Drugs for the Treatment of Lupus
Introduction
It
is difficult to believe that often, people diagnosed with having lupus, often do
come off all treatment. The disease is cyclical and does frequently subside.
The
medication commonly used in lupus will be considered under four main headings:
non-steroidals, antimalarials, steroids and immunosuppressives. In reading about
a drug, often there will be two names. This is because has a trade name, for
example, Plaquenil and a chemical name, in this case, hydroxychloroquine. Seeing
one or other name on the prescription often confuses patients. Usually, the
trade name is capitalized, but not the chemical (generic) name.
Non-steroids (NSAIDs: non-steroid
anti-inflammatory drugs)
These
include Feldene, Naprosyn, Voltarol, Relifex, and Oruvail etc. Until 25 years
ago, aspirin was the main treatment for arthritis. Although NSAIDs are less
toxic than full dose aspirin, the main problem is their propensity to cause
indigestion and, especially in the elderly, stomach bleeding and ulceration.
Generally,
these drugs are safe and do not require regular blood tests, but they can cause
indigestion. If the patient notices this, NSAIDs should be stopped. NSAIDs are
safe taken with a majority of drugs, but they do, in some patients, interact
with coagulants such as warfarin. Patients need to be closely monitored.
Antimalarials
The
reason why these drugs work in lupus is unclear. About a hundred years ago, Dr.
Payne published clinical reports of the use of antimalarials in discoid lupus,
at St. Thomas' Hospital, London. He pointed out that they helped combat the skin
problems and also the more general symptoms of fever and joint pain. The family
of antimalarials is similar but have important differences. They are not
steroids. The three most commonly used are hydroxychloroquine (Plaquenil),
chloroquine (Nivaquine) and mepacrine (Atabrine). At Dr. Hughes' Lupus Clinic at
St. Thomas', Plaquenil is the favoured drug, as it seems to be less indigestible
and has fewer side effects. Although mepacrine is useful, at higher doses it
causes a yellow pigmentation of the skin, so that low doses can only be given.
Side effects of antimalarials
They
can affect the retina of the eye. Hydroxychloroquine is less toxic and lower
doses are safer. However, it is vital that annual eye checks are carried out by
an ophthalmologist. This is different from an optician or optometrist Other side
effects include indigestion (usually mild), occasional tinnitis (noises in the
eye), very occasional headaches. An extremely rare problem is darkening of the
skin and nails, although this is normally only seen in patients on higher doses.
One
rare side effect which is not widely known, even by doctors, is when
hydroxychloroquine is started in moderate doses, such as two or three tablets
daily, there is a subtle effect on the eye muscles leading to focussing or to
mild double vision. Obviously, this is frightening, but when the drug is
stopped, the symptom goes away.
Antimalarials
have been regarded as contra-indicated in pregnancy. However, there have been an
increasing number of patients world wide, who have had successful pregnancies
whilst taking hydroxychloroquine and so it looks like it is safe in pregnancy.
One
of the main useful effects is that in those patients with blood clotting
problems, such as with the antiphospholipid syndrome); antimalarials have a mild
anti-clotting effect.
Incidentally,
patients taking Plaquenil for lupus still require other antimalarials for travel
in certain countries. Hydroxychloroquine alone does not protect against malaria.
Steroids (corticosteroids)
Steroids,
such as prednisolone, have revolutionized the management of lupus.
Unfortunately, the side effects - the weight gain, moon face, rather than their
beneficial effects, are remembered. They are life saving and are vital in the
management of the majority of lupus patients at some stage during their disease.
However, modern management has advanced with the use of steroid alternative
drugs and better prescription of steroid dosage.
Commonly
used steroids
The
most common is prednisolone, which is easy to take and monitor
Steroid
reduction
Any
patient taking steroids ought to carry with them a card indicating their dosage.
Alternatively, a Medic Alert bracelet, containing diagnosis and medications
taken, is essential. Steroids must never be stopped suddenly and their reduction
must be carried out under strict medical supervision. At first, the reduction
can be steep but flattens later. For example, a dosage of 60 mgs can be reduced
quickly to 40 mgs or 20 mgs daily, but after that, reduction must be slower.
Often for a patient at 10 mgs daily, reduction can be as little as 1 mg every
month. Most steroid tablets are enteric coated which irritate the stomach less.
Side
effects of steroids
Low
doses of 7.5 mgs daily have very few side effects, especially in the short term.
The two common side effects are sleep disturbances and increased appetite. Other
more serious effects, usually associated with high doses over longer periods are
muscle weakness, a raised blood sugar level (sometimes diabetes) and softening
of the bones (including the hips) and especially in older, post-menopausal
patients, osteoporosis.
Immunosuppressives
These
drugs help to calm the immune system down and are important as part of the
management of lupus, in some patients. There are a large number of these drugs
and considerable experience has been built up over the years, notably in
patients with cancer. Generally, far lower doses are used in lupus. The two most
regularly used are azathiaprine (Imuran), cyclophosphamide (Endoxan, Cytoxan).
Two others are used less frequently: methotrexate and cyclosporin.
Azathiaprine
(Imuran)
Azathiaprine
is one of the most widely used drugs in the management of lupus. Although it can
lower the white blood count, it still has a very acceptable safety margin and is
prescribed for children and occasionally pregnant women.
Uses of azathiaprine
Azathiaprine
is a "steroid-sparing" drug. This means that with patients whose lupus
is active, especially with kidney disease, it is common to combine two drugs
rather than use high-dose steroids. For patients with kidney disease, fairly
strong treatment early one may reverse the inflammation and return kidney
function to normal. Azathiaprine is used over a long period, often for years.
Although it can be stopped quickly, there is some evidence to suggest that it is
best to stop the drug in stages, for example, down to 1 tablet daily for a month
or two and then to stop altogether. Many trials have shown that azathiaprine has
positive effects on other aspects of lupus, such as in improving blood tests. It
is not a steroid and has none of its major side effects, such as weight gain.
Side effects of azathiaprine
The
most important side effect is depression of the bone-marrow cells with a
resulting fall in the white blood count and less commonly, a lower platelet and
red cell count. Regular blood counts are imperative. Common side effects include
nausea and indigestion (although it does not cause heartburn and the burning
stomach problems of NSAIDs) and sometimes a loss of appetite, which can lead to
stopping treatment because of its severity. In some cases, liver function tests
are affected.
It is important to remember that the liver itself is rarely involved in lupus and therefore abnormal liver tests are suggestive of another cause such as a side effect or a viral infection.
Cyclophosphamide
This
is a more powerful and more toxic drug than azathiaprine. It used to be in
tablet form, but because of fewer side effects, it is commonly given as a
periodic injection or "pulse".
Side effects
Cyclophosphamide
affects dividing cells and can reduce the blood count. A close watch must be
maintained. More seriously, it can affect the dividing cells of the reproductive
system, such as ovary cells or sperm. Other side effects include nausea and
diarrhoea and marked hair loss. A specific side effect concerns the bladder and
patients can suffer from bladder irritability and a severe form of cystitis
called haemorrhagic cystitis. Many of these side effects have been overcome by
the change from oral to intravenous pulse doses.
Methotrexate
This
drug has revolutionized the management of rheumatoid arthritis because of its
power effects on joint inflammation. Its value is in those lupus patients for
whom arthritis is a major problem.
Cyclosporin
This is a "wonder
drug" used in transplantation. It has a slightly different effect on the
immune system from other immunosuppressants; in lupus it has some value, though
its role is yet to be fully established. Unfortunately, even in small doses, it
has many side effects - pins and needles, due to its irritant effect on the
nerves (neuropathy) and its tendency to increase blood pressure. The increase in
blood pressure is a major problem for patients with kidney involvement.