Browsing by Author "Macfarlane, GJ"

Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis
    Li, ZX; Wu, X; Leo, PJ; De Guzman, E; Akkoc, N; Breban, M; Macfarlane, GJ; Mahmoudi, M; Marzo-Ortega, H; Anderson, LK; Wheeler, L; Chou, CT; Harrison, AA; Stebbings, S; Jones, GT; Bang, SY; Wang, G; Jamshidi, A; Farhadi, E; Song, J; Lin, L; Li, MM; Wei, JCC; Martin, NG; Wright, MJ; Lee, M; Wang, YQ; Zhan, J; Zhang, JS; Wang, XB; Jin, ZB; Weisman, MH; Gensler, LS; Ward, MM; Rahbar, MH; Diekman, L; Kim, TH; Reveille, JD; Wordsworth, BP; Xu, HJ; Brown, MA
    Objective We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain. Methods PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), HLA-B27 and sacroiliac MRI. Results In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924.This was significantly better than for HLA-B27 testing alone (AUC=0.869), MRI (AUC=0.885) or C-reactive protein (AUC=0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC=0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with HLA-B27 testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for HLA-B27, these values were 51.9% and 97.9%, respectively. Conclusions PRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or HLA-B27 status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied.
  • No Thumbnail Available
    Item
    European bio-naive spondyloarthritis patients initiating TNF inhibitor: time trends in baseline characteristics, treatment retention and response
    Christiansen, SN; Ornbjerg, LM; Rasmussen, SH; Loft, AG; Askling, J; Iannone, F; Zavada, J; Michelsen, B; Nissen, M; Onen, F; Santos, MJ; Pombo-Suarez, M; Relas, H; Macfarlane, GJ; Tomsic, M; Codreanu, C; Gudbjornsson, B; Van der Horst-Bruinsma, I; Di Giuseppe, D; Glintborg, B; Gremese, E; Pavelka, K; Kristianslund, EK; Ciurea, A; Akkoc, N; Barcelos, A; Sánchez-Piedra, C; Peltomaa, R; Jones, GT; Rotar, Z; Ionescu, R; Grondal, G; Van de Sande, MGH; Laas, K; Ostergaard, M; Hetland, ML
    Objectives To investigate time trends in baseline characteristics and retention, remission and response rates in bio-naive axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating TNF inhibitor (TNFi) treatment. Methods Prospectively collected data on bio-naive axSpA and PsA patients from routine care in 15 European countries were pooled. Three cohorts were defined according to year of TNFi initiation: A (1999-2008), B (2009-2014) and C (2015-2018). Retention, remission and response rates were assessed at 6, 12 and 24 months. Results In total, 27 149 axSpA and 17 446 PsA patients were included. Cohort A patients had longer disease duration compared with B and C. In axSpA, cohort A had the largest proportion of male and HLA-B27 positive patients. In PsA, baseline disease activity was highest in cohort A. Retention rates in axSpA/PsA were highest in cohort A and differed only slightly between B and C. For all cohorts, disease activity decreased markedly from 0 to 6 months. In axSpA, disease activity at 24 months was highest in cohort A, where also remission and response rates were lowest. In PsA, remission rates at 6 and 12 months tended to be lowest in cohort A. Response rates were at all time points comparable across cohorts, and less between-cohort disease activity differences were seen at 24 months. Conclusion Our findings indicate that over the past decades, clinicians have implemented more aggressive treatment strategies in spondyloarthritis. This was illustrated by shorter disease duration at treatment initiation, decreased retention rates and higher remission rates during recent years.