The clinical efficacy of intravenous IgM-enriched immunoglobulin (pentaglobin) in sepsis or septic shock: a meta-analysis with trial sequential analysis

Abstract

Background Sepsis is characterized by a complex immune response. This meta-analysis evaluated the clinical effectiveness of intravenous IgM-enriched immunoglobulin (IVIgGM) in patients with sepsis and septic shock. Methods Four databases, PubMed, the Cochrane Library, the ISI Web of Knowledge, and Embase, were systematically searched from inception to June 2018 to update the 2013 edition of the Cochrane review by two investigators, who independently selected studies, extracted relevant data, and evaluated study quality. Data were subjected to a meta-analysis and trial sequential analysis (TSA) for the primary and secondary outcomes. Level of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scale. Results Nineteen studies comprising 1530 patients were included in this meta-analysis. Pooled analyses showed that the use of IVIgGM reduced the mortality risk of septic patients (relative risk 0.60; 95% confidence interval [CI] 0.52–0.69, I 2 = 0%). TSA showed that IVIgGM had a significant effect on mortality. Additionally, the meta-analysis suggested that use of IVIgGM shortened length of mechanical ventilation (mean difference − 3.16 days; 95% CI − 5.71 to − 0.61 days) and did not shorten length of stay in the intensive care unit (mean difference − 0.38 days; 95% CI − 3.55 to 2.80 days). The GRADE scale showed that the certainty of the body of evidence was low for both benefits and IVIgGM. Conclusion Administration of IVIgGM to adult septic patients may be associated with reduced mortality. Treatment effects tended to be smaller or less consistent when including only those studies deemed adequate for each indicator. The available evidence is not clearly sufficient to support the widespread use of IVIgGM in the treatment of sepsis. Trial registration PROSPERO registration number: CRD42018084120. Registered on 11 February 2018. Electronic supplementary material The online version of this article (10.1186/s13613-019-0501-3) contains supplementary material, which is available to authorized users.

Clinical, laboratory features and prognosis of children receiving IgM-enriched immunoglobulin (3 days vs. 5 days) as adjuvant treatment for serious infectious disease in pediatric intensive care unit: a retrospective single-center experience (PIGMENT study)

“…The relative risk for mortality was 0.51 (0.34-0.75; 95% CI). Other reports regarding the 5-day IgM-enriched intravenous immunoglobulin treatment 14 Our study represents the first pediatric study on the use of a 5-day IgM-enriched intravenous immunoglobulin treatment.…”

“…21 Results from recent trials and systemic meta-analyses seem more promising with regard to the use of IgM-enriched intravenous immunoglobulin in septic patients. 13,14,22,23 IgM-enriched intravenous immunoglobulin in different dosing schemes has been used in retrospective or prospective studies of adults and newborns, generating different 28-day mortality results. Alejandria et al 24 evaluated seven studies on the use of IgM-enriched intravenous immunoglobulin as an adjuvant therapy in adult patients with bacterial sepsis or septic shock and showed a significant reduction in mortality when compared with placebo or nonintervention.…”

“…While six studies showed no effects of IgM-enriched intravenous immunoglobulin on mortality, nine studies showed that IgM-enriched intravenous immunoglobulin administration increases survival in patients with sepsis or septic shock. 13 Cui et al 14 conducted a meta-analysis that included 15 randomized controlled clinical trials (n = 712) and four observational cohort studies (n = 818) and showed that IgM-enriched intravenous immunoglobulin reduced mortality in adults with sepsis by 40%. Cavazutti et al 25 evaluated whether an association existed between adjunctive therapy with IgM-enriched immunoglobulin and a 30-day mortality rate in 92 adult patients with septic shock in an ICU between 2008 and 2011.…”

Use of Intravenous Immunoglobulins in Sepsis Therapy—A Clinical View

“…However, systematic reviews and meta-analyses suggest that the use of preparations with enriched IgA and IgM (IgGAM) is associated with a higher survival rate [67][68][69][70][71]. A recent meta-analysis, including 19 trials with more than 1500 patients showed a significant reduction in mortality when using IgM-and IgA-enriched immunoglobulins compared to human albumin solution or no special treatment as a control intervention [67]. In addition, a post-hoc analysis of the CIGMA trial demonstrated a significant relative reduction in all-cause mortality of 54-68% using IgM-and IgA enriched immunoglobulins in patients with severe pneumonia and had high C-reactive protein (CRP), low IgM and high CRP/low IgM ratios at baseline compared to placebo [72].…”

Immune Response Resetting as a Novel Strategy to Overcome SARS-CoV-2–Induced Cytokine Storm

“…Despite lack of consensus (68,69), one of the most comprehensive meta-analyses found lack of evidence of survival benefit of this therapy in pediatric patients and unclear benefit for adults (70). However, another meta-analysis of 19 smaller studies found that IgM-enriched Ig (IVIgM) reduced mortality in adults with sepsis (71). A trial to test IVIgM in 200 peritonitis/sepsis patients was initiated, but its status is currently suspended (NCT03334006) (72).…”