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Kidney Week

Abstract: PO1916

A Multicenter Double-Blinded Preclinical Randomized Controlled Trial (pRCT) on Jak1/2 Inhibition in Lupus Nephritis

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Lei, Yutian, Division of Nephrology, Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
  • Sehnert, Bettina, Department of Rheumatology and Clinical Immunology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  • Voll, Reinhard E., Department of Rheumatology and Clinical Immunology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  • Jacobs Cachá, Conxita, Nephrology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Nephrology Research Group, Vall d’Hebron Research Institute (VHIR) and REDINREN, Barcelona, Spain
  • Soler, Maria Jose, Nephrology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Nephrology Research Group, Vall d’Hebron Research Institute (VHIR) and REDINREN, Barcelona, Spain
  • Sanchez-Nino, Maria Dolores, IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autonoma de Madrid, Fundacion Renal Iñigo Alvarez de Toledo-IRSIN and REDINREN, Madrid, Spain
  • Ortiz, Alberto, IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autonoma de Madrid, Fundacion Renal Iñigo Alvarez de Toledo-IRSIN and REDINREN, Madrid, Spain
  • Bülow, Roman David, Institute of Pathology and Department of Nephrology, RWTH University of Aachen, Aachen, Germany
  • Boor, Peter, Institute of Pathology and Department of Nephrology, RWTH University of Aachen, Aachen, Germany
  • Anders, Hans J., Division of Nephrology, Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
Background

We conducted the first multicenter double-blinded pRCT in the field of nephrology and tested the Jak1/2 inhibitor baricitinib in experimental lupus nephritis.

Methods

We conducted a pRCT at two Spanish and two German academic sites. One site included MRL/lpr mice from their own breeding colony and the other sites purchased MRL/lpr mice from the Jackson lab. Eligibility criteria included female and 13-14 weeks old. Mice were randomized at a 1:1 ratio and orally dosed with 20 mg/kg/d baricitinib or vehicle for 4 weeks. Samples were assembled for blinded analyses, including histology, which was assessed by an independent pathology institute. The primary endpoint was proteinuria.

Results

A total of 55 mice were randomly assigned to the vehicle (n=28) and baricitinib group (n=27). Baricitinib-treated mice showed a trend towards decreased proteinuria, but this did not reach statistical significance (p=0.104). In contrast, plasma total IgG and lymphadenopathy score were significantly improved in the baricitinib group. In the vehicle group, at the initiation of treatment, self-breed mice had less proteinuria, less plasma total IgG, and worse skin lesion compared to commercial-source mice.

Conclusion

In a pRCT, targeting Jak1/2 with baricitinib for 4 weeks had no significant effect on the primary end-point proteinuria in MRL/lpr mice, whereas total plasma IgG and lymphadonpathy score significantly improved. Mice of different origins had different lupus phenotypes and increased the variability. Placebo controlled multicenter trials are feasible in animal models of lupus, however, standard deviations may increase due to multiple factors, which requires higher numbers of animals.