A systematic review of the effectiveness of adalimumab
A systematic review of the effectiveness of adalimumab
A systematic review of the effectiveness of adalimumab
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76<br />
Health economics<br />
TABLE 20 Summary <strong>of</strong> published ICERs for TNF inhibitor a (cont’d)<br />
Drug Comparator Study Date Time-horizon ICER<br />
Baseline level Kobelt163 2004 NA After 3 months <strong>of</strong> treatment €43,500 per QALY<br />
(failed at least<br />
two DMARDs,<br />
including MTX)<br />
After 6 weeks <strong>of</strong> treatment: €36,900 per QALY<br />
DMARD sequence Bansback 166 2005 Lifetime ACR50/DAS28 good:<br />
€48,333 per QALY (+ MTX)<br />
ACR20/DAS28 moderate:<br />
€64,935 per QALY (+ MTX)<br />
DMARD sequence Jobanputra 1 2002 Lifetime £115,937 per QALY<br />
Anakinra Chiou164 2004 1 year Infliximab + MTX dominated<br />
a Industry-sponsored studies are highlighted in shaded cells.<br />
b Cost-<strong>effectiveness</strong> analysis; all o<strong>the</strong>r studies are cost–utility analyses.<br />
Etan, etanercept; LEF, leflunomide; QALY, quality-adjusted life-year.<br />
is no response; leflunomide followed by etanercept<br />
if <strong>the</strong>re is no response to leflunomide (LEF–Etan);<br />
and finally, etanercept switching to leflunomide<br />
with non-response (Etan–LEF)]. Kobelt and<br />
colleagues 167 considered etanercept alone and<br />
etanercept combined with methotrexate.<br />
Two studies found high ICERs. Choi and<br />
colleagues 159 suggested that recommendations<br />
regarding use depended on whe<strong>the</strong>r an ICER over<br />
$40,000 per ACR20 or ACR70WR was considered<br />
acceptable. Welsing and colleagues 165<br />
recommended use <strong>of</strong> etanercept following<br />
leflunomide after two o<strong>the</strong>r DMARDs (where <strong>the</strong><br />
first is methotrexate) had failed. In contrast,<br />
Brennan and colleagues 160,168 reported a much<br />
lower ICER and suggested “etanercept was costeffective<br />
when compared with non-biologic<br />
agents”. Kobelt and colleagues 167 reported <strong>the</strong><br />
ICER for etanercept in combination with<br />
methotrexate to be within <strong>the</strong> “acceptable range”.<br />
Each study used a different modelling approach.<br />
Choi and colleagues 159 used a simple decision-tree<br />
structure and modelled costs and outcomes over 6<br />
months. Welsing and colleagues 165 and Kobelt and<br />
colleagues 167 used a Markov model structure with<br />
a 5-year time-horizon and a 5- and 10-year timehorizon,<br />
respectively. Brennan and colleagues 160<br />
developed an individual patient-level simulation<br />
model to calculate lifetime costs and outcomes.<br />
RCT data were used to model outcomes; it has<br />
been suggested that observational data are a more<br />
realistic representation <strong>of</strong> outcomes in practice<br />
and <strong>the</strong>refore more suitable for cost-<strong>effectiveness</strong><br />
analyses. 169<br />
Each study took different approaches; for<br />
example, <strong>the</strong> evaluation undertaken (cost-<br />
<strong>effectiveness</strong> or cost–utility analysis), <strong>the</strong><br />
treatment comparators and <strong>the</strong> time-horizon<br />
chosen (each used a different time-horizon,<br />
varying from 6 months to lifetime). Kobelt 167 used<br />
a cycle length <strong>of</strong> 1 year, which is not clinically<br />
relevant. A cycle length <strong>of</strong> around 4 months is<br />
more clinically relevant as decisions about<br />
<strong>the</strong> efficacy <strong>of</strong> DMARDs are generally made<br />
over this time. Three analyses were from a<br />
societal perspective, an approach that leads to a<br />
more favourable ICER. If a treatment is more<br />
effective, <strong>the</strong>n patients are more able to work,<br />
thus leading to lower indirect costs. The Choi<br />
study 159 did not calculate cost per QALYs,<br />
<strong>the</strong>refore comparison with o<strong>the</strong>r results is not<br />
possible.<br />
Two <strong>of</strong> <strong>the</strong> ten identified published studies report<br />
an economic analysis <strong>of</strong> infliximab in combination<br />
with methotrexate (Table 22), and were sponsored<br />
by <strong>the</strong> manufacturer Schering-Plough. Both<br />
studies were cost–utility analyses using a societal<br />
perspective and <strong>the</strong> comparator explored was<br />
methotrexate alone. The quality <strong>of</strong> life data used<br />
by Wong and colleagues 161 was based on selfreported<br />
global health using a visual analogue<br />
scale (VAS) from ATTRACT and <strong>the</strong> Arthritis,<br />
Rheumatism and Aging Medical Information<br />
System (ARAMIS) database. However, <strong>the</strong>re are<br />
problems with VAS such as context bias and endpoint<br />
aversion, and <strong>the</strong> method is not truly<br />
preference based. O<strong>the</strong>r methods are more<br />
appropriate, for example using a utility measure<br />
such as EuroQol 5 Dimensions (EQ-5D).<br />
Therefore, results should be treated with some<br />
caution. Costs were obtained from <strong>the</strong> ARAMIS<br />
database, based on a North American population,<br />
and are not directly transferable to a UK