A systematic review of the effectiveness of adalimumab

Summary
A comprehensive search for randomised
controlled trials (RCTs) was undertaken.
Studies were selected, and assessed for quality,
and data were extracted by two reviewers
independently.
Twenty-nine trials met the inclusion criteria.
One trial, the Behandel–Strategieën (BeSt), did
not meet the inclusion criteria but is reported
in detail as it is relevant to informing the
decision on the most appropriate use of TNF
inhibitors. Most trials were of good quality and
compared one of the TNF inhibitors with placebo.
Only three trials looked at a head-to-head
comparison between a TNF inhibitor and
methotrexate. No trial compared TNF inhibitors
with each other.
When used alone, adalimumab was slightly less
effective and etanercept was slightly more effective
than methotrexate in patients who had not been
treated with methotrexate or who had not
previously failed methotrexate treatment.
All three TNF inhibitors, used either alone (where
licensed) or in combination with ongoing
conventional DMARDs, were effective in
controlling the signs and symptoms of RA
compared with placebo in patients who had
had an inadequate response to conventional
DMARDs.
Combination of a TNF inhibitor plus
methotrexate was more effective than
methotrexate alone in patients who had not been
treated with methotrexate or who had not
previously failed methotrexate treatment. The
combination involving infliximab, however, was
associated with an increased risk of serious
infection.
Patients’ previous experience with the therapy has
to be taken into account when interpreting
treatment effects observed in trials, particularly
when combination therapy is involved. No clear
relationship between disease duration and
treatment effects was observed among the limited
evidence from trials.
Chapter 3
Effectiveness
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Health Technology Assessment 2006; Vol. 10: No. 42
Methods for reviewing
effectiveness
Search strategy
Clinical effectiveness
The following resources were used to identify
relevant studies:
● Searches of bibliographic databases:
– Cochrane Library 2005 Issue 1
– MEDLINE (Ovid) 1966 to February 2005,
EMBASE (Ovid) 1980 to week 8 2005
– Science Citation Index (ISI Web of Science)
1981–2005
● National Research Register 2005 Issue 1
● Internet sites of the Food and Drug
Administration (FDA) and EMEA
● manufacturers’ submissions to NICE 2005
appraisal process
● citation lists
● contact with experts and researchers.
Searches used index and text words encompassing
rheumatoid arthritis, tumour necrosis factor,
tumour necrosis factor receptors, anti-tumour
necrosis factor, adalimumab, etanercept and
infliximab. Search filters were used in MEDLINE
and EMBASE to identify RCTs. Searches for
adalimumab were not limited by date; searches
for etanercept and infliximab started from 2001 as
the previous report had covered the earlier
period. 1 There were no restrictions by language.
Full details of strategies are contained in
Appendix 2.
Inclusion and exclusion criteria
Clinical effectiveness: efficacy outcomes
Inclusion criteria
● RCTs that compared adalimumab, etanercept or
infliximab with any other agent including
placebo in adult RA patients.
● Trial reports were only included if the
recruitment of patients was complete.
● A trial had to be fully published as a paper or
be available as a complete trial report to be
included. Trial reports were requested on all
major trials from the manufacturers.
Exclusion criteria
● Trials of adalimumab, etanercept or infliximab
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