Clinical Effects of Intermittent, Intravenous Cyclophosphamide in Severe Systemic Lupus erythematosus

Abstract

To evaluate the clinical effectiveness of intermittent intravenous cyclophosphamide in the treatment of severe systemic lupus erythematosus, 20 patients with systemic lupus erythematosus (SLE) and evidence of severe renal involvement or systemic vasculitis, consecutively admitted to the hospital were studied. Cyclophosphamide was administered intravenously at a dosage of 1.0 g/m² monthly, during 6 months and maintained every 3 months during 12 additional months. Of 10 patients with active lupus nephritis, a reduction or disappearance of proteinuria and maintenance of normal renal function was recorded in 6. Improvement of renal function was observed in 4 out of 7 patients with renal insufficiency at initial evaluation; resolution of renal insufficiency was more frequently observed in patients with recent onset renal failure. At the end of the follow-up (18.0 ± 14.5 months) disappearance or reduction of nephrotic range proteinuria was recorded in 6 out of 14 patients; there was progression toward renal failure in 4 patients (20%). Response to intravenous cyclophosphamide therapy was observed in 4 of 5 patients with severe extrarenal SLE. Side effects, recorded in 12 patients, were mild and transient and in no patient was the treatment discontinued. Four patients died during the follow-up, although in 2 of them the deaths were not attributable to therapy. Even though this was an open and uncontrolled study, intermittent, intravenous cyclophosphamide was an effective therapy for severe, steroid refractory SLE.

The American college of rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials

“…The committee defined improved as a 50% reduction in the urinary protein: urinary creatinine ratio. The literature is replete with definitions of improvement based on the 24-hour urine protein excretion level (5,9,15,16,18,24,32,34,35,38,47,52,66,72,74,75,80,81,(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98). In addition, the committee thought that a reduction in proteinuria from the nephrotic range (Ն3.5 gm/day) to the non-nephrotic range was an important and distinctive end point.…”

“…Nephrotic syndrome was defined as hypoproteinemia, edema, and proteinuria, and thus, we distinguish the nephrotic syndrome from nephrotic proteinuria in this discussion. There have been numerous definitions of nephrotic proteinuria (8,24,38,40,42,54,57,72,73,79,90,94,(98)(99)(100)(101); the committee chose a 24-hour urinary protein level of Ն3.5 gm. A partial response was defined as a urinary protein:urinary creatinine ratio of 0.2-2.0 (15,24,32,47,(90)(91)(92).…”

Evaluation the effectiveness of intravenous cyclophosphamide treatment in children with lupus nephritis

“…Buna karşılık, siklofosfamid tedavisinin renal sonuçlar açısından diğer tedavilere üstün olmadığını gösteren çalışmalar da mevcuttur (21,22) . Yapılan bazı çalışmalarda (23,24) intravenöz siklofosfamid sonrası SDBY gelişme oranı çalışmamıza göre daha yüksek bulunurken, intravenöz siklofosfamid kullanımı ile daha düşük oranlar bildirilen çalışmalar da mevcuttur (14,25) . Çalışmamızda, intravenöz siklofosfamid alan 4 hastada (%14.3) SDBY gelişmiştir.…”

“…Bazı çalışma-larda, hipertansiyon varlığı kötü renal prognoz ile ilişkili bulunmuştur (21,24,35) . Yüksek aktiflik (31,36) ve kroniklik indeksinin (25,31,32,36) renal sonuçlar üzerine prognostik etkisi olduğunu gösteren çalışmalar vardır.…”

Expression of the c-Fos gene in hypothalamic cells and cytotoxic activity of natural killer cells in the spleen of rats after treatment with cytoxan

“…Administration of Cytoxan in a dose of 60 mg/kg increased the number of c-Fos-positive cells in the ventromedial hypothalamus and lateral hypothalamic area and reduced interferon-α-induced cytotoxic activity of natural killer cells. Our findings attest to the involvement of central mechanisms of regulation of splenic natural killer cells into side effects of Cytoxan.Cytostatics (e.g., cyclophosphamide-containing drugs) widely used in clinical practice produce pronounced side effects, which limits the duration or even makes impossible their use [2,5,6,8,9]. Deciphering of the mechanisms of side effects of these drugs will allows us to develop new approaches to diminish their adverse impact.…”