Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis: a spin-off study of the NORD-STAR randomized clinical trial

Marit Stockfelt*, Anna Carin Lundell, Merete Lund Hetland, Mikkel Østergaard, Till Uhlig, Marte Schrumpf Heiberg, Espen A. Haavardsholm, Michael T. Nurmohamed, Jon Lampa, Dan Nordström, Kim Hørslev Petersen, Bjorn Gudbjornsson, Gerdur Gröndal, Jonathan Aldridge, Kerstin Andersson, Kaj Blennow, Henrik Zetterberg, Ronald van Vollenhoven, Anna Rudin

*Corresponding author for this work

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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.

Original languageEnglish
Article number189
JournalArthritis Research and Therapy
Volume23
Number of pages11
ISSN1478-6354
DOIs
Publication statusPublished - 13. Jul 2021

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • Anti-Citrullinated Protein Antibodies
  • Antirheumatic Agents/therapeutic use
  • Arthritis, Rheumatoid/diagnosis
  • Autoantibodies
  • Humans
  • Interferon-alpha/therapeutic use
  • Rheumatoid Factor

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