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

Jennifer C. Cooper, Kelly Rouster-Stevens, Tracey Wright, Joyce J. Hsu, Marisa S. Klein-Gitelman, Stacy P. Ardoin, Laura E. Schanberg, Hermine I. Brunner, B. Anne Eberhard, Linda Wagner-Weiner, Jay Mehta, Kathleen Haines, Deborah K. McCurdy, Thomas A. Phillips, Zhen Huang, Emily Von Scheven

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: To 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. Methods: Forty-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. Results: 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. Conclusions: Overall, 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.

Original languageEnglish (US)
Article number65
JournalPediatric Rheumatology
Volume16
Issue number1
DOIs
StatePublished - Oct 22 2018

Fingerprint

Lupus Nephritis
Rheumatology
Arthritis
Research
Mycophenolic Acid
Cyclophosphamide
Therapeutics
Steroids
Immunosuppression
Comparative Effectiveness Research
Kidney
Selection Bias
Hematuria
Patient Compliance

Keywords

  • Consensus
  • Corticosteroids
  • Cyclophosphamide
  • Juvenile systemic lupus erythematosus
  • Lupus nephritis
  • Mycophenolate

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Rheumatology
  • Immunology and Allergy

Cite this

Pilot study comparing the childhood arthritis and rheumatology research alliance consensus treatment plans for induction therapy of juvenile proliferative lupus nephritis. / Cooper, Jennifer C.; Rouster-Stevens, Kelly; Wright, Tracey; Hsu, Joyce J.; Klein-Gitelman, Marisa S.; Ardoin, Stacy P.; Schanberg, Laura E.; Brunner, Hermine I.; Eberhard, B. Anne; Wagner-Weiner, Linda; Mehta, Jay; Haines, Kathleen; McCurdy, Deborah K.; Phillips, Thomas A.; Huang, Zhen; Von Scheven, Emily.

In: Pediatric Rheumatology, Vol. 16, No. 1, 65, 22.10.2018.

Research output: Contribution to journalArticle

Cooper, JC, Rouster-Stevens, K, Wright, T, Hsu, JJ, Klein-Gitelman, MS, Ardoin, SP, Schanberg, LE, Brunner, HI, Eberhard, BA, Wagner-Weiner, L, Mehta, J, Haines, K, McCurdy, DK, Phillips, TA, Huang, Z & Von Scheven, E 2018, 'Pilot study comparing the childhood arthritis and rheumatology research alliance consensus treatment plans for induction therapy of juvenile proliferative lupus nephritis', Pediatric Rheumatology, vol. 16, no. 1, 65. https://doi.org/10.1186/s12969-018-0279-0
Cooper, Jennifer C. ; Rouster-Stevens, Kelly ; Wright, Tracey ; Hsu, Joyce J. ; Klein-Gitelman, Marisa S. ; Ardoin, Stacy P. ; Schanberg, Laura E. ; Brunner, Hermine I. ; Eberhard, B. Anne ; Wagner-Weiner, Linda ; Mehta, Jay ; Haines, Kathleen ; McCurdy, Deborah K. ; Phillips, Thomas A. ; Huang, Zhen ; Von Scheven, Emily. / Pilot study comparing the childhood arthritis and rheumatology research alliance consensus treatment plans for induction therapy of juvenile proliferative lupus nephritis. In: Pediatric Rheumatology. 2018 ; Vol. 16, No. 1.
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abstract = "Background: To 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. Methods: Forty-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. Results: 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. Conclusions: Overall, 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.",
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T1 - Pilot study comparing the childhood arthritis and rheumatology research alliance consensus treatment plans for induction therapy of juvenile proliferative lupus nephritis

AU - Cooper, Jennifer C.

AU - Rouster-Stevens, Kelly

AU - Wright, Tracey

AU - Hsu, Joyce J.

AU - Klein-Gitelman, Marisa S.

AU - Ardoin, Stacy P.

AU - Schanberg, Laura E.

AU - Brunner, Hermine I.

AU - Eberhard, B. Anne

AU - Wagner-Weiner, Linda

AU - Mehta, Jay

AU - Haines, Kathleen

AU - McCurdy, Deborah K.

AU - Phillips, Thomas A.

AU - Huang, Zhen

AU - Von Scheven, Emily

PY - 2018/10/22

Y1 - 2018/10/22

N2 - Background: To 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. Methods: Forty-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. Results: 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. Conclusions: Overall, 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.

AB - Background: To 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. Methods: Forty-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. Results: 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. Conclusions: Overall, 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.

KW - Consensus

KW - Corticosteroids

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KW - Juvenile systemic lupus erythematosus

KW - Lupus nephritis

KW - Mycophenolate

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