Pilot study comparing the childhood arthritis and rheumatology research alliance consensus treatment plans for induction therapy of juvenile proliferative lupus nephritis

Abstract

BackgroundTo reduce treatment variability and facilitate comparative effectiveness studies, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) published consensus treatment plans (CTPs) including one for juvenile proliferative lupus nephritis (LN). Induction immunosuppression CTPs outline treatment with either monthly intravenous (IV) cyclophosphamide (CYC) or mycophenolate mofetil (MMF) in conjunction with one of three corticosteroid (steroid) CTPs: primarily oral, primarily IV or mixed oral/IV. The acceptability and in-practice use of these CTPs are unknown. Therefore, the primary aims of the pilot study were to demonstrate feasibility of adhering to the LN CTPs and delineate barriers to implementation in clinical care in the US. Further, we aimed to explore the safety and effectiveness of the treatments for induction therapy.MethodsForty-one patients were enrolled from 10 CARRA sites. Patients had new-onset biopsy proven ISN/RPS class III or IV proliferative LN, were starting induction therapy with MMF or IV CYC and high-dose steroids and were followed for up to 24 months. Routine clinical data were collected at each visit. Provider reasons for CTP selection were assessed at baseline. Adherence to the CTPs was evaluated by provider survey and medication logs. Complete and partial renal responses were reported at 6 months.ResultsThe 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.ConclusionsOverall, the immunosuppression CTPs were followed as intended in the majority of patients however, adherence to the steroid CTPs was poor indicating revision is necessary. In addition, our pilot study revealed several sources of treatment selection bias that will need to be addressed in for future comparative effectiveness research.Electronic supplementary materialThe online version of this article (10.1186/s12969-018-0279-0) contains supplementary material, which is available to authorized users.

S2k guideline: Diagnosis and management of cutaneous lupus erythematosus – Part 2: Therapy, risk factors and other special topics

“…Since these drugs have a range of well-known side effects, they should only be used for a limited time. There is no consensus on the dosage of glucocorticoids in childhood CLE or on dose reduction [57,58]. However, some studies have shown that a more restrive use of systemic glucocorticoids is not a disadvantage and has fewer side effects [59].…”

S2k‐Leitlinie zur Diagnostik und Therapie des kutanen Lupus erythematodes – Teil 2: Therapie, Risikofaktoren und spezielle Fragestellungen

“…Da diese Medikamente eine Reihe von bekannten Nebenwirkungen haben, sollte der Einsatz zeitlich begrenzt sein. Es gibt keinen Konsensus über die Dosierung von Glukokortikoiden bei CLE im Kindesalter beziehungsweise über die Reduktion der Glukokortikoide [57,58]. Es zeigt sich aber in einigen Studien, dass der restriktivere Einsatz von systemischen Glukokortikoiden kein Nachteil ist und weniger Nebenwirkungen hat [59].…”

International Consensus for the Dosing of Corticosteroids in Childhood‐Onset Systemic Lupus Erythematosus With Proliferative Lupus Nephritis

“…Delphi surveys and expert opinion were previously employed to propose standards for CS use (2,3), including for proliferative LN in children as part of the consensus treatment plans for pediatric LN (4). However, when tested in real‐life settings, providers were following the CS dosing recommended by the consensus treatment plans for pediatric LN in only 68% of patients by 3 months of induction therapy for LN and in just 37% of patients by 6 months of induction therapy for LN (5).…”