Fidaxomicin for the treatment of Clostridium difficile infection (CDI) in at-risk patients with inflammatory bowel disease, fulminant CDI, renal impairment or hepatic impairment: a retrospective study of routine clinical use (ANEMONE)
Information is limited or lacking on fidaxomicin treatment of Clostridium difficile infection (CDI) in patients with inflammatory bowel disease, fulminant or life-threatening CDI, severe renal impairment, moderate-to-severe hepatic impairment and pregnancy. The ANEMONE study investigated fidaxomicin use in a routine clinical setting, focusing on these medical conditions of specific interest (MCSIs). This retrospective, post-authorisation study reviewed hospital records from Austria, Germany, Spain and the UK (June 2012–June 2015), collecting data from hospital admission to 30 days after last fidaxomicin dose. The primary objective was to identify the proportion of fidaxomicin-treated patients with MCSIs. Secondary objectives were to describe 30-day mortality, changes in ECG and laboratory parameters, fidaxomicin exposure and CDI response (resolution of diarrhoea; 30-day recurrence). 45.3% (261/576) of patients had ≥ 1 MCSI. Thirty-day mortality (post-first dose) was 17.0% (98/576) in the total population and slightly higher (24.6–27.6%) in patients with fulminant CDI or severe renal impairment. 29.6% (24/81) deaths of known cause were attributable to CDI. Of changes in laboratory parameters or ECG findings, only a decrease in leucocyte counts appeared associated with fidaxomicin, consistent with a positive treatment response. Diarrhoea resolved in 78.0% (404/518) of treatment episodes; diarrhoea resolution was lowest in patients with fulminant CDI (investigator-defined, 67.5%, 56/88) and severe renal impairment (68.0%, 68/100). Thirty-day recurrence (18.8%, 79/420) was similar across MCSI subgroups. Although almost half of fidaxomicin-treated patients had ≥ 1 MCSI, the majority of patients in all subgroups had positive responses to treatment, and no particular safety concerns were identified.
KeywordsClostridium difficile Fidaxomicin Inflammatory bowel disease Fulminant CDI Renal impairment Hepatic impairment
This study was developed, managed and funded by Astellas Pharma Europe B.V. Site recruitment and data monitoring, management and analysis were outsourced to Quintiles Outcomes (later IQVIA); Christelle da Cruz was the project manager and Elodie Incera was involved in data analysis and interpretation. Medical writing support was provided by Annie Rowe, PhD, and Iona Easthope, DPhil, for Cello Health MedErgy, and funded by Astellas Pharma, Inc.
Study design: MJGTV, SDG, ST, EB, FT, JvO, GW
Conduct and acquisition of data: MJGTV, SDG, ST, EB, FT, JvO, GW
Analysis and interpretation of data: MJGTV, SDG, ST, EB, FT, AG, GW, JvO
Writing of the manuscript: MJGTV, SDG, ST, EB, FT, AG, GW, JvO
Compliance with ethical standards
Conflict of interest
Maria JGT Vehreschild is a consultant to Astellas Pharma, Berlin Chemie, Maat Pharma and MSD/Merck; has served at the speakers’ bureaux of Astellas Pharma, Basilea, Falk Foundation, Gilead Sciences, Merck/MSD, Organobalance and Pfizer; and received research funding from 3M, Astellas Pharma, DaVolterra, Gilead Sciences, Merck/MSD, Morphochem, Organobalance and Seres Therapeutics. Surabhi Taori has received conference attendance sponsorship and speaker fees from Astellas Pharma, Inc. Simon D. Goldenberg has received consultancy fees from Astellas, Pfizer and MSD; speaker fees from Astellas and MSD; and research funding from Astellas. Joop van Oene is a full-time employee of Astellas Pharma Europe B.V. Graham Wetherill is a consultant statistician for Astellas Pharma Europe B.V. Areti Georgopali is a full-time employee of Astellas Pharma, Inc. Florian Thalhammer and Emilio Bouza have no conflicts of interest to declare.
This study was conducted in accordance with the Declaration of Helsinki and with the approval of the Independent Ethics Committee/Institutional Review Board of each country and site, where required. This was a retrospective study and all patient data were anonymised; informed consent was therefore not required under country-specific regulations. No direct access to source data by the clinical research organisation or the sponsor was allowed.
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