Welte T, et al. - In the CIGMA study, a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG was assessed as add-on therapy for patients with severe community-acquired pneumonia (sCAP). Comparison between trimodulin and placebo groups revealed no significant differences in ventilator-free days (VFDs) and mortality. In subsets of patients with elevated C-reactive protein (CRP), reduced IgM, or both, improved mortality with trimodulin was supported in post hoc analyses.

• This is a double-blind, phase II study (NCT01420744), including 160 patients with sCAP requiring invasive mechanical ventilation.
• Patients were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for 5 consecutive days.
• Ventilator-free days (VFDs) was the primary endpoint and secondary endpoints included 28-day all-cause and pneumonia-related mortality.
• Safety and tolerability were monitored.
• In subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L), exploratory post hoc analyses were carried out.

• No statistically significant difference was noted in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p=0.173).
• Researchers noted that 28-day all-cause mortality was 22.2% vs 27.8%, respectively (p=0.465).
• Between groups, the observed time to discharge from intensive care unit and mean duration of hospitalization were comparable.
• Findings showed that adverse-event incidences were also comparable.
• As noted in post hoc subset analyses, which included the majority of patients (58–78%), patients with high CRP, low IgM, and high CRP/low IgM at baseline had significant reductions in all-cause mortality (trimodulin vs placebo).