Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis

Boumpas, Dimitrios T.; Austin, Howard A.; Balow, James E.; Vaughan, Ellen M.; Yarboro, Cheryl; Klippel, John H.; Steinberg, Alfred D.

doi:10.1016/0140-6736(92)92292-n

Cited by 745 publications

(439 citation statements)

References 21 publications

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“…Previous reports (11, 13,[17][18][19][20][21] did not analyze in detail the effect of method of CYC administration on rate of relapse. In systemic vasculitis, Fauci et a1 (28) demonstrated that daily oral CYC is more effective than intravenous CYC in preventing new events of vasculitis.…”

Section: Discussionmentioning

confidence: 99%

“…However, followup of patients in these studies was short or was not mentioned in the reports (11, 13,[17][18][19]. Boumpas et a1 (20) and Wagner-Weiner et a1 (21) found that short courses of intravenous CYC pulses were associated with a higher rate of disease exacerbation than were longer courses. Information regarding the influence of demographic and clinical variables, renal histology, and methods of CYC administration is lack-ing.…”

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confidence: 99%

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Cumulative rate of relapse of lupus nephritis after successful treatment with cyclophosphamide

Ciruelo

Cruz

López

et al. 1996

Arthritis & Rheumatism

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Objective. To determine the cumulative rate of relapse of lupus nephritis that has been treated successfully with cyclophosphamide (CYC), and to estimate the association between time to relapse and demographic, clinical, laboratory, and treatment variables.Methods. This was an observational study of 48 systemic lupus erythematosus (SLE) patients who were treated successfully with CYC between 1979 and 1993 and followed up thereafter a t 3 university hospitals. Demographic and clinical variables, laboratory data during the first month of nephritis, and therapy-related variables were recorded from charts. Renal biopsy specimens were retrieved and analyzed by a pathologist. Relapse of nephritis was the outcome of interest. Descriptive analysis of patients who did and those who did not have a relapse was performed by chi-square test, Fisher's exact test, and Wilcoxon 2-sample test. The cumulative rate of relapse was computed using the actuarial method. Univariate comparisons of time to relapse were computed by log-rank test. Proportional hazards modeling was used to assess the combined effect of patient characteristics that have been hypothesized to be prognostic factors.ResuZts. Nephritis relapsed in 11 patients. Previous hematologic disorder, arthritis or arthralgia, and the use of CYC in oral form were more frequent in patients who had a relapse. The cumulative rate of relapse was 25% and 46% at 5 years and 10 years, respectively. A significant univariate difference in time to relapse was found when patients were stratified by Renal disease is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) (1-4). The use of immunosuppressive agents has been associated with a better prognosis (5-12). Combined cyclophosphamide (CYC) and glucocorticoid therapy is deemed to yield significant improvement in renal survival (13-15) and positive economic impact, compared with glucocorticoid therapy alone (16). However, several questions regarding the use of CYC in lupus nephritis remain unresolved. The optimum dosage, length of therapy, and method of administration have not been fully established. Toxicity and side effects are major limiting factors.The rate of relapse of nephritis following CYC therapy is largely unknown. This issue is important because recurrent episodes of nephritis may lead to progressive renal failure. In various studies, the rate of relapse of nephritis has ranged between 0 and 50%. However, followup of patients in these studies was short or was not mentioned in the reports (11,13,(17)(18)(19). Boumpas et a1 (20) and found that short courses of intravenous CYC pulses were associated with a higher rate of disease exacerbation than were longer courses. Information regarding the influence of demographic and clinical variables, renal histology, and methods of CYC administration is lack-

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Cumulative rate of relapse of lupus nephritis after successful treatment with cyclophosphamide

Ciruelo

Cruz

López

et al. 1996

Arthritis & Rheumatism

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“…Though high-dose IV CYC in combination with glucocorticoids viewed as the most effective immunosuppressive medication for LN, no final conclusion has yet been reached on this matter so far. With development of further research into this issue, several investigators have raised concerns about the high-dose CYC regimen for the treatment of SLE, especially the risks of infection and ovarian failure [9,10]. Meanwhile, other researchers put forward a question on whether the patients with mild damage should use this regimen or not.…”

Section: Discussionmentioning

confidence: 99%

Short-interval lower-dose intravenous cyclophosphamide as induction and maintenance therapy for lupus nephritis: a prospective observational study

Zhang

et al. 2014

Clin Rheumatol

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Cyclophosphamide (CYC) has long been considered a gold standard in inducing renal remission and preventing renal flares for patients with systemic lupus erythematosus (SLE). However, the rational use of CYC has not reached a consensus, such as the timing and length of treatment, the route of administration, and the ideal dosage. The objective of this study was to assess the efficacy and safety of short-interval lower-dose (SILD) intravenous (IV) CYC in the treatment of SLE. A total of 225 patients with lupus nephritis were randomly assigned to a 1-year trial, either the SILD group (12 fortnightly pulses at a fixed dose of 400 mg followed by 6 monthly pulses) or high-dose (HD) group (6 monthly pulses followed by two quarterly pulses at a dose of 0.5~1.0 g/m 2 ). At 6 months of treatment, 28 % (30/107) of patients in the SILD group reached a complete remission (CR), and 51.4 % (55/107) were in partial remission (PR), as compared with 32.7 % (35/107) and 45.8 % (49/107) in the HD group, respectively. Serum albumin, 24-h urinary protein, and the scores of disease activity were significantly improved in both groups at 6 months and maintained at the end of clinical trial. However, the SILD group showed much less menstrual disturbances (11.5 %), gastrointestinal adverse effects (5.3 %), and leukopenia (9.7 %) than the HD group (28.6, 26.8, and 19.8 %, respectively) at the end of clinical trial. The efficacy of the short-interval lower-dose (SILD) IV CYC regimen in the treatment of lupus nephritis is equivalent to that of the high-dose (HD) regimen, whereas the incidence of adverse events is much lower in the SILD group.

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“…One of the plausible reasons for choosing CYC is that data on the use of MMF for severe LN are still limited as compared to those on the use of CYC, which has a long history of clinical trials and clinical treatment for LN. For example, one of the NIH clinical trials demonstrated that long-course CYC therapy can prevent deterioration of renal function more effectively than mPSL pulse therapy in patients with severe LN [11].…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of severe crescentic lupus nephritis by multi-target therapy using tacrolimus and mycophenolate mofetil

et al. 2014

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Treatment of severe lupus nephritis (LN) has been controversial, and according to recent guidelines and recommendations, cyclophosphamide still remains a firstline therapy. Herein, we present the case of a 37-year-old female patient who developed rapidly progressive glomerulonephritis, which was histologically diagnosed as class IV ? V LN, with a large number of cellular to fibrocellular crescents (62 % of glomeruli). Although the patient was considered to have the most severe form of LN, complete remission was achieved within 6 months by multi-target therapy using tacrolimus and mycophenolate mofetil combined with methylprednisolone pulse therapy. Our experience suggests that multi-target therapy could be a potential treatment option for patients with severe crescentic LN.

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Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis

Cited by 745 publications

References 21 publications

Cumulative rate of relapse of lupus nephritis after successful treatment with cyclophosphamide

Cumulative rate of relapse of lupus nephritis after successful treatment with cyclophosphamide

Short-interval lower-dose intravenous cyclophosphamide as induction and maintenance therapy for lupus nephritis: a prospective observational study

Successful treatment of severe crescentic lupus nephritis by multi-target therapy using tacrolimus and mycophenolate mofetil

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