Background/Purpose:   Childhood-onset systemic lupus erythematous (cSLE) patients are at higher risk for renal disease than those with adult-onset disease. Mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC), commonly used for induction immunosuppression therapy of proliferative lupus nephritis (LN), are considered equally efficacious in adults. Comparative data in the pediatric population are lacking. To reduce treatment variability and facilitate comparative effectiveness studies, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) published a consensus treatment plan (CTP) for induction therapy in childhood proliferative LN. The CTP recommended treatment with MMF or IV CYC and one of three steroid regimens: primarily oral, primarily IV, or mixed oral/IV. We report treatment group allocation and provider adherence for induction agents and steroid regimens in a multi-center pilot feasibility study.

Methods:  This observational study enrolled 41 cSLE patients from 10 CARRA sites. Subjects had new-onset biopsy proven class III or IV proliferative LN and were starting induction therapy with MMF or IV CYC and steroids. Baseline demographics, disease-related features, physician decision-making regarding choice of induction agent and steroid regimen were reported. Subjects were followed for up to 24 months. Providers reported adherence to the CTP for induction agents and steroid regimen at 3 and 6 month visits. Complete renal response (CRR), defined as normal renal function, inactive urine sediment, and urine protein to creatinine ratio of < 0.2, was reported at 6 months.

Results:  A majority of participants were female (83%) with a median age of 14 years. There were no significant differences in demographics between MMF or CYC groups or among the three steroid regimens. However, 78% (18/23) of those treated with CYC had class IV nephritis versus 33% (6/18) of those treated with MMF (p = 0.004). Physicians reported adherence concerns as a reason for selecting treatment for 5 of the patients in the CYC group but none in the MMF group (22% versus 0%, p = 0.04). MMF or CYC regimen was followed as intended per the CTP in 75% of subjects at 3 months and 56% at 6 months. CRR at 6 months was achieved for 56% with MMF and 64% with IV CYC (p = 0.6); the study was not powered to evaluate treatment efficacy. Steroid regimen chosen differed significantly by induction agent; those treated with MMF were more likely to receive the primarily oral steroid regimen and those treated with CYC were more likely to receive the mixed oral/IV regimen. Steroid regimen was followed as intended per the CTP in 59% of patients at 3 months and 37% of patients at 6 months.

Conclusion:  This feasibility study revealed two important issues. First, there was confounding by indication present as patients with class IV nephritis (vs class III) were more likely to receive CYC. Second, a substantial number of patients did not continue treatment according to the CTP. For future comparative effectiveness studies using observational methodologies, large sample sizes may be needed to allow sufficient adjustment for confounders and modification of the CTP regimens may needed to ensure better usability.

« Back to 2016 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-pilot-study-of-consensus-treatment-plans-for-induction-therapy-in-childhood-proliferative-lupus-nephritis/