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

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

Sustained Improvements in Clinical and Patient-Reported Outcomes and Quality of Life Through 5 Years Among Ixekizumab-Treated Patients with Complete Clearance of Scalp Psoriasis by Week 60.

INTRODUCTION: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of moderate-to-severe plaque psoriasis. Since scalp psoriasis can be burdensome and challenging to treat with non-systemic therapies, this post hoc analysis focused on scalp psoriasis in patients with moderate-to-severe plaque psoriasis and baseline scalp involvement. The analysis considered a holistic concept of clearance through 5 years of ixekizumab treatment. METHODS: Ixekizumab-treated patients with baseline scalp involvement were pooled from three multicenter, randomized, double-blind, placebo-controlled, phase 3 trials (integrated UNCOVER-1/2 and UNCOVER-3). Analyses were performed on a subpopulation of patients who achieved complete resolution of scalp psoriasis at Week 60 (i.e., Week 60 Psoriasis Scalp Severity Index [PSSI-0] responders) and on the overall patient population (i.e., Week 60 PSSI-0 responders and non-responders), which was used as a reference. Clinical outcomes (PSSI), patient-reported outcomes (Itch Numeric Rating Scale [NRS] score, Skin Pain Visual Analogue Scale [VAS]), quality of life (Dermatology Life Quality Index [DLQI]), and concurrent outcomes were assessed from baseline through 5 years. Descriptive statistics of observed data were reported. RESULTS: After 60 weeks of ixekizumab treatment, 88.4% (UNCOVER-1/2) and 75.9% (UNCOVER-3) of patients with baseline scalp involvement achieved complete clearance (PSSI-0) of scalp psoriasis. Substantial improvements in the clinical outcomes (PSSI), patient-reported outcomes (Itch NRS, Skin Pain VAS), and quality of life (DLQI) were achieved by Week 60 and sustained through Week 264 in the Week 60 PSSI-0 responders and in the overall patient population. Additionally, a significant proportion of Week 60 PSSI-0 responders achieved concurrent complete scalp and skin clearance and quality of life improvement through 5 years. CONCLUSIONS: Continued treatment with ixekizumab provided long-term sustained scalp clearance over 5 years to patients with moderate-to-severe plaque psoriasis and baseline scalp involvement, and holistic improvements occurred across clinical outcomes, patient-reported outcomes, and quality of life. CLINICAL TRIAL NUMBERS: NCT01474512 (UNCOVER-1), NCT01597245 (UNCOVER-2), and NCT01646177 (UNCOVER-3).

Topical clindamycin for acne vulgaris: analysis of gastrointestinal events.

Purpose: 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.

Expanding the Psoriasis Framework: Immunopathogenesis and Treatment Updates.

Psoriasis is a chronic heterogeneous condition with multiple available treatment options that have resulted in dramatic disease improvements for patients. IL-23/IL-17 signaling is the central immune signaling pathway driving psoriasis, though recent research has uncovered other key contributing signals such as IL-17C, IL-17F, IL-36, and tyrosine kinase 2 (TYK2). Novel therapeutic targets inhibiting these cytokines have expanded our understanding of the pathogenesis of psoriasis. IL-23/IL-17 signaling is critical for the development of epidermal hyperplasia and the mature psoriatic plaque in susceptible individuals. Increased IL-17 and IL-23 expression works synergistically with other cytokines, such as IL-12, IL-22, IL-36, tumor necrosis factor (TNF), and interferon (IFN), to help create a self-sustaining, feed-forward circuit in keratinocytes, which contributes to the chronicity of the disease. This clinical review highlights recent discoveries in the immunopathogenesis of psoriasis and summarizes new antipsoriasis therapies targeting IL-36, IL-17F, aryl hydrocarbon receptors (AHRs), phosphodiesterase 4 (PDE4), and TYK2 signaling. Despite recent success in the treatment of psoriasis, continued research is needed to further advance disease understanding and shape management strategies.

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.

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.

Review of Teledermatology: Lessons Learned from the COVID-19 Pandemic.

Utilization of telemedicine for dermatology has greatly expanded since the start of the COVID-19 pandemic, with over 500 new teledermatology studies published since 2020. An updated review on teledermatology is necessary to incorporate new findings and perspectives, and educate dermatologists on effective utilization. We discuss teledermatology in terms of diagnostic accuracy and clinical outcomes, patient and physician satisfaction, considerations for special patient populations, published practice guidelines, cost effectiveness and efficiency, as well as administrative regulations and policies. Our findings emphasize the need for dermatologist education, prioritization of reliable reimbursement systems, and technological innovations to support the continued development of teledermatology in the post-pandemic era.

INDIVIDUAL ARTICLE: An Algorithm for the Management of Atopic Dermatitis in People With Skin of Color.

BACKGROUND: Variations in the epidemiology, clinical presentation, and disease course in skin of color (SOC) atopic dermatitis (AD) patients have been reported that may impact treatment approach and skincare recommendations. METHODS: The project used a modified Delphi hybrid process comprising face-to-face discussions and an online review process. A panel of physicians (advisors) who treat SOC patients with AD used information from literature searches, expert opinions, and their experience to develop a practical algorithm to improve outcomes for SOC patients with AD. RESULTS: The algorithm for SOC patients with AD aims to inform dermatologists and other healthcare professionals caring for these patients. The first section of the algorithm addresses education and behavioral measures. Treatment adherence is a considerable challenge in chronic inflammatory conditions such as AD, making education essential. The second section discusses the assessment of the skin condition. The third section informs on treatment and maintenance measures for AD. Treatment and maintenance of AD in patients with SOC should be proactive, effectively control inflammation longitudinally, include effective skin barrier protective strategies, and consider cultural practices. CONCLUSION: Robust comparative studies are needed to better understand racial/ethnic variations in AD. The algorithm supports educating healthcare professionals and patients to foster individualized treatment, prevention, and adjunctive skincare approaches across diverse patient populations. J Drugs Dermatol. 2023;22:8(Suppl 2):s3-10.

Validity of Lichen Planus and Lichen Planopilaris Case Identification Using Diagnostic Codes from a Clinical Database.

BACKGROUND: Case identification strategies to conduct population-based studies have not been developed for lichen planus (LP) or lichen planopilaris (LPP). OBJECTIVES: The aim of this study was to assess the validity of using diagnostic codes to establish both a cutaneous (non-oral) LP cohort and an LPP cohort from a large clinical database. METHODS: A retrospective chart review was performed to determine whether patients with ICD-9 or ICD-10 codes for LP and ICD-10 codes for LPP are confirmed cases of LP and LPP. Validation samples were used to estimate the positive predictive value (PPV) of three case definitions any LP, non-oral LP, and LPP defined as: at least one code by any physician, at least two codes by any physician, and at least one code by a dermatologist. RESULTS: Among the 199 reviewed LP charts, 166 and 123 were confirmed cases of any LP and non-oral LP, respectively. The PPVs for any LP were: 83.4% (166/199) for one code by any physician, 84.6% (77/91) for two codes by any physician, and 95.1% (97/102) for one code by a dermatologist. The PPVs for non-oral LP were: 61.8% (123/199) for one code by any physician, 70.3% (64/91) for two diagnoses by any physician, and 86.3% (88/102) for one diagnosis by a dermatologist. Of the 139 patients with at least one code for LPP, 122 were confirmed cases of LPP. The case definition for one LPP code applied by any physician had a PPV of 87.8% (122/139) to identify a true case of LPP, whereas two diagnoses by any physician had a PPV of 96.2% (76/79) and a diagnosis by a dermatologist had a PPV of 93% (107/115). CONCLUSIONS: Diagnosis codes for LP and LPP, restricted by the diagnosing physician's specialty, may be used to accurately identify case cohorts of overall LP, non-oral LP, or LPP in large clinical databases.

Sociodemographic and clinical characteristics associated with multiple biologic failure in psoriasis: A 2015-2022 prospective cohort analysis of the CorEvitas psoriasis registry.

BACKGROUND: Psoriasis patients with poor therapeutic response to multiple biologic agents are not well-characterized. OBJECTIVE: To describe the characteristics associated with development of multiple biologic failure (MBF) versus good clinical response (GR) to the first biologic. METHODS: This prospective cohort analysis evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for ≥24 months. Multivariable logistic regression identified sociodemographic, clinical, and patient-reported outcomes that differed between MBF (discontinued ≥2 biologics of different classes, each used for ≥90 days, due to inadequate efficacy) and GR (continued use of first biologic for ≥2 years) patients. RESULTS: One thousand thirty-nine patients were analyzed (490 GR [47.2%], 65 MBF [6.3%]). Female sex, shorter psoriasis duration, earlier year of biologic initiation, prior nonbiologic systemic therapy use, history of hyperlipidemia, and Medicaid insurance were significantly associated with MBF, though the latter 2 variables exhibited wider confidence intervals, indicating a lower level of support. The first-to-second biologic sequence most observed with MBF was Tumor necrosis factor-α inhibitor to IL-17 inhibitor use. LIMITATIONS: Biologic adherence between visits was not evaluated. CONCLUSION: Approximately 6% of psoriasis patients met MBF criteria. The results identify characteristics associated with MBF that may distinguish patients warranting more frequent follow-up.

Biologic Vs Conventional Therapies: Comparing Risk of Psoriasis-Associated Comorbidities.

Psoriasis is associated with multiple comorbidities. In this retrospective cohort analysis, we compared the comorbidities in patients who received biologic treatments with those who received conventional treatments. Our data indicates that biologics may be associated with lower rates of comorbidities in comparison to conventional therapy. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7119.

National Psoriasis Foundation Telemedicine Task Force guidance for management of psoriatic disease via telemedicine.

Telemedicine emerged as an alternative care delivery system used to offer effective long-term management to patients with chronic, inflammatory conditions such as psoriatic disease. Teledermatology can provide reliable clinical information through thorough history-taking and virtual evaluations that include patient-provided images and disease activity assessment tools that may help accurately diagnose and manage patients with psoriasis. The integration of validated screening tools for psoriatic arthritis and effective teledermatology practices may improve access to specialists, thus avoiding preventable delays in the diagnosis and treatment of patients with psoriatic arthritis. Although the provision of telehealthcare should not completely replace high quality, in-person dermatologic or rheumatologic visits, the convenience and collaborative nature of teledermatology may lead to expanded access and expedited care in the appropriate setting, whether it be in a virtual or in-person visit.

Association Between Atopic Dermatitis, Anxiety, and Symptoms of Panic Among United States Adults in the 2001-2004 National Health and Nutrition Examination Survey.

Atopic dermatitis (AD) is a common, chronic inflammatory dermatologic condition that can cause discomfort and thus negatively influence the mental health of patients. Research directly exploring the relationship between AD, anxiety, and symptoms of panic in a large United States (US) adult population is limited. We studied the relationship between AD and anxiety versus panic in US adults aged 20 to 39 years. The association between AD and anxiety was significant, but not between AD and panic. This association between AD and anxiety was significantly increased in adults aged 30 to 39 years and female adults. Our study may demonstrate that a focus on the wellbeing of patients might be helpful in clinical practice. Further longitudinal studies can help to elucidate these relationships.

The use of ultrasound to detect enthesitis as a potential guide for intervention in patients with psoriasis at risk of psoriatic arthritis: a systematic review.

INTRODUCTION: Psoriatic arthritis is estimated to develop in 2% of patients with psoriasis per year and can result in significant morbidity. Early diagnosis and treatment of psoriatic arthritis are imperative to prevent irreversible arthritic joint damage. Dermatologists play a key role in identifying patients who are at risk for or with early signs of psoriatic arthritis. Subclinical enthesopathy may be a risk factor for psoriatic arthritis or an early sign of the disease and can be detected using ultrasound. METHODS: In this systematic review, we determined the prevalence of ultrasound-diagnosed enthesitis in psoriasis patients, as well as their risk of subsequent progression to psoriatic arthritis. RESULTS: We determined that the detection of enthesitis on ultrasound was associated with higher risk of future psoriatic arthritis. Systemic therapy was associated with improvement in enthesitis findings in patients with psoriasis but not in those with chronic structural damage or established psoriatic arthritis. Additionally, one study showed that ustekinumab treatment resulted in a significantly lower rate of psoriatic arthritis development. CONCLUSIONS: These studies support the value of early detection and treatment in the prevention of progression to psoriatic arthritis, as well as the use of ultrasound for screening for risk factors in psoriasis patients. Future studies are needed to further evaluate when preventative therapy can be useful among patients with psoriasis with risk factors for psoriatic arthritis.

New Treatments for Psoriasis: An Update on a Therapeutic Frontier.

The landscape of psoriasis treatments has undergone rapid change within the last decade and the dizzying speed of drug development has not slowed, with 4 notable entries into the psoriasis treatment armamentarium within the last year: tapinarof, roflumilast, deucravacitinib, and spesolimab. Several others are in late-stage development, and these therapies represent new mechanisms, pathways, and delivery systems, meaningfully broadening the spectrum of treatment choices for our patients. However, it can be quite difficult to keep track of all the medication options. This review aims to present the mechanisms and data on both newly available therapeutics for psoriasis and products in the pipeline that may have a notable impact on our treatment paradigm for psoriasis in the near future.