ImportanceOnce-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.ObjectiveTo 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 ParticipantsTwo 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.InterventionsPatients 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 MeasuresThe 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).ResultsAmong 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 RelevanceAmong 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 RegistrationClinicalTrials.gov Identifiers: NCT04211363, NCT04211389

Projecting the mean costs per patient to the afflicted population yields an estimated total annual cost of $1.7 billion (95% CI: $0.8-$2.6 billion) attributable to moderate to severe psoriasis in Canada. Understanding the interplay between direct costs, lost productivity, and quality of life is critical for accurately identifying and evaluating effective treatments for this disease.

ImportanceLebrikizumab (LEB), a high-affinity monoclonal antibody targeting interleukin (IL)-13, demonstrated efficacy and safety in patients with moderate-to-severe atopic dermatitis (AD) during 16 weeks of monotherapy in a phase 2b trial, and two 52-week phase 3 trials.ObjectiveTo evaluate efficacy and safety of LEB combined with low- to mid-potency topical corticosteroids (TCS) in patients with moderate-to-severe AD.Design, Setting, and ParticipantsThe ADhere trial was a 16-week randomized, double-blinded, placebo (PBO)-controlled, multicenter, phase 3 clinical trial conducted from February 3, 2020, to September 16, 2021. The study was conducted at 54 outpatient sites across Germany, Poland, Canada, and the US and included adolescent (aged ≥12 to <18 years weighing ≥40 kg) and adult patients with moderate-to-severe AD. The treatment allocation ratio was 2:1 (LEB:PBO).InterventionsOverall, 211 patients were randomized to subcutaneous LEB (loading dose of 500 mg at baseline and week 2, followed by 250 mg every 2 weeks [Q2W] thereafter) or PBO Q2W in combination with TCS for 16 weeks.Main Outcomes and MeasuresEfficacy analyses at week 16 included proportions of patients achieving Investigator’s Global Assessment score of 0 or 1 (IGA [0,1]) with 2 or more points improvement from baseline, and 75% improvement in the Eczema Area and Severity Index (EASI-75). Key secondary end points included evaluation of itch, itch interference on sleep, and quality of life. Safety assessments included monitoring adverse events (AEs).ResultsThe mean (SD) age of patients was 37.2 (19.3) years, 103 (48.8%) patients were women, 31 (14.7%) patients were Asian, and 28 (13.3%) patients were Black/African American. At week 16, IGA (0,1) was achieved by 145 (41.2%) patients in the LEB+TCS group vs 66 (22.1%) receiving PBO+TCS (P = .01); corresponding proportions of patients achieving EASI-75 were 69.5% vs 42.2% (P < .001). The LEB+TCS group showed statistically significant improvements in all key secondary end points. Most treatment-emergent adverse events (TEAEs) were nonserious, mild or moderate in severity, and did not lead to study discontinuation. The TEAEs frequently reported in the LEB+TCS group included conjunctivitis (7 [4.8%]), headache (7 [4.8%]), hypertension (4 [2.8%]), injection site reactions (4 [2.8%]), and herpes infection (5 [3.4%]) vs 1.5% or less patient-reported frequencies in the PBO+TCS group. Similar frequencies of patient-reported serious AEs following LEB+TCS (n = 2, 1.4%) and PBO+TCS (n = 1, 1.5%).Conclusions and RelevanceIn this randomized phase 3 clinical trial, LEB+TCS was associated with improved outcomes in adolescents and adults with moderate-to-severe AD compared with TCS alone, and safety was consistent with previously reported AD trials.Trial RegistrationClinicalTrials.gov Identifier: NCT04250337

The objectives of therapy for atopic dermatitis (AD) are to reduce skin inflammation and pruritus, restore skin barrier function, and improve quality of life (QoL). Treatments can be classified as moisturizing and basic care, topical therapy, phototherapy, and systemic therapy. In this review, we summarize the treatments for AD and recommendations for their use.

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