This BIA estimated the impact of biosimilar infliximab on the healthcare budget over a 3-year time frame in six CEE countries. The model was constructed in compliance with the principles of good practice for BIA from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) [3]. The perspective of analysis was that of a third party payer.
Modelling framework
A prevalence-based, country-specific budget impact model was developed for RA. The budget impact model evaluated the impact of introducing biosimilar infliximab into the current treatment mix of biological drugs available for the treatment of RA in the six countries by comparing total costs (drug, administration and monitoring) of scenarios where biosimilar infliximab is introduced (BSc1 and BSc2) to the total costs of the RSc (where no biosimilar agent is available). Since there is a great uncertainty in policy discussions around interchanging originator infliximab with biosimilar infliximab (see the paper of Tóthfalusi et al. [8] in this supplement) we decided to explore the budget impact in two extreme scenarios:
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Biosimilar scenario 1 (BSc1) Interchanging originator infliximab with biosimilar infliximab is disallowed. Only patients who start a new biological therapy are allowed to use biosimilar infliximab.
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Biosimilar scenario 2 (BSc2) Interchanging of originator infliximab with biosimilar infliximab is allowed after 6 months from treatment start, and originator infliximab is interchanged by biosimilar infliximab in 80 % of patients. Also patients who start a new biological therapy are allowed to receive biosimilar infliximab as first-line therapy.
The model tracked the movement of patients between different biological treatments. At the end of each model cycle, patients could either remain on the original treatment, or switch to another biological treatment, or leave the model (switch to a conventional synthetic disease modifying antirheumatic drug [csDMARD] therapy). The model functioned in quarter-year time cycles according to a 3-month-long evaluation period. The number of RA patients treated with biological agents in any quarter year was the sum of the population in the previous quarter year and the estimated growth. The number of patients starting new biologic treatment (first drug or switch) was the sum of discontinuations from all causes in the previous quarter year and the estimated growth. New patients receiving biological drugs exactly compensated for patients exiting the model.
Total costs of scenarios were estimated as the aggregation of the product of patients in different model states and costs associated with these states. Incremental costs were calculated as the difference of BScs (BSc1 and BSc2) and RSc. Cost savings are reported in 2013 prices; no discounting was applied. Besides cost savings in monetary terms, we also provide estimations for gains in terms of possible number of new patients who could be treated additionally if the savings were reinvested in additional biosimilar infliximab treatment.
Patient population
The size of initial populations (Table 1) in both the reference (RSc) and the two BScs (BSc1 and Bsc2) were set on the basis of real 2013 penetration data in the six CEE countries (i.e. the number of patients with RA treated with different biological drugs in 2013). The number of RA patients in the six countries treated with abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab and tocilizumab were 153, 4,055, 1,376, 4,197, 860, 1,643, 3,098 and 1,944, respectively [9]. The model also accounted for the possibility of patient number expansion. A future growth rate of treated patients was assumed to predict the number of treated patients over the 3 years. Also, budget impact estimates included calculations on the numbers of previously untreated patients who started new biological drugs. We made no restriction on the number of potential patients. We only assumed that growth in the number of patients treated with biological drug would not exceed the number of patients eligible for biological therapy on a 3-year time horizon.
Costs associated with model states
Only direct costs of the drug treatment were considered, including the acquisition costs of drugs, the cost of administration and the cost of treatment-related monitoring (laboratory test, rheumatology visits, X-ray, cardiology and pulmonology monitoring). The model accounted for those biological agents that are reimbursed in a given country for the treatment of RA (Table 2).
Table 2 Retail prices of biological treatments in €
Drug acquisition costs were derived from official national price lists in each country. We used retail prices for the analysis. Retail price of biosimilar infliximab was assumed as 75 % of originator infliximab in all six countries. Drug acquisition costs were calculated on a quarterly basis for both the induction and maintenance periods for each drug (Table 3). The doses and administration schedules for each biological agent were those provided by the European Medicines Agency summaries of product characteristics. The calculation took into account both induction and maintenance dosing schedule in the case of infliximab, certolizumab and abatacept. For these drugs, different dosing schedules were used in the first and the subsequent quarter after starting the treatment. Furthermore, the dosage of some biological drugs (infliximab, abatacept and tocilizumab) depends on body weight. The average body weight of an RA patient was estimated at 75 kg (SD17), based on Hungarian survey among patients treated with infliximab [10]. If a full package is not used for one patient, the rest of the dosage might or might not be used for others. The latter is considered as waste. We assumed that the rest of a dosages was administered to the next patient.
Table 3 Quarterly drug costs in rheumatoid arthritis, in euros
Monitoring and administration costs were estimated according to clinical guidelines. Tariffs from the National Health Insurance Fund Administrations (NHIFA) were used to assess monitoring (outpatient visits, lab tests, imaging) and administration (visits to nurse, outpatients visit) costs. In the case of unavailable price data in a country, Hungarian tariffs were converted to estimate these costs.
Assumptions in model
Movements between model states
Based on the results of a previous review [11], we assumed that the 3-month discontinuation probability is 0.049 % for all treatments. The probabilities that a given biological drug will be selected as second-line treatment are presented in Table 1. These rates were derived from the Hungarian NHIFA database [10] and were applied to each of the six countries.
Infliximab biosimilar as first-line and second-line treatment
We assumed that in 65 % of the cases when originator infliximab would have been selected as a first-line or second-line treatment, the physician would prescribe biosimilar infliximab. Also, an assumption was made that in 25 % of the cases when a non-infliximab tumour necrosis factor inhibitor (TNF-inhibitor, namely adalimumab, certolizumab, etanercept and golimumab) would have been selected as a first-line or second-line treatment, the physician would prescribe biosimilar infliximab (linearly reaching these percentages until the end of the first year, and remaining until the end of the third year).
Interchanging
The rate of interchanging originator infliximab treatment with biosimilar infliximab treatment is 0 % in BSc1 and 80 % in BSc2 (linearly reaching 80 % until the end of the first year, and remaining until the end of the third year). BSc1, when interchangeability is not allowed at all, is the strictest possible option, while BSc2 is a potential extreme case, with 80 % replacement of originator by biosimilar (e.g., in an extreme situation where the payer would oblige providers to replace the originator treatment).
Sensitivity analysis
One-way sensitivity analysis was performed by changing different parameters of the model by ±10 %: the assumption on the acquisition cost of biosimilar infliximab, the size of the initial population and its growth rate over time, the discontinuation rates of biological drugs, and the rate of interchanging infliximab with biosimilar infliximab.