A systematic review of the effectiveness of adalimumab

62
Effectiveness
significant advantages over sequential
monotherapy with DMARDs or step-up
combination DMARD use.
Meta-analysis of infliximab results
The principles of analysis and data presentation of
infliximab trials are the same as described in the
section ‘Data analysis’ (p. 14), towards the
beginning of this chapter.
Infliximab versus other active treatment
The licence for infliximab stipulates that
infliximab has to be used in conjunction with
methotrexate, thus head-to-head comparison
between infliximab and methotrexate is not
considered here. However, relevant data from a
small, dose-ranging study 137 are summarised in
Table 74 (Appendix 4). Infliximab 3 mg kg –1 at 0,
2 and 6 weeks was more effective in all efficacy
outcomes than a single infusion of
methylprednisolone (1 g i.v.) in a small open-label
RCT by Durez and colleagues. 139
Infliximab versus placebo (with concurrent,
ongoing methotrexate)
Two trials (START 105,111 and ATTRACT 133 )
compared infliximab at licensed dose to placebo
in patients who had had an inadequate response
to methotrexate treatment. The results for these
primary analyses (licensed dose) are summarised
in Table 15 and the upper parts of Figures 35–45.
Additional data from a small, dose-ranging
study 136 for the comparison between infliximab
alone (not licensed use) and placebo without
concomitant methotrexate are not considered here
but are summarised in Table 74 (Appendix 4).
Efficacy Infliximab was significantly more effective
than placebo for all the efficacy outcomes being
meta-analysed.
Tolerability Significant heterogeneity in withdrawal
for any reasons was observed between ATTRACT
and START (test for heterogeneity p = 0.03).
Infliximab was better tolerated than placebo in
ATTRACT but not in the START.
Safety No significant differences were found
between infliximab and placebo in any of the
safety outcomes being meta-analysed. The number
of patients who had malignancy [Commercial-inconfidence
information removed].
Sensitivity analyses Three trials (Maini, 137
Kavanaugh 138 and Taylor 140 ) included
comparisons between infliximab and placebo at
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: 01 ACR20 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: 235 (infliximab), 102 (placebo)
Test for heterogeneity: 2 = 0.07, df = 1 (p = 0.79), I2 199/343 87/341
36/86 15/88
429 429
= 0%
Test for overall effect: z = 8.63 (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: 227 (infliximab), 153 (placebo)
Test for heterogeneity: 2 = 0.19, df = 1 (p = 0.66), I2 8/10 6/10
219/351 147/274
361 284
= 0%
Test for overall effect: z = 2.29 (p = 0.02)
Total (95% CI)
Total events: 462 (infliximab), 255 (placebo)
Test for heterogeneity: 2 = 35.12, df = 3 (p < 0.00001), I2 790 713
= 91.5%
Test for overall effect: z = 8.20 (p < 0.00001)
FIGURE 35 ACR20 RR: infliximab licensed dose versus placebo (with concurrent MTX)
RR (fixed)
95% CI
0.1 0.2 0.5 1 2 5 10
Favours placebo Favours infliximab
Weight
%
31.94
5.43
37.37
2.20
60.44
62.63
100.00
RR (fixed)
95% CI
2.27 (1.86 to 2.78)
2.46 (1.45 to 4.15)
2.30 (1.90 to 2.78)
1.33 (0.74 to 2.41)
1.16 (1.01 to 1.33)
1.17 (1.02 to 1.34)