A systematic review of the effectiveness of adalimumab

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Effectiveness
in juvenile arthritis, Crohn’s disease, psoriatic
arthritis and other forms of spondyloarthritis.
● Trials of adalimumab, etanercept or infliximab
comparing different doses or routes of
administration without including another active
or a placebo control group were only assessed
for safety outcomes.
● Studies reporting solely on laboratory measures
aimed at investigating disease or treatment
mechanisms and which did not report relevant
clinical outcomes.
● Observational studies of TNF inhibitor
therapies that did not include a control group,
except for information on adverse events.
● Trials only available as abstracts.
Clinical effectiveness: safety outcomes
Inclusion criteria
● RCTs that met the inclusion criteria for the
review on efficacy outcomes.
● In addition to RCTs, data from postmarketing
surveillance, major observational studies and
various registries including the BSRBR were
used to inform the assessment of the safety of
these three agents.
Based on the above inclusion and exclusion
criteria, study selection was made independently
by two reviewers. Discrepancies were resolved by
discussion, with involvement of a third reviewer
when necessary.
Data extraction strategy
Data included in the previous peer-reviewed,
published, assessment report 1 were taken directly
from the report and incorporated into updated
analyses. Data for outcomes that were not assessed
in the previous assessment report, and additional
data from new trials not included in the previous
report, were extracted independently by two
reviewers using an agreed data extraction form.
Results were extracted, where possible, for intentionto-treat
(ITT) populations as raw numbers, plus
any summary measures with standard deviations,
confidence intervals and p-values. Discrepancies
were resolved by discussion, with involvement of a
third reviewer when necessary.
Quality assessment strategy
The quality of RCTs was judged by adequacy of
randomisation, allocation concealment, blinding,
differential withdrawal between treatment arms,
and use of ITT analysis. Two reviewers
independently examined trial quality.
Discrepancies were resolved by discussion with
involvement of a third reviewer when necessary.
Results of quality assessment were tabulated.
Data analysis
Outcomes of interest
Meta-analyses were carried out on selected key
outcomes listed below, as specified in the review
protocol (http://www.pcpoh.bham.ac.uk/
publichealth/wmhtac/pdf/protocols/Anti-
TNF_2004_final_protocol%20.pdf).
Efficacy
● Proportions of patients meeting the ACR20,
ACR50 and ACR70 response criteria. Where
ACR response was not reported, Paulus20 and
Paulus50 were assumed to be equivalent to
ACR20 and ACR50, respectively, for the
purposes of meta-analysis
● swollen joint count (SJC)
● patient’s global assessment of disease activity
● Health Assessment Questionnaire (HAQ)
● Disease Activity Score (DAS or DAS28)
● accepted indices of joint damage (van der
Heijde modified Sharp score).
Further descriptions of the ACR response criteria,
HAQ, DAS and modified Sharp score can be
found in Appendix 1.
Tolerability
● Withdrawals for lack of efficacy
● withdrawals due to adverse events
● withdrawals for any reason.
Safety
● Serious adverse events (SAEs)
● serious infections
● malignancy.
SAEs are defined as an adverse event that met any
of the following criteria:
● fatal
● life-threatening
● results in an unplanned inpatient
hospitalisation, or prolongs an existing
hospitalisation
● significantly or permanently disabling
● a congenital anomaly or birth defect.
Important medical events that may not result in
death, be life-threatening or require
hospitalisation may still be considered SAEs if,
based on appropriate medical judgement, they
require medical or surgical intervention to prevent
one of the outcomes listed in the definition above.
Serious infections are defined as any infections
that require hospitalisation or parenteral
antimicrobial treatment. If the number of patients