Comparative data in the pediatric lupus nephritis (LN) population are lacking. To reduce treatment variability and facilitate comparative effectiveness studies, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) published consensus treatment plans (CTPs) for induction therapy in childhood proliferative LN. The CTPs recommend treatment with MMF or IV CYC and one of three corticosteroid (CS) regimens: primarily oral, primarily IV or mixed oral/IV. We describe CS regimen usage and report overall adherence and reasons for non-adherence in a multi-center pilot feasibility study.

Methods:

This observational cohort study enrolled 41 cSLE patients from 10 CARRA sites. Subjects had new-onset biopsy proven class III or IV active proliferative LN and were starting induction therapy with MMF or IV CYC and CS. Subjects were followed for up to 24 months. In addition to clinical parameters, providers were surveyed about reasons for CS regimen selection and overall adherence to the regimens. In addition, providers recorded prescribed medication use including CS taper schedule. Reasons for regimen selection, provider-reported adherence to regimens, adverse events, and weight gain (absolute and change in BMI percentile) were compared among the three regimens. To quantify the degree of deviation from the oral component of the CS regimens, the percent daily difference from the expected prednisone/prednisolone dose was calculated according to the assigned CS regimen.

Results:

CS regimen selection (9 primarily oral, 17 mixed oral/IV and 15 primarily IV) differed significantly by study site (p =0.007) and induction agent (oral CS regimens were more commonly prescribed with MMF and IV containing CS regimens were more commonly prescribed with CYC, p=0.002). Providers reported following the CS regimen as intended in 37% of patients at the 6 month visit (47% for primarily IV regimen, 33% for primarily oral regimen and 29% for mixed oral/IV regimen). Over the 24 week induction period there was a tendency to prescribe less oral CS in weeks 1-8 compared to published regimens (median -20% less, IQR -20,10). The most common reasons for not following the published regimen were subject non-compliance (20%) and intolerance (12%). There was one hospitalization for infection in a patient treated with the mixed oral/IV regimen. There were no reported cases of cataracts or osteonecrosis. The median baseline BMI was at the 84%ile. The 6 month median change in BMI %ile was 4 and from month 6 to month 12 the median change in BMI %ile was 1.2, this did not significantly differ among CS regimens.

Conclusion:

In this pilot there was substantial deviation from the CS regimens suggesting that revision may be needed to ensure implementation into clinical practice and to support comparative effectiveness research. No single regimen was superior in minimizing steroid-associated weight gain at month 6 or month 12. Patient-level adherence with oral CS tapers was not assessed by this study and warrants further investigation.