The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) to compare monthly intravenous (IV) cyclophosphamide (CYC) and mycophenolate mofetil (MMF) in conjunction with one of three corticosteroid (steroid) regimens for the treatment of pediatric lupus nephritis (LN).
In a pilot study at 10 sites, 41 patients with new-onset biopsy proven ISN/RPS class III or IV proliferative LN were started on induction therapy with MMF or IV CYC and high-dose steroids by their physicians, and enrolled in the CARRA registry so they could be evaluated over 24 months.
The majority of patients were female (83%) with a mean age of 14.7 years, SD 2.8. CYC was used more commonly than MMF for patients with ISN/RPS class IV LN (vs. class III), those who had hematuria, and those with adherence concerns. Overall adherence to the immunosuppression induction CTPs was acceptable with a majority of patients receiving the target MMF (86%) or CYC (63%) dose. However, adherence to the steroid CTPs was poor (37%) with large variability in dosing. Renal response endpoints were exploratory and did not show a significant difference between CYC and MMF. We observed selection bias that will need to be addressed in future comparative effectiveness research.
The intent is for the CTPs to be used in routine clinical practice and for patients to be enrolled in the ongoing CARRA Registry. Use of CTPs in clinical practice reduces treatment variability, thereby allowing for more accurate and reliable comparison of treatment effects when analyzing the observational data collected in the registry. A secondary benefit is the availability of CTPs to clinicians with less experience caring for children with rheumatic diseases. It is important to recognize that CTPs are NOT practice guidelines. Practice guidelines require an evidence base which unfortunately is often not available in pediatric rheumatology. And thus, rather than describing a single treatment recommendation as is done with Practice Guidelines, CTPs describe several treatment options currently in practice, the comparison of which is not currently known.