B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study

Arthritis Rheum. 2011 Apr;63(4):933-8. doi: 10.1002/art.30233.

Abstract

Objective: To examine whether serum B cell markers can predict response to rituximab, a B cell-depleting monoclonal antibody, in patients with refractory rheumatoid arthritis (RA).

Methods: This rituximab re-treatment dose study (SMART [eSsai MAbthera sur la dose de Re-Traitement]) involved 208 patients with refractory RA. Serum markers of B cell activation (anti-cyclic citrullinated peptide [anti-CCP] antibodies, rheumatoid factor [RF], serum IgG, IgA, and IgM levels, serum κ and λ free light chains, and serum BAFF) were assessed before the first rituximab cycle (1,000 mg on days 1 and 15). Univariate and multivariate analyses were performed to identify factors associated with a European League Against Rheumatism (EULAR) response at 24 weeks.

Results: There were 149 responders (72%). Two baseline factors were associated with a EULAR response at 24 weeks in multivariate analysis: the presence of anti-CCP antibodies or RF (odds ratio 3.5 [95% confidence interval 1.6-7.6]) and a serum IgG concentration above normal (odds ratio 2.11 [95% confidence interval 1.02-4.33]), with synergy between them (odds ratio 6.0 [95% confidence interval 2.2-16.2]).

Conclusion: The presence of RF or anti-CCP antibodies and elevated IgG are 2 simple biomarkers that can be used routinely before therapy to predict response to rituximab in patients with refractory RA.

Trial registration: ClinicalTrials.gov NCT01126541.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Anti-Idiotypic / blood*
  • Antibodies, Anti-Idiotypic / immunology
  • Antibodies, Monoclonal, Murine-Derived / pharmacology
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / pathology*
  • Biomarkers / blood
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunoglobulin G / blood*
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology*
  • Predictive Value of Tests
  • Rheumatoid Factor / blood*
  • Rituximab
  • Treatment Outcome

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Biomarkers
  • Immunoglobulin G
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Rituximab
  • Rheumatoid Factor

Associated data

  • ClinicalTrials.gov/NCT01126541