Evaluation of Clazakizumab (Anti–Interleukin-6) in Patients With Treatment-Resistant Chronic Active Antibody-Mediated Rejection of Kidney Allografts

Abstract

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Anti-interleukin-6 Antibody Clazakizumab in Antibody-mediated Kidney Transplant Rejection: Effect on Donor-derived Cell-free DNA and C-X-C Motif Chemokine Ligand 10

“…8 We have recently published the results of a randomized, controlled phase 2 study including 20 kidney transplant recipients diagnosed with late chronic active or active AMR. 6 Consistent with other uncontrolled studies, 5,7 our trial revealed that IL-6 antagonism was associated with a reduction in donor-specific antibody (DSA) levels and after 9–12 mo of treatment with a decrease in AMR activity. In addition, a preliminary analysis of renal function suggested a possible less pronounced decline in estimated glomerular filtration rate (eGFR).…”

Imagining a Better Outcome for Chronic Antibody-Mediated Rejection—Will Blocking Interleukin-6 Signaling Help?

“…Molecular rejection scores and peritubular capillary deposition of the complement protein 4d were reduced; however, microvascular inflammation remained largely unchanged. 8 In the current issue of the KI Reports, Jordan et al 9 report the results of a phase-2, single-center, open-labeled study of clazakizumab in 10 adults with CAAMR. Participants received monthly subcutaneous injections of clazakizumab for 12 months, with a protocol biopsy at 6 months.…”

“…As C-reactive protein levels were not elevated in any patient-suggesting the absence of IL-6-IL-6R signaling-this increase in serum IL-6 level was likely because of circulating IL-6clazakizumab complex. 9 The Jordan study and the Doberer trial, despite its limitations, have provided encouraging safety and efficacy signals on the benefits of clazakizumab in CAAMR. The "Interleukin-6 Blockade Modifying Antibody-Mediated Graft Injury and Estimated Glomerular Filtration Rate Decline (IMAGINE)" trial is an ongoing quadruple-blinded, pivotal phase-3 trial (ClinicalTrials.gov identifier: NCT03744910) to evaluate the efficacy and safety of clazakizumab for the treatment of CAAMR in kidney transplant recipients.…”

“…In the current issue of the KI Reports , Jordan et al. 9 report the results of a phase-2, single-center, open-labeled study of clazakizumab in 10 adults with CAAMR. Participants received monthly subcutaneous injections of clazakizumab for 12 months, with a protocol biopsy at 6 months.…”

“…As C-reactive protein levels were not elevated in any patient—suggesting the absence of IL-6–IL-6R signaling—this increase in serum IL-6 level was likely because of circulating IL-6–clazakizumab complex. 9 …”