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Published on 5 May 2017

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Use of extended-pulsed regimen with fidaxomicin more effective than standard vancomycin in CDI

Data presented  at the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2017, demonstrate benefits of extended-pulsed fidaxomicin (EPFX), compared to standard vancomycin.1

Data presented  at the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2017, demonstrate benefits of extended-pulsed fidaxomicin (EPFX), compared to standard vancomycin.1
Data from the EXTEND study1 show that EPFX provides a superior rate of sustained clinical cure at 30 days following treatment compared to standard vancomycin.1 At 40 days, recurrence rates were also found to be almost 10 times lower in patients treated with EPFX compared with standard vancomycin.1 EPFX is currently not an approved dosing regimen.2
The results of the study show at 30 days after end of treatment (i.e. day 55 for extended fidaxomicin (EPFX) and day 40 for vancomycin), recurrence occurred in 4.0% and 16.8% of patients receiving EPFX and vancomycin, respectively”, commented study author Professor Benoit Guery, Infectious Diseases Services, University Hospital of Lausanne. “The EXTEND study shows superiority of extended fidaxomicin over vancomycin1 and importantly this result is obtained with the same number of tablets and therefore does not change the cost and clearly improves the cost-efficacy ratio.” The extended-pulsed fidaxomicin regimen means that patients receive the same number of tablets as the standard licensed course of fidaxomicin (one tablet administered twice-daily for 10 days), but over a longer period of time.
A randomised, controlled, open-label study, the EXTEND trial is the first multicentre study of clinical outcomes for EPFX and was conducted in hospitals in 22 European countries.1,3 356 patients aged 60 years or older with CDI were randomised (1:1) to receive fidaxomicin 200mg oral tablets, twice-daily on days 1 to 5, then once-daily on alternate days on days 6 to 25, or vancomycin 125mg oral capsules, four-times daily on days 1 to 10.1 EPFX dosing was specifically designed to maintain efficacy in treating C. difficile bacteria, while maximising preservation of gut flora through alternate day dosing. This methodology allowed for an accurate assessment of the benefits of extended, rather than increased, use of fidaxomicin. The regimen was tested in an in vitro gut model at the University of Leeds prior to use in this study.4
At 30 days after end of treatment, sustained clinical cure was significantly higher for EPFX dosing compared with standard vancomycin (70.1% [95% confidence interval (CI) 63.3–76.8] versus 59.2% [CI 52.0–66.4], p=0.03).1 CDI recurrence rates were significantly lower for EPFX than standard vancomycin: day 40, 1.7% versus 16.8%; day 55, 4.0% versus 17.9%; day 90, 6.2% versus 19.0%; all p<0.001.1 Both treatment regimens presented similar safety profiles.1
Dr Andreas Karas, Senior Medical Director, Astellas Pharma EMEA, commented, “Recurrence of disease is one of the largest ongoing unmet needs of CDI treatment and the EXTEND study was designed to specifically get this as low as possible by minimising the impact on the gut flora by using a pulsed dosing regimen. Getting recurrence to levels as low as shown in this trial is a positive outcome for patients but also for health systems that bear the economic burden”.
Economic analyses of the EXTEND study data indicate that EPFX is a cost-effective treatment strategy compared with standard vancomycin.5 This finding was driven by the reduction in hospitalisation costs, resulting from the reduced recurrence rates associated with EPFX.5
Fidaxomicin is indicated in adults for the treatment of CDI. The recommended dose is one 200mg tablet administered twice-daily for 10 days. Extended-pulsed regimen with fidaxomicin is not currently approved.2

 

References

  1. Guery B, et al. Randomised, controlled, open-label study comparing the efficacy of extended-pulsed fidaxomicin (EPFX) with vancomycin therapy for sustained clinical cure of Clostridium difficile infection in an older population: the EXTEND study. Abstract presented at ECCMID 2017.
  2. Dificlir Summary of Product Characteristics (SmPC) for European Union, 2016.
  3. Guery B, et al. Randomised, controlled, open-label study comparing the efficacy of extended-pulsed fidaxomicin (EPFX) with vancomycin therapy for sustained clinical cure of Clostridium difficile infection in an older population: the EXTEND study. NCT02254967 study information. https://clinicaltrials.gov/ct2/show/NCT02254967 (last accessed April 2017).
  4. Chilton CH, et al. Successful treatment of simulated Clostridium difficile infection in a human gut model by fidaxomicin first line and after vancomycin or metronidazole failure. J Antimicrob Chemother. 2014;69(2):451-62.
  5. Watt M, et al. Cost-effectiveness of extended-pulsed fidaxomicin (EPFX) versus standard vancomycin (SV) in older patients with Clostridium difficile infection in England. Abstract presented at ECCMID 2017.


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