Systemic Lupus Erythematosus - Treatment for Severe SLE

Leflunomide. Leflunomide (Arava), an anti-rheumatic drug,blocks autoimmune antibodies and reduces inflammation in patients with rheumatoid arthritis. The drug is now being used for lupus with good results, but requires further study.

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Sitaxsenten. Sitaxsenten, an endothelin receptor antagonist, is being investigated for treatment of pulmonary hypertension as a complication of lupus. A study presented at the 2004 annual scientific meeting of the American College of Rheumatology indicated that sitaxsenten improved patients? ability to perform a walking test.

Riquent. Riquent is being developed to treat lupus patients with kidney disease (lupus nephritis). Initial trial results appeared promising, with fewer side effects than current treatments, but in October 2004 the FDA requested an additional clinical trial before approval would be considered.

Autologous Stem Cell Transplantation. Some patients with severe SLE have achieved at least short term remission after undergoing autologous transplantation of stem-cells and high-dose drug therapy to suppress the damaging immune factors. Stem cells are the early forms for all blood cells in the body. An autologous transplant is one in which marrow or blood cells used are the patient's own. (The advantage to an autologous transplant is that the patient's own cells are not at risk for rejection by the immune system.)

The procedure itself first removes the cells from the patient, who then receives high-dose immunotherapy. The stem cells are then reintroduced. Early results of small studies are encouraging, especially for treatment of antiphospholipid syndrome. Evidence suggests that these re-introduced stem cells do not repeat the original autoimmune errors. In some cases, SLE has remained inactive for more than2 years. In 2004, the NIH launched a pilot 5-year study of autologous blood stem cell transplantation. Fourteen patients will be followed to see if they remain in remission and relapse-free. Researchers will also compare the ?before? and ?after? activity of the patients? B and T cells.

UVA-1 Phototherapy. A promising treatment uses ultraviolet A-1 (UVA-1) radiation, which are long UVA wave lengths that do not promote sunburn and may actually block inflammatory immune factors. Small studies have suggested that UVA-1 phototherapy may have some benefits for lowering disease activity in SLE.

Treatments for Some Complications of Systemic Lupus Erythematosus
Infections, Inflammation, or Hypertension in the Lungs	Preventive Measures. Immunizations with inactive viruses and preventive antibiotics should be considered for patients with SLE at high risk for infection. Treating Infections. Lung infections need to be treated aggressively with antibiotics. (Note: Antibiotic drugs such as penicillin or the sulfa drugs may cause sensitivity rashes that can be confused with SLE rash.) Treating Lung Inflammation. While inflammation of the lung (pneumonitis) resembles pneumonia, it is not an infection but is a result of the autoimmune process. This condition needs to be treated with corticosteroids or immunosuppressants, but only if the doctor is sure infection is not present. Treating Pulmonary Hypertension. Pulmonary hypertension is very serious. Drugs known as prostacylins, which include epoprostenol, iloprost, and treprostinil, are standard drugs. Bosentan (Tracleer) is the first oral drug approved for pulmonary hypertension. An inhaled iloprost formulation (Ventavis) was approved in 2004. Sildenafil (Viagara) is also be used for this condition. Lung transplantation may be required.
Bleeding and Clotting Disorders	Antiphospholipid Syndrome and Clotting Disorders. Hydroxychloroquine or aspirin may help prevent blood clots in women with antiphospholipid syndrome (APS). (Aspirin does not appear to be protective in men with who carry the autoantibodies responsible for APS.) In patients who have experienced blood clots, treatment with the anticoagulant warfarin (Coumadin) is advisable. This blood-thinning drug may be needed life long. Scientists are investigating other treatment options including autologous stem cell transplantation. This procedure involves removing stem cells from a patient?s blood or bone marrow and then introducing them back into the patient. The procedure has shown promise in studies for treating lupus-associated APS, but it is still experimental. Excess Bleeding from Thrombocytopenia (Drop in Blood Platelets). Treatments that may be effective for thrombocytopenia include combinations of a corticosteroid and either danazol (a male hormone) or the antimalarial hydroxychloroquine. Immunosuppressants or intravenous immunoglobulin IgG may be helpful in some patients. Surgical removal of the spleen may be advisable if bleeding disorders are a serious problem, but this option should be considered carefully, because the spleen provides one line of defense against infection. (Abnormal spleen function, in any case, appears to be fairly common in SLE.)

The spleen is an organ that helps produce and maintain red blood cells. It also aids the body's immune system by producing white blood cells that destroy harmful substances in the body. Removal of the spleen makes a person more susceptible to infection.

Kidney Disease

Drugs. Mycophenolate mofetil (CellCept), a newer drug, is proving to be helpful in treating kidney disease associated with SLE and hasfewer side effects than other immunosuppressants. It is taken by mouth. Recent studies suggest that it works better than cyclophosphamide. CellCept may be best for patients with mild to moderate lupus kidney disease and may not be appropriate for patients with advanced kidney disease.

Intravenous cyclophosphamide is the most effective drug at this time for proliferative lupus nephritis, and, in combination with a steroid, has been shown to controladvanced kidney diseasein between 60 -90% of patients. It has severe side effects including nausea, vomiting, hair loss, and infertility.

Steroids are also useful for treating active kidney disease and for managing milder forms of nephritis.

Procedures. Kidney transplant or dialysis should be considered for patients with SLE with severe kidney damage. For unknown reasons, SLE does not generally recur in the transplanted kidneys. Studies are conflicting, however, over whether SLE transplant patients have higher organ-rejection rates than other kidney-transplant recipients. Both transplantation and dialysis have potentially serious complications.

Plasmapheresis.It is not clear ifplasmapheresis is beneficial for SLE kidney disease.

Click the icon to see an illustrated series detailing kidney transplant.

Osteoporosis

Treatments for osteoporosis include calcium, vitamin D, bisphosphonates, parathyroid hormone, and selective estrogen-receptor modulators (SERM).

SERMs, such as tamoxifen (Nolvadex), raloxifene (Evista), and tibolone (Livial), are of particular interest in SLE because they have been designed to produce the benefits of estrogen without some of its adverse effects, such as hormone-related breast cancer.

Heart Disease

The need for aggressive treatment of high blood pressure often accompanies kidney disease. SLE is also accompanied by high cholesterol levels, which also require diet and usually drug therapies. [See In-Depth Reports #3: Angina and Coronary Artery Disease; #14: High Blood Pressure; #23: Cholesterol;#43: Heart Healthy Diet.]