A systematic review of the effectiveness of adalimumab

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Appendix 8
TABLE 86 Kobelt et al., 2005 167
Authors Kobelt, Lindgren, Singh, Klareskog
Date 2005
Type of economic evaluation Cost–utility analysis
Country of origin Sweden, France, USA
Currency used Euros
Year to which costs apply 2004
Perspective Societal
Study population Patients with active RA who failed to respond to at least two DMARDs, other than MTX.
Patients who had been previously exposed to MTX were included provided they were
deemed to be appropriate candidates for MTX treatment at the time of enrolment to the
study
Intervention 1 Etanercept
Intervention 2 MTX
Intervention 3 Etanercept and MTX
Source of effectiveness data A double-blind randomised clinical trial of 682 patients (TEMPO). Disease progression is
based on observed transitions in the clinical trial for patients with an HAQ measurement
used at both the start and the end of each year for the first 2 years. Transition probabilities
for the model beyond the trial data are based on the average reported annual progression of
HAQ (0.03). Disease activity and severity was measured in TEMPO by correlating the
patient global VAS with the DAS28. As a result, it was found that a DAS28 of 3.2
corresponds to a score of 41 on the global VAS
Cost data handled Yes: direct resource use included all healthcare and community services, as well as
appropriately investments, devices, transportation and informal help. Indirect costs included early
retirement due to RA, long- and short-term sick leave, and loss of leisure time. Costs and
benefits were discounted at 3%. Cost data came from a survey of 616 Swedish patients,
related to function and disease activity, plus 1810 patients’ early retirement data
Modelling summary A Markov model was developed, with five main functional states and cut-off points at HAQ
0.6, 1.1, 1.6 and 2.1. Each state is further separated into two substrates representing high
and low disease activity. All resulting ten states are further subdivided according to those
receiving study treatments or not. Changes in disease status are modelled as transitions
between the states at intervals of 1 year (cycles). Costs and utility are assigned to each of the
20 states, and the model estimates expected costs and QALYs for defined cohorts of patients
over given periods. A Monte Carlo simulation was run and bootstrapping was used to
estimate uncertainty around input values. The model was run for 10 years of treatment, or
for treatment in trial only for 2 years and extrapolation to 10 years
Outcome measures used in Data related to function and disease activity (EQ-5D) obtained from a survey of 1016
economic evaluations patients with confirmed RA, carried out in 1997, and a more recent follow-up survey,
conducted in 2002, of 616 patients. EQ-5D was related to HAQ scores and disease activity
using multiple regression
Direction of result with NE quadrant. Treatment for 2 years, extrapolation to 10 years: etanercept alone dominated.
appropriate quadrant location Etanercept/MTX vs MTX €37,331 per QALY
Treatment for 2 years, extrapolation to 5 years: etanercept alone dominated.
Etanercept/MTX vs MTX €54,548 per QALY
Treatment for 10 years: etanercept/MTX vs MTX €46,494 per QALY
Treatment for 5 years, extrapolation to 10 years: etanercept/MTX vs MTX €47,316 per
QALY
Statistical analysis for Not undertaken
patient-level stochastic data
Appropriateness of statistical NA
analysis
Uncertainty around Yes
cost-effectiveness expressed
Appropriateness of method Yes: the methods used were appropriate. A Monte Carlo simulation was run and
dealing with uncertainty bootstrapping was used to estimate the uncertainty around the model parameter values.
around cost effectiveness Cost effectiveness acceptability curves were also used
continued