WHAT IS THE TREATMENT?

Commonly used drugs

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. Patients often become confused by seeing one or other name on the prescription. Usually, the trade name is capitalised, but not the chemical (generic) name.

Non-steroids (NSAIDs: non-steroid anti-inflammatory drugs)

These include Feldene, Naprosyn, Voltarol, Relifex, Oruvail etc. Until 25 years ago, asprin was the main treatment for arthritis. Although NSAIDs are less toxic than full dose asprin, 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 are similar but have important differences. They are not steroids. the 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 less 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.

Plaquenil /hydroxychloroquine

This is given at the dosage of one tablet (200mgs) daily, or (less often) two tablets (400mgs) daily, in patients with skin lupus and joint pain. The drug takes two to three weeks to start working effectively but in many patients there is improvement in the skin and their general well-being, less joint pain, tiredness, muscle aches and sometimes, where there is a temperature, less fever. Antimalarials can be given for months and years.

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, a medical doctor who specialises in eyes. This is different from an optician or optometrist. At St. Thomas', a five year study on patients revealed no cases of eye damage.

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 (Hughes' 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 revolutionised 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. There is an injectionable form ACTH (adreno-cortico-trophic-hormone), which can be given, for example, twice a week. A third form of steroids, which is used for acute situations and often for patients who are acutely ill, or whom a boost to the system is required, is the "pulse" of methylprednisolone. This is a drip via the vein of large doses of between 500mgs or 1000mgs and surprisingly without major side effects. The major routine steroid throughout the world is prednisolone or prednisone (the prescription can say one or the other and in the body prednisone is converted to prednisolone).

Doses

The dose is variable, but here are some examples. An unwell patient, newly-diagnosed with acute lupus may require 60mgs daily, reducing to 40 or 30 mgs daily over two weeks. For milder cases, a patient whose lupus has flared, a dose of between 15-20 mgs daily might be given for a few weeks. In the vast majority of milder lupus, a "maintenance" dose of between 5-10 mgs daily is given. Many years ago, doses of over 80 mgs daily were given, but this is now regarded as excessive. High doses are toxic and has side effects.

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. The drug is in tablet form, most commonly at a dose of 2.5 mgs for every kilogram of body weight. This generally means either two tablets a day (100 mgs) or three tablets daily (150 mgs).

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.

Pulse cyclophosphamide

At St. Thomas' Hospital, London, a weekly injection of 500 mgs for three successive weeks and thereafter a monthly injection for three to six months, is the standard regime. The advantages of this "drip" regime is: (1) fewer side effects; and (2) there is a drug called Mesna which almost totally blocks the irritant effect on the bladder and the cystitis. Higher doses have been associated with frequent infections, particularly the virus herpes zoster (shingles). Using this lower dose, St. Thomas' have found the incidence of shingles to be negligible. In most practices, pulse cyclophosphamide is used for a bad flare or in a new patient to bring the disease under control.

Methotrexate

This drug has revolutionised 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.

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