title: An Economic Evaluation of Tofacitinib Treatment in Rheumatoid Arthritis: Modeling the Cost of Treatment Strategies in the United States.
abstract: BACKGROUND
  Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib is approved in the United States for use in adults with moderately to severely active RA and an inadequate response or intolerance to methotrexate.
  
  
  OBJECTIVE
  To (a) evaluate, using an economic model, the treatment costs of an RA strategy including tofacitinib, compared with adalimumab, etanercept, certolizumab and tocilizumab biologic RA treatment strategies, which are commonly prescribed in the United States, and (b) assess the economic impact of monotherapy and combination therapy in patients who had an inadequate response to methotrexate therapy (MTX-IR analysis) and to combination therapy in patients who had an inadequate response to a tumor necrosis factor inhibitor (TNF-IR analysis).
  
  
  METHODS
  A transparent, Excel-based economic model with a decision-tree approach was developed to evaluate costs over a 1- and 2-year time horizon. The model compared tofacitinib 5 mg twice a day (BID) either as monotherapy or in combination with MTX with similarly labeled biologic therapies. Response to treatment was modeled as American College of Rheumatology (ACR) 20/50/70 response. ACR20 represented clinical response and determined whether patients continued therapy. ACR response rates at 6-month intervals were sourced from prescribing information and safety event rates from a published meta-analysis. Following an adverse event or a lack of response to treatment, it was assumed that 75% of patients switched to the next line of treatment (first to abatacept and then to rituximab). The perspective was that of a U.S. payer. Costs were reported in 2015 U.S. dollars and included drug wholesale acquisition costs, monitoring, drug administration, and treatment for minor and serious adverse events. The patient population eligible for treatment was based on the total number of members (i.e., RA and non-RA) in a payer organization; members with RA treated with biologic therapies were estimated using epidemiological data. Sensitivity analyses were conducted to explore the impact of varying key parameters, including treatment-switching probability, product rebate, major rates of adverse drug reaction, and ACR20 rates, on the model outcomes.
  
  
  RESULTS
  Tofacitinib combination therapy after MTX failure was associated with the lowest cost per member per month (PMPM) over a 2-year time frame at $5.53, compared with $6.49 for adalimumab, $6.43 for etanercept, $5.95 for certolizumab, and $5.89 for tocilizumab. Similar savings were observed when all biologics were administered as monotherapy. Tofacitinib combination therapy was also associated with the lower PMPM cost compared with adalimumab combination therapy in the TNF-IR analysis. Tofacitinib was also among the lowest cost per ACR20 responder in each analysis. Sensitivity analyses demonstrated that tofacitinib would potentially be cost saving even in the least optimistic scenarios.
  
  
  CONCLUSIONS
  This analysis suggests that tofacitinib 5 mg BID following MTX failure is a lower cost per patient treatment option when used either as monotherapy or combination therapy, compared with adalimumab, etanercept, certolizumab and tocilizumab biologic regimens. Tofacitinib + MTX in TNF-IR patients was also predicted to be a lower-cost treatment option compared with adalimumab+MTX and was associated with the lowest cost per ACR 20/50/70 responder.
  
  
  BACKGROUND
  This study was funded by Pfizer, which determined the research topic and paid York Health Economics Consortium to develop the analysis and conduct the research. York Health Economics Consortium has received consultancy fees from Pfizer. Gerber, Wallenstein, Mendelsohn, Bourret, Singh, and Moynagh are employees and shareholders of Pfizer. Editorial support was funded by Pfizer and was provided by Claxton, Jenks, and Taylor, who are employees of York Health Economics Consortium. Study concept and design were contributed primarily by Taylor, Jenks, Gerber, and Singh, along with the other authors. Gerber, Moynagh, and Singh collected the data, assisted by Bouret and Mendelsohn; data interpretation was performed by Claxton, Gerber, Bouret, and Mendelsohn. The manuscript was written primarily by Claxton, with assistance from the other authors, and revised by Claxton, Gerber, Bouret, and Mendelsohn, with assistance from the other authors.
authors: 1 York Health Economics Consortium, University of York, United Kingdom.
authors: Lindsay
authors: L
authors: Claxton
authors: 1 York Health Economics Consortium, University of York, United Kingdom.
authors: Michelle
authors: M
authors: Jenks
authors: 1 York Health Economics Consortium, University of York, United Kingdom.
authors: Matthew
authors: M
authors: Taylor
authors: 2 Pfizer, Groton, Connecticut.
authors: Gene
authors: G
authors: Wallenstein
authors: 3 Pfizer, Collegeville, Pennsylvania.
authors: Alan M
authors: AM
authors: Mendelsohn
authors: 3 Pfizer, Collegeville, Pennsylvania.
authors: Jeffrey A
authors: JA
authors: Bourret
authors: 3 Pfizer, Collegeville, Pennsylvania.
authors: Amitabh
authors: A
authors: Singh
authors: 3 Pfizer, Collegeville, Pennsylvania.
authors: Dermot
authors: D
authors: Moynagh
authors: 2 Pfizer, Groton, Connecticut.
authors: Robert A
authors: RA
authors: Gerber
mesh_terms: D018501:Antirheumatic Agents / Q000191:economics* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000191:economics*; D003362:Cost-Benefit Analysis / Q000379:methods*; D006801:Humans; D018803:Models, Economic; D010880:Piperidines / Q000191:economics* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000191:economics* / Q000627:therapeutic use; D011743:Pyrimidines / Q000191:economics* / Q000627:therapeutic use; D011758:Pyrroles / Q000191:economics* / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib