Secukinumab in patients with moderate-to-severe hidradenitis suppurativa based on prior biologic exposure: an efficacy and safety analysis from the SUNSHINE and SUNRISE phase III trials.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a substantial disease burden. Secukinumab has previously been reported to have sustained efficacy with a favourable safety profile in patients with moderate-to-severe HS. It is unknown whether prior biologic exposure affects the efficacy and safety of secukinumab. OBJECTIVES: To investigate the efficacy and safety of secukinumab in patients with moderate-to-severe HS based on prior exposure to -biologics. METHODS: This was an analysis of the SUNSHINE and SUNRISE phase III trials of secukinumab in patients with moderate-to-severe HS. Patients were randomized at baseline to receive secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W), or placebo for 16 weeks. After week 16, patients on the SECQ2W and SECQ4W schedules remained on the same treatment regimen, while patients randomized to placebo were switched to either SECQ2W or SECQ4W up to week 52. Assessments based on prior exposure to biologics included Hidradenitis Suppurativa Clinical Response (HiSCR), abscess and inflammatory nodule (AN) count, flare rates, HS-related pain [numerical rating scale 30 (NRS30)], 55% reduction in the International Hidradenitis Suppurativa Severity Score System (IHS4-55), Dermatology Life Quality Index, EuroQol-5D and safety. RESULTS: Overall, 1084 patients were randomized in the SUNSHINE and SUNRISE trials and included in this analysis; 255 (23.5%) were biologic-experienced [SECQ2W (n = 80); SECQ4W (n = 81); placebo (n = 94)] and 829 (76.5%) were biologic-naïve [SECQ2W (n = 281); SECQ4W (n = 279); placebo (n = 269)]. At week 16, responses were more efficacious for secukinumab than for placebo with regard to HiSCR in patients who were biologic-experienced {SECQ2W 37.0% [odds ratio (OR) 1.60, 95% confidence interval (CI) 0.83-3.08]; SECQ4W 38.8% [OR 1.67, 95% CI 0.86-3.22]; placebo 27.3%} and biologic-naïve [SECQ2W 45.6% (OR 1.64, 95% CI 1.15-2.33); SECQ4W 45.4% (OR 1.61, 95% CI 1.13-2.29); placebo 34.2%]. Similar results were observed for AN count, NRS30 and IHS4-55. The higher response seen at week 16 with secukinumab was sustained, with a trend toward improvement over time, through to week 52 in both subgroups. Additional efficacy was observed for quality-of-life assessments, and no differences in safety between subgroups were observed. CONCLUSIONS: Regardless of prior biologic exposure, secukinumab was efficacious in improving the signs and symptoms of HS. This finding positions secukinumab as the first option in patients who are biologic-naïve, as well as in patients who have previously been treated with other biologic therapy, based on individual patient needs.

Hidradenitis suppurativa (HS) is a chronic skin disease that causes painful boils. HS is common and affects about 0.4% of the world's population. Treating the condition is difficult, but drugs called 'biologics' can help to improve the symptoms. For example, secukinumab is a biologic drug that has been shown to be effective and well-tolerated for the treatment of HS. In this analysis, we investigated whether previous treatment with biologics could affect the effectiveness and tolerability of secukinumab. This analysis included data from two identical clinical trials (called SUNSHINE and SUNRISE) that recruited adult patients with HS who had moderate-to-severe disease. In these trials, patients took secukinumab 300 mg every 2 weeks or every 4 weeks for 1 year, or a placebo for 4 months and then switched to secukinumab until 1 year. At regular intervals, the effectiveness and tolerability of secukinumab were examined and the results were compared between patients who had previously used another biologic and patients who had never used a biologic before. After 16 weeks, patients who took secukinumab had better results than the patients who took a placebo, independent of previous biologic use. Secukinumab was still effective and had improved results over 1 year of treatment in both subgroups. Regardless of whether patients had previously been taking another biologic, secukinumab was just as tolerable as placebo and there were no new safety risks. Our analysis shows that secukinumab is effective and tolerable, regardless of whether patients have previously used another biologic drug.

Treatment Satisfaction and Acceptability of 20% Aminolevulinic Acid Photodynamic Therapy for the Treatment of Actinic Keratoses of the Face, Scalp, and Upper Extremities.

Background: Actinic keratoses (AKs) are precancerous, dysplastic, epidermal lesions caused by chronic sun exposure that may progress to squamous cell carcinoma. Aminolevulinic acid 20% solution with blue light photodynamic therapy (ALA-PDT) has previously been shown to be superior to vehicle plus PDT (VEH-PDT) for treatment of AKs of the face, scalp, and upper extremities. Objective: We report detailed patient satisfaction data for ALA-PDT. Methods: Patient satisfaction for ALA-PDT versus VEH-PDT and patient-reported acceptability of ALA-PDT versus previous treatments for AKs were assessed in three randomized, vehicle-controlled studies (two Phase II and one Phase III) in adults. Patients in the Phase II studies were treated on the scalp and/or face, and those in the Phase III study were treated on the upper extremities. Results: A total of 234, 166, and 269 patients were enrolled in the two Phase II studies and one Phase III study, respectively; overall, 79.8 percent of patients were male. Overall treatment satisfaction ranged from 79 to 88 percent for ALA-PDT, compared to 35 to 56 percent for VEH-PDT. Patients generally considered ALA-PDT to be equivalent to or more acceptable than prior treatments, including cryotherapy, 5-fluorouracil, imiquimod, previous PDT, and surgery. Similar proportions of patients receiving ALA-PDT or VEH-PDT on the upper extremities considered in-office time, side effects/adverse events (AEs), and duration of side effects/AEs to be acceptable. Limitations: The majority of patients were male, and no statistical comparisons were conducted. Conclusion: Patients were generally satisfied with ALA-PDT for the treatment of AKs of the face, scalp, and upper extremities and considered ALA-PDT to be equal to or more acceptable than previous treatments. Trial Registry Information: ClinicalTrials.gov: NCT01475955; NCT02239679; NCT02137785.

Building a Group Practice and Going Big.

Guided by experiences learned over 50 years of guiding a solo practice to an independent private practice with 28 providers and 7 practice locations in southeastern Virginia, the author describes some of the pros and cons as well as pearls and pitfalls and gives practical advice on how to evolve from a small practice to a large group while maintaining independence in today's ever-changing medical marketplace.

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.

Integrating Precision Medicine into Medical Dermatology Clinical Practice: An Expert Consensus Panel.

BACKGROUND: Precision medicine utilizes an individual’s genomics to improve diagnosis, prognosis, and therapy. The joint American Academy of Dermatology and National Psoriasis Foundation 2019 guidelines recognized the need to identify biomarkers that can predict the optimal biologic agent for an individual patient. This paper examines the current state of precision medicine in dermatology and how its use can improve outcomes in psoriasis. METHODS: A search of PubMed/MEDLINE using the terms precision medicine, personalized medicine, biomarkers, genomics, and dermatology was performed to identify relevant publications. An expert consensus panel was then convened to assign levels of evidence to each article using strength of recommendation taxonomy and create consensus statements requiring a two-thirds supermajority for agreement utilizing a modified Delphi approach. RESULTS: Thirteen articles met inclusion and exclusion criteria and were assigned levels of evidence. The panel created 10 consensus statements on how precision medicine can improve patient outcomes, all of which received a unanimous (6/6) vote. CONCLUSION: Choosing a biologic medication for psoriasis often relies on patient preference, provider preference, and a trial-and-error approach. Utilizing precision medicine tests such as Mind.Px can help providers identify biomarkers unique to a patient’s pathophysiology and choose the optimal medication through a targeted and evidence-based approach. Zakria D, Brownstone N, Armstrong AW, et al. Integrating precision medicine into medical dermatology clinical practice: an expert consensus panel. J Drugs Dermatol. 2023;22(6):588-593. doi:10.36849/JDD.7432.

Efficacy of Roflumilast Foam, 0.3%, in Patients With Seborrheic Dermatitis: A Double-blind, Vehicle-Controlled Phase 2a Randomized Clinical Trial.

Importance: Current topical treatment options for seborrheic dermatitis are limited by efficacy and/or safety. Objective: To assess safety and efficacy of roflumilast foam, 0.3%, in adult patients with seborrheic dermatitis affecting the scalp, face, and/or trunk. Design, Setting, and Participants: This multicenter (24 sites in the US and Canada) phase 2a, parallel group, double-blind, vehicle-controlled clinical trial was conducted between November 12, 2019, and August 21, 2020. Participants were adult (aged ≥18 years) patients with a clinical diagnosis of seborrheic dermatitis for a 3-month or longer duration and Investigator Global Assessment (IGA) score of 3 or greater (at least moderate), affecting 20% or less body surface area, including scalp, face, trunk, and/or intertriginous areas. Data analysis was performed from September to October 2020. Interventions: Once-daily roflumilast foam, 0.3% (n = 154), or vehicle foam (n = 72) for 8 weeks. Main Outcomes and Measures: The main outcome was IGA success, defined as achievement of IGA score of clear or almost clear plus 2-grade improvement from baseline, at week 8. Secondary outcomes included IGA success at weeks 2 and 4; achievement of erythema score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8; achievement of scaling score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8; change in Worst Itch Numeric Rating Scale (WI-NRS) score from baseline; and WI-NRS success, defined as achievement of 4-point or greater WI-NRS score improvement in patients with baseline WI-NRS score of 4 or greater. Safety and tolerability were also assessed. Results: A total of 226 patients (mean [SD] age, 44.9 [16.8] years; 116 men, 110 women) were randomized to roflumilast foam (n = 154) or vehicle foam (n = 72). At week 8, 104 (73.8%) roflumilast-treated patients achieved IGA success compared with 27 (40.9%) in the vehicle group (P < .001). Roflumilast-treated patients had statistically significantly higher rates of IGA success vs vehicle at week 2, the first time point assessed. Mean (SD) reductions (improvements) on the WI-NRS at week 8 were 59.3% (52.5%) vs 36.6% (42.2%) in the roflumilast and vehicle groups, respectively (P < .001). Roflumilast was well tolerated, with the rate of adverse events similar to that of the vehicle foam. Conclusions and Relevance: The results from this phase 2a randomized clinical trial of once-daily roflumilast foam, 0.3%, demonstrated favorable efficacy, safety, and local tolerability in the treatment of erythema, scaling, and itch caused by seborrheic dermatitis, supporting further investigation as a nonsteroidal topical treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04091646.

Double-Blind, Placebo-Controlled Study of Onabotulinumtoxin A for the Treatment of Hailey-Hailey Disease.

BACKGROUND: Hailey-Hailey disease (HHD) can be treated with topical steroids, antibiotics, and invasive surgical procedures. Since sweating often exacerbates HHD lesions, the use of onabotulinumtoxin A could serve as an adjunctive treatment. OBJECTIVE: The goal of this study was to evaluate the safety and efficacy of onabotulinumtoxin A for the treatment of HHD. METHODS: A double-blind, placebo-controlled single center study was conducted. Six HHD patients who successfully completed this trial in addition to 1 patient who exited early are reported and discussed. Four of these patients received an initial injection of Btx-A and 3 received the placebo initially. RESULTS: All patients except 1 who received an initial or reinjection of Btx-A decreased 2 levels on a 4-point clinical severity scale at weeks 8 or 12 after treatment. Patient 6 received an initial placebo injection and maintained clearance for 6 months, while patients 5 and 7 did not have any improvement in their target lesions after a placebo injection. All patients who received a reinjection of Btx-A at the week 4 follow-up decreased by at least 1 level on the HHD severity scale. CONCLUSION: Btx-A is a safe treatment that is effective for most cases of HHD. The most severe cases of HHD may not respond to Btx-A as sole treatment. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.6857 Citation: Saal R, Oldfield C, Bota J, et al. Double-blind, placebo-controlled study of Onabotulinumtoxin A for the treatment of Hailey-Hailey disease. J Drugs Dermatol. 2023;22(4):339-343. doi:10.36849/JDD.6857.

Psoriasis improvements and inflammatory biomarker normalization with secukinumab: the randomized ObePso-S study.

BACKGROUND: The IL-17A inhibitor secukinumab has demonstrated consistent efficacy and safety in patients with moderate-to-severe plaque psoriasis, with normalization of molecular and histopathologic psoriasis markers. OBJECTIVE: To investigate treatment effects of secukinumab on clinical signs and psoriatic inflammation markers over 52 weeks in patients with psoriasis. METHODS: In the ObePso-S study (NCT03055494), patients with psoriasis were randomized 2:1 to receive secukinumab 300 mg (n = 54) or placebo (n = 28), stratified by body weight (<90 or ≥90 kg), for 52 weeks. At Week 12, patients receiving placebo were switched to secukinumab. Psoriasis Area and Severity Index improvement of 90% (PASI90) and Investigator's Global Assessment modified 2011 0/1 responses were assessed at Weeks 12 and 52. Immunohistochemistry for keratin 16 (K16) and gene expression profiles were evaluated in lesional and non-lesional skin biopsies collected at baseline, Week 12, and Week 52. RESULTS: Of patients receiving secukinumab, 55.8% and 59.6% achieved PASI90 at Weeks 12 and 52, respectively. K16 was absent in 93.1% of Week 12 PASI90 responders and 93.6% of Week 52 PASI90 responders, which mirrored the down-regulated expression of psoriatic inflammation. Week 52 PASI90 non-responders experienced regression of clinical and inflammatory marker responses toward baseline levels. Lower control of inflammatory gene expression at Week 12 was associated with suboptimal clinical responses at Week 52. CONCLUSION: Sustained clinical responses with secukinumab were associated with rapid and sustained normalization of K16 and inflammatory gene expression in most patients. Molecular anti-inflammatory effects of secukinumab at Week 12 were associated with clinical responses at Week 52.

Safety and efficacy of bimekizumab through 2 years in patients with moderate-to-severe plaque psoriasis: longer-term results from the BE SURE randomized controlled trial and the open-label extension from the BE BRIGHT trial.

BACKGROUND: BE SURE 1-year results demonstrated the superior efficacy of bimekizumab compared with adalimumab with no unexpected safety findings. OBJECTIVES: To provide efficacy and safety data over 2 years of bimekizumab treatment compared with adalimumab from BE SURE and the BE BRIGHT open-label extension (OLE) in patients with moderate-to-severe plaque psoriasis. METHODS: The 56-week double-blinded BE SURE phase III randomized controlled trial randomized patients 1 : 1 : 1 to bimekizumab 320 mg every 4 weeks (Q4W), bimekizumab 320 mg Q4W to week 16 then every 8 weeks (Q8W), or adalimumab 40 mg every 2 weeks to week 24 then bimekizumab 320 mg Q4W. After completing BE SURE, patients could enter the ongoing BE BRIGHT OLE, with possible dosing adjustments based on Psoriasis Area and Severity Index (PASI). The primary outcome in BE BRIGHT was incidence of treatment-emergent adverse events (TEAEs); safety data are reported by study period through week 104. Efficacy data are reported for the intention-to-treat population through week 104 by initial randomization group, with ≥ 90% improvement from baseline PASI (PASI 90) and 100% improvement (PASI 100) as key outcomes. RESULTS: Of the patients randomized to bimekizumab, 158 were assigned to Q4W, and 161 to Q4W/Q8W. At week 104, PASI 90 was achieved by 91.2% and 89.7%, and PASI 100 was achieved by 72.3% and 68.1%, for Q4W and Q4W/Q8W, respectively; comparable to week 16 results. Among the 159 patients randomized to adalimumab, responses rapidly and substantially increased after the week 24 bimekizumab switch; at week 104, 96.9% and 70.2% of patients achieved PASI 90 and PASI 100 respectively. Through weeks 24-104, the three most common TEAEs in any bimekizumab-treated group were nasopharyngitis, oral candidiasis and upper respiratory tract infection. Rates of serious TEAEs were low. CONCLUSIONS: Clinical responses observed through week 16 of BE SURE in patients randomized to bimekizumab were sustained through 104 weeks of treatment, regardless of Q4W or Q8W maintenance dosing. Response rates were also sustained through week 104 in patients who switched from adalimumab to bimekizumab at week 24, and were similar to those observed in the bimekizumab groups. Bimekizumab was well tolerated with no new safety signals.

Effect of Roflumilast Cream (ARQ-151) on Itch and Itch-Related Sleep Loss in Adults with Chronic Plaque Psoriasis: Patient-Reported Itch Outcomes of a Phase 2b Trial.

BACKGROUND: Itch is the most bothersome symptom reported by patients with psoriasis. Safe and effective treatments for psoriasis that also address itch are needed. OBJECTIVES: To report effects of roflumilast cream on itch-related outcomes from a Phase 2b trial. METHODS: Adults with chronic plaque psoriasis were randomized to roflumilast 0.3%, roflumilast 0.15%, or vehicle once-daily for 12 weeks. Psoriasis severity was assessed via the Investigator Global Assessment (IGA; a 5-point scale assessing plaque thickening, scaling, and erythema ranging from 0 [clear] to 4 [severe]) and ≥ 2 on a modified Psoriasis Area and Severity Index (PASI-HD, which combines severity of lesions and area affected, ranging from 0 [no disease] to 72 [maximal disease], with the actual percentage of the anatomical area involved in those patients with < 10% of anatomical area involved [e.g., 0.1 for 1% to 0.9 for 9%]). Itch was evaluated via Worst Itch Numeric Rating Scale (WI-NRS), Psoriasis Symptom Diary (PSD) Items 1 (severity of itch) and 2 (bother of itch), and itch-related sleep loss NRS scores. Post hoc correlation analyses between WI-NRS and PASI, WI-NRS and itch-related sleep loss, and WI-NRS and DLQI were also performed. RESULTS: Roflumilast-treated patients had significantly greater improvements than vehicle-treated patients in WI-NRS and PSD Items 1 and 2 beginning at Week 2 and in itch-related sleep loss Weeks 6 through 12. Among patients with baseline WI-NRS ≥ 6, significantly more patients achieved ≥ 4-point improvement with roflumilast than with vehicle as early as Week 2. Itch severity had low correlation with PASI while WI-NRS and IGA were not always aligned. LIMITATIONS: The first assessment was at 2 weeks, limiting the ability to assess early onset of itch response. CONCLUSION: Roflumilast cream improved itch and itch-related sleep loss associated with chronic plaque psoriasis. GOV IDENTIFIER: NCT03638258.

The Future of Contract Research Organizations in Dermatology and Aesthetic Research.

Objective: Dermatology and aesthetic medicine has experienced significant growth in recent years, driven by industry-sponsored research performed by clinical investigators. Contract research organizations (CROs) play an important role to ensure clinical trials are run efficiently, ethically, and according to Good Clinical Practice. An advisory group of dermatologists and aesthetic researchers was assembled to obtain feedback about CRO experiences for developing a "next-generation" specialty CRO for dermatology and aesthetic medicine. Methods: Experienced dermatologists and aesthetic physician researchers convened during the 2022 Winter Dermatology Annual Meeting in Kauai, Hawaii, to discuss experiences and make suggestions regarding CROs. Topics included positive and negative aspects of CRO experiences, desirable CRO services, and how CROs can be improved. Results: Benefits of working with CROs include project, data, and resource management and availability of technology. Desired functions include rapid study start-up, subject recruitment, and accurate and organized site-related documentation. Other qualities include access to large subject populations close to study locations, use of CRO-based clinical research assistants to support principal investigators across study sites, and scientific consultation, protocol development, medical writing, project management, clinical and medical monitoring, data management, biostatistics, and pharmacovigilance. Conclusion: CROs serve a vital role in the development process of drug, device, and therapeutics; however, it is important that changes to traditional CRO models are made to provide improved interactions with researchers in dermatology and aesthetic medicine.

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.

Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides): The FLASH Phase 3 Randomized Clinical Trial.

Importance: Given that mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT). Objectives: To determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL. Design, Settings, and Participants: This was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL. Interventions: In cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks. Main Outcomes and Measures: The primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020. Results: The study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P < .001 vs cycle 1 hypericin) and to 49% after 3 cycles (P < .001 vs cycle 1 hypericin). Significant clinical responses were observed in both patch and plaque type lesions and were similar regardless of age, sex, race, stage IA vs IB, time since diagnosis, and number of prior therapies. The most common treatment-related AEs were mild local skin (13.5%-17.3% across cycles 1-3 vs 10.5% for placebo in cycle 1) and application-site reactions (3.2%-6.9% across cycles 1-3 vs 4% for placebo in cycle 1). No drug-related serious AEs occurred. Conclusion and Relevance: The findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT02448381.

Evidence Threshold for a Precision Medicine Test that Predicts Optimal Response to a Biologic Agent in Patients With Psoriasis: A Consensus Panel.

Precision medicine approaches are receiving increased attention in dermatology, including inflammatory skin diseases. In psoriasis, a precision medicine treatment paradigm could temper the rapid increase in pharmacy costs that have resulted from a tremendous expansion in the number of available biologic drug options. However, without a clear and agreed upon proof of clinical utility in a real-world setting, costly new pharmacotherapies are often burdened with barriers to coverage by payers and ultimately, routine patient care. This panel was assembled to discuss the evidence threshold required to demonstrate the clinical utility of a precision medicine diagnostic that predicts the biologic therapeutic class for treating psoriasis patients. The panel reviewed clinical utility study designs and economic impact study designs aimed at delineating net savings and waste reduction. A psoriasis biologic precision medicine test could optimize pharmacotherapy management of psoriasis patients. The consensus opinion of this panel was that positive results from the study described here would prove the clinical utility of this precision medicine test. J Drugs Dermatol. 2022;21(6):630-636. doi:10.36849/JDD.6864.

Baseline Demographics and Severity and Burden of Atopic Dermatitis in Adult Patients Initiating Dupilumab Treatment in a Real-World Registry (PROSE).

INTRODUCTION: Dupilumab was initially approved in 2017 as the first biologic therapy for atopic dermatitis (AD). We characterized adults with AD initiating dupilumab in a real-world setting in the USA/Canada. METHODS: PROSE is an ongoing, longitudinal, prospective, observational, multicenter registry of patients with AD initiating dupilumab per country-specific prescribing information. We report baseline data (day of first dupilumab injection) for patients enrolled from April 2018 through July 2019. RESULTS: Among 315 patients (mean age 42.5 years, 55.2% female), the median AD duration was 17.0 years; 65.4% reported a history of type 2 inflammatory comorbidities (e.g., allergic rhinitis, asthma), and 93.3% reported treatment(s) for AD in the previous year, including topical corticosteroids (90.8%), systemic corticosteroids (36.2%), and nonsteroidal systemic therapies (14.0%). In total, 89.2% had an Overall Disease Severity score of 3 (moderate) or 4 (severe). Other mean disease severity scores included the following: Eczema Area and Severity Index 16.9 (range 0-72), body surface area affected 26.8%, Patient-Oriented Eczema Measure 18.5 (range 0-28), Dermatology Life Quality Index 12.7 (range 0-30), and pruritus Numerical Rating Scale score 6.9 (range 0-10). CONCLUSION: Patients initiating dupilumab have longstanding moderate-to-severe AD with significant disease burden and frequent type 2 comorbidities. GOV IDENTIFIER: NCT03428646.

Open-Label Cohort Study to Evaluate Efficacy and Safety of Application of Glycopyrronium Cloth, 2.4% for Palmar Hyperhidrosis.

BACKGROUND: Hyperhidrosis of the palms has a significant negative impact on quality of life. There is no FDA-approved treatment; however, clinicians often use glycopyrronium cloth off-label for this indication despite the lack of published guidance on optimal method of application for treatment of palms. OBJECTIVE: To compare the safety and efficacy of 4 different methods of application of glycopyrronium cloth to give clinicians guidance when treating palmar hyperhidrosis. STUDY DESIGN: This study, conducted completely virtually using live interactive telemedicine, compared application times of 15 minutes, 30 minutes, and overnight without occlusion and 30 minutes under occlusion. The primary endpoint was a decrease in the mean of the Hand Severity Score (HHS) after 4 weeks of once-daily application. Safety data, including local skin reactions and other adverse events, were tabulated by cohort. RESULTS: Of the application times and methods tested, 30 minutes without occlusion produced the greatest decrease in the HHS with an acceptable safety profile. The most common adverse event was unilateral mydriasis, which presumably occurred from inadvertent introduction of study drug into the eye despite multiple warnings to the subjects to avoid eye contact. A few subjects had adverse events presumably due to systemic absorption of the drug similar to those seen in the pivotal trials for treatment of axillary hyperhidrosis. CONCLUSION: Glycopyrronium cloth can be used successfully to treat palmar hyperhidrosis. Occlusion for 30 minutes had the poorest response presumably due to the increased sweating causing dilution of the study drug. CLINICALTRIALS: gov: NCT04906655 J Drugs Dermatol. 2022;21(5):488-494. doi:10.36849/JDD.6688.

Approaches to Field Therapy for Actinic Keratoses: Relating Clinical Trial Results to Real-world Practice-A Commentary.

There have been multiple direct and indirect comparison studies evaluating different field therapies used in the treatment of actinic keratosis (AK). A recent clinical trial directly compared 5% fluorouracil (5-FU), imiquimod, ingenol mebutate, and methyl aminolevulinate photodynamic therapy (MAL-PDT), reporting that 5-FU was superior to the other treatments in achieving sustained clearance of 75 percent or greater of AK lesions compared to baseline. In this commentary, the author reviews and discusses the methods and results of this comparison study and propose these results are limited by a number of factors, such as the selected primary % clearance endpoint, grade range of included AKs, and treatments included in the comparison, when considered in the context of other clinical and real-world comparison studies evaluating AK field therapies. The author postulates that patient acceptance of and adherence to field therapy regimens for the treatment of AK may be better evaluated in a real-world setting. Additionally, the author suggests that selection of field therapy in the treatment of AK should be driven by consideration of relevant patient-, disease-, and treatment-related factors, and what is considered best may differ from patient to patient, depending on each patient's individual needs and expectations.

Efficacy and Safety of a Fixed-Dose Clindamycin Phosphate 1.2%, Benzoyl Peroxide 3.1%, and Adapalene 0.15% Gel for Moderate-to-Severe Acne: A Randomized Phase II Study of the First Triple-Combination Drug.

BACKGROUND: A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance. OBJECTIVES: We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne. METHODS: In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed. RESULTS: A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8-30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6-26.8; noninflammatory, 21.8-30.0; P < 0.05, all), corresponding to > 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity. CONCLUSIONS: Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03170388 (registered 31 May, 2017).

The Future of Contract Research Organizations in Dermatology and Aesthetic Research.

Objective: Dermatology and aesthetic medicine has experienced significant growth in recent years, driven by industry-sponsored research performed by clinical investigators. Contract research organizations (CROs) play an important role to ensure clinical trials are run efficiently, ethically, and according to Good Clinical Practice. An advisory group of dermatologists and aesthetic researchers was assembled to obtain feedback about CRO experiences for developing a "next-generation" specialty CRO for dermatology and aesthetic medicine. Methods: Experienced dermatologists and aesthetic physician researchers convened during the 2022 Winter Dermatology Annual Meeting in Kauai, Hawaii, to discuss experiences and make suggestions regarding CROs. Topics included positive and negative aspects of CRO experiences, desirable CRO services, and how CROs can be improved. Results: Benefits of working with CROs include project, data, and resource management and availability of technology. Desired functions include rapid study start-up, subject recruitment, and accurate and organized site-related documentation. Other qualities include access to large subject populations close to study locations, use of CRO-based clinical research assistants to support principal investigators across study sites, and scientific consultation, protocol development, medical writing, project management, clinical and medical monitoring, data management, biostatistics, and pharmacovigilance. Conclusion: CROs serve a vital role in the development process of drug, device, and therapeutics; however, it is important that changes to traditional CRO models are made to provide improved interactions with researchers in dermatology and aesthetic medicine.