A systematic review of the effectiveness of adalimumab

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Health economics
TABLE 29 SAE parameters
Etan MTX Etan + SSZ GST Infl + DMARD Adal LEF Salvage
MTX MTX
Probability 0.07 0.07 0.05 0.07 0.06 0.10 0.06 0.07 0.08 0.10
of SAE
Probability 0.33 0.33 0.33 0.33 0.33 0.33 0.33 0.33 0.33 0.33
of switching
if SAE
experience different HAQ changes from those not
in remission. However, the definition of
remission is problematic, and the change in HAQ
may have been sufficient to represent remission
without assuming further treatment benefits in
modelling.
SAEs in the model were dependent on the
treatment received (Table 29). Their occurrence
affected costs, utility and the likelihood of
switching therapy. SAEs were assumed to occur for
one cycle only. “Due to lack of reliable evidence
for this parameter, it was assumed that one-third
of patients who experience an SAE would switch
therapies during that (6-month) period.” This
assumption would be unnecessary if actual data on
switching were used, and the probability of
switching may actually be much higher than onethird.
In addition, SAEs and switching appear to
be able to occur with salvage therapy, but is it
unclear how or why this happens.
Switching occurs for one of two reasons: lack of
effectiveness or occurrence of an SAE. The
treatment switch criteria used in the model were:
● if a patient does not have an initial (i.e. first
6 months) improvement of 0.3468 in HAQ
● if, after an initial improvement, the patient’s
HAQ worsens by 0.3468 over 12 months or
0.3468 over a 6-month period.
Mortality rates for RA were assumed to be 1.63
times that of the general population of the same
age. The change in mortality rate was adjusted
taking change in HAQ into account. Inflating the
already increased mortality on the basis of HAQ
appears to introduce double-counting and is
therefore inappropriate. Utility weights were
assumed to vary linearly with HAQ score
[i.e. U = 0.76 + (HAQ × –0.28)]. This was further
adjusted to consider SAEs, with a loss of 0.05 for
each SAE experienced, but this assumption for a
6-month period for someone experiencing an SAE
appears to be an underestimate.
Resource-use and cost data were taken from expert
opinion and national sources. One blood test per
year is assumed for those on TNF inhibitors and
two for those on DMARDs. However, if those on
TNF inhibitors are to receive methotrexate, then
more frequent blood tests (e.g. monthly) are likely.
This larger number of blood tests would apply to
both arms. Rituximab is suggested for the salvage
therapy, with a 6-month cost of almost £900. This
is in contrast with the equivalent ‘palliation’ used
in other analyses where costs are much lower,
which may be a more accurate reflection of reality.
For the base case, costs were discounted at 6% and
QALYs at 1.5%. Simple one-way sensitivity analysis
was undertaken on HAQ changes, mortality rate,
SAE utility, cost, discount rates and switching
threshold. The upper value for initial change in
HAQ on etanercept of –1.3 appears to be rather
high.
The base-case results suggest that etanercept is
cost-effective first-line therapy. The ICERs
indicate:
● first line: £16,000 per QALY
● second line: £20,000 per QALY
● third line: £18,000 per QALY.
Sensitivity analysis results are interpreted as
showing that the results for all three models (first,
second and third line) are “relatively robust to
changes in key parameters”.
Schering-Plough submission (infliximab)
The economic analysis presented in this
submission assessed the cost-effectiveness of
infliximab in combination with methotrexate
compared with methotrexate alone in patients
with severe RA. Data on effectiveness were drawn
from ATTRACT and ASPIRE and so the patient
populations seen in those trials were assumed for
the modelling work: patients with active RA
despite DMARD use and patients with severe
active early RA. The perspective adopted was that
of the NHS and Personal and Social Services (PSS).