Effect of Treatment With Tabalumab, a B Cell-Activating Factor Inhibitor, on Highly Sensitized @entity1 With XXXX Awaiting Transplantation.

@entity1 @entity55 @entity8410 @entity1897 @entity158 @entity551 @entity454
UNASSIGNED: B cell-activation factor ( @entity8410 ) is critical for B cell maturation. Inhibition of @entity8410 represents an appealing target for desensitization of sensitized @entity454 ( @entity454 ) @entity1 . We conducted a Phase 2a, single-arm, open-label exploratory study investigating the effect of tabalumab ( @entity8410 inhibitor) in @entity1 with @entity454 and calculated panel reactive antibodies (cPRAs) >50%. The treatment period duration was 24 weeks. Eighteen @entity1 received tabalumab, at doses of 240-mg subcutaneous (SC) at Week 0 followed by 120-mg SC monthly for 5 additional months. @entity1 were followed for an additional 52 weeks. Immunopharmacologic effects were characterized through analysis of blood for HLA antibodies, @entity8410 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 ( @entity55 , worsening of @entity1897 ), while the most common other adverse events were injection-site @entity158 and @entity551 . Three @entity1 received matched deceased donor transplants during follow-up. Treatment with a @entity8410 inhibitor resulted in statistically significant, but not clinically meaningful reduction in the cPRA from baseline (NCT01200290, Clinicaltrials.gov).
