Drug Therapy of Lupus
Lupus (SLE) is a condition where patients develop problems as a result of inflammation in different organs and of varying severity. The spectrum varies from lupus causing mild skin and joint symptoms to more serious life threatening disease involving major organs like kidneys, lungs and brain. SLE can affect almost any organ system in the body. Organ involvement is unpredictable with simultaneous or sequential organ involvement occurring during the course of disease. It is important that both patient and clinician are vigilant and recognise major organ involvement at the earliest. Treatment can then be introduced promptly. Based on research and experience, clinicians have learnt to use these drugs more effectively. It is also encouraging to note that research in lupus is constantly growing with some ongoing clinical trials promising new exciting treatment in near future. Until they become available we will have to make the best use of limited treatment choice available to us.
Primary aim of drug therapy is to suppress lupus inflammation and avoid organ damage. The next step is maintaining control or remission of lupus. Drugs that suppress or calm down the immune system are employed for this purpose. Some medications like non steroidal anti inflammatory drugs (NSAIDs) and analgesics are used mainly for symptom relief. An important aspect of lupus is treating the lupus related condition that itself can have significant impact on life.
NSAIDs are commonly used in patients with lupus. Commonly used NSAIDs include ibuprofen, diclofenac, naproxen, celecoxib etc. They are helpful for treating joint and muscle pain. Short courses of NSAIDs can also be used for treating pleurisy. NSAIDs can cause peptic ulcers, affect kidneys, increase blood pressure and risk of cardiovascular disease. Current recommendation is to use short courses. Patients requiring regular NSAIDS should be on smallest possible dosage that provides symptom relief. NSAIDs are best avoided in patients with known kidney and peptic ulcer disease.
Corticosteroids are the corner stone of treatment in lupus. They are available as oral tablets (prednisolone, deltacortil), topical creams (betnovate), and injections (hydrocortisone, depomedrone). Injections can be given into the joint or muscle and also administered as an intravenous infusion. Corticosteroids can be life saving treatment for severe lupus. Side effects like osteoporosis (brittle bone disease), diabetes, raised blood pressure, weight gain, mood changes and premature cataracts are seen with long term use of steroids. These side effects have made corticosteroids unpopular. However, when used appropriately their benefits clearly outweigh the risks. The abovementioned side effects are not seen with one off intramuscular or joint injection of corticosteroids.
Hydroxychloroquine (plaquenil), chloroquine and mepacrine are antimalarial drugs that are used to treat lupus. Hydroxychloroquine is the most commonly used antimalarial. They are helpful in treating lupus related arthritis, skin disease, pleurisy and fatigue. Side effects are uncommon. A rare complication of this treatment is eye problems. Currently an annual eye check after 5 years of continuous therapy is advised. Hydroxychloroquine is considered to be safe for use in pregnancy and breast feeding period.
Drugs that suppress the immune system are reserved for severe cases of lupus where the disease affects a major organ or is potentially life threatening. Drugs that fall in this category are cyclophosphamide, intravenous corticosteroids, intravenous immunoglobulins, azathioprine, mycophenolate mofetil, methotrexate and rituximab. Cyclophosphamide is a cancer chemotherapy drug. It is typically employed for lupus affecting the brain, kidney and cardiovascular system. It is given as an intravenous infusion or tablets. There is an increased risk of infection with this treatment. Longer and frequent courses also increase risk of bladder cancer in the long term. It may cause infertility and the risk is proportional to the total dose of cyclophosphamide used and patient’s age. Younger patients are less likely to develop infertility. The drug can cause foetal abnormalities if administered to pregnant patients. Regular blood tests are essential for monitoring this treatment.
Azathioprine is used for controlling lupus once remission is achieved. It is available in tablet form. It can cause liver and blood count abnormalities and therefore needs regular monitoring tests. On the whole it is a safe drug and can be used long term. It can be continued through pregnancy. Mycophenolate mofetil has grown in popularity as a lupus drug and is reserved for more severe lupus. It is particularly useful in lupus affecting the kidney. Diarrhoea is a relatively frequent side effect. It can also affect blood counts and needs regular blood monitoring tests. Pregnancy should be avoided whilst on this drug. Methotrexate is commonly used for treating rheumatoid arthritis and can be used in treating arthritis in lupus.
Rituximab is relatively new to the lupus armamentarium. It is licensed for use in lymphoma (a type of blood cancer) and rheumatoid arthritis. It has been used in patients with severe lupus who have failed to respond to cyclophosphamide, mycophenolate mofetil and corticosteroids. The literature is limited but so far the responses noted are encouraging particularly in patients with kidney and haematological involvement.
Controlling lupus inflammation is a vital component of managing lupus but there are other aspects of health that should be dealt with simultaneously. Lupus is an independent risk factor for cardiovascular disease. There is evidence to suggest that drugs like statins that reduce blood cholesterol levels are known to reduce cardiovascular disease. Cholesterol level check and statins introduced as appropriate. Patients should also get their blood pressure checked regularly and if identified to have hypertension (high blood pressure) treatment should be initiated promptly. Lupus patients are at increased risk of osteoporosis (brittle bone disease) when they are on regular corticosteroids. They should be evaluated for risk factors for osteoporosis and have a bone density scan. There are effective treatments available if osteoporosis is confirmed.
Fatigue is a frequently encountered symptom in lupus. There is no specific drug treatment available for treating this symptom. Conditions like anaemia, thyroid problem etc. can cause fatigue and need to be identified as treatment is available and can improve fatigue related to them. Fibromyalgia or chronic fatigue syndrome is another important cause of fatigue in lupus patients. Anxiety and depression need to be recognised as they are associated with fatigue. Anti depressants can be beneficial in fatigue secondary to depression and in the setting of chronic fatigue syndrome.
Antiphospholipid antibody syndrome is seen in lupus patients. They are at risk of developing thrombosis and clots. In women of child bearing age, there is increased risk of foetal loss. Lupus specialists and obstetricians are familiar with this condition and will screen for this problem. Treatment includes heparin injections and oral anticoagulants like warfarin depending on the clinical picture.
In summary, early recognition and introduction of treatment is the key to prevent damage caused by lupus. It is vital that patients are educated and informed about recognising features of active lupus. Patients should be aware and updated of local arrangements for access to help and support. This prevents an undesirable and avoidable delay in taking prompt action. Early effective treatment limits organ damage, saves lives and can have significant beneficial effect on patient’s life in short and long term.
We are grateful to Dr Kamath for kindly attending the LUPUS UK National Conference in Stoke on Trent this year, where he presented the above talk to delegates.
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