LEDDEGIGT – - Sundhedsstyrelsen

The annual additional costs for referral and diagnosis are calculated to be
DKK 5.6-8.9 million, to which should be added an initial additional cost of
DKK 1.5-4.6 million due to the earlier initiation of treatment. In addition to
the above-mentioned additional costs, informing general practitioners about
the importance of early diagnosis and of preparing guidelines for early referral
will cost an estimated DKK 4.5 million provided the information campaign
is not repeated. Expected, but non-calculated savings as a result of a less severe
course of the disease are not incorporated into the calculations.
The effects and side effects of anti-rheumatic drugs
There are various types of anti-rheumatic drugs for the treatment of rheumatoid
arthritis. This HTA report focuses on the slowly-acting anti-rheumatic
drugs and the TNF-alpha antagonists, which are central in the treatment of
rheumatoid arthritis. Other well-known preparations used in the pharmacotherapy
of rheumatoid arthritis (but which were not included in the HTA)
are analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids.
The patients often need treatment with several of these drugs simultaneously.
Slowly-acting anti-rheumatic drugs
The slowly-acting anti-rheumatic drugs encompass eight different preparations,
of which methotrexate is the most commonly used. Slowly-acting antirheumatic
drugs can diminish symptoms in the majority of patients and to
some extent prevent permanent joint damage. The effects of the slowly-acting
anti-rheumatic drugs can be summarized as follows:
In two thirds of patients, disease activity is reduced by at least 20%.
With specific drugs it has been shown that approximately one third attain
50% improvement, and one fifth attain 70% improvement.
Despite pharmacotherapy, approximately 50% of the rheumatoid arthritis
patients lose their ability to work within six to ten years of onset.
Of the slowly-acting anti-rheumatic drugs, only methotrexate, leflunomide
and sulphasalazine have had a clearly demonstrable inhibitory effect
on the development of joint damage.
Among rheumatoid arthritis patients, 10-20% of those attended by rheumatologists
2 are estimated to be inadequately responsive to slowly-acting antirheumatic
drugs. This group of patients has hitherto had to undergo protracted
treatment with high doses of glucocorticoids as well as various slowlyacting
anti-rheumatic drugs, either singly or in combination.
Moreover, frequent change of drug is the rule due to the limited time (1-2
years) that individual anti-rheumatic drugs remain effective. Treatment withdrawal
is due to unacceptable side effects. In patients who are responsive to
the medication, complete cessation of treatment entails a considerable risk
that the disease activity will increase.
The new drugs
In approximately half of the patients who do not respond satisfactorily to the
traditional anti-rheumatic drugs, or who suffer from side effects, the new biological
drugs in the form of TNF-alpha antagonists have proven to have a rapid
and marked inhibitory effect on the disease activity in the affected joints.
TNF-alpha antagonists are able to delay or completely prevent the development
of permanent joint damage that leads to physical invalidity.
The two TNF-alpha antagonists presently available are administered differently:
Infliximab is administered intravenously as drop treatment, usually at 8-week
intervals, while etanercept is administered subcutaneously twice weekly.
As the TNF-alpha antagonists have only been in use for a few years, their
long-term effects are as yet unknown although treatment for up to five years
seems to entail few serious side effects. Due to the effects of the substances on
the immune system, however, it is theoretically possible that the drugs could
increase the risk of the development of cancer and serious infections.
Both substances seem to entail a slightly elevated risk of tuberculosis in certain
risk groups. With both substances, moreover, there is a slight risk of
symptoms that resemble connective tissue disease, although these disappear
when the treatment is terminated. In rare cases, etanercept treatment has
been reported to cause serious bone marrow depression and disorders corresponding
to disseminated sclerosis, while intravenous administration of infliximab
has been reported to cause severe allergic reactions.
Organizational aspects
Medical treatment of rheumatoid arthritis can be carried out in either the primary
sector through rheumatology specialists or in the secondary sector at
the various hospital rheumatology departments. General practitioners are also
involved in the treatment but usually in cooperation with the rheumatology
specialist. In general, however, the treatment of rheumatoid arthritis patients
requires specialist experience in rheumatology and hence should primarily by
carried out at specialist level. There are major geographical differences in
2 Treatment with the slowly-acting anti-rheumatic drugs is generally only carried out by rheumatologists.
28 LEDDEGIGT – medicinsk teknologivurdering af diagnostik og behandling
LEDDEGIGT – medicinsk teknologivurdering af diagnostik og behandling 29