Cost-effectiveness analysis of nilotinib versus imatinib for the treatment of chronic phase philadelphia chromosome positive chronic myeloid leukaemia

Background: Nilotinib is a tyrosine kinase inhibitor (TKI) for the treatment of adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML) in chronic phase. The ENESTnd phase III trial demonstrated that nilotinib has clinical superiority over current standard treatment of first-line imatinib in patients with chronic phase Ph+ CML, on the basis that fewer patients progressed to accelerated phase/blast crisis. Whilst the clinical benefits of nilotinib have been demonstrated, the cost-effectiveness of first-line nilotinib has not been explored.

Aim: To evaluate the cost-effectiveness of first-line nilotinib followed by second-line dasatinib compared to first-line imatinib followed by second-line dasatinib for patients newly diagnosed with chronic phase Ph+ CML.

Methods: A Markov state-transition model based on the 24 month follow-up from the ENESTnd randomised controlled trial was developed to simulate the transitions of a hypothetical cohort of patients over a lifetime. The model estimates when one treatment will fail and hence the patient is switched to an alternative treatment. Patients who discontinue first-line treatment go on to second-line dasatinib. Patients who fail on second-line dasatinib receive stem cell transplantation or HU therapy. Patients transition from chronic phase, to accelerated phase, to blast crisis, to CML-related mortality. Patients may die from other causes at any time. EQ-5D utilities were applied to patients in each health state and utility decrements were estimated for patients experiencing severe (grade 3 and 4) adverse events (AEs) on TKI therapy. Costs (2010/11 Sterling) were estimated from the perspective of the UK National Health Service (NHS) and Personal Social Services (PSS). These include the costs associated with the different drug therapies, stem cell transplantation, routine hospital appointments for administration and monitoring, and treatment for severe AEs. A patient access scheme is available for first-line nilotinib therapy and is included in the analysis. All costs and QALYs were discounted by 3.5% as recommended by NICE. Probabilistic sensitivity analysis (PSA) was conducted to explore the impact of the joint uncertainty of all model parameters on the cost-effectiveness results. Cost-effectiveness was expressed in terms of incremental cost per quality-adjusted life-years (QALYs) gained. Cost-effectiveness acceptability curves (CEACs) were also generated.

Results: The mean undiscounted survival in the nilotinib arm was estimated to be 13.96 years compared to 13.32 years in the imatinib arm. Over a lifetime horizon patients are estimated to gain an additional 0.64 life-years (LYs) and 0.49 quality-adjusted life-years (QALYs) in the nilotinib arm compared to the imatinib arm. Using a discount rate of 3.5% patients are estimated to accrue an additional 0.35 LYs and 0.28 QALYs in the nilotinib arm compared to the imatinib arm. Expected lifetime (discounted) costs in the nilotinib arm were £220,416 compared to £232,941 in the imatinib arm. The nilotinib arm dominates the imatinib arm as it is more effective and less costly.

Conclusions: The results suggest that nilotinib produces improvements in survival and QALYs compared to standard treatment of first-line imatinib and it is likely to offer a cost-effective use of NHS resources.