26 research outputs found

    Pharmacokinetics and safety of fidaxomicin in patients with inflammatory bowel disease and Clostridium difficile infection: An open-label Phase IIIb/IV study (PROFILE)

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    ©The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. Objectives Inflammatory bowel disease (IBD) poses an increased risk for Clostridium difficile infection (CDI). Fidaxomicin has demonstrated non-inferiority to vancomycin for initial clinical cure of CDI in patients without IBD; however, lack of data has caused concerns regarding potential systemic absorption of fidaxomicin in patients with IBD. Methods The plasma pharmacokinetics (PK) of fidaxomicin and its primary metabolite OP-1118 were evaluated in a multicentre, open-label, single-arm, Phase IIIb/IV study enrolling patients with active IBD and CDI. Patients received fidaxomicin, 200 mg twice daily for 10 days. The primary and secondary endpoints were, respectively, plasma and stool PK of fidaxomicin and OP-1118 on Days 1, 5 and 10 of treatment. Other secondary endpoints included safety of fidaxomicin treatment (assessed until Day 180). ClinicalTrials.gov identifier: NCT02437591. Results Median T max of fidaxomicin and OP-1118 for the PK analysis set (PKAS; 24 patients) was 1-2 h across Days 1, 5 and 10. C max ranges were 1.2-154 ng/mL for fidaxomicin and 4.7-555 ng/mL for OP-1118 across Days 1, 5 and 10 (PKAS). The ranges of concentrations in stool were 17.8-2170 μg/g for fidaxomicin and 0-1940 μg/g for OP-1118. Sixty percent (15/25) of patients experienced treatment-emergent adverse events (TEAEs), none of which led to treatment discontinuation or death. Conclusions Maximum fidaxomicin and OP-1118 plasma concentrations observed in this study population suggest no increase in absorption, compared with patients without IBD. Incidence of TEAEs was similar to previous Phase III trials, suggesting that fidaxomicin is comparatively well tolerated in patients with IBD

    Modelling the benefits of an optimised treatment strategy for 5-ASA in mild-to-moderate ulcerative colitis.

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    peer reviewedOBJECTIVES: 5-aminosalicylate (mesalazine; 5-ASA) is an established first-line treatment for mild-to-moderate ulcerative colitis (UC). This study aimed to model the benefits of optimising 5-ASA therapy. METHODS: A decision tree model followed 10 000 newly diagnosed patients with mild-to-moderately active UC through induction and 1 year of maintenance treatment. Optimised treatment (maximising dose of 5-ASA and use of combined oral and rectal therapy before treatment escalation) was compared with standard treatment (standard doses of 5-ASA without optimisation). Modelled data were derived from published meta-analyses. The primary outcomes were patient numbers achieving and maintaining remission, with an analysis of treatment costs for each strategy conducted as a secondary outcome (using UK reference costs). RESULTS: During induction, there was a 39% increase in patients achieving remission through the optimised pathway without requiring systemic steroids and/or biologics (6565 vs 4725 for standard). Potential steroidal/biological adverse events avoided included: seven venous thromboembolisms and eight serious infections. Out of the 6565 patients entering maintenance following successful induction on 5-ASA, there was a 21% reduction in relapses when optimised (1830 vs 2311 for standard). This translated into 297 patients avoiding further systemic steroids and 214 biologics. Optimisation led to an average net saving of £272 per patient entering the model for the induction and maintenance of remission over 1 year. CONCLUSION: Modelling suggests that optimising 5-ASA therapy (both the inclusion of rectal 5-ASA into a combined oral and rectal regimen and maximisation of 5-ASA dose) has clinical and cost benefits that supports wider adoption in clinical practice
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