A Randomized Pilot Trial Comparing Cyclosporine and Azathioprine for Maintenance Therapy in Diffuse Lupus Nephritis over Four Years

Abstract

There is not agreement about the best maintenance treatment for patients with diffuse lupus nephritis. This multicenter, randomized trial compared the safety and efficacy of cyclosporine and azathioprine. Seventy-five patients with diffuse proliferative lupus were given three intravenous methylprednisolone pulses followed by prednisone and oral cyclophosphamide for a median of 90 d. Subsequently, patients were randomly assigned either to cyclosporine or to azathioprine for 2 yr (core study). Treatment continued for up to 4 yr (follow-up study). The primary outcome measure was the incidence of disease flares. Secondary end points were proteinuria per day, creatinine clearance, and adverse effects. Seven flares occurred in the cyclosporine group, and eight occurred in the azathioprine group. At the end of the core study, mean proteinuria decreased from 2.

Population Pharmacokinetic Approach to the Use of Low Dose Cyclosporine in Patients with Connective Tissue Diseases

“…12) Recent studies reported low dose cyclosporine therapy, which was adjusted to gain of blood trough concentration approximate 80-150 ng/mL, was an effective and less toxic cyclosporine therapy for the regulation of connective tissue diseases with RA, 13) SLE, [14][15][16] and lupus nephritis. [17][18][19] Population pharmacokinetic methods, with the ability to incorporate covariates from sparse drug concentration data, offer an opportunity to generate a dosing regimen. Although a dosing method that takes into account the various factors that influence the pharmacokinetics of cyclosporine is needed, pharmacokinetic studies on cyclosporine in collagen disease patients are limited, as are population pharmacokinetic studies.…”

Lupus Nephritis

“…Currently available clinical trials propound sequential therapy as an effective and safe alternative for treating severe LN in patients of white, Asian, African, or Hispanic ancestry (18)(19)(20)(21)(22)(23)(24)(25)(26). We have seen a comforting decline in CKD (7% or less) and mortality (10% or less) with the use of sequential therapies in the past two decades.…”

“…The risk for CKD from long-term exposure to calcineurin inhibitors is still not known because clinical trials limited the exposure of those drugs to a maximum of 24 months of active therapy. Moroni et al (25) in a maintenance RCT compared cyclosporine (n536) with AZA (n533) for 24 months in predominantly white patients with SLE who had diffuse proliferative LN. Relapses were similar in the two groups (19.4% and 24.2%).…”

New Therapies for Lupus Nephritis

“…Clinical and histologic improvement with cyclosporine has been reported also in proliferative lupus nephritis both when the drug was given in patients resistant to IV cyclophosphamide (14) or when given for maintenance (15). In a randomized, controlled trial of proliferative lupus nephritis, Moroni et al showed equivalence between cyclosporine and azathioprine for maintenance therapy up to four years (16).…”