Long-Term Safety and Efficacy of Roflumilast Foam 0.3% in Patients with Seborrheic Dermatitis: A Phase II, Open-Label Trial of up to 52 Weeks

Abstract

Background

The efficacy and safety of once-daily roflumilast foam 0.3%, a potent phosphodiesterase 4 inhibitor, has been demonstrated in patients with seborrheic dermatitis (SD).

Objectives

To evaluate long-term effects of roflumilast foam 0.3% in patients with SD.

Methods

A phase II, open-label trial (no. NCT04445987) was conducted in patients (aged ≥ 12 years) with SD who completed a prior roflumilast foam trial or were naïve to roflumilast and vehicle. Patients applied roflumilast foam 0.3% once daily to all affected areas, including the scalp, face, trunk, and intertriginous areas, for 24 or 52 weeks (during the course of the trial, the protocol was amended to extend the duration of treatment from 24 weeks to 52 weeks). The primary endpoints were occurrence of treatment-emergent adverse events (AEs); local tolerability and efficacy (via Investigator Global Assessment [IGA]) were also assessed.

Results

Overall, 400 patients participated, among whom 62 were enrolled for 52 weeks. AE rates were low, and ≤ 1.1% reported stinging sensation at the application site at each visit. Durable improvement in signs and symptoms of SD was observed at weeks 24 and 52, with 76.0% and 80.4% of patients, respectively, achieving an IGA of clear or almost clear.

Conclusions

Roflumilast foam 0.3% was well tolerated and improved and/or maintained improvements in signs and symptoms of SD for up to 52 weeks.

ClinicalTrials.gov Listing

NCT04445987.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40257-025-00984-2.

Key Points

Seborrheic dermatitis causes considerable burden, and current treatments are limited because of low efficacy and/or risk of side effects.

Once-daily roflumilast foam 0.3%, a potent phosphodiesterase 4 inhibitor, was well tolerated and effective for long-term continuous treatment of seborrheic dermatitis on any affected body area, addressing limitations of current treatments.

Introduction

Seborrheic dermatitis (SD) is a common chronic relapsing inflammatory skin disease that affects patients of all ages, with a global prevalence of ≥ 5% [1]. Patients develop pruritic, erythematous patches with easily detachable scales in sebum-rich areas of the body, particularly the scalp, face, upper chest, and back [2]. Although research on the pathogenesis of SD has been limited, a recent study in adults suggests that SD has a unique immunological and molecular profile including prominent Th17/Th22 polarization, abnormalities in lipid metabolism pathways, and skin barrier dysfunction that is distinct from psoriasis and atopic dermatitis [3–7]. Inflammation associated with SD may be exacerbated by the proliferation of commensal yeasts (specifically Malassezia spp.), which metabolize lipids secreted by sebaceous glands into molecules that further activate the inflammatory response [3], precipitating flares of SD [1].

Topical treatments that are commonly used for SD include antifungal agents, such as ketoconazole and ciclopirox [8]. Anti-inflammatory topical corticosteroid treatments and keratolytic products are also used [1]. However, the use of these treatments is limited because of low efficacy, side effects, and/or formulation ingredients that may cause breakage or dry hair or not accommodate the various hairstyles and cultural considerations of hair care [1, 9].

Phosphodiesterase 4 (PDE4) inhibition reduces cyclic adenosine monophosphate degradation, resulting in decreased proinflammatory mediator production, decreased sensory neuron activation mediating the itch sensation, and normalization of keratinocyte activation and differentiation, which can lead to mitigation of epidermal barrier dysfunction [10–15]. Roflumilast is a selective, highly potent PDE4 inhibitor; [12] it has approximately 25 to > 300-fold higher potency than apremilast and crisaborole, and more closely mimics cyclic adenosine monophosphate binding to PDE4 [12, 16]. Roflumilast foam 0.3% is an emollient, water-based (65% water) foam without fragrances, propylene glycol, polyethylene glycol, isopropyl alcohol, or ethanol [17]. The foam has a propellant that dissipates rapidly when applied. Roflumilast foam is specifically formulated to maintain the integrity of the skin barrier and the hair [18]. Topical roflumilast has demonstrated safety and efficacy in patients with psoriasis [19, 20], atopic dermatitis [21, 22], and SD [17, 23]. This manuscript presents safety, efficacy, and local tolerability results from a long-term phase II open-label trial of patients with SD treated with roflumilast foam 0.3% for up to 52 weeks.

Methods

Trial Design and Oversight

This was a phase II, multicenter, single-arm, open-label, long-term trial (no. NCT04445987) conducted at 39 sites in the USA between 12 June 2020 and 15 December 2021. The first patient was enrolled on 12 June 2020, and the trial was registered on 22 June 2020. The trial was conducted in accordance with the principles of the Declaration of Helsinki [24] and the Good Clinical Practice guidelines of the International Council for Harmonisation (ICH) [25]. Written informed consent was obtained from all patients at screening prior to trial enrollment; assent was also obtained when applicable.

Patients

Eligible patients included males and females aged ≥ 18 years who met eligibility for and completed a prior roflumilast foam trial and patients aged ≥ 12 years who had not participated in a prior trial. Patients who had completed a prior roflumilast foam trial could immediately enroll in this trial on the final visit of the prior trial and did not need to meet additional eligibility criteria. Patients who had not participated in a prior roflumilast trial were required to have a clinical diagnosis of SD with a duration of at least 3 months and SD involving the scalp, face, trunk, and/or intertriginous areas affecting ≤ 20% of the body surface area (BSA). In addition, on day 1, patients were required to have an Investigator Global Assessment (IGA; a static evaluation of overall SD severity) of at least moderate (3) and overall assessments of erythema and scaling of at least moderate (2). Key exclusion criteria were inability to discontinue treatment with excluded medications (which included antifungal topical agents, topical corticosteroids, and medicated shampoos) and treatments for SD within the washout period (Supplementary Table S1) and, for patients who had completed a prior roflumilast foam trial, a treatment-related adverse event (AE) or a serious adverse event (SAE) that precluded further treatment with roflumilast foam.

Trial Treatments

Patients were assigned kits containing 60-g canisters of roflumilast foam 0.3% (provided to all trial sites by Arcutis Biotherapeutics, Inc., Westlake Village, CA). The number of kits dispensed to each patient at their respective trial site was based on the percentage BSA involved. Patients applied roflumilast foam 0.3% once daily to all areas affected, including the face, scalp, trunk, and/or intertriginous/genital regions. Treatment duration was initially up to 24 weeks; a protocol amendment extended the treatment period to up to 52 weeks. On day 1, trial site staff showed patients how to apply the foam. On all subsequent days, patients were instructed to apply the foam in the evening at least 20 min before going to bed. Patients were to maintain treatment with roflumilast foam and document each application in the provided trial diary. If the investigator determined that the IGA was completely clear (0) at any visit, the investigator instructed the patient to discontinue treatment with roflumilast. The patient was also instructed to contact the clinical trial site when SD returned before restarting treatment (and document in the trial diary). Patients were to treat any new lesions that developed during the trial unless otherwise instructed by the investigator.

Non-medicated emollients, moisturizers, and sunscreens were allowed once daily as normally used by patients and applied at least 3 h after application of the investigational product to untreated areas only.

Trial

The primary objective was safety, and the primary endpoints were occurrence of treatment-emergent AEs (TEAEs) and SAEs. Safety was also monitored through physical examinations, local tolerability assessments, vital signs/weight, clinical laboratory parameters, the eight-item Patient Health Questionnaire depression scale (PHQ-8)/modified nine-item Patient Health Questionnaire for adolescents (PHQ-A), Columbia-Suicide Severity Rating Scale (C-SSRS), and pigmentation assessments. Local tolerability at application sites was assessed by investigators (prior to roflumilast application in the clinic) and patients (recall of their experience 10–15 min after application) at baseline and weeks 4, 12, 24, 36, and 52. Investigators rated local tolerability on an 8-point scale (range: no evidence of irritation [0] to strong reaction spreading beyond application site [7]). Patient-reported local tolerability was evaluated on a 4-point scale (range: none [0; no sensation] to severe [3; hot, tingling/stinging sensation that has caused definite discomfort]). Hyperpigmentation and hypopigmentation were assessed on 4-point scales (range: none [0] to severe [3]). Adolescent patients (aged 12–17 years, inclusive) completed the PHQ-A and adults (aged ≥ 18 years) completed the PHQ-8.

Efficacy was measured at each study visit through 52 weeks. Efficacy endpoints were IGA (a 5-point scale ranging from completely clear [0] to severe [4]); Worst Itch-Numeric Rating Scale (WI-NRS; an 11-point scale ranging from 0 [no itch] to 11 [worst itch imaginable]) [26]; overall assessments of erythema and scaling (4-point scales ranging from 0 [none] to 3 [severe]); percentage of BSA affected; and Scalpdex (a 23-item quality-of-life instrument specific for scalp dermatitis, with each item answered on a 5-point scale ranging from never [1] to all the time [5]) [27]. Demographic information was also collected for each patient, including sex, age, race, and ethnicity, according to categories required by regulatory agencies.

Statistical Analysis

A sample size of approximately 410 patients was expected to provide a sufficient population size to evaluate long-term safety of roflumilast foam 0.3% over up to 52 weeks of treatment and was not based on any calculations of power or precision.

Summaries of variables were calculated using Statistical Analysis System, version 9.4 or later (SAS Institute Inc., Cary, NC, USA). No adjustments for multiple comparisons, inferential statistical analyses, or imputation for missing data were performed for this study. All summaries were conducted in the safety population, which included all patients who received one or more confirmed doses of roflumilast foam 0.3% regardless of prior roflumilast trial participation. Baseline was defined as the last observation recorded before the first dose of roflumilast foam 0.3% in a prior trial or this trial (for patients who had not participated in a prior trial or who received vehicle in a prior trial).

Results

Patients

A total of 400 patients received one or more confirmed doses of roflumilast foam and were included in the safety population, of whom 338 were enrolled for 24 weeks and 62 were eligible and enrolled to continue through 52 weeks (Supplementary Fig. S1). Of these, 327 patients (81.8%) completed the duration of treatment for which they were enrolled (i.e., 24 or 52 weeks). The most common reasons for trial discontinuation were patients lost to follow-up (n = 38 [9.5%]) and withdrawal by the patient (n = 23 [5.8%]). The mean age of patients was 43.3 years, and 51% were female. The population was 80% white, 13% Black or African American, and 7% of other races (Asian, Native Hawaiian or Other Pacific Islander, other, and more than one race; Table 1).

Table 1.

Demographics and baseline disease characteristics (safety population)

Characteristic	Roflumilast foam 0.3% (n = 400)
Age, years, mean (standard deviation)	43.3 (16.4)
Age group, n (%)
12–17 years	13 (3.3)
18–64 years	333 (83.3)
≥ 65 years	54 (13.5)
Female, n (%)	203 (50.8)
Hispanic or Latino, n (%)a	115 (28.8)
Race, n (%)b
American Indian or Alaskan Native	0
Asian	17 (4.3)
Black or African American	51 (12.8)
Native Hawaiian or Other Pacific Islander	1 (0.3)
White	319 (79.8)
Other	6 (1.5)
More than one race	3 (0.8)
Inadequate response, intolerance, or contraindication to, n (%)
Topical corticosteroids	117 (29.3)
Topical antifungals	108 (27.0)
Body area involvement, n (%)
Facial involvement	239 (59.8)
Scalp involvement	368 (92.0)
BSA affected, %, mean (standard deviation)	3.6 (3.08)
IGA, n (%)
Completely clear (0)	2 (0.5)
Almost clear (1)	9 (2.3)
Mild (2)	4 (1.0)
Moderate (3)	341 (85.3)
Severe (4)	44 (11.0)
WI-NRS
Mean (standard deviation)	5.7 (2.58)
Patients with baseline score ≥ 4, n (%)	316 (79.0)
Scaling score, n (%)
0 (none)	6 (1.5)
1 (mild)	11 (2.8)
2 (moderate)	314 (78.5)
3 (severe)	69 (17.3)
Erythema score, n (%)
0 (none)	4 (1.0)
1 (mild)	12 (3.0)
2 (moderate)	339 (84.8)
3 (severe)	45 (11.3)
Scalpdex total score, mean (standard deviation)	39.5 (20.1)

Baseline was defined as the last observation recorded before the first dose of roflumilast foam 0.3% in a prior trial or this trial (for patients who had not participated in a prior trial or who received vehicle in a prior trial).

BSA body surface area, IGA Investigator Global Assessment, WI-NRS Worst Itch-Numeric Rating Scale

^aEthnicity was not reported for two (0.5%) patients

^bRace was not reported for three (0.8%) patients

Safety

Adverse Events

TEAEs were reported for 130 patients (32.5%; Table 2). Incidence rates were consistent regardless of race (white [32.3%], Black or African American [33.3%], and other races [33.3%]) or age (12–17 years [30.8%], 18–64 years [31.8%], and ≥ 65 years [36.8%]). Most TEAEs (91.5%) were mild or moderate. The most common TEAE was coronavirus disease 2019 (COVID-19), which was reported for 15 of 400 (3.8%) patients, followed by headache (13/400 [3.3%]). Overall, 22 patients (5.5%) had an AE that was considered treatment related by the investigator, and 5 of 400 patients (1.3%) discontinued the trial because of an AE. SAEs were reported for 7 of 400 patients (1.8%), none of which were considered treatment related. Few patients reported gastrointestinal AEs (nausea: 5/400 [1.3%] and diarrhea: 4/400 [1.0%]). Insomnia was reported for 4 of 400 patients (1.0%).

Table 2.

Adverse events

n (%)	Roflumilast foam 0.3% (n = 400)
Patients with any TEAE	130 (32.5)
Patients with any treatment-related TEAE	22 (5.5)
Patients with any SAE	7 (1.8)
Patients with treatment-related SAE	0
Patients who discontinued trial because of AEa	5 (1.3)
Most common TEAE (≥ 2%), preferred term
COVID-19	15 (3.8)
Headache	13 (3.3)

AE adverse event, SAE serious adverse event, TEAE treatment-emergent adverse event

^aThree patients had AEs leading to discontinuation considered possibly related to trial treatment: diffuse alopecia (n = 1); ocular rosacea (n = 1); and diarrhea, nausea, vomiting, and headache (these four events were reported by a single patient). Two patients had AEs leading to discontinuation considered not related to trial treatment: lymphadenopathy (n = 1) and brain neoplasm, malignant (n = 1)

Local Tolerability

On the basis of investigator-rated local tolerability assessments, ≥ 96.0% of patients had no evidence of irritation at each timepoint. For patient-reported local tolerability assessments, ≤ 1.1% reported stinging sensation at the application site at each visit.

Pigmentation

Most patients with hyperpigmentation or hypopigmentation at baseline experienced full resolution. Of the patients who had hyperpigmentation at baseline who were assessed at week 24 (n = 29), 23 (79.3%) experienced full resolution at week 24. Of the patients who had hypopigmentation at baseline who were assessed at week 24 (n = 34), 25 (73.5%) experienced full resolution at week 24. At week 24, new instances of hyperpigmentation (n = 7) and hypopigmentation (n = 3) were uncommon. Of the patients with hyperpigmentation or hypopigmentation at baseline who were assessed at 52 weeks (n = 7 and n = 11, respectively), six (85.7%) of those with hyperpigmentation at baseline experienced full resolution at week 52, while eight (72.7%) of those with hypopigmentation at baseline experienced full resolution at week 52.

Vital Signs, Laboratory Parameters, and Other Safety Assessments

No clinically meaningful changes in vital signs were observed, and laboratory values did not indicate any safety concerns. Assessments of depression and suicidal ideation or behavior did not identify any safety concerns. No AEs associated with hair breakage were reported.

Efficacy

Once-daily treatment with roflumilast foam 0.3% resulted in durable improvements in IGA (Figs. 1, 3, and Supplementary Table S2). In patients who were treated for 52 weeks in this trial (n = 46), 24 patients (52.2%) achieved IGA 0 at week 52 (Fig. 3). Similarly, 56.4% (219/388) achieved IGA 0/1 at week 4, 76.0% (260/342) at week 24, and 80.4% (37/46) at week 52 (Fig. 1). The proportion of patients achieving IGA 0/1 at week 24 was consistent regardless of age: 11/13 (84.6%) in patients aged 12–17 years, 207/277 (74.7%) in patients aged 18–64 years, and 42/52 (80.1%) in patients aged ≥ 65 years. For the 34.5% of patients who achieved IGA of 0 and stopped treatment, the median treatment-free interval was 22.7 weeks. Patients also responded consistently regardless of race. For white patients, 201/271 (74.2%) achieved IGA 0/1 at week 24, while proportions for Black or African American patients and other races were 35/45 (77.8%) and 22/24 (91.7%), respectively.

Fig. 1.

Proportion of patients with IGA completely clear or almost clear. CI confidence interval, IGA Investigator Global Assessment

Fig. 3.

Proportion of patients with IGA, erythema, and scaling scores of 0. CI confidence interval, IGA Investigator Global Assessment

Patients also experienced durable improvements in WI-NRS, erythema, scaling, and Scalpdex scores (Figs. 2, 3, and Supplementary Table S2). Treatment with roflumilast foam 0.3% reduced pruritus, with 71.3% (189/265) of patients with WI-NRS ≥ 4 at baseline (last observation recorded before the first dose of roflumilast foam 0.3% in a prior trial or this trial) achieving a ≥ 4-point improvement at week 24 and 58.1% at week 52 (18/31; Fig. 2). Similarly, 51.1% (187/366) of patients achieved WI-NRS 0/1 at week 12, 55.8% (191/342) at week 24, and 52.2% at week 52 (24/46; Fig. 2). Moreover, roflumilast treatment resulted in high proportions of patients with erythema and scaling scores of 0 throughout the trial (erythema: 30.7–67.4%; scaling: 31.4–58.7%; Fig. 3). Mean Scalpdex total scores improved consistently from baseline through week 52 (Supplementary Table S2).

Fig. 2.

Proportion of patients with a ≥ 4-point improvement from baseline on WI-NRS and WI-NRS 0/1. WI-NRS ≥ 4-point improvement was evaluated in patients with baseline WI-NRS score ≥ 4, whereas WI-NRS 0/1 was evaluated in all patients. Baseline was defined as the last observation recorded before the first dose of roflumilast foam 0.3% in a prior trial or this trial (for patients who had not participated in a prior trial or who received vehicle in a prior trial). CI confidence interval, WI-NRS Worst Itch-Numeric Rating Scale

Photographs of improvement in patients with SD following treatment with roflumilast foam 0.3% are shown in Supplementary Fig. S2.

Discussion

Long-term treatment with roflumilast foam 0.3% for up to 52 weeks in this trial extends the safety and tolerability profile reported for earlier trials in SD. Specifically, treatment with roflumilast foam 0.3% was associated with low rates of TEAEs and local tolerability findings and durable improvements in IGA and WI-NRS in patients with SD [17, 23]. No new safety or local tolerability signals were observed over the up to 52 weeks of treatment. Most TEAEs were mild or moderate with low rates of SAEs and TEAEs leading to discontinuation.

In contrast to oral roflumilast and oral apremilast, which are associated with gastrointestinal AEs [28, 29], patients in this trial of once-daily topical roflumilast experienced low rates of these AE categories, consistent with the phase IIa and III randomized controlled trials [17, 23]. Specifically, only 1.3% of patients in this trial experienced nausea, and only 1.0% experienced diarrhea, compared with 4.7% and 9.5%, respectively, in patients treated with 500 µg oral roflumilast daily [29]. Likewise, the psychiatric AEs commonly observed with oral PDE4 inhibitors occurred infrequently, and no safety concerns were identified by assessments of depression and suicidal ideation or behavior conducted at each study visit. Thus, the frequency of AEs that often occur with oral PDE4 inhibitors was much lower with long-term topical roflumilast foam, which is consistent with prior studies [17, 23].

The investigator-rated and patient-reported local tolerability profiles were also consistent with the phase IIa and III randomized controlled trials [17, 23]. Nearly all patients reported no or mild sensation at each visit. Most patients with hyper- or hypopigmentation at baseline experienced full resolution, which could be because of reduced inflammation; new instances of hyper- or hypopigmentation were also infrequent. No AEs associated with hair breakage were reported, which can be a concern with other topical foams [30].

Durable improvements were also observed for multiple efficacy endpoints, including IGA 0/1 and pruritus. Chronic pruritus greatly affects patients’ quality of life [31], with the amount of impact comparable to that of chronic pain [32]. In the current trial, > 70% of patients with WI-NRS ≥ 4 at baseline experienced a ≥ 4-point improvement from baseline at week 24. Although the subgroups were small, efficacy improvements were consistent regardless of age or race and similar to the parent phase IIa trial [23].

A limitation of this trial is that, although roflumilast foam 0.3% is approved for use in patients as young as 9 years of age with SD, only patients aged ≥ 12 years were included in the trial. Second, as the trial was extended to 52 weeks during the trial, the number of patients treated through 52 weeks was limited to 62 of the original 400 patients enrolled.

Conclusions

These data extend the results of previous randomized controlled trials of acute use of roflumilast foam 0.3% for SD and suggest that it is a well-tolerated and efficacious once-daily topical monotherapy option with durable efficacy in chronic treatment of SD across all affected areas, including the face, scalp, and trunk.

Supplementary Information

Below is the link to the electronic supplementary material.

Funding

This work was supported by Arcutis Biotherapeutics Inc.

Declarations

Conflict of interest

Andrew F. Alexis received grants (funds to institution) from AbbVie, Amgen, Arcutis, Castle Biosciences, Dermavant, Galderma, Incyte, and LEO Pharma; served on advisory boards or as a consultant for AbbVie, Allergan, Almirall, Alphyn Biologics, Amgen, Apogee Therapeutics, Arcutis, AVITA Medical, Bausch Health, Beiersdorf, BMS, Boehringer Ingelheim, Canfield Scientific, Cara Therapeutics, Castle Biosciences, Cutera, Dermavant, EPI Health, Galderma, Genentech, Genzyme, Incyte, LEO Pharma, Lilly, L’Oreal, Janssen, Ortho Dermatologics, Pfizer, Sanofi Regeneron, Swiss American, UCB, and VisualDx; is a speaker for Aerolase, BMS, Janssen, Johnson & Johnson, L’Oreal, Regeneron, and Sanofi Genzyme; receives royalties from Elsevier, Wiley-Blackwell, and Wolters Kluwer Health; and received equipment from Aerolase. Michael Bukhalo is an investigator for Arcutis and received grants/research funding and honoraria. Fran E. Cook-Bolden serves as an advisory board member for AbbVie, Dermavant, Galderma, Novartis, Ortho Dermatologics, and Pfizer; as an investigator for Arcutis; as a speaker for Galderma, Journey Medical Corporation, and Ortho Dermatologics; and has received other financial benefit from Topix Pharmaceuticals. James Q. Del Rosso received investigator fees, speaker fees, clinical research grants, and/or honoraria from Aclaris, Almirall, Amgen, AnaptysBio, Arcutis, Athēnix, Biofrontera, BioPharmX, Biorasi, BlueCreek Dermatologics, BMS, Botanix, Brickell Biotech, Cara Therapeutics, Cassiopea SpA, Dermata, Dermavant, Dermira, Encore Dermatology, Evommune, Ferndale Laboratories, Foamix, Galderma, Genentech, Incyte, JEM Health, L’Oreal, La Roche-Posay, LEO Pharma, Lilly, Mayne Pharma, Menlo Therapeutics, Novan, Ortho Dermatologics, Pfizer, Promius Pharma, Ralexar, Regeneron, Sanofi Genzyme, Sebacia, Senté, Sol-Gel Technologies, Sonoma Pharmaceuticals, Sun Pharma, Trevi Therapeutics, UCB, Unilever Home & Personal Care, Verrica, and Viamet; and received salary as an employee of Regeneron. Zoe D. Draelos received a research grant from Arcutis to contribute to the study presented in the paper. Janet C. DuBois is an investigator for and receives grants/research funding from AbbVie, Accure for Acne, Acrotech Biopharma, Amplifica, Arcutis, Biofrontera, Bluefin Biomedicine, BMS, Brickell Biotech, Caliway Biopharmaceuticals, Cara Therapeutics, Cassiopea SpA, Croma-Pharma, Dermata, DermBiont, Incyte, Medytox, Merck, Moberg Pharma, Nail Genesis, Nielsen Biosciences, Q32 Bio, RAPT Therapeutics, Sanofi, Scarless Laboratories, TechnoDerma, Therapeutics Inc., and VeraDermics. Laura K. Ferris received consulting fees, investigator fees, speaker fees, clinical research grants, sponsored research, and/or honoraria from AbbVie, Amgen, Boehringer Ingelheim, BMS, Dermavant, Janssen, Lilly, Nimbus Therapeutics, Novartis, and UCB. Seth B. Forman is an investigator for Arcutis and received grants/research funding and honoraria. Steven E. Kempers is an investigator for Arcutis and received grants/research funding and honoraria. Leon H. Kircik received investigator fees, speaker fees, clinical research grants, and/or honoraria from 3M Pharmaceuticals, Abbott, Ablynx, Acambis, Allergan, Almirall, Amgen, AnaptysBio, Aqua Pharmaceuticals, Arcutis, Astellas, Asubio, Bayer Consumer Health, Beiersdorf, Biogen, Biolife, Biopelle, BMS, Boehringer Ingelheim, Botanix, Breckinridge Pharma, Cassiopea SpA, Celgene, Cellceutix, Centocor, ChemoCentryx, ColBar LifeScience, CollaGenex Pharmaceuticals, Connetics Corporation, Coria Laboratories, Dermavant, Dermik (a business of Sanofi Aventis), Dow Pharmaceutical Sciences, DUSA Pharmaceuticals, Embil Pharmaceutical Co, EOS Pharmaceutical Corp, Ferndale Laboratories, Galderma, Genentech, GSK, Healthpoint, Incyte, Intendis, ISDIN, Johnson & Johnson Consumer Products, Laboratory Skin Care, LEO Pharma, MC2 Therapeutics, Medical International Technologies, Medicis, Merck, Merck Serono, Merz Pharmaceuticals, NanoBio Corporation, Novartis, Nucryst, Obagi Medical, Onset Dermatologics, Ortho Dermatologics, Pfizer, Pharmaderm, Promius Pharma, PuraCap, QLT Inc., Sandoz (a Novartis company), SkinMedica, Stiefel (a GSK company), Sun Pharma, Taro Pharmaceuticals, TolerRx, Triax Pharmaceuticals, Valeant, Warner Chilcott, Xenoport, and Zalicus. Edward Lain is an investigator for Arcutis and received grants/research funding and honoraria. Angela Y. Moore received research funds or honoraria from AbbVie, Almirall, Arcutis, BMS, Cara Therapeutics, Dermavant, Galderma, Janssen, Incyte, Lilly, Novartis, Pfizer, Sanofi, Takeda, UCB, and Vyne. David M. Pariser is an investigator for and receives grants/research funding and/or honoraria from Almirall, Amgen, AOBiome, Asana BioSciences, Brickell Biotech, Celgene, Dermira, LEO Pharma, Lilly, Menlo Therapeutics, Novartis, Novo Nordisk, Ortho Dermatologics, Pfizer, and Regeneron; is a consultant and/or serves on an advisory board for and receives honoraria from Biofrontera, Brickell Biotech, Dermira, Novartis, Pfizer, Regeneron, and Sanofi; and is on the data safety monitoring board and receives honoraria from BMS. Joseph Raoof has served as an investigator for AbbVie, Arcutis, AstraZeneca, Bausch Health, BMS, Boehringer Ingelheim, Dermavant, Dermira, Galderma, GSK, Incyte, Janssen, LEO Pharma, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and UCB. Matthew J. Zirwas received consulting fees, investigator fees, speaker fees, clinical research grants, and/or honoraria from and/or has participated in sponsored research for AbbVie, All Free Clear/Sun, AnaptysBio, Arcutis, Asana Biosciences, Aseptic MD, Avillion, Bausch Health, Cara Therapeutics, Concert Pharmaceuticals, Dermavant, Edesa, EPI Health, Fitbit, Galderma, Genentech/Novartis, Incyte, Janssen, L’Oreal, LEO Pharma, Level Ex, Lilly, LUUM, Oculus, Peloton, Pfizer, Sanofi Regeneron, Sol-Gel Technologies, Trevi Therapeutics, UCB, and Vyne. Melissa S. Seal, Saori Kato, David H. Chu, David Krupa, Scott Snyder, Patrick Burnett, and David R. Berk are employees of Arcutis.

Availability of data and material

Data collected for this study will be made available to others. Proposals for data requests will be reviewed and considered for sharing following approval of the indication.

Code availability

Not applicable.

Ethics approval

The protocol was approved by the WCG Institutional Review Board (IRB Tracking Number: 20201067), and local institutional review boards for sites not covered by this central institutional review board. The trial was conducted in accordance with the principles of the 1964 Declaration of Helsinki and its later amendments, with the exception that this trial was retrospectively registered. The trial was posted to clinicaltrials.gov no later than 21 days after enrollment of the first participant in accordance with the Food and Drug Administration Amendments Act (FDAAA) 801 guidance.

Patient consent on file: consent to participate

Written informed consent was obtained from all patients at screening prior to trial enrollment; assent was also obtained when applicable.

Consent for publication

The investigators obtained written consent from patients for their photographs and medical information to be published in print and online with the understanding that this information may be publicly available. Patient consent forms were not provided to the journal but were retained by the investigators.

Author contributions

Andrew F. Alexis had full access to all data in the trial and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Seal, Kato, Chu, Krupa, Snyder, Burnett, and Berk. Acquisition, analysis, or interpretation of data: all authors. Drafting of the manuscript: all authors. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: Krupa. Supervision: Seal, Kato, Chu, Krupa, Snyder, Burnett, and Berk. All authors read and approved the final manuscript.