EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis

Yee, CS; Gordon, Caroline; Dostál, C; Petera, P; Dadonienė, Jolanta; Griffiths, Bethany E; Rozman, B; Isenberg, David; Sturfelt, Gunnar; Nived, Ola; Turney, J. H.; Venalis, Algirdas; Adu, Dwomoa; Smolen, JS; Emery, P

doi:10.1136/ard.2002.003574

Cited by 81 publications

(44 citation statements)

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“…To our knowledge this is the first study from a developing country comparing DOC and PIVC. Other studies have reported leucopenic episodes in 17 -26% of PIVC and 19 -45% of DOC participants [7,14,16] and infection in 10 -39% of PIVC and 14 -57% of DOC participants. Similar infection rates were observed in our study (DOC 36% v. PIVC 43%), while leucopenia was more frequent (DOC 51% v. PIVC 33%).…”

Section: Discussionmentioning

confidence: 84%

“…This led to PIVC becoming the standard treatment in lupus nephritis, with fewer subsequent trials and recommendations that include DOC. [3,6] This practice is now contested, as subsequent trials [4,7,8] and a recent Cochrane review [9] showed no difference in outcomes or adverse events. An increased tendency to relapse has also been shown in patients with lupus nephritis treated with PIVC.…”

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confidence: 99%

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Oral v. pulse intravenous cyclophosphamide: A retrospective analysis of adverse events in a setting with a high burden of infectious disease

2015

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Background. Cyclophosphamide (CPM) is still considered to be the first-line treatment for many life-threatening autoimmune conditions. It does, however, carry a significant risk of serious adverse events, especially infections. At present CPM is administered as either a daily oral dose (DOC) or an intravenous pulse (PIVC). There is uncertainty regarding the safety profiles of both regimens in settings with a high burden of infectious diseases. Objective. To compare the frequency and nature of adverse events related to the use of DOC and PIVC in such a setting. Methods. A cohort of patients treated with CPM for autoimmune diseases at Tygerberg Academic Hospital, Cape Town, South Africa, from 1 January 2008 to 31 May 2013 was studied. We compared participants receiving DOC and PIVC with regard to disease characteristics and the occurrence of major adverse events. Results. A total of 134 participants (92 DOC and 42 PIVC) were included. Participants in the DOC group were treated for longer (174 v. 101 days; p<0.01) and with higher cumulative doses (17 276 v. 3 327 mg; p<0.01). Risk of infection was similar in the two groups, although there were 6 deaths from leucopenic sepsis in the DOC group (v. 0; p=0.18). Nadir leucocyte counts were also lower in the DOC group (median 3.8 v. 5.3 × 10

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Section: Discussionmentioning

confidence: 84%

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confidence: 99%

Oral v. pulse intravenous cyclophosphamide: A retrospective analysis of adverse events in a setting with a high burden of infectious disease

2015

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“…From our data, the SILD regimen seems to be more efficient in reducing the positive rate of antidsDNA antibody than the HD regimen. Many studies have come up with several different regimens for remission-maintaining treatment followed by azathioprine (AZA), mycophenolate mofetil (MMF), and oral or IV CYC [5,[14][15][16]. And the MMF regimen seems to be the most effective one; however, there would be limitations in longterm using of MMF because of its high expense in developing countries.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the rate of severe adverse events was much lower [3]. However, both regimens present a high relapse rate, and some patients fail to respond to the treatment [4,5]. These phenomena probably attributed to the longer interval of the high-dose IV CYC regimen or the shorter duration of the lower-dose regimen (only 3 months).…”

Section: Introductionmentioning

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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“…Current therapies for severe forms of lupus nephritis are various combinations of corticosteroids with other cytotoxic agents or immunomodulators, such as cyclophosphamide, azathioprine, or cyclosporin (6,41,69), but many of these have various side effects (16,28). The immunomodulatory activity of various traditional Chinese medicinal herbs is now widely acknowledged (35).…”

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confidence: 99%

Therapeutic potential of DCB-SLE1, an extract of a mixture of Chinese medicinal herbs, for severe lupus nephritis

Tsai

Ka²,

Chang³

et al. 2011

American Journal of Physiology-Renal Physiology

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. Therapeutic potential of DCB-SLE1, an extract of a mixture of Chinese medicinal herbs, for severe lupus nephritis. Am J Physiol Renal Physiol 301: F751-F764, 2011. First published June 15, 2011 doi:10.1152/ajprenal.00706.2010.-The pathogenesis of lupus nephritis is mainly attributable to a complex interaction between the innate and adaptive immune systems, including T and B cell function abnormalities. In addition to autoantibody production and immune complex deposition, Th1 and Th17 cytokines may play key roles in the development and progression of lupus nephritis. Acute onset of severe lupus nephritis remains a challenge in terms of prevention and treatment. In the present study, we evaluated the therapeutic effects of DCB-SLE1, an extract of a mixture of four traditional Chinese medicinal herbs (Atractylodis macrocephalae Rhizoma, Eucommiae cortex, Lonicerae caulis, and Hedyotidis diffusae Herba), on an accelerated severe lupus nephritis model, characterized by acute onset of proteinuria, azotemia, autoantibody production, and development of severe nephritis, induced by twice weekly injection of New Zealand black/white F1 mice with Salmonella-type lipopolysaccharide. DCB-SLE1 was administered daily by gavage starting 2 days after the first dose of induction of lipopolysaccharide, and the mice were euthanized at week 1 or week 5. The results showed that DCB-SLE1 significantly ameliorated the hematuria, proteinuria, renal dysfunction, and severe renal lesions by 1) suppression of B cell activation and decreased autoantibody production; 2) negative regulation of T cell activation/proliferation and natural killer cell activity; 3) suppression of IL-18, IL-6, and IL-17 production and blocking of NF-B activation in the kidney; and 4) prevention of lymphoid and renal apoptosis. These results show that DCB-SLE1 can protect the kidney from autoimmune response-mediated acute and severe damage through systemic immune modulation and anti-inflammation pathways.hematuria; proteinuria; natural killer cell; IL-17; IL-18

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EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis

Cited by 81 publications

References 13 publications

Oral v. pulse intravenous cyclophosphamide: A retrospective analysis of adverse events in a setting with a high burden of infectious disease

Oral v. pulse intravenous cyclophosphamide: A retrospective analysis of adverse events in a setting with a high burden of infectious disease

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

Therapeutic potential of DCB-SLE1, an extract of a mixture of Chinese medicinal herbs, for severe lupus nephritis

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