A systematic review of the effectiveness of adalimumab

78
Health economics
TABLE 22 Published infliximab economic analyses
Study Sponsor Patient Comparator(s) Base case ICER
group
Wong et al., Schering-Plough, RA Placebo and MTX $30,500 per QALY
2002 161 Centocor Corp.,
National Institutes of
Health
Kobelt et al., Schering-Plough RA MTX For 1 year of treatment:
2003 162 €3440 per QALY in Sweden
€34,800 per QALY in UK
from a healthcare perspective. The model builds
on two previous RA models. 1,160 Etanercept and
adalimumab were considered as monotherapies
and in combination with methotrexate, with two
separate analyses for adalimumab plus
methotrexate. The second analysis contained
additional information from a larger adalimumab
trial in a pooled analysis. Infliximab was only
considered in combination with methotrexate.
Results were presented as ICERs versus traditional
DMARDs for two separate groups: an ACR50
response which corresponded to a good DAS28
response and an ACR20 response which
corresponded to a moderate DAS28 response.
Using such dichotomous data, unfortunately, does
not reflect clinical reality, or practice, as many
patients may continue, or cease, therapy despite
such thresholds; actual drug continuation rates
from observational studies are more appropriate
for modelling. Chiou and colleagues 170 used a
decision tree to carry out a cost–utility analysis of
anakinra, adalimumab, etanercept and infliximab
used alone or in combination with methotrexate
during 1 year. Separate analyses were conducted
for monotherapies and combination therapies. A
preference weight was attached to each of the 16
health states representing a combination of the
level of adverse effects and ACR response criteria.
However, preference weights were derived from
VAS, which is not ideal.
Kobelt and colleagues 163 reported QALYs within
the generally accepted threshold of €50,000 per
QALY; however, analysis was from a societal
perspective, therefore results are not directly
relevant to a UK healthcare perspective. Bansback
and colleagues 166 suggested that adalimumab was
cost-effective for the treatment of moderate to
severe RA and was at least as cost-effective as
etanercept or infliximab, but there was uncertainty
about which drug was the most cost-effective. In
addition, they concluded that with the exception
of infliximab, the cost results were in a range
normally considered cost-effective in Europe.
Chiou and colleagues 170 found anakinra to be the
least cost-effective option, and etanercept (as
monotherapy and combined with methotrexate)
was dominant over other TNF inhibitors.
Compared with anakinra, both etanercept
treatment regimens were below US $15,000 per
QALY. However, the study is US based and uses
US healthcare costs, therefore the results cannot
be applied to the UK.
Direct comparison of these ICERs is inappropriate
as the analyses are very different in terms of
treatment comparators and time-horizons. The
Kobelt analysis 167 is without modelling, Bansback
and colleagues 166 conduct modelling over a
patient’s lifetime and Chiou and colleagues 170
model over 1-year. Modelling the response over a
1-year cycle is not clinically appropriate, especially
as it is assumed that treatment will continue over
this period with no switching of therapy. In reality,
patients will switch from one drug to another in a
period much shorter than 1 year owing to lack of
response or adverse effects. In addition, Chiou 170
is the only study that does not use traditional
DMARDs as the comparator, using anakinra
monotherapy instead. However, anakinra was not
recommended for routine use in the NHS by
NICE in its November 2003 guidance
(http://www.nice.org.uk/pdf/TA072guidance.pdf)
because of its poor incremental cost-effectiveness,
which was over £100,000 per QALY. 3
Summary of review of existing
economic evaluations
● Results of published economic evaluations vary:
some analyses suggest that use of TNF
inhibitors may fall within the usual acceptable
cost-effectiveness ranges, whereas others report
very high ICERs.
● A direct comparison of ICERs between studies is
not possible because of different approaches to
modelling, in particular time-horizon, cycle