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.

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.

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.

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.

Early and Sustained Acne Lesion Reductions With Fixed-Dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel.

BACKGROUND: A once-daily, three-pronged approach using an antibiotic, antibacterial, and retinoid may provide faster acne improvement versus monotherapy or dual-combination products. This post hoc analysis compared threshold acne lesion reductions with clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel—the first FDA-approved triple-combination topical acne product—to its dyads and vehicle. METHODS: Phase 2 (N=741; NCT03170388) and phase 3 (N=183; N=180; NCT04214639; NCT04214652), double-blind, 12-week studies randomized participants aged ≥9 years with moderate-to-severe acne to once-daily CAB or vehicle gel; the phase 2 study included three additional dyad gel arms. The pooled percentage of participants achieving ≥33%, ≥50%, and ≥75% reduction in inflammatory and noninflammatory acne lesions was evaluated. RESULTS: As early as week 4 in the phase 2 study, ≥33% reduction in inflammatory lesions occurred in a significantly greater percentage of CAB gel-treated participants (82.7%) than with the 3 dyads and vehicle (61.1-69.8%; P<0.05, all). These early reductions were sustained throughout the study, with significantly (P<0.05) more CAB-treated participants achieving ≥50% reduction in inflammatory lesions versus dyads and vehicle from weeks 4-12. By week 12, CAB led to substantial reductions of ≥75% in significantly more participants than dyads and vehicle (65.8% vs 49.9-51.2% and 21.6%; P<0.05, all). Similar trends were observed for noninflammatory lesions in the phase 2 study and for inflammatory and noninflammatory lesions in the phase 3 studies. CONCLUSIONS: Lesion count reductions were significantly greater with CAB versus its dyads and vehicle gel as early as week 4, with substantial reductions observed after 12 weeks of treatment. This faster-acting and sustained efficacy of CAB gel—coupled with its optimized formulation, once-daily dosing, and tolerability—may positively impact treatment adherence. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7907.

Trial of Roflumilast Cream for Chronic Plaque Psoriasis.

BACKGROUND: Systemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis. METHODS: In this phase 2b, double-blind trial, we randomly assigned adults with plaque psoriasis in a 1:1:1 ratio to use roflumilast 0.3% cream, roflumilast 0.15% cream, or vehicle (placebo) cream once daily for 12 weeks. The primary efficacy outcome was the investigator's global assessment (IGA) of a status of clear or almost clear at week 6 (assessed on a 5-point scale of plaque thickening, scaling, and erythema; a score of 0 indicates clear, 1 almost clear, and 4 severe). Secondary outcomes included an IGA score indicating clear or almost clear plus a 2-grade improvement in the IGA score for the intertriginous area and the change in the Psoriasis Area and Severity Index (PASI) score (range, 0 to 72, with higher scores indicating worse disease). Safety was also assessed. RESULTS: Among 331 patients who underwent randomization, 109 were assigned to roflumilast 0.3% cream, 113 to roflumilast 0.15% cream, and 109 to vehicle cream. An IGA score indicating clear or almost clear at week 6 was observed in 28% of the patients in the roflumilast 0.3% group, in 23% in the roflumilast 0.15% group, and in 8% in the vehicle group (P<0.001 and P = 0.004 vs. vehicle for roflumilast 0.3% and 0.15%, respectively). Among the approximately 15% of patients overall who had baseline intertriginous psoriasis of at least mild severity, an IGA score at week 6 indicating clear or almost clear plus a 2-grade improvement in the intertriginous-area IGA score occurred in 73% of the patients in the roflumilast 0.3% group, 44% of those in the roflumilast 0.15% group, and 29% of those in the vehicle group. The mean baseline PASI scores were 7.7 in the roflumilast 0.3% group, 8.0 in the roflumilast 0.15% group, and 7.6 in the vehicle group; the mean change from baseline at week 6 was -50.0%, -49.0%, and -17.8%, respectively. Application-site reactions occurred with similar frequency in the roflumilast groups and the vehicle group. CONCLUSIONS: Roflumilast cream administered once daily to affected areas of psoriasis was superior to vehicle cream in leading to a state of clear or almost clear at 6 weeks. Longer and larger trials are needed to determine the durability and safety of roflumilast in psoriasis. (Funded by Arcutis Biotherapeutics; ARQ-151 201 ClinicalTrials.gov number, NCT03638258.).

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.

Triple-combination clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel for moderate-to-severe acne in children and adolescents: Randomized phase 2 study.

BACKGROUND/OBJECTIVES: Topical clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel (IDP-126) is the first fixed-dose triple-combination formulation in development for acne. This post hoc analysis investigated efficacy and safety of IDP-126 in children and adolescents with moderate-to-severe acne. METHODS: In a randomized, double-blind phase 2 study (NCT03170388), participants ≥9 years of age with moderate-to-severe acne were eligible for randomization (1:1:1:1:1) to once-daily IDP-126, one of three dyad combination gels, or vehicle gel for 12 weeks. This post hoc analysis of pediatric participants (n = 394) included children and adolescents up to 17 years of age. Assessments included treatment success, 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 were significantly greater with IDP-126 (55.8%) than with vehicle (5.7%; p < .001) or any of the dyad combinations (range: 30.8%-33.9%; p < .01, all). Lesion reductions with IDP-126 were also significantly greater than with vehicle (inflammatory: 78.3% vs. 45.1%; noninflammatory: 70.0% vs. 37.6%; p < .001, both) and 9.2%-16.6% greater than with any of the dyad combinations. Increases (improvements) from baseline in Acne-QoL domain scores were generally greater with IDP-126 than in any other treatment group. The most common treatment-related TEAEs across treatment groups were application site pain and dryness. Most treatment-related TEAEs were of mild-to-moderate severity. CONCLUSION: IDP-126 gel-a novel fixed-dose, triple-combination topical formulation for acne-demonstrated superior efficacy to vehicle and three dyad component gels and was well tolerated in children and adolescents with moderate-to-severe acne.

Effect of Roflumilast Cream vs Vehicle Cream on Chronic Plaque Psoriasis: The DERMIS-1 and DERMIS-2 Randomized Clinical Trials.

Importance: Once-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis. Objective: To evaluate the efficacy of roflumilast cream, 0.3%, applied once daily for 8 weeks in 2 trials of patients with plaque psoriasis. Design, Setting, and Participants: Two phase 3, randomized, double-blind, controlled, multicenter trials (DERMIS-1 [trial 1; n = 439] and DERMIS-2 [trial 2; n = 442]) were conducted at 40 centers (trial 1) and 39 centers (trial 2) in the US and Canada between December 9, 2019, and November 16, 2020, and between December 9, 2019, and November 23, 2020, respectively. Patients aged 2 years or older with plaque psoriasis involving 2% to 20% of body surface area were enrolled. The dates of final follow-up were November 20, 2020, and November 23, 2020, for trial 1 and trial 2, respectively. Interventions: Patients were randomized 2:1 to receive roflumilast cream, 0.3% (trial 1: n = 286; trial 2: n = 290), or vehicle cream (trial 1: n = 153; trial 2: n = 152) once daily for 8 weeks. Main Outcomes and Measures: The primary efficacy end point was Investigator Global Assessment (IGA) success (clear or almost clear status plus ≥2-grade improvement from baseline [score range, 0-4]) at week 8, analyzed using a Cochran-Mantel-Haenszel test stratified by site, baseline IGA score, and intertriginous involvement. There were 9 secondary outcomes, including intertriginous IGA success, 75% reduction in Psoriasis Area and Severity Index (PASI) score, and Worst Itch Numeric Rating Scale score of 4 or higher at baseline achieving 4-point reduction (WI-NRS success) at week 8 (scale: 0 [no itch] to 10 [worst imaginable itch]; minimum clinically important difference, 4 points). Results: Among 881 participants (mean age, 47.5 years; 320 [36.3%] female), mean IGA scores in trial 1 were 2.9 [SD, 0.52] for roflumilast and 2.9 [SD, 0.45] for vehicle and in trial 2 were 2.9 [SD, 0.48] for roflumilast and 2.9 [SD, 0.47]) for vehicle. Statistically significantly greater percentages of roflumilast-treated patients than vehicle-treated patients had IGA success at week 8 (trial 1: 42.4% vs 6.1%; difference, 39.6% [95% CI, 32.3%-46.9%]; trial 2: 37.5% vs 6.9%; difference, 28.9% [95% CI, 20.8%-36.9%]; P < .001 for both). Of 9 secondary end points, statistically significant differences favoring roflumilast vs vehicle were observed for 8 in trial 1 and 9 in trial 2, including intertriginous IGA success (71.2% vs 13.8%; difference, 66.5% [95% CI, 47.1%-85.8%] and 68.1% vs 18.5%; difference, 51.6% [95% CI, 29.3%-73.8%]; P < .001 for both), 75% reduction in PASI score (41.6% vs 7.6%; difference, 36.1% [95% CI, 28.5%-43.8%] and 39.0% vs 5.3%; difference, 32.4% [95% CI, 24.9%-39.8%]; P < .001 for both), WI-NRS success (67.5% vs 26.8%; difference, 42.6% [95% CI, 31.3%-53.8%] and 69.4% vs 35.6%; difference, 30.2% [95% CI, 18.2%-42.2%]; P < .001 for both). The incidence of treatment-emergent adverse events was 25.2% with roflumilast vs 23.5% with vehicle in trial 1 and 25.9% with roflumilast vs 18.4% with vehicle in trial 2. The incidence of serious adverse events was 0.7% with roflumilast vs 0.7% with vehicle in trial 1 and 0% with roflumilast vs 0.7% with vehicle in trial 2. Conclusions and Relevance: Among patients with chronic plaque psoriasis, treatment with roflumilast cream, 0.3%, compared with vehicle cream resulted in better clinical status at 8 weeks. Further research is needed to assess efficacy compared with other active treatments and to assess longer-term efficacy and safety. Trial Registration: ClinicalTrials.gov Identifiers: NCT04211363, NCT04211389.

Oral Sarecycline for Treatment of Papulopustular Rosacea: Results of a Pilot Study of Effectiveness and Safety.

BACKGROUND: Cutaneous rosacea is a common inflammatory skin disorder that often presents with facial papulopustular lesions that are frequently bothersome to patients. Studies have shown oral sarecycline to be effective and safe for acne, with a low risk of side effects that are historically associated with other tetracycline-class drugs such as doxycycline and minocycline, in addition to offering a reduced risk of emergence of resistant bacteria due to its narrow-spectrum of antibiotic activity. Oral sarecycline is FDA-approved for the treatment of acne (2018). OBJECTIVE: A pilot study to evaluate the efficacy and safety of oral sarecycline in papulopustular rosacea. METHODS: A 12-week, prospective, parallel-group, investigator-blinded, controlled pilot study was completed evaluating once-daily sarecycline, using weight-based oral dosing as recommended for acne vs control (multivitamin tablet), for the treatment of moderate-to-severe papulopustular rosacea in adult subjects (n=102), aged ≥18 years. The primary efficacy endpoint was Investigator's Global score (IGA; clear or almost clear) and percent reduction in inflammatory lesion count at week 12. Safety and tolerability assessments were performed as well. RESULTS: A total of 102 subjects were randomized; 97 completed the study. At week 12, IGA improvement was significantly greater for oral sarecycline when compared to the control (P<0.0001). Furthermore, absolute and percent reductions in inflammatory lesion counts were significantly greater in the sarecycline group for all weeks (4, 8, and 12) when compared to the control (P<0.001). Significant improvement in facial burning, erythema, and pruritus was reported in the sarecycline group, when compared to the control (P<0.05). No serious AEs were reported. CONCLUSION: Sarecycline was effective, safe, and well-tolerated for treating papulopustular rosacea in adults with marked superiority in efficacy compared to subjects in the control group. With its narrow-spectrum activity, oral sarecycline may be a good option for the treatment of papulopustular rosacea. Additional studies are warranted to confirm the positive results of this pilot study.

INDIVIDUAL ARTICLE: Safety and Tolerability of Topical Agents for Actinic Keratosis: A Systematic Review of Phase 3 Clinical Trials.

BACKGROUND: Topical agents for actinic keratosis (AK), along with cryotherapy and phototherapy, are the most commonly used therapies for areas of skin with multiple AKs. Multiple options for the topical treatment of AK exist; newer therapies aim to balance efficacy with an acceptable safety and tolerability profile for the patient. OBJECTIVE: To describe the safety and tolerability of FDA-approved topical agents for the treatment of AK. METHODS: A systematic review of phase III clinical trials of topical agents for AK available on PubMed and clinicaltrials.gov was conducted on January 10th, 2021. RESULTS: 29 phase III clinical trials meeting the inclusion criteria were included in the qualitative synthesis. No serious adverse events or systemic adverse events were determined to be due to topical therapies for AK. The highest rates of treatment-related application-site adverse events and local skin reactions occurred with the various formulations of topical 5-FU and imiquimod; newer topical agents such as ingenol mebutate and tirbanibulin had more favorable tolerability profiles. CONCLUSIONS: FDA-approved topical agents for the treatment of multiple AKs have minimal safety concerns. Tolerability profiles vary among the available options, and new agents such as tirbanibulin offer a favorable combination of safety, tolerability, and efficacy. J Drugs Dermatol. 2021;20:10(Suppl):s4-11.

ARTICLE: Advances in Oral Isotretinoin Therapy.

Since its approval in 1982, oral isotretinoin has revolutionized acne therapy. However, oral isotretinoin use has long been associated with challenges of variable bioavailability and food dependence. It is recommended to ingest oral isotretinoin with a high-fat meal in order to maximize absorption, but many patients fail to adhere to this recommendation. This may lead to inadequate isotretinoin absorption levels. Patients who fail to achieve isotretinoin target cumulative dose are more likely to experience symptom relapse. To address the challenge of traditional isotretinoin variable bioavailability, subsequent isotretinoin formulations have attempted to improve its absorption abilities. In 2014, an isotretinoin formulation utilizing Lidose technology, known as Absorica, showed significant improvements in absorption levels compared to traditional oral isotretinoin in the fasted state. In 2019, isotretinoin absorption levels were further advanced in a new formulation approved by the FDA known as Absorica LD. Utilizing advanced micronization technology that physically reduces the size of the drug molecule, Absorica LD exhibits twice the absorption levels of Absorica under fasting conditions. In the fed state, Absorica LD achieves similar plasma levels to Absorica with a 20 percent lower dose. Absorica LD also produces consistent serum isotretinoin levels irrespective of gastrointestinal contents. By eliminating the “food effect” seen in traditional oral isotretinoin, Absorica LD has the potential to improve patient adherence and long-term patient outcomes. J Drugs Dermatol. 20:5(Suppl):s5-11.

Treatment of Impetigo and Antimicrobial Resistance.

BACKGROUND: Impetigo is a contagious bacterial infection that affects the superficial skin layers. Increasing worldwide antimicrobial resistance (AMR) to existing topical agents commonly prescribed to treat impetigo is central to treatment failure. The Worldwide Health Organization developed a global action plan on AMR, but omitted information about AMR stewardship programs for topical antibiotics. OBJECTIVES: The review aims to provide information to clinicians and stakeholders regarding AMR and antimicrobial stewardship on topical antimicrobial drugs for impetigo treatment. METHODS: The literature searches reviewed the status of AMR to current topical antibiotics in impetigo, current therapeutic behavior, and concordance with antimicrobial stewardship principles. Two international panels convened to discuss the output of the searches, and the results of the panel discussions were used in the development of the manuscript. RESULTS: The literature search included clinical trials, research studies, clinical guidelines, consensus papers, and reviews (if they provided original data), published between January 2008 and May 2019. The articles were selected based on clinical relevancy of impetigo management, clinical efficacy, and safety of the treatment and antimicrobial resistance. The searches resulted in one-hundred and ninety-eight articles. After applying the eligibility criteria, nineteen articles met inclusion criteria and were considered in the present review. CONCLUSIONS: While published antimicrobial stewardship guidelines have focused on systemic antibiotics, few studies have attempted to evaluate topical antibiotic prescribing practices for impetigo treatment. Many of the topical impetigo treatments currently in use have developed resistance. The appropriate use of topical ozenoxacin can help eradicate impetigo while minimizing AMR.J Drugs Dermatol. 20(4):366-372. doi:10.36849/JDD.5795.

Four-Week Daily Calcipotriene/Betamethasone Dipropionate Foam Is Highly Efficacious in Patients With Psoriasis (PSO-LONG Lead-in Phase).

BACKGROUND: Psoriasis is a chronic disease requiring long-term treatment strategies. Optimal strategies should include initial rapid relief of symptoms followed by long-term management to maintain remission. This 4-week open-label phase of a long-term proactive management phase 3 trial aimed to select responders to once daily, fixed-dose combination calcipotriene 0.005% and betamethasone dipropionate 0.064% (Cal/BD) foam in adults with psoriasis and assess patient-reported outcomes. METHOD: This phase 3 trial in adults with psoriasis included a 4-week open-label lead-in phase to determine treatment success prior to entering the randomized maintenance phase. Success was defined as Physician Global Assessment (PGA) score ‘clear’/‘almost clear’ (PGA <2) with ≥2-grade improvement from baseline. Those achieving treatment success at week 4 entered the maintenance phase; non-responders were withdrawn from the trial. RESULTS: 650 patients enrolled in the open-label phase, and 623 were treated with Cal/BD foam for 4 weeks; 521 (80%) patients achieved treatment success and were included in the maintenance phase. In those patients achieving success (responders), 21.1% and 78.9% achieved a PGA score of ‘clear’ and ‘almost clear’, respectively. Mean change from baseline in modified Psoriasis Area and Severity Index (± standard deviation [SD]) and body surface area (± SD) in responders at week 4 was −82.1% (16.4%) and −56.6% (38.3%), respectively. Mean Dermatology Life Quality Index score reduced by 6.0 from baseline to week 4 (n=521). 17.7% of patients experienced AEs; with only one severe AE reported. CONCLUSION: Cal/BD foam was highly efficacious and well tolerated during the 4-week lead-in phase of PSO-LONG. J Drugs Dermatol. 2021;20(4):436-441, doi:10.36849/JDD.5728.

ARTICLE: A Novel Antibiotic Just for Acne.

Dermatologists consistently rank as the most frequent prescribers of systemic antibiotics, and one of the most common diagnoses for which we recommend these agents is acne vulgaris. Up to three quarters of the antibiotics that dermatologists prescribe are in the tetracycline class.1 Even though dermatology as a specialty is well-known for off-label prescribing, it may be surprising to note that no systemic antibiotic had been FDA approved solely for treatment of acne—until recently.

The New Psoriasis Paradigm: Striving for Complete Clearance.

Newer biologics have introduced the possibility of higher and more complete clearance rates than previously possible. For many patients, PASI 90 and PASI 100 responses are realistic. Furthermore, higher levels of clearance, particularly total clearance, is associated with marked improvements in quality of life. Little data is available on the clinical benefits of higher clearance levels and how this might relate to improvements in other comorbidities. Is it time for dermatologists to strive for total clearance for our patients? We will examine the evidence that is available around this important topic. J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.4975.

Game Changer in Acne Treatment.

Of the four primary pathogenic factors that drive acne vulgaris—androgen excess, increased sebum production, faulty keratinization, and overgrowth of C. acnes—androgen excess has been the most elusive therapeutic target. Oral contraceptive pills (OCPs) have direct effect on circulating hormones, but their potential use is limited to a subset of women. As such, a sizable portion of the population affected by acne vulgaris cannot even consider treatment with OCPs. While these systemic agents are generally associated with a low risk profile and have a history of safe and effective use, they are not entirely risk-free. Indirect androgen modulation through the use of spironolactone has become increasingly popular.

Oral Tetracyclines and Acne: A Systematic Review for Dermatologists.

Oral tetracyclines are the most widely prescribed systemic antibiotic for acne. Synthesis of efficacy and safety of traditional and novel oral tetracyclines is highly informative to clinical practice. We conducted a systematic search of PubMed to identify large interventional and observational studies utilizing oral tetracyclines as an acne treatment. We identified 13 articles meeting inclusion for this review, which represented 226,019 pediatric and adult acne patients. Oral tetracyclines that were included in this systematic review were sarecycline (a novel narrow-spectrum tetracycline), doxycycline, minocycline, and tetracycline. Based on shared and divergent outcome measures, different oral tetracyclines were variably effective against facial acne. Sarecycline also demonstrated efficacy in truncal acne. Members of the oral tetracycline class also differed in their ability to minimize antibiotic resistance and gut dysbiosis. J Drugs Dermatol. 2020;19:11(Suppl):s4-11.

Efficacy and Safety of Calcipotriene 0.005%/Betamethasone Dipropionate 0.064% Foam With Apremilast for Moderate Plaque Psoriasis.

OBJECTIVE: To demonstrate the efficacy and safety of adding fixed-dose combination calcipotriene 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) foam to oral apremilast in treating moderate plaque psoriasis. METHODS: A 16-week, investigator-blinded study in patients with moderate psoriasis (Physician’s Global Assessment [PGA] score of 3). Patients were randomized 1:1 to Cal/BD foam plus apremilast or vehicle foam plus apremilast for 4 weeks, followed by 8 weeks of apremilast monotherapy, and then 4 weeks of combination therapy as in the original randomization schedule. Efficacy assessments – Psoriasis Area and Severity Index (PASI), PGA, body surface area (BSA), visual analog scale (VAS) for pruritus, and quality of life (QoL) – and safety were evaluated at weeks 1, 2, 3, 4, 12, and 16. RESULTS: 28 subjects were enrolled (mean age, 64 years; 67.9% males). Cal/BD foam plus apremilast group achieved statistically significantly greater improvement than vehicle foam plus apremilast in PASI75 (50% vs 7%; P=.003), PGA score of “clear” or “almost clear” (43% vs 7%; P=.001), and VAS score (2 vs 5; P=.0079) at week 4. BSA and QoL improvements were also observed. Most efficacy assessments worsened after withdrawing Cal/BD foam for 8 weeks but recovered after reinitiating Cal/BD foam from week 12 to week 16. Cal/BD foam plus apremilast appeared to be safe and well tolerated. CONCLUSIONS: In the treatment of moderate plaque psoriasis, Cal/BD foam plus apremilast provided more benefits than with apremilast alone. These improvements appeared to be lost when Cal/BD foam was withdrawn but recovered when Cal/BD foam was reinitiated. J Drugs Dermatol. 2020;19(9):874-880. doi:10.36849/JDD.2020.5020.

Evaluation of Patient-Reported Outcomes With Etanercept in Moderate to Severe Plaque Psoriasis Patients After Therapy With Apremilast.

Background: Patients with moderate-to-severe psoriasis can have symptoms resulting in significant impact on patient-reported outcomes (PROs). The effect of etanercept (ETN) in moderate-to-severe psoriasis patients who previously received apremilast (APR) was studied, including impact on PRO endpoints. Methods: In this multicenter, open-label, single-arm, phase 4 estimation study, patients with moderate-to-severe psoriasis who did not have adequate response to APR in the opinion of the investigator received ETN 50mg subcutaneous (SC) twice weekly for 12 weeks, followed by ETN 50mg SC once weekly for an additional 12 weeks. Analysis was conducted for PROs directly and by the Psoriasis Area and Severity Index (PASI) achievement thresholds. Results: Of the 80 patients enrolled, the Psoriasis Symptom Inventory (PSI; total and individual items) had substantial improvement at weeks 12 and 24. Improvement in PSI total score (percent; mean [SD]) in patients who achieved PASI 50, -75, and -90 at week 12 was 57% (30), 67% (24), and 83% (18), respectively and at week 24 was 56% (40), 68% (29), and 80% (25). DLQI responders by PASI 50, -75, and 90 achievements were 69%, 68%, and 90%, respectively, at week 12 and 68%, 77%, and 82% at week 24. The percent of patients reported being "very satisfied" or "satisfied" with treatment at week 12 was 79%, 81%, and 100%, respectively, and at week 24 was 77%, 86%, and 88%. Conclusion: Patient-reported symptoms are important outcomes to consider in psoriasis management. ETN provided benefits in patients who did not have adequate response with APR, with improvements seen in both psoriasis symptoms and patient impact. Clinical Trial Number: NCT02749370 J Drugs Dermatol. 2020;19(4):378-383. doi:10.36849/JDD.2020.4910.