A systematic review of the effectiveness of adalimumab
A systematic review of the effectiveness of adalimumab A systematic review of the effectiveness of adalimumab
66 Effectiveness Review: Infliximab for rheumatoid arthritis 2006 Comparison: 03 Infliximab i.v. licensed dose only (3 mg kg –1 every 8 weeks) + MTX vs Placebo + MTX, end of trial Outcome: 03 ACR70 responder Study or subcategory Infliximab n/N Placebo n/N 01 With concurrent, ongoing MTX START, 111 [22 weeks] (+) ATTRACT, 132,133 [54 weeks] (+) Subtotal (95% CI) Total events: 57 (infliximab), 18 (placebo) Test for heterogeneity: 2 = 0.07, df = 1 (p = 0.79), I2 48/343 16/341 9/86 2/88 429 429 = 0% Test for overall effect: z = 4.77 (p < 0.00001) 02 With concurrent, newly initiated MTX (infliximab + MTX vs MTX) Quinn, 2005, 141 [54 weeks] (+) ASPIRE, 135 [54 weeks] (+) Subtotal (95% CI) Total events: 121 (infliximab), 61 (placebo) Test for heterogeneity: 2 = 1.90, df = 1 (p = 0.17), I2 7/10 3/10 114/351 58/274 361 284 = 47.5% Test for overall effect: z = 3.53 (p = 0.0004) Total (95% CI) Total events: 178 (infliximab), 79 (placebo) Test for heterogeneity: 2 = 2.77, df = 3 (p = 0.43), I2 790 713 = 0% Test for overall effect: z = 5.68 (p < 0.00001) FIGURE 40 ACR70 RD: infliximab licensed dose versus placebo (with concurrent MTX) RD (fixed) 95% CI –1 –0.5 0 0.5 1 Favours placebo Favours infliximab Review: Infliximab for rheumatoid arthritis 2006 Comparison: 03 Infliximab i.v. licensed dose only (3 mg kg –1 every 8 weeks) + MTX vs Placebo + MTX, end of trial Outcome: 12 HAQ, mean change from baseline Study or subcategory 01 With concurrent, ongoing MTX START, 111 [22 weeks] (+) ATTRACT, 132,133 [54 weeks] (+) Subtotal (95% CI) N Inflaximab mean (SD) N Test for heterogeneity: 2 = 0.46, df = 1 (p = 0.50), I 2 = 0% Test for overall effect: z = 6.74 (p < 0.00001) 02 With concurrent, newly initiated MTX (infliximab + MTX vs MTX) Quinn, 2005, 141 [54 weeks] (+) ASPIRE, 135 [54 weeks] (+) Subtotal (95% CI) Placebo mean (SD) 337 –0.39 (0.60) 336 –0.11 (0.51) 77 –0.50 (0.66 68 –0.30 (0.66) 414 404 10 –1.09 (0.65) 10 –0.22 (0.72) 311 –0.83 (0.71) 232 –0.72 (0.72) 321 242 Test for heterogeneity: 2 = 5.90, df = 1 (p = 0.02), I 2 = 83.0% Test for overall effect: z = 2.30 (p = 0.02) Total (95% CI) Test for heterogeneity: 2 = 9.52, df = 3 (p = 0.02), I2 735 646 = 68.5% Test for overall effect: z = 6.89 (p < 0.00001) WMD (fixed) 95% CI –1 –0.5 0 0.5 1 Favours infliximab Favours placebo FIGURE 41 HAQ change: infliximab licensed dose only versus placebo (with concurrent MTX) Weight % 45.80 11.65 57.45 1.34 41.21 42.55 100.00 Weight % 60.60 9.26 69.85 1.19 28.96 30.15 100.00 RD (fixed) 95% CI 0.09 (0.05 to 0.14) 0.08 (0.01 to 0.15) 0.09 (0.05 to 0.13) 0.40 (0.00 to 0.80) 0.11 (0.04 to 0.18) 0.12 (0.05 to 0.19) 0.10 (0.07 to 0.14) WMD (fixed) 95% CI –0.20 (–0.36 to –0.20) –0.20 (–0.42 to 0.02) –0.27 (–0.35 to –0.19) –0.87 (–1.47 to –0.27) –0.11 (–0.23 to 0.01) –0.14 (–0.26 to –0.02) –0.23 (–0.30 to –0.16)
Review: Infliximab for rheumatoid arthritis 2006 Comparison: 03 Infliximab i.v. licensed dose only (3 mg kg –1 every 8 weeks) + MTX vs Placebo + MTX, end of trial Outcome: 07 SAEs Study or subcategory Infliximab n/N Placebo n/N 01 With concurrent, ongoing MTX START, 111 [22 weeks] (+) ATTRACT, 132,133 [54 weeks] (+) Subtotal (95% CI) Total events: 38 (infliximab), 45 (placebo) Test for heterogeneity: 2 = 2.11, df = 1 (p = 0.15), I2 28/360 27/361 10/88 18/86 448 447 = 52.7% Test for overall effect: z = 0.84 (p = 0.40) 02 With concurrent, newly initiated MTX (infliximab + MTX vs MTX) ASPIRE, 135 [54 weeks] (+) Subtotal (95% CI) Total events: 52 (infliximab), 32 (placebo) Test for heterogeneity: NA Test for overall effect: z = 1.14 (p = 0.25) 52/372 32/291 372 291 Total (95% CI) Total events: 90 (infliximab), 77 (placebo) Test for heterogeneity: 2 = 4.09, df = 2 (p = 0.13), I2 820 738 = 51.1% Test for overall effect: z = 0.21 (p = 0.84) FIGURE 42 SAE RR: infliximab licensed dose versus placebo (with concurrent MTX) © Queen’s Printer and Controller of HMSO 2006. All rights reserved. Health Technology Assessment 2006; Vol. 10: No. 42 RR (fixed) 95% CI 0.1 0.2 0.5 1 2 5 10 Favours infliximab Favours placebo Review: Infliximab for rheumatoid arthritis 2006 Comparison: 03 Infliximab i.v. licensed dose only (3 mg kg –1 every 8 weeks) + MTX vs Placebo + MTX, end of trial Outcome: 07 SAEs Study or subcategory Infliximab n/N Placebo n/N 01 With concurrent, ongoing MTX START, 111 [22 weeks] (+) ATTRACT, 132,133 [54 weeks] (+) Subtotal (95% CI) Total events: 38 (infliximab), 45 (placebo) Test for heterogeneity: 2 = 3.00, df = 1 (p = 0.08), I2 28/360 27/361 10/88 18/86 448 447 = 66.7% Test for overall effect: z = 0.84 (p = 0.40) 02 With concurrent, newly initiated MTX (infliximab + MTX vs MTX) ASPIRE, 135 [54 weeks] (+) Subtotal (95% CI) Total events: 52 (infliximab), 32 (placebo) Test for heterogeneity: NA Test for overall effect: z = 1.16 (p = 0.25) 52/372 32/291 372 291 Total (95% CI) Total events: 90 (infliximab), 77 (placebo) Test for heterogeneity: 2 = 4.26, df = 2 (p = 0.12), I2 820 738 = 53.0% Test for overall effect: z = 0.21 (p = 0.84) FIGURE 43 SAE RD: infliximab licensed dose versus placebo (with concurrent MTX) RD (fixed) 95% CI –1 –0.5 0 0.5 1 Favours infliximab Favours placebo Weight % 33.25 22.46 55.71 44.29 44.29 100.00 Weight % 46.57 11.24 57.81 42.19 42.19 100.00 RR (fixed) 95% CI 1.04 (0.63 to 1.73) 0.54 (0.27 to 1.11) 0.84 (0.56 to 1.26) 1.27 (0.84 to 1.92) 1.27 (0.84 to 1.92) 1.03 (0.77 to 1.38) RD (fixed) 95% CI 0.00 (–0.04 to 0.04) –0.10 (–0.20 to 0.01) –0.02 (–0.05 to 0.02) 0.03 (–0.02 to 0.08) 0.03 (–0.02 to 0.08) 0.00 (–0.03 to 0.03) 67
- Page 32 and 33: 16 Effectiveness adalimumab plus me
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66<br />
Effectiveness<br />
Review: Infliximab for rheumatoid arthritis 2006<br />
Comparison: 03 Infliximab i.v. licensed dose only (3 mg kg –1 every 8 weeks) + MTX vs Placebo + MTX, end <strong>of</strong> trial<br />
Outcome: 03 ACR70 responder<br />
Study<br />
or subcategory<br />
Infliximab<br />
n/N<br />
Placebo<br />
n/N<br />
01 With concurrent, ongoing MTX<br />
START, 111 [22 weeks] (+)<br />
ATTRACT, 132,133 [54 weeks] (+)<br />
Subtotal (95% CI)<br />
Total events: 57 (infliximab), 18 (placebo)<br />
Test for heterogeneity: 2 = 0.07, df = 1 (p = 0.79), I2 48/343 16/341<br />
9/86 2/88<br />
429 429<br />
= 0%<br />
Test for overall effect: z = 4.77 (p < 0.00001)<br />
02 With concurrent, newly initiated MTX (infliximab + MTX vs MTX)<br />
Quinn, 2005, 141 [54 weeks] (+)<br />
ASPIRE, 135 [54 weeks] (+)<br />
Subtotal (95% CI)<br />
Total events: 121 (infliximab), 61 (placebo)<br />
Test for heterogeneity: 2 = 1.90, df = 1 (p = 0.17), I2 7/10 3/10<br />
114/351 58/274<br />
361 284<br />
= 47.5%<br />
Test for overall effect: z = 3.53 (p = 0.0004)<br />
Total (95% CI)<br />
Total events: 178 (infliximab), 79 (placebo)<br />
Test for heterogeneity: 2 = 2.77, df = 3 (p = 0.43), I2 790 713<br />
= 0%<br />
Test for overall effect: z = 5.68 (p < 0.00001)<br />
FIGURE 40 ACR70 RD: infliximab licensed dose versus placebo (with concurrent MTX)<br />
RD (fixed)<br />
95% CI<br />
–1 –0.5 0 0.5 1<br />
Favours placebo Favours infliximab<br />
Review: Infliximab for rheumatoid arthritis 2006<br />
Comparison: 03 Infliximab i.v. licensed dose only (3 mg kg –1 every 8 weeks) + MTX vs Placebo + MTX, end <strong>of</strong> trial<br />
Outcome: 12 HAQ, mean change from baseline<br />
Study<br />
or subcategory<br />
01 With concurrent, ongoing MTX<br />
START, 111 [22 weeks] (+)<br />
ATTRACT, 132,133 [54 weeks] (+)<br />
Subtotal (95% CI)<br />
N<br />
Inflaximab<br />
mean (SD) N<br />
Test for heterogeneity: 2 = 0.46, df = 1 (p = 0.50), I 2 = 0%<br />
Test for overall effect: z = 6.74 (p < 0.00001)<br />
02 With concurrent, newly initiated MTX (infliximab + MTX vs MTX)<br />
Quinn, 2005, 141 [54 weeks] (+)<br />
ASPIRE, 135 [54 weeks] (+)<br />
Subtotal (95% CI)<br />
Placebo<br />
mean (SD)<br />
337 –0.39 (0.60) 336 –0.11 (0.51)<br />
77 –0.50 (0.66 68 –0.30 (0.66)<br />
414 404<br />
10 –1.09 (0.65) 10 –0.22 (0.72)<br />
311 –0.83 (0.71) 232 –0.72 (0.72)<br />
321 242<br />
Test for heterogeneity: 2 = 5.90, df = 1 (p = 0.02), I 2 = 83.0%<br />
Test for overall effect: z = 2.30 (p = 0.02)<br />
Total (95% CI)<br />
Test for heterogeneity: 2 = 9.52, df = 3 (p = 0.02), I2 735 646<br />
= 68.5%<br />
Test for overall effect: z = 6.89 (p < 0.00001)<br />
WMD (fixed)<br />
95% CI<br />
–1 –0.5 0 0.5 1<br />
Favours infliximab Favours placebo<br />
FIGURE 41 HAQ change: infliximab licensed dose only versus placebo (with concurrent MTX)<br />
Weight<br />
%<br />
45.80<br />
11.65<br />
57.45<br />
1.34<br />
41.21<br />
42.55<br />
100.00<br />
Weight<br />
%<br />
60.60<br />
9.26<br />
69.85<br />
1.19<br />
28.96<br />
30.15<br />
100.00<br />
RD (fixed)<br />
95% CI<br />
0.09 (0.05 to 0.14)<br />
0.08 (0.01 to 0.15)<br />
0.09 (0.05 to 0.13)<br />
0.40 (0.00 to 0.80)<br />
0.11 (0.04 to 0.18)<br />
0.12 (0.05 to 0.19)<br />
0.10 (0.07 to 0.14)<br />
WMD (fixed)<br />
95% CI<br />
–0.20 (–0.36 to –0.20)<br />
–0.20 (–0.42 to 0.02)<br />
–0.27 (–0.35 to –0.19)<br />
–0.87 (–1.47 to –0.27)<br />
–0.11 (–0.23 to 0.01)<br />
–0.14 (–0.26 to –0.02)<br />
–0.23 (–0.30 to –0.16)
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