Abstract
BackgroundThe 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.MethodsPatients 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.ResultsIFNα 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.ConclusionIFNα 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.
Highlights
Rheumatoid arthritis (RA) is a chronic disease characterized by joint inflammation, which if untreated may lead to progressive bone destruction
IFNα protein positivity is associated with doublepositivity for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) To determine the demographic and clinical characteristics of the IFNα protein-positive subgroup, we compared patients who were positive or negative for IFNα protein at baseline
IFNα protein positivity was associated with double-positivity for RF and ACPA, and of IFNαpositive patients, 92% were double-positive for RF and ACPA compared to 57% of IFNα-negative patients
Summary
Rheumatoid arthritis (RA) is a chronic disease characterized by joint inflammation, which if untreated may lead to progressive bone destruction. In RA, the expression of IRG is upregulated in peripheral blood compared to controls [10] and was suggested to associate with disease activity [11] and predict treatment response to tumor necrosis factor inhibitors (TNFi) [12,13,14], interleukin-6 receptor inhibitors (IL-6Ri) [15], and B-cell depletion therapy [16,17,18,19]. In SLE, IFNα protein associated with disease activity and predicted the duration of remission [21], but protein levels of IFNα have previously neither been reliably measured in RA nor related to clinical characteristics or treatment effect. Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect
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