Impact of omitting the intravenous heparin bolus on outcomes of leadless pacemaker implantation.

BACKGROUND: Early guidance recommended a bolus of intravenous heparin at the beginning of leadless pacemaker (LP) implantation procedures. However, due to concern about bleeding complications, more recent practice has tended toward omitting the bolus and only running a continuous heparin infusion through the introducer sheath. The impact of omitting the heparin bolus on procedural outcomes is not clear. METHODS: We reviewed all Medtronic Micra LP implants at our institution from 9/2014 to 9/2022. The decision to bolus with heparin was at operator discretion. RESULTS: Among 621 LP implants, 326 received an intravenous heparin bolus, 243 did not, and 52 patients were excluded because heparin bolus status could not be confirmed. There was a trend toward more frequent omission of the heparin bolus with more recent implants. Median follow-up after LP implant was 14.3 (interquartile range [IQR]: 8.4-27.9) months. There was no difference between heparin bolus and no bolus groups in the number of device deployments/recaptures (1.42 ± 0.81 vs. 1.31 ± 0.66, p = .15). Implant-related adverse events were also similar between heparin bolus and no bolus groups: access-site hematoma requiring intervention (7 vs. 5, p = .99), pseudoaneurysm (1 vs. 1, p = .99), cardiac perforation (1 vs. 1, p = .99), intraprocedural device thrombus formation (2 vs. 4, p = .41), 30-day rehospitalization (21 vs. 15, p = .98), and 30-day all-cause mortality (16 vs. 14, p = .70). There was one additional nonfatal cardiac perforation in a patient who was excluded due to unknown heparin bolus status. Regarding device electrical parameters between heparin bolus and no bolus groups, there were no significant differences at the time of implant: pacing capture threshold 0.5 ± 0.4 vs. 0.5 ± 0.3, p = .10; pacing impedance 739.9 ± 226.4 vs. 719.1 ± 215.4, p = .52; R wave sensing 11.7 ± 5.7 vs. 12.0 ± 5.4, p = .34). Long-term device performance was also similar between groups. CONCLUSION: Omission of the systemic heparin bolus at the time of LP implantation appears safe in appropriately selected patients. Heparin bolus may still be considered in long cases requiring multiple device deployments or in patients at high risk for thrombotic complications.

Outcomes of tricuspid regurgitation after lead extraction.

INTRODUCTION: Transvenous leads have been implicated in tricuspid valve (TV) dysfunction, but limited data are available regarding the effect of extracting leads across the TV on valve regurgitation. The aim of this study is to quantify tricuspid regurgitation (TR) before and after lead extraction and identify predictors of worsening TR. METHODS: We studied 321 patients who had echocardiographic data before and after lead extraction. TR was graded on a scale (0 = none/trivial, 1 = mild, 2 = moderate, 3 = severe). A change of >1 grade following extraction was considered significant. RESULTS: A total of 321 patients underwent extraction of a total of 338 leads across the TV (1.05 ± 0.31 leads across the TV per patient). There was no significant difference on average TR grade pre- and postextraction (1.18 ± 0.91 vs. 1.15 ± 0.87; p = 0.79). TR severity increased after extraction in 84 patients, but was classified as significantly worse (i.e., >1 grade change in severity) in only 8 patients (2.5%). Use of laser lead extraction was associated with a higher rate of worsening TR postextraction (44.0% vs. 31.6%, p = 0.04). CONCLUSION: In our single-center analysis, extraction of leads across the TV did not significantly affect the extent of TR in most patients. Laser lead extraction was associated with a higher rate of worsening TR after extraction.

Roflumilast foam 0.3% for adolescent and adult patients with seborrheic dermatitis: A randomized, double-blinded, vehicle-controlled, phase 3 trial.

BACKGROUND: The topical phosphodiesterase 4 inhibitor roflumilast has been studied in several dermatologic conditions. OBJECTIVE: Roflumilast foam 0.3% is being investigated as a topical treatment for seborrheic dermatitis (SD). METHODS: In this phase 3, double-blinded trial, patients with SD were randomly assigned (2:1 ratio) to once-daily roflumilast foam 0.3% or vehicle foam for 8 weeks. The primary efficacy outcome was Investigator Global Assessment (IGA) Success at week 8, defined as IGA of 0 (Clear) or 1 (Almost Clear) plus ≥2-point improvement from baseline. Safety was also assessed. RESULTS: 79.5% of roflumilast-treated and 58.0% of vehicle-treated patients met the primary endpoint (P < .001); statistically significant differences in IGA Success also favored roflumilast at week 2 (roflumilast: 43.0%; vehicle: 25.7%; P < .001) and week 4 (roflumilast: 73.1%; vehicle: 47.1%; P < .001). Roflumilast was well-tolerated with a low rate of treatment-emergent adverse events. LIMITATIONS: Study limitations include the 8-week treatment period for this chronic condition. CONCLUSIONS: Once-daily roflumilast foam was superior to vehicle in leading to IGA of Clear or Almost Clear plus ≥2-point improvement from baseline at 8 weeks in patients with SD. Longer trials are needed to determine durability and safety of roflumilast foam in SD.

Hypothalamic-Pituitary-Adrenal Axis Response in Patients With Acne Vulgaris Treated With Clascoterone.

BACKGROUND: Clascoterone cream 1% is a topical androgen receptor inhibitor approved to treat acne vulgaris in patients =>12 years of age. This report provides details of patients who developed laboratory signs of hypothalamic-pituitary-adrenal (HPA) axis suppression without clinical signs of adrenal suppression during the clascoterone development program. METHODS: Two open-label, multicenter, Phase 2 trials evaluated HPA axis suppression in patients with moderate-to-severe acne vulgaris. Study 1 (NCT01831960) enrolled cohorts of adults =>18 years of age and adolescents =>12 to <18 years of age. Study 2 (NCT02720627) enrolled adolescents 9 to <12 years of age. Patients applied clascoterone twice daily at maximum-exposure dosages for 14 days. Adrenal suppression was evaluated via cosyntropin stimulation test (CST) at baseline and day 14. Patients with an abnormal CST result (serum cortisol level =<18 µg/dL) had a follow-up CST approximately 4 weeks later. Blood was collected for pharmacokinetic analysis. Other safety assessments included adverse events (AEs), physical examination/vital signs, and electrocardiography. RESULTS: Overall, 5/69 clascoterone-treated patients had an abnormal CST result on day 14, including 1/20 adults, 2/22 patients aged =>12 to <18 years, and 2/27 patients aged 9 to <12 years. All patients had normal cortisol levels at follow-up testing approximately 4 weeks later. No relationship was observed between abnormal CST results and clascoterone plasma concentrations or the amount of study drug applied. No clinically relevant AEs or clinically significant changes in safety measures were observed in patients with adrenal suppression. CONCLUSION: Clascoterone induced laboratory evidence of mild, reversible HPA axis suppression under maximum-use exposure. J Drugs Dermatol. 2024;23(6):433-437.     doi:10.36849/JDD.7997.

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.

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.

Efficacy and Tolerability of Topical 0.1% Stabilized Bioactive Retinol for Photoaging: A Vehicle-Controlled Integrated Analysis.

INTRODUCTION: Chronic exposure to ultraviolet light photoages skin. Retinol, a precursor molecule to retinoic acid that causes less irritation, is available as a nonprescription, cosmetic retinoid and improves collagen production, skin elasticity, and signs of photoaging. Advances in formulation science have allowed the production of stabilized bioactive retinol formulations. This integrated analysis aims to build on previous studies and further examine the comprehensive efficacy and tolerability of topical 0.1% stabilized bioactive retinol. METHODS: This analysis included 6 vehicle-controlled studies of 0.1% stabilized bioactive retinol in women with mild-to-moderate signs of photodamage. Across all studies, the same dermatologist investigator assessed overall photodamage; wrinkles on the forehead, cheeks, and undereye area; crow’s feet wrinkles and fine lines; lack of even skin tone; and brown spots at baseline and weeks 4, 8, and 12 on a numerical scale. Tolerability was also assessed. RESULTS: Participants (retinol, N=237; vehicle, N=234) had a mean (SD) age of 47.4 (6.6) years. Retinol induced greater improvements from baseline in all signs of photoaging vs vehicle as early as week 4 and through 12 weeks of application. Few participants experienced irritation; all events were mild to moderate and transient. The most common signs of irritation were erythema (n=2) and skin scaling/peeling (n=5). CONCLUSIONS: This pooled analysis of 6 vehicle-controlled clinical studies provides new evidence for the efficacy of 0.1% stabilized bioactive retinol in improving signs of photoaging without causing major irritation. Topical 0.1% stabilized bioactive retinol was well tolerated with only a few reported cases of skin irritation. J Drugs Dermatol. 2024;23(4):     doi:10.36849/JDD.8124.

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.

Novel use of an irrigated ablation catheter to monitor real-time hemodynamics during ablation.

INTRODUCTION: Hemodynamic decompensation during catheter ablation occurs due to prolonged procedure time and irrigant delivery directly into the cardiac chambers. Real-time hemodynamic monitoring of patients undergoing catheter ablation procedures may identify patients at risk of decompensation; we set out to assess the feasibility of a novel, real-time, intracardiac pressure monitoring system using a standard irrigated ablation catheter. METHODS: We studied 13 consecutive who underwent pressure measurement of the left atrium (LA) and left ventricle (LV) via transeptal access with a Swan Ganz (SG) catheter followed by two commercially available irrigated ablation catheters. Pressure waveform data was extracted to compare LA peak pressure, LV peak systolic pressure, LV end-diastolic pressure, and waveform analysis. RESULTS: Comparison between the SG and ablation catheters (AblA; AblB) demonstrated that LV systolic pressure (0.61-16.8 mmHg; 1.32-18.2 mmHg), and LV end-diastolic pressure (-3.4 to 2.8 mmHg; -3.0 to 3.35 mmHg) were well correlated and had accepted repeatability. Ablation waveforms demonstrated an 89.9 ± 6.4% correlation compared to SG waveforms. CONCLUSION: Pressure measurements derived from an irrigated ablation catheter are accurate and reliable when compared to an SG catheter. Further studies are needed to determine how real-time pressure monitoring can improve outcomes during ablation procedures.

Outcomes of leadless pacemaker implantation after cardiac surgery and transcatheter structural valve interventions.

INTRODUCTION: Permanent pacing indications are common after cardiac surgery and transcatheter structural valve interventions. Leadless pacemakers (LPs) have emerged as a useful alternative to transvenous pacemakers. However, current commercially available LPs are unable to provide atrial pacing or cardiac resynchronization and relatively little is known about LP outcomes after cardiac surgery and transcatheter valve interventions. METHODS: This retrospective study included patients who received a Micra VR (MicraTM MC1VR01) or Micra AV (MicraTM MC1AVR1) (Medtronic) leadless pacemaker following cardiac surgery or transcatheter structural valve intervention between September 2014 and September 2022. Device performance and clinical outcomes, including ventricular pacing burden, ejection fraction, and need for conversion to transvenous pacing systems, were evaluated during follow-up. RESULTS: A total of 78 patients were included, of whom 40 received a Micra VR LP implant, and 38 received a Micra AV LP implant. The mean age of the cohort was 65.9 ± 17.9 years, and 48.1% were females. The follow-up duration for the entire cohort was 1.3 ± 1.1 years: 1.6 ± 1.3 years for the Micra VR group and 0.8 ± 0.5 years for the Micra AV group. Among the cohort, 50 patients had undergone cardiac surgery and 28 underwent transcatheter structural valve interventions. Device electrical performance was excellent during follow-up, with a small but clinically insignificant increase in ventricular pacing threshold and a slight decrease in pacing impedance. The mean right ventricle pacing (RVP) burden significantly decreased over time in the entire cohort (74.3% ± 37.2% postprocedure vs. 47.7% ± 40.6% at last follow-up, p < .001), and left ventricle ejection fraction (LVEF) showed a modest but significant downward trend during follow-up (55.0% ± 10.6% vs. 51.5% ± 11.2% p < .001). Patients with Micra VR implants had significantly reduced LVEF during follow-up (54.1% ± 11.9% vs. 48.8% ± 11.9%, p = .003), whereas LVEF appeared stable in the Micra AV group during follow-up (56.1% ± 9.0% vs. 54.6% ± 9.7%, p = .06). Six patients (7.7%) required conversion to transvenous pacing systems, four who required cardiac resynchronization for drop in LVEF with high RVP burden and two who required dual-chamber pacemakers for symptomatic sinus node dysfunction. CONCLUSION: Leadless pacemakers provide a useful alternative to transvenous pacemakers in appropriately selected patients after cardiac surgery and transcatheter structural valve interventions. Device performance is excellent over medium-term follow-up. However, a significant minority of patients require conversion to transvenous pacing systems for cardiac resynchronization or atrial pacing support, demonstrating the need for close electrophysiologic follow-up in this cohort.

Once-daily roflumilast foam 0.3% for scalp and body psoriasis: a randomized, double-blind, vehicle-controlled phase IIb study.

BACKGROUND: Scalp psoriasis affects most patients with psoriasis, but it can be difficult to treat. OBJECTIVES: To evaluate the efficacy and safety of once-daily roflumilast foam 0.3% on scalp and body psoriasis. METHODS: In a phase IIb randomized controlled trial, adults and adolescents aged ≥ 12 years with scalp and body psoriasis were randomized (2 : 1) to roflumilast foam 0.3% or vehicle for 8 weeks. The primary efficacy endpoint was scalp Investigator Global Assessment (S-IGA) success (score of 'clear' or 'almost clear' plus ≥ 2-grade improvement from baseline) at week 8. Safety and tolerability were also evaluated. RESULTS: Significantly more roflumilast-treated patients (59.1%) than vehicle-treated patients (11.4%) achieved S-IGA success at week 8 (P < 0.001); differences favoured roflumilast as early as the first postbaseline visit at week 2 (P < 0.001). Significant improvements were also seen for secondary endpoints, including body IGA success, Scalp Itch Numeric Rating Scale and the Psoriasis Scalp Severity Index. The safety of roflumilast was generally similar to vehicle. Patients treated with roflumilast experienced low rates of treatment-emergent adverse events (AEs), with few discontinuations due to an AE. Few patients with skin of colour (11%) and few adolescents (0.7%) were included. CONCLUSIONS: The results support the further development of roflumilast foam for treating scalp and body psoriasis.

Long-term performance of single-connector (DF4) implantable defibrillator leads.

AIMS: Single-connector (DF4) defibrillator leads have become the predominantly implanted transvenous implantable cardioverter-defibrillator lead. However, data on their long-term performance are derived predominantly from manufacturer product performance reports. METHODS AND RESULTS: We reviewed medical records in 5289 patients with DF4 leads between 2011 and 2023 to determine the frequency of lead-related abnormalities. We defined malfunction as any single or combination of electrical abnormalities requiring revision including a sudden increase (≥2×) in stimulation threshold, a discrete jump in high-voltage impedance, or sensing of non-physiologic intervals or noise. We documented time to failure, predictors of failure, and management strategies. Mean follow-up after implant was 4.15 ± 3.6 years (median = 3.63), with 37% of leads followed for >5 years. A total of 80 (1.5%) leads demonstrated electrical abnormalities requiring revision with an average time to failure of 4 ± 2.8 years (median = 3.5). Of the leads that malfunctioned, 62/80 (78%) were extracted and replaced with a new lead and in the other 18 cases, malfunctioned DF4 leads were abandoned, and a new lead implanted. In multivariable models, younger age at implant (OR 1.03 per year; P < 0.001) and the presence of Abbott/St. Jude leads increased the risk of malfunction. CONCLUSION: DF4 defibrillator leads demonstrate excellent longevity with >98.3% of leads followed for at least 5 years still functioning normally. Younger age at implant and lead manufacturer are associated with an increased risk of DF4 lead malfunction. The differences in lead survival between manufacturers require further investigation.

Complex repolarization dynamics in ex vivo human ventricles are independent of the restitution properties.

AIMS: The mechanisms of transition from regular rhythms to ventricular fibrillation (VF) are poorly understood. The concordant to discordant repolarization alternans pathway is extensively studied; however, despite its theoretical centrality, cannot guide ablation. We hypothesize that complex repolarization dynamics, i.e. oscillations in the repolarization phase of action potentials with periods over two of classic alternans, is a marker of electrically unstable substrate, and ablation of these areas has a stabilizing effect and may reduce the risk of VF. To prove the existence of higher-order periodicities in human hearts. METHODS AND RESULTS: We performed optical mapping of explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Signals recorded from the right ventricle endocardial surface were processed to detect global and local repolarization dynamics during rapid pacing. A statistically significant global 1:4 peak was seen in three of six hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of Periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel. CONCLUSION: We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.

Tapinarof cream 1% once daily for the treatment of plaque psoriasis: Patient-reported outcomes from the PSOARING 3 trial.

BACKGROUND: Tapinarof cream 1% once daily demonstrated significant efficacy versus vehicle and was well tolerated in two 12-week, phase 3 pivotal trials in adults with mild-to-severe plaque psoriasis. OBJECTIVE: To assess long-term, health-related quality of life and patient satisfaction with tapinarof. METHODS: Patients completing the 12-week trials were eligible for 40 weeks of open-label tapinarof based on Physician Global Assessment score in PSOARING 3, with a 4-week follow-up. Dermatology Life Quality Index was assessed at every visit; Patient Satisfaction Questionnaire responses were assessed at week 40 or early termination. RESULTS: Seven hundred sixty-three (91.6%) eligible patients enrolled; 78.5% completed the Patient Satisfaction Questionnaire. DLQI scores improved and were maintained. By week 40, 68.0% of patients had a DLQI of 0 or 1, indicating no impact of psoriasis on health-related quality of life. Most patients strongly agreed or agreed with all Patient Satisfaction Questionnaire questions assessing confidence in tapinarof and satisfaction with efficacy (62.9%-85.8%), application ease and cosmetic elegance (79.9%-96.3%), and preference for tapinarof versus prior psoriasis therapies (55.3%-81.7%). LIMITATIONS: Open-label; no control; may not be generalizable to all forms of psoriasis. CONCLUSIONS: Continued and durable improvements in health-related quality of life, high rates of patient satisfaction, and positive perceptions of tapinarof cream were demonstrated.

The Interventions to Minimize Pain During Photodynamic Therapy With 5-Aminolevulinic Acid for the Treatment of Cutaneous Diseases.

Photosensitization with 5-aminolevulinic acid (ALA) combined with photodynamic therapy (PDT) is approved in the United States for the treatment of actinic keratosis (AK) and is used off-label for other indications including acne treatment and photo rejuvenation. However, pain, particularly during the initial illumination period, limits the utility of this highly efficacious therapy. Although modifications to conventional ALA-PDT protocols that improve tolerability without diminishing efficacy have been identified, few have been evaluated in randomized, controlled trials, and the number of variables involved in ALA incubation (eg, duration, occlusion, ALA formulation, and strength) and PDT illumination (eg, light source, fluence rate, irradiance, and duration) confounds standardization.  Perhaps the most promising modifications to date involve continuous activation of low levels of protoporphyrin IX, the photoactive metabolite of ALA, as well as using shorter incubation times (with or without prolongation of illumination), lower irradiance, and daylight or combined (daylight and conventional) PDT. However, reimbursement of PDT with alternative light sources in the US is hampered by the US Food and Drug Administration (FDA) labeling, which specifies the blue or red light devices approved for use with corresponding marketed ALA 20% solution and 10% gel, respectively. This review summarizes the existing evidence with respect to pain control in patients undergoing ALA-PDT, recommendations from clinical experience, and goals for future research. J Drugs Dermatol. 2023;22(11):1082-1087   doi:10.36849/JDD.7637.

Breaking the Frustrating Cycle of Topical Steroids in Psoriasis: A Review of a Novel Vehicle for Fixed-Dose Combination Halobetasol Propionate/Tazarotene.

Topical therapies are commonly used to treat psoriasis, either as monotherapy for milder disease or as adjuncts to systemic and biologic drugs. Topical steroids and tazarotene are both options for topical psoriasis treatment, but as monotherapies, they are associated with adverse events (AEs) that make adherence to prescribed treatment challenging. In addition, the topical vehicles may have an unappealing appearance or texture that proves impractical for patients. Consequently, patients may not use treatments as prescribed. This noncompliance can lead to a frustrating cycle of treatment, discontinuation, and retreatment without achieving treatment goals. Psoriasis is a chronic disease; thus, topical treatment options are needed that address these barriers to use and promote long-term adherence, making satisfactory improvement of psoriasis more attainable. In this review, we discuss patient preferences for topical therapies with vehicles that are moisturizing, nongreasy, and quickly absorbed. We then introduce the vehicle formulation of fixed-dose combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion, which has a unique matrix mesh formulation that enhances uniform absorption, allows for efficient drug delivery, and aligns with patient preferences. In addition to vehicle benefits, the combination of HP and TAZ has been shown to minimize AEs seen with either monotherapy. In clinical trials, HP/TAZ was efficacious and associated with a low rate of AEs with long-term use. This evidence supports the use of HP/TAZ as a topical treatment for patients with psoriasis facing challenges adhering to prescribed treatments and looking to break the cycle of unsatisfactory treatment outcomes. J Drugs Dermatol. 2023;22(3):247-251. doi:10.36849/JDD.7399.

Real-World Effectiveness and Safety of Tildrakizumab in Patients With Moderate-to-Severe Psoriasis: Week 28 Interim Analysis of a Phase 4 Study.

BACKGROUND: Tildrakizumab is an anti­interleukin-23 p19 monoclonal antibody approved for the treatment of adults with moderate-to-severe plaque psoriasis. This analysis evaluated real-world effectiveness and safety of tildrakizumab for 28 weeks. METHODS: In this Phase 4 study (NCT03718299), adults with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg subcutaneously at week 0, week 4, and every 12 weeks thereafter. Clinical improvement was assessed from Psoriasis Area and Severity Index (PASI) score change from baseline; disease activity from body surface area (BSA) percentage affected, static Physician's Global Assessment (sPGA), and sPGA x BSA; and safety from adverse events (AEs). RESULTS: At week 28, 52/55 enrolled patients were assessed. Mean (standard deviation [SD]) PASI score decreased significantly (P<0.001) from 11.6 (7.1) at baseline to 1.8 (3.0; 82.1% improvement) at week 28; 55.8% of patients achieved PASI 90 response. From baseline to week 28, mean (SD) BSA decreased significantly from 14.5% (11.5%) to 2.9% (6.4%), sPGA from 3.2 (0.6) to 1.2 (0.9), and BSA x sPGA from 47.0 (41.5) to 6.8 (20.3; all P<0.001). Serious AEs were infrequent. No treatment-emergent AEs were considered related to tildrakizumab. Conclusions: Real-world tildrakizumab treatment significantly improved clinical status and reduced disease activity, with no new safety concerns. Heim J, Gabriel Vasquez J, Schenkel B, et al. Real-world effectiveness and safety of tildrakizumab in patients with moderate- to-severe psoriasis: week 28 interim analysis of a phase 4 study. J Drugs Dermatol. 2023;22(8):754-760. doi:10.36849/JDD.7471.

Efficacy, Convenience, and Safety of Calcipotriene-Betamethasone Dipropionate Cream in Skin of Color Patients With Plaque Psoriasis.

BACKGROUND: Psoriasis affects diverse racial and ethnic groups. In July 2021, the US Food and Drug Administration approved calcipotriene/betamethasone dipropionate (CAL/BDP) 0.005%/0.065% cream to treat plaque psoriasis in adults. The efficacy and safety of CAL/BDP in patients with skin of color (SOC) who have psoriasis is not well characterized. METHOD: A post hoc analysis of phase 3 clinical trial data (NCT03308799) was conducted to assess the efficacy, convenience, and safety of CAL/BDP cream versus CAL/BDP topical solution and vehicle cream in people with Fitzpatrick skin types IV to VI.   Results: This study included 784 participants, 280 (35.7%) of whom had Fitzpatrick skin types IV to VI. Patients treated with CAL/BDP cream had greater disease improvement, treatment convenience scores, and overall satisfaction than those treated with CAL/BDP topical solution in the subgroup with skin types IV to VI and the total study population.  Adverse event rates were similar between the subgroup with skin types IV to VI and the total study population for all treatment arms.  Conclusion: Psoriasis is associated with a greater physical and psychosocial impact in patients with SOC. While many effective topical therapies exist, it may be helpful to conduct separate analyses of patients with SOC to assess the efficacy and safety of treatment in this population. This sub-analysis of phase 3 clinical trial data supports the efficacy and safety of CAL/BDP cream in the treatment of plaque psoriasis in patients with SOC. CAL/BDP cream also had greater convenience, formula acceptability, and overall satisfaction in both the subgroup with SOC and the total trial population, which may improve adherence to topical therapy and treatment outcomes for people with SOC who have psoriasis. Kontzias CL, Curcio A, Gorodokin B, et al. Efficacy, convenience, and safety of calcipotriene-betamethasone dipropionate cream in skin of color patients with plaque psoriasis. J Drugs Dermatol. 2023;22(7):668-672. doi:10.36849/JDD.7497.

The Safety and Efficacy of Roflumilast Cream 0.15% and 0.05% in Patients With Atopic Dermatitis: Randomized, Double-Blind, Phase 2 Proof of Concept Study.

BACKGROUND: Patients with atopic dermatitis (AD) need safe and effective topical treatments. OBJECTIVE: To assess safety and efficacy of roflumilast cream in patients with mild to moderate AD. METHODS: In this phase 2, proof of concept trial, patients (N=136) aged ≥12 years with AD were randomized to once-daily roflumilast cream 0.15%, roflumilast cream 0.05%, or vehicle cream for 4 weeks. Absolute change from baseline in Eczema Area and Severity Index (EASI) score at week 4 (primary endpoint), percentage change and responder rates, Validated Investigator Global Assessment-AD (vIGA-AD), and safety were assessed. RESULTS: At week 4, mean absolute changes in EASI were −6.4 (P=0.097 vs vehicle), −6.0 (P=0.356), and −4.8 with roflumilast 0.15%, roflumilast 0.05%, and vehicle, respectively. Significant improvements were observed for percentage change from baseline in EASI, patients reaching 75% improvement in EASI, and patients achieving vIGA-AD score of “clear” or “almost clear.” Treatment-related adverse events (AEs) occurred in 2 (2.2%) patients receiving roflumilast (mild rash and moderate application site pain). Only 1 (1.1%) patient receiving roflumilast discontinued study/drug due to an AE. LIMITATIONS: Small number of patients. CONCLUSIONS: Results support additional larger clinical trials of roflumilast cream to assess its potential as a once-daily, nonsteroidal topical AD treatment. CLINICALTRIALS: gov identifier NCT03916081 J Drugs Dermatol. 2023;22(2):139-147. doi:10.36849/JDD.7295.