A systematic review of the effectiveness of adalimumab

30
Effectiveness
Review: Adalimumab for rheumatoid arthritis 2006
Comparison: 03 Adalimumab s.c. licensed dose only (40 mg every other week or equivalent) vs placebo, end of trial
Outcome: 12 HAQ, mean change from baseline
Study
or subcategory
N
Adalimumab
mean (SD) N
01 With (+) or without (–) concurrent, ongoing conventional DMARDs
van de Putte, 2003 119 [12 weeks] (–)
van de Putte, 2004 113 [26 weeks] (–)
STAR 115 [24 weeks] (±)
ARMADA 112 [24 weeks] (+)
Keystone, 2004 114 [52 weeks] (+)
Subtotal (95% CI)
Test for heterogeneity: 2 = 4.90, df = 4 (p = 0.30), I 2 = 18.4%
Test for overall effect: z = 12.41 (p < 0.00001)
TEMPO, 127,128 Keystone, 129 and Baumgartner. 104
Additional data from these reports were included
in this systematic review. The report by Lan and
colleagues 130 was only available as a published
paper.
A list of these trials, including comparators and
baseline patient characteristics, is shown in Table 6.
Quality assessments of these trials, which are
generally of high quality, are summarised in
Table 7. In all trials, except for Baumgartner, 104
Control
mean (SD)
71 –0.45 (0.46) 70 –0.04 (0.37)
225 –0.38 (0.61) 110 –0.07 (0.49)
312 –0.51 (0.56) 314 –0.26 (0.48)
67 –0.62 (0.63) 62 –0.27 (0.57)
419 –0.60 (0.56) 200 –0.25 (0.56)
1094 756
02 With concurrent, newly initiated MTX (adalimumab + MTX vs MTX)
PREMIER102,109 [104 weeks] (+) 201 –1.00 (0.70) 166 –0.90 (0.60)
Subtotal (95% CI)
201 166
Test for heterogeneity: NA
Test for overall effect: z = 1.47 (p = 0.14)
Total (95% CI)
Test for heterogeneity: 2 = 13.65, df = 5 (p = 0.02), I2 1295 922
= 63.4%
Test for overall effect: z = 12.14 (p < 0.00001)
WMD (fixed)
(95% CI)
–1 –0.5
Favours
0 0.5 1
Favours
adalimumab control
Weight
(%)
11.40
14.67
32.37
5.04
24.30
87.78
12.22
12.22
100.00
FIGURE 8 HAQ change: adalimumab licensed dose versus placebo (including adalimumab plus MTX versus MTX)
FIGURE 9 SAE RR: adalimumab licensed dose versus placebo
(including adalimumab plus MTX versus MTX)
[Commercial-in-confidence information
removed].
FIGURE 10 SAE RD: adalimumab licensed dose versus placebo
(including adalimumab plus MTX versus MTX)
[Commercial-in-confidence information
removed].
FIGURE 11 Malignancy RR: adalimumab licensed dose versus
placebo (including adalimumab plus MTX versus MTX)
[Commercial-in-confidence information
removed].
FIGURE 12 Malignancy RD: adalimumab licensed dose versus
placebo (including adalimumab plus MTX versus MTX)
[Commercial-in-confidence information
removed].
WMD (fixed)
(95% CI)
–0.41 (–0.55 to –0.27)
–0.31 (–0.43 to –0.19)
–0.25 (–0.33 to –0.17)
–0.35 (–0.56 to –0.14)
–0.35 (–0.44 to –0.26)
–0.31 (–0.36 to –0.26)
–0.10 (–0.23 to 0.03)
–0.10 (–0.23 to 0.03)
patients had active disease defined according to a
number of tender and swollen joints and other
parameters such as ESR and CRP. All patients met
agreed disease classification criteria. Stable doses of
oral prednisolone (≤ 10 mg per day) and NSAIDs
were allowed. With the exception of the trial by
Baumgartner and colleagues, 104 patients with a
recent history of infection and significant comorbidity
were excluded. Only one trial, ERA, 123,124
recruited exclusively early RA patients. Key
features for each of the studies are described below.
Moreland and colleagues, 1996 120
Results from this study are not included in the
meta-analyses because of very small patient
numbers (three or four patients in each treatment
group), short duration and imbalances in baseline
patient characteristics (Table 6).
Moreland and colleagues, 1997 121
This double-blind, multicentre RCT compared
three doses of etanercept (0.25, 2 or 16 mg m –2
body surface area s.c. twice weekly) with placebo for
three months. Patients who had failed up to four
DMARDs and had at least ten swollen joints and 12
tender joints were included. Primary efficacy
measures were percentage change from baseline to
3 months in swollen joint count, tender joint count
and total count of swollen or tender joints.