A systematic review of the effectiveness of adalimumab

8
Background
medication costs, especially in those treated with
biological agents such as TNF inhibitors, account
for a majority of the direct costs of RA. 57 Some
drug intervention studies have shown reduced
work absence with aggressive treatment
strategies, 58 although only one-third of employed
patients cease because of disease and,
unsurprisingly, manual workers are much more
likely to stop work. 59
Current service provision
Most patients with RA are referred to hospital
services for assessment, but up to one-quarter of
those with early inflammatory arthritis (not
necessarily RA) are managed in primary care. Most
district general hospitals now have a department
of rheumatology with varied support from clinical
nurse specialists and other professionals allied to
medicine. The majority of patients followed up in
a hospital rheumatology department have RA or
another type of inflammatory arthritis or
connective-tissue disease. A proportion of such
patients may also require inpatient treatment,
although there are considerable variations in
inpatient facilities and hospitalisation rates for RA.
The Arthritis and Musculoskeletal Alliance
(ARMA) has recently proposed standards of care
for patients with inflammatory arthritis. The
principal motive for these standards 60 is to
improve service provision and delivery and to
reduce regional variations in access to services. 61–63
For example, access to TNF inhibitors varies
depending on local funding arrangements, such
that some districts operate waiting lists for patients
to begin treatment despite wide drug availability.
A recent survey, commissioned by ARMA and the
British Society for Rheumatology (BSR), with
support from Schering-Plough, indicated that
around one-third of 148 rheumatologists, mainly
from England and Wales, were unable to prescribe
TNF inhibitors. 64 Principal barriers to prescribing
were identified as difficulties with local funding
arrangements or problems of infrastructure such
as the availability of day-case facilities or nursing
support. Variable implementation of guidance on
the use of TNF inhibitors was also confirmed by a
survey of 196 hospitals and PCTs undertaken by
the Audit Commission, which found that ‘the
biggest perceived barrier to implementation
among NHS bodies, for both clinical guidelines
and technology appraisals, was lack of money. We
found that 85 per cent of respondents identified
that the funds available to implement technology
appraisals were insufficient, particularly in relation
to high-cost appraisals, such as … etanercept and
infliximab for rheumatoid arthritis.’ 60 Access to
adalimumab has caused particular difficulties in
some areas because this drug has not yet been
evaluated by NICE.
However, some services have managed to secure
additional funding for drugs and junior medical
and nursing staff to enable NICE guidance to be
implemented. 65
Description of the technology
Adalimumab (Humira ® ; Abbott
Laboratories)
Adalimumab is a recombinant monoclonal
antibody, made from human peptide sequences,
which binds specifically to TNF and neutralises its
biological functions by blocking interactions with
the p55 and p75 cell-surface TNF receptors.
Treatment is currently recommended for use in
people with moderate or severe RA who have not
responded to one or more DMARDs, including
methotrexate. An application to extend the licence
of adalimumab for use in severe, active,
progressive RA in adults not previously treated
with methotrexate was submitted by Abbott
Laboratories in December 2004 66 and approved in
June 2005. 67 Concomitant treatment with
methotrexate is recommended for optimum
efficacy, but adalimumab may be used alone where
methotrexate is not tolerated or is
contraindicated. Clearance of adalimumab from
the body is decreased with age and by concomitant
methotrexate administration, whereas adalimumab
increases methotrexate clearance. 68 Patients
normally self-administer adalimumab by
subcutaneous injections, after training, at a
standard dose of 40 mg every other week; but the
dose may be increased to 40 mg weekly if disease
is poorly controlled. 69
Etanercept (Enbrel ® ; Wyeth
Laboratories)
Etanercept is a combination protein consisting of
the extracellular portion of two of the 75-kDa
TNF receptors (TNF-R2) for TNF combined with
a human Fc portion of human IgG class 1 (IgG 1).
Etanercept binds soluble and cell-bound TNF-
with high affinity and does this by competing with
TNF receptors. Etanercept is administered as a
twice-weekly subcutaneous injection of 25 mg or a
once-weekly injection of 50 mg. Patients or
caregivers normally administer etanercept, after
suitable training. No dose changes are necessary
for patients with renal or hepatic failure or in
elderly subjects. Etanercept may be used in