Emerging drugs for the treatment of atopic dermatitis: a focus on phase 2 and phase 3 trials

References

• Silverberg JI. Public health burden and epidemiology of atopic dermatitis. Dermatol Clin. 2017 Jul 1;35(3):283–289. doi: 10.1016/j.det.2017.02.002
   PubMed Web of Science ®Google Scholar
• Ständer S. Atopic dermatitis. Ropper AH, editor. N Engl J Med. 2021 Mar 25;384(12):1136–1143. doi: 10.1056/NEJMra2023911
   PubMed Web of Science ®Google Scholar
• PromoCell [Internet]. [cited 2024 Feb 10]. Keratinocytes. Available from: https://promocell.com/cell-culture-basics/keratinocytes/
   Google Scholar
• Das P, Mounika P, Yellurkar ML, et al. Keratinocytes: an enigmatic factor in atopic dermatitis. Cells. 2022 May 19;11(10):1683. doi: 10.3390/cells11101683
   PubMed Web of Science ®Google Scholar
• Ong PY. Atopic dermatitis: is innate or adaptive immunity in control? A clinical perspective. Front Immunol. 2022 Jul 27;13:943640. doi: 10.3389/fimmu.2022.943640
   PubMed Web of Science ®Google Scholar
• Deng L, Costa F, Blake KJ, et al. S. aureus drives itch and scratch-induced skin damage through a V8 protease-PAR1 axis. Cell. 2023 Nov 22;186(24):5375–5393.e25. doi: 10.1016/j.cell.2023.10.019
   PubMed Web of Science ®Google Scholar
• Andersen R, Thyssen J, Maibach H Qualitative vs. quantitative atopic dermatitis criteria – in historical and present perspectives. J Eur Acad Dermatol Venereol. 2016;30(4):p. 604–618.
   Google Scholar
• Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol. 1980 Nov 11;60:44–47. doi: 10.2340/00015555924447
   Google Scholar
• Hanifin JM, Baghoomian W, Grinich E, et al. The eczema area and severity index—a practical guide. Dermatitis. 2022;33(3):187–192. doi: 10.1097/DER.0000000000000895
   PubMed Web of Science ®Google Scholar
• Description and appraisal of outcome measures. In: clinical review report: Dupilumab (Dupixent): (Sanofi Genzyme, a division of sanofi-aventis Canada Inc): indication: indicated for the treatment of patients aged 12 years and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable [internet]. Canadian Agency for Drugs and Technologies in Health; 2020 [cited 2024 Feb 10]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK565237/
   Google Scholar
• Simpson EL, Bissonnette R, Paller AS, et al. The validated Investigator global assessment for atopic dermatitis (vIGA‐ADTM): a clinical outcome measure for the severity of atopic dermatitis. Br J Dermatol. 2022; Oct187:(4):531–538.
   PubMed Web of Science ®Google Scholar
• Naik PP. Treatment-resistant atopic dermatitis: novel therapeutics, digital tools, and precision medicine. Asia Pac Allergy. 2022 Apr 28;12(2):e20. doi: 10.5415/apallergy.2022.12.e20
   PubMed Web of Science ®Google Scholar
• Spada F, Barnes TM, Greive KA. Emollient formulations containing antiseptics reduce effectively the level of staphylococcus aureus on skin. Clin Cosmet Investig Dermatol. 2019 Sep 4;12:639–645. doi: 10.2147/CCID.S215023
   PubMed Web of Science ®Google Scholar
• Coondoo A, Sengupta S. Topical corticophobia among parents and caregivers of atopic children. Indian J Paediatr Dermatol. 2016 Dec;17(4):255. doi: 10.4103/2319-7250.188422
   Google Scholar
• Kapur S, Watson W, Carr S. Atopic dermatitis. Allergy Asthma Clin Immunol. 2018 Sep 12;14(Suppl 2):52.
   PubMedGoogle Scholar
• Arellano FM, Wentworth CE, Arana A, et al. Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis. J Invest Dermatol. 2007; Apr127:(4):808–816.
   PubMed Web of Science ®Google Scholar
• Hoy SM. Ruxolitinib cream 1.5%: a review in mild to moderate atopic dermatitis. Am J Clin Dermatol. 2023;24(1):143–151. doi: 10.1007/s40257-022-00748-2
   PubMed Web of Science ®Google Scholar
• Davis DM, Borok J, Udkoff J, et al. Atopic dermatitis: phototherapy and systemic therapy. Semin Cutan Med Surg. 2017; Sep36:(3):118–123.
   PubMed Web of Science ®Google Scholar
• Gao Q, Zhao Y, Zhang J. Efficacy and safety of abrocitinib and upadacitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: a systematic review and meta-analysis. Heliyon. 2023 Jun 2;9(6):e16704.v
   PubMed Web of Science ®Google Scholar
• Li H, Zuo J, Tang W. Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases. Front Pharmacol. 2018 Oct 17;9:1048. doi: 10.3389/fphar.2018.01048
   PubMed Web of Science ®Google Scholar
• Fernández-Gallego N, Sánchez-Madrid F, Cibrian D. Role of AHR ligands in skin homeostasis and cutaneous inflammation. Cells. 2021 Nov 15;10(11):3176. doi: 10.3390/cells10113176
   PubMed Web of Science ®Google Scholar
• Lé AM, Torres T. OX40-OX40L inhibition for the treatment of atopic dermatitis—focus on Rocatinlimab and Amlitelimab. Pharmaceutics. 2022 Dec 8;14(12):2753. doi: 10.3390/pharmaceutics14122753
   PubMed Web of Science ®Google Scholar
• Elsner JSH, Carlsson M, Stougaard JK, et al. The OX40 Axis is associated with both systemic and local involvement in atopic dermatitis. Acta Derm Venereol. 2020 Mar 31;100(6):1–5. doi: 10.2340/00015555-3452
   Google Scholar
• He R, Geha RS. Thymic stromal lymphopoietin. Ann N Y Acad Sci. 2010 Jan;1183(1):13–24. doi: 10.1111/j.1749-6632.2009.05128.x
   PubMedGoogle Scholar
• DS Biopharma. Efficacy and safety of orally administered DS107 in adult patients with moderate to severe atopic dermatitis. Clinicaltrial.gov [cited 2023 Dec 31]. Report No.: NCT03817190.
   Google Scholar
• Rapp M, Wintergerst MWM, Kunz WG, et al. CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes. J Exp Med. 2019 Mar 25;216(5):1170–1181. doi: 10.1084/jem.20170277
   PubMed Web of Science ®Google Scholar
• Tiper IV, East JE, Subrahmanyam PB, et al. Sphingosine 1-phosphate signaling impacts lymphocyte migration, inflammation and infection. Pathog Dis. 2016 Aug 1;74(6):ftw063. doi: 10.1093/femspd/ftw063
   PubMed Web of Science ®Google Scholar
• Bodmer M, Itano A, McInnes I. Harnessing the small intestinal axis to resolve systemic inflammation. Front Immunol. 2022 Nov 15;13:1060607. doi: 10.3389/fimmu.2022.1060607
   PubMed Web of Science ®Google Scholar
• Ogonowska P, Gilaberte Y, Barańska-Rybak W, et al. Colonization With Staphylococcus aureus in Atopic Dermatitis Patients: Attempts to Reveal the Unknown. Front Microbiol. 2021 Jan 11;11:567090. PMID: 33505363; PMCID: PMC7830525. 10.3389/fmicb.2020.567090.
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Lio PA, Simpson EL, et al. Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: a randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial. EClin Med. 2023 May 16;60:102002. doi:10.1016/j.eclinm.2023.102002.
   PubMedGoogle Scholar
• Bissonnette R, Papp KA, Poulin Y, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016 Nov;175(5):902–911. doi: 10.1111/bjd.14871
   PubMed Web of Science ®Google Scholar
• Aclaris Therapeutics, Inc. A Phase 2a, Multicenter, Randomized, Double-blind, Vehicle-controlled, Parallel-group Study to Determine the Safety, Tolerability, Pharmacokinetics and Efficacy of ATI-1777 in Adult Patients With Moderate or Severe Atopic Dermatitis [Internet]. clinicaltrials.gov; 2023 Sep [cited 2023 Dec 31]. Report No.: NCT04598269. Available from: https://clinicaltrials.gov/study/NCT04598269
   Google Scholar
• Changelian P, Xu C, Mnich S, et al. ATI-1777 a topical JAK1/3 inhibitor may benefit atopic dermatitis without systemic drug exposure, results from preclinical development and Phase 2a randomized-control study ATI-1777-AD-201. JID Innov [Internet]. 2024 Mar 1. doi: 10.1016/j.xjidi.2023.100251
   Google Scholar
• Galderma R&D. Safety and Efficacy of CD5024 0.3% Cream in Subjects With Atopic Dermatitis [Internet]. clinicaltrials.gov; 2022 Jun [cited 2023 Dec 31]. Report No.: NCT03250624. Available from: https://clinicaltrials.gov/study/NCT03250624
   Google Scholar
• Pfizer. clinicaltrials.gov; 2022 Aug [cited 2023 Dec 31]. Report No.: NCT04664153. Available from: https://clinicaltrials.gov/study/NCT04664153
   Google Scholar
• Eichenfield LF, Tarabar S, Forman S, et al. Efficacy and Safety of PF-07038124 in Patients With Atopic Dermatitis and Plaque Psoriasis: A Randomized Clinical Trial. JAMA Dermatol. 2024 Dec 20;160(2):e234990. doi: 10.1001/jamadermatol.2023.4990
   Web of Science ®Google Scholar
• Bissonnette R, DuBois J, Facheris P, et al. Clinical and molecular effects of oral CCR4 antagonist RPT193 in atopic dermatitis: A Phase 1 study. Allergy. 2024 Nov 20;79(4):924–936. doi: 10.1111/all.15949
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Pavel A, Facheris P, et al. 822 RPT193, a CCR4 inhibitor, improves the inflammatory skin transcriptomic profile in patients with atopic dermatitis. J Invest Dermatol. 2022 Aug 1;142(8):S143. doi: 10.1016/j.jid.2022.05.836
   Web of Science ®Google Scholar
• Zhang L, Ding Y, Wang Q, et al. Preclinical immunological characterization of rademikibart (CBP-201), a next-generation human monoclonal antibody targeting IL-4Rα, for the treatment of Th2 inflammatory diseases. Sci Rep. 2023 Jul 31;13(1):12411. doi: 10.1038/s41598-023-39311-2
   PubMed Web of Science ®Google Scholar
• Wang J, White J, Sansone KJ, et al. Rademikibart (CBP-201), a next-generation monoclonal antibody targeting human IL-4Rα: two phase I randomized trials, in healthy individuals and patients with atopic dermatitis. Clin Transl Sci. 2023;16(12):2614–2627. doi: 10.1111/cts.13656
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Strober B, Feinstein B, et al. Efficacy and safety of rademikibart (CBP-201), a next-generation monoclonal antibody targeting IL-4Rα, in adults with moderate-to-severe atopic dermatitis: a phase 2 randomized trial (CBP-201-WW001). J Allergy Clin Immunol. 2023 Dec 27. S0091-6749(23)02546-0. doi: 10.1016/j.jaci.2023.11.924
   Google Scholar
• Simpson EL, Imafuku S, Poulin Y, et al. A Phase 2 Randomized Trial of Apremilast in Patients with Atopic Dermatitis. J Invest Dermatol. 2019; May139:(5):1063–1072.
   PubMed Web of Science ®Google Scholar
• LEO Pharma. A Phase 2a, Randomized, Double-blind, Placebo-controlled, Multi-site, Proof of Concept Trial to Evaluate the Efficacy and Safety of LEO 138559 in Adult Subjects With Moderate to Severe Atopic Dermatitis (AD). [Internet]. clinicaltrials.gov; 2023 Jul [cited 2023 Dec 31]. Report No.: NCT04922021. Available from: https://clinicaltrials.gov/study/NCT04922021
   Google Scholar
• LEO. Pharma Presents Late-Breaking Positive Phase 2a Efficacy and Safety Results of LEO 138559 in Moderate-to-Severe Atopic Dermatitis at the 2023 AAD Annual Meeting [Internet]. 2023 [cited 2024 Feb 11]. Available from: https://www.businesswire.com/news/home/20230318005014/en/LEO-Pharma-Presents-Late-Breaking-Positive-Phase-2a-Efficacy-and-Safety-Results-of-LEO-138559-in-Moderate-to-Severe-Atopic-Dermatitis-at-the-2023-AAD-Annual-Meeting
   Google Scholar
• Zhao Y, Zhang L, Ding Y, et al. Efficacy and Safety of SHR0302, a Highly Selective Janus Kinase 1 Inhibitor, in Patients with Moderate to Severe Atopic Dermatitis: A Phase II Randomized Clinical Trial. Am J Clin Dermatol. 2021; Nov22:(6):877–889.
   PubMed Web of Science ®Google Scholar
• Rewerska B, Sher LD, Alpizar S, et al. Phase 2b randomized trial of OX40 inhibitor telazorlimab for moderate-to-severe atopic dermatitis. J Allergy Clin Immunol Glob. 2023 Nov 22;3(1):100195. doi: 10.1016/j.jacig.2023.100195
   PubMedGoogle Scholar
• Tyring SK, Rich P, Tada Y, et al. Risankizumab in Patients with Moderate-to-Severe Atopic Dermatitis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study. Dermatol Ther (Heidelb). 2023 Feb;13(2):595–608. doi: 10.1007/s13555-022-00876-x
   PubMed Web of Science ®Google Scholar
• AbbVie. A Phase 2, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Risankizumab in Adult and Adolescent Subjects With Moderate to Severe Atopic Dermatitis [Internet]. clinicaltrials.gov; 2021 Oct [cited 2023 Dec 31]. Report No.: NCT03706040. Available from: https://clinicaltrials.gov/study/NCT03706040
   Google Scholar
• Botanix Pharmaceuticals. A Randomized, Double-Blind, Vehicle-Controlled Study of the Safety, Tolerability and Efficacy of BTX 1204 in Patients With Moderate Atopic Dermatitis [Internet]. clinicaltrials.gov; 2022 Sep [cited 2023 Dec 31]. Report No.: NCT03824405. Available from: https://clinicaltrials.gov/study/NCT03824405
   Google Scholar
• Evelo Biosciences Inc. A Long-Term Extension Trial in Participants With Atopic Dermatitis Who Participated in Previous EDP1815 Trials. [Internet]. clinicaltrials.gov; 2023 Sep [cited 2023 Dec 31]. Report No.: NCT05439941.
   Google Scholar
• Efficacy and Safety of MEDI3506 in Adult Subjects with Atopic Dermatitis [Internet]. [cited 2024 Feb 11]. Available from: https://www.astrazenecaclinicaltrials.com/study/D9182C00001/
   Google Scholar
• AstraZeneca. A phase 2 multinational, randomized, double-blind, parallel-group, 16-week placebo-controlled study with a 36-week extension to investigate the use of benralizumab for patients with moderate to severe atopic dermatitis despite treatment with topical medications (the HILLIER study) [internet]. clinicaltrials.gov; 2023 Aug [cited 2023 Dec 31]. Report No.: NCT04605094. Available from: https://clinicaltrials.gov/study/NCT04605094
   Google Scholar
• Silverberg JI, Bissonnette R, Kircik L, et al. Efficacy and safety of etrasimod, a sphingosine 1-phosphate receptor modulator, in adults with moderate-to-severe atopic dermatitis (ADVISE). J Eur Acad Dermatol Venereol. 2023;37(7):1366–1374. doi: 10.1111/jdv.18914
   PubMed Web of Science ®Google Scholar
• Simpson EL, Parnes JR, She D, et al. Tezepelumab, an anti–thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: a randomized phase 2a clinical trial. J Am Acad Dermatol. 2019 Apr;80:(4):1013–1021.
   PubMed Web of Science ®Google Scholar
• Bissonnette R, Abramovits W, Saint-Cyr Proulx É, et al. Spesolimab, an anti-interleukin-36 receptor antibody, in patients with moderate-to-severe atopic dermatitis: Results from a multicentre, randomized, double-blind, placebo-controlled, phase IIa study. J Eur Acad Dermatol Venereol. 2023 Mar;37(3):549–557. doi: 10.1111/jdv.18727
   PubMed Web of Science ®Google Scholar
• Boehringer Ingelheim. An Open Label Extension Study to Assess the Long Term Safety of Treatment With BI 655130 Administered Subcutaneously in Adult Patients With Moderate to Severe Atopic Dermatitis [Internet]. clinicaltrials.gov; 2022 Jun [cited 2023 Dec 31]. Report No.: NCT04086121. Available from: https://clinicaltrials.gov/study/NCT04086121
   Google Scholar
• Pavel AB, Song T, Kim HJ, et al. Oral Janus kinase/SYK inhibition (ASN002) suppresses inflammation and improves epidermal barrier markers in patients with atopic dermatitis. J Allergy Clin Immunol. 2019 Oct 1;144(4):1011–1024. doi: 10.1016/j.jaci.2019.07.013
   PubMed Web of Science ®Google Scholar
• Bissonnette R, Maari C, Forman S, et al. The oral Janus kinase/spleen tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate-to-severe atopic dermatitis: results from a randomized double-blind placebo-controlled study. Br J Dermatol. 2019 Oct;181(4):733–742. doi: 10.1111/bjd.17932
   PubMed Web of Science ®Google Scholar
• Maurer M, Cheung DS, Theess W, et al. Phase 2 randomized clinical trial of astegolimab in patients with moderate to severe atopic dermatitis. J Allergy Clin Immunol. 2022; Dec150:(6):1517–1524.
   PubMed Web of Science ®Google Scholar
• Chen YL, Gutowska-Owsiak D, Hardman CS, et al. Proof-of-concept clinical trial of etokimab shows a key role for IL-33 in atopic dermatitis pathogenesis. Sci Transl Med. 2019 Oct 23;11(515):eaax2945. doi: 10.1126/scitranslmed.aax2945
   PubMed Web of Science ®Google Scholar
• AnaptysBio, Inc. A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study Investigating the Efficacy, Safety, and Pharmacokinetic Profile of ANB020 Administered to Adult Subjects With Moderate-to-Severe Atopic Dermatitis [Internet]. clinicaltrials.gov; 2023 Apr [cited 2023 Dec 31]. Report No.: NCT03533751. Available from: https://clinicaltrials.gov/study/NCT03533751
   Google Scholar
• DS Biopharma. A Randomised, Double-blind, Placebo-controlled, Phase 2b Study to Assess the Efficacy and Safety of Orally Administered DS107 in Patients With Moderate to Severe Atopic Dermatitis [Internet]. clinicaltrials.gov; 2022 Sep [cited 2023 Dec 31]. Report No.: NCT02864498. Available from: https://clinicaltrials.gov/study/NCT02864498
   Google Scholar
• Nogueira S, Rodrigues MA, Vender R, et al. Tapinarof for the treatment of psoriasis. Dermatol Ther. 2022; Dec35:(12):e15931.
   PubMed Web of Science ®Google Scholar
• Smith SH, Jayawickreme C, Rickard DJ, et al. Tapinarof is a natural AhR agonist that resolves skin inflammation in mice and humans. J Invest Dermatol. 2017 Oct 1;137(10):2110–2119. doi: 10.1016/j.jid.2017.05.004
   PubMed Web of Science ®Google Scholar
• Negishi T, Kato Y, Ooneda O, et al. Effects of aryl hydrocarbon receptor signaling on the modulation of TH1/TH2 balance. J Immunol Baltim Md 1950. 2005 Dec 1;175(11):7348–7356. doi: 10.4049/jimmunol.175.11.7348
   Google Scholar
• Peppers J, Paller AS, Maeda-Chubachi T, et al. A phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of atopic dermatitis. J Am Acad Dermatol. 2019; Jan80:(1):89–98.e3.
   PubMed Web of Science ®Google Scholar
• Paller AS, Stein Gold L, Soung J, et al. Efficacy and patient-reported outcomes from a phase 2b, randomized clinical trial of tapinarof cream for the treatment of adolescents and adults with atopic dermatitis. J Am Acad Dermatol. 2021; Mar84:(3):632–638.
   PubMed Web of Science ®Google Scholar
• Simpson EL, Silverberg JI, Bissonnette R, et al. Rapid and early onset of itch relief with topical tapinarof cream 1% once daily in two pivotal phase 3 trials in adults and children down to two years of age with moderate to severe atopic dermatitis. J Skin. 2023 Oct 11-14;7(6):s281. doi: 10.25251/skin.7.supp.281
   Google Scholar
• Gold LS, Rubenstein DS, Peist K, et al. Tapinarof cream 1% once daily and benvitimod 1% twice daily are 2 distinct topical medications. J Am Acad Dermatol. 2021 Sep 1;85(3):e201–2. doi: 10.1016/j.jaad.2021.04.103
   PubMed Web of Science ®Google Scholar
• Cai L, Zhao Y, Zheng M, et al. A multi-center, double-blind, randomized, placebo- and positive-controlled phase II clinical study of benvitimod for the treatment of atopic dermatitis. Chin Med J (Engl). 2023 Jan 20;136(2):251–252. doi: 10.1097/CM9.0000000000002489
   PubMed Web of Science ®Google Scholar
• Jianzhong Z. A randomized, double-blind, multicenter, placebo-controlled phase III clinical study to evaluate the efficacy and safety of benvitimod cream in the treatment of mild to moderate atopic dermatitis [internet]. clinicaltrials.gov; 2022 Apr [cited 2023 Dec 31]. Report No.: NCT05326672. Available from: https://clinicaltrials.gov/study/NCT05326672
   Google Scholar
• Saeki H, Baba N, Ito K, et al. Difamilast, a selective phosphodiesterase 4 inhibitor, ointment in paediatric patients with atopic dermatitis: a phase III randomized double‐blind, vehicle‐controlled trial. Br J Dermatol. 2022; Jan186:(1):40–49.
   PubMed Web of Science ®Google Scholar
• Saeki H, Ito K, Yokota D, et al. Difamilast ointment in adult patients with atopic dermatitis: a phase 3 randomized, double-blind, vehicle-controlled trial. J Am Acad Dermatol. 2022; Mar86:(3):607–614.
   PubMed Web of Science ®Google Scholar
• Park CW, Kim BJ, Lee YW, et al. Asivatrep, a TRPV1 antagonist, for the topical treatment of atopic dermatitis: Phase 3, randomized, vehicle-controlled study (CAPTAIN-AD). J Allergy Clin Immunol. 2022 Apr 1;149(4):1340–1347.e4. doi: 10.1016/j.jaci.2021.09.024
   PubMed Web of Science ®Google Scholar
• Yadav M, Chaudhary PP, D’Souza BN, et al. Diisocyanates influence models of atopic dermatitis through direct activation of TRPA1. PLOS ONE. 2023;18(3):e0282569. doi: 10.1371/journal.pone.0282569
   PubMed Web of Science ®Google Scholar
• Jacobson ME, Myles IA, Paller AS, et al. A randomized, double-blind, placebo-controlled, multicenter, 16-week trial to evaluate the efficacy and safety of FB-401 in children, adolescents, and adult subjects (ages 2 years and older) with mild-to-moderate atopic dermatitis. Dermatology. 2024 Aug 14;240(1):85–94. doi: 10.1159/000532054
   PubMed Web of Science ®Google Scholar
• National Institute of Allergy and Infectious Diseases (NIAID). A phase 3, double-blind, randomized, placebo-controlled trial of cardamom and topical roseomonas in atopic dermatitis [internet]. clinicaltrials.gov; 2024 Feb [cited 2023 Dec 31]. Report No.: NCT06096857. Available from: https://clinicaltrials.gov/study/NCT06096857
   Google Scholar
• Simpson E, Eichenfield L, Gooderham M, et al. Efficacy and safety of roflumilast cream 0.15% in adults and children aged 6 years with mild to moderate atopic dermatitis in two phase 3 trials (INTEGUMENT-1 and INTEGUMENT-2). Br J Dermatol. 2023;188(supp):390. doi: 10.1093/bjd/ljad162.016
   PubMedGoogle Scholar
• Arcutis Biotherapeutics, Inc. Trial of PDE4 Inhibition With Roflumilast for the Management of Atopic Dermatitis (Integument-PED). [Internet]. clinicaltrials.gov; 2023 Jul [cited 2023 Dec 31]. Report No.: NCT04845620.
   Google Scholar
• Fitch J Arcutis submits roflumilast 0.15% sNDA for AD in children 6 years and up. Contemporary Pediatrics. 2023 Sep 21. Available from: https://www.contemporarypediatrics.com/view/arcutis-submits-roflumilast-0-15-snda-for-ad-in-children-6-years-and-up
   Google Scholar
• van der BJ. Arcutis Announces Positive Results from INTEGUMENT-PED Pivotal Phase 3 Trial of Roflumilast Cream 0.05% for the Treatment of Atopic Dermatitis in Children Ages 2 to 5 [Internet]. Arcutis Biotherapeutics. 2023 [cited 2024 Feb 12]. Available from: https://www.arcutis.com/arcutis-announces-positive-results-from-integument-ped-pivotal-phase-3-trial-of-roflumilast-cream-0-05-for-the-treatment-of-atopic-dermatitis-in-children-ages-2-to-5
   Google Scholar
• Eli Lilly and Company. Evaluation of the Efficacy and Safety of Lebrikizumab (LY3650150) in Moderate to Severe Atopic Dermatitis (ADvocate1). [Internet]. clinicaltrials.gov; 2023 Jul [cited 2023 Dec 31]. Report No.: NCT04146363.
   Google Scholar
• Labib A, Ju T, Yosipovitch G. Managing Atopic Dermatitis with Lebrikizumab – the Evidence to Date. Clin Cosmet Investig Dermatol. 2022 Jun 8;15:1065–1072. doi: 10.2147/CCID.S295672
   PubMed Web of Science ®Google Scholar
• Simpson EL, Flohr C, Eichenfield LF, et al. Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE). J Am Acad Dermatol. 2018; May78:(5):863–871.e11.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Blauvelt A, Eichenfield LF, et al. Efficacy and safety of lebrikizumab, a high-affinity interleukin 13 inhibitor, in adults with moderate to severe atopic dermatitis: a phase 2b randomized clinical trial. JAMA Dermatol. 2020 Apr 1;156(4):411–420. doi: 10.1001/jamadermatol.2020.0079
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Guttman-Yassky E, Thaçi D, et al. Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis. N Engl J Med. 2023 Mar 23;388(12):1080–1091. doi: 10.1056/NEJMoa2206714
   PubMed Web of Science ®Google Scholar
• Borgia F, Custurone P, Li Pomi F, et al. IL-31: State of the Art for an Inflammation-Oriented Interleukin. Int J Mol Sci. 2022 Jun 10;23(12):6507. doi: 10.3390/ijms23126507
   PubMed Web of Science ®Google Scholar
• Saleem MD, Oussedik E, D’Amber V, et al. Interleukin-31 pathway and its role in atopic dermatitis: a systematic review. J Dermatol Treat. 2017 Oct 3;28(7):591–599. doi: 10.1080/09546634.2017.1290205
   PubMed Web of Science ®Google Scholar
• Nemoto O, Furue M, Nakagawa H, et al. The first trial of CIM331, a humanized antihuman interleukin‐31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double‐blind, placebo‐controlled study. Br J Dermatol. 2016 Feb 1;174(2):296–304. doi: 10.1111/bjd.14207
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Pinter A, Pulka G, et al. Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus. J Allergy Clin Immunol. 2020; Jan145:(1):173–182.
   PubMed Web of Science ®Google Scholar
• Kabashima K, Matsumura T, Komazaki H, et al. Trial of Nemolizumab and Topical Agents for Atopic Dermatitis with Pruritus. N Engl J Med. 2020 Jul 9;383(2):141–150. doi: 10.1056/NEJMoa1917006
   PubMed Web of Science ®Google Scholar
• Nemolizumab JP01 andJP02 Study Group, Kabashima K, Matsumura T, et al. Nemolizumab plus topical agents in patients with atopic dermatitis (AD) and moderate-to-severe pruritus provide improvement in pruritus and signs of AD for up to 68 weeks: results from two phase III, long-term studies. Br J Dermatol. 2022 Apr;186(4):642–651. doi: 10.1111/bjd.20873
   PubMed Web of Science ®Google Scholar
• Redmond WL, Weinberg AD. Targeting OX40 and OX40L for the treatment of autoimmunity and cancer. Crit Rev Immunol. 2007;27(5):415–436. doi: 10.1615/CritRevImmunol.v27.i5.20
   PubMed Web of Science ®Google Scholar
• Hudak S, Hagen M, Liu Y, et al. Immune Surveillance and Effector Functions of CCR10+ Skin Homing T Cells. J Immunol. 2002 Aug 1;169(3):1189–1196. doi: 10.4049/jimmunol.169.3.1189
   PubMed Web of Science ®Google Scholar
• Weidinger S, Bieber T, Cork M. 34312 Treatment with amlitelimab (KY1005, SAR445229): A novel nondepleting anti-OX40Ligand (OX40L) mAb reduces IL-13 serum levels in a phase 2a randomized placebo-controlled trial in patients with moderate to severe atopic dermatitis. J Am Acad Dermatol. 2022 Sep 1;87(3):AB123.
   Web of Science ®Google Scholar
• Nakagawa H, Iizuka H, Nemoto O, et al. Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal antibody, in Japanese patients with moderate to severe atopic dermatitis. J Dermatol Sci. 2020 Aug 1;99(2):82–89. doi: 10.1016/j.jdermsci.2020.06.005
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Simpson EL, Reich K, et al. Summary of Research: An Anti-OX40 Antibody to Treat Moderate-to-Severe Atopic Dermatitis: A Multicentre, Double-Blind, Placebo-Controlled Phase 2b Study. Adv Ther. 2024 Jan 8;41(3):928–931. Epub ahead of print. doi:10.1007/s12325-023-02755-z.
   PubMedGoogle Scholar
• Zhao Y, Zhang J, Yang B, et al. Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial. Chin Med J (Engl). 2024 Jan 20;137(2):200–208. doi: 10.1097/CM9.0000000000002747
   PubMed Web of Science ®Google Scholar
• Biosciences Co K, Ltd. A study of CM310 in patients with moderate-to-severe atopic dsermatitis. Clinicaltrial.gov. [cited 2023 Dec 31]. Report No.: NCT05265923.
   Google Scholar
• Welsh SE, Xiao C, Kaden AR, et al. Neurokinin‐1 receptor antagonist tradipitant has mixed effects on itch in atopic dermatitis: results from EPIONE, a randomized clinical trial. J Eur Acad Dermatol Venereol. 2021; May35:(5):e338–40.
   PubMed Web of Science ®Google Scholar
• Viscusi ER, Torjman MC, Munera CL, et al. Effect of difelikefalin, a selective kappa opioid receptor agonist, on respiratory depression: A randomized, double‐blind, placebo‐controlled trial. Clin Transl Sci. 2021; Sep14:(5):1886–1893.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Facheris P, Rosa JCD, et al. Oral difelikefalin reduces moderate to severe pruritus and expression of pruritic and inflammatory biomarkers in subjects with atopic dermatitis. J Allergy Clin Immunol. 2023 Oct 1;152(4):916–926. doi: 10.1016/j.jaci.2023.06.023
   PubMed Web of Science ®Google Scholar
• Chen ML, Nopsopon T, Akenroye A. Incidence of Anti-Drug Antibodies to Monoclonal Antibodies in Asthma: A Systematic Review and Meta-Analysis. J Allergy Clin Immunol Pract. 2023 May;11(5):1475–1484.e20. doi: 10.1016/j.jaip.2022.12.046
   PubMed Web of Science ®Google Scholar