DIFICLIR^TM▼(fidaxomicin) significantly reduces recurrence and all-cause mortality when used first-line in all patients with Clostridium difficile infection (CDI)

In the UK, there were 16,947 reported cases of CDI between April 2013 and March 2014^1,2,3,4 and in 2012 CDI contributed to nearly 1,900 deaths^5,6,7

BLED, Slovenia, May 19, 2015 /PRNewswire/ - Data presented today from the CDI Service Evaluation study shows that the adoption pattern of treatment impacts CDI outcomes. Compared to traditional broad-spectrum antibiotics, first-line use of fidaxomicin - a targeted treatment - in all CDI patients provides improved outcomes in terms of recurrence rate, all-cause mortality and cost effectiveness, compared to use in selected patients only.⁸ CDI is associated with high-mortality^5,6,7 and cost burden,⁹therefore reducing the incidence and recurrence of CDI is a priority for clinicians, payers and health authorities alike.

Presented today at the 5^th International Clostridium Difficile Symposium (ICDS) in Bled, Slovenia, the CDI Service Evaluation Study analysed a large dataset of over 1,450 CDI patient episodes. As a real-world multi-centre study, it assessed the effectiveness of current CDI treatment for UK patients in NHS Secondary Care Trusts in England.⁸

"CDI is a significant burden for patients and the NHS, and reducing its incidence and recurrence is a priority", comments Dr Simon Goldenberg, Consultant Microbiologist and Infection Control Doctor, Guy's and St Thomas' NHS Foundation Trust. "This study builds on the growing evidence that adopting fidaxomicin as first-line treatment for all patients with CDI, rather than reserving it for more severe cases, provides more optimal outcomes in terms of recurrence, all-cause mortality and cost effectiveness compared to older treatments - vancomycin and metronidazole. A previous study also showed that first-line use of fidaxomicin could reduce environmental contamination compared to those treated with vancomycin or metronidazole, further demonstrating the role fidaxomicin may play in reducing the spread and incidence of CDI alongside stringent hospital hygiene protocols."

Over 1,450 patient episodes were included in the analysis conducted in seven UK hospitals that introduced fidaxomicin, a narrow-spectrum antibiotic for the treatment of confirmed CDI in adults, between July 2012 and July 2013.⁸ Data collected were compared with a retrospective cohort treated with broad-spectrum antibiotics - vancomycin or metronidazole - during the previous 12-month period.⁸

Patterns of fidaxomicin use differed between the seven centres, with centres A and B treating with fidaxomicin as first-line treatment for all patients and the other five centres using fidaxomicin as first-line treatment only in selected patients for both primary and recurrent CDI.⁸

Data collected on 177 patient episodes treated first-line with fidaxomicin in centres A and B, showed a significant reduction in 28-day all-cause mortality, from 18.2% to 3.1% (P<0.001) and 17.3% to 6.3% (P<0.05) respectively.^8,10 The real-world analysis also supports clinical trial data in highlighting dramatically reduced recurrence rates: from 12.1% and 23.5% in centres A and B with standard of care treatments (vancomycin and metronidazole), to 3.1% in both these centres where fidaxomicin was used first-line.⁸ For every 50 patients treated, this would result in 5 and 10 recurrences avoided in the two centres respectively.⁸

"Good antimicrobial stewardship includes using, where possible, narrow-spectrum rather than a broad-spectrum treatment," comments Professor Mark Wilcox, Professor of Medical Microbiology, Leeds Teaching Hospitals & University of Leeds. "Fidaxomicin has limited activity against the 'good bacteria' in the gut and so can be considered to be a targeted treatment option. Preservation of the gut microflora likely contributes to the lower rates of recurrence seen after fidaxomicin treatment of CDI compared with those associated with broader-spectrum antibiotics like vancomycin."

A CDI recurrence adds an additional £20,249 on top of the £13,146 spent to treat the initial infection due to prolonged hospital stay, ICU stay, high cost drugs and the surgery necessary to tackle it, as seen in the real-world evidence.¹¹ An in-depth costing analysis at the two centres that adopted fidaxomicin as a first-line treatment revealed that in centre A the 5 recurrences that could be avoided for every 50 patients treated with the narrow-spectrum antibiotic would result in a cost saving of £19,490, and in centre B, for the 10 recurrences avoided, a cost saving of £121,144.⁸ With 16,947 cases of CDI reported in the UK between April 2013 and March 2014,^1,2,3,4 the potential NHS cost saving for the treatment of this potentially fatal condition is likely to be far greater.

Guidance from Public Health England recommends fidaxomicin as an initial treatment option for severe cases of CDI in patients at high risk for recurrence; in addition, fidaxomicin is the preferred treatment for recurrent CDI.¹²

NOTES TO EDITORS

About the CDI Service Evaluation study⁸

The CDI Service Evaluation Project is the first and only real-world multi-centre study assessing the effectiveness of current CDI treatment for UK patients in NHS Secondary Care Trusts. This evaluation looked specifically at the cost-effectiveness of fidaxomicin in clinical practice versus standard of care treatments (vancomycin and metronidazole) in seven trial centres from across the UK:

Leeds Teaching Hospitals NHS Trust
Guy's and St Thomas' NHS Foundation Trust
County Durham & Darlington NHS Foundation Trust
University Hospitals of Morecambe Bay - NHS Foundation Trust
St George's Healthcare NHS Trust
University Hospitals of Leicester NHS Trust
Derby Hospitals NHS Foundation Trust

Its full results were presented at the 5^th International Clostridium Difficile Symposium (ICDS) in Bled, Slovenia (19-21 May 2015).

The study was sponsored by Astellas Pharma Ltd.

About Clostridium difficile Infection (CDI)

CDI is a potentially serious illness resulting from infection of the internal lining of the colon by Clostridium difficile bacteria. The bacteria produce toxins that cause inflammation of the colon, diarrhoea and, in some cases, death. Patients typically develop CDI after the use of broad-spectrum antibiotics that disrupt normal bowel flora, allowing C. difficile bacteria to flourish. The majority of CDI cases are reported in people aged over 65,¹³ but younger patients are also affected. CDI results in substantial costs to healthcare systems, in particular because of extended hospitalisation.¹⁴

About DIFICLIR^TM (fidaxomicin)

DIFICLIR is a first-in-class macrocyclic antibiotic, of which the active substance is fidaxomicin.¹⁵ It is indicated for the treatment of (CDI) also known as C. difficile-associated diarrhoea (CDAD).¹⁶ It is the first licensed antibiotic treatment for CDI since the 1950s.¹⁷ Fidaxomicin is a targeted narrow spectrum antibiotic with highly selective activity against C. difficile bacteria rather than other gut flora.¹⁸

About Astellas Pharma EMEA

Astellas Pharma EMEA operates in 40 countries across Europe, the Middle East and Africa, and is the EMEA regional business of Tokyo-based Astellas Pharma Inc. Astellas is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceuticals. The organisation's focus is to deliver outstanding R&D and marketing to continue growing in the world pharmaceutical market. Astellas presence in Europe also includes an R&D site and three manufacturing plants. The company employs over 4,500 people across the EMEA region. In 2013 Astellas was awarded SCRIP Pharmaceutical Company of the Year in recognition of its commercial success and pipeline development.

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