High doses of cyclophosphamide in the treatment of severe systemic lupus erythematosus
2001
TREATMENT of patients with systemic lupus erythematosus (SLE) has not changed substantially in the last 10 years. In general, low to moderate doses of corticosteroids and antimalarics are sufficient for mild forms of the disease, whereas high doses of corticosteroids, combined with other immunosuppressive drugs, are required for cases with affected kidneys or central nervous system (CNS). As an immunosuppressive drug, cyclophosphamide (Cy) may be applied according to different protocols, but the protocol from the National Institutes of Health (NIH), is used most frequently. 4 Side effects of therapy with Cy are numerous, some of which are very serious. The most common adverse effects include alopecia, amenorrhea, bone marrow suppression, hemorrhagic cystitis, risk of infection, and malignancy. If the dose of Cy and route of administration are carefully selected, even severe forms of SLE could be successfully treated with minimal side effects. The aim of this work was to report on our 10-year experience with high “pulse” doses of Cy in the treatment of most severe forms of SLE. For the period 1988 to 1999, a total of 178 patients (162 women and 16 men) who met the ARA criteria for diagnosis of SLE were submitted to treatment at the Clinic of Rheumatology and Clinical Immunology, MMA, Belgrade. Among these patients, 78% (139 of 178) had arthritis, 64% (114 of 178) facial butterfly erythema, 42% (75 of 178) glomerulonephritis, 19% (34 of 178) CNS manifestations according to ARA criteria, 10% (18 of 178) a severe form of skin vasculitis, and 7% (12 of 178) carditis. Of the patients with glomerulonephritis, type IIb was diagnosed in 21, type III in 21, type IV in 30, and type V in 9, according to WHO classification. In the group of patients with affected CNS, 26 had epilepsy and 8 had psychosis. High “pulse” doses of Cy were applied in 68 patients with the most severe disease: 38 patients (56%) had glomerulonephritis, about half of whom had kidney insufficiency; 24 patients (35%) had glomerulonephritis and CNS involvement; and 6 patients (9%) had CNS manifestations only (Table 1). For 22% (15 of 68) of patients, therapy with Cy came first. Another 78% (53 of 68) patients were treated previously with other therapeutic modalities, but unsuccessfully. Cyclophosphamide was administered at a dose of 10 to 15 mg/kg body weight, depending on creatinine clearance in infusion of physiologic solution, together with 40 mg methylprednisolone. Antiemetics were given before and after each infusion. In addition, extensive hydration with at least 2 L of liquid was performed. The above procedure was repeated monthly during 6 months and, thereafter, a maximum of six more times in intervals of 3 months, depending on the effect achieved after the first 6 months. Between infusions, patients were treated with corticosteroids at a dose of 15 to 30 mg/d, and also with antimalarics. Treatment efficacy was evaluated as positive if clinical, biochemical, and immunoserologic signs of disease activity were absent (complete remission), or biochemical and immunoserologic signs persisted (incomplete remission). Complete remission of disease was achieved in 75% (51 of 68) and incomplete remission in 10% (7 of 68) of patients (Table 2). A positive effect was usually obtained after a third “pulse” of Cy (range 1 to 8). These patients were treated further with low doses of corticosteroids or antimalarics, or in eight cases with azathioprine. Therapy with Cy was ineffective in 15% (10 of 68) of patients. Four patients from this group developed terminal kidney insufficiency. They did not reach remission after 6-month treatment. In such cases, cyclosporine or high doses of human intravenous immunoglobulins were applied. At present, treatment lasting 6 to 24 months
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