title: Cost-effectiveness of abatacept, rituximab, and TNFi treatment after previous failure with TNFi treatment in rheumatoid arthritis: a pragmatic multi-centre randomised trial.
abstract: BACKGROUND
  For patients with rheumatoid arthritis (RA) whose treatment with a tumour necrosis factor inhibitor (TNFi) is failing, several biological treatment options are available. Often, another TNFi or a biological with another mode of action is prescribed. The objective of this study was to compare the effectiveness and cost-effectiveness of three biologic treatments with different modes of action in patients with RA whose TNFi therapy is failing.
  
  
  METHODS
  We conducted a pragmatic, 1-year randomised trial in a multicentre setting. Patients with active RA despite previous TNFi treatment were randomised to receive abatacept, rituximab or a different TNFi. The primary outcome (Disease Activity Score in 28 joints) and the secondary outcomes (Health Assessment Questionnaire Disability Index and 36-item Short Form Health Survey scores) were analysed using linear mixed models. Cost-effectiveness was analysed on the basis of incremental net monetary benefit, which was based on quality-adjusted life-years (calculated using EQ-5D scores), and all medication expenditures consumed in 1 year. All analyses were also corrected for possible confounders.
  
  
  RESULTS
  Of 144 randomised patients, 5 were excluded and 139 started taking abatacept (43 patients), rituximab (46 patients) or a different TNFi (50 patients). There were no significant differences between the three groups with respect to multiple measures of RA outcomes. However, our analysis revealed that rituximab therapy is significantly more cost-effective than both abatacept and TNFi over a willingness-to-pay range of 0 to 80,000 euros.
  
  
  CONCLUSIONS
  All three treatment options were similarly effective; however, when costs were factored into the treatment decision, rituximab was the best option available to patients whose first TNFi treatment failed. However, generalization of these costs to other countries should be undertaken carefully.
  
  
  BACKGROUND
  Netherlands Trial Register number NTR1605. Registered 24 December 2008.
authors.affiliation: Department of IQ Healthcare, Radboud Institute for Health Sciences, Radboud University Medical Centre, Postbus 9101, Geert Grooteplein Noord 21 (Route 114), 6500 HB, Nijmegen, Netherlands. sofie.manders@radboudumc.nl.
authors.forename: Sofie H M
authors.initials: SH
authors.lastname: Manders
authors.affiliation: Department of Health Evidence, Radboud University Medical Centre, Nijmegen, Netherlands. wietske.kievit@radboudumc.nl.
authors.forename: Wietske
authors.initials: W
authors.lastname: Kievit
authors.affiliation: Department of Health Evidence, Radboud University Medical Centre, Nijmegen, Netherlands. eddy.adang@radboudumc.nl.
authors.forename: Eddy
authors.initials: E
authors.lastname: Adang
authors.affiliation: Department of Rheumatology, TweeSteden Hospital, Dr. Deelenlaan 5, Tilburg, 5042, AD, Netherlands. hbrus@tsz.nl.
authors.forename: Herman L
authors.initials: HL
authors.lastname: Brus
authors.affiliation: Department of Rheumatology, Ziekenhuisgroep Twente, Zilvermeeuw 1, Almelo, 7609 PP, Netherlands. h.moens@zgt.nl.
authors.forename: Hein J Bernelot
authors.initials: HJ
authors.lastname: Moens
authors.affiliation: Department of Rheumatology, Jeroen Bosch Hospital, Henri Dunantstraat 1, 's-Hertogenbosch, 5223, GZ, Netherlands. a.hartkamp@jbz.nl.
authors.forename: Andre
authors.initials: A
authors.lastname: Hartkamp
authors.affiliation: Department of Rheumatology, Medical Centre Leeuwarden, Henri Dunantweg 2, Leeuwarden, 8934, AD, Netherlands. l.hendriks@znb.nl.
authors.forename: Lidy
authors.initials: L
authors.lastname: Hendriks
authors.affiliation: Department of Rheumatology, University Medical Centre Groningen, Hanzeplein 1, Groningen, 9700, RB, Netherlands. e.brouwer@umcg.nl.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brouwer
authors.affiliation: Department of Rheumatology, Rijnstate Hospital, Postbus 9555, Arnhem, 6800, TA, Netherlands. hvisser@alysis.nl.
authors.forename: Henk
authors.initials: H
authors.lastname: Visser
authors.affiliation: Department of Rheumatology and Clinical Immunology, Medisch Spectrum Twente, Haaksbergerstraat 55, Enschede, 7513, ER, Netherlands. h.vonkeman@mst.nl.
authors.forename: Harald E
authors.initials: HE
authors.lastname: Vonkeman
authors.affiliation: Department of Rheumatic Diseases, Radboud University Medical Centre, Nijmegen, Netherlands. jos.hendrikx@radboudumc.nl.
authors.forename: Jos
authors.initials: J
authors.lastname: Hendrikx
authors.affiliation: Department of Rheumatic Diseases, Radboud University Medical Centre, Nijmegen, Netherlands. tim.jansen@radboudumc.nl.
authors.forename: Tim L
authors.initials: TL
authors.lastname: Jansen
authors.affiliation: Skeletal Biology and Engineering Research Centre, Department of Development and Regeneration, KU Leuven, Oude Markt 13, Leuven, 3000, Belgium. rene.westhovens@uzleuven.be.|Department of Rheumatology, University Hospitals Leuven, Oude Markt 13, Leuven, 3000, Belgium. rene.westhovens@uzleuven.be.
authors.forename: Rene
authors.initials: R
authors.lastname: Westhovens
authors.affiliation: Department of Rheumatology and Clinical Immunology, Medisch Spectrum Twente, Haaksbergerstraat 55, Enschede, 7513, ER, Netherlands. m.vandelaar@mst.nl.
authors.forename: Mart A F J
authors.initials: MA
authors.lastname: van de Laar
authors.affiliation: Department of IQ Healthcare, Radboud Institute for Health Sciences, Radboud University Medical Centre, Postbus 9101, Geert Grooteplein Noord 21 (Route 114), 6500 HB, Nijmegen, Netherlands. piet.vanriel@radboudumc.nl.
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: van Riel
mesh_terms: D000069594:Abatacept / Q000191:economics / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000191:economics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D003362:Cost-Benefit Analysis; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069283:Rituximab / Q000191:economics / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D000069594:Abatacept