A systematic review of the effectiveness of adalimumab

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)
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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