title: Effect of Treatment With Tabalumab, a B Cell-Activating Factor Inhibitor, on Highly Sensitized Patients With End-Stage Renal Disease Awaiting Transplantation.
abstract: B cell-activation factor (BAFF) is critical for B cell maturation. Inhibition of BAFF represents an appealing target for desensitization of sensitized end-stage renal disease (ESRD) patients. We conducted a Phase 2a, single-arm, open-label exploratory study investigating the effect of tabalumab (BAFF inhibitor) in patients with ESRD and calculated panel reactive antibodies (cPRAs) >50%. The treatment period duration was 24 weeks. Eighteen patients received tabalumab, at doses of 240-mg subcutaneous (SC) at Week 0 followed by 120-mg SC monthly for 5 additional months. Patients were followed for an additional 52 weeks. Immunopharmacologic effects were characterized through analysis of blood for HLA antibodies, BAFF concentrations, immunoglobulins, T and B cell subsets, as well as pre- and posttreatment tonsil and bone marrow biopsies. Significant reductions in cPRAs were observed at Weeks 16 (p = 0.043) and 36 (p = 0.004); however, absolute reductions were small (<5%). Expected pharmacologic changes in B cell subsets and immunoglobulin reductions were observed. Two tabalumab-related serious adverse events occurred (pneumonia, worsening of peripheral neuropathy), while the most common other adverse events were injection-site pain and hypotension. Three patients received matched deceased donor transplants during follow-up. Treatment with a BAFF inhibitor resulted in statistically significant, but not clinically meaningful reduction in the cPRA from baseline (NCT01200290, Clinicaltrials.gov).
authors.affiliation: Division of Nephrology, University of Texas Medical Branch, Galveston, TX.
authors.forename: M A
authors.initials: MA
authors.lastname: Mujtaba
authors.affiliation: Bio-Medicines Business Unit, Eli Lilly and Company, Indianapolis, IN.
authors.forename: W J
authors.initials: WJ
authors.lastname: Komocsar
authors.affiliation: Bio-Medicines Business Unit, Eli Lilly and Company, Indianapolis, IN.
authors.forename: E
authors.initials: E
authors.lastname: Nantz
authors.affiliation: Department of Internal Medicine-Nephrology, University of Michigan Health System, Ann Arbor, MI.
authors.forename: M D
authors.initials: MD
authors.lastname: Samaniego
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: S L
authors.initials: SL
authors.lastname: Henson
authors.affiliation: Clinical Trial Management, Eli Lilly and Company, Indianapolis, IN.
authors.forename: J A
authors.initials: JA
authors.lastname: Hague
authors.affiliation: Transplant Immunology, Indiana University Health, Indianapolis, IN.
authors.forename: A L
authors.initials: AL
authors.lastname: Lobashevsky
authors.affiliation: Transplant Immunology, Indiana University Health, Indianapolis, IN.
authors.forename: N G
authors.initials: NG
authors.lastname: Higgins
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: M
authors.initials: M
authors.lastname: Czader
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: B K
authors.initials: BK
authors.lastname: Book
authors.affiliation: Department of Medicine-Nephrology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: M D
authors.initials: MD
authors.lastname: Anderson
authors.forename: M D
authors.initials: MD
authors.lastname: Pescovitz
authors.affiliation: Department of Medicine-Nephrology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: T E
authors.initials: TE
authors.lastname: Taber
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D011379:Prognosis; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor; D007518:Isoantibodies; C575974:tabalumab
keywords: B cell biology; alloantibody; basic (laboratory) research/science; clinical research/practice; desensitization; fusion proteins and monoclonal antibodies: B cell specific; immunobiology; immunosuppressant; kidney transplantation/nephrology