Matching-Adjusted Indirect Comparison of the Long-Term Efficacy of Deucravacitinib Versus Adalimumab for Moderate to Severe Plaque Psoriasis

Armstrong, April W.; Park, Sang Hee; Patel, Vardhaman; Hogan, Malcolm; Wang, Wei-Jhih; Davidson, David; Chirikov, Viktor

doi:10.1007/s13555-023-00977-1

Cited by 8 publications

(3 citation statements)

References 20 publications

(31 reference statements)

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“…The first small molecule TYK2 inhibitor was approved by the FDA in 2022 for the treatment of psoriasis, with additional agents under investigation for use in other autoimmune conditions (57)(58)(59). TYK2 mediates signaling through several cytokines that have been linked with T1D pathogenesis, including IFNα, IL-12, and IL-23.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice

Syed,

Ballew,

Lee

et al. 2024

Preprint

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SUMMARYTyrosine protein-kinase 2 (TYK2), a member of the Janus kinase family, mediates inflammatory signaling through multiple cytokines, including interferon-α (IFNα), interleukin (IL)-12, and IL-23. Missense mutations in TYK2 are associated with protection against type 1 diabetes (T1D), and inhibition of TYK2 shows promise in the management of other autoimmune conditions. Here, we evaluated the effects of specific TYK2 inhibitors (TYK2is) in pre-clinical models of T1D. First, human β cells, cadaveric donor islets, and iPSC-derived islets were treatedin vitrowith IFNα in combination with a small molecule TYK2i (BMS-986165 or a related molecule BMS-986202). TYK2 inhibition prevented IFNα-induced β cell HLA class I up-regulation, endoplasmic reticulum stress, and chemokine production. In co-culture studies, pre-treatment of β cells with a TYK2i prevented IFNα-induced activation of T cells targeting an epitope of insulin.In vivoadministration of BMS-986202 in two mouse models of T1D (RIP-LCMV-GPmice and NOD mice) reduced systemic and tissue-localized inflammation, prevented β cell death, and delayed T1D onset. Transcriptional phenotyping of pancreatic islets, pancreatic lymph nodes (PLN), and spleen during early disease pathogenesis highlighted a role for TYK2 inhibition in modulating signaling pathways associated with inflammation, translational control, stress signaling, secretory function, immunity, and diabetes. Additionally, TYK2i treatment changed the composition of innate and adaptive immune cell populations in the blood and disease target tissues, resulting in an immune phenotype with a diminished capacity for β cell destruction. Overall, these findings indicate that TYK2i has beneficial effects in both the immune and endocrine compartments in models of T1D, thus supporting a path forward for testing TYK2 inhibitors in human T1D.

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Section: Discussionmentioning

confidence: 99%

Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice

Syed,

Ballew,

Lee

et al. 2024

Preprint

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“…At long-term follow-up (44–60 weeks), deucravacitinib PASI75 was 65.9% (58.0–73.4), also close to the PASI75 achieved by first-generation biologics adalimumab 62.8% (55.3–69.6) and ustekinumab 68.0% (64.6–71.5). Furthermore, a matching-adjusted indirect comparison (MAIC) of the long-term efficacy of deucravacitinib versus adalimumab for patients with moderate-to-severe plaque psoriasis was recently published [ 47 ]. This MAIC concluded that patients treated with deucravacitinib showed a higher long-term response rate at 2 years than with adalimumab.…”

Section: Emerging Oral Treatments For Psoriasismentioning

confidence: 99%

New and Emerging Oral/Topical Small-Molecule Treatments for Psoriasis

Carmona-Rocha,

Rusiñol,

Puig

2024

Pharmaceutics

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The introduction of biologic therapies has led to dramatic improvements in the management of moderate-to-severe psoriasis. Even though the efficacy and safety of the newer biologic agents are difficult to match, oral administration is considered an important advantage by many patients. Current research is focused on the development of oral therapies with improved efficacy and safety compared with available alternatives, as exemplified by deucravacitinib, the first oral allosteric Tyk2 inhibitor approved for the treatment of moderate to severe psoriasis in adults. Recent advances in our knowledge of psoriasis pathogenesis have also led to the development of targeted topical molecules, mostly focused on intracellular signaling pathways such as AhR, PDE-4, and Jak-STAT. Tapinarof (an AhR modulator) and roflumilast (a PDE-4 inhibitor) have exhibited favorable efficacy and safety outcomes and have been approved by the FDA for the topical treatment of plaque psoriasis. This revision focuses on the most recent oral and topical therapies available for psoriasis, especially those that are currently under evaluation and development for the treatment of psoriasis.

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“…3-69.6) and ustekinumab 68.0% (64.6-71.5). Furthermore, a matching-adjusted indirect comparison (MAIC) of the long-term efficacy of deucravacitinib versus adalimumab for patients with moderate-to-severe plaque psoriasis was recently published [47]. This MAIC concluded that patients treated with deucravacitinib showed a higher long-term response rate at 2 years than with adalimumab.…”

Section: Deucravacitinibmentioning

confidence: 99%

New and Emerging Biological and Oral/Topical Small-Molecule Treatments for Psoriasis

Carmona-Rocha,

Rusiñol,

Puig

2024

Preprint

View full text Add to dashboard Cite

The introduction of biologic therapies has led to dramatic improvements in the management of moderate-to-severe psoriasis. Even though the efficacy and safety of the newer biologic agents are difficult to match, oral administration is considered an important advantage by many patients. Current research is focused on development of oral therapies with improved efficacy and safety compared to available alternatives, as exemplified by deucravacitinib, the first oral allosteric Tyk2 inhibitor approved for the treatment of moderate-to-severe psoriasis in adults. Recent advances in our knowledge of psoriasis pathogenesis have also led to the development of targeted topical molecules, mostly focused on intracellular signaling pathways, such as AhR, PDE-4 and Jak-STAT. Topical tapinarof, an AhR modulator, and roflumilast, a PDE-4 inhibitor, have exhibited favorable efficacy and safety outcomes have been approved by the FDA for the topical treatment of plaque psoriasis. This revision focuses on the most recent oral and topical therapies available for psoriasis and specially on those that are currently under evaluation and development for the treatment of psoriasis.

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Matching-Adjusted Indirect Comparison of the Long-Term Efficacy of Deucravacitinib Versus Adalimumab for Moderate to Severe Plaque Psoriasis

Cited by 8 publications

References 20 publications

Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice

Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice

New and Emerging Oral/Topical Small-Molecule Treatments for Psoriasis

New and Emerging Biological and Oral/Topical Small-Molecule Treatments for Psoriasis

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