Infection Control & Hospital Epidemiology
cure and recurrence, for every 100 patients treated with vanco- mycin, 10 fewer patients will experience a recurrence if treated with fidaxomicin. Furthermore, among those who do experience a recurrence, their subsequent outcomes should be similar because the treatment options for additional recurring episodes do not differ. The current findings of vancomycin being the most cost-
pared with placebo was completed.16 This analysis was performed for patients with either their initial episode or recurrent episode of CDI, and it evaluated a bezlotoxumab-containing regimen or standard of care. In this analysis, bezlotoxumab was associated with a 0.12 QALY gain compared to standard of care with an ICER of $19,824 per QALY gained. The discordant findings from the current study may be attributable to several factors. The current study evaluated specifically fidaxomicin and vancomycin as comparators, whereas the analysis by Prabhu et al16 utilized standard of care as a comparator. In the clinical studies of bezlotoxumab, standard of care can include metronidazole, van- comycin, or fidaxomicin. Furthermore, the current analysis spe- cifically evaluated patients with their first recurrent episode of CDI, as opposed to an analysis of either the index or recurrent episodes. Given the novelty of bezlotoxumab, no clinical guide- lines currently include recommendations for its use. As such, the decision to specifically evaluate the first recurrent episode was made in conjunction with local clinicians who believe they are most likely to consider bezlotoxumab in that setting. This dif- ference may have limited the cost-effectiveness of fidaxomicin and bezlotoxumab because prevention of the initial recurrence may have more dramatic downstream cost and outcome differ- ences. Finally, in the study by Prabhu et al, they utilized a one- time cost to estimate the cost of recurrence, without considering subsequent treatment options for further recurrent CDI episodes (eg, vancomycin taper or FMT). As such, based on these differ- ences, the discrepant results of the 2 CEAs may be a result of evaluating different clinical scenarios and different choices in cost inputs. This CEA has several limitations. First, the analysis required
effective pharmacologic strategy and marginal improvements in QALY between different pharmacologic treatment options is corroborated in several other CEAs. Konijeti et al13 evaluated different treatment strategies for the management of recurrent CDI and found that vancomycin was the most cost-effective pharmacologic regimen. Fidaxomicin was associated with a marginally higher QALY (0.865 vs 0.858), which translated into an ICER of $184,023 per QALY gained. Similarly, Lapointe-Shaw et al14 performed a CEA that utilized a lifetime health effects calculation and demonstrated a marginal improvement of 0.13 QALY gained when comparing fidaxomicin and vancomycin.14 The current study adds to these CEAs by incorporating the recently approved strategy of bezlotoxumab plus vancomycin. In addition, it specifically evaluates the first recurrence while incorporating FMT as a mechanism of treatment for patients with further recurrences, which is more representative of current clinical practice. A recent pharmacoeconomic analysis of bezlotoxumab com-
compiling data from multiple comparative studies. Although patients all had similar diagnoses, it is not possible to balance the baseline differences among patients that may have accounted for the treatment outcome differences. To account for this, sensitivity analyses were performed, and despite accounting for uncertain- ties, both one-way sensitivity and PSA did not demonstrate drastically different results. Second, the data were all collected
929
from randomized controlled trials, where care and follow-up are likely more abundant than for patients in a clinical setting. As such, the cure rates and recurrence rates may represent best-case scenarios. Third, this CEA did not consider adverse effects. This decision was made in conjunction with several clinicians who did not believe that the differences in adverse effects among the treatment arms were significant enough to warrant incorporation into the model. Fourth, the current analysis does not account for different strains of C. difficile and their influence on recurrence rates. As such, if a center has a high proportion of BI/NAP1/O27 clones of C. difficile, the findings from this pharmacoeconomic analysis may not be applicable.32 Fifth, due to the paucity of data, the probabilities of recurrence, cure, and hospitalizations beyond the second recurrence were all assumed to be similar to the first recurrence. This likely underestimates the clinical sequelae asso- ciated with subsequent recurrences. Sixth, the rate of hospitaliza- tions fromrecurrent CDI was derived fromonly 1 study.10 Because hospitalizations are such costly interventions, if the rate of hospi- talization was dramatically different than those used in this study, theremay be significant differences in the cost-effectiveness of each therapy. Seventh, the costs associated with bezlotoxumab were not included in the cost evaluations because there aremany options for outpatient infusion therapy. However, adding further cost to bezlotoxumab would presumably further contribute to its lack of cost-effectiveness. Lastly, as with all pharmacoeconomic models, it is not possible to simulate all treatment decisions during a patient’s course. As such, the current model represents a reasonable approach to treatments and subsequent therapies associated with each successive recurrent CDI episode. In conclusion, our cost-effectiveness analysis illustrated van-
comycin alone as a cost-effective regimen for the treatment of the first recurrent episode of CDI. Bezlotoxumab plus vancomycin was a dominated strategy; therefore, it was not likely to be cost- effective. Fidaxomicin did lead to the highest QALY gained, but at a significantly higher cost than the specified WTP threshold.
Acknowledgments.
Financial support. No Please provide the Acknowledgment
section.financial support was provided relevant to this article.
Potential conflicts of interest. All authors report no conflicts of interest relevant to this article.
References
1. Loo VG, Poirier L, Miller MA, et al. A predominantly clonal multi- institutional outbreak of Clostridium difficile–associated diarrhea with high morbidity and mortality. N Engl J Med 2005;353:2442–2449.
2. Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology 2012;143:1179–1187.
3. Bouza E. Consequences of Clostridium difficile infection: understanding the healthcare burden. Clin Microbiol Infect 2012;18(Suppl 6):5–12.
4. Kwon JH, Olsen MA, Dubberke ER. The morbidity, mortality, and costs associated with Clostridium difficile infection. Infect Dis Clin North Am 2015;29:123–134.
5. McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile Infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018;66:987–994.
6. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015;372:825–834.
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116 |
Page 117 |
Page 118 |
Page 119 |
Page 120 |
Page 121 |
Page 122 |
Page 123 |
Page 124 |
Page 125 |
Page 126 |
Page 127 |
Page 128 |
Page 129 |
Page 130 |
Page 131 |
Page 132 |
Page 133 |
Page 134 |
Page 135 |
Page 136 |
Page 137 |
Page 138 |
Page 139 |
Page 140
