#2813 Eculizumab for treatment-resistant lupus—a friend or foe? A case report

Abstract Background Thrombotic microangiopathy (TMA) is a rare but devastating complication of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). It typically responds poorly to standard immunosuppression. Eculizumab, a recombinant monoclonal antibody C5 inhibitor, is now known to be efficacious for primary complement-mediated TMA due to genetic mutations in the complement pathway, or atypical haemolytic uraemic syndrome (aHUS). Its use is less established in secondary TMA such as that associated with SLE, but case report data have indicated benefit particularly in resistant cases. Since complement activation plays a key role in the pathogenesis of TMA secondary to SLE, it is thought that a therapy targeting the complement pathway could be effective. Case Report We present a case of a 35-year-old South Indian female with the most severe and refractory form of SLE, with background antiphospholipid syndrome (APS) and extensive history of thrombosis. She was strongly positive for lupus anticoagulant, anti-cardiolipin antibodies and anti beta2 glycoprotein 1 antibodies. She had multi-organ involvement of SLE with bilateral lupus related retinochoroiditis, tendinopathies, renal involvement, and unilateral sensorineural hearing loss. During a hospital admission, she became thrombocytopenic and blood film was consistent with microangiopathy. Thrombocytopenia screen including heparin induced thrombocytopenia (HIT) IgG ELISA test was negative; ADAMST13 assay was within normal range. A bone marrow biopsy showed bone marrow necrosis and marrow vessel thrombosis. Given her presentation, the initial proposed diagnosis was catastrophic antiphospholipid syndrome (CAPS) therefore she was treated with plasma exchange, intravenous immunoglobulin (IVIG), high dose steroids as well as continuation of anticoagulation with platelet support. However, thrombocytopenia and microangiopathy persisted despite treatment which was unusual for true CAPS. Therefore, this prompted urgent need for a kidney biopsy. The kidney biopsy confirmed presence of intra-capillary thrombus formation and red cell fragmentation consistent with acute thrombotic microangiopathy. Following this, eculizumab was commenced. She responded to treatment briefly with some resolution of thrombocytopenia for 6 months. However, her symptoms persisted and she had no renal recovery. Discussion Our patient with treatment-resistant SLE was treated with eculizumab for secondary TMA. Unfortunately, the response was not as hoped, and she remained thrombocytopenic with no real evidence of sustained renal or platelet recovery. The evidence is not clear on the benefit of C5-inhibitors in secondary TMA, and the existing literature tends to pull together a heterogenous group with various underlying aetiology; this may explain the differing results. The exact mechanism of TMA in SLE is not fully understood which can make it difficult to predict the type of patients who may or may not respond to eculizumab. Some cases of TMA in SLE/APS may be driven by direct endothelial damage or immune complex deposition; in which case the use of eculizumab which targets complement cascade would be deemed ineffective. Our patient was started on eculizumab after her kidney biopsy confirmed the diagnosis of TMA secondary to SLE. This meant there was a delay in starting treatment, as tissue diagnosis was confounded by thrombocytopenia and deranged coagulation screen. This does beg the question whether the overall outcome would have been more favourable if eculizumab was commenced at presentation without any delay. Conclusion Recommendations for the treatment of SLE and APS-related TMA are currently solely based on case reports and expert opinions. Plasma exchange and /or IVIG are used only in severe and refractory forms. Despite several reported cases of successful outcomes with eculizumab under similar circumstances we present a case that has not shown meaningful benefit.