Oral Cyclophosphamide for Lupus Glomerulonephritis

Abstract

Background and objectives: In our center, systemic lupus erythematosus nephritis is routinely treated with an oral cyclophosphamide (POCY) regimen. POCY is easy to administer and less expensive than intravenous cyclophosphamide (IVCY) as it is currently used in the United States; however, the use of POCY has declined in favor of IVCY. Our experience with POCY suggests that it is well tolerated and consistently associated with good long-term outcomes. Here we report this experience to build a case for maintaining POCY as a therapeutic option in lupus nephritis.Design, setting, participants, & measurements: This is a single-center, retrospective analysis of the outcome of 46 patients who had systemic lupus erythematosus with nephritis and were treated with POCY between 1995 and 2006. POCY was given for 2 to 4 mo at a dosage of 1.0 to 1.5 mg/kg ideal body weight. After completing POCY, the patients received either azathioprine or mycophenolate mofetil.Results: Median follow-up was 23.5 mo, and median duration of POCY was 4 mo (range 1 to 16 mo). Durable complete or partial remission of proteinuria was achieved in 32 (70%) patients, whereas 5 (11%) progressed to ESRD. Outcomes were comparable in black and white individuals. Adverse effects occurred in fewer than 10% of the cohort, and only four patients discontinued POCY.Conclusions: These results suggest that sequential therapy of POCY followed by azathioprine or mycophenolate mofetil is comparable to IVCY regimens but that efficacy may not be affected by race.

Lupus Nephritis

“…In response to these studies, MMF became the immunosuppressive of choice for many but not all physicians for induction of remission in proliferative forms of LN (7,(11)(12)(13). However, cyclophosphamide still seems to be used routinely for patients with severe LN.…”

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

“…Overall it seems that DOC has the advantages of lower cost, simpler administration and avoidance of high-dose exposure should the drug be inappropriately administered. [3,4] PIVC has the advantage of a reduced incidence of short-and long-term adverse events and avoids the need for daily compliance with treatment. Data regarding the comparative efficacy of the two regimens are conflicting and briefly discussed below.…”

“…Patients need to take time off work and have additional travel expenses, which all contribute to the overall cost of this regimen. [3,4] Although DOC is associated with an increase in long-term sideeffects, adverse events due to inappropriate dosing are more easily managed. Examples include administration when a contraindication exists, mistaking sepsis for a flare of disease or not adjusting doses for renal function.…”

“…Reducing or omitting further oral doses under these circumstances, which cannot be done with PIVC, reduces the toxicity. [4] Austin et al [5] initially published data in 1986 supporting superior treatment outcomes and reduced side-effect profiles with the use of PIVC as opposed to DOC in patients with lupus nephritis. This led to PIVC becoming the standard treatment in lupus nephritis, with fewer subsequent trials and recommendations that include DOC.…”

“…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.…”