Table 2.

Studies evaluating antibody-mediated therapeutics in humans.

Agent	Study (author, year)	Study design	Efficacy
SYSTEMIC APPLICATION ROUTE
Actoxumab (CDA1)	Wilcox et al., 2017	Clinical Phase III study MODIFY I:
		Addition of actoxumab, bezlotoxumab, a-b or placebo to SoC treatment in adult (r)CDI patients	Higher mortality and more AE in actoxumab group; evaluation terminated
Bezlotoxumab (MDX1388)	Wilcox et al., 2017	Clinical Phase III study Addition of bezlotoxumab (n = 781) vs. placebo (n = 773) to SoC treatment in adult (r)CDI patients
		MODIFY I	No difference initial cure rate (77% vs. 83%) Significant lower rCDI (17% vs. 28%)
		MODIFY II	No difference initial cure rate (83% vs. 78%) Significant lower rCDI (16% vs. 26%)
Actoxumab-bezlotoxumab	Lowy et al., 2010	Clinical Phase II studyAddition of CDA1+ and MDX1388 in single infusion (n = 101) vs. placebo (n = 99) to SoC treatment for CDI	Significant lower laboratory-documented rCDI: 7% comparator vs. 25% placebo
	Wilcox et al., 2017	Clinical phase III study Addition of actoxumab-bezlotoxumab (n = 773) vs. placebo (n = 773) to SoC treatment in adult (r)CDI patients
		MODIFY I	No difference initial cure rate (75% vs. 83%) Significant lower rCDI(16% vs. 28%)
		MODIFY II	No difference initial cure rate (72% vs. 78%) Significant lower rCDI (15% vs. 26%)
IVIG	Leung et al., 1991	Case series5 pediatric patients with hypoglobulinaemia and rCDI, 400 mg/kg IVIG	All patients had full resolution of symptoms
	Wilcox, 2004; McPherson et al., 2006; Negm et al., 2017	Retrospective studies 36 adult patients with (r)CDI, 150–500 mg/kg IVIG	24 patients showed therapeutic response, 12 did not respond
	Juang et al., 2007; Shahani and Koirala, 2015	Retrospective studies 39 adult patients with severe CDI, 82 control patients, 400 mg/kg IVIG	No significant differences regarding outcome and severity of symptoms
ORAL APPLICATION ROUTE
IgAbulin	Tjellström et al., 1993	Case study 1 pediatric patient with severe CDI	Full resolution of symptoms
MucoMilk	van Dissel et al., 2005	Prospective cohort study 15 adult patients, 1 pediatric patient with completed antibiotic therapy, under which 9 patients with rCDI	No relapse within a median follow-up period of 333 days
	Numan et al., 2007	Prospective cohort study 101 adult patients, with completed antibiotic therapy, 61 patients with CDI 40 patients with rCDI (40%)	Prevention of relapse by 50% during a follow up period of 60 days
Cediff	Mattila et al., 2008	Prospective study 38 adult patients with rCDI 20 were treated with Cediff, 18 were treated with metronidazole	Cediff was as effective as metronidazole in the prevention of CDI recurrences during a 70 day follow up (sustained recovery 56% vs. 55%)

a-b, actoxumab-bezlotoxumab; AE, adverse event; SOC, standard-of-care; CDI, C. difficile disease; CDA1, human monoclonal anti-toxin A; CDB1, human monoclonal anti-toxin B; rCDI, recurrent CDI; SoC, standard-of-care antibiotic treatment for CDI; TcdA, C. difficile toxin A; TcdB, C. difficile toxin B; vs., versus; IVIG, intravenous immunoglobulin.