Cost-effectiveness analysis of fidaxomicin versus vancomycin in <i>Clostridium difficile</i> infection

Fidaxomicin was non-inferior to vancomycin with respect to clinical cure rates in the treatment of Clostridium difficile infections (CDIs) in two Phase III trials, but was associated with significantly fewer recurrences than vancomycin. This economic analysis investigated the cost-effectiveness of fidaxomicin compared with vancomycin in patients with severe CDI and in patients with their first CDI recurrence. A 1 year time horizon Markov model with seven health states was developed from the perspective of Scottish public healthcare providers. Model inputs for effectiveness, resource use, direct costs and utilities were obtained from published sources and a Scottish expert panel. The main model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY), for fidaxomicin versus vancomycin; ICERs were interpreted using willingness-to-pay thresholds of A 20aEuroS000 pound/QALY and A 30aEuroS000 pound/QALY. One-way and probabilistic sensitivity analyses were performed. Total costs were similar with fidaxomicin and vancomycin in patients with severe CDI (A 14aEuroS515 pound and A 14aEuroS344 pound, respectively) and in patients with a first recurrence (A 16aEuroS535 pound and A 16aEuroS926 pound, respectively). Improvements in clinical outcomes with fidaxomicin resulted in small QALY gains versus vancomycin (severe CDI, +0.010; patients with first recurrence, +0.019). Fidaxomicin was cost-effective in severe CDI (ICER A 16aEuroS529 pound/QALY) and dominant (i.e. more effective and less costly) in patients with a first recurrence. The probability that fidaxomicin was cost-effective at a willingness-to-pay threshold of A 30aEuroS000 pound/QALY was 60% for severe CDI and 68% in a first recurrence. Fidaxomicin is cost-effective in patients with severe CDI and in patients with a first CDI recurrence versus vancomycin

Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in Clostridium difficile infections:a meta-analysis and indirect treatment comparison

To evaluate the efficacy of fidaxomicin treatment, which has a limited effect on the normal gut flora, compared with vancomycin and metronidazole treatment in Clostridium difficile infections (CDIs). A systematic literature review was conducted in July to August 2011 and updated in July 2013. For fidaxomicin versus vancomycin, efficacy was evaluated using meta-analysis of data from two Phase III direct comparative studies (naEuroS=aEuroS1164). As there were no studies comparing fidaxomicin and metronidazole, an indirect comparison was made using data from three vancomycin versus metronidazole studies (naEuroS=aEuroS345), using the methodology of Bucher et al. (J Clin Epidemiol 1997; 50: 683-91). This provides an OR for the indirect comparison of fidaxomicin versus metronidazole when direct evidence of fidaxomicin versus vancomycin and vancomycin versus metronidazole is available. Clinical cure rates were similar for fidaxomicin and vancomycin; the OR (95% CI) was 1.17 (0.82, 1.66). Recurrence [0.47 (0.34, 0.65)] was significantly lower and sustained cure rates [1.75 (1.35, 2.27)] significantly higher for fidaxomicin than vancomycin. Similar results were obtained in patient subgroups with severe CDI and with non-severe CDI. From the indirect comparison, the likelihood of recurrence [0.42 (0.18, 0.96)] and sustained cure [2.55 (1.44, 4.51)] were significantly improved for fidaxomicin versus metronidazole. Again, similar results were obtained in those with severe and non-severe CDI. Fidaxomicin provides improved sustained cure rates in patients with CDI compared with vancomycin. An indirect comparison indicates that the same is also true for fidaxomicin versus metronidazole. In view of these data, fidaxomicin may be considered as first-line therapy for CDI