A systematic review of the effectiveness of adalimumab

24
Effectiveness
change in modified total Sharp score from
baseline to week 52 between the combination
therapy and the methotrexate monotherapy only.
Keystone and colleagues, 2004 (DE019) 114
This 52-week, double-blind, multicentre trial
compared adalimumab 40 mg s.c. every other
week, 20 mg s.c. every week and placebo in
patients receiving concomitant methotrexate.
Patients who either were rheumatoid factor
positive or had at least one joint erosion on
radiographs of the hands and feet were recruited.
The primary end-points were ACR20 response at
24 weeks, change in modified Sharp score at week
52 and change in HAQ at week 52.
STAR: Furst and colleagues, 2003 (DE031) 115
This 24-week, double-blind, multicentre safety
trial compared adalimumab 40 mg s.c. every other
week with placebo in RA patients who continued
to receive their standard antirheumatic therapy
(including DMARDs). Concomitant DMARDs were
permitted if doses had been stable for at least 28
days before screening, and a single increase in
DMARD dosage was allowed at week 12 or
subsequent visits if a patient failed to meet or
maintain ACR20 response. Eighty-three per cent
of patients received at least one DMARD. The
primary end-point, safety, was assessed by types
and frequencies of adverse events, physical
examination findings and standard laboratory test
results.
Meta-analyses of adalimumab trials
The approaches to meta-analyses and data
presentation are described in detail in the section
‘Data analysis’ (p. 14). The only adalimumab trial
that recruited exclusively methotrexate-naïve
patients with disease duration of less than 3 years
was the PREMIER 102,109 trial and included three
treatment arms which allow more than one
comparison: adalimumab versus methotrexate and
combination (adalimumab plus methotrexate)
versus methotrexate.
Adalimumab versus methotrexate
The PREMIER 102,109 trial is the only trial that
included head-to-head comparison between
adalimumab and a DMARD (methotrexate). The
results are summarised in Table 3.
Efficacy The only effectiveness result reaching
conventional levels of statistical significance
between adalimumab and methotrexate is
radiographic joint damage. Patients treated with
adalimumab had a smaller increase in modified
Sharp score compared with those treated with
methotrexate (mean difference over 2 years –4.90,
95% CI [Commercial-in-confidence information
removed]). Adalimumab appears to be marginally
less effective than methotrexate in reducing
disease activity as measured by other means, for
example the ACR20 response (RR 0.88, 95% CI
0.75 to 1.03) and ACR50 response (RR 0.86, 95%
CI 0.70 to 1.06).
Tolerability No significant difference was found
between adalimumab and methotrexate.
Safety One death occurred in the methotrexate
arm and four occurred in the adalimumab arm.
The number of patients with malignancy was
similar ([Commercial-in-confidence information
removed] in the methotrexate arm and four in the
adalimumab arm). More patients experienced
SAEs in the adalimumab arm, although this did
not reach statistical significance ([Commercial-inconfidence
information removed]). [Commercialin-confidence
information removed] patients had
serious infections in the methotrexate arm
compared with [Commercial-in-confidence
information removed] in the adalimumab arm,
but no difference was found in the risk of overall
infection between the treatment groups.
Adalimumab versus placebo
Five trials 112–115,119 included a comparison of
adalimumab with placebo at the licensed dose (or
equivalent). Three additional trials 116–118 included
this comparison at above or under licensed doses.
The results of primary analyses (licensed dose
only) for the comparison between adalimumab
and placebo are summarised in Table 4. Forest
plots for the ACR20, ACR50, ACR70, HAQ, SAEs
and malignancy are shown in the upper parts of
Figures 2–12.
Efficacy Adalimumab at the licensed dose is
significantly more effective than placebo for all the
efficacy outcomes included in the meta-analyses.
Tolerability Significantly [Commercial-inconfidence
information removed] patients
withdrew for any reasons and for lack of efficacy
in the adalimumab group compared with the
placebo group. Slightly more patients withdrew
owing to adverse events in the adalimumab
group, but these did not reach statistical
significance.
Safety Adalimumab is associated with a slight, but
significantly increased, risk of any infection
compared with placebo. It also appears to be
associated with an increased risk of death,