A systematic review of the effectiveness of adalimumab

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40 Effectiveness TABLE 9 Summary of 2-year results from TEMPO study: etanercept s.c. licensed dose alone (25 mg twice weekly) versus MTX alone in MTX-naïve patients/responders, 2-year results Comparison or outcome N included Statistical method Effect size (95% CI) in analysis ACR20 responder 451 RR (fixed) 1.28 (1.06 to 1.54)* ACR50 responder 451 RR (fixed) 1.47 (1.15 to 1.89)* ACR70 responder 451 RR (fixed) 1.46 (1.00 to 2.14) RD ACR20 responder 451 RD (fixed) 0.12 (0.03 to 0.21)* RD ACR50 responder 451 RD (fixed) 0.14 (0.05 to 0.23)* RD ACR70 responder 451 RD (fixed) 0.08 (0.00 to 0.15) SJC, end of study result Patient’s global assessment, end of 451 WMD (fixed) –1.10 (–3.08 to 0.88) study result 451 WMD (fixed) –0.20 (–0.51 to 0.11) HAQ, end of study result 451 WMD (fixed) –0.10 (–0.23 to 0.03) DAS, end of study result 451 WMD (fixed) –0.10 (–0.31 to 0.11) Modified van de Heijde–Sharp score, mean change from baseline (1-year result) 424 WMD (fixed) –2.28 (–4.11 to –0.45)* Withdrawal for any reasons 451 RR (fixed) 0.81 (0.65 to 1.00) Withdrawal due to lack of efficacy 451 RR (fixed) 0.93 (0.59 to 1.47) Withdrawal due to adverse events 451 RR (fixed) 0.75 (0.50 to 1.11) Death 451 RR (fixed) 1.02 (0.06 to 16.25) SAEs 451 RR (fixed) 1.10 (0.75 to 1.61) Malignancy: all 451 RR (fixed) 2.56 (0.50 to 13.04) Malignancy: skin cancer excluding melanoma 451 RR (fixed) 2.04 (0.19 to 22.39) Malignancy: all cancer excluding non-melanoma skin cancer 451 RR (fixed) 3.07 (0.32 to 29.27) Serious infection 451 RR (fixed) 0.95 (0.47 to 1.93) Any infection 451 RR (fixed) 0.95 (0.85 to 1.06) * Statistically significant result (p < 0.05). Etanercept versus placebo Eight trials 103,104,121,122,125,126,129,130 compared etanercept at the licensed dose (or equivalent) to placebo. Three of the trials 121,122,126 also included sublicensed doses. No trial included doses above the licensed dose. Results of the primary analyses (licensed dose) are summarised in Table 10, and are also shown in the upper parts of Figures 24–34. Efficacy Etanercept was significantly more effective than placebo for all the efficacy outcomes being meta-analysed. Figure 24 shows a pattern of decreasing effect size for ACR20 in terms of relative risk in trials in that patients: (1) were not receiving any concurrent DMARDs; (2) were receiving concurrent DMARDs that had failed to provide adequate disease control; and (3) were receiving concurrent, newly initiated methotrexate. This pattern, however, is not clearly observed for other outcome measures, nor is it observed in trials of other TNF inhibitors. Tolerability Etanercept is better tolerated than placebo. Safety There were no significant differences between etanercept and placebo. In the trial by Baumgartner and colleagues, 104 which recruited patients with co-morbidity, five deaths occurred in the etanercept arm compared with one in the placebo arm. Sensitivity analysis The results of the sensitivity analysis, which included sublicensed doses, are summarised in Table 73 (Appendix 4). These are consistent with the primary analysis.
Review: Etanercept for rheumatoid arthritis 2006 Comparison: 03 Etanercept s.c. licensed dose only (25 mg twice weekly) vs other active treatment Outcome: 01 ACR20 responder Study or subcategory 01 Partial responders to comparator DMARD (SSZ) Codreanu, 2003 103 [24 weeks] Subtotal (95% CI) Total events: 76 (etanercept), 14 (control) Test for heterogeneity: NA Test for overall effect: z = 4.14 (p < 0.0001) Etanercept n/N © Queen’s Printer and Controller of HMSO 2006. All rights reserved. Control n/N 76/103 14/50 103 50 02 Responders or naive to comparator DMARD (MTX) TEMPO110 [100 weeks] ERA124 [104 weeks] Subtotal (95% CI) Total events: 275 (etanercept), 229 (control) Test for heterogeneity: 2 = 0.14, df = 1 (p = 0.70), I2 126/223 149/207 101/228 128/217 430 445 = 0% Test for overall effect: z = 3.78 (p = 0.0002) Total (95% CI) Total events: 351 (etanercept), 243 (control) Test for heterogeneity: 2 = 10.57, df = 2 (p = 0.005), I2 533 495 = 81.1% Test for overall effect: z = 5.28 (p < 0.00001) FIGURE 13 ACR20 RR: etanercept licensed dose versus other active treatment Review: Etanercept for rheumatoid arthritis 2006 Comparison: 03 Etanercept s.c. licensed dose only (25 mg twice weekly) vs other active treatment Outcome: 01 ACR20 responder Study or subcategory 01 Partial responders to comparator DMARD (SSZ) Codreanu, 2003 103 [24 weeks] Subtotal (95% CI) Total events: 76 (etanercept), 14 (control) Test for heterogeneity: NA Test for overall effect: z = 5.96 (p < 0.00001) Etanercept n/N Control n/N 76/103 14/50 103 50 02 Responders or naive to comparator DMARD (MTX) TEMPO110 [100 weeks] ERA124 [104 weeks] Subtotal (95% CI) Total events: 275 (etanercept), 229 (control) Test for heterogeneity: 2 = 0.01, df = 1 (p = 0.90), I2 126/223 149/207 101/228 128/217 430 445 = 0% Test for overall effect: z = 3.78 (p = 0.0001) Total (95% CI) Total events: 351 (etanercept), 243 (control) Test for heterogeneity: 2 = 15.84, df = 2 (p = 0.0004), I2 533 495 = 87.4% Test for overall effect: z = 5.64 (p < 0.00001) FIGURE 14 ACR20 RD: etanercept licensed dose versus other active treatment Health Technology Assessment 2006; Vol. 10: No. 42 RR (fixed) 95% CI 0.1 0.2 0.5 1 2 5 10 Favours control Favours etanercept RD (fixed) 95% CI –1 –0.5 0 0.5 1 Favours control Favours etanercept Weight % 7.73 7.73 40.98 51.28 92.27 100.00 Weight % 13.34 13.34 44.68 41.98 86.66 100.00 RR (fixed) 95% CI 2.64 (1.67 to 4.17) 2.64 (1.67 to 4.17) 1.28 (1.06 to 1.54) 1.22 (1.06 to 1.40) 1.24 (1.11 to 1.39) RD (fixed) 95% CI 0.46 (0.31 to 0.61) 0.46 (0.31 to 0.61) 0.12 (0.03 to 0.21) 0.13 (0.04 to 0.22) 0.13 (0.06 to 0.19) 41
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A systematic review of the effectiv
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A systematic review of the effectiv
Page 5 and 6: Objectives: This report reviews the
Page 7: Glossary and list of abbreviations
Page 10 and 11: viii Glossary and list of abbreviat
Page 13 and 14: Background Rheumatoid arthritis (RA
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Page 19 and 20: Summary RA is a common, chronic, in
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Page 36 and 37: 20 TABLE 1 Description of included
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een quit on grounds of toxicity, ad
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TABLE 39 Strategy set: adalimumab a
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TABLE 43 Beta distributions for HAQ
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TABLE 44 Early cessation of DMARDs:
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TABLE 46 Unit costs for tests and v
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following properties, according to
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TABLE 52 Base case: TNF inhibitors
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TABLE 54 Base case: TNF inhibitors
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TABLE 59 Third TNF inhibitor follow
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TABLE 65 Sensitivity analyses: TNF
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TABLE 67 Sensitivity analyses: TNF
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The substantial economic impact of
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Summary Effectiveness: principal fi
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inhibitors, although the incrementa
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introduce bias which generally exag
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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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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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A systematic review of the effectiveness of adalimumab

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