Cost-effectiveness of bezlotoxumab and fidaxomicin for initial Clostridioides difficile infection.

OBJECTIVES: Treatment of Clostridioides difficile infection (CDI) has undergone significant change in recent years with the introduction of fidaxomicin and bezlotoxumab. This study evaluated the cost-effectiveness of fidaxomicin and bezlotoxumab for initial CDI compared with standard therapy with oral vancomycin. METHODS: A Markov model with eight health states was built based on transition probabilities, costs and health utilities derived from literature to evaluate the cost-effectiveness of standard fidaxomicin, bezlotoxumab plus vancomycin, and extended-pulsed fidaxomicin versus standard oral vancomycin over a lifetime horizon from the US societal perspective. RESULTS: For overall CDI treatment, oral vancomycin had a cost of $39 178 and was associated with a gain of 11.64 quality-adjusted life-years (QALYs). Extended-pulsed fidaxomicin had a higher QALY gain of 11.65 at a lower cost of $37 613, and therefore was dominant over vancomycin. Standard fidaxomicin had a QALY gain of 11.94 versus vancomycin at an incremental cost of $495 per QALY. Bezlotoxumab plus vancomycin led to a QALY gain of 11.77 at an incremental cost of $17 746 per QALY. At the willingness-to-pay (WTP) threshold of $150 000 per QALY, extended-pulsed fidaxomicin, bezlotoxumab plus vancomycin and standard fidaxomicin were more cost-effective compared with vancomycin alone, yielding incremental net monetary benefits of $3248, $17 011 and $44 308, respectively. One-way sensitivity analysis suggested that the probabilities of sustained cure from the initial episode were the most sensitive inputs, and results were overall not particularly sensitive to any drug costs. CONCLUSIONS: Based on a WTP threshold of $150 000, standard fidaxomicin was estimated to be the most cost-effective treatment. Standard-of-care vancomycin was dominated by extended-pulsed fidaxomicin for treating an episode of CDI and preventing further recurrence, and the addition of bezlotoxumab to vancomycin was dominated by standard fidaxomicin.

Cost-effectiveness analysis of fidaxomicin for the treatment of Clostridioides (Clostridium) difficile infection in Japan.

BACKGROUND: The cost of treating Clostridioides difficile infection (CDI), particularly recurrent disease, is high. In clinical trials, fidaxomicin has been associated with significantly lower recurrence rates and higher sustained cure rates versus vancomycin. The high acquisition cost of fidaxomicin has limited its acceptance into clinical practice. OBJECTIVE: To evaluate the cost-effectiveness of fidaxomicin versus vancomycin in patients with CDI after failure of metronidazole in the Japanese healthcare setting. METHODS: Clinical results from three phase III trials and inputs based on assumptions validated by clinical experts in Japan were used in a semi-Markov model with 1-year time horizon. Incremental cost-effectiveness ratios (ICERs) for fidaxomicin versus vancomycin were expressed as cost per quality-adjusted life year (QALY) and interpreted using willingness-to-pay thresholds of JPY 5,000,000 (primary) and JPY 7,500,000 (secondary) per QALY gained in Japan. Probabilistic sensitivity analyses and scenario analyses were performed. RESULTS: Higher drug acquisition costs for fidaxomicin were partially offset by lower hospitalization costs driven by fewer recurrences, lower costs of complications, and fewer general practitioner visits versus vancomycin. The ICER for fidaxomicin versus vancomycin was estimated at JPY 5,715,183 per QALY gained. Sensitivity analyses showed a 46% probability of fidaxomicin being cost-effective versus vancomycin at a willingness-to-pay threshold of JPY 5,000,000 per QALY gained. At a threshold of JPY 7,500,000, there was a 54% probability of fidaxomicin being cost-effective. CONCLUSIONS: Fidaxomicin treatment in patients with CDI following failure of metronidazole improves health outcomes with partial offset of higher drug acquisition costs versus vancomycin.

[Recommendations from a panel of experts on the usefulness of fidaxomicin for the treatment of infections caused by Clostridium difficile]. / Recomendaciones de un panel de expertos sobre la utilidad de fidaxomicina para el tratamiento de las infecciones causadas por Clostridium difficile.

OBJECTIVE: Clostridium difficile infections have a high recurrence rate, which can complicate the prognosis of affected patients. It is therefore important to establish an early detection and an appropriate therapeutic strategy. The objective of this manuscript was to gather the opinion of an expert group about the predictive factors of poor progression, as well as when to use fidaxomicin in different groups of high-risk patients. METHODS: A scientific committee of three experts in infectious diseases reviewed the most recent literature on the management of C. difficile infections, and the use of fidaxomicin. They developed a questionnaire of 23 items for consensus by 15 specialists in this type of infection using a modified Delphi method. RESULTS: The consensus reached by the panelists was 91.3% in terms of agreement. The most important agreements were: recurrence is a risk criterion per se; fidaxomicin is effective and safe for the treatment of infections caused by C. difficile in critical patients, immunosuppressed patients, or patients with chronic renal failure; fidaxomicin is recommended from the first episode of infection to ensure maximum efficacy in patients with well-contrasted recurrence risk factors. CONCLUSIONS: The experts consulted showed a high degree of agreement on topics related to the selection of patients with poorer prognosis, as well as on the use of fidaxomicin in groups of high-risk patients, either in the first line or in situations of recurrence.

Cost-effectiveness of three different strategies for the treatment of first recurrent Clostridium difficile infection diagnosed in a community setting.

OBJECTIVE: A significant portion of patients with Clostridium difficile infections (CDI) experience recurrence, and there is little consensus on its treatment. With the availability of newer agents for CDI and the added burdens of recurrent disease, a cost-effectiveness analysis may provide insight on the most efficient use of resources. DESIGN: A decision-tree analysis was created to compare the cost-effectiveness of 3 possible treatments for patients with first CDI recurrence: oral vancomycin, fidaxomicin, or bezlotoxumab plus vancomycin. The model was performed from a payer's perspective with direct cost inputs and a timeline of 1 year. A systematic review of literature was performed to identify clinical, utility, and cost data. Quality-adjusted life years (QALY) and incremental cost-effectiveness ratios were calculated. The willingness-to-pay (WTP) threshold was set at $100,000 per QALY gained. The robustness of the model was tested using one-way sensitivity analyses and probabilistic sensitivity analysis. RESULTS: Vancomycin had the lowest cost ($15,692) and was associated with a QALY gain of 0.8019 years. Bezlotoxumab plus vancomycin was a dominated strategy. Fidaxomicin led to a higher QALY compared to vancomycin, at an incremental cost of $500,975 per QALY gained. Based on our WTP threshold, vancomycin alone was the most cost-effective regimen for treating the first recurrence of CDI. Sensitivity analyses demonstrated the model's robustness. CONCLUSIONS: Vancomycin alone appears to be the most cost-effective regimen for the treatment of first recurrence of CDI. Fidaxomicin alone led to the highest QALY gained, but at a cost beyond what is considered cost-effective.

Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients aged ≥60 years (EXTEND): analysis of cost-effectiveness.

Objectives: The randomized Phase IIIb/IV EXTEND trial showed that extended-pulsed fidaxomicin significantly improved sustained clinical cure and reduced recurrence versus vancomycin in patients ≥60 years old with Clostridium difficile infection (CDI). Cost-effectiveness of extended-pulsed fidaxomicin versus vancomycin as first-line therapy for CDI was evaluated in this patient population. Methods: Clinical results from EXTEND and inputs from published sources were used in a semi-Markov treatment-sequence model with nine health states and a 1 year time horizon to assess costs and QALYs. The model was based on a healthcare system perspective (NHS and Personal Social Services) in England. Sensitivity analyses were performed. Results: Patients receiving first-line extended-pulsed fidaxomicin treatment had a 0.02 QALY gain compared with first-line vancomycin (0.6267 versus 0.6038 QALYs/patient). While total drug acquisition costs were higher for extended-pulsed fidaxomicin than for vancomycin when used first-line (£1356 versus £260/patient), these were offset by lower total hospitalization costs (which also included treatment monitoring and community care costs; £10 815 versus £11 459/patient) and lower costs of managing adverse events (£694 versus £1199/patient), reflecting the lower incidence of CDI recurrence and adverse events with extended-pulsed fidaxomicin. Extended-pulsed fidaxomicin cost £53 less per patient than vancomycin over 1 year. The probability that first-line extended-pulsed fidaxomicin was cost-effective at a willingness-to-pay threshold of £30 000/QALY was 76% in these patients. Conclusions: While fidaxomicin acquisition costs are higher than those of vancomycin, the observed reduced recurrence rate with extended-pulsed fidaxomicin makes it a more effective and less costly treatment strategy than vancomycin for first-line treatment of CDI in older patients.