A systematic review of the effectiveness of adalimumab

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Effectiveness
TABLE 9 Summary of 2-year results from TEMPO study: etanercept s.c. licensed dose alone (25 mg twice weekly) versus MTX alone
in MTX-naïve patients/responders, 2-year results
Comparison or outcome N included Statistical method Effect size (95% CI)
in analysis
ACR20 responder 451 RR (fixed) 1.28 (1.06 to 1.54)*
ACR50 responder 451 RR (fixed) 1.47 (1.15 to 1.89)*
ACR70 responder 451 RR (fixed) 1.46 (1.00 to 2.14)
RD ACR20 responder 451 RD (fixed) 0.12 (0.03 to 0.21)*
RD ACR50 responder 451 RD (fixed) 0.14 (0.05 to 0.23)*
RD ACR70 responder 451 RD (fixed) 0.08 (0.00 to 0.15)
SJC, end of study result
Patient’s global assessment, end of
451 WMD (fixed) –1.10 (–3.08 to 0.88)
study result 451 WMD (fixed) –0.20 (–0.51 to 0.11)
HAQ, end of study result 451 WMD (fixed) –0.10 (–0.23 to 0.03)
DAS, end of study result 451 WMD (fixed) –0.10 (–0.31 to 0.11)
Modified van de Heijde–Sharp score,
mean change from baseline (1-year result)
424 WMD (fixed) –2.28 (–4.11 to –0.45)*
Withdrawal for any reasons 451 RR (fixed) 0.81 (0.65 to 1.00)
Withdrawal due to lack of efficacy 451 RR (fixed) 0.93 (0.59 to 1.47)
Withdrawal due to adverse events 451 RR (fixed) 0.75 (0.50 to 1.11)
Death 451 RR (fixed) 1.02 (0.06 to 16.25)
SAEs 451 RR (fixed) 1.10 (0.75 to 1.61)
Malignancy: all 451 RR (fixed) 2.56 (0.50 to 13.04)
Malignancy: skin cancer excluding melanoma 451 RR (fixed) 2.04 (0.19 to 22.39)
Malignancy: all cancer excluding
non-melanoma skin cancer
451 RR (fixed) 3.07 (0.32 to 29.27)
Serious infection 451 RR (fixed) 0.95 (0.47 to 1.93)
Any infection 451 RR (fixed) 0.95 (0.85 to 1.06)
* Statistically significant result (p < 0.05).
Etanercept versus placebo
Eight trials 103,104,121,122,125,126,129,130 compared
etanercept at the licensed dose (or equivalent) to
placebo. Three of the trials 121,122,126 also included
sublicensed doses. No trial included doses above
the licensed dose. Results of the primary analyses
(licensed dose) are summarised in Table 10, and
are also shown in the upper parts of Figures 24–34.
Efficacy Etanercept was significantly more effective
than placebo for all the efficacy outcomes being
meta-analysed. Figure 24 shows a pattern of
decreasing effect size for ACR20 in terms of
relative risk in trials in that patients: (1) were not
receiving any concurrent DMARDs; (2) were
receiving concurrent DMARDs that had failed to
provide adequate disease control; and (3) were
receiving concurrent, newly initiated methotrexate.
This pattern, however, is not clearly observed for
other outcome measures, nor is it observed in
trials of other TNF inhibitors.
Tolerability Etanercept is better tolerated than
placebo.
Safety There were no significant differences
between etanercept and placebo. In the trial by
Baumgartner and colleagues, 104 which recruited
patients with co-morbidity, five deaths occurred in
the etanercept arm compared with one in the
placebo arm.
Sensitivity analysis The results of the sensitivity
analysis, which included sublicensed doses, are
summarised in Table 73 (Appendix 4). These are
consistent with the primary analysis.