A systematic review of the effectiveness of adalimumab

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102 Health economics TABLE 51 Base case: TNF inhibitors third (late RA values) (40,000 patients) Option Cost (£) QSE QALYs QSE Adal 47,442 154 5.6365 0.0234 Etan 60,341 188 6.3415 0.0246 Adal+MTX 47,963 155 5.9053 0.0232 Etan+MTX 60,329 188 6.2974 0.0250 Infl+MTX 47,278 148 5.6380 0.0235 Base 16,509 36 5.4169 0.0218 Comparison Diff. cost (£) QSE Diff. QALY QSE Adal – Base 30,934 150 0.2196 0.0224 Etan – Base 43,832 181 0.9246 0.0237 Ad+M – Base 31,454 151 0.4884 0.0226 Et+M – Base 43,821 182 0.8805 0.0241 In+M – Base 30,770 145 0.2212 0.0224 Ad+M – Adal 520 204 0.2688 0.0288 Etan – Et+M 12 243 0.0441 0.0252 Etan – Adal 12,899 225 0.7050 0.0238 Et+M – Ad+M 12,367 225 0.3920 0.0242 Ad+M – In+M 684 200 0.2673 0.0228 Et+M – In+M 13,051 221 0.6593 0.0241 Comparison ICER (£ per QALY) Quasi-CI Adal – Base 141,000 117,000 to 177,000 Etan – Base 47,400 45,100 to 50,000 Ad+M – Base 64,400 58,900 to 71,000 Et+M – Base 49,800 47,200 to 52,700 In+M – Base 139,000 116,000 to 174,000 Ad+M – Adal 1,940 382 to 3,490 Etan – Et+M Comparison is inconclusive Etan – Adal 18,300 17,000 to 19,800 Et+M – Ad+M 31,500 27,900 to 36,200 Ad+M – In+M 2,560 999 to 4,120 Et+M – In+M 19,800 18,300 to 21,500 QSE, quasi-standard error. Ad, adalimumab; Et, etanercept; In, infliximab; M, methotrexate. Sequential use of TNF inhibitors Sequential use of TNF inhibitors was modelled with the TNF inhibitors starting as third line therapy and using the ‘late RA’ values for the TNF inhibitors. Base-case ICERs are summarised in Table 55 and the individual results for the sequential use of TNF inhibitors are given in Tables 56–64. The results are similar to those using the ‘Following TNF inhibitor’ as the sole TNF inhibitor in third place as shown in Table 51, except that the two other TNF inhibitors are somewhat less cost-effective if used after etanercept. Similar results were obtained for TNF inhibitors as the third in the sequence. Sensitivity analysis Extensive sensitivity analysis has been carried out for all strategy sets involving use of a single TNF inhibitor. As in the base case, for the HAQ improvement on starting a TNF inhibitor, the early RA values were used for the strategy set involving TNF inhibitors at the start, the late RA values were used for TNF inhibitors last, and both sets of values were used for TNF inhibitors in third place. Full details of the sensitivity analysis are given in Appendix 10. Summarised forms are given in Tables 65–68. Summary of model results When the effectiveness values for early RA were used for TNF inhibitors in third place, the results for the three TNF inhibitors were broadly similar. They are sensitive to assumptions about HAQ progression while on treatment, and to assumptions about effectiveness and long-term survival on conventional DMARDs. When the effectiveness values for late RA were used instead, the results were considerably less favourable.
TABLE 52 Base case: TNF inhibitors third (early RA values) (100,000 patients) © Queen’s Printer and Controller of HMSO 2006. All rights reserved. Health Technology Assessment 2006; Vol. 10: No. 42 Option Cost (£) QSE QALYs QSE Adal 48,264 98 6.3183 0.0150 Etan 60,948 119 6.8617 0.0159 Adal+MTX 48,536 99 6.4613 0.0149 Etan+MTX 61,254 119 6.9715 0.0160 Infl+MTX 48,173 94 6.4405 0.0149 Base 16,494 23 5.3995 0.0138 Comparison Diff. cost (£) QSE Diff. QALY QSE Adal – Base 31,770 96 0.9188 0.0148 Etan – Base 44,454 116 1.4623 0.0157 Ad+M – Base 32,042 96 1.0619 0.0148 Et+M – Base 44,761 116 1.5720 0.0157 In+M – Base 31,679 92 1.0410 0.0147 Ad+M – Adal 272 131 0.1430 0.0154 Et+M – Etan 306 155 0.1097 0.0169 Etan – Adal 12,684 144 0.5434 0.0162 Et+M – Ad+M 12,719 144 0.5101 0.0163 Ad+M – In+M 362 128 0.0208 0.0154 Et+M – In+M 13,081 142 0.5310 0.0162 Comparison ICER (£ per QALY) Quasi-CI Adal – Base 34,600 33,500 to 35,700 Etan – Base 30,400 29,700 to 31,100 Ad+M – Base 30,200 29,300 to 31,100 Et+M – Base 28,500 27,900 to 29,100 In+M – Base 30,400 29,600 to 31,300 Ad+M – Adal 1,900 23 to 3,780 Et+M – Etan Etan+MTX more effective than Etan alone; diff. cost not significant Etan – Adal 23,300 21,900 to 24,900 Et+M – Ad+M 24,900 23,400 to 26,700 In+M – Ad+M Adal+MTX more costly than Infl+MTX; diff. QALY not significant Et+M – In+M 24,600 23,100 to 26,300 When the effectiveness values for early RA were used for TNF inhibitors at the start, the results were somewhat less favourable than the results obtained using early RA values for TNF inhibitors in third place. The results for combinations with methotrexate were much worse than for monotherapy. This reflects the definition of the strategy options, in that starting with a TNF inhibitor in combination with methotrexate precludes the later use of methotrexate alone. An important limitation of this work is the poor quality of the data on effectiveness of conventional DMARDs. It has not been possible to find data that would support quantification of a reduction in effectiveness with disease duration. 103
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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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24 Effectiveness change in modified
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26 Effectiveness TABLE 4 Meta-analy
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28 Effectiveness Review: Adalimumab
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30 Effectiveness Review: Adalimumab
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32 TABLE 6 Effectiveness Descriptio
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34 TABLE 6 Effectiveness Descriptio
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36 TABLE 7 Effectiveness Quality of
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38 Effectiveness etanercept trials.
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40 Effectiveness TABLE 9 Summary of
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42 Effectiveness Review: Etanercept
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Page 68 and 69: 52 Effectiveness Review: Etanercept
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Page 74 and 75: 58 TABLE 13 Quality of included RCT
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Page 80 and 81: 64 Effectiveness Review: Infliximab
Page 82 and 83: 66 Effectiveness Review: Infliximab
Page 84 and 85: 68 Effectiveness FIGURE 44 Malignan
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Page 89 and 90: Summary of review of existing econo
Page 91 and 92: TABLE 20 Summary of published ICERs
Page 93 and 94: TABLE 21 Published etanercept econo
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Page 97 and 98: TABLE 25 Treatment sequences: adali
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Page 103 and 104: TABLE 32 TNF inhibitors as last act
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Page 109 and 110: TABLE 39 Strategy set: adalimumab a
Page 111 and 112: TABLE 43 Beta distributions for HAQ
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Page 115 and 116: TABLE 46 Unit costs for tests and v
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Page 121 and 122: TABLE 54 Base case: TNF inhibitors
Page 123 and 124: TABLE 59 Third TNF inhibitor follow
Page 125 and 126: TABLE 65 Sensitivity analyses: TNF
Page 127 and 128: TABLE 67 Sensitivity analyses: TNF
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Page 133 and 134: Summary Effectiveness: principal fi
Page 135 and 136: inhibitors, although the incrementa
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Page 139: Adalimumab, etanercept and inflixim
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Page 145 and 146: 46. Young A, Dixey J, Cox N, Davies
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Page 149 and 150: arthritis: a 12-week, double-blind,
Page 151 and 152: 171. Geborek P, Crnkic M, Petersson
Page 153 and 154: 216. Schotte H, Willeke P, Mickholz
Page 155 and 156: The Health Assessment Questionnaire
Page 157 and 158: Cochrane Library (CENTRAL) 2005 Iss
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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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