title: Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed: pooled data from 10 European registries.
abstract: OBJECTIVE
  To assess the 6-month effectiveness of the first rituximab (RTX) course in rheumatoid arthritis (RA) and to identify possible predictors of response.
  
  
  METHODS
  10 European registries submitted anonymised datasets (baseline, 3- and 6-month follow-up) from patients with RA who had started RTX, and datasets were pooled and analysed. Heterogeneity between countries was analysed by analysis of variance. Predictors of response were identified by logistic regression.
  
  
  RESULTS
  2019 patients were included (mean age/disease duration 53.8/12.1 years, 80.3% female, 85.6% rheumatoid factor (RF) positive and 76.8% (456/594 patients) anti-cyclic citrullinated peptide antibodies (anti-CCP) positive). For these patients an average of 2.7 disease-modifying antirheumatic drugs (DMARDs) (range 0-10) had failed, and RTX was given as the first biological agent in 36.6% of patients. There was significant heterogeneity between countries for several baseline characteristics, including the number of previous biological agents. Disease Activity Score based on 28 joint counts (DAS28) decreased from 5.8±1.4 at baseline to 4.2±1.4 at 6 months (p<0.0001) and 22.2%/42.5% achieved European League Against Rheumatism (EULAR) good/moderate response. Larger 6-month improvement in DAS28 was observed in RF-positive and anti-CCP-positive versus seronegative patients. The following predictors of EULAR good response at 6 months were identified in a multivariate analysis: anti-CCP positivity (OR=2.86, p=0.003), number of previous DMARDs (OR=0.84, p=0.06), ≤1 previous biological agents (OR=1.89, p=0.04), baseline DAS28 level (OR=0.74, p=0.003).
  
  
  CONCLUSIONS
  In this large observational cohort of patients with RA treated with RTX, seropositive patients achieved significantly greater reductions in DAS28 at 6 months than seronegative patients. Effectiveness was best when RTX was used as the first biological agent or after failure of no more than one anti-tumour necrosis factor agent.
authors.affiliation: Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden. aikaterini.chatzidionysiou@karolinska.se
authors.forename: Katerina
authors.initials: K
authors.lastname: Chatzidionysiou
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lie
authors.forename: Evgeny
authors.initials: E
authors.lastname: Nasonov
authors.forename: Galina
authors.initials: G
authors.lastname: Lukina
authors.forename: Merete Lund
authors.initials: ML
authors.lastname: Hetland
authors.forename: Ulrik
authors.initials: U
authors.lastname: Tarp
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: van Riel
authors.forename: Dan C
authors.initials: DC
authors.lastname: Nordström
authors.forename: Juan
authors.initials: J
authors.lastname: Gomez-Reino
authors.forename: Karel
authors.initials: K
authors.lastname: Pavelka
authors.forename: Matija
authors.initials: M
authors.lastname: Tomsic
authors.forename: Tore K
authors.initials: TK
authors.lastname: Kvien
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004341:Drug Evaluation / Q000379:methods; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D011379:Prognosis; D012217:Rheumatoid Factor / Q000097:blood; D000069283:Rituximab; D017211:Treatment Failure; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D000069283:Rituximab; D012217:Rheumatoid Factor