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Article ; Online: TYK2 as a novel therapeutic target in psoriasis.

Elyoussfi, Sarah / Rane, Shraddha S / Eyre, Steve / Warren, Richard B

Expert review of clinical pharmacology

2023 Volume 16, Issue 6, Page(s) 549–558

Abstract: Introduction: Psoriasis is a chronic inflammatory skin disease affecting approximately 60 million people worldwide. Genome-wide association studies (GWAS) have allowed identification of novel therapeutic targets in psoriasis including tyrosine kinase 2 ( ...

Abstract	Introduction: Psoriasis is a chronic inflammatory skin disease affecting approximately 60 million people worldwide. Genome-wide association studies (GWAS) have allowed identification of novel therapeutic targets in psoriasis including tyrosine kinase 2 (TYK2) where an exonic variant within the gene increases the risk of developing psoriasis. Areas covered: This review discusses the role of TYK2 in psoriasis pathogenesis, how that relates to genetic variants and recently published ground-breaking clinical trials of novel TYK2 inhibitors. Keyword searches of PubMed were made until January 2023, using the terms: 'TYK2 inhibitor,' 'TYK2 inhibitor AND psoriasis' and 'TYK2 AND GWAS.' Articles and references have been thoroughly reviewed by the authors. Expert opinion: The TYK2 inhibitor deucravacitinib shows promise as an effective oral agent for treating psoriasis. Longer term data are needed to know if thrombotic risk/cancer risk is distinct from other Janus kinase (JAK) inhibitors. Psoriasis is a complex genetic disease for which risk is influenced by genes and environmental factors. GWAS studies have identified several regions of DNA associated with increased risk of disease. We believe that pathway analysis by genetic and genomic means will be key to optimizing TYK2 therapy for the right person at the right time.
MeSH term(s)	Humans ; TYK2 Kinase/genetics ; TYK2 Kinase/metabolism ; Genome-Wide Association Study ; Psoriasis/drug therapy ; Psoriasis/genetics ; Janus Kinase Inhibitors/therapeutic use
Chemical Substances	TYK2 Kinase (EC 2.7.10.2) ; Janus Kinase Inhibitors ; TYK2 protein, human (EC 2.7.10.2)
Language	English
Publishing date	2023-06-07
Publishing country	England
Document type	Journal Article ; Review
ISSN	1751-2441
ISSN (online)	1751-2441
DOI	10.1080/17512433.2023.2219054
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Article ; Online: Ixekizumab for the treatment of psoriasis: up-to-date.

Craig, Sarah / Warren, Richard B

Expert opinion on biological therapy

2020 Volume 20, Issue 6, Page(s) 549–557

Abstract: ... ...

Abstract	Introduction
MeSH term(s)	Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/pharmacokinetics ; Antibodies, Monoclonal, Humanized/therapeutic use ; Clinical Trials as Topic ; Dermatologic Agents/adverse effects ; Dermatologic Agents/pharmacokinetics ; Dermatologic Agents/therapeutic use ; Half-Life ; Humans ; Interleukin-17/antagonists & inhibitors ; Interleukin-17/metabolism ; Neutropenia/etiology ; Psoriasis/drug therapy ; Psoriasis/pathology ; Severity of Illness Index ; Treatment Outcome
Chemical Substances	Antibodies, Monoclonal, Humanized ; Dermatologic Agents ; IL17A protein, human ; Interleukin-17 ; ixekizumab (BTY153760O)
Language	English
Publishing date	2020-03-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2052501-1
ISSN	1744-7682 ; 1471-2598
ISSN (online)	1744-7682
ISSN	1471-2598
DOI	10.1080/14712598.2020.1729736
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Article: Brodalumab in psoriasis: evidence to date and clinical potential.

Foulkes, Amy C / Warren, Richard B

Drugs in context

2019 Volume 8, Page(s) 212570

Abstract: Brodalumab is a recombinant, fully human monoclonal antibody (IgG2) which binds with high affinity to the interleukin (IL) 17 receptor A (IL17R). Brodalumab is now licensed and approved for the treatment of moderate-to-severe chronic plaque psoriasis in ... ...

Abstract	Brodalumab is a recombinant, fully human monoclonal antibody (IgG2) which binds with high affinity to the interleukin (IL) 17 receptor A (IL17R). Brodalumab is now licensed and approved for the treatment of moderate-to-severe chronic plaque psoriasis in North America and Europe. As the third to market in the class of agents targeting IL-17, we review its place in the expanding armamentarium of cytokine-directed therapies for patients with severe psoriasis. Brodalumab is a highly efficacious therapy for psoriasis, whose mechanism of action is separate from other treatments targeting IL-17. Its use is associated with rapid control of the disease. We suggest that brodalumab is likely to be considered in those patients requiring rapid control of disease, where there is no known history of depression or suicidal ideation.
Language	English
Publishing date	2019-04-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2719560-0
ISSN	1740-4398 ; 1745-1981
ISSN (online)	1740-4398
ISSN	1745-1981
DOI	10.7573/dic.212570
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Article ; Online: Bimekizumab versus Adalimumab in Plaque Psoriasis. Reply.

Warren, Richard B / Cioffi, Christopher / Peterson, Luke

The New England journal of medicine

2021 Volume 385, Issue 12, Page(s) 1150

Language	English
Publishing date	2021-09-15
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2113092
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Article ; Online: Biosimilars for the Treatment of Psoriasis: A Systematic Review of Clinical Trials and Observational Studies.

Phan, Duc Binh / Elyoussfi, Sarah / Stevenson, Michael / Lunt, Mark / Warren, Richard B / Yiu, Zenas Z N

JAMA dermatology

2023 Volume 159, Issue 7, Page(s) 763–771

Abstract: Importance: Biosimilars have the potential to reduce costs for the management of moderate-to-severe psoriasis compared with originators. However, the extrapolation of evidence enables the approval of a biosimilar for use in indications held by the ... ...

Abstract	Importance: Biosimilars have the potential to reduce costs for the management of moderate-to-severe psoriasis compared with originators. However, the extrapolation of evidence enables the approval of a biosimilar for use in indications held by the originator without directly being studied in clinical trials. Thus, biosimilars can be approved for psoriasis based on extrapolated evidence from other diseases. The availability of evidence for the effectiveness and safety of biosimilars for the treatment of psoriasis is therefore unclear. Objective: To compare the efficacy/effectiveness and safety of biosimilars with originator biologics for the treatment of patients with psoriasis. Evidence review: MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and The European Union Clinical Trials Register were searched in August 2022. Eligible studies were appraised using the Cochrane Risk of Bias 2 and ROBINS-I tools. All analyses were conducted from September 2022 to November 2022. Findings: Fourteen trials (10 adalimumab, 2 etanercept, 1 infliximab, and 1 ustekinumab) and 3 cohort studies (1 adalimumab, 1 etanercept, 1 infliximab and etanercept) were included. Twelve trials compared biosimilars with originators in originator-naive patients (starters), and 11 trials compared switching from originator to biosimilar (switchers) with continuous originator treatments. There was no clinically or statistically significant difference in rates of achieving 75% improvement in Psoriasis Area and Severity Index scores and risks of adverse events (AEs) at week 16 and week 52 between the comparators. Two cohort studies showed no difference in effectiveness and safety outcomes between originators and biosimilars, whereas 1 study reported more AEs in patients who switched to biosimilars of adalimumab at 12 months. Three trials showed low risk of bias, whereas 11 trials had moderate risk of bias. All cohort studies had moderate to high risk of bias. Conclusions and relevance: In this systematic review, there was no clinically or statistically significant difference in the efficacy and safety between biosimilars and originators for the treatment of patients with psoriasis. Most of the available evidence was based on randomized clinical trials, although high-quality real-world evidence was lacking. Future studies are needed to examine the long-term effectiveness and safety of biosimilars for the treatment of patients with psoriasis.
MeSH term(s)	Humans ; Etanercept/adverse effects ; Biosimilar Pharmaceuticals/adverse effects ; Infliximab/adverse effects ; Adalimumab/adverse effects ; Psoriasis/drug therapy ; Psoriasis/chemically induced
Chemical Substances	Etanercept (OP401G7OJC) ; Biosimilar Pharmaceuticals ; Infliximab (B72HH48FLU) ; Adalimumab (FYS6T7F842)
Language	English
Publishing date	2023-05-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2701761-8
ISSN	2168-6084 ; 2168-6068
ISSN (online)	2168-6084
ISSN	2168-6068
DOI	10.1001/jamadermatol.2023.1338
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Article ; Online: The risk of venous thromboembolism in atopic dermatitis: a matched cohort analysis in UK primary care.

Warren, Richard B / Basey, Victoria / Lynam, Anita / Curtis, Charlotte / Ardern-Jones, Michael R

The British journal of dermatology

2023 Volume 189, Issue 4, Page(s) 427–436

Abstract: Background: Atopic dermatitis (AD) is a common chronic inflammatory skin condition. While other chronic inflammatory conditions are associated with increased risk of venous thromboembolism (VTE), associations between AD and VTE have not been established. ...

Abstract	Background: Atopic dermatitis (AD) is a common chronic inflammatory skin condition. While other chronic inflammatory conditions are associated with increased risk of venous thromboembolism (VTE), associations between AD and VTE have not been established. Objectives: We examined whether AD is associated with an increased risk of VTE in a population-based study. Methods: Electronic health records were extracted from UK general practices contributing to the Optimum Patient Care Research Database (1 January 2010 to 1 January 2020). All adults with AD were identified (n = 150 975) and age- and sex-matched with unaffected controls (n = 603 770). The risk of VTE, consisting of pulmonary embolism (PE) or deep-vein thrombosis (DVT), was compared in people with AD vs. controls using Cox proportional hazard models. PE and DVT were examined separately as secondary outcomes. Results: We identified 150 975 adults with active AD and matched them with 603 770 unaffected controls. During the study, 2576 of those with active AD and 7563 of the matched controls developed VTE. Individuals with AD had a higher risk of VTE than controls [adjusted hazard ratio (aHR) 1.17, 95% confidence interval (CI) 1.12-1.22]. When assessing VTE components, AD was associated with a higher risk of DVT (aHR 1.30, 95% CI 1.23-1.37) but not PE (aHR 0.94, 95% CI 0.87-1.02). The VTE risk was greater in older people with AD (≥ 65 years: aHR 1.22, 95% CI 1.15-1.29; 45-65 years: aHR 1.15, 95% CI 1.05-1.26; < 45 years: aHR 1.07, 95% CI 0.97-1.19) and those with obesity [body mass index (BMI) ≥ 30: aHR 1.25, 95% CI 1.12-1.39; BMI < 30: aHR 1.08, 95% CI 1.01-1.15). Risk was broadly consistent across mild, moderate or severe AD. Conclusions: AD is associated with a small increase in risk of VTE and DVT, with no increase in risk of PE. The magnitude of this risk increase is modest in younger people, and those without obesity.
MeSH term(s)	Adult ; Humans ; Aged ; Venous Thromboembolism/etiology ; Venous Thromboembolism/complications ; Venous Thrombosis/epidemiology ; Venous Thrombosis/etiology ; Dermatitis, Atopic/complications ; Dermatitis, Atopic/epidemiology ; Pulmonary Embolism/etiology ; Pulmonary Embolism/complications ; Cohort Studies ; Obesity/complications ; Primary Health Care ; United Kingdom/epidemiology ; Risk Factors
Language	English
Publishing date	2023-07-07
Publishing country	England
Document type	Journal Article
ZDB-ID	80076-4
ISSN	1365-2133 ; 0007-0963
ISSN (online)	1365-2133
ISSN	0007-0963
DOI	10.1093/bjd/ljad212
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Article ; Online: The use of serum methotrexate level as an assessment of biochemical drug adherence in psoriasis.

Ra, Amelle G / Littlewood, Zoe / Barton, Anne / Keevil, Brian / McTaggart, Malcolm / Warren, Richard B / Bluett, James

The British journal of dermatology

2024

Language	English
Publishing date	2024-03-08
Publishing country	England
Document type	Journal Article
ZDB-ID	80076-4
ISSN	1365-2133 ; 0007-0963
ISSN (online)	1365-2133
ISSN	0007-0963
DOI	10.1093/bjd/ljae096
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Article ; Online: Correction to: OX40 in the Pathogenesis of Atopic Dermatitis-A New Therapeutic Target.

Croft, Michael / Esfandiari, Ehsanollah / Chong, Camilla / Hsu, Hailing / Kabashima, Kenji / Kricorian, Greg / Warren, Richard B / Wollenberg, Andreas / Guttman-Yassky, Emma

American journal of clinical dermatology

2024 Volume 25, Issue 3, Page(s) 463

Language	English
Publishing date	2024-02-17
Publishing country	New Zealand
Document type	Published Erratum
ZDB-ID	1502476-3
ISSN	1179-1888 ; 1175-0561
ISSN (online)	1179-1888
ISSN	1175-0561
DOI	10.1007/s40257-024-00850-7
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Article ; Online: OX40 in the Pathogenesis of Atopic Dermatitis-A New Therapeutic Target.

Croft, Michael / Esfandiari, Ehsanollah / Chong, Camilla / Hsu, Hailing / Kabashima, Kenji / Kricorian, Greg / Warren, Richard B / Wollenberg, Andreas / Guttman-Yassky, Emma

American journal of clinical dermatology

2024 Volume 25, Issue 3, Page(s) 447–461

Abstract: Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities ...

Abstract	Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities and secondary complications, which can result in significant clinical burden that impacts the patient's overall quality of life. The complex interplay of immune dysregulation and skin barrier disruption drives AD pathogenesis, of which T-cell-dependent inflammation plays a critical role in patients with AD. Despite new targeted therapies, many patients with moderate-to-severe AD fail to achieve or sustain their individual treatment goals and/or may not be suitable for or tolerate these therapies. There remains a need for a novel, efficacious, well-tolerated therapeutic option that can deliver durable benefits across a heterogeneous AD patient population. Expression of OX40 [tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], a prominent T-cell co-stimulatory molecule, and its ligand [OX40L; tumor necrosis factor superfamily, member 4 (TNFSF4)] is increased in AD. As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD.
MeSH term(s)	Dermatitis, Atopic/immunology ; Dermatitis, Atopic/drug therapy ; Humans ; Receptors, OX40/antagonists & inhibitors ; Receptors, OX40/immunology ; Receptors, OX40/metabolism ; OX40 Ligand/antagonists & inhibitors ; OX40 Ligand/metabolism ; Molecular Targeted Therapy ; Severity of Illness Index ; Skin/immunology ; Skin/pathology ; Quality of Life ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Signal Transduction/immunology ; Signal Transduction/drug effects ; Treatment Outcome
Chemical Substances	Receptors, OX40 ; TNFRSF4 protein, human ; OX40 Ligand ; TNFSF4 protein, human
Language	English
Publishing date	2024-01-18
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	1502476-3
ISSN	1179-1888 ; 1175-0561
ISSN (online)	1179-1888
ISSN	1175-0561
DOI	10.1007/s40257-023-00838-9
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Article: Ustekinumab for the treatment of psoriasis: an evidence update.

Yiu, Zenas Zn / Warren, Richard B

Seminars in cutaneous medicine and surgery

2018 Volume 37, Issue 3, Page(s) 143–147

Abstract: Ustekinumab is an interleukin-12/23 inhibitor used for the treatment of moderate-to-severe psoriasis. Here, we review new evidence since ustekinumab was licensed for relative efficacy in comparison with other biologic therapies from head-to-head ... ...

Abstract	Ustekinumab is an interleukin-12/23 inhibitor used for the treatment of moderate-to-severe psoriasis. Here, we review new evidence since ustekinumab was licensed for relative efficacy in comparison with other biologic therapies from head-to-head randomized controlled trials and network meta-analyses for the treatment of psoriasis. We also review observational data emerging from psoriasis registries reporting the effectiveness and safety of ustekinumab. Overall, new evidence suggests that ustekinumab has a favorable balance between efficacy/effectiveness, safety, and tolerability and should remain a first-line biologic therapy option for patients with severe psoriasis at present.
MeSH term(s)	Dermatologic Agents/adverse effects ; Dermatologic Agents/therapeutic use ; Humans ; Infections/chemically induced ; Observational Studies as Topic ; Psoriasis/drug therapy ; Psoriasis/genetics ; Randomized Controlled Trials as Topic ; Ustekinumab/adverse effects ; Ustekinumab/therapeutic use
Chemical Substances	Dermatologic Agents ; Ustekinumab (FU77B4U5Z0)
Language	English
Publishing date	2018-09-14
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1355511-x
ISSN	1558-0768 ; 1085-5629
ISSN (online)	1558-0768
ISSN	1085-5629
DOI	10.12788/j.sder.2018.040
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