PMID- 38051972 OWN - NLM STAT- MEDLINE DCOM- 20240419 LR - 20240419 IS - 1365-2133 (Electronic) IS - 0007-0963 (Linking) VI - 190 IP - 5 DP - 2024 Apr 17 TI - 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). PG - 689-700 LID - 10.1093/bjd/ljad481 [doi] AB - 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: 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: Data from patients in the UK and the Republic of Ireland registered in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007 to 2022 on a 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 in patients 40 years of age). BADBIR patients with available information in BSTOP were categorized as HLA-C*06:02- or HLA-C*06:02 + . 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: Final analytical cohorts included 4250 patients in the age at psoriasis onset group [2929 EOP (69%) vs. 1321 LOP (31%)] and 3094 patients in the HLA-C*06:02 status group [1603 HLA-C*06:02+ (52%) vs. 1491 HLA-C*06:02- (48%)]. There was no significant difference between EOP and LOP in drug survival associated with ineffectiveness or AEs for any biologics. However, compared with patients who were HLA-C*06:02-, patients who were HLA-C*06:02 + were less likely to discontinue ustekinumab for reasons associated with ineffectiveness (aHR 0.56, 95% CI 0.42-0.75). CONCLUSIONS: HLA-C*06:02, but not age at psoriasis onset, is a predictive biomarker for biologic survival in patients with psoriasis. Findings from this large cohort provide further, important information to aid clinicians using biologic therapies to manage patients with psoriasis. CI - (c) 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. FAU - Alabas, Oras A AU - Alabas OA AUID- ORCID: 0000-0003-2002-0781 AD - 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. FAU - Mason, Kayleigh J AU - Mason KJ AUID- ORCID: 0000-0002-5419-0669 AD - Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, UK. FAU - Yiu, Zenas Z N AU - Yiu ZZN AUID- ORCID: 0000-0002-1831-074X AD - 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. FAU - Warren, Richard B AU - Warren RB AUID- ORCID: 0000-0002-2918-6481 AD - 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. FAU - Dand, Nick AU - Dand N AUID- ORCID: 0000-0002-1805-6278 AD - Department of Medical and Molecular Genetics, School of Basic & Medical Biosciences, King's College London, UK. FAU - Barker, Jonathan N AU - Barker JN AD - St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK. FAU - Smith, Catherine H AU - Smith CH AD - St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK. FAU - Grif fi ths, Christopher E M AU - Grif fi ths CEM AD - 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. CN - BADBIR and BSTOP study group LA - eng GR - British Association of Dermatologists Biologic Register Ltd/ GR - National Institute for Health and Care Research/ GR - MR/L011808/1/Medical Research Council Stratified Medicine award/ GR - National Institute for Health Research Biomedical Research Centre/ PT - Journal Article PL - England TA - Br J Dermatol JT - The British journal of dermatology JID - 0004041 RN - FU77B4U5Z0 (Ustekinumab) RN - 0 (HLA-C Antigens) RN - 0 (Biological Factors) RN - FYS6T7F842 (Adalimumab) RN - OP401G7OJC (Etanercept) RN - 0 (Immunologic Factors) RN - 0 (Adjuvants, Immunologic) RN - 0 (Biological Products) SB - IM CIN - Br J Dermatol. 2024 Jan 04;:. PMID: 38174815 CIN - Br J Dermatol. 2024 Apr 17;190(5):e55. PMID: 38630931 MH - Humans MH - Adult MH - Cohort Studies MH - Ustekinumab/therapeutic use MH - HLA-C Antigens MH - Dermatologists MH - Registries MH - Biological Factors/therapeutic use MH - Adalimumab/therapeutic use MH - *Psoriasis/drug therapy MH - Etanercept/therapeutic use MH - Immunologic Factors/therapeutic use MH - Adjuvants, Immunologic/therapeutic use MH - *Biological Products/therapeutic use MH - Treatment Outcome COIS- Conflicts of interest J.N.B. has received honoraria, travel support and/or research grants (King's College London) from AbbVie, Amgen, Almirall, Bristol Myers Squibb, Pfizer, Novartis, Janssen, Lilly, UCB, Sun Pharma, Boehringer Ingelheim and GlaxoSmithKline. R.B.W. has acted as a consultant and/or speaker for and/or received research grants from AbbVie, Amgen, Almirall, Celgene, Eli Lilly, Pfizer, LEO Pharma, Novartis, Janssen Cilag, Medac, UCB Pharma and Xenoport. C.H.S. reports grants from a Medical Research Council-funded stratified medicine consortium with multiple industry partners, grants from an Innovative Medicines Initiative (Horizon 2020)-funded European consortium with multiple industry partners, and others from AbbVie, Novartis, Pfizer, Sanofi, Boehringer Ingelheim and SOBI, outside the submitted work; she is also chair of UK guidelines on biologic therapy in psoriasis. C.E.M.G. has received honoraria and/or research grants from AbbVie, Almirall, Amgen, Anaptysbio, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Evelo Bioscience, Galderma, GSK, Inmagene, Kyowa Kerin, LEO Pharma, Janssen, ONO Pharmaceuticals, Novartis, Pfizer, Sandoz and UCB Pharma. FIR - Barker, Jonathan IR - Barker J FIR - Morrison, Simon IR - Morrison S FIR - Bewley, Anthony IR - Bewley A FIR - Evans, Ian IR - Evans I FIR - Griffiths, Christopher IR - Griffiths C FIR - Ahmed, Shehnaz IR - Ahmed S FIR - Kirby, Brian IR - Kirby B FIR - Kleyn, Elise IR - Kleyn E FIR - Laws, Philip IR - Laws P FIR - Hampton, Philip IR - Hampton P FIR - Alabas, Oras IR - Alabas O FIR - McElhone, Kathleen IR - McElhone K FIR - Yiu, Zenas IR - Yiu Z FIR - Mackenzie, Teena IR - Mackenzie T FIR - McPherson, Tess IR - McPherson T FIR - Murphy, Ruth IR - Murphy R FIR - Ormerod, Anthony IR - Ormerod A FIR - Walton, Shernaz IR - Walton S FIR - Reynolds, Nick IR - Reynolds N FIR - Smith, Catherine IR - Smith C FIR - Shipman, Alexa IR - Shipman A FIR - Ye, Christina IR - Ye C FIR - Hughes, Olivia IR - Hughes O FIR - Warren, Richard IR - Warren R FIR - Strangfeld, Anja IR - Strangfeld A FIR - Weller, Richard IR - Weller R FIR - Gupta, Girish IR - Gupta G FIR - Zietemann, Vera IR - Zietemann V FIR - Barker, Jonathan IR - Barker J FIR - Barnes, Michael R IR - Barnes MR FIR - Burden, A David IR - Burden AD FIR - Meglio, Paola di IR - Meglio PD FIR - Emsley, Richard IR - Emsley R FIR - Evans, Anea IR - Evans A FIR - Griffiths, Christopher E M IR - Griffiths CEM FIR - Payne, Katherine IR - Payne K FIR - Reynolds, Nick J IR - Reynolds NJ FIR - Smith, Catherine IR - Smith C FIR - Stocken, Deborah IR - Stocken D FIR - Warren, Richard B IR - Warren RB EDAT- 2023/12/06 03:41 MHDA- 2024/04/19 06:43 CRDT- 2023/12/05 16:02 PHST- 2023/04/23 00:00 [received] PHST- 2023/09/29 00:00 [revised] PHST- 2023/11/27 00:00 [accepted] PHST- 2024/04/19 06:43 [medline] PHST- 2023/12/06 03:41 [pubmed] PHST- 2023/12/05 16:02 [entrez] AID - 7459199 [pii] AID - 10.1093/bjd/ljad481 [doi] PST - ppublish SO - Br J Dermatol. 2024 Apr 17;190(5):689-700. doi: 10.1093/bjd/ljad481.