A systematic review of the effectiveness of adalimumab

management of RA, i.e. 1st and 2nd line”.
Etanercept and methotrexate were used in
combination as “the body of evidence suggests
that combination therapy is more effective than
monotherapy”. Using combination data, however,
will weigh ICERs in favour of etanercept since
patients responding to combined therapy, if they
are DMARD naïve, have the opportunity of
responding to two agents and many may have
responded to methotrexate alone.
The model uses 6-monthly cycles and allows
patients to: experience changes in disease severity;
enter a remission state; develop drug tolerance
problems; experience an SAE; or die. At the end
of each 6-month cycle the patient can:
● change disease severity
● experience an SAE
● switch treatment therapy
● die.
The model run consisted of 10,000 hypothetical
patients, followed until death. Costs were
calculated from the perspective of a healthcare
provider. The main driver of the model result is
the patient’s disease severity. Disease severity
determines several factors in the model, including
the likelihood of switching therapy, health-related
utility and mortality. HAQ was used to represent
disease severity as it was not practical to measure
both HAQ and DAS28 scores simultaneously.
However, for the purpose of ‘switching thresholds’
a relationship between HAQ and DAS28 was
required and changes in HAQ score were used as a
proxy for changes in the DAS28. Perhaps here it
would have been more appropriate to use actual
switching rates from clinical observation rather
TABLE 28 HAQ change parameters
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Health Technology Assessment 2006; Vol. 10: No. 42
than this conversion, which potentially introduces
more uncertainty into the model. A baseline HAQ
of 1.74 was obtained from TEMPO. Using a fixed
HAQ at start of treatment has limitations and the
heterogeneity of response is not taken into
account. Patients’ HAQ scores are updated every 6
months, with the changes based on evidence from
clinical trials and other published sources (see
Table 28 for estimates).
A robust approach was applied, where
distributions rather than point estimates were used
to introduce a random element into HAQ
change. The HAQ change estimates were derived
from TEMPO for etanercept, methotrexate and
combination therapy. The HAQ change for
unspecified DMARD was based on the Tight
Control for Rheumatoid Arthritis (TICORA). This
is inappropriate since data for individual drugs
are available. The initial HAQ change for
sulfasalazine was assumed to be –0.29. This
improvement is based on an ITT analysis of trial
data, and HAQ improvement for those that
continue the drug was –0.43. For the purposes of
economic modelling, patients who continue
treatment are of interest, since those who do not
are accounted for elsewhere. Thus, a figure of
–0.29 underestimated the benefit of continuing
with sulfasalazine. Data from trials such as
TEMPO represent ideal responses and the data
may not reflect outcomes in routine care. For
other therapies, the estimates were based on
‘published sources’, and where data were not
available for 6-month changes, estimates were
converted to 6-month rates using a simple
formula. In all cases, the first 6 months’ change
was accounted for when calculating medium-term
changes. Patients in remission were assumed to
Etan MTX Etan+ SSZ GST Infl + DMARD Adal LEF Salvage
MTX MTX
Initial HAQ
change
–0.690 –0.650 –0.890 –0.290 –0.430 –0.080 –0.270 –0.560 –0.500 –0.040
Medium-term –0.005
non-remission:
mean HAQ
change
–0.001 –0.052 0.075 0.045 –0.087 –0.080 –0.030 0.000 0.200
Remission:
mean HAQ
change
–0.0276 –0.0037 –0.0145 0.075 0.045 –0.087 –0.080 –0.030 0.000 0.200
Long-term: 0.00 0.02 0.00 0.10 0.10 0.00 0.1 0.00 0.10 0.28
change per
cycle
83