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.

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.

Steroids Used to Treat Acne Vulgaris: A Review of Efficacy, Safety, and Clinical Considerations.

Acne vulgaris is prevalent among adolescents and adults worldwide and can significantly impact patients' quality of life. Steroidal molecules, including oral and intralesional corticosteroids, combined oral contraceptives (COCs), oral spironolactone, and topical clascoterone, are an important part of the acne treatment armamentarium. The recommended use, mechanism of action, and available evidence supporting the use of steroids for acne treatment are reviewed, and differences in acne clinical presentation and treatment approaches based on patient characteristics relevant to the selection of an appropriate steroid are also discussed. Steroid-based approaches target the systemic or local hormones (ie, testosterone and androgens) and inflammation that contribute to acne pathogenesis. Oral corticosteroids are primarily used as a short-term adjunctive therapy early in treatment, whereas intralesional corticosteroid injections are used for individual acne lesions. COCs and oral spironolactone are limited to female patients who wish to avoid pregnancy. Topical clascoterone can be used by female and male patients 12 years of age and older. Patients' characteristics (including age and patients with darker skin color) and preferences for the route of administration can impact treatment response and adherence, respectively. Overall, healthcare providers must be aware of the differences among steroidal acne treatments and use shared decision-making to select the optimal therapy. J Drugs Dermatol. 2024;23(6):404-409.     doi:10.36849/JDD.7846.

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.

Evaluating the Cost Burden of Alopecia Areata Treatment: A Comprehensive Review for Dermatologists.

Alopecia areata (AA) is managed with prolonged medical treatments and cosmetic therapies, whose cost can be burdensome. We sought to identify the costs of AA treatment and consolidate the available data for the practicing dermatologist by performing a PubMed search of articles indexed for MEDLINE. Ten studies including approximately 16,000 patients with AA across a range of Oxford Centre for Evidence-Based Medicine Levels of Evidence were included. Studies showed that despite the limited efficacy of many AA therapies, patients incurred substantial expenses to manage their AA.

Topical Prescription Management.

With recent advances in topical therapies for atopic dermatitis (AD), steroid-sparing options like calcineurin inhibitors, Janus kinase (JAK) inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors are becoming mainstays in therapy, underscoring the importance of careful selection and usage of topical corticosteroids (TCSs) to minimize side effects. Alongside the necessity of emollient use, these steroid-sparing alternatives offer rapid itch relief and efficacy in improving disease severity. While TCSs still hold a prominent role in AD management, promising novel topical treatments like tapinarof and live biotherapeutics to modulate the skin microbiome are also discussed. Overall, the recent addition of novel topical therapies offers diverse options for AD management and underscores the importance of topical treatments in the management of AD.

Rx -to- OTC switch increased access and lowered cost of topical adapalene.

Topical adapalene gel is an effective and well tolerated acne treatment that transitioned from prescription to over-the-counter (OTC) availability in 2016. Historically, prescription to OTC transitions have lowered costs to patients and payers and increased access to medications. This study used sales and prescriber data to assess access to topical retinoid therapies and their costs in the pre- and post- Rx-to-OTC transition. We demonstrate that the prescription to OTC transition of adapalene gel increased access to this medication, while lowering costs to patients and payers, including Medicare patients. These results provide a necessary call to action for future OTC shifts with other high safety profile, well-tolerated medications in ultimate efforts and hopes of cost savings for patients, insurers, and Medicare within our healthcare industry.

Calcipotriol Nanosuspension-Loaded Trilayer Dissolving Microneedle Patches for the Treatment of Psoriasis: In Vitro Delivery and In Vivo Antipsoriatic Activity Studies.

Psoriasis, affecting 2-3% of the global population, is a chronic inflammatory skin condition without a definitive cure. Current treatments focus on managing symptoms. Recognizing the need for innovative drug delivery methods to enhance patient adherence, this study explores a new approach using calcipotriol monohydrate (CPM), a primary topical treatment for psoriasis. Despite its effectiveness, CPM's therapeutic potential is often limited by factors like the greasiness of topical applications, poor skin permeability, low skin retention, and lack of controlled delivery. To overcome these challenges, the study introduces CPM in the form of nanosuspensions (NSs), characterized by an average particle size of 211 ± 2 nm. These CPM NSs are then incorporated into a trilayer dissolving microneedle patch (MAP) made from poly(vinylpyrrolidone) and w poly(vinyl alcohol) as needle arrays and prefrom 3D printed polylactic acid backing layer. This MAP features rapidly dissolving tips and exhibits good mechanical properties and insertion capability with delivery efficiency compared to the conventional Daivonex ointment. The effectiveness of this novel MAP was tested on Sprague-Dawley rats with imiquimod-induced psoriasis, demonstrating efficacy comparable to the marketed ointment. This innovative trilayer dissolving MAP represents a promising new local delivery system for calcipotriol, potentially revolutionizing psoriasis treatment by enhancing drug delivery and patient compliance.

Assessing the Impact of Oral Isotretinoin on the Menstrual Cycle: A Prospective Study on Predictors of Menstrual Irregularities.

Background and Objectives: This study aims to evaluate the association between the use of oral isotretinoin and menstrual irregularities in acne patients with previously regular menstrual cycles. Materials and Methods: A prospective observational study was conducted on 58,599 female patients aged 14 to 36 at King Abdullah University Hospital in Irbid, Jordan. The patients were followed for a period of 4.5 to 8 months during treatment and for 2 months post-treatment. Menstrual cycle changes were documented, and statistical analysis was performed to identify any significant associations. Results: A total of 111 (37.1%) patients, who were previously known to have regular menstrual cycles, complained of menstrual changes while using oral isotretinoin. Ninety-nine of those patients who complained of menstrual changes had their cycles back to normal post-treatment. There is a significant difference in the total accumulative dose between those with changes in menses and those without; p-value [0.008]. The most common change that occurred was amenorrhea (p < 0.001), followed by oligomenorrhea and menorrhagia (p < 0.001 and p = 0.050, respectively). The duration of treatment was a significant predictor of menstrual irregularities, with an odds ratio (OR) of 5.106 (95% CI: 1.371-19.020, p = 0.015), indicating a higher likelihood of menstrual changes with increased treatment duration. The total accumulative dose was also significantly associated with menstrual irregularities (OR = 0.964; 95% CI: 0.939-0.990; p = 0.006). Additionally, a family history of PCOS significantly increased the odds of menstrual irregularities (OR = 3.783; 95% CI: 1.314-10.892; p = 0.014). Conclusions: The study identified that 37.1% of the participants experienced changes in their menstrual cycles while undergoing isotretinoin therapy, with the vast majority (89.2%) returning to normal within two months post-treatment. Our logistic regression analysis pinpointed the duration of isotretinoin treatment, the total accumulative dose, and a family history of PCOS as significant predictors of menstrual irregularities.

Oral Psoriasis Therapies.

Oral psoriasis therapies include both older traditional immunosuppressants, such as methotrexate, cyclosporine, and acitretin, as well as newer, more targeted agents, such as apremilast, deucravacitinib, and oral interleukin-23 receptor antagonists. Patients may prefer oral therapies to injectable therapies based on the route of administration. Both older and newer oral psoriasis therapies can be utilized effectively in the treatment of psoriasis. Here, we will review oral agents used in the treatment of psoriasis as well as provide commentary on their role in our current, evolving psoriasis treatment paradigm.

Analysis of factors influencing target PASI responses and side effects of methotrexate monotherapy in plaque psoriasis: a multicenter study of 1521 patients.

Methotrexate (MTX) is commonly used as first-line systemic treatment agent in psoriasis. We aimed to evaluate the clinical characteristics and treatment responses of patients with psoriasis undergoing MTX monotherapy. Data from adult patients with plaque psoriasis who received MTX monotherapy for at least 3 months between April 2012 and April 2022 were retrospectively evaluated in 19 tertiary care centers. Our study included 722 female and 799 male patients, a total of 1521 participants. The average age of the patients was 44.3 ± 15.5 years. Mode of treatment was oral in 20.4% of patients while in 79.4% it was subcutaneous. The median treatment duration was 8 months (IQR = 5-15). The median weekly dose was 15 mg (IQR = 11-15). 1448 (95.2%) patients were taking folic acid supplementation. At week 12, 16.3% of the patients achieved PASI (Psoriasis Area and Severity Index) 90 response while at week 24, 37.3% achieved it. Logistic regression analysis for week 12 identified the following independent factors affecting PASI 90 achievement positively: median weekly MTX dose ≤ 15 mg (P = 0.011), subcutaneous administration (P = 0.005), no prior systemic treatment (< 0.001) and folic acid use (0.021). In logistic regression analysis for week 24; median weekly MTX dose ≤ 15 mg (P = 0.001), baseline PASI ≥ 10 (P < 0.001), no prior systemic treatment (P < 0.004), folic acid use (P = 0.001) and absence of comorbidities (P = 0.009) were determined as independent factors affecting the achievement of PASI 90. Adverse effects were observed in 38.8% of the patients, with nausea/vomiting (23.9%) and transaminase elevation (13%) being the most common. The most common reasons for interruptions (15.3%) and discontinuations (27.1%) of the treatment were patient related individual factors. The use of MTX as the first systemic treatment agent, at doses ≤ 15 mg/week and concurrent folic acid application are positive predictive factors for achieving the target PASI response both at weeks 12 and 24. In our study, which is one of the most comprehensive studies on MTX treatment in psoriasis, we observed that MTX is an effective and safe treatment option.

Real-world use, perception, satisfaction, and adherence of calcipotriol and betamethasone dipropionate PAD-cream in patients with plaque psoriasis in Spain and Germany: results from a cross-sectional, online survey.

BACKGROUND: Psoriasis significantly impacts patients' quality of life (QoL). Dissatisfaction and non-adherence are major barriers associated with topical treatments. A cream based on the polyaphron dispersion (PAD) Technology containing a fixed-dose of calcipotriol (CAL) and betamethasone dipropionate (BDP) was designed for a patient-friendly psoriasis management. The CAL/BDP PAD-cream demonstrated efficacy, convenience, and safety/tolerability in clinical trials. OBJECTIVES: This research assesses the real-world use, perception, satisfaction, and adherence of CAL/BDP PAD-cream among plaque psoriasis patients. METHODS: Between September-November 2023, psoriasis patients from Spain and Germany using or having used CAL/BDP PAD-cream for >2 weeks were recruited via Wefight network to complete a 30-questions online survey. Anonymized results were pooled for descriptive statistical analysis. RESULTS: The survey was completed by 129 patients (mean age: 43 years; 66% females; mean psoriasis duration: 12 years). Most patients (93%) were satisfied with CAL/BDP PAD-cream. The 66% reported high adherence (visual analogue scale 80-100) and 91% preferred CAL/BDP PAD-cream to their previous topical(s). Patients highlighted its ease/convenience of application, tolerability, and lack of itching/burning. CONCLUSIONS: Psoriasis patients treated with CAL/BDP PAD-cream in a real-world setting show high satisfaction, good adherence, and a positive perception of the product, suggesting that favorable outcomes observed in clinical trials translate to real clinical practice.

Comparative effectiveness of tildrakizumab 200 mg versus tildrakizumab 100 mg in psoriatic patients with high disease burden or above 90 kg of body weight: a 16-week multicenter retrospective study - IL PSO (Italian landscape psoriasis).

PURPOSE: Tildrakizumab is a selective inhibitor of IL-23 approved for the treatment of moderate-to-severe plaque psoriasis in two dosages. We conducted a 16-week multicenter retrospective study to compare the effectiveness and safety of tildrakizumab 200 mg versus tildrakizumab 100 mg in patients with a high disease burden or high body weight. MATERIALS AND METHODS: Our retrospective study included 134 patients treated with tildrakizumab 200 mg and 364 patients treated with tildrakizumab 100 mg from 28 Italian Dermatology Units affected by moderate-to-severe plaque psoriasis. The patients had a body weight above 90 kg or a high disease burden (Psoriasis Area and Severity Index [PASI] ≥ 16 or the involvement of difficult-to-treat areas). We evaluated the effectiveness of tildrakizumab at the week-16 visit in terms of PASI90, PASI100 and absolute PASI ≤ 2. RESULTS: After 16 weeks of treatment with tildrakizumab 200 mg, PASI90 was reached by 57.5% of patients and PASI100 by 39.6% of patients. At the same time point, 34.3% and 24.2% of patients treated with tildrakizumab 100 mg achieved PASI90 and PASI100, respectively. CONCLUSIONS: Our data suggest that tildrakizumab 200 mg has better effectiveness than tildrakizumab 100 mg in patients with a body weight ≥ 90 kg and a high disease burden.

Dose escalation of biologic treatment in patients with moderate-to-severe psoriasis in Japan.

Patients receiving interleukin (IL)-inhibiting biologics for moderate-to-severe psoriasis (PsO) may be treated with escalated doses to optimize outcomes. This study evaluated escalation prevalence in a Japanese claims analysis of patients with PsO diagnosis preceding IL-inhibiting biologic treatment and ≥1 post-induction maintenance claim (index date) with sufficient data availability from January 2014 to May 2022. Patients with non-persistence were excluded. Expected daily dose (EDD) was calculated as the recommended maintenance dose divided by the treatment interval. Dose escalation was defined as ≥2 claims showing a ≥20% increase in the observed average daily dose (ADD) over the EDD (with sensitivities requiring ≥1 claim and ≥30%). Significant differences were tested using multivariable regressions. The study included 982 unique patients treated with brodalumab (BRO; n = 104), guselkumab (GUS; n = 207), ixekizumab (IXE; n = 159), risankizumab (RIS; n = 135), secukinumab (SEC; n = 215) and ustekinumab (UST; n = 196). Within 12 months, dose escalation was observed for all IL-inhibiting biologics other than GUS and RIS: 44.4% for UST, 37.2% for IXE, 3.4% for SEC and 1.4% for BRO. In multivariable-adjusted analyses, odds of dose escalation were significantly lower for all products relative to UST. In sensitivities, escalation was observed for all products except RIS.

Atopic Dermatitis.

Atopic dermatitis (AD) is a common, chronic relapsing, and remitting inflammatory skin disease that is characterized by erythematous, scaly, and pruritic lesions often located over the flexural surfaces. Treatment goals of AD include the reduction of itching and burning, as well as the reduction of skin changes. Treatment of AD includes emollients and skin care, topical therapies including topical corticosteroids and steroid-sparing therapies, systemic therapies, and phototherapy.

Efficacy and safety of deucravacitinib for the management of psoriasis: a drug safety evaluation.

INTRODUCTION: Nowadays, despite the wide availability of biological drugs and apremilast for psoriasis management, there is always a need for new therapies to customize the therapeutic approach on the basis of the patient's clinical features and comorbidities, especially in order to achieve a prolonged therapeutic response. Thus, new treatment strategies are required to offer patients a personalized approach. In this scenario, major knowledge on psoriasis pathogenesis led to the development of deucravacitinib, an orally administered selective TYK2 inhibitor. AREAS COVERED: The aim of this manuscript is to review the current literature on the effectiveness and safety of deucravacitinib in psoriasis to offer readers a wide perspective. The current English literature was analyzed using the PubMed, Google Scholar, Embase, Cochrane Skin, and clinicaltrials.gov databases, selecting the most relevant manuscripts. EXPERT OPINION: Deucravacitinib appears to be an innovative weapon for the management of moderate to severe psoriasis. Despite its efficacy and safety profiles have been revealed by RCTs, real-life data are still scant. Certainly, deucravacitinib broadens the range of therapeutic alternatives for psoriasis patients, thus enhancing the holistic and personalized approaches required for the treatment of this disease.