Randomized Phase 2b Trial of Tofacitinib (CP-690,550) in De Novo Kidney Transplant Patients: Efficacy, Renal Function and Safety at 1 Year.
Vincenti F, Tedesco Silva H, et al.American Journal of Transplantation, 12(9): 2446-2456, 2012.
Aims
To evaluate the efficacy and safety of tofacitinib in combination with basiliximab induction, mycophenolic acid and corticosteroids in de novo kidney transplant recipients.
Interventions
More intensive tofacitinib (tofacitinib 15 mg twice daily in Month 1–6, 10 mg twice daily in Month 7–12) versus less intensive tofacitinib (tofacitinib 15 mg twice daily in Month 1–3, 10 mg twice daily in Month 4–12) or cyclosporine. All patients received basiliximab induction, mycophenolic acid and corticosteroids.
Participants
331 de novo kidney transplant patients.
Outcomes
The primary efficacy endpoint was the incidence of first clinical biopsy proven acute rejection (BPAR) at Month 6, measured glomerular filtration rate (GFR) at Month 12. Secondary endpoints included total BPAR rate at Month 6 and 12, estimated GFR and chronic allograft lesions at Month 12. Safety assessment included adverse events, new-onset diabetes and hypertension.
Follow-up
12 months
CET Conclusions
This is an interesting report of a phase 2b trial of Tofacitinib (Tof) which is an oral Janus kinase inhibitor. All patients who had been induced with basiliximab and were also to receive mycophenolic acid and corticosteroids were randomised to either Tof in 2 doses or cyclosporine. Both regimens of Tof produced a more frequent occurrence of significant adverse events including anaemia, neutropenia, infection and post-transplant lymphoproliferative disorder. There was no difference in the incidence of acute rejection, the primary endpoint, but histologically there was less evidence of chronic allograft injury. Further evaluation is required.
Data analysis
Modified intention-to-treat analysis
Trial registration
NCT00483756 (ClinicalTrials.gov)