A systematic review of the effectiveness of adalimumab

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74 Health economics TABLE 19 Summary of published economic analyses Study TNF inhibitor(s) Form of economic Model used Time-horizon considered analysis Choi et al., 2002159 Etanercept Cost-effectiveness Decision tree 6 months Brennan et al., 2004160 Etanercept Cost–utility Patient-level simulation Lifetime Wong et al., 2002161 Infliximab Cost–utility Markov Lifetime Kobelt et al., 2003162 Infliximab Cost–utility Markov 10 years Jobanputra et al., 20021 Etanercept, infliximab Cost–utility Patient-level simulation Lifetime Kobelt et al., 2004163 Etanercept, infliximab Cost–utility NA NA Chiou et al., 2004164 Etanercept, infliximab, adalimumab Cost–utility Decision tree 1 year Welsing et al., 2004 165 Etanercept Cost–utility Markov 5 years Bansback et al., 2005166 Etanercept, infliximab, adalimumab Cost–utility Patient-level simulation Lifetime Kobelt et al., 2005 167 Etanercept Cost–utility Markov 10 years Study selection, data extraction, and quality assessment strategy An experienced health economist applied the inclusion and exclusion criteria. Data were extracted by one reviewer using a predesigned data extraction form and were independently checked by a second reviewer. Data on the following were sought: ● study characteristics, such as form of economic analysis, population, interventions, comparators, perspective, time-horizon and modelling used ● effectiveness and cost parameters, such as effectiveness data, health state valuations (utilities), resource-use data, unit cost data, price year, discounting and key assumptions ● results and sensitivity analyses. These characteristics and the main results of included economic evaluations are summarised in subsequent tables. The quality of included studies and industry submissions was assessed using the CHEC list. 158 The study question, selection of alternatives, form of evaluation, effectiveness data, costs, benefit measurement and valuation, decision modelling, discounting, allowance for uncertainty and presentation of results were all evaluated as part of this process. Results of systematic review of economic evaluations Ten published studies, including one by the current authors, 1 met the inclusion criteria. Given that Jobanputra 1 describes the initial version of BRAM which is updated in this report, it will not be further discussed here. Key features of the nine other studies are summarised in Table 19. In addition, all three manufacturers submitted economic analyses and models. These submissions are reviewed in detail in the section ‘Review of industry cost-effectiveness submissions’ (p. 80). Details of the nine studies are presented in Appendix 8, using a simplified version of the Drummond and Jefferson checklist. A summary of the ICERs for TNF inhibitors reported in published papers is provided in Table 20. Four economic evaluations only considered etanercept compared with specified DMARDs or sequences of DMARDs (Table 21). Three studies were cost–utility analyses, with the cost-effectiveness ratio (ICER) reported as cost per QALY gained (Table 21). In addition to cost per QALY, Welsing and colleagues 165 considered cost per patient-year in three DAS28 states. Choi and colleagues 159 used the ACR20 response and a weighted average of proportions of patients achieving ACR70, ACR50 and ACR20 (ACR weighted response, ACR70WR) and reported the cost-effectiveness ratio as cost per ACR20 or ACR70WR. Brennan and colleagues 160 carried out the analysis from a healthcare perspective, whereas the other studies included direct and indirect costs. The four studies differed in how etanercept use was modelled: Choi and colleagues 159 considered etanercept alone over a short period of 6 months; Brennan and colleagues 160 placed etanercept as third line therapy in a DMARD sequence over a patient lifetime; Welsing and colleagues 165 considered three different etanercept pathways (etanercept first, then switch to conventional DMARDs if there
TABLE 20 Summary of published ICERs for TNF inhibitor a Drug Comparator Study Date Time-horizon ICER © Queen’s Printer and Controller of HMSO 2006. All rights reserved. Health Technology Assessment 2006; Vol. 10: No. 42 Adalimumab DMARD sequence Bansback166 2005 Lifetime ACR50/DAS28 good: €34,167 per QALY (MTX) €34,922 per QALY (MTX) (from pooled analysis) €41,561 per QALY (monotherapy) ACR20/DAS28 moderate: €40,875 per QALY (+ MTX) €44,018 per QALY (+ MTX) (from pooled analysis) €65,499 per QALY (monotherapy) Anakinra Chiou 164 2004 1 year Adalimumab alone dominated Adalimumab + MTX dominated Etanercept Anakinra Chiou164 2004 1 year US $13,387 per QALY (monotherapy) US $7,925 per QALY (+ MTX) DMARD sequence Brennan 160,168 2004 Lifetime £16,330 per QALY DMARD sequence Bansback166 2005 Lifetime ACR50/DAS28 good: €35,760 per QALY (+ MTX) €36,927 per QALY (monotherapy) ACR20/DAS28 moderate: €51,976 per QALY (+ MTX) €42,480 per QALY (monotherapy) Baseline level Kobelt 163 2004 NA After 3 months of treatment: €43,500 per QALY (failed at least two DMARDs, including methotrexate) After 6 weeks of treatment: €36,900 per QALY MTX Kobelt 167 2005 10 years Etanercept alone dominated. Treatment for 2 years, extrapolation to 10 years: Etan–MTX €37,331 per QALY Treatment for 2 years, extrapolation to 5 years: Etan–MTX €54,548 per QALY Treatment for 10 years: Etan–MTX €46494 per QALY Treatment for 5 years, extrapolation to 10 years. Etan–MTX €47,316 per QALY DMARD sequence Jobanputra 1 2002 Lifetime £83,095 per QALY Usual treatment, Welsing165 2004 5 years Etanercept monotherapy dominated by leflunomide leflunomide/etanercept combinations Etanercept vs usual treatment: €163,556 per QALY for LEF–Etan €297,151 per QALY for Etan–LEF Etanercept vs leflunomide: €317,627 per QALY for LEF––Etan €517,061 per QALY for Etan–LEF Monotherapy Choi 159b 2002 6 months Etanercept–SSZ: $41,900 per ACR20 leflunomide, MTX, SSZ, no second line agent Etanercept–MTX: $40,800 per ACR70WR Infliximab Placebo and MTX Wong 161 2002 Lifetime $30,500 per QALY MTX Kobelt162 2003 10 years For 1 year of treatment: €3440 per QALY in Sweden €34,800 per QALY in UK continued 75
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A systematic review of the effectiv
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A systematic review of the effectiv
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Objectives: This report reviews the
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Glossary and list of abbreviations
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viii Glossary and list of abbreviat
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Background Rheumatoid arthritis (RA
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increased risk of serious infection
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Summary RA is a common, chronic, in
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(IL-2) and interleukin-6 (IL-6), pr
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Assessment of response to DMARDs Re
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combination with methotrexate or al
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disease between clinic appointments
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14 Effectiveness in juvenile arthri
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16 Effectiveness adalimumab plus me
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18 Effectiveness Monoclonal Antibod
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20 TABLE 1 Description of included
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22 TABLE 2 Quality of included RCTs
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Page 54 and 55: 38 Effectiveness etanercept trials.
Page 56 and 57: 40 Effectiveness TABLE 9 Summary of
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Page 89: Summary of review of existing econo
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Page 97 and 98: TABLE 25 Treatment sequences: adali
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Page 109 and 110: TABLE 39 Strategy set: adalimumab a
Page 111 and 112: TABLE 43 Beta distributions for HAQ
Page 113 and 114: TABLE 44 Early cessation of DMARDs:
Page 115 and 116: TABLE 46 Unit costs for tests and v
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Page 119 and 120: TABLE 52 Base case: TNF inhibitors
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Page 123 and 124: TABLE 59 Third TNF inhibitor follow
Page 125 and 126: TABLE 65 Sensitivity analyses: TNF
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Page 129: The substantial economic impact of
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Page 139: Adalimumab, etanercept and inflixim
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1. Jobanputra P, Barton P, Bryan S,
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46. Young A, Dixey J, Cox N, Davies
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tumor necrosis factor therapy in th
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arthritis: a 12-week, double-blind,
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171. Geborek P, Crnkic M, Petersson
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216. Schotte H, Willeke P, Mickholz
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The Health Assessment Questionnaire
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Cochrane Library (CENTRAL) 2005 Iss
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Appendix 3 © Queen’s Printer and
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TABLE 69 Studies excluded from clin
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148 Appendix 4 TABLE 71 Meta-analys
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150 Appendix 4 TABLE 73 Meta-analys
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152 Appendix 4 Infliximab versus pl
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154 Appendix 4 Infliximab plus MTX
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Ovid MEDLINE(R) 1966 to February we
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Appendix 8 © Queen’s Printer and
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TABLE 79 Wong et al., 2002 161 © Q
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TABLE 80 Kobelt et al., 2003 162 (c
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TABLE 82 Brennan et al., 2004 160
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TABLE 85 Bansback et al., 2005 166
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176 Appendix 9 TABLE 89 Strategy se
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Extensive sensitivity analysis was
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TABLE 96 Variation 1: TNF inhibitor
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TABLE 99 Variation 2: TNF inhibitor
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TABLE 102 Variation 3: TNF inhibito
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TABLE 132 Variation 10: TNF inhibit
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Volume 1, 1997 No. 1 Home parentera
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No. 3 Screening for sickle cell dis
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No. 25 A rapid and systematic revie
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No. 11 First and second trimester a
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No. 28 Outcomes of electrically sti
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246 Health Technology Assessment Pr
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A systematic review of the effectiveness of adalimumab

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