title: Comparative effectiveness and safety of rituximab versus subsequent anti-tumor necrosis factor therapy in patients with rheumatoid arthritis with prior exposure to anti-tumor necrosis factor therapies in the United States Corrona registry.
abstract: BACKGROUND
  Patients with active rheumatoid arthritis (RA) despite anti-tumor necrosis factor(anti-TNF)agent treatment can switch to either a subsequent anti-TNF agent or a biologic with an alternative mechanism of action, such as rituximab; however, there are limited data available to help physicians decide between these 2 strategies. The objective of this analysis was to examine the effectiveness and safety of rituximab versus a subsequent anti-TNF agent in anti-TNF-experienced patients with RA using clinical practice data from the Corrona registry.
  
  
  METHODS
  Rituximab-naive patients from the Corrona registry with prior exposure to ≥1 anti-TNF agent who initiated rituximab or anti-TNF agents (2/28/2006-10/31/2012) were included. Two cohorts were analyzed: the trimmed population (excluding patients who fell outside the propensity score distribution overlap) and the stratified-matched population (stratified by 1 vs.  ≥2 anti-TNF agents, then matched based on propensity score). The primary effectiveness outcome was achievement of low disease activity (LDA)/remission (Clinical Disease Activity Index ≤10) at 1 year. Secondary outcomes included achievement of modified American College of Rheumatology (mACR) 20/50/70 responses and meaningful improvement (≥0.25) in modified Health Assessment Questionnaire (mHAQ) score at 1 year. New cardiovascular, infectious and cancer events were reported.
  
  
  RESULTS
  Estimates for LDA/remission, mACR response and mHAQ improvement were consistently better for rituximab than for anti-TNF agent users in adjusted analyses. The odds ratio for likelihood of LDA/remission in rituximab versus anti-TNF patients was 1.35 (95% CI, 0.95-1.91) in the trimmed population and 1.54 (95% CI, 1.01-2.35) in the stratified-matched population. Rituximab patients were significantly more likely than anti-TNF patients to achieve mACR20/50 and mHAQ improvement in the trimmed population and mACR20 and mHAQ in the stratified-matched population. The rate of new adverse events per 100 patient-years was similar between groups.
  
  
  CONCLUSIONS
  In anti-TNF-experienced patients with RA, rituximab was associated with an increased likelihood of achieving LDA/remission, mACR response and physical function improvement, with a comparable safety profile, versus subsequent anti-TNF agent users.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01402661 . Registered 25 July 2011.
authors.affiliation: Department of Orthopedics, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA, 01532, USA. leslie.harrold@umassmed.edu.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Harrold
authors.affiliation: Corrona, LLC, 352 Turnpike Rd, Suite 325, Southborough, MA, 01772, USA. GReed@corrona.org.
authors.forename: George W
authors.initials: GW
authors.lastname: Reed
authors.affiliation: Department of Orthopedics, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA, 01532, USA. robert.magner@umassmed.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Magner
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080, USA. shewade.ashwini@gene.com.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Shewade
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080, USA. john.ani@gene.com.
authors.forename: Ani
authors.initials: A
authors.lastname: John
authors.affiliation: Corrona, LLC, 352 Turnpike Rd, Suite 325, Southborough, MA, 01772, USA. JGreenberg@corrona.org.|New York University School of Medicine, 550 1st Ave, New York, NY, 10016, USA. JGreenberg@corrona.org.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Greenberg
authors.affiliation: Albany Medical Center and The Center of Rheumatology, 1367 Washington Ave, Suite 101, Albany, NY, 12206, USA. JKremer@corrona.org.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Kremer
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012042:Registries; D000069283:Rituximab / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014481:United States
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab