Treatment aims to suppress the overactive immune system and diminish inflammation. Treatment may be aggressive (e.g. steroids), but milder drugs are also widely used (e.g. antimalarials).
With time the aim is to reduce drugs and ultimately discontinue their use. Patients may experience a fluctuating course of lupus, but most patients do get better and in the long term and aggressive treatment may not be needed.
Generally drugs used in the treatment of lupus fall into 4 groups:
Aspirin and Non Steroidals - low dose aspirin (75mg per day) "junior aspirin" is widely used in those patients with Antiphospholipid syndrome or "sticky blood". Non-steroidal anti-inflammatory drugs are also useful for joint and muscle pains but should be used sparingly because of their side effects on the stomach.
Anti-malarials - Hydroxychloroquine is a mainstay of treatment for mild to moderate lupus. It has an anti-inflammatory effect as well as providing some protection against sunlight and is often used as the first line of treatment.
Steroids - are vital and even life saving in acute flares but modern treatment aims at reducing or even stopping steroid treatment wherever possible.
Immuno suppressives - in lupus the immune system is overactive hence the development of a number of drugs used to suppress the overactive immune response. These include Azathioprine, Methotrexate, Mycophenolate and Mofetil (MMF) as well as the stronger cyclo-phosphamide. The latter drug is reserved for patients with severe disease and is usually administered by injection.
The bark of certain trees has, for many centuries, been known to have healing powers. Aspirin, for example, from the bark of the willow tree - long known for its pain relieving properties - has also come into its own as a protection against blood clotting such as heart attacks & strokes.
Similarly, the bark of the cinchona tree has been known for centuries by the South Americans as a treatment for fever. The essential ingredients of this particular bark were quinines (found in small amounts in tonic water). Quinines were found to have a variety of healing powers; in fever, aches & pains, cramp and more widely, in treating malaria. In the quinine family, chloroquine became used world wide, not only for malaria but also for a variety of skin diseases. One of the recognised skin diseases was lupus and during the nineteenth century chloroquine became widely used for cutaneous lupus.
In 1894, Dr Thomas Payne, a physician in St. Thomas' Hospital London, recognised that chloroquine might have more general healing powers in lupus, for example healing joint pain & fatigue. This discovery paved the way for a century of 'antimalarial' use in various forms of lupus.
The 'older' drug chloroquine, whilst very effective, had a number of serious side effects including nausea, and in high doses, retinal damage in the eye. The move to the 'son of chloroquine' - Hydroxychloroquine, has changed all this. HCQ has a very high degree of safety (particularly regarding the eyes) and in most countries in the world (sadly not all) has replaced chloroquine. The brand plaquenil was discontinued by the manufacturere in 2016.
What does it do?
Hydroxychloroquine has beneficial effects on 3 major aspects of lupus; skin rashes, aches & pains and fatigue. It has also been found to help in a number of other features of the disease, though less predictably.
It is very effective in the treatment of a whole variety of lupus skin rashes, particularly those found to be worsened by sunlight. Thus it is widely used as first choice (or 'first line') treatment in lupus. As well as helping the skin itself, it is often helpful in treating hair loss in lupus. It helps the muscle & joint pains, though in cases where these are severe, its effects may be too mild. One of the most successful uses is in fatigue, many patients showing improvement after several weeks' treatment.
How does Hydroxychloroquine work?
Surprisingly, the reason for its success in lupus still remains somewhat mysterious. It has a wide variety of known effects - aspirin-like anti-inflammatory, mild immunomodulatory and (mild) cholesterol lowering amongst others. Perhaps an important property is that of sun-protection. This may contribute to its success in treating many sun-sensitive rashes in lupus. It is the practice of some patients from sunnier countries, such as Greece, to take Hydroxychloroquine in the summer months, coming off for winter.
The normal dose of Hydroxychloroquine is 1 tablet a day (200mg/day). Some doctors recommend 2 a day (400mg/day) but we find that 1 a day suits most people - the dose can always be increased for a flare. One of the attractions of this medication is its long 'half-life' - it stays in the system for weeks. Thus many patients find they can gradually lower the dose - for example to 3 tablets a week - Monday, Wednesday & Friday.
For how long?
The answer is 'for years', if necessary. There are no firm rules about duration, though many lupus patients find they benefit by staying on a 'long term - low dose regime'. An interesting study from Canada found that there were more flares of lupus if the drug was stopped, suggesting it was keeping the disease at bay.
Hydroxychloroquine is one of the safest drugs in medicine. Serious side effects are rare & routine blood tests are not required. Allergy (new skin rashes) is unusual but it means ruling out future use. Commoner, usually mild, side effects are indigestion, 'gurgly tummy', diarrhoea & headache. A rare, but important, side effect, usually on higher doses (2 tablets a day) is of 'lazy eye' - slight difficulty in focussing. Although harmless, it is important as it causes patients to worry about blindness - and needlessly stop the drug as this usually resolves.
Another reason for wrongly stopping the drug is pregnancy. Hydroxychloroquine is safe in pregnancy and is in routine use in our own lupus pregnancy clinic at St. Thomas' Hospital.
The older drug, chloroquine, in higher doses, was found to cause damage to the retina of the eye - in extreme cases, blindness. Fortunately, Hydroxychloroquine is considered safe. A few years ago we published a careful study, with our eye colleagues, of patients taking Hydroxychloroquine daily for 5 years. No eye toxicity was seen.
Guidelines have been issued on Hydroxychloroquine monitoring. It remains a very safe drug, but when used for very long periods regular monitoring is a requirement. Please click here for further information.
Another drug with similar properties to Hydroxychloroquine is Mepacrine (in some countries Atabrine). It is very much a second choice for 2 reasons. Firstly, it can cause yellowing of the skin. Secondly, it is very bitter & most unpleasant to take. Nevertheless, it is an extremely effective medicine in patients with severe skin rashes.
Some 20 years ago we introduced a 'combination regime' of Hydroxychloroquine & Mepacrine for patients with severe skin lupus - Hydroxychloroquine 1 or 2 a day plus Mepacrine (50-100mg) or alternate days. This combination is now widely used in lupus clinics around the world.
Note: Patients often find difficulty in obtaining Mepacrine from pharmacies. The drug is available. Some years ago, Boots, the makers & distributors of Mepacrine in the UK gave an assurance that although demand for the drug was low, the company would undertake to continue to make it available for lupus sufferers. It has become very expensive recently.
On 9th March 2011 Benlysta (Bellumimab), the first new treatment developed to treat systemic lupus in over 50 years, was approved by the FDA (US Food & Drug Administration).
Benlytsa is the first in a new class of drugs called BLyS-specific inhibitors, which work by targeting a naturally occurring protein believed to play a role in the production of antibodies which attack and destroy the body's own healthy tissues. It was developed by Human Genome Sciences, a biotechnology company based in Rockville, Maryland, together with London-based pharmaceutical company GSK (GlaxoSmithKline).
NICE (National Institute for Health and Clinical Excellence ) would not approve the use of the drug in the UK on cost grounds until May 2016 when Benlysta was approved by NICE for limited use in the NHS. NICE guidelines say treatment with Benlysta can be funded by the health service, for patients meeting specific criteria under a managed access agreement between GSK and NHS England, which will provide the drug at a discounted price and on the condition that data is collected to help address remaining questions over its efficacy.
In November 2017 GSK received FDA approval for a single-dose prefilled pen (autoinjector) presentation, administered as a once weekly subcutaneous injection of 200mg. This enables patients to self-administer their medicine at home, after initial supervision from their clinical team if considered appropriate. The subcutaneous version of the medicine adds to the existing intravenous (IV) formulation, but it is not yet available in the UK.
For over half a century, steroids have formed the basis of treatment of the sick lupus patient. Steroids are either given as tablets ('Prednisolone') or as injection (e.g. 'pulse' methyl prednisolone). Their effect is almost immediate and they can be life saving. They are used in many aspects of lupus e.g. low platelet counts, pleurisy, severe skin disease, arthritis and kidney disease.
One of the most important advances in lupus has been the more conservative use of steroids - lower doses and for shorter periods of time. The other has been the consistent use of other drugs (such as Hydroxychloroquine, azathioprine or mycophenolate) as steroid 'sparing' drugs.
The down side of steroids is their long list of side effects. These are dose related: on small doses, side effects are few. The more well known are increased appetite (and weight gain), sleeplessness and sometimes more 'crotchety' behaviour. Weight gain can be minimised by cutting out sugar in the diet.
The more serious side effects - associated with long term use, are cataracts, muscle weakness and bone osteoporosis
These agents, notably hydroxychloroquine are used in lupus clinics throughout the world and are particularly useful for skin rashes, joint pains & fatigue. They are discussed in detail in a separate section.
These are agents which suppress the over-active immune system in lupus. There are 4 main drugs currently in use - Azathioprine, Cyclophosphamide, Methotrexate and Mycophenolate.
This drug, in use for decades, has become the traditional 'first choice', particularly in combination with steroids, for active disease. Like all drugs in its class, it can lower the blood count and regular blood counts are necessary. Some patients are very intolerant of the drug with nausea and vomiting making a change of choice necessary.
This is a more toxic drug, kept for more severe cases, especially very active disease. It is almost always given as a 'drip' or 'pulse'. At the lupus clinic at St. Thomas' we have pioneered a more conservative dose regime. This has not only resulted in fewer side effects, but has almost totally eradicated one of the most feared side effects - ovary failure and infertility.
This drug, given weekly, is used worldwide in the treatment of rheumatoid & other chronic arthritis. In those patients with severe arthritis methotrexate does have a place in management. The two major side effects - low blood count & liver disturbance are monitored by regular blood tests.
This drug is now the standard treatment of lupus kidney disease. It is now used as 'first line' treatment of kidney disease and it is well tolerated.
There are a whole range of medical problems which can effect a lupus patient (as well as the rest of the population), but which are now increasingly effectively treated. These include thrombosis, arthritis, blood pressure, depression, osteoporosis, raised cholesterol & heart disease.
Thrombosis (blood clotting)
Those lupus patients with a clotting tendency usually require medication to keep the blood 'thinner'. The commonly used medicines are aspirin and in more severe cases, Heparin or Warfarin.
The commonly used drugs are known as 'non-steroidals' (non-steroidal, anti-inflammatory drugs). The older drugs such as ibuprofen and diclofenac are now being largely replaced by the new agents which are less irritant on the stomach. For more serious arthritis, stronger 'second line' drugs such as methotrexate are used. Non-steroidal drugs are now used very sparingly, if at all, due to their long term side effects.
Long term steroid treatment can lead to bone thinning. Nowadays, many patients on steroids are given supplementary calcium and Vitamin D. The good news is that there are a whole range of effective treatments available, including alendronate and in some patients, (including lupus patients), hormone replacement therapy (HRT).
It is now recognised that coronary artery disease is a significant problem in some lupus patients. The causes for this tendency are unclear. However, one potential risk factor, raised cholesterol, can be treated very effectively indeed. A family of drugs called statins are used. There are over a dozen to choose between, the differences are very minor. Fortunately, they are generally well tolerated by lupus patients.