Efficacy of mycophenolate mofetil in adolescent patients with lupus nephritis: Evidence from a two-phase, prospective randomized trial

1Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, USA.
Lupus (Impact Factor: 2.2). 08/2012; 21(13):1433-43. DOI: 10.1177/0961203312458466
Source: PubMed


The safety and efficacy of mycophenolate mofetil (MMF) were evaluated in adolescent patients with systemic lupus erythematosus and active or active/chronic class III-V lupus nephritis. During the 24-week induction phase, patients were randomized to oral MMF (target dose 3.0 g/day) or intravenous cyclophosphamide (IVC) (0.5-1.0 g/m(2)/month), plus prednisone. Response was defined as a decrease in 24-hour urine protein:creatinine ratio (P:Cr) to <3 in patients with baseline nephrotic range proteinuria, or by ≥50% if subnephrotic baseline proteinuria, and stabilization (±25%) or improvement in serum creatinine. In the 36-month maintenance phase, induction therapy responders were randomized 1:1 to MMF (1.0 g twice daily) or oral azathioprine (AZA) (2 mg/kg/day), plus prednisone. In the induction phase, 10 patients received MMF and 14 received IVC; 15 (62.5%) achieved treatment response (MMF, 7 (70%); IVC, 8/15 (57.1%); p = 0.53, odds ratio (95% confidence interval) 2.0 (0.2, 15.5)). There was a non-statistically significant difference in maintenance of response to MMF (7/8; 87.5%) versus AZA (3/8; 37.5%). Seven patients withdrew (MMF, 2; AZA, 5). During both phases, rates of serious adverse events were similar in both arms. During both phases treatment response with MMF was as effective as the comparator.

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    • "Recent clinical studies including a number of randomized controlled treatment trials of SLE patients with renal disease have clarified the therapeutic role of a variety of immunosuppressive regimens both in proliferative and membranous LN.[6789] The goal of each of these trials has been to achieve clinical efficacy with a remission of the nephritis while minimizing deleterious side effects of treatment.[1011121314151617] "
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    ABSTRACT: Chronic kidney disease is one of the most common complication of systemic lupus erythematosus, which if untreated can lead to the end-stage renal disease (ESRD). Early diagnosis and adequate treatment of lupus nephritis (LN) is critical to prevent the chronic kidney disease incidence and to reduce the development of ESRD. The treatment of LN has changed significantly over the past decade. In patients with active proliferative LN (Classes III and IV) intravenous methylprednisolone 1 g/m2/day for 1-3 days then prednisone 0.5-1.0 mg/kg/day, tapered to <0.5 mg/kg/day after 10-12 weeks of treatment plus mycophenolate mofetile (MMF) 1.2 g/m2/day for 6 months followed by maintenance lower doses of MMF 1-2 g/day or azathioprine (AZA) 2 mg/kg/day for 3 years have proven to be efficacy and less toxic than cyclophosphamide (CYC) therapy. Patients with membranous LN (Class V) plus diffuse or local proliferative LN (Class III and Class IV) should receive either the standard 6 monthly pulses of CYC (0.5-1 g/m2/month) then every 3(rd) month or to a shorter treatment course consisting of 0.5 g/m2 IV CYC every 2 weeks for six doses (total dose 3 g) followed by maintenance therapy with daily AZA (2 mg/kg/day) or MMF (0.6 g/m2/day) for 3 years. Combination of MMF plus rituximab or MMF plus calcineurin inhibitors may be an effective co-therapy for those refractory to induction or maintenance therapies. This report introduces a new treatment algorithm to prevent the development of ESRD in children with LN.
    International journal of preventive medicine 03/2014; 5(3):250-255.
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    • "Mycophenolate mofetil and cyclophosphamide are deemed cornerstones of lupus nephritis therapy. A subanalysis of a total of only 25 children with lupus nephritis who were enrolled in a large randomized clinical trial of mycophenolate mofetil (target dose 3.0 g/ day) versus cyclophosphamide (0.5 to 1.0 g/m2/month) [72] showed a trend towards better renal response to 24-week induction therapy with mycophenolate mofetil than with cyclophosphamide (7/10 (70%) vs. 8/15 (53%)) [73]. Although this subanalysis is vastly underpowered, the trend is in line with the results of larger trial published in 2005 [72]. "
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    ABSTRACT: Systemic lupus erythematosus (SLE) is a complex autoimmune disease and occurs worldwide in both children and adults. The estimated annual incidence among children is 2.22/100,000 and among adults is 23.2/100,000 in the United States. There is increasing understanding about differences in disease manifestations, medication use, and disease severity between those with childhood-onset SLE as compared with adult-onset SLE. Children have a more fulminant disease onset and course than adults with SLE, resulting in two to three times higher mortality. In future years, we anticipate more insight into the genetics between childhood-onset SLE and adult-onset SLE to help delineate the best therapies for both subsets of patients.
    Arthritis Research & Therapy 08/2013; 15(4):218. DOI:10.1186/ar4256 · 3.75 Impact Factor
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    ABSTRACT: Over the last decade, therapy for lupus nephritis in children has begun to shift from the provision of long-term steroids and intravenous cyclophosphamide to regimens with limited or no cyclophosphamide, lower steroid burdens, and increased reliance on oral mycophenolate mofetil. As the molecular immunology underlying the pathophysiology of lupus is further discerned, more targeted therapies, including the use of monoclonal antibodies against immune cells or cell signaling factors, may come to play a larger role in the treatment of pediatric lupus. Similarly, as experience with autologous stem cell transplantation for therapy-resistant disease is gained in adults, its potential applicability to such situations in children may be clarified. Over the next few decades, children with lupus will benefit as well from the identification of new biomarkers that are both sensitive and specific to disease activity, allowing clinicians to more readily assess response to therapy and diagnose disease flare.
    03/2012; 1(1). DOI:10.1007/s40124-012-0005-1
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