Journal Club : Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection.
MODIFY I and MODIFY II
2017年1月NEJMに報告された、日本を含む30カ国322施設におけるC. difficile の初感染または再発に対し標準治療である経口抗菌薬投与を受けている成人に対する二重盲検無作為化プラセボ対照第 3 相試験。
ベズロトクスマブ（10 mg/kg）、アクトクスマブ＋ベズロトクスマブ（それぞれ 10 mg/kg）またはプラセボによる点滴静注後 12 週間以内に再発した感染を主アウトカムとした試験。
- Journal Club : Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection.
- MODIFY I and MODIFY II
P : 2655 adults receiving oral standard-of-care antibiotics for primary or re- current C. difficile infection
bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each)
C : placebo
In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001).
The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea.
T : double-blind, randomized, placebo-controlled, phase 3 trials,
First, the selection of standard-of-care antibiotic was not standardized but rather was at the discretion of the investigator. To control for this, the study groups were stratified according to the standard- of-care antibiotic and therefore were balanced with regard to that variable. Moreover, the efficacy of bezlotoxumab with regard to the rate of recurrent infection was not affected by the choice of standard-of-care antibiotic.
Second, although the time of study infusion relative to the onset of symptoms was balanced across treatment groups, the time interval was broad; thus, an assessment of the effect of neutralization of toxin B or toxin A on the severity and duration of the baseline episode could not be performed.
Third, the proportion of participants with a severe baseline episode of C. difficile infection is probably an underestimate, since more than 90% of partici- pants were receiving standard-of-care antibiotics when the severity assessment was performed.
Fourth, other therapies that are currently used for the prevention of recurrent C. difficile infec- tion were not allowed; therefore, the combined effect of bezlotoxumab and other approaches (e.g., fecal microbiota transplantation) is not known.
Finally, safety assessments were limited because of the relatively small number of pa- tients who received bezlotoxumab, which makes it difficult to detect potentially serious but lowfrequency toxic effects.