title: Cost-effectiveness of adding novel or group 5 interventions to a background regimen for the treatment of multidrug-resistant tuberculosis in Germany.
abstract: Treatment of multidrug-resistant tuberculosis (MDR-TB) is complex, lengthy, and involves a minimum of four drugs termed a background regimen (BR), that have not previously been prescribed or that have proven susceptible to patient sputum culture isolates. In recent years, promising new treatment options have emerged as add-on therapies to a BR. The aim of this study was to evaluate the long-term costs and effectiveness of adding the novel or group 5 interventions bedaquiline, delamanid, and linezolid to a background regimen (BR) of drugs for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis (MDR-TB), within their marketing authorisations, from a German healthcare cost-effectiveness perspective.
  
  
  
  A cohort-based Markov model was developed to simulate the incremental cost-effectiveness ratio of bedaquiline plus BR, delamanid plus BR, or linezolid plus BR versus BR alone in the treatment of MDR-TB, over a 10-year time horizon. Effectiveness of treatment was evaluated in Quality-Adjusted Life-Years (QALYs) and Life-Years Gained (LYG), using inputs from clinical trials for bedaquiline and delamanid and from a German observational study for linezolid. Cost data were obtained from German Drug Directory costs (€/2015), published literature, and expert opinion. A 3% yearly discount rate was applied. Probabilistic and deterministic sensitivity analyses were conducted.
  
  
  
  The total discounted costs per-patient were €85,575 for bedaquiline plus BR, €81,079 for delamanid plus BR, and €80,460 for linezolid plus BR, compared with a cost of €60,962 for BR alone. The total discounted QALYs per-patient were 5.95 for bedaquiline plus BR, 5.36 for delamanid plus BR, and 3.91 for linezolid plus BR, compared with 3.68 for BR alone. All interventions were therefore associated with higher QALYs and higher costs than BR alone, with incremental costs per QALY gained of €22,238 for bedaquiline, €38,703 for delamanid, and €87,484 for linezolid, versus BR alone. In a fully incremental analysis, bedaquiline plus BR was the most cost-effective treatment option at thresholds greater than €22,000 per QALY gained. In probabilistic analyses, the probability that bedaquiline plus BR was the most cost-effective treatment strategy at a willingness-to-pay threshold of €30,000 was 54.5%, compared with 22.9% for BR alone, 18.2% for delamanid plus BR, and 4.4% for linezolid.
  
  
  
  In Germany, the addition of bedaquiline, delamanid, or linezolid to a BR would result in QALY gains over BR alone. Based on this analysis, bedaquiline is likely to be the most cost-effective intervention for the treatment of MDR-TB, when added to a BR regimen at thresholds greater than €22,000 per QALY.
authors.affiliation: Health Economics & Market Access, Janssen-Cilag GmbH, Johnson & Johnson Platz 1, 41470, Neuss, Germany. dwirth2@its.jnj.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wirth
authors.affiliation: Janssen-Cilag Ltd, High Wycombe, UK.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Dass
authors.affiliation: PAREXEL International, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Hettle
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000191:economics / Q000627:therapeutic use*; D002985:Clinical Protocols; D002986:Clinical Trials as Topic; D003362:Cost-Benefit Analysis; D064687:Diarylquinolines / Q000191:economics / Q000627:therapeutic use; D016527:Drug Costs; D004359:Drug Therapy, Combination; D005260:Female; D005858:Germany; D006801:Humans; D000069349:Linezolid / Q000191:economics / Q000627:therapeutic use; D008297:Male; D009593:Nitroimidazoles / Q000191:economics / Q000627:therapeutic use; D064887:Observational Studies as Topic; D010080:Oxazoles / Q000191:economics / Q000627:therapeutic use; D019057:Quality-Adjusted Life Years; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000191:economics; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000191:economics
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; D009593:Nitroimidazoles; C516022:OPC-67683; D010080:Oxazoles; C493870:bedaquiline; D000069349:Linezolid
keywords: Bedaquiline; Cost-effectiveness; Delamanid; ICER; LYG; Linezolid; Multidrug-resistant tuberculosis; QALY