Eculizumab-Every Fifteen Days Forever?

Noris, Marina; Remuzzi, Giuseppe

doi:10.1016/j.ekir.2022.11.006

Cited by 2 publications

(2 citation statements)

References 9 publications

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“…Indeed, Noris et al [49], in their comment on this study, underlined that in the high-risk group of aHUS patients with pathogenic or likely pathogenic complement gene variants, 50% to 75% of patients did not relapse. Hence, it is not clear yet if we may offer high-risk patients the opportunity to discontinue eculizumab and how it is possible safely, considering the current absence of early and reliable predictors of aHUS relapse.…”

Section: C5 Inhibitors Discontinuation: Is There a Path To Follow?mentioning

confidence: 73%

Underlying Genetics of aHUS: Which Connection with Outcome and Treatment Discontinuation?

Spasiano,

Palazzetti,

Dimartino

et al. 2023

IJMS

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Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by a genetic dysregulation of the alternative complement pathway, characterized by thrombocytopenia, hemolytic anemia, and acute kidney injury, and included in the group of thrombotic microangiopathies. With the introduction of humanized monoclonal antibodies that inhibit C5 activation, the natural history of aHUS completely changed, with a better prognosis, a quick recovery of renal function, and a significant reduction of end-stage renal disease incidence. Nowadays, there is an increasing interest in the molecular and genetic bases of this severe disease. The aim of this narrative review is to provide readers with a practical guide about different possible involved genes, elucidating the specific role of each transcribed protein in the pathogenesis of aHUS. Moreover, we analyzed the main current evidence about the relationship among genetic mutations, outcomes, and the risk of recurrence of this manifold disease.

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Section: C5 Inhibitors Discontinuation: Is There a Path To Follow?mentioning

confidence: 73%

Underlying Genetics of aHUS: Which Connection with Outcome and Treatment Discontinuation?

Spasiano,

Palazzetti,

Dimartino

et al. 2023

IJMS

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“…However, plasma therapy served only as a temporising measure, often improving peripheral hemolytic abnormalities but having no effect on overall survival or development of end stage kidney disease (ESRD) (1,10). In 2011, the introduction of the humanized anti-C5 monoclonal antibody eculizumab radically transformed the landscape of aHUS management, with most patients responding to C5 inhibition and the risk of ESRD dropping to 10-15% (11)(12)(13). Lifelong treatment with eculizumab had since become the standard of care, mainly owing to concerns about the risk of aHUS relapses and further kidney injury.…”

Section: Introductionmentioning

confidence: 99%

Treatment discontinuation in atypical hemolytic uremic syndrome (aHUS): A qualitative study of international experts’ perspectives with associated cost-consequence analysis

Germeni,

Cooper,

Briggs

et al. 2024

Preprint

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Background Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA) related to congenital mutations impeding control of the alternative pathway of complement. Following approval of the complement C5 inhibitor eculizumab by the European Medicines Agency and the US Food and Drug Administration, initial guidelines suggested lifelong therapy. Yet, growing evidence indicates that discontinuation of eculizumab, or its long-acting form ravulizumab, is possible for many patients. This mixed-methods study sought to explore international experts’ perspectives and experiences related to treatment duration in adult patients with aHUS, while also estimating the financial and potential health consequences of early discontinuation. Methods Between January and December 2023, we conducted 10 qualitative interviews with experts in the treatment of aHUS, based upon which we constructed a quantitative decision tree, designed to estimate time on treatment and treatment- and disease-related adverse events. Results Thematic analysis of the interview data identified four main themes: (1) Concerns and prior experience; (2) High-risk vs. low-risk groups; (3) Patient preference and adherence; and (4) Funding for monitoring and re-treatment. Although most interviewees were in favour of considering treatment discontinuation for many patients (citing the high cost, burden, and potential side effects of lifelong treatment as key reasons), a prior negative experience of discontinuation seemed to make others more reluctant to stop. Deciding which patients required lifelong treatment and which not involved consideration of a wide range of factors, including patient- and system-related factors. Cost-consequence analysis demonstrated the financial savings associated with early treatment discontinuation at the expense of increased risk of recurrent TMA events. Close monitoring for these events had the potential to minimise any long-term injury, primarily renal, with an estimated one event per 100 patient years. For patients at high risk of TMA and with poor adherence to monitoring, rates of renal injury rose to three events per 100 patient years. Conclusions aHUS treatment protocols are changing globally in response to new clinical evidence. Against this backdrop, our mixed-methods study provides compelling evidence on the complexity of factors influencing treatment discontinuation decisions in aHUS, as well as the financial and health consequences of early discontinuation.

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Eculizumab-Every Fifteen Days Forever?

Cited by 2 publications

References 9 publications

Underlying Genetics of aHUS: Which Connection with Outcome and Treatment Discontinuation?

Underlying Genetics of aHUS: Which Connection with Outcome and Treatment Discontinuation?

Treatment discontinuation in atypical hemolytic uremic syndrome (aHUS): A qualitative study of international experts’ perspectives with associated cost-consequence analysis

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