A systematic review of the effectiveness of adalimumab

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Health economics
disability. Data for non-responders were based on
an observational study by Young and colleagues. 46
This study does not report specifically on DMARD
responders and non-responders and it is unclear
how these data were obtained. In addition, the
study is a hospital-based study of early RA patients
where data were collected annually. As HAQ is
especially labile in this population, single annual
measurements have limited reliability.
Patient HAQ scores are updated every 6 months
and the mean level of HAQ improvement was
obtained from clinical trial data and published
literature. HAQ scores are converted to QALYs by
using regression of HAQ against utility from trial
data. The relationship between HAQ and utility
scores was given as U = 0.76 – (0.28 × HAQ) +
0.05 × Female. This relationship was derived from
analysis of Health Utility Index (HUI) 3 data
obtained from the adalimumab trials.
Data on the incidence of mild, moderate and
serious adverse events were estimated from an
observational study. The same study and a review
provided data on long-term withdrawal; the
limitations of using data from Geborek 171 are
discussed above. Mortality risk for patients with RA
was adjusted by HAQ score and Gompertz models
were fitted, with the minimum age set at 50 years.
The 6-monthly hazard rate was calculated in the
model for patients’ age and midpoint HAQ score
during each therapy line. This simplification may
be acceptable; however, exploratory analyses would
be worthwhile to test this assumption.
Resource use and costs were derived from
published data, costing BSR guidelines and expert
clinical opinion. In addition, some healthcare
resource use was estimated based on HAQ-DI
scores. Costs and benefits were discounted at 6%
and 1.5%, respectively. Costs were calculated from
a healthcare perspective. Both simple one-way and
probabilistic sensitivity analyses were undertaken.
The base-case results using ACR50 suggest that
adalimumab is cost-effective as fourth line therapy,
TABLE 27 Treatment sequences: etanercept
with an ICER of £17,860. In total, 32 one-way
sensitivity analyses were conducted, all giving
ICERs under £30,000 per QALY. Probabilistic
sensitivity analysis showed adalimumab in
combination with methotrexate to have a 99.8%
probability of being cost-effective at a willingnessto-pay
threshold of £30,000 per QALY.
Comparison with etanercept gave a lower ICER of
£14,388 and a 96% probability of being costeffective
at £30,000 per QALY.
Secondary analyses were also reported. Using an
ACR20 response the cost per QALY for
adalimumab plus methotrexate was £19,251. Costeffectiveness
ratios at different lines of entry were
also explored for ACR50 and ACR20.
The ICERs for ACR50 are:
● first line: £19,095 per QALY
● second line: £18,166 per QALY
● third line: £18,479 per QALY.
The ICERs for ACR20 are:
● first line: £21,228 per QALY
● second line: £19,794 per QALY
● third line: £19,596 per QALY.
The study concluded that adalimumab “should be
considered cost-effective when compared against
conventional DMARDs” and on the basis of this
“the cost-effectiveness of adalimumab is very
similar to that of etanercept and infliximab”.
Wyeth submission (etanercept)
A sequential model was developed whereby a
simulated patient receives a given treatment until
DMARD switching occurs as a result of either
failure of effectiveness or SAEs. The main
treatment sequences considered are shown in
Table 27, but others were explored and are not
presented in the report.
The submission indicates that “the aim of the
economic model and treatment sequences was to
demonstrate that etanercept + MTX is a costeffective
intervention when used earlier in the
Therapy line Treatment sequence (1st line) Comparator sequence
First Etan + MTX MTX
Second MTX SSZ
Third SSZ LEF
Fourth LEF GST
Fifth GST DMARD (non-specified)
Sixth Salvage therapy Salvage therapy