Quantifying the economic effects of ravulizumab versus eculizumab treatment in patients with atypical hemolytic uremic syndrome.

AIMS: This study compared the aggregate duration of treatment administration of approved eculizumab and ravulizumab treatment regimens and resultant productivity implications for patients with atypical hemolytic uremic syndrome (aHUS) and their caregivers. METHODS: The aggregate duration of treatment administration (which includes waiting time for medication preparation and time for infusion, recovery, and travel to and from the clinic) was determined for a hypothetical population of patients with aHUS treated with eculizumab (10 mg/mL) or ravulizumab (10 or 100 mg/mL), in the clinic or at home, for 1 year, in Germany, Italy, the UK, and the US. The data for US patients treated in the clinic was used to extend a previously published cost-minimization model (CMM) to estimate the annual lost productivity associated with treatment administration and to compare the overall annual treatment costs for hypothetical adult and pediatric patients in the US. RESULTS: The aggregate duration of treatment administration associated with ravulizumab 10 mg/mL and 100 mg/mL was reduced by 44-52% and 69-74%, respectively, compared with eculizumab 10 mg/mL, across all four countries. Using the CMM, the adult and pediatric US patient lost productivity costs due to treatment were reduced by 56-60% and 73-76% with ravulizumab 10 mg/mL and 100 mg/mL, respectively, compared with eculizumab 10 mg/mL, and overall discounted annual treatment costs (direct and lost productivity costs owing to treatment) were reduced for ravulizumab (10 mg/mL and 100 mg/mL) vs eculizumab 10 mg/mL for adult and pediatric patients. LIMITATIONS: This study was based on hypothetical patients, and assumptions were made regarding caregiver involvement, patient characteristics, and treatment patterns. CONCLUSIONS: Compared with eculizumab, ravulizumab reduces the lost productivity costs associated with treatment. This reduction in costs is greater with the ravulizumab 100 mg/mL formulation, compared with ravulizumab 10 mg/mL, owing to shorter infusion times with this more concentrated formulation.

PLAIN LANGUAGE SUMMARY[Figure: see text][Figure: see text].

Economic Impact of Early-in-Hospital Diagnosis and Initiation of Eculizumab in Atypical Haemolytic Uraemic Syndrome.

BACKGROUND: Atypical haemolytic uraemic syndrome (aHUS) is a rare, potentially life-threatening condition caused by dysregulation of the complement pathway. Eculizumab is currently the only approved treatment for this disorder. OBJECTIVE: Our objective was to investigate the impact of early administration of eculizumab on inpatient resource use and hospitalisation costs in 222 patients with aHUS. METHODS: We conducted a retrospective analysis of the Premier Perspective® Hospital Database, including patients with a diagnosis of aHUS and evidence of eculizumab use for aHUS. Early initiation was defined as having received eculizumab within 7 days of admission, with late initiation defined as starting eculizumab on day 8 or later. This date represents the average time required to obtain a specific diagnostic test to discriminate aHUS from a similar haemolytic syndrome that requires a different treatment. Outcome measures were time from first eculizumab initiation to discharge, discharge status or death, days spent in the intensive care unit (ICU), readmission indicators, dialysis indicators, and total hospital costs. Time from first eculizumab initiation to discharge was analysed using a generalised linear model with a log link and an assumed underlying negative binomial distribution. Logistic regression models were used to test the statistical significance of early versus late initiation as a predictor of the occurrence of readmissions, dialysis, and death. Total hospital costs were analysed using a generalised linear model with a log link and an assumed underlying gamma distribution. RESULTS: Before modelling, total length of stay and ICU duration were significantly longer for late initiators than for early initiators, and significantly more late initiators were readmitted within 90 days. Late initiation was associated with significantly higher hospital costs than early initiation. After multivariable analysis, late initiators were 3.2 times more likely to require dialysis. However, there was no significant association between early initiation and time to discharge, readmission, or death for any definition or early initiation after multivariable analysis. Estimated total hospital costs (year 2017 values) were $US103,557 in late initiators and $US85,776 in early initiators (p = 0.0024). CONCLUSION: Initiation of eculizumab within 7 days of hospitalisation is associated with lower dialysis rates, less time in ICU, less plasmapheresis, and lower hospitalisation costs compared with late initiation.

When to Stop Eculizumab in Complement-Mediated Thrombotic Microangiopathies.

The terminal complement-inhibitor eculizumab has dramatically changed the management of patients with atypical hemolytic uremic syndrome (aHUS), and has also shown promise for treating certain forms of secondary HUS (sHUS), including that caused by drugs and solid-organ/hematopoietic stem cell transplant. While effective, eculizumab is costly and inconvenient. In this review, we evaluate the literature on eculizumab cessation in these diseases to better inform clinicians who consider stopping therapy. Reported relapse rates in aHUS after stopping eculizumab are as high as 30%, suggesting indefinite therapy is reasonable and that patients who choose to stop should be closely monitored. In sHUS, relapse is rare, justifying short courses of eculizumab.

Cost-effectiveness of eculizumab treatment after kidney transplantation in patients with atypical haemolytic uraemic syndrome.

Background: Kidney transplantation in patients with atypical haemolytic uraemic syndrome (aHUS) is frequently complicated by recurrence of aHUS, often resulting in graft loss. Eculizumab prophylaxis prevents recurrence, improving graft survival. An alternative treatment strategy has been proposed where eculizumab is administered upon recurrence. We combined available evidence and performed a cost-effectiveness analysis of these competing strategies. Methods: A cost-effectiveness analysis using a decision analytical approach with Markov chain analyses was used to compare alternatives for aHUS patients with end-stage renal disease (ESRD): (i) dialysis treatment, (ii) kidney transplantation, (iii) kidney transplantation with eculizumab therapy upon recurrence of aHUS, (iv) kidney transplantation with eculizumab induction consisting of 12 months of prophylaxis and (v) kidney transplantation with lifelong eculizumab prophylaxis. We assumed that all patients received a graft from a living donor and that recurrence probability was 28.4% within the first year of transplantation. Results: At 8.34 quality-adjusted life years (QALYs) gained and a cost of €402 412, kidney transplantation without eculizumab was the least costly alternative. By comparison, dialysis was more costly and resulted in fewer QALYs gained. Eculizumab upon recurrence resulted in 9.55 QALYs gained at a cost of €425 097. The incremental cost-effectiveness ratio (ICER) was €18 748 per QALY. Both eculizumab induction and lifelong eculizumab were inferior to eculizumab upon recurrence, as both resulted in fewer QALYs gained and higher costs. Conclusions: Kidney transplantation is more cost effective than dialysis to treat ESRD due to aHUS. Adding eculizumab treatment results in a substantial gain in QALYs. When compared with eculizumab upon recurrence, neither eculizumab induction nor lifelong eculizumab prophylaxis resulted in more QALYs, but did yield far higher costs. Therefore, eculizumab upon recurrence of aHUS is more acceptable.

Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases.

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy, and as many as 70% of patients with aHUS have mutations in the genes encoding complement regulatory proteins. Eculizumab, a humanized recombinant monoclonal antibody targeting C5, has been used successfully in patients with aHUS since 2009. The standard maintenance treatment requires life-long eculizumab therapy, but the possibility of discontinuation has not yet been tested systematically. We report the safety of discontinuing eculizumab treatment in 10 patients who stopped treatment with the aim of minimizing the risk of adverse reactions, reducing the risk of meningitis, and improving quality of life while also reducing the considerable treatment costs. Disease activity was monitored closely at home by means of urine dipstick testing for hemoglobin. During the cumulative observation period of 95 months, 3 of the 10 patients experienced relapse within 6 weeks of discontinuation, but then immediately resumed treatment and completely recovered. Our experience supports the possibility of discontinuing eculizumab therapy with strict home monitoring for early signs of relapse in patients with aHUS who achieve stable remission.