A Randomized Clinical Trial of Anti-IL-6 Antibody Clazakizumab in Late Antibody-Mediated Kidney Transplant Rejection
In a small phase 2 trial, the anti-IL-6 antibody clazakizumab lowered donor-specific antibodies and slowed the decline in kidney function in transplant recipients with late antibody-mediated rejection, but serious infections signaled the need for caution.
Background
Late antibody-mediated rejection is a leading cause of kidney allograft failure with no proven effective therapy; blocking interleukin-6 had been proposed as a way to interrupt the alloantibody response.
Study design
Twenty kidney transplant recipients with donor-specific-antibody-positive antibody-mediated rejection at least one year post-transplant were randomized 1:1 to subcutaneous clazakizumab 25 mg or placebo every 4 weeks for 12 weeks, followed by a 40-week open-label extension in which all received clazakizumab.
Key findings
Clazakizumab significantly decreased donor-specific antibodies and modulated rejection-related gene expression; eGFR decline during the placebo-controlled phase was slower with clazakizumab (-0.96 vs -2.43 mL/min/1.73 m2 per month; p=0.04), and follow-up biopsies showed resolution of morphologic rejection activity in a subset.
Safety
Five of 20 patients (25%) on active treatment developed serious infectious events and two (10%) had diverticular complications leading to withdrawal, indicating that careful patient selection and monitoring are essential.
Category
Transplant
Source
Journal of the American Society of Nephrology
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