A systematic review of the effectiveness of adalimumab

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Health economics
TABLE 49 Treatment costs
Treatment Start-up Annual usage
(£) (£)
Palliation 0.00 364.00
Adal 515.88 9714.84
Adal+MTX 515.88 9751.34
AZA 694.81 1380.26
CyA 350.37 2482.08
Etan 515.88 9714.84
Etan+MTX 515.88 9751.34
GST 2765.24 1581.48
HCQ 101.89 448.97
Infl 1676.14 9333.54
LEF 986.91 1211.72
MTX 512.76 1222.34
DPen 476.94 1401.77
SSZ 584.47 514.88
Combination CyA+MTX 350.37 2566.34
MTX+SSZ 584.47 1341.94
MTX+SSZ+HCQ 101.89 1346.85
All costs discounted at 6% per annum from divergence
point.
Combining the above information leads to the
model inputs shown in Table 49. It should be
noted that palliation does not include
hospitalisation. Hospital admissions may be
higher for RA patients with no DMARD options,
but no data were available as a guide.
The base model does not include costs for
hospitalisation as a result of RA. This is because of
wide variation in rates dictated by local facilities
and practice. The ERA study shows a large range
of hospitalisation for RA, but there are no data for
the impact of DMARDs on hospital admission
rates. 46 The effects of DMARDs on joint
replacement have also not been included in the
base model. Again, this is because of the absence
of data on the effects of DMARDs on joint
replacement rates. These uncertainties are
explored later in a sensitivity analysis.
Basic mortality comes from standard life tables. A
relative risk of 1.33 per unit HAQ is applied. 198
More recently, Sokka and colleagues 199 reported a
risk of 2.73 per unit HAQ. The present analysis
maintained the relative risk of 1.33 for the base
case, but used the range from 1 to 2.73 for
sensitivity analysis.
In the base case, the following assumptions
were made concerning HAQ increases over time.
It was assumed that patients remaining on TNF
inhibitors experience a worsening (increase) in
HAQ equivalent to the general population. Based
on the study by Krishnan and colleagues, 200 this
was set a progression of 0.03 per year, making a
mean time of 4 years between each 0.125 unit
increase in HAQ. It was assumed that TNF
inhibitors halve the general worsening in HAQ, so
that patients on palliation have a progression rate
of 0.06 per year, a mean time of 2 years between
each 0.125 unit increase in HAQ. For conventional
DMARDs, an intermediate progression rate of
0.045 per year was assumed, a mean time of 2.7
years between each 0.125 unit increase in HAQ.
These assumptions were varied in sensitivity
analysis.
On quitting any treatment, it is assumed that the
HAQ improvement (reduction) obtained on
starting treatment is exactly reversed. For
example, if the HAQ score improves from 1.25
to 0.875 on starting treatment, and the
HAQ score is 1 before quitting treatment, then
the HAQ score will be 1.375 after quitting. If
applying this rule would take the post-treatment
HAQ score above 3, then the post-treatment HAQ
score is set to 3.
Quality of life (QoL) scores
Conversion from HAQ to QALYs is by the formula
QoL = 0.862 – 0.327HAQ calculated from the
data set supplied by Hurst, and reported in
Hurst and colleagues. 201 It was assumed that start
and end effects can be modelled as one-off
deductions equal to 0.2 years times the change in
QoL score.
QALYs are discounted at 1.5% per annum from
the divergence point between strategies.
Results
The model was run for each of the strategy sets
shown above. A fixed random number seed was
used, and the model was run for at least 10,000
(virtual) patients. Comparisons between each pair
of options can be found in the form of an ICER
with a quasi-confidence interval, reflecting the
sampling in running the model, not parameter
uncertainty. Fixed stopping rules were used to
determine whether the quasi-confidence interval
was sufficiently precise, or whether the run-length
needed to be increased. The definition of
‘sufficiently precise’ used was as follows. In cases of
dominance (north-west or south-east quadrants),
95% quasi-confidence intervals for cost difference
and QALY difference each had to avoid zero. In
other cases, a quasi-confidence interval [lower (L),
upper (U)] for the ICER had to satisfy the