Difamilast ointment in adult patients with atopic dermatitis: A phase 3 randomized, double-blind, vehicle-controlled trial

Saeki, Hidehisa; Ito, Kensuke; Yokota, Daisuke; Tsubouchi, Hidetsugu

doi:10.1016/j.jaad.2021.10.027

Cited by 43 publications

(40 citation statements)

References 21 publications

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“…The efficacy results herein are consistent with those of the previous studies [ 9 – 14 ]. Our data show cumulative success rates in EASI-75 increasing from week 4 to week 52 in both adult and pediatric patients, and cumulative success rates in IGA score showing the same trend.…”

Section: Discussionsupporting

confidence: 92%

“…No new safety concerns were identified during difamilast application for 52 weeks. Namely, safety profiles of difamilast in this study were consistent with those in the previous clinical studies conducted in Japan [ 10 , 12 – 14 ]. The overall discontinuation rates were 25.3% in adult patients and 11.0% in pediatric patients, and most patients could complete the 52-week treatment with difamilast ointments.…”

Section: Discussionsupporting

confidence: 90%

“…The study enrolled patients with an IGA score of 4 (severe/very severe), with no restriction on the upper limit for the AD-affected BSA. Thus, this study included patients with more severe disease compared with those in the previous phase III studies [ 13 , 14 ], closely reflecting the real-world clinical setting in Japan.…”

Section: Methodsmentioning

confidence: 99%

“…At each visit, the investigator instructed the patient (and for children, the legal guardian) to apply difamilast to the currently affected areas of skin excluding the scalp. The method used to calculate the dose for each patient has been reported previously [ 13 , 14 ]. If needed, interruption or resumption of difamilast application was permitted for all patients on the basis of an existing condition.…”

Section: Methodsmentioning

confidence: 99%

“…Difamilast, a selective PDE4 inhibitor developed by Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan) [8], has shown favorable efficacy and safety profiles in the phase II studies conducted in Japan and the USA [9][10][11][12]. Furthermore, difamilast has shown superior efficacy to vehicle and was well tolerated in Japanese phase III studies, leading to its marketing approval recently in Japan [13,14]. Here, we report a phase III, long-term, open-label study to evaluate the safety and efficacy of topical difamilast in Japanese adult and pediatric patients with AD.…”

Section: Introductionmentioning

confidence: 99%

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Difamilast Ointment in Japanese Adult and Pediatric Patients with Atopic Dermatitis: A Phase III, Long-Term, Open-Label Study

Saeki

Imamura

Yokota

et al. 2022

Dermatol Ther (Heidelb)

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Introduction Phosphodiesterase 4 (PDE4), which regulates inflammatory cytokine production leading to atopic dermatitis (AD), is selectively inhibited by difamilast. The objective of this phase III, long-term, open-label study was to evaluate the safety and efficacy of topical difamilast in Japanese adult and pediatric patients with AD. Methods Adult patients ( n = 166) began treatment with difamilast 1% ointment, and pediatric patients began treatment with difamilast 0.3% ointment ( n = 144) or difamilast 1% ointment ( n = 56). Treatment was continued twice daily for 52 weeks. All patients had an Investigator’s Global Assessment (IGA) score of 2 (mild), 3 (moderate), or 4 (severe/very severe), and an AD-affected body surface area (BSA) of ≥ 5% before treatment, with no restriction on the upper limit for the AD-affected BSA. Results During therapy, 120 adult patients (72.3%) and 178 pediatric patients (89.0%) experienced treatment-emergent adverse events (TEAEs), most of which were mild or moderate in severity. Discontinuation due to TEAEs was reported in 13 adult patients (7.8%) and in 7 pediatric patients (3.5%). Treatment-related adverse events were reported in 14 adult patients (8.4%) and 16 pediatric patients (8.0%), most frequently dermatitis atopic (1.8%) and acne (1.2%) in adult patients and dermatitis atopic and pigmentation disorder (each 2.0%) in pediatric patients. The cumulative success rates in Eczema Area and Severity Index (EASI)-75 in adult and pediatric patients were 55.4% and 73.5%, respectively, at week 52, and the cumulative success rates increased from week 4 to week 52. The cumulative success rates in IGA score showed the same trend as those in EASI -75. Conclusions This study demonstrates that difamilast ointments are well tolerated and effective in Japanese adult and pediatric patients with AD when applied twice daily for 52 weeks, and are expected to be used for a long-term treatment for AD. Clinical Trial Registration Clinical Trials.gov identifier: NCT03961529. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-022-00751-9.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Difamilast Ointment in Japanese Adult and Pediatric Patients with Atopic Dermatitis: A Phase III, Long-Term, Open-Label Study

Saeki

Imamura

Yokota

et al. 2022

Dermatol Ther (Heidelb)

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Topical anti-inflammatory treatments for eczema: network meta-analysis

Lax,

Van Vogt,

Candy

et al. 2024

Cochrane Database of Systematic Reviews

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Background Eczema (atopic dermatitis) is the most burdensome skin condition worldwide and cannot currently be prevented or cured. Topical anti‐inflammatory treatments are used to control eczema symptoms, but there is uncertainty about the relative effectiveness and safety of different topical anti‐inflammatory treatments. Objectives To compare and rank the efficacy and safety of topical anti‐inflammatory treatments for people with eczema using a network meta‐analysis. Search methods We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries on 29 June 2023, and checked the reference lists of included studies. Selection criteria We included within‐participant or between‐participant randomised controlled trials (RCTs) in people of any age with eczema of any severity, but excluded trials in clinically infected eczema, seborrhoeic eczema, contact eczema, or hand eczema. We included topical anti‐inflammatory treatments used for at least one week, compared with another anti‐inflammatory treatment, no treatment, or vehicle/placebo. Vehicle is a 'carrier system' for an active pharmaceutical substance, which may also be used on its own as an emollient for dry skin. We excluded trials of topical antibiotics used alone, complementary therapies, emollients used alone, phototherapy, wet wraps, and systemic treatments. Data collection and analysis We used standard Cochrane methods. Primary outcomes were patient‐reported eczema symptoms, clinician‐reported eczema signs and investigator global assessment. Secondary outcomes were health‐related quality of life, long‐term control of eczema, withdrawal from treatment/study, and local adverse effects (application‐site reactions, pigmentation changes and skin thinning/atrophy were identified as important concerns through patient and public involvement). We used CINeMA to quantify our confidence in the evidence for each outcome. Main results We included 291 studies involving 45,846 participants with the full spectrum of eczema severity, mainly conducted in high‐income countries in secondary care settings. Most studies included adults, with only 31 studies limited to children aged < 12 years. Studies usually included male and female participants, multiple ethnic groups but predominantly white populations. Most studies were industry‐funded (68%) or did not report their funding sources/details. Treatment duration and trial participation were a median of 21 and 28 days (ranging from 7 days to 5 years), respectively. Interventions used were topical corticosteroids (TCS) (172), topical calcineurin inhibitors (TCI) (134), phosphodiesterase‐4 (PDE‐4) inhibitors (55), janus kinase (JAK) inhibitors (30), aryl hydrocarbon receptor activators (10), or other topical agents (21). Comparators included vehicle (170) or other anti‐inflammatory treatments. The risk of bias was high in 2...

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