A systematic review of the effectiveness of adalimumab

Summary
Effectiveness: principal findings
● All the TNF inhibitors were effective treatments
for patients with RA.
● For patients who were naïve to methotrexate,
adalimumab monotherapy was marginally less
effective and etanercept monotherapy was
marginally more effective than methotrexate.
● Combination of a TNF inhibitor with
methotrexate was more effective than
methotrexate alone in patients naïve to
methotrexate.
● An increased risk of serious infections cannot
be ruled out for infliximab and adalimumab
plus methotrexate.
Cost-effectiveness: principal findings
● Last active therapy in sequence:
– TNF inhibitors are most cost-effective when
used last
– the ICER for etanercept used last is £24,000
per QALY and substantially lower than the
ICERs for adalimumab (£30,000 per QALY)
or infliximab (£38,000 per QALY).
● Third-line use (as recommended in the 2002
NICE guidance):
– gives ICERs around £30,000 per QALY using
early RA effectiveness data
– gives ICERs of around £50,000 per QALY for
etanercept (with or without methotrexate)
using late RA data
– ICERs for adalimumab and infliximab are
somewhat higher using late RA data.
● First-line use:
– gives ICERs around £50,000 per QALY for
adalimumab and etanercept monotherapy
– much higher ICERs for combinations
including methotrexate as first-line therapy.
● Sequential use:
– similar results to use of the equivalent TNF
inhibitor as sole TNF inhibitor in the
sequence
– ICERs for adalimumab and infliximab
increased somewhat if used after etanercept.
Principal findings
The key findings of this review were as follows.
Chapter 7
Discussion
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Health Technology Assessment 2006; Vol. 10: No. 42
Quality and quantity of evidence
Twenty-nine RCTs (nine adalimumab, 11
etanercept and nine infliximab), including ten
trials reviewed in the previous assessment report, 1
were included in this review. The trials were
generally of high quality and recruited a total of
9939 patients. Five of the trials 102,123,135,140,141
recruited exclusively RA patients with short disease
duration (≤ 3 years). In addition, the BeSt study is
described and discussed in this review in view of
its novel approach and clinical relevance, although
it does not strictly meet the inclusion criteria.
Head-to-head comparisons
Only a small number of included RCTs looked at
head-to-head comparisons of TNF inhibitors with
methotrexate: ERA 123 and TEMPO 127 for
etanercept and PREMIER 102 for adalimumab. No
identified RCT directly compared a TNF inhibitor
with a conventional DMARD other than
methotrexate. BeSt is the only RCT that compares
different sets of sequential treatments in early RA
patients.
In the PREMIER trial, 102 adalimumab alone (at
licensed dose) was marginally less effective than
methotrexate in controlling the symptoms of RA
in patients who were naïve to methotrexate, and
was associated with slight, but not significant,
increase in SAEs (RR [Commercial-in-confidence
information removed]). The only advantage of
adalimumab monotherapy over methotrexate was
a reduction in radiographic joint damage. The
results are reflected in the extension of marketing
authorisation for adalimumab recently issued by
the EMEA, 67 which recommended the use of
adalimumab in combination with methotrexate,
rather than adalimumab alone, in early RA
patients.
Etanercept alone (at licensed dose) was as effective
or slightly more effective than methotrexate in
controlling RA symptoms and retarding joint
damage in patients who were naïve to or who had
no treatment failure with methotrexate in the
ERA 123 and TEMPO 127 trials. Although the mean
disease duration for the patients was only 1 year in
the ERA trial, compared with over 6 years in the
TEMPO, the results from these two studies are
remarkably similar, with no statistical
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