title: Modelling the cost-effectiveness of combination therapy for early, rapidly progressing rheumatoid arthritis by simulating the reversible and irreversible effects of the disease.
abstract: OBJECTIVE
  To estimate the cost-effectiveness of adalimumab plus methotrexate (MTX) versus MTX monotherapy in early, aggressive rheumatoid arthritis (RA) when explicitly modelling short-term (reversible) and long-term (irreversible, ie, joint damage) disease activity and physical function.
  
  
  METHODS
  A microsimulation model was developed to unify, in a single cost-effectiveness model, measures of reversible and irreversible disease activity and physical function based on data from the PREMIER trial. Short term, reversible disease activity was modelled using DAS28 variables, including swollen joint counts, tender joint counts, C reactive protein concentration and pain. The DAS28 variables were then used in a logistic regression to predict short-term American College of Rheumatology (ACR) responses, which informed treatment continuation and switches. Long term, irreversible, radiographically documented joint damage was modelled using modified Total Sharp Score (mTSS). The model then linked both short-term disease activity and mTSS to the Health Assessment Questionnaire score, which was used to calculate direct and indirect costs, and quality adjusted life-years (QALYs).
  
  
  RESULTS
  When both reversible and irreversible effects of therapy were included, combination therapy was estimated to produce 6-month 50% ACR responses in 75% of patients versus 54% in MTX monotherapy. Compared to MTX monotherapy, combination therapy resulted in 2.68 and 3.04 discounted life years and QALYs gained, respectively. Combination therapy also resulted in a net increase in direct costs of £106,207 for a resulting incremental cost/QALY gain of £32,425. When indirect costs were included in the analysis, the ICER (incremental cost-effectiveness ratio) decreased to £27,238. Disregarding irreversible effects increased the incremental cost-effectiveness ratio to £78,809 (when only direct costs were included).
  
  
  CONCLUSIONS
  Starting with adalimumab plus MTX combination therapy in early, aggressive RA is cost-effective when irreversible damage is adequately considered.
authors.affiliation: Pharmerit Ltd, York, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Stephens
authors.affiliation: Pharmerit North America, Bethesda, Maryland, USA.
authors.forename: Marc F
authors.initials: MF
authors.lastname: Botteman
authors.affiliation: AbbVie Inc., North Chicago, Illinois, USA.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Cifaldi
authors.affiliation: Pharmerit Ltd, York, UK School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
authors.forename: Ben A
authors.initials: BA
authors.lastname: van Hout
mesh_terms: D000068879:Adalimumab / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D017048:Health Care Costs; D006801:Humans; D007596:Joints / Q000187:drug effects* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D008954:Models, Biological; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D019057:Quality-Adjusted Life Years; D012720:Severity of Illness Index
chemical_list: D018501:Antirheumatic Agents; D002097:C-Reactive Protein; D000068879:Adalimumab; D008727:Methotrexate
keywords: Rheumatoid arthritis; biological therapy; cost-effectiveness; disease-modifying antirheumatic drugs; methotrexate