Secondary thrombotic microangiopathy in systemic lupus erythematosus and antiphospholipid syndrome, the role of complement and use of eculizumab: Case series and review of literature.

Thrombotic microangiopathy (TMA) is a life-threatening, albeit infrequent, complication of systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). Recommendations for the treatment of SLE- and APS-related secondary TMA are currently based solely on case reports and expert opinion. Unfortunately, interventions may not yield timely results or effectively halt the progression of TMA. Since complement activation plays a key role in the pathogenesis of secondary TMA due to SLE, APS, a therapy that targets the complement pathway is an attractive intervention. Eculizumab, a recombinant, fully humanized IgG2/IgG4 monoclonal antibody inhibits C5 activation and is FDA-approved for PNH and atypical HUS (aHUS). However, limited case reports are available on its use in treatment of secondary TMA. We present the largest case series to date that includes 9 patients with SLE and/or APS who were successfully treated with eculizumab for refractory secondary TMA. In this case series, we report significant responses in hematology values, renal function and other organs following treatment with eculizumab. At 4 weeks, 75% improvement in platelet counts was observed in 78% of patients. Two-thirds of patients demonstrated >75% improvement of haptoglobin and LDH at four weeks. At 4 weeks, eGFR improved by 25% in half of the patients, and 43% had reductions in proteinuria. Two of 3 patients that required hemodialysis were able to be taken off hemodialysis. Based on these observations, we suggest that eculizumab may be a potential treatment option for acutely ill patients with secondary TMA due to SLE and/or APS who have failed standard of care. A collective approach is needed to better elucidate the role and optimal timing of eculizumab use in the management of TMA complicating SLE and/or APS.

Kello N ，Khoury LE ，Marder G ，Furie R ，Zapantis E ，Horowitz DL ... -  《-》

A systematic review of the role of eculizumab in systemic lupus erythematosus-associated thrombotic microangiopathy.

Wright RD ，Bannerman F ，Beresford MW ，Oni L ... -  《BMC Nephrology》

Use of eculizumab in a systemic lupus erythemathosus patient presenting thrombotic microangiopathy and heterozygous deletion in CFHR1-CFHR3. A case report and systematic review.

de Holanda MI ，Pôrto LC ，Wagner T ，Christiani LF ，Palma LMP ... -  《-》

Eculizumab in secondary atypical haemolytic uraemic syndrome.

Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab. We identified 29 patients with so-called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 × 10 9 /L) and haemoglobin, disappearance of all the markers of microangiopathic haemolytic anaemia (MAHA), and improvement of renal function, with a ≥25% reduction of serum creatinine from the onset of eculizumab administration. Twenty-nine patients with secondary aHUS (15 drug-induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer-related, 1 associated with acute humoral rejection and 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a ≥50% serum creatinine reduction at the last follow-up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses. Short treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA-inducing condition.

Cavero T ，Rabasco C ，López A ，Román E ，Ávila A ，Sevillano Á ，Huerta A ，Rojas-Rivera J ，Fuentes C ，Blasco M ，Jarque A ，García A ，Mendizabal S ，Gavela E ，Macía M ，Quintana LF ，María Romera A ，Borrego J ，Arjona E ，Espinosa M ，Portolés J ，Gracia-Iguacel C ，González-Parra E ，Aljama P ，Morales E ，Cao M ，Rodríguez de Córdoba S ，Praga M ... -  《-》

[Eculizumab as rescue therapy for lupus nephritis-related thrombotic microangiopathy].

Thrombotic microangiopathy (TMA) is a frequent and severe complication in systemic lupus erythematosus (SLE). It is reported in almost 20-25% of renal biopsies of patients with lupus nephritis (LN) and is associated with a poor renal prognosis. We report the case of a patient suffering from an aggressive form of proliferative LN in association with thrombotic microangiopathy (TMA-LN), who was resistant to standard combined immunosuppressive treatment with corticosteroids and cyclophosphamide, as well as to plasma exchange (PEX). Eculizumab was given as a rescue therapy with an optimal clinical response. We performed a systematic review of the literature and identified 11 papers, published between 2011 and 2018, with a total of 20 patients, in which eculizumab was used, always as rescue therapy, to treat TMA-LN. All reported cases showed a positive clinical response to eculizumab with a high rate of remission. Even if sparse, available clinical cases and case series support the use of eculizumab in highly selected cases as rescue treatment for LN-TMA resistant to conventional combined immunosuppressive treatment.

Fani FM ，Patera A ，Delsante M ，Rossi GM ，Manenti L ，Landini S ，Regolisti G ，Fiaccadori E ... -  《-》