Pharmacodynamic analysis of tofacitinib and basiliximab in kidney allograft recipients.
Vafadari R, Quaedackers M.E, et al.Transplantation. 94(5): 465-72, 2012.
Aims
To compare the effect of the immunosuppressive drugs tofacitinib and basiliximab on the Janus kinas (JAK)-signal transducer and activator of transcription (STAT) pathways.
Interventions
Patients were randomised to tofacitinib versus cyclosporine . All patients received basiliximab, mycophenolate mofetil (MMF) and prednisolone. A third, non-randomised group received tacrolimus, MMF and prednisolone without basiliximab and served as the control group.
Participants
9 de novo kidney transplant patients. The non-randomised control group consisted of 6 patients.
Outcomes
Immune cell counts and STAT5 phosphorylation.
Follow-up
2 months.
CET Conclusions
Tofacitinib (an inhibitor of JAK3 and JAK1 activation) was studied in vitro in 9 patients selected from a large phase 2 study. Its in vitro activity in patients who received Tofacitinib and Basiliximab was compared with patients who receive Basiliximab induction with tacrolimus and mycophenolate and a further control group who received a tacrolimus based immunosuppressive therapy only. Tofacitinib in selected populations of T cells isolated from peripheral blood in these patients strongly inhibited cytokine induced Jak/STAT5 activation, whereas in contrast Basiliximab in the absence of Tofacitinib suppressed IL2 stimulated activity only. The authors conclude that pharmacodynamic monitoring may provide a unique tool to evaluate the biological effects of immunosuppressive drugs, and they develop their argument extremely well in this small but interesting study.
Data analysis
Modified intention-to-treat analysis
Quality notes
Score based on Vincenti F, Silva H, et al. Randomized phase 2b trial of tofacitinib in de novo kidney transplant patients: efficacy, renal function, and safety at one year. American Journal of Transplantation 2012; 12 (9):2446-56.
Trial registration
Not reported