IL-23 to its receptor activates TYK2 and JAK2, which trigger signal transducer and activator of transcription (STAT) translocation to the nucleus to regulate target gene transcription, including genes of proinflammatory mediators such as IL-17. Physiologically, TYK2 solely mediates immune function, whereas JAK1,2,3 mediate broad systemic and immune functions. Inhibition of individual JAK family members is being evaluated in many dermatologic indications, including psoriasis. Selective TYK2 inhibition is therefore expected to be associated with few adverse effects in patients with psoriasis. People with genetic mutations leading to loss of function of TYK2 are protected from the development of psoriasis without an increased risk of infections or malignancies. In contrast, treatments with JAK1,2,3 inhibitors are associated with various systemic effects. We review the unique allosteric mechanism of action of the selective TYK2 inhibitor, deucravacitinib, which binds to the TYK2 regulatory (pseudokinase) domain, and the mechanisms of action of JAK1,2,3 inhibitors, which bind to the adenosine 5'-triphosphate-binding active (catalytic) site in the kinase domains of JAK1,2,3. Deucravacitinib, which is approved for the treatment of moderate to severe plaque psoriasis in adults in the United States and several other countries, represents a novel, targeted systemic treatment approach with a favorable safety profile. J Drugs Dermatol. 2024;23(8):645-652.  doi:10.36849/JDD.8293.

First Use of Combination Oral Deucravacitinib With Tapinarof Cream for Treatment of Severe Plaque Psoriasis.

Plaque psoriasis is a chronic, immune-mediated, cutaneous, and systemic inflammatory dermatosis. Its pathogenesis involves the dysregulation of the interleukin (IL)-23/IL-17 signaling pathway. There are a range of treatment options available, encompassing topical agents, biologics, oral systemic therapy, and phototherapy. The utility of combination treatment has also been described and is a budding field of research. Here we describe the first case of adult severe generalized plaque psoriasis treated with once-daily oral deucravacitinib 6 mg combined with tapinarof cream 1% applied once daily. To our knowledge, the combination of these agents has not yet been described in the literature. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.8091.

Preference for Cal/BDP Cream or Foam in Patients With Mild to Moderate Plaque Psoriasis.

BACKGROUND: The combined use of topical calcipotriol/betamethasone dipropionate (Cal/BDP) is commonly used and demonstrated to be effective for the management of psoriasis and is shown to confer local anti-inflammatory and immunoregulatory effects. The use of the two agents in combination is synergistic. Despite the demonstrated efficacy of topically applied combination Cal/BDP, successful management of a chronic, relapsing inflammatory skin disease such as psoriasis in the real-world setting may be hindered if patients do not adhere to the dosing or frequency of application recommendations from their prescriber. Patient preference for and satisfaction with the topical treatment vehicle have been shown to influence adherence. A recent analysis has determined that patients perceived Cal/BDP cream vehicle with PAD technology as having favorable characteristics. This randomized, split-body study was undertaken to further assess patient satisfaction with Cal/BDP cream and Cal/BDP foam formulations. TRIAL DESIGN: This was a split-body, subject-blind study. Study cream was administered in a single application to one side of the scalp and/or body; study foam was applied to the contralateral side. Patient self-administered questionnaires were completed before and after product application after a single site visit. RESULTS: Mean overall Vehicle Preference Measure (VPM) scores were higher for Cal/BDP cream than Cal/BDP foam (P=0.0043). Cal/BDP cream also achieved higher individual scores for ease of application, feeling to the touch, smell, and feeling on the skin (P<0.03). With regards to scalp application, subject assessments show that the cream was significantly more preferred in terms of limiting daily disruption (P=0.0008) Conclusion: Results of this study suggest that patients may prefer Cal/BDP cream over Cal/BDP foam for the management of psoriasis on the body and the scalp. Cal/BDP cream outperformed Cal/BDP foam on several specific measures of satisfaction and overall satisfaction measures. J Drugs Dermatol. 2024;23(8):607-611.  doi:10.36849/JDD.7993.

Topical Clindamycin in the Management of Acne Vulgaris: Current Perspectives and Recent Therapeutic Advances.

Clindamycin is a lincosamide-derivate antibiotic that has been widely used both systemically and topically for approximately 5 decades. The antimicrobial profile of clindamycin primarily covers several gram-positive bacteria and anaerobic bacteria, with multiple clinical applications supported in the literature and with widespread real-world use. Topical clindamycin has been used primarily for the treatment of acne vulgaris, with both monotherapy and combination therapy formulations available commercially. This article reviews the use of clindamycin as a topical agent with emphasis on therapy for acne vulgaris, and addresses modes of action, reported anti-inflammatory properties that may relate to therapeutic outcomes, recommendations to avoid the emergence of antibiotic-resistant bacteria, tolerability and safety considerations, and published data from clinical studies completed over a span of several years. A discussion of a newly FDA-approved triple-combination formulation is also included.  J Drugs Dermatol. 2024;23(6):438-445.     doi:10.36849/JDD.8318.

Promoting a Healthy Skin Barrier Using Skin Care in People With Mature Skin Xerosis.

INTRODUCTION: Most people are living into their sixties and beyond. Fundamental changes in chronologically aged skin have significant and widespread dermatological implications. This review discusses aging-associated alterations in epidermal function leading to xerosis and related pruritus and the benefits of maintaining or restoring a healthy skin barrier using skincare, specifically ceramide-containing skincare.   Methods: A panel of 7 dermatologists convened for a meeting to review aspects of xerosis in mature skin, skin barrier changes, and nuances in the treatment and maintenance of mature skin using gentle cleansers and moisturizers. From the selected literature, 13 statements were drafted. During the meeting, the draft statements underwent the panel's evaluation at a workshop, followed by a plenary discussion adopting 5 statements using evidence from the literature coupled with the panel's opinions and experiences. RESULTS: The exact etiology of xerosis is not entirely understood and likely depends on several genetic and environmental mechanisms. Aging-associated changes in epidermal function include a marked reduction in total lipids in the stratum corneum relative to young skin due to reduced epidermal lipid synthesis. In aging skin, xerosis is significantly associated with pruritus. Studies have shown that lipid-containing skin care, such as a gentle ceramide-containing cleanser and moisturizer, promotes a healthy barrier reducing xerosis and pruritus in individuals with mature skin.  Conclusions: The development of xerosis in mature skin involves several genetic and environmental mechanisms. Skincare, including gentle cleansers and moisturizers, has reduced xerosis and pruritus in mature skin individuals.     J Drugs Dermatol. 2024;23(1):1253-1259.     doi:10.36849/JDD.7560.

Attenuation of Atopic Dermatitis in Newborns, Infants, and Children With Prescription Treatment and Ceramide-Containing Skin Care: A Systematic Literature Review and Consensus.

BACKGROUND: Atopic dermatitis (AD) typically starts in infancy and early childhood. The chronic skin disorder is associated with recurrent flares, pruritus, and genetic predisposition. Daily use of moisturizers that contain lipids, such as ceramides, reduces the rate of AD flares and the need for topical steroid treatment. We aimed to provide insights on AD attenuation to tailor AD prescription therapy, skin care, and maintenance treatment to improve pediatric patients with AD and families. METHODS: A panel of 6 pediatric dermatologists and dermatologists who treat neonates, infants, and children developed a consensus paper on AD attenuation for pediatric patients. The modified Delphi process comprised a face-to-face panel meeting and online follow-up to discuss the systematic literature search results and draw from clinical experience and opinion of the panel to adopt and agree on 5 statements.  Results: Understanding the functional properties of newborn and infant skin, discussing skincare product use with parents, and recommending tailored prescription and skincare routines can improve newborn, infant, and children’s skin health. Studies on the prophylactic application of moisturizers initiated in early infancy suggest moisturizers may delay rather than prevent AD, especially in high-risk populations and when used continuously. Increasingly there is evidence that moisturizer application reduces the severity of AD and extends the time to flares, which may help attenuate the atopic march. The protective effect of skin care for AD has been observed in studies where its daily use is ongoing; these beneficial effects may be lost in less than 1year after cessation. It is therefore important to emphasize that skin care should be routinely used when counseling patients and caregivers.  Conclusion: Healthcare providers can improve patient outcomes in atopic-prone infants and children by providing instructions regarding the daily benefits of applying skin care with gentle cleansers and moisturizers. Using gentle cleansers and moisturizers containing barrier lipids from birth onward may delay AD occurrence and mitigate severity in predisposed infants.J Drugs Dermatol. 2024;23(3): doi:10.36849/JDD.7894.

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

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

Patient- and Clinician-Reported Outcomes for Tirbanibulin in Actinic Keratosis in Clinical Practice Across the United States (PROAK).

BACKGROUND: The Patient-Reported Outcomes in Actinic Keratosis (PROAK) study evaluated patient- and clinician-reported outcomes (PRO; ClinRO) during 24 weeks of follow-up among adult patients with actinic keratosis (AK) on the face or scalp who were administered tirbanibulin 1% ointment in real-world community practices in the United States.  Methods: Quality of life (QoL) was assessed by Skindex-16 at week (W) 8. Additionally, effectiveness (Investigator Global Assessment [IGA]), PRO and ClinRO (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire), safety, and tolerability were assessed at W8 and W24. RESULTS: The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P<0.03) was observed for Skindex-16 domains in all assessed subgroups. Clinicians and patients reported high global satisfaction (mean [SD] scores of 74.9 [23.9] and 72.0 [24.6], respectively) at W24. Overall skin appearance improved from baseline to W24 (83.6% clinicians; 78.5% patients). IGA success (IGA score of 0-1) was achieved by 71.9% of patients at W24 with a similar % at W8 (73.8%) suggesting a stable effectiveness over time. About 5% of patients reported at least one adverse event, 4% reported at least one serious adverse event and no patients reported serious adverse drug reactions. At W8, the most frequently reported local skin reactions were mild/moderate erythema (47.6%) and flaking/scaling (49.6%). CONCLUSIONS: Treatment with tirbanibulin demonstrated effectiveness in the management of AK lesions and a favorable safety and tolerability profile. Furthermore, QoL was improved as early as W8, and both patients and clinicians reported high levels of treatment satisfaction, independently of patients' characteristics. J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264.

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

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

Benefit of Topical Combination Therapy for Acne: Analyzing Effect Size Using Number Needed to Treat.

BACKGROUND: Topical acne trials often are confounded by high vehicle response rates and differing outcome measures, making it difficult to compare treatments. Number needed to treat (NNT) can be a simple, clinically meaningful way to indirectly compare treatment options without head-to-head data. NNT is the number of patients who need to be treated with an intervention to observe one additional patient successfully achieving a desired outcome versus vehicle/placebo. While treatment attributes such as adverse events may not be captured, lower NNT is a good indicator of a more effective treatment. METHODS: Following a search of combination topical treatments for acne vulgaris, all treatments that reported pivotal trial efficacy data consistent with the 2018 FDA definition of success were included in NNT analyses.  Results: Of 13 treatments, 7 reported 12-week treatment success rates in 11 phase 3 trials, with similar baseline demographics/disease severity. Treatment success ranged from 26.8% with tretinoin 0.1%/benzoyl peroxide (BPO) 3% cream to 50% with triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel. NNTs for the triple-combination gel were 4 and 5 (from 2 pivotal trials). Adapalene 0.3%/BPO 2.5% gel had an NNT of 5. Tretinoin/BPO had the largest range between trials, with NNTs of 4 and 9. The other 4 treatments had NNTs ranging from 6 to 8. CONCLUSION: A comparison of combination topical acne treatment trial data, using the same treatment outcome and similar patient populations, resulted in triple-combination clindamycin phosphate/adapalene/BPO gel and adapalene/BPO gel having the most favorable NNTs.J Drugs Dermatol. 2024;23(2):42-49.  doi:10.36849/JDD.7927.