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Emerging systemic JAK inhibitors in the treatment of atopic dermatitis: a review of abrocitinib, baricitinib, and upadacitinib.

ABSTRACT: The Janus kinases (JAK) are a group of molecules, composed of JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2), which are key components within the JAK-signal transducers and activators of transcription pathway, where cytokine receptor signaling takes place. These molecules play a foundational role in the underlying pathogenesis of multiple immune-related conditions such as atopic dermatitis (AD), rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, and others. Thus far, JAK inhibitors for inflammatory conditions have only been marketed for the treatment of rheumatoid arthritis and psoriatic arthritis, but ongoing phase II and phase III clinical trials for other immune-mediated diseases, such as AD, have also shown promising results. This review summarizes the clinical data available from various trials and reports on the safety and efficacy of abrocitinib, baricitinib, and upadacitinib, the three oral systemic JAK inhibitors used in the treatment of AD. The safety and efficacy of JAK inhibitors for the treatment of AD are emerging in the literature. It is important that dermatologists are aware of any potential adverse events or risks associated with the use of JAK inhibitors in order to promote a higher standard of treatment and quality of living.

SUBMITTER: Nezamololama N

PROVIDER: S-EPMC7673622 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Emerging systemic JAK inhibitors in the treatment of atopic dermatitis: a review of abrocitinib, baricitinib, and upadacitinib.

Nezamololama Novin N Fieldhouse Keira K Metzger Kristy K Gooderham Melinda M

Drugs in context 20201116

The Janus kinases (JAK) are a group of molecules, composed of JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2), which are key components within the JAK-signal transducers and activators of transcription pathway, where cytokine receptor signaling takes place. These molecules play a foundational role in the underlying pathogenesis of multiple immune-related conditions such as atopic dermatitis (AD), rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, and others. Thus far, JAK inhi ...[more]

PMID: 33240390

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Project description:IntroductionAtopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by itchy, painful, and dry skin. Despite the great number of available therapies, economic evaluations are still needed to provide evidence on their cost efficiency. This research aimed to evaluate the cost effectiveness of the Janus kinase (JAK) inhibitor abrocitinib (200 mg) compared with dupilumab (300 mg), tralokinumab (300 mg), baricitinib (2 and 4 mg), and upadacitinib (15 and 30 mg) for the treatment of patients with severe AD from the Spanish National Health System (NHS) perspective.MethodsA hybrid model consisting of a decision tree linked to a Markov model was developed to estimate costs, quality-adjusted life-years (QALYs), total years in response and incremental cost-per-QALY gained (willingness-to-pay [WTP] threshold: €25,000/QALY). Adults with severe AD entered the decision tree and response (75% reduction in baseline Eczema Area and Severity Index score, EASI-75) was considered at 16 and 52 weeks. After this time, patients entered the Markov model (remainder of the 10-year time horizon), which consisted of three health states: maintenance with active therapy, subsequent treatment, or death. All costs were presented in 2022 euros (€). Additionally, cost per number-needed-to-treat (NNT) was calculated for abrocitinib and dupilumab based on a head-to-head post-hoc analysis.ResultsAbrocitinib 200 mg was dominant (i.e., lower incremental costs and higher incremental benefit) compared with all studied alternatives (dupilumab 300 mg, tralokinumab 300 mg, baricitinib 2 and 4 mg, upadacitinib 15 and 30 mg) with a QALYs gain of 0.49, 0.60, 0.64, 0.43, 0.45, and 0.08, respectively, and per-person costs savings of €22,097, €24,140, €14,825, €7,116, €12,805, and €45,189, respectively. Considering the WTP threshold, abrocitinib was dominant or cost effective compared with all alternatives for most simulations. Additionally, abrocitinib was dominant compared with all alternatives when evaluating the cost effectiveness over a 5-year time horizon. NNT showed that abrocitinib was dominant versus dupilumab.ConclusionsThe results of the study show that abrocitinib is a cost-effective therapy compared with other JAK inhibitors and biological therapies from the Spanish NHS perspective.

Dataset Information

Emerging systemic JAK inhibitors in the treatment of atopic dermatitis: a review of abrocitinib, baricitinib, and upadacitinib.

Publications

Emerging systemic JAK inhibitors in the treatment of atopic dermatitis: a review of abrocitinib, baricitinib, and upadacitinib.

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