title: Reduced-dose rituximab in rheumatoid arthritis: efficacy depends on degree of B cell depletion.
abstract: OBJECTIVE
  Studies comparing 500 mg rituximab and 1,000 mg rituximab doses in rheumatoid arthritis have yielded conflicting data on clinical outcomes, but in all of these studies a subgroup of patients has had excellent responses at the lower dose. Historically, it was considered that rituximab uniformly depleted B cells at both doses. Using highly sensitive assays, we have shown that B cell depletion is variable and predictive of clinical response. Using the same techniques, we undertook the present study to test the hypothesis that the level of B cell depletion, rather than the rituximab dose, determines clinical response.
  
  
  METHODS
  Nineteen patients were treated with two 500-mg infusions of rituximab, and 61 patients were treated with two 1,000-mg infusions of rituximab. Highly sensitive flow cytometry was performed at 0, 2, 6, 14, and 26 weeks. European League Against Rheumatism (EULAR) response rates at 6 months were compared between patients with and those without complete depletion at each dose.
  
  
  RESULTS
  The median B cell count was numerically higher at all time points following therapy in the 500 mg rituximab group. Twenty-five percent of patients in the 500 mg rituximab group had complete depletion at 2 weeks, compared with 49% of those in the 1,000 mg rituximab group. Complete depletion at 2 weeks after treatment with 500 mg rituximab was associated with lower baseline preplasma cell counts (P = 0.047). Most patients responded after either dose, but response was related to B cell depletion. Notably, in the 500 mg rituximab group all patients with complete depletion had a EULAR good response (P = 0.011).
  
  
  CONCLUSIONS
  This pilot study suggests that the degree of B cell depletion, rather than the dose of rituximab, determines clinical response. It may be possible to predict which patients will respond to lower-dose rituximab, and this may allow more cost-effective treatment.
authors.affiliation: National Institute for Health Research Leeds Musculoskeletal Biomedical Research Unit and University of Leeds, Leeds, UK.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Vital
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Rawstron
authors.forename: Shouvik
authors.initials: S
authors.lastname: Dass
authors.forename: Karen
authors.initials: K
authors.lastname: Henshaw
authors.forename: Julie
authors.initials: J
authors.lastname: Madden
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: Dennis
authors.initials: D
authors.lastname: McGonagle
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D011237:Predictive Value of Tests; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D005938:Glucocorticoids; D000069283:Rituximab; D008775:Methylprednisolone; D008727:Methotrexate