Shin-Shin Ho1, Tsen-Fang Tsai2,3. 1. National Taiwan University Hospital, No. 7 Chung San South Road, Taipei, Taiwan. 2. National Taiwan University Hospital, No. 7 Chung San South Road, Taipei, Taiwan. tftsai@yahoo.com. 3. Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. tftsai@yahoo.com.
Abstract
INTRODUCTION: Psoriasis is a chronic inflammatory disease with a strong genetic background, particularly the human leukocyte antigen (HLA). HLA-Cw6 has been shown to be the major disease susceptibility locus and affects the phenotypes and treatment response in psoriasis; however, the prevalence of HLA-Cw6 is far lower than HLA-Cw1 in some Asian countries. OBJECTIVES: The aim of this study was to determine whether HLA-Cw1 predisposes psoriasis patients to different treatment responses of biologics and other systemic therapy. METHODS: This retrospective case-control study included 126 patients with moderate to severe plaque-type psoriasis who had been genotyped and treated in a special psoriasis clinic. HLA-Cw1-positive and -negative patients were compared. RESULTS: Our results showed that HLA-Cw1-negative patients were significantly more likely to respond (achieve Psoriasis Area and Severity Index [PASI] 75 after a 12- to 16-week treatment course) to biologics (including etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab; odds ratio [OR] 1.99, 95% confidence interval [CI] 1.17-3.44, p = 0.0122) and especially to ustekinumab (OR 3.27, 95% CI 1.03-11.30; p = 0.0496). An HLA-Cw1 allele dose effect was also found. The results remained after multivariate logistic regression analysis. HLA-Cw1-negative patients also showed significantly greater improvement of PASI in ustekinumab and biologics (p = 0.0044 and p = 0.0064, respectively), with other biologics showing non-significant trends. HLA-Cw1 status did not affect the treatment responses of non-biologic systemic treatment, including phototherapy. CONCLUSION: There is an association between HLA-Cw1 and treatment response to biologics, but not to non-biologics, in our Asian population of patients with moderate to severe psoriasis; however, the exact mechanism and role of HLA-Cw1 remain to be investigated.
INTRODUCTION: Psoriasis is a chronic inflammatory disease with a strong genetic background, particularly the human leukocyte antigen (HLA). HLA-Cw6 has been shown to be the major disease susceptibility locus and affects the phenotypes and treatment response in psoriasis; however, the prevalence of HLA-Cw6 is far lower than HLA-Cw1 in some Asian countries. OBJECTIVES: The aim of this study was to determine whether HLA-Cw1 predisposes psoriasis patients to different treatment responses of biologics and other systemic therapy. METHODS: This retrospective case-control study included 126 patients with moderate to severe plaque-type psoriasis who had been genotyped and treated in a special psoriasis clinic. HLA-Cw1-positive and -negative patients were compared. RESULTS: Our results showed that HLA-Cw1-negative patients were significantly more likely to respond (achieve Psoriasis Area and Severity Index [PASI] 75 after a 12- to 16-week treatment course) to biologics (including etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab; odds ratio [OR] 1.99, 95% confidence interval [CI] 1.17-3.44, p = 0.0122) and especially to ustekinumab (OR 3.27, 95% CI 1.03-11.30; p = 0.0496). An HLA-Cw1 allele dose effect was also found. The results remained after multivariate logistic regression analysis. HLA-Cw1-negative patients also showed significantly greater improvement of PASI in ustekinumab and biologics (p = 0.0044 and p = 0.0064, respectively), with other biologics showing non-significant trends. HLA-Cw1 status did not affect the treatment responses of non-biologic systemic treatment, including phototherapy. CONCLUSION: There is an association between HLA-Cw1 and treatment response to biologics, but not to non-biologics, in our Asian population of patients with moderate to severe psoriasis; however, the exact mechanism and role of HLA-Cw1 remain to be investigated.
Authors: Amy Strange; Francesca Capon; Chris C A Spencer; Jo Knight; Michael E Weale; Michael H Allen; Anne Barton; Gavin Band; Céline Bellenguez; Judith G M Bergboer; Jenefer M Blackwell; Elvira Bramon; Suzannah J Bumpstead; Juan P Casas; Michael J Cork; Aiden Corvin; Panos Deloukas; Alexander Dilthey; Audrey Duncanson; Sarah Edkins; Xavier Estivill; Oliver Fitzgerald; Colin Freeman; Emiliano Giardina; Emma Gray; Angelika Hofer; Ulrike Hüffmeier; Sarah E Hunt; Alan D Irvine; Janusz Jankowski; Brian Kirby; Cordelia Langford; Jesús Lascorz; Joyce Leman; Stephen Leslie; Lotus Mallbris; Hugh S Markus; Christopher G Mathew; W H Irwin McLean; Ross McManus; Rotraut Mössner; Loukas Moutsianas; Asa T Naluai; Frank O Nestle; Giuseppe Novelli; Alexandros Onoufriadis; Colin N A Palmer; Carlo Perricone; Matti Pirinen; Robert Plomin; Simon C Potter; Ramon M Pujol; Anna Rautanen; Eva Riveira-Munoz; Anthony W Ryan; Wolfgang Salmhofer; Lena Samuelsson; Stephen J Sawcer; Joost Schalkwijk; Catherine H Smith; Mona Ståhle; Zhan Su; Rachid Tazi-Ahnini; Heiko Traupe; Ananth C Viswanathan; Richard B Warren; Wolfgang Weger; Katarina Wolk; Nicholas Wood; Jane Worthington; Helen S Young; Patrick L J M Zeeuwen; Adrian Hayday; A David Burden; Christopher E M Griffiths; Juha Kere; André Reis; Gilean McVean; David M Evans; Matthew A Brown; Jonathan N Barker; Leena Peltonen; Peter Donnelly; Richard C Trembath Journal: Nat Genet Date: 2010-10-17 Impact factor: 38.330
Authors: Lam C Tsoi; Philip E Stuart; Chao Tian; Johann E Gudjonsson; Sayantan Das; Matthew Zawistowski; Eva Ellinghaus; Jonathan N Barker; Vinod Chandran; Nick Dand; Kristina Callis Duffin; Charlotta Enerbäck; Tõnu Esko; Andre Franke; Dafna D Gladman; Per Hoffmann; Külli Kingo; Sulev Kõks; Gerald G Krueger; Henry W Lim; Andres Metspalu; Ulrich Mrowietz; Sören Mucha; Proton Rahman; Andre Reis; Trilokraj Tejasvi; Richard Trembath; John J Voorhees; Stephan Weidinger; Michael Weichenthal; Xiaoquan Wen; Nicholas Eriksson; Hyun M Kang; David A Hinds; Rajan P Nair; Gonçalo R Abecasis; James T Elder Journal: Nat Commun Date: 2017-05-24 Impact factor: 14.919