Difamilast, a Selective Phosphodiesterase 4 Inhibitor, Ointment in Paediatric Patients with Atopic Dermatitis: a Phase III Randomized Double-blind, Vehicle-controlled Trial

Overview

Journal Br J Dermatol

Publisher Oxford University Press

Specialty Dermatology

Date 2021 Jul 21

PMID 34289086

Citations 15

Authors

H Saeki

N Baba

K Ito

D Yokota

H Tsubouchi

Affiliations

Soon will be listed here.

Abstract

Background: In atopic dermatitis (AD), phosphodiesterase 4 (PDE4) inhibition reduces proinflammatory mediators and cytokines. Difamilast is a new selective PDE4 inhibitor.

Objectives: To demonstrate the superiority of topical difamilast to vehicle in Japanese paediatric patients with AD.

Methods: This was a phase III randomized, double-blind, vehicle-controlled trial. Patients aged 2-14 years with an Investigator Global Assessment (IGA) score of 2 or 3 received difamilast 0·3% (n = 83), difamilast 1% (n = 85) or vehicle (n = 83) ointment twice daily for 4 weeks.

Results: The primary endpoint was the percentage of patients with an IGA score of 0 or 1 with improvement by at least two grades at week 4. The success rates in IGA score at week 4 were 44·6%, 47·1% and 18·1% in the difamilast 0·3%, difamilast 1% and vehicle groups, respectively. Both difamilast groups demonstrated significantly higher success rates in IGA score compared with vehicle at week 4 [difamilast 0·3% (P < 0·001); difamilast 1% (P < 0·001)]. Regarding secondary endpoints, improvements in Eczema Area and Severity Index (EASI; improvement of ≥ 50%, ≥ 75% and ≥ 90% in overall score) at week 4 were significantly higher in patients in the difamilast 0·3% and 1% groups than those in the vehicle group. EASI score in the difamilast 0·3% and 1% groups was significantly reduced compared with that of patients in the vehicle group at week 1. The significant difference between both the difamilast groups and the vehicle groups was maintained from week 1 through to week 4. Most treatment-emergent adverse events were mild or moderate, and no serious events or deaths were reported.

Conclusions: Difamilast 0·3% and 1% ointments are superior to vehicle and well tolerated in Japanese paediatric patients with AD.

Citing Articles

Exploring the Therapeutic Landscape: A Narrative Review on Topical and Oral Phosphodiesterase-4 Inhibitors in Dermatology.

Carmona-Rocha E, Rusinol L, Puig L Pharmaceutics. 2025; 17(1).

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Cost-Effectiveness Study of Difamilast 1% for the Treatment of Atopic Dermatitis in Adult Japanese Patients.

Nakahara T, Noto S, Matsukawa M, Takeda H, Zhang Y, Kondo T Dermatol Ther (Heidelb). 2024; 14(11):3113-3132.

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Biologic and Small Molecule Therapy in Atopic Dermatitis.

Shergill M, Bajwa B, Yilmaz O, Tailor K, Bouadi N, Mukovozov I Biomedicines. 2024; 12(8).

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

Lax S, Van Vogt E, Candy B, Steele L, Reynolds C, Stuart B Cochrane Database Syst Rev. 2024; 8():CD015064.

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An Interim Report of a Phase 3, Long-Term, Open-Label Study to Evaluate Efficacy and Safety of Difamilast Ointment in Japanese Infants with Atopic Dermatitis.

Saeki H, Ohya Y, Baba N, Imamura T, Yokota D, Tsubouchi H Dermatol Ther (Heidelb). 2024; 14(9):2443-2455.

PMID: 39075274 PMC: 11393375. DOI: 10.1007/s13555-024-01236-7.

References

Phan N, Blome C, Fritz F, Gerss J, Reich A, Ebata T . Assessment of pruritus intensity: prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with chronic pruritus. Acta Derm Venereol. 2011; 92(5):502-7. DOI: 10.2340/00015555-1246. View

Zebda R, Paller A . Phosphodiesterase 4 inhibitors. J Am Acad Dermatol. 2017; 78(3 Suppl 1):S43-S52. DOI: 10.1016/j.jaad.2017.11.056. View

Weidinger S, Novak N . Atopic dermatitis. Lancet. 2015; 387(10023):1109-1122. DOI: 10.1016/S0140-6736(15)00149-X. View

Mosteller R . Simplified calculation of body-surface area. N Engl J Med. 1987; 317(17):1098. DOI: 10.1056/NEJM198710223171717. View

Pavlis J, Yosipovitch G . Management of Itch in Atopic Dermatitis. Am J Clin Dermatol. 2017; 19(3):319-332. DOI: 10.1007/s40257-017-0335-4. View

Silverberg J, Nelson D, Yosipovitch G . Addressing treatment challenges in atopic dermatitis with novel topical therapies. J Dermatolog Treat. 2016; 27(6):568-576. DOI: 10.1080/09546634.2016.1174765. View

Saeki H, Baba N, Oshiden K, Abe Y, Tsubouchi H . Phase 2, randomized, double-blind, placebo-controlled, 4-week study to evaluate the safety and efficacy of OPA- 15406 (difamilast), a new topical selective phosphodiesterase type-4 inhibitor, in Japanese pediatric patients aged 2-14 years with.... J Dermatol. 2019; 47(1):17-24. PMC: 6972691. DOI: 10.1111/1346-8138.15137. View

Hanifin J, Ellis C, Frieden I, Folster-Holst R, Stein Gold L, Secci A . OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study. J Am Acad Dermatol. 2016; 75(2):297-305. DOI: 10.1016/j.jaad.2016.04.001. View

Hanifin J, Thurston M, Omoto M, Cherill R, Tofte S, Graeber M . The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol. 2001; 10(1):11-8. DOI: 10.1034/j.1600-0625.2001.100102.x. View

10.

Furue M, Yamazaki S, Jimbow K, Tsuchida T, Amagai M, Tanaka T . Prevalence of dermatological disorders in Japan: a nationwide, cross-sectional, seasonal, multicenter, hospital-based study. J Dermatol. 2011; 38(4):310-20. DOI: 10.1111/j.1346-8138.2011.01209.x. View

11.

Hoy S . Crisaborole Ointment 2%: A Review in Mild to Moderate Atopic Dermatitis. Am J Clin Dermatol. 2017; 18(6):837-843. DOI: 10.1007/s40257-017-0327-4. View

12.

Nygaard U, Deleuran M, Vestergaard C . Emerging Treatment Options in Atopic Dermatitis: Topical Therapies. Dermatology. 2017; 233(5):333-343. DOI: 10.1159/000484407. View

13.

Futamura M, Leshem Y, Thomas K, Nankervis H, Williams H, Simpson E . A systematic review of Investigator Global Assessment (IGA) in atopic dermatitis (AD) trials: Many options, no standards. J Am Acad Dermatol. 2015; 74(2):288-94. DOI: 10.1016/j.jaad.2015.09.062. View

14.

Roduit C, Frei R, Depner M, Karvonen A, Renz H, Braun-Fahrlander C . Phenotypes of Atopic Dermatitis Depending on the Timing of Onset and Progression in Childhood. JAMA Pediatr. 2017; 171(7):655-662. PMC: 5710337. DOI: 10.1001/jamapediatrics.2017.0556. View

15.

Saeki H, Kawashima M, Sugaya S, Oshiden K, Tsubouchi H . Efficacy and safety of topical OPA-15406, a new phosphodiesterase 4 inhibitor, in Japanese patients with atopic dermatitis for 8 weeks: A phase 2, randomized, double-blind, placebo-controlled study. J Dermatol. 2021; 46(8):672-679. PMC: 6771806. DOI: 10.1111/1346-8138.14979. View

16.

Bass A, Anderson K, Feldman S . Interventions to Increase Treatment Adherence in Pediatric Atopic Dermatitis: A Systematic Review. J Clin Med. 2015; 4(2):231-42. PMC: 4470122. DOI: 10.3390/jcm4020231. View

17.

Katayama I, Aihara M, Ohya Y, Saeki H, Shimojo N, Shoji S . Japanese guidelines for atopic dermatitis 2017. Allergol Int. 2017; 66(2):230-247. DOI: 10.1016/j.alit.2016.12.003. View

18.

Drucker A, Wang A, Li W, Sevetson E, Block J, Qureshi A . The Burden of Atopic Dermatitis: Summary of a Report for the National Eczema Association. J Invest Dermatol. 2016; 137(1):26-30. DOI: 10.1016/j.jid.2016.07.012. View

19.

Malajian D, Guttman-Yassky E . New pathogenic and therapeutic paradigms in atopic dermatitis. Cytokine. 2014; 73(2):311-8. DOI: 10.1016/j.cyto.2014.11.023. View

20.

Paller A, Tom W, Lebwohl M, Blumenthal R, Boguniewicz M, Call R . Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016; 75(3):494-503.e6. DOI: 10.1016/j.jaad.2016.05.046. View