A systematic review of the effectiveness of adalimumab

Summary
RA is a common, chronic, inflammatory
condition causing systemic illness and pain,
swelling and destruction of the joints. The cause is
not known. Treatment aims to control pain and
inflammation, reduce joint damage and disability,
and maintain or improve physical function and
quality of life.
Although there are a number of diseasemodifying
drugs for this condition these are of
limited efficacy and are often withdrawn because
of toxicity or loss of effectiveness. New
treatments are needed. Tumour necrosis factor
(TNF) inhibitors are new biological agents that
have been designed to interrupt the
inflammatory pathway. Three are licensed for use
in the UK: adalimumab, etanercept and
infliximab.
National Institute for Health and Clinical
Excellence (NICE) guidance for the use of TNF
inhibitors was produced in 2002. Guidance
recommends that etanercept and infliximab
should only be used in patients who have tried
and failed conventional agents and that details of
patients and their treatment should be recorded in
a registry. There is variable implementation of the
guidance with limited access to these agents in
some areas. Where the drugs are used they tend to
be used after people have failed two or more
disease-modifying antirheumatic drugs
(DMARDs), as recommended, but they are also
used sequentially when patients fail on a previous
TNF inhibitor (not recommended). There are
currently around 10,000 patients on these drugs
in the UK, with an annual cost to the NHS of
£100 million. These figures are rising.
Since this guidance more evidence has become
available and a new agent, adalimumab, has
been licensed for use in the UK. All three agents
have also now been licensed for use early in the
disease.
This report reviews evidence about the
effectiveness and cost-effectiveness of all three
agents when used both early and later in the
disease.
Chapter 2
Background
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Health Technology Assessment 2006; Vol. 10: No. 42
Description of underlying health
problem
Clinical features of RA
RA is a systemic inflammatory disorder that most
often begins between the ages of 40 and 70 years.
It is more common in women than in men and is
characterised, pathologically, by an inflammatory
reaction and increased cellularity of the lining
layer of synovial joints. RA causes pain, swelling
and stiffness of affected joints: these symptoms are
often worse in the morning and after periods of
inactivity. Other organ systems, occasionally with
potentially life-threatening complications, may
also be affected. Patients commonly experience
fatigue and blood abnormalities such as anaemia
and a raised platelet count. Weight loss, lymphnode
enlargement, lung diseases (such as pleurisy,
pleural fluid and alveolitis), pericarditis, vascular
inflammation (vasculitis), skin nodules and eye
diseases (reduced tear production or
inflammation) may also occur.
The severity of disease, its clinical course and
individual responses to treatment vary greatly. For
example, in a community cohort nearly one in five
patients were in ‘remission off treatment’ after
3 years of follow-up. By contrast, half of the
patients attending hospital clinics were at least
moderately disabled, as rated by a Health
Assessment Questionnaire (HAQ) of greater than
1.0 (see Appendix 1). 4 Symptoms of RA may
develop within days or evolve over many weeks
and months. 5 Several distinct patterns of joint
disease are recognised, including predominantly
small or medium joint disease, predominantly
large joint disease, flitting or transient attacks of
joint pain (palindromic rheumatism), pain and
stiffness of the shoulder and pelvic girdles
(polymyalgic disease), and disease associated with
weight loss and fever (systemic onset), or any
combination of these. Pain and disability, in early
RA, are linked to disease severity and to measures
of psychological distress. 4 Disease progression can
be relentless, or punctuated by partial or complete
remissions, of variable and unpredictable intervals.
Diagnosis of RA
RA is diagnosed from a constellation of clinical,
laboratory and radiographic abnormalities.
3