A systematic review of the effectiveness of adalimumab

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52 Effectiveness Review: Etanercept for rheumatoid arthritis 2006 Comparison: 01 Etanercept s.c. licensed dose only (25 mg twice weekly or 50 mg once weekly) vs placebo, end of trial Outcome: 07 SAEs Study or subcategory Etanercept n/N Control n/N 01 With (+) or without (–) concurrent, ongoing conventional DMARDs Moreland, 1999122 [26 weeks] (–) Keystone, 2004129 [8 weeks] (±) Baumgartner, 2004104 [20 weeks] (±) Weinblatt, 1999125 [24 weeks] (+) Codreanu, 2003103 [24 weeks] (+) Subtotal (95% CI) Total events: 37 (etanercept), 23 (control) Test for heterogeneity: 2 = 3.27, df = 4 (p = 0.51), I2 2/78 5/367 23/266 2/59 5/101 3/80 0/53 16/269 3/30 1/50 871 482 = 0% Test for overall effect: z = 0.95 (p = 0.34) 02 With concurrent, newly initiated MTX (etanercept + MTX) TEMPO 110 [104 weeks] (+) Subtotal (95% CI) Total events: 52 (etanercept), 41 (control) Test for heterogeneity: NA Test for overall effect: z = 1.21 (p = 0.23) 52/231 41/228 231 228 Total (95% CI) Total events: 89 (etanercept), 64 (control) Test for heterogeneity: 2 = 4.55, df = 5 (p = 0.47), I2 1102 710 = 0% Test for overall effect: z = 1.54 (p = 0.12) RD (fixed) 95% CI –0.5 –0.25 0 0.25 0.5 Favours etanercept Favours control Weight % 10.19 11.95 34.50 5.13 8.63 70.40 29.60 29.60 100.00 FIGURE 32 SAE RD: etanercept licensed dose only versus placebo (including etanercept plus MTX versus MTX) Review: Etanercept for rheumatoid arthritis 2006 Comparison: 01 Etanercept s.c. licensed dose only (25 mg twice weekly or 50 mg once weekly) vs placebo, end of trial Outcome: 09 Malignancy Study or subcategory Etanercept n/N Control n/N 01 With (+) or without (–) concurrent, ongoing conventional DMARDs Wadjula, 2000126 [12 weeks] (–) Moreland, 1999122 [26 weeks] (–) Keystone, 2004129 [8 weeks] (±) Baumgartner, 2004104 [20 weeks] (±) Weinblatt, 1999125 [24 weeks] (+) Codreanu, 2003103 [24 weeks] (+) Subtotal (95% CI) Total events: 2 (etanercept), 5 (control) Test for heterogeneity: 2 = 0.60, df = 2 (p = 0.74), I2 0/111 0/78 0/367 2/266 0/59 0/101 1/105 0/80 0/53 3/269 1/30 0/50 982 587 = 0% Test for overall effect: z = 1.21 (p = 0.23) 02 With concurrent, newly initiated MTX (etanercept + MTX) TEMPO 110 [104 weeks] (+) Subtotal (95% CI) Total events: 5 (etanercept), 2 (control) Test for heterogeneity: NA Test for overall effect: z = 1.09 (p = 0.28) 5/231 2/228 231 228 Total (95% CI) Total events: 7 (etanercept), 7 (control) Test for heterogeneity: 2 = 30.3, df = 3 (p = 0.39), I2 1213 815 = 1.0% Test for overall effect: z = 0.18 (p = 0.86) RR (fixed) 95% CI 0.01 0.1 1 10 100 Favours etanercept Favours control Weight % FIGURE 33 Malignancy RR: etanercept licensed dose only versus placebo (including etanercept plus MTX versus MTX) 18.10 35.03 23.23 76.36 23.64 23.64 100.00 RD (fixed) 95% CI –0.01 (–0.07 to 0.04) 0.01 (–0.01 to 0.04) 0.03 (–0.02 to 0.07) –0.07 (–0.18 to 0.05) 0.03 (–0.03 to 0.09) 0.01 (–0.01 to 0.04) 0.05 (–0.03 to 0.12) 0.05 (–0.03 to 0.12) 0.02 (–0.01 to 0.05) RR (fixed) 95% CI 0.32 (0.01 to 7.66) Not estimable Not estimable 0.67 (0.11 to 4.00) 0.17 (0.01 to 4.10) Not estimable 0.44 (0.11 to 1.68) 2.47 (0.48 to 12.59) 2.47 (0.48 to 12.59) 0.92 (0.35 to 2.37)
Review: Etanercept for rheumatoid arthritis 2006 Comparison: 01 Etanercept s.c. licensed dose only (25 mg twice weekly or 50 mg once weekly) vs placebo, end of trial Outcome: 09 Malignancy Study or subcategory Etanercept n/N manufacturer. Results beyond week 54 were not included in meta-analyses for the following reasons: first, there was a substantial difference in the proportion of patients entering the second year between treatment arms (32% for the placebo plus methotrexate arm and 68% for the infliximab plus methotrexate arms combined); secondly, treatment was unblinded for 12% of the patients before completion of all HAQ evaluations; and thirdly, 94 of the 259 patients in the infliximab groups had a treatment gap between first year and second year of more than 8 weeks (mean 19.4 weeks) because of the timing of the protocol amendment. Consequently, the 54-week results are referred to as the end of study results in metaanalyses, unless otherwise specified. ASPIRE: St Clair and colleagues, 2004 135 This 54-week, double-blind, multicentre RCT compared treatment with methotrexate alone (starting at 7.5 mg per week and escalated to 20 mg per week) and infliximab (3 or 6 mg kg –1 i.v. every 8 weeks) with methotrexate. Only patients with early RA, disease duration of 3 months to 3 years, were included. A minimum of ten swollen joints and 12 tender joints were Control n/N 01 With (+) or without (–) concurrent, ongoing conventional DMARDs Wadjula, 2000126 [12 weeks] (–) Moreland, 1999122 [26 weeks] (–) Keystone, 2004129 [8 weeks] (±) Baumgartner, 2004104 [20 wks] (±) Weinblatt, 1999125 [24 weeks] (+) Codreanu, 2003103 [24 weeks] (+) Subtotal (95% CI) Total events: 2 (etanercept), 5 (control) Test for heterogeneity: 2 = 1.06, df = 5 (p = 0.96), I2 0/111 0/78 0/367 2/266 0/59 0/101 1/105 0/80 0/53 3/269 1/30 0/50 982 587 = 0% Test for overall effect: z = 0.91 (p = 0.36) 02 With concurrent, newly initiated MTX (etanercept + MTX) TEMPO 110 [104 weeks] (+) Subtotal (95% CI) Total events: 5 (etanercept), 2 (control) Test for heterogeneity: NA Test for overall effect: z = 1.13 (p = 0.26) 5/231 2/228 231 228 Total (95% CI) Total events: 7 (etanercept), 7 (control) Test for heterogeneity: 2 = 2.67, df = 6 (p = 0.85), I2 1213 815 = 0% Test for overall effect: z = 0.08 (p = 0.93) © Queen’s Printer and Controller of HMSO 2006. All rights reserved. Health Technology Assessment 2006; Vol. 10: No. 42 RD (fixed) 95% CI –0.05 –0.25 0 0.25 0.5 Favours etanercept Favours control Weight % FIGURE 34 Malignancy RD: etanercept licensed dose only versus placebo (including etanercept + MTX versus MTX) 12.22 8.94 10.49 30.29 4.50 7.57 74.02 25.98 25.98 100.00 RD (fixed) 95% CI –0.01 (–0.04 to 0.02) 0.00 (–0.02 to 0.02) 0.00 (–0.03 to 0.03) 0.00 (–0.02 to 0.01) –0.03 (–0.11 to 0.05) 0.00 (–0.03 to 0.03) –0.01 (–0.02 to 0.01) 0.01 (–0.01 to 0.04) 0.01 (–0.01 to 0.04) 0.01 (–0.01 to 0.01) required. Patients who had received more than three doses of methotrexate or received other DMARDs within 4 weeks of study entry were not eligible. Forty-five patients from two study sites out of 1049 randomised patients were excluded from efficacy analysis because the data could not be verified with source documents. The study had three primary end-points: ACR-N from baseline to week 54 (for reduction of signs and symptoms), van der Heijde modification of the total Sharp score (for radiographic progression of joint damage) and change from baseline in HAQ scores averaged over weeks 30–54 (for improvement in physical function). The safety outcomes for this trial were reported and analysed according to the actual treatment that the patient had received. Durez and colleagues, 2004 139,142 This small open-label, single-centre RCT compared a single pulse of methylprednisolone (1 gm i.v.) with three infusions (at weeks 0, 2 and 6) of infliximab 3 mg kg –1 i.v. in patients receiving concurrent methotrexate (10–15 mg per week). Patients with disease for more than 1 year and at 53
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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
Page 19 and 20: Summary RA is a common, chronic, in
Page 21 and 22: (IL-2) and interleukin-6 (IL-6), pr
Page 23 and 24: Assessment of response to DMARDs Re
Page 25 and 26: combination with methotrexate or al
Page 27: disease between clinic appointments
Page 30 and 31: 14 Effectiveness in juvenile arthri
Page 32 and 33: 16 Effectiveness adalimumab plus me
Page 34 and 35: 18 Effectiveness Monoclonal Antibod
Page 36 and 37: 20 TABLE 1 Description of included
Page 38 and 39: 22 TABLE 2 Quality of included RCTs
Page 40 and 41: 24 Effectiveness change in modified
Page 42 and 43: 26 Effectiveness TABLE 4 Meta-analy
Page 44 and 45: 28 Effectiveness Review: Adalimumab
Page 46 and 47: 30 Effectiveness Review: Adalimumab
Page 48 and 49: 32 TABLE 6 Effectiveness Descriptio
Page 50 and 51: 34 TABLE 6 Effectiveness Descriptio
Page 52 and 53: 36 TABLE 7 Effectiveness Quality of
Page 54 and 55: 38 Effectiveness etanercept trials.
Page 56 and 57: 40 Effectiveness TABLE 9 Summary of
Page 58 and 59: 42 Effectiveness Review: Etanercept
Page 70 and 71: 54 Effectiveness TABLE 11 Summary o
Page 72 and 73: 56 TABLE 12 Description of included
Page 74 and 75: 58 TABLE 13 Quality of included RCT
Page 76 and 77: 60 Effectiveness per week and escal
Page 78 and 79: 62 Effectiveness significant advant
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
Page 86 and 87: 70 TABLE 17 Effectiveness Summary o
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
Page 95 and 96: TABLE 23 Published economic analyse
Page 97 and 98: TABLE 25 Treatment sequences: adali
Page 99 and 100: management of RA, i.e. 1st and 2nd
Page 101 and 102: To estimate the long-term consequen
Page 103 and 104: TABLE 32 TNF inhibitors as last act
Page 105 and 106: TABLE 34 Basic structure of the mod
Page 107 and 108: een quit on grounds of toxicity, ad
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
Page 117 and 118: 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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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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No. 25 A rapid and systematic revie
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A systematic review of the effectiveness of adalimumab

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