Eculizumab in the management of drug-induced thrombotic microangiopathy: A scoping review of the literature

Abstract

Drug-induced TMA (DI-TMA) is a thrombotic microangiopathy (TMA) caused by certain drugs, usually managed by drug discontinuation and supportive measures. Data on the use of complement-inhibition with eculizumab in DI-TMA is scarce, and its benefit in cases of severe or refractory DI-TMA is unclear. We conducted a comprehensive search in PubMed, Embase and MEDLINE databases (2007-2021). We included articles that reported on DI-TMA patients treated with eculizumab and its clinical outcomes. All other causes of TMA were excluded. We evaluated the outcomes of hematologic recovery, renal recovery, and a composite of both (complete TMA recovery). 35 studies fulfilled our search criteria, which included 69 individual cases of DI-TMA treated with eculizumab. Most cases were secondary to chemotherapeutic agents, and the most implicated drugs were gemcitabine (42/69), carfilzomib (11/69), and bevacizumab (5/69). The median number of eculizumab doses given was 6 (range 1-16). 55/69 (80 %) patients achieved renal recovery, after 28-35 days (5-6 doses). 13/22 (59 %) patients were able to discontinue hemodialysis. 50/68 (74 %) patients achieved complete hematologic recovery after 7-14 days (1-2 doses). 41/68 (60 %) patients met criteria for complete TMA recovery. Eculizumab was safely tolerated in all cases, and appeared to be effective in achieving both hematologic and renal recovery in DI-TMA refractory to drug discontinuation and supportive measures, or with severe manifestations associated with significant morbidity or mortality. Our findings suggest that eculizumab may be considered as a potential treatment for severe or refractory DI-TMA that does not improve after initial management, although larger studies are needed.

Keywords: Drug-induced thrombotic microangiopathy; Eculizumab; Thrombotic microangiopathy.