{
  "abstract": "Background For rheumatoid arthritis (RA), the HLA-DRB1 ‘shared epitope’ (SE) allele has been proposed as a predictive biomarker for the effectiveness of mainly abatacept and other biologic disease-modifying antirheumatic drugs (bDMARDs).Objective To explore the relative impact of SE positivity on the effectiveness of different bDMARDs in European patients with RA.Methods Nested cohort study in the Swiss (Swiss Clinical Quality Management) and Danish (DANBIO) rheumatology registries. Patients with RA who initiated bDMARD treatment and had available DNA samples to define SE were included. Four bDMARD groups were defined: abatacept, tumour necrosis factor inhibitors (TNFi), rituximab, tocilizumab. Patients were matched 1:1 using propensity scores and the effectiveness compared between patients being SE positive versus SE negative. For sensitivity, the number of SE alleles was included. Primary end point was treatment retention (crude by SE status, adjusted Cox regression analyses including relevant covariates). Secondary end points were low disease activity (LDA) and remission (1, 2 years).Results Of the 5248 treatment courses initially identified, 464 patients in each of the four bDMARD groups were matched (SE negative: 31%, one SE allele: 48%, two alleles: 21%). For all bDMARD groups, crude 1-year treatment retention was unaffected by SE status. Cox regression analyses showed non-significant HRs for SE-positive versus SE-negative patients: abatacept 0.99 (95% CI 0.71 to 1.38), TNFi 1.01 (0.66 to 1.54), rituximab 1.14 (0.71 to 1.84), tocilizumab 1.48 (0.92 to 2.40). LDA and remission rates were unaffected by SE status for all four bDMARDs. Sensitivity analyses showed similar results.Conclusion In the current study, the SE was not associated with bDMARD effectiveness in patients with RA of mainly European ancestry.",
  "authors": [
    {
      "affiliations": [
        "Division of Rheumatology, Geneva University Hospitals, Geneva, Switzerland",
        "Geneva Center for Inflammation Research (GCIR), University of Geneva, Geneva, Switzerland",
        "SCQM Biobank Study Group, SCQM Registry, Foundation SCQM, Zürich, Switzerland"
      ],
      "name": "Axel Finckh"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Geneva University Hospitals, Geneva, Switzerland"
      ],
      "name": "Delphine S Courvoisier"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Geneva University Hospitals, Geneva, Switzerland"
      ],
      "name": "Romain Aymon"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Geneva University Hospitals, Geneva, Switzerland"
      ],
      "name": "Denis Mongin"
    },
    {
      "affiliations": [
        "Amgen deCODE genetics, Reykjavik, Iceland",
        "Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland"
      ],
      "name": "Saedis Saevarsdottir"
    },
    {
      "affiliations": [
        "Amgen deCODE genetics, Reykjavik, Iceland",
        "Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland"
      ],
      "name": "Ingileif Jonsdottir"
    },
    {
      "affiliations": [
        "Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland"
      ],
      "name": "Kari Stefansson"
    },
    {
      "affiliations": [
        "DANBIO Registry, Danish Rheumatologic Biobank and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Rigshospitalet Glostrup, Glostrup, Denmark",
        "Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"
      ],
      "name": "Merete Lund Hetland"
    },
    {
      "affiliations": [
        "Division of Rheumatology and Immunology and Allergology, Inselspital Universitatsspital Bern, Bern, Switzerland"
      ],
      "name": "Burkhard Moeller"
    },
    {
      "affiliations": [
        "Geneva Center for Inflammation Research (GCIR), University of Geneva, Geneva, Switzerland",
        "Plateforme des laboratoires de thérapie cellulaire et de transplantation, Geneva University Hospitals, Geneva, Switzerland"
      ],
      "name": "Jean Villard"
    },
    {
      "affiliations": [
        "Geneva Center for Inflammation Research (GCIR), University of Geneva, Geneva, Switzerland"
      ],
      "name": "Kim Lauper"
    },
    {
      "affiliations": [
        "SCQM Biobank Study Group, SCQM Registry, Foundation SCQM, Zürich, Switzerland"
      ],
      "name": "the Danish Rheumatologic Biobank Study Group"
    },
    {
      "affiliations": [
        "SCQM Biobank Study Group, SCQM Registry, Foundation SCQM, Zürich, Switzerland"
      ],
      "name": "the SCQM Biobank Study Group"
    },
    {
      "affiliations": [
        "DANBIO Registry, Danish Rheumatologic Biobank and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Rigshospitalet Glostrup, Glostrup, Denmark",
        "Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"
      ],
      "name": "Bente Glintborg"
    }
  ],
  "title": "Influence of the shared epitope on the effectiveness of biologic antirheumatic agents in European patients with rheumatoid arthritis",
  "uid": "fd1a9dd7-8c21-5650-b84d-38d082bb9821"
}