The association of age at psoriasis onset and HLA-C*06:02 with biologic survival in patients with moderate-to-severe psoriasis: a cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR).


Journal

The British journal of dermatology
ISSN: 1365-2133
Titre abrégé: Br J Dermatol
Pays: England
ID NLM: 0004041

Informations de publication

Date de publication:
05 Dec 2023
Historique:
received: 23 04 2023
revised: 29 09 2023
accepted: 02 12 2023
medline: 6 12 2023
pubmed: 6 12 2023
entrez: 5 12 2023
Statut: aheadofprint

Résumé

Few studies have used real-world data to investigate the association between biologic therapy survival and age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis. The robustness of these studies is limited by small sample size, short follow-up and diverse safety and effectiveness measures. To describe biologic survival and explore whether the response to biologics is modified by age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis. Data from patients in the UK and the Republic of Ireland registering to the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007-2022 on first course of adalimumab, etanercept, secukinumab or ustekinumab with at least 6 months' follow-up and a subset of BADBIR patients with available HLA-C*06:02 information registered to Biomarkers and Stratification To Optimise outcomes in Psoriasis (BSTOP) were analysed. Patients aged ≥50 years at treatment initiation were classified into early onset psoriasis (EOP; presenting ≤40 years of age) and late onset (LOP; presenting > 40 years of age); BADBIR patients with available information in BSTOP were categorised into HLA-C*06:02-ve and HLA-C*06:02+ve. Biologic survival was defined as treatment discontinuation associated with ineffectiveness or occurrence of adverse events (AEs). Adjusted survival function and hazard ratio (aHR) with 95% confidence interval (CI) were estimated using a flexible parametric model to compare discontinuing therapy between age at psoriasis onset and HLA-C*06:02 groups. Each model included exposure (biologics), effect modifier (age at onset or HLA-C*06:02 status), interaction terms and several baseline demographic, clinical and disease severity covariates. Final analytical cohorts included 4250 patients (2929 [69%] EOP vs. 1321 [31%] LOP) and 3094 patients (1603 [52%] HLA-C*06:02+ve vs. 1491 [48%] HLA-C*06:02-ve). There was no significant difference between EOP and LOP in drug survival associated with ineffectiveness or AEs for any biologics. However, HLA-C*06:02+ve compared with HLA-C*06:02-ve patients were less likely to discontinue ustekinumab associated with ineffectiveness 0.56 [0.42, 0.75]. HLA-C*06:02 but not age at psoriasis onset is a predictive biomarker for biologic survival in psoriasis patients. Findings from this large cohort provide further, important information to aid clinicians using biologic therapies to manage psoriasis patients.

Sections du résumé

BACKGROUND BACKGROUND
Few studies have used real-world data to investigate the association between biologic therapy survival and age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis. The robustness of these studies is limited by small sample size, short follow-up and diverse safety and effectiveness measures.
OBJECTIVES OBJECTIVE
To describe biologic survival and explore whether the response to biologics is modified by age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis.
METHODS METHODS
Data from patients in the UK and the Republic of Ireland registering to the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007-2022 on first course of adalimumab, etanercept, secukinumab or ustekinumab with at least 6 months' follow-up and a subset of BADBIR patients with available HLA-C*06:02 information registered to Biomarkers and Stratification To Optimise outcomes in Psoriasis (BSTOP) were analysed. Patients aged ≥50 years at treatment initiation were classified into early onset psoriasis (EOP; presenting ≤40 years of age) and late onset (LOP; presenting > 40 years of age); BADBIR patients with available information in BSTOP were categorised into HLA-C*06:02-ve and HLA-C*06:02+ve. Biologic survival was defined as treatment discontinuation associated with ineffectiveness or occurrence of adverse events (AEs). Adjusted survival function and hazard ratio (aHR) with 95% confidence interval (CI) were estimated using a flexible parametric model to compare discontinuing therapy between age at psoriasis onset and HLA-C*06:02 groups. Each model included exposure (biologics), effect modifier (age at onset or HLA-C*06:02 status), interaction terms and several baseline demographic, clinical and disease severity covariates.
RESULTS RESULTS
Final analytical cohorts included 4250 patients (2929 [69%] EOP vs. 1321 [31%] LOP) and 3094 patients (1603 [52%] HLA-C*06:02+ve vs. 1491 [48%] HLA-C*06:02-ve). There was no significant difference between EOP and LOP in drug survival associated with ineffectiveness or AEs for any biologics. However, HLA-C*06:02+ve compared with HLA-C*06:02-ve patients were less likely to discontinue ustekinumab associated with ineffectiveness 0.56 [0.42, 0.75].
CONCLUSIONS CONCLUSIONS
HLA-C*06:02 but not age at psoriasis onset is a predictive biomarker for biologic survival in psoriasis patients. Findings from this large cohort provide further, important information to aid clinicians using biologic therapies to manage psoriasis patients.

Identifiants

pubmed: 38051972
pii: 7459199
doi: 10.1093/bjd/ljad481
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Investigateurs

Jonathan Barker (J)
Simon Morrison (S)
Anthony Bewley (A)
Ian Evans (I)
Christopher Griffiths (C)
Shehnaz Ahmed (S)
Brian Kirby (B)
Elise Kleyn (E)
Philip Laws (P)
Philip Hampton (P)
Oras Alabas (O)
Kathleen McElhone (K)
Zenas Yiu (Z)
Teena Mackenzie (T)
Tess McPherson (T)
Ruth Murphy (R)
Anthony Ormerod (A)
Shernaz Walton (S)
Nick Reynolds (N)
Catherine Smith (C)
Alexa Shipman (A)
Christina Ye (C)
Olivia Hughes (O)
Richard Warren (R)
Richard Weller (R)
Girish Gupta (G)
Vera Zietemann (V)
Jonathan Barker (J)
Michael R Barnes (MR)
A David Burden (AD)
Paola di Meglio (P)
Richard Emsley (R)
Anea Evans (A)
Christopher E M Griffiths (CEM)
Katherine Payne (K)
Nick J Reynolds (NJ)
Catherine Smith (C)
Deborah Stocken (D)
Richard B Warren (RB)

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Auteurs

Oras A Alabas (OA)

Dermatology Centre, Northern Care Alliance NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, UK. On behalf of the BADBIR study group.

Kayleigh J Mason (KJ)

Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, UK.

Zenas Z N Yiu (ZZN)

Dermatology Centre, Northern Care Alliance NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, UK. On behalf of the BADBIR study group.

Richard B Warren (RB)

Dermatology Centre, Northern Care Alliance NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, UK. On behalf of the BADBIR study group.

Nick Dand (N)

Department of Medical and Molecular Genetics, School of Basic & Medical Biosciences, King's College London, UK.

Jonathan N Barker (JN)

St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, United Kingdom. On behalf of BSTOP study group.

Catherine H Smith (CH)

St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, United Kingdom. On behalf of BSTOP study group.

Christopher E M Griffiths (CEM)

Dermatology Centre, Northern Care Alliance NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, UK. On behalf of the BADBIR study group.

Classifications MeSH