Lupus: Systemic Lupus Erythematosus (SLE)
Conventional Medicine’s Approach to Lupus Treatment
Since lupus potentially targets multiple organ systems, the type of treatment should be tailored for each individual person. Doctors may prescribe one, two, or more medicines at a time to maximize treatment response. An effective overall treatment strategy includes maintaining a healthy lifestyle—which may include conventional medicine, complementary medicine, exercise, good nutrition, and avoiding smoking and excessive sunlight—in order to reduce the frequency and severity of lupus flares. It is important to consider both the positive and detrimental effects of any treatment type before commencing a treatment plan.
Several categories of conventional medications are available that reduce inflammation, which is the chief cause of symptoms in lupus. Many of these medicines are often quite effective at reducing symptoms and preventing severe flare-ups. Unfortunately, these medicines are commonly associated with significant adverse long-term side effects.
Corticosteroids. Corticosteroids (glucocorticoids) are one type of steroid with powerful, anti-inflammatory effects. Synthetic corticosteroids mimic the effects of natural corticosteroids produced in the body and effectively reduce inflammation in people with lupus.
The most common corticosteroid medicine prescribed to treat lupus is prednisone. It may be taken orally in pill form, or injected into the skin to treat rashes, or intramuscularly (IM) to treat muscle inflammation. Other corticosteroids include hydrocortisone, dexamethasone, and methylprednisolone.
The possible side effects of corticosteroids include easy bruising; fat redistribution leading to an increase in fat around the abdomen; weight-gain and insulin resistance; and psychological changes ranging from irritability and depression to euphoria. They may also lead to increased risk of complications from diabetes, high blood pressure, glaucoma, and may cause elevated triglyceride and cholesterol levels. If taken over the long term, corticosteroids cause bone loss and therefore leads to an elevated risk of bone fracture. Due to effects on triglyceride and cholesterol, long-term corticosteroid use could also contribute to an increased risk for atherosclerosis.37
Due to these potentially severe side effects, the lowest dose of corticosteroids that provides symptom relief is prescribed. Injected corticosteroids are usually only used to treat very severe disease flares; once symptoms come under control, oral administration is resumed.37,38
Non-steroidal anti-inflammatory drugs. Like corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) also suppress inflammation. However, NSAIDs are less effective for individuals with severe lupus than corticosteroids. NSAIDs, of which there are more than 20 types available, are both anti-inflammatory and analgesic, meaning they provide pain relief as well as reduce inflammation. Examples of NSAIDs include ibuprofen and naproxen. Although adverse effects are possible, and these risks are elevated in people with lupus, administration of NSAIDS with close monitoring by physicians can be helpful.39
NSAIDs operate by inhibiting the secretion of leukotrienes and prostaglandins that cause inflammation and pain. Possible side effects include stomach upset, nausea, and even gastrointestinal bleeding; fluid retention; kidney damage, and increases in blood pressure and heart attack risk.40
Aspirin may be particularly helpful in individuals who have anti-phospholipid antibodies, which can make blood particularly "sticky" and prone to clotting. In the case of patients who are discovered to have anti-phospholipid antibodies without any known thrombotic problems, the question of preventative (prophylactic) treatment is unresolved. Currently, aspirin is the general recommendation.41
Due to aspirin’s blood thinning, anti-inflammatory, and analgesic effects, doctors may recommend taking low-dose aspirin to reduce the risk of heart disease in people with lupus and relieve the pain of aching joints.42
Although the original purpose was to treat the parasitic disease malaria, it was discovered more than 50 years ago that anti-malarial drugs were also effective in treating the symptoms of lupus through minor immune suppression. In people with lupus, these drugs have been shown to reduce inflammation in the lining of the lung (pleurisy) and heart (pericarditis), improve joint and muscle pain, and reduce fever and fatigue. Examples of anti-malarial drugs include chloroquine, hydroxychloroquine, and quinacrine.43-45
Possible side effects include gastrointestinal symptoms like nausea, vomiting, diarrhea, stomach cramps; headache, dizziness, and irritability; and the skin may darken in color and become very dry.45
Immune System Modulators
Immune system modulators treat lupus by altering the number or function of immune cells. As lupus is an immune-mediated disease, this approach is often effective.
Some immune system modulating drugs globally suppress the immune system, and are thus called immunosuppressive drugs. While the self-reactive immune cells are suppressed, the cells that fight against infections are also inhibited, which can lead to increased susceptibility to infections. Potentially severe side effect may occur with all immunosuppressive drugs. Examples of commonly prescribed immunosuppressive drugs include the following:
Cyclophosphamide. Cyclophosphamide has been used for several decades and is quite effective in treating lupus-related kidney disease. However, the side effects of cyclophosphamide can be severe and include nausea, vomiting, infertility, and hair loss. One study indicates that low-dose cyclophosphamide is still effective in treating individuals with lupus nephritis.46
Mycophenolate mofetil. This medicine is newer, more effective, and causes fewer side effects than cyclophosphamide. Due to these positive characteristics, mycophenolate mofetil has replaced cyclophosphamide as the first-line drug for the treatment of lupus.47-49
Azathioprine. Azathioprine is an immunosuppressive drug that also has fewer severe side effects than cyclophosphamide, and overall, data suggest it is similar in effectiveness.50
When an antibody "sticks" to the surface of a cell, it either blocks its function and/or tags the cell for removal from the body. Scientists have taken advantage of this quality of antibodies to design ones that stick to and induce the clearance of many different cell types, including B and T cells.
Monoclonal antibodies are created through a complex process involving culturing specialized immune cells with disease-specific stimuli (antigens) and purifying the antibodies that are produced as a result.
Monoclonal antibodies represent one of the greatest advancements in lupus treatment in recent history. The advent of monoclonal antibodies targeted towards receptors on the surface of B cells allows physicians to turn the immune system against itself, in a sense, and eradicate self-reactive B cells that underlie lupus pathology.
The Food and Drug Administration (FDA) has approved a few of these drugs to treat some diseases, especially certain types of cancer. Monoclonal antibodies also show promise as drugs to treat lupus.
One monoclonal antibody drug recently approved by the FDA to treat lupus is belimumab, which targets B-cell activating factor (BAFF), a protein involved in activation, differentiation, and proliferation of B cells.51-53 The FDA’s approval of belimumab for the treatment of lupus is a groundbreaking achievement, as this is the first new drug developed specifically for lupus that has been approved for the last 50 years.51 Belimumab is co-marketed by Human Genome Sciences and GlaxoSmithKline under the name Benlysta, with cost estimates exceeding $30,000 annually. However, insurance should cover this therapy in most cases, as few new therapeutic options for lupus exist.54
Rituximab is also a monoclonal antibody drug that targets a receptor on B-cell surfaces called CD20, thereby causing the immune system to destroy B cells. It was originally approved to treat lymphoma, and may be effective in other diseases characterized by too many or malfunctional B cells, including lupus. Currently, studies are mixed as to whether this drug is effective in treating lupus.55 Rituximab is not approved to treat lupus, but is often used off-label for this purpose by many physicians.
Other monoclonal antibody drugs that may be effective in treating lupus and are still being studied include epratuzumab, abetimus, ocrelizumab, and atacicept, all of which target B cells.55 Additional drugs are being developed and tested with targets such as T cells and pro-inflammatory proteins.
Currently, monoclonal antibody drugs face several challenges and may cause adverse reactions in some patients. However, scientists are quickly elucidating the role of particular proteins and receptors in the molecular physiology of lupus and it is very likely that monoclonal antibody therapy will become much more efficacious in the near future.