Biomarkers of good EULAR response to the B cell depletion therapy in all seropositive rheumatoid arthritis patients: clues for the pathogenesis

PLoS One. 2012;7(7):e40362. doi: 10.1371/journal.pone.0040362. Epub 2012 Jul 30.

Abstract

Objective: To find out whether a high number of auto-antibodies can increase the probability of a "good-EULAR response" and to identify the possible biomarkers of response in seropositive rheumatoid arthritis (RA) patients undergoing the B cell depletion therapy (BCDT).

Patients and methods: One hundred and thirty-eight patients with long standing RA (LSRA), 75% non or poorly responsive to one or more TNFα blockers, all seropositive for at least one autoantibody (AAB) (RF-IgM, RF-IgA, RF-IgG, anti-MCV, ACPA-IgG, ACPA-IgA, ACPA-IgM) received one full course of BCDT. The major outcomes (moderate or good-EULAR response) were assessed after 6 months of therapy. The IL6 and BAFF levels were also determined.

Results: At a 6-month follow-up, 33 (23.9%) of the RA patients achieved a good EULAR response. Having up to 5-AABs positivity increased the chances for treatment response. After a logistic regression analysis, however, only 4 baseline factors arose as associated with a good-EULAR response: no steroid therapy (OR = 6.25), a lymphocyte count <1875/uL (OR = 10.74), a RF-IgG level >52.1 IU/ml (OR = 8.37) and BAFF levels <1011 pg/ml (OR = 7.38). When all the AABs, except for RF-IgM and ACPA-IgG, were left in the analysis, the two final predictors were no-steroid therapy and low lymphocyte count.

Discussion: The number of AABs increased the chances of being a "good-EULAR" responder. The only predictors, however, at the baseline of a good response in this seropositive cohort of RA patients were 2 simple variables--no steroids and lymphocyte count--and two laboratory assays--IgG-RF and BAFF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antirheumatic Agents / therapeutic use
  • Area Under Curve
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / therapy*
  • Autoantibodies / blood
  • B-Cell Activating Factor / blood*
  • B-Lymphocytes
  • Biomarkers / blood
  • Female
  • Humans
  • Interleukin-6 / blood*
  • Logistic Models
  • Lymphocyte Depletion*
  • Male
  • Middle Aged
  • ROC Curve
  • Retrospective Studies
  • Rituximab
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Autoantibodies
  • B-Cell Activating Factor
  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • TNFSF13B protein, human
  • Rituximab

Grants and funding

This study was supported by Hoffmann-La Roche, Genentech, Inc. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.