A systematic review of the effectiveness of adalimumab

46
Effectiveness
Review: Etanercept for rheumatoid arthritis 2006
Comparison: 03 Etanercept s.c. licensed dose only (25 mg twice weekly) vs other active treatment
Outcome: 09 Malignancy
Study
or subcategory
01 Partial responders to comparator DMARD (SSZ)
Codreanu, 2003 103 [24 weeks]
Subtotal (95% CI)
Total events: 2 (etanercept), 0 (control)
Test for heterogeneity: NA
Test for overall effect: z = 0.95 (p = 0.34)
Etanercept
n/N
Etanercept plus methotrexate versus
methotrexate
Only TEMPO 110,127 included this comparison and
the results are summarised in Table 11 and are also
shown in the lower parts of Figures 24–34.
Efficacy The combination of etanercept plus
methotrexate was significantly more effective than
methotrexate monotherapy for all the efficacy
outcomes considered.
Tolerability The combination was better tolerated
than methotrexate monotherapy. Significantly
fewer patients withdrew owing to lack of
efficacy and for any reason in the combination
group.
Safety No significant differences were found in any
of the outcomes being meta-analysed.
Nevertheless, SAEs and malignancy occurred more
frequently in the combination group.
Infliximab
Description of included infliximab trials
Nine trials comprising a total of 2835 patients
(2823 actually treated) were included in the metaanalyses.
A prepublication manuscript of BeSt was
Control
n/N
2/103 0/50
103 50
02 Responders or naive to comparator DMARD (MTX)
TEMPO110 [104 weeks]
ERA124 [104 weeks]
Subtotal (95% CI)
Total events: 10 (etanercept), 7 (control)
Test for heterogeneity: 2 = 0.46, df = 1 (p = 0.50), I2 5/223 2/228
5/207 5/217
430 445
= 0%
Test for overall effect: z = 0.81 (p = 0.42)
Total (95% CI)
Total events: 12 (etanercept), 7 (control)
Test for heterogeneity: 2 = 0.70, df = 2 (p = 0.71), I2 533 495
= 0%
Test for overall effect: z = 1.07 (p = 0.28)
FIGURE 23 Malignancy RD: etanercept licensed dose versus other active treatment
RD (fixed)
95% CI
–0.5 –0.25 0 0.25 0.5
Favours etanercept Favours control
Weight
%
13.34
13.34
44.68
41.98
86.66
100.00
RD (fixed)
95% CI
0.02 [–0.02, 0.06]
0.02 [–0.02, 0.06]
0.01 [–0.01, 0.04]
0.00 [–0.03, 0.03]
0.01 [–0.01, 0.03]
0.01 [–0.01, 0.03]
made available by the investigators, but did not
meet the inclusion criteria. However, because
of its importance it is described in detail, but
the data are not used in the meta-analyses.
Clinical study reports were provided by
Schering-Plough for three of the studies:
ATTRACT, 132–134 Active-controlled Study of
Patient Receiving Infliximab for the Treatment of
Rheumatoid Arthritis of Early Onset, (ASPIRE) 135
and START. 105,111 Additional data from these
reports were included in this systematic review.
Data were available only from published papers
for the remaining six studies: Elliott, 136
Maini, 137 Kavanaugh, 138 Durez, 139 Taylor, 140
and Quinn. 141
Treatment comparators and baseline patient
characteristics are shown in Table 12. Quality
assessments of trials are summarised in Table 13.
In most trials active RA was defined by six or more
swollen joints (ten for ASPIRE), with additional
criteria related to tender joints, ESR, CRP and
morning stiffness. Taylor 140 and Quinn 141 focused
on ultrasonographic and MRI outcomes,
respectively. Low-dose oral steroids (