OBJECTIVES: Invasive candidiasis (IC) is a severe invasive fungal infection associated with high mortality, morbidity and prolonged hospital stay. Echinocandins are recommended for first-line treatment due to their efficacy and low rates of toxicity. The aim was to determine the relative efficacy of a new, weekly echinocandin (rezafungin) compared to daily echinocandins, on mortality and response.

METHODS: A network meta-analysis (NMA) was performed based on a systematic literature review conducted in MEDLINE, EMBASE and CENTRAL (18/10/23) to identify randomized controlled trials of licenced antifungal treatments reporting clinical outcomes in patients with IC. Studies evaluating azoles and polyenes were retained if they provided network connectivity for echinocandin treatments. Random-effects (informative priors) Bayesian models were used to compare treatment effects where possible.

RESULTS: Six of the 16 studies identified were included in the NMA for mortality and global response (n=1276 randomized patients). Comparators included once-daily: caspofungin (70/50mg) (reference treatment), micafungin (100mg) and anidulafungin (100mg) and once-weekly rezafungin (400/200mg). There were no significant differences between echinocandins for mortality: anidulafungin (odds ratio [OR] 0.50; 95% credible interval [Crl]: 0.15 to 1.74; sucra 0.83), rezafungin (OR 0.88; 95% Crl: 0.47 to 1.61; sucra 0.50) and micafungin (OR 1.30; 95% Crl: 0.78 to 2.20; sucra 0.13) versus caspofungin. There were also no significant differences for global response. Three studies were included for mycological and clinical response (n=704 randomized patients) for comparators caspofungin, rezafungin and micafungin. No significant differences were found, however the rezafungin trials were based on early eradication response (day 14) compared to end of treatment response in the other trials.

CONCLUSIONS: There was no evidence of a difference in efficacy among the echinocandins evaluated. However, rezafungin is a differentiated echinocandin with a low clearance and long half-life, enabling a once weekly front-loaded dosing regimen which may confer additional benefits not recognized herein.