Marit Stockfelt1,2, Anna-Carin Lundell3, Merete Lund Hetland4,5, Mikkel Østergaard4,5, Till Uhlig6, Marte Schrumpf Heiberg6, Espen A Haavardsholm6,7, Michael T Nurmohamed8,9, Jon Lampa10, Dan Nordström11, Kim Hørslev Petersen12,13, Bjorn Gudbjornsson14,15, Gerdur Gröndal14,15, Jonathan Aldridge3, Kerstin Andersson3, Kaj Blennow16,17, Henrik Zetterberg16,17,18,19, Ronald van Vollenhoven9,10, Anna Rudin3,20. 1. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Guldhedsgatan 10A, S-405 30, Gothenburg, Sweden. marit.stockfelt@gu.se. 2. Rheumatology Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden. marit.stockfelt@gu.se. 3. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Guldhedsgatan 10A, S-405 30, Gothenburg, Sweden. 4. Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark. 5. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 6. Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway. 7. Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 8. Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands. 9. Department of Rheumatology and Amsterdam Rheumatology Center, Amsterdam University Medical Centres, Amsterdam, The Netherlands. 10. Department of Medicine, Rheumatology Unit, Center for Molecular Medicine (CMM), Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden. 11. Department of Medicine and Rheumatology, Helsinki University and University Hospital, Helsinki, Finland. 12. Danish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg, Denmark. 13. Department of Regional Health Research, University of Southern Denmark, Odense, Denmark. 14. Centre for Rheumatology Research, Landspitali University Hospital, Reykjavik, Iceland. 15. Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 16. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. 17. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 18. UK Dementia Research Institute at UCL, London, UK. 19. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. 20. Rheumatology Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden.
Abstract
BACKGROUND: The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. METHODS:Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. RESULTS:IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. CONCLUSION:IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, https://clinicaltrials.gov/ct2/show/NCT01491815 .
RCT Entities:
BACKGROUND: The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. METHODS:Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. RESULTS:IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. CONCLUSION:IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, https://clinicaltrials.gov/ct2/show/NCT01491815 .
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