The Benefits and Risks of Treatment Regimes for SLE Cocktails or Dogs Breakfast?
By Dr Ian Bruce
Consultant Rheumatologist, Manchester Royal Infirmary.
Introduction A major concern for many patients with SLE is that they often seem to end up on an increasingly long list of medications. It is not unusual for some lupus patients to take more than five different medications every day. In view of the chronic nature of the condition and the specific instructions regarding timing of taking each medication etc this is often a source of frustration. One may also worry about the potential hazards of some treatments and whether the drugs interact with one another to cause potential harm. This article aims to consider some of these issues in more detail.
Treatment for lupus works!
Over the past 50 years there has been a huge improvement in the overall survival rates of patients with SLE. In the 1950s, 5-year mortality rates of 50% were quoted. Currently, the 5-year survival is greater than 90%. There is no doubt that the introduction of new therapies particularly steroids, anti-malarials and immunosuppressant drugs have all contributed to the improved survival rates in SLE. In addition, there are many advances in medicine in general e.g. better antibiotics, better intensive care facilities and a wider use of dialysis treatment etc. All these give patients a higher chance of coping with serious complications, thus improving survival.
As patient survival has improved and doctors have been able to follow patients up for a longer period of time, many new problems have been noted which now cause significant concern. Complications such as osteoporosis and fractures, atherosclerosis leading to heart disease and cataract formation etc have all been noted. Studies in various centres across the world have demonstrated that many of these problems are a consequence of either the long-term effects of the disease itself and/or a consequence of the treatment used. Therefore, osteoporosis and cataract formation are both largely a consequence of steroid therapy. In contrast chronic renal failure and pulmonary fibrosis, when they occur, are a result of the disease process. Other complications such as cardiovascular disease may represent a combination of disease and treatment-related effects. Regardless of the cause, advances in medicine have provided us with important new treatments that allow us to begin to prevent and treat many of these long-term complications.
Treatments commonly prescribed for lupus patients
The types of treatments that lupus patients take fall broadly into 3 groups. There are drugs primarily prescribed to treat one of the underlying disease processes in lupus such as inflammation, Raynauds phenomenon or risk of clotting. Other drugs are used to control symptoms associated with the disease e.g. anti-epileptic drugs, anti-depressants etc. The third group of drugs tend to be used for the prevention and treatment of complications e.g. bone protective agents, blood pressure tablets etc (see drug therapy table). It is the third group of drugs in particular that are contributing to the increasingly lengthy list of treatments prescribed in patients with lupus. The main reason for this is the many major advances in areas of medicine of relevance to lupus patients. For example, in the past decade new and effective therapies have been developed to reduce the risk of fractures in patients with osteoporosis and reduce the risk of heart disease associated with high cholesterol. These developments are extremely good news for patients with SLE. Within the same time period, the role of older more established treatments have also become much clearer, for example, the role of warfarin in the treatment of anti-phospholipid syndrome (APS).
Are there hazards with taking several drugs at a time?
There are three ways in which drugs may cause problems in the context of SLE. Firstly, certain drugs may exacerbate some of the underlying disease processes and increase the risk of disease-related complications. Some patients with Raynauds phenomenon find that beta-blocker treatment, which can be very effective for the treatment of high blood pressure, may make their Raynauds worse. Similarly, certain oestrogen-containing compounds e.g. the oral contraceptive pill or hormone replacement therapy increase the risk of clotting in patients with APS. Secondly, many drugs do have the potential to cause side effects. Generally these are either predictable and dose-related or idiosyncratic (unpredictable) and while recognised to happen are impossible to predict in an individual patient. Predictable and dose-related side effects include weight gain with steroids, reduced white cell counts with high-dose cyclophosphamide and bleeding with too much warfarin. Idiosyncratic reactions include allergic rashes, drug fevers, acute hepatitis etc. The third problem is the potential for certain drugs to interact with one another. A drug interaction is said to occur when the taking of two drugs together significantly increases the risk of side effects from one or the other. For example, certain drugs can affect the dose of warfarin required and if this goes unnoticed the risk of clotting or bleeding on warfarin may be increased. Another important drug interaction is that of azathioprine with the gout treatment allupurinol. If allupurinol is added to the regime of someone taking azathioprine then the risk of serious toxicity increases. It is therefore recommended that the dose of azathioprine be significantly reduced if allupurinol is prescribed.
Another increasingly-recognised issue is the use of complementary treatments, including herbal remedies, dietary supplements etc. It should be pointed out that, historically, modern medicine has derived many of its best agents, e.g. aspirin, warfarin and digoxin, from herbs and plants. Also, it should not be assumed that because complementary therapies are natural that they do not have the potential to interact with prescription drugs. Another difficulty with some complementary therapies is that the exact dose of the active ingredient cannot be predicted or guaranteed. Complementary therapies may therefore add an additional complicating factor that your treating physician needs to be aware of.
Just keep taking the tablets?
A frequently-asked question is whether a patients treatment for SLE will be life-long. SLE is a long-term condition and requires ongoing follow-up to assess and manage the disease and prevent complications. In some circumstances, the treatment may inevitably require to be life-long, e.g. anticoagulation in APS. In a study performed in the Toronto Lupus Clinic, it was found that when it came to treatments such as steroids and antimalarial drugs, approximately 1 in 8 patients were able to stop all such drugs for periods of at least 5 years at some point during their illness. Many other patients were controlled on very low doses of treatment over a long period of time. Therefore treatment for lupus or its complications may not essentially be life-long. For example, bone-protecting agents may only be necessary during the time that the patient is actually taking steroids. Also, under certain circumstances, anti-convulsive therapy may be safely withdrawn after a seizure-free period.
The key is therefore for patients to be fully informed as to why they are taking individual treatments and the potential benefits and risks involved with each drug and drug combination. Adherence with therapy i.e. taking treatment in the way in which it is prescribed, is in itself an extremely important aspect of lupus disease management. We have found in a study of patients who developed chronic renal impairment that in about a third of cases, not taking the tablets in the prescribed manner contributed significantly to the development of this complication. As a result, it is important that patients and professionals work together to ensure that treatments prescribed are necessary and at the correct dose. It is also important to ensure that the benefits do indeed outweigh the potential risks and that potential side-effects and interactions are closely monitored. In many situations, hospitals and pharmacies will have drug information leaflets that are of great value. For certain treatments, a monitoring regime is recommended and forms a cornerstone of on-going management. Therefore patients taking warfarin have their INR checked on a regular basis. In addition, certain immunosuppressive drugs require careful blood monitoring to anticipate and minimise the risk of toxicity.
What does the future hold?
In the short-term, it is likely that patients with lupus will be prescribed more treatment! Audits of various aspects of long-term management such as prevention of cardiac disease and osteoporosis suggest we may need to treat more patients. As was pointed out by Dr DCruz in a recent article in News and Views there are however many exciting developments in the treatment of SLE. If some of these therapies prove themselves to be superior to current treatment then the overall amount of therapy needed may actually be reduced. Ultimately, if a treatment can be proven to cure or provide a long-term remission then the necessity for many drugs would be dramatically reduced.
Conclusions
In the past 50 years we have witnessed significantly improved survival rates for patients with SLE. There have also been major advances in medicine in general which allow us to begin to treat the risk factors for long-term complications. As a result, many patients with lupus now find themselves taking a large number of different medications. The risks associated with these therapies can often be anticipated and with a close partnership between the doctor, patient and other health professionals, as well as careful monitoring and follow-up, these risks can be minimised. A key goal of long-term follow-up is to continually revise and, where possible, reduce treatment regimes. While even now many treatments are not necessarily life-long, in the future when more effective treatments for lupus become available we should be able to further reduce the overall treatment burden in SLE.
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