A systematic review of the effectiveness of adalimumab

TABLE 25 Treatment sequences: adalimumab
inhibitors were also explored and results presented
in the report. The first- to third-line therapies are
not stated here as the analysis assumed that patients
had failed three DMARDs including methotrexate.
The model used 6-monthly cycles in which
patients can experience a number of events. In the
first 6-month period on a therapy a patient can:
have a positive response to treatment; have a
negative response to treatment; suffer an SAE, or
die. In subsequent periods a patient can: have
continued efficacy; have a loss of efficacy; suffer an
SAE; or die. Therefore, at the end of a cycle the
patient can: continue on the same therapy;
withdraw and proceed to the next therapy when a
negative response, loss of efficacy or SAE has
occurred; or die.
The model run was for 10,000 patients, and
applied a single baseline profile rather than
sampling individual patient characteristics. The
baseline characteristics were set to reflect patients
in adalimumab trials. Patients had a mean age of
54.7 years, 77% were women, with a baseline HAQ
of 1.6 and a mean DMARD use of 3. However,
assuming a fixed HAQ score at baseline ignores
the heterogeneity of response.
Data used in the base-case analyses came from
trials where the comparator was methotrexate, with
the exception of the data for DMARDs. Here, an
observational study (Geborek 171 ) of leflunomide
was used and was assumed to be representative of
all DMARDs. It is inappropriate to use leflunomide
data derived from populations that had failed two
Health Technology Assessment 2006; Vol. 10: No. 42
Therapy line Treatment sequence (fourth line) Comparator sequence
Fourth Adal + MTX GST
Fifth GST LEF
Sixth LEF CyA + MTX
Seventh CyA + MTX Rescue
Eighth Rescue Rescue
Adal, adalimumab; CyA, ciclosporin A; GST, injectable gold.
TABLE 26 HAQ changes by response type
ACR improvement Observed HAQ change HAQ change given New HAQ score for
baseline of 1.6 responders
70% –64.6% –1.034 0.566
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DMARDs to represent all DMARDs, particularly in
early RA. This is because this observational study
looks at RA patients who had failed at least two
DMARDs before testing leflunomide, etanercept or
infliximab. In addition, using annual withdrawal
rates for leflunomide from this study and assuming
that this applies to all DMARDs is inappropriate.
No meta-analyses of biological trials were
undertaken for their analysis, and main trial data
for each of the TNF inhibitors were used instead.
ACR50 data were used in the base case to
determine response rate on each therapy, with
patient-level trial data used for adalimumab and
published data for other DMARDs. Average
improvement in HAQ for ACR20, ACR50 and
ACR70 responders was available from the
adalimumab trials. These data were not available
for other DMARDs, therefore an assumption was
made that HAQ improvement would be the same
as for adalimumab and independent of treatment.
The calculated HAQ change, categorised by
response, is shown in Table 26. Long-term change
in HAQ was obtained from a systematic review,
assuming a slight progression of disability over
time, with data for a successful response
recalculated to account for the variation in patient
numbers in the studies. However, to assume yearon-year
decrease in HAQ response in early disease
is problematic as HAQ is very labile in the first
5 years of disease. Withdrawal from treatment was
assumed to change the HAQ score by the
equivalent amount of the initial improvement,
therefore giving a slightly higher HAQ score than
at baseline, but due to gradual progression of
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