title: B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study.
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]).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hôpital Bicêtre, Assistance Publique Hôpitaux de Paris, Le Kremlin Bicêtre, France. jeremie.sellam@sat.aphp.fr
authors.forename: Jérémie
authors.initials: J
authors.lastname: Sellam
authors.forename: Houria
authors.initials: H
authors.lastname: Hendel-Chavez
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Rouanet
authors.forename: Karim
authors.initials: K
authors.lastname: Abbed
authors.forename: Bernard
authors.initials: B
authors.lastname: Combe
authors.forename: Xavier
authors.initials: X
authors.lastname: Le Loët
authors.forename: Jacques
authors.initials: J
authors.lastname: Tebib
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.forename: Yassine
authors.initials: Y
authors.lastname: Taoufik
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
mesh_terms: D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood* / Q000276:immunology; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology*; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011237:Predictive Value of Tests; D012217:Rheumatoid Factor / Q000097:blood*; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000888:Antibodies, Anti-Idiotypic; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D015415:Biomarkers; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D000069283:Rituximab; D012217:Rheumatoid Factor