Relationship Between the Type I Interferon Signature and the Response to Rituximab in Rheumatoid Arthritis Patients

Arthritis Rheum. 2010 Dec;62(12):3607-14. doi: 10.1002/art.27702.

Abstract

Objective: To analyze the relationship between the type I interferon (IFN) signature and clinical response to rituximab in rheumatoid arthritis (RA) patients.

Methods: Twenty RA patients were treated with rituximab (cohort 1). Clinical response was defined as a decrease in the Disease Activity Score evaluated in 28 joints (DAS28) and as a response according to the European League Against Rheumatism (EULAR) criteria at week 12 and week 24. The presence of an IFN signature was analyzed in peripheral blood mononuclear cells by measuring the expression levels of 3 IFN response genes by quantitative polymerase chain reaction analysis. After comparison with the findings in healthy controls, patients were classified as having an IFN high or an IFN low signature. The data were confirmed in a second independent cohort (n = 31). Serum IFNα bioactivity was analyzed using a reporter assay.

Results: In cohort 1, there was a better clinical response to rituximab in the IFN low signature group. Consistent with these findings, patients with an IFN low signature had a significantly greater reduction in the DAS28 and more often achieved a EULAR response at weeks 12 and 24 as compared with the patients with an IFN high signature in cohort 2 versus cohort 1. The pooled data showed a significantly stronger decrease in the DAS28 in IFN low signature patients at weeks 12 and 24 as compared with the IFN high signature group and a more frequent EULAR response at week 12. Accordingly, serum IFNα bioactivity at baseline was inversely associated with the clinical response, although this result did not reach statistical significance.

Conclusion: The type I IFN signature negatively predicts the clinical response to rituximab treatment in patients with RA. This finding supports the notion that IFN signaling plays a role in the immunopathology of RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy*
  • Biomarkers / blood
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Humans
  • Interferon Type I / blood*
  • Interferon-alpha / blood
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Rituximab
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Biomarkers
  • Interferon Type I
  • Interferon-alpha
  • Rituximab