A systematic review of the effectiveness of adalimumab
A systematic review of the effectiveness of adalimumab A systematic review of the effectiveness of adalimumab
78 Health economics TABLE 22 Published infliximab economic analyses Study Sponsor Patient Comparator(s) Base case ICER group Wong et al., Schering-Plough, RA Placebo and MTX $30,500 per QALY 2002 161 Centocor Corp., National Institutes of Health Kobelt et al., Schering-Plough RA MTX For 1 year of treatment: 2003 162 €3440 per QALY in Sweden €34,800 per QALY in UK from a healthcare perspective. The model builds on two previous RA models. 1,160 Etanercept and adalimumab were considered as monotherapies and in combination with methotrexate, with two separate analyses for adalimumab plus methotrexate. The second analysis contained additional information from a larger adalimumab trial in a pooled analysis. Infliximab was only considered in combination with methotrexate. Results were presented as ICERs versus traditional DMARDs for two separate groups: an ACR50 response which corresponded to a good DAS28 response and an ACR20 response which corresponded to a moderate DAS28 response. Using such dichotomous data, unfortunately, does not reflect clinical reality, or practice, as many patients may continue, or cease, therapy despite such thresholds; actual drug continuation rates from observational studies are more appropriate for modelling. Chiou and colleagues 170 used a decision tree to carry out a cost–utility analysis of anakinra, adalimumab, etanercept and infliximab used alone or in combination with methotrexate during 1 year. Separate analyses were conducted for monotherapies and combination therapies. A preference weight was attached to each of the 16 health states representing a combination of the level of adverse effects and ACR response criteria. However, preference weights were derived from VAS, which is not ideal. Kobelt and colleagues 163 reported QALYs within the generally accepted threshold of €50,000 per QALY; however, analysis was from a societal perspective, therefore results are not directly relevant to a UK healthcare perspective. Bansback and colleagues 166 suggested that adalimumab was cost-effective for the treatment of moderate to severe RA and was at least as cost-effective as etanercept or infliximab, but there was uncertainty about which drug was the most cost-effective. In addition, they concluded that with the exception of infliximab, the cost results were in a range normally considered cost-effective in Europe. Chiou and colleagues 170 found anakinra to be the least cost-effective option, and etanercept (as monotherapy and combined with methotrexate) was dominant over other TNF inhibitors. Compared with anakinra, both etanercept treatment regimens were below US $15,000 per QALY. However, the study is US based and uses US healthcare costs, therefore the results cannot be applied to the UK. Direct comparison of these ICERs is inappropriate as the analyses are very different in terms of treatment comparators and time-horizons. The Kobelt analysis 167 is without modelling, Bansback and colleagues 166 conduct modelling over a patient’s lifetime and Chiou and colleagues 170 model over 1-year. Modelling the response over a 1-year cycle is not clinically appropriate, especially as it is assumed that treatment will continue over this period with no switching of therapy. In reality, patients will switch from one drug to another in a period much shorter than 1 year owing to lack of response or adverse effects. In addition, Chiou 170 is the only study that does not use traditional DMARDs as the comparator, using anakinra monotherapy instead. However, anakinra was not recommended for routine use in the NHS by NICE in its November 2003 guidance (http://www.nice.org.uk/pdf/TA072guidance.pdf) because of its poor incremental cost-effectiveness, which was over £100,000 per QALY. 3 Summary of review of existing economic evaluations ● Results of published economic evaluations vary: some analyses suggest that use of TNF inhibitors may fall within the usual acceptable cost-effectiveness ranges, whereas others report very high ICERs. ● A direct comparison of ICERs between studies is not possible because of different approaches to modelling, in particular time-horizon, cycle
TABLE 23 Published economic analyses for more than one TNF inhibitor therapy length, country of origin, perspective chosen, source of preference weights and comparator drugs. ● Many of the previous analyses are based on clinical estimates that are derived from single trials, or a small number of trials, rather than a formal systematic review, meta-analysis of evidence, or observational data of effectiveness in clinical practice. ● Drug manufacturers have sponsored four published analyses, with a further two having links with a drug company. Two studies do not state the sponsors of the study. The two remaining studies were not linked with any drug manufacturers. ● Each study was considered to be of adequate quality, in terms of criteria in the CHEC list, © Queen’s Printer and Controller of HMSO 2006. All rights reserved. Health Technology Assessment 2006; Vol. 10: No. 42 Study Sponsor Patient Comparator(s) Base case ICER group Etanercept, infliximab Jobanputra et al., NHS HTA Programme RA DMARD sequence Etanercept 2002 1 £83,095 per QALY Infliximab £115,937 per QALY Kobelt et al., Österlund and Kock RA Baseline level (failed After 3 months of treatment: 2004 163 Foundations, King at least 2 DMARDs, €43,500 per QALY Gustav V 80 year fund, including MTX) After 6 weeks of treatment: Reumatikerförbundet. €36,900 per QALY Etanercept, infliximab, adalimumab Chiou et al., Not stated RA Anakinra US $13,387 per QALY 2004 170 (Etanercept alone) Adalimumab alone dominated US $7925 per QALY (etanercept + MTX) Adalimumab + MTX and infliximab + MTX dominated Bansback et al., Abbott Laboratories RA DMARD sequence ACR50/DAS28 good: 2005 166 €34,167 per QALY (adalimumab+MTX) €34,922 per QALY (adalimumab+MTX) a a Including additional information from a larger adalimumab trial in a pooled analysis. €35,760 per QALY (etanercept + MTX) €48,333 per QALY (infliximab + MTX) €41,561 per QALY (adalimumab) €36,927 per QALY (etanercept) ACR20/DAS28 moderate: €40,875 per QALY (adalimumab+MTX) €44,018 per QALY (adalimumab+MTX) a €51,976 per QALY (etanercept+MTX) €64,935 per QALY (infliximab+MTX) €65,499 per QALY (adalimumab) €42,480 per QALY (etanercept) where at least 15 of 19 were met by all. All fulfilled criteria related to design and conduct; that is, each study was a cost-effectiveness evaluation addressing a clearly defined research question applied to a clearly defined population. An appropriate perspective was chosen in each and the outcomes identified were relevant and measured appropriately. Incremental analyses, to which appropriate sensitivity analyses had been applied, were reported without exception. ● Quality assessment criteria that were not met included failure to report the following: discounted future costs and benefits in two studies, potential conflicts of interest in five studies, competing interests in two studies; the generalisability of results in one study, and 79
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TABLE 23 Published economic analyses for more than one TNF inhibitor <strong>the</strong>rapy<br />
length, country <strong>of</strong> origin, perspective chosen,<br />
source <strong>of</strong> preference weights and comparator<br />
drugs.<br />
● Many <strong>of</strong> <strong>the</strong> previous analyses are based on<br />
clinical estimates that are derived from single<br />
trials, or a small number <strong>of</strong> trials, ra<strong>the</strong>r than a<br />
formal <strong>systematic</strong> <strong>review</strong>, meta-analysis <strong>of</strong><br />
evidence, or observational data <strong>of</strong> <strong>effectiveness</strong><br />
in clinical practice.<br />
● Drug manufacturers have sponsored four<br />
published analyses, with a fur<strong>the</strong>r two having<br />
links with a drug company. Two studies do not<br />
state <strong>the</strong> sponsors <strong>of</strong> <strong>the</strong> study. The two<br />
remaining studies were not linked with any drug<br />
manufacturers.<br />
● Each study was considered to be <strong>of</strong> adequate<br />
quality, in terms <strong>of</strong> criteria in <strong>the</strong> CHEC list,<br />
© Queen’s Printer and Controller <strong>of</strong> HMSO 2006. All rights reserved.<br />
Health Technology Assessment 2006; Vol. 10: No. 42<br />
Study Sponsor Patient Comparator(s) Base case ICER<br />
group<br />
Etanercept, infliximab<br />
Jobanputra et al., NHS HTA Programme RA DMARD sequence Etanercept<br />
2002 1 £83,095 per QALY<br />
Infliximab<br />
£115,937 per QALY<br />
Kobelt et al., Österlund and Kock RA Baseline level (failed After 3 months <strong>of</strong> treatment:<br />
2004 163 Foundations, King at least 2 DMARDs, €43,500 per QALY<br />
Gustav V 80 year fund, including MTX) After 6 weeks <strong>of</strong> treatment:<br />
Reumatikerförbundet. €36,900 per QALY<br />
Etanercept, infliximab, <strong>adalimumab</strong><br />
Chiou et al., Not stated RA Anakinra US $13,387 per QALY<br />
2004 170 (Etanercept alone)<br />
Adalimumab alone dominated<br />
US $7925 per QALY<br />
(etanercept + MTX)<br />
Adalimumab + MTX and infliximab +<br />
MTX dominated<br />
Bansback et al., Abbott Laboratories RA DMARD sequence ACR50/DAS28 good:<br />
2005 166 €34,167 per QALY (<strong>adalimumab</strong>+MTX)<br />
€34,922 per QALY (<strong>adalimumab</strong>+MTX) a<br />
a Including additional information from a larger <strong>adalimumab</strong> trial in a pooled analysis.<br />
€35,760 per QALY (etanercept + MTX)<br />
€48,333 per QALY (infliximab + MTX)<br />
€41,561 per QALY (<strong>adalimumab</strong>)<br />
€36,927 per QALY (etanercept)<br />
ACR20/DAS28 moderate:<br />
€40,875 per QALY (<strong>adalimumab</strong>+MTX)<br />
€44,018 per QALY (<strong>adalimumab</strong>+MTX) a<br />
€51,976 per QALY (etanercept+MTX)<br />
€64,935 per QALY (infliximab+MTX)<br />
€65,499 per QALY (<strong>adalimumab</strong>)<br />
€42,480 per QALY (etanercept)<br />
where at least 15 <strong>of</strong> 19 were met by all. All<br />
fulfilled criteria related to design and conduct;<br />
that is, each study was a cost-<strong>effectiveness</strong><br />
evaluation addressing a clearly defined research<br />
question applied to a clearly defined<br />
population. An appropriate perspective was<br />
chosen in each and <strong>the</strong> outcomes identified<br />
were relevant and measured appropriately.<br />
Incremental analyses, to which appropriate<br />
sensitivity analyses had been applied, were<br />
reported without exception.<br />
● Quality assessment criteria that were not met<br />
included failure to report <strong>the</strong> following:<br />
discounted future costs and benefits in two<br />
studies, potential conflicts <strong>of</strong> interest in five<br />
studies, competing interests in two studies; <strong>the</strong><br />
generalisability <strong>of</strong> results in one study, and<br />
79
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