Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies

Papp, Kim; Szepietowski, Jacek C.; Kircik, Leon; Toth, Darryl; Eichenfield, Lawrence F.; Leung, Donald Y.M.; Forman, Seth; Venturanza, May E.; Sun, Kang; Kuligowski, Michael E.; Simpson, Eric L.

doi:10.1016/j.jaad.2021.04.085

Cited by 165 publications

(212 citation statements)

References 29 publications

(32 reference statements)

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“…In both phase II and III studies, baseline demographics and characteristics were similar across treatment groups; for further details of patient characteristics, see [ 43 , 46 ].…”

Section: Resultsmentioning

confidence: 99%

“…Efficacy and safety of treatment with ruxolitinib cream in adolescent and adult patients with atopic dermatitis with cream strengths up to 1.5% BID were reported in separate publications for the phase II trial [ 43 , 44 ] and the two phase III studies [ 46 , 50 ]. The plasma PK profiles after topical ruxolitinib treatment from the phase II and 3 studies are reported here.…”

Section: Discussionmentioning

confidence: 99%

“…The two identically designed vehicle-controlled, double-blind, 8-week, phase III studies (ClinicalTrials.gov identifiers: NCT03745638 [TRuE AD1]; NCT03745651 [TRuE AD2]) were conducted in adolescent and adult patients with atopic dermatitis [ 46 ]. Patients were stratified based on their Investigator’s Global Assessment (IGA) score (2 or 3) and region (North America or Europe), and randomized (2:2:1) to topical treatment with ruxolitinib 0.75% BID, ruxolitinib 1.5% BID, or vehicle cream.…”

Section: Methodsmentioning

confidence: 99%

“…Ruxolitinib is a selective inhibitor of JAK1 and JAK2 that is approved as an oral formulation for the treatment of patients with myeloproliferative neoplasms, including myelofibrosis, polycythemia vera, and steroid-refractory acute graft-versus-host disease [ 45 ]. A topical cream formulation of ruxolitinib phosphate (ruxolitinib cream) was evaluated for the treatment of patients with atopic dermatitis in a phase II, dose-ranging study [ 43 , 44 ], and was investigated in two controlled, randomized, identically designed, phase III studies followed by a 44-week follow-up period [ 46 ].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of Ruxolitinib in Patients with Atopic Dermatitis Treated With Ruxolitinib Cream: Data from Phase II and III Studies

et al. 2021

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Background Pathogenesis of atopic dermatitis (AD) involves the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. A cream formulation of ruxolitinib, a potent selective JAK1/JAK2 inhibitor, was developed for topical delivery. Method Pharmacokinetic data were obtained from three double-blind, vehicle-controlled studies in patients with AD: a phase II study with ruxolitinib cream 0.15%, 0.5%, or 1.5% once daily or 1.5% twice daily (BID), and two phase III studies with 0.75% or 1.5% BID. Effects of baseline characteristics on pharmacokinetics were examined. Correlations were attempted between plasma concentrations and change in hematological parameters over time. Results Ruxolitinib plasma concentrations at steady-state (C ss ) increased with cream strength in a less-than-dose-proportional manner. In the phase III studies, overall mean (standard deviation [SD]) C ss after ruxolitinib cream 0.75% and 1.5% BID (23.8 [35.0] and 35.7 [55.0] nM) were a fraction of the half-maximal inhibitory concentration for thrombopoietin-stimulated phosphorylated STAT3 inhibition (281 nM), a JAK/STAT signaling marker. Three covariates were identified for C ss : dose, percent body surface area (%BSA) treated, and baseline Investigator's Global Assessment score. Mean (SD) bioavailability of ruxolitinib cream 1.5% BID was 6.22% (7.66%). There were no correlations between C ss and any hematological changes except for a transient increase in platelets at week 2. Conclusions Plasma ruxolitinib concentrations after treatment with topical ruxolitinib cream in patients with up to 20% BSA affected by AD are not expected to lead to systemic plasma concentrations that may be associated with adverse effects commonly associated with oral JAK inhibitors. ClinicalTrials.gov NCT03011892; NCT03745638; NCT03745651.

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“…In both phase II and III studies, baseline demographics and characteristics were similar across treatment groups; for further details of patient characteristics, see [ 43 , 46 ].…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of Ruxolitinib in Patients with Atopic Dermatitis Treated With Ruxolitinib Cream: Data from Phase II and III Studies

et al. 2021

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“…Ruxolitinib is a selective JAK1 and JAK2 inhibitor. Topical Ruxolitinib Evaluation in Atopic Dermatitis studies (TRuE-AD) demonstrated the safety and efficacy from clinical trials ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

Drug Repurposing for Atopic Dermatitis by Integration of Gene Networking and Genomic Information

et al. 2021

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Atopic Dermatitis (AD) is a chronic and relapsing skin disease. The medications for treating AD are still limited, most of them are topical corticosteroid creams or antibiotics. The current study attempted to discover potential AD treatments by integrating a gene network and genomic analytic approaches. Herein, the Single Nucleotide Polymorphism (SNPs) associated with AD were extracted from the GWAS catalog. We identified 70 AD-associated loci, and then 94 AD risk genes were found by extending to proximal SNPs based on r2 > 0.8 in Asian populations using HaploReg v4.1. Next, we prioritized the AD risk genes using in silico pipelines of bioinformatic analysis based on six functional annotations to identify biological AD risk genes. Finally, we expanded them according to the molecular interactions using the STRING database to find the drug target genes. Our analysis showed 27 biological AD risk genes, and they were mapped to 76 drug target genes. According to DrugBank and Therapeutic Target Database, 25 drug target genes overlapping with 53 drugs were identified. Importantly, dupilumab, which is approved for AD, was successfully identified in this bioinformatic analysis. Furthermore, ten drugs were found to be potentially useful for AD with clinical or preclinical evidence. In particular, we identified filgotinub and fedratinib, targeting gene JAK1, as potential drugs for AD. Furthermore, four monoclonal antibody drugs (lebrikizumab, tralokinumab, tocilizumab, and canakinumab) were successfully identified as promising for AD repurposing. In sum, the results showed the feasibility of gene networking and genomic information as a potential drug discovery resource.

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Topical Therapies for Atopic Dermatitis

Xu,

Alexander

2023

JAMA

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Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies

Abstract: Background: Ruxolitinib (RUX) cream demonstrated potent anti-inflammatory and antipruritic efficacy in a phase 2 study in adults with atopic dermatitis (AD).

Cited by 165 publications

References 29 publications

Pharmacokinetics of Ruxolitinib in Patients with Atopic Dermatitis Treated With Ruxolitinib Cream: Data from Phase II and III Studies

Pharmacokinetics of Ruxolitinib in Patients with Atopic Dermatitis Treated With Ruxolitinib Cream: Data from Phase II and III Studies

Drug Repurposing for Atopic Dermatitis by Integration of Gene Networking and Genomic Information

Topical Therapies for Atopic Dermatitis

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