Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial

Blauvelt, Andrew; Silverberg, Jonathan I.; Lynde, Charles; Bieber, Thomas; Eisman, Samantha; Zdybski, Jacek; Gubelin, Walter; Simpson, Eric L.; Valenzuela, Fernando; Criado, Paulo Ricardo; Lebwohl, Mark; Feeney, Claire; Khan, Tahira; Biswas, Pinaki; DiBonaventura, Marco; Valdez, Hernán; Cameron, Michael C.; Rojo, Ricardo

doi:10.1016/j.jaad.2021.05.075

Cited by 91 publications

(102 citation statements)

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“…Maintenance of abrocitinib monotherapy-induced responses was evaluated in adults and adolescents aged ≥ 12 years with moderate-to-severe AD in a responder-enriched, phase 3, withdrawal study (NCT03627767; JADE REGIMEN) [ 17 ]. Eligibility criteria included an inadequate response to ≥ 4 consecutive weeks of medicated topical therapy or required systemic treatments for AD control.…”

Section: Scientific Summarymentioning

confidence: 99%

“…Oral antihistamines and topical non-medicated emollients were allowed throughout the study. In total, 798 of 1233 patients achieved a protocol-defined response after receiving 12 weeks of abrocitinib 200 mg/day in phase 1 and entered into the maintenance phase [ 17 ].…”

Section: Scientific Summarymentioning

confidence: 99%

“…During the maintenance phase, the proportion of patients who had a protocol-defined flare was numerically lower with abrocitinib 200 mg/day (44 of 266; 16.5%) and 100 mg/day (105 of 265; 39.6%) than with placebo (207 of 267; 77.5%) [ 17 ]. A significant ( p < 0.0001) reduction in flare risk was evident with abrocitinib 200 mg/day (hazard ratio [HR] 0.10; 95% CI 0.07–0.14) and 100 mg/day (HR 0.27; 95% CI 0.21–0.34) versus placebo, and with abrocitinib 200 versus 100 mg/day (HR 0.36; 95% CI 0.26–0.52).…”

Section: Scientific Summarymentioning

confidence: 99%

“…A total of 351 patients entered the rescue phase after receiving abrocitinib 200 mg/day ( n = 43), abrocitinib 100 mg/day ( n = 104) or placebo ( n = 204) in the maintenance phase. After 12 weeks of rescue treatment with abrocitinib 200 mg/day plus topical corticosteroids in these respective groups, 55.0%, 74.5% and 91.8% of patients recaptured an EASI-75 response, 36.6%, 58.8% and 81.6% recaptured an IGA response and 30.0%, 35.3% and 73.2% recaptured a PP-NRS4 response [ 17 ]. Findings in adolescent patients (aged < 18 years) were consistent with those in the overall trial population [ 3 – 5 ].…”

Section: Scientific Summarymentioning

confidence: 99%

“…The longer-term efficacy of abrocitinib, used with or without medicated topical therapy, as a treatment for moderate-to-severe AD was demonstrated in the ongoing extension study, JADE EXTEND (NCT03422822) [ 3 – 5 ]. To be eligible for this trial, patients must have completed the full treatment period of the parent trial (JADE MONO-1, MONO-2, COMPARE, TEEN or REGIMEN [ 3 – 5 ]; patients in REGIMEN [ 17 ] who did not meet the responder criteria at the end of the open-label induction period had the option to enter the extension study). Those who had been randomized to abrocitinib 100 or 200 mg once daily in one of these parent studies continued to receive abrocitinib at the same dosage (with maintenance of blinding) in JADE EXTEND.…”

Section: Scientific Summarymentioning

confidence: 99%

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Abrocitinib: First Approval

Deeks

Duggan

2021

Drugs

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Abrocitinib (Cibinqo ® ) is an oral small-molecule inhibitor of Janus kinase 1 (JAK1) being developed by Pfizer for the treatment of moderate-to-severe atopic dermatitis (AD). In September 2021, abrocitinib was approved in the UK and Japan for the treatment of moderate-to-severe AD in adults and adolescents 12 years and older who are candidates for systemic therapy. Abrocitinib has also received a positive CHMP opinion in the EU for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy. Regulatory applications for the drug have also been submitted for review to several other countries, including the USA and Australia. This article summarizes the milestones in the development of abrocitinib leading to this first approval for the treatment of moderate-to-severe AD. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01638-3.

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Section: Scientific Summarymentioning

confidence: 99%

Section: Scientific Summarymentioning

confidence: 99%

Section: Scientific Summarymentioning

confidence: 99%

Section: Scientific Summarymentioning

confidence: 99%

Section: Scientific Summarymentioning

confidence: 99%

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Abrocitinib: First Approval

Deeks

Duggan

2021

Drugs

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Association of Risk of Incident Venous Thromboembolism With Atopic Dermatitis and Treatment With Janus Kinase Inhibitors

et al. 2022

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ImportanceThe risk of venous thromboembolism (VTE) among patients with atopic dermatitis (AD), especially when receiving treatment with Janus kinase (JAK) inhibitors, is unclear.ObjectiveTo determine the association of AD with incident VTE and evaluate the risk of incident VTE among patients with AD who were receiving treatment with JAK inhibitors.Data SourcesThe MEDLINE, Embase, Cochrane Library, and Web of Science databases were searched with no restrictions on language nor geographic locations from their respective inception to February 5, 2022.Study SelectionCohort studies examining the association of AD with incident VTE and randomized clinical trials (RCTs) reporting VTE events in participants with AD receiving JAK inhibitors were included. Around 0.7% of initially identified articles met the selection criteria.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The risk of bias of included cohort studies and RCTs was assessed by the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool 2, respectively. A random-effects model meta-analysis was conducted to calculate the pooled hazard ratio (HR) and risk difference for incident VTE.Main Outcomes and MeasuresThe HRs for incident VTE associated with AD and risk difference for incident VTE between participants with AD who were receiving treatment with JAK inhibitors and controls receiving placebo or dupilumab.ResultsTwo cohort studies and 15 RCTs with a total of 466 993 participants were included. The meta-analysis found no significant association of AD with incident VTE (HR, 0.95; 95% CI 0.62-1.45; incidence rate of VTE, 0.23 events/100 patient-years). Overall, 3 of 5722 patients with AD (0.05%) who were receiving treatment with JAK inhibitors experienced VTE compared with 1 of 3065 patients with AD (0.03%) receiving placebo or dupilumab (Mantel-Haenszel risk difference, 0; 95% CI, 0-0). The incidence rate of VTE was 0.15 and 0.12 events per 100 patient-years in participants with AD receiving JAK inhibitors and placebo, respectively. The findings were similar in 4 unique JAK inhibitors (abrocitinib, baricitinib, upadacitinib, and SHR0302).Conclusions and RelevanceThe results of this systematic review and meta-analysis suggest that the currently available evidence does not detect an increased risk of VTE associated with AD or treatment with JAK inhibitors. These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD.

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Cardiovascular and Venous Thromboembolic Risk With JAK Inhibitors in Immune-Mediated Inflammatory Skin Diseases

Ingrassia,

Maqsood,

Gelfand

et al. 2024

JAMA Dermatol

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ImportanceJanus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions.ObjectiveTo determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions.Data SourcesPubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023.Study SelectionThis review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded.Data Extraction and SynthesisThis study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO.Main Outcomes and MeasuresPrimary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE.ResultsThe analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04).Conclusions and RelevanceIn this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.

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Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial

Cited by 91 publications

References 18 publications

Abrocitinib: First Approval

Abrocitinib: First Approval

Association of Risk of Incident Venous Thromboembolism With Atopic Dermatitis and Treatment With Janus Kinase Inhibitors

Cardiovascular and Venous Thromboembolic Risk With JAK Inhibitors in Immune-Mediated Inflammatory Skin Diseases

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