IVIG Plus Glucocorticoids Lowers Risk of Cardiovascular Dysfunction in Children With Multisystem Inflammatory Syndrome

Because of its rapid emergence during the COVID-19 pandemic, experts have had to make quick decisions regarding treatment of multisystem inflammatory syndrome with no evidence base and little understanding of its pathophysiological characteristics.

Initiating treatment with intravenous immunoglobulin (IVIG) plus glucocorticoids reduced the risk of new or persistent cardiovascular dysfunction in children with multisystem inflammatory syndrome better than IVIG alone, according to research published in the New England Journal of Medicine.

Rapidly emerging multisystem inflammatory syndrome in children (MIS-C) is believed to be a post-infection complication of COVID-19, according to the study authors. However, because of its rapid emergence during the pandemic, health care professionals have had to make quick decisions regarding treatment with no evidence base and little understanding of its pathophysiological characteristics.

Patients with MIS-C experienced significant cardiovascular involvement, including shock, echocardiographic evidence of decreased function, and coronary-artery aneurysms that require urgent intervention. MIS-C resembles Kawasaki disease, which is a childhood vasculitis that can cause coronary-artery aneurysms and sometimes a shock-like presentation. Because IVIG is the standard treatment for Kawasaki disease, most patients with MIS-C received this treatment, as well.

As physicians scrambled to treat pediatric patients with MIS-C, contemporaneous studies worked to identify specific characteristics of the illness. Although they found clinical and immunophenotypic differences between Kawasaki disease and MIS-C, myocarditis findings in many patients with MIS-C also supported continued treatment with IVIG.

Patients with acute COVID-19 who also showed evidence of cytokine storm received dexamethasone, and the frequent findings of a severe shock-like presentation in patients with MIS-C led to the use of glucocorticoids in varying doses.

Randomized trials of treatment strategies for MIS-C have been challenging because cases are sporadic after waves of COVID-19, but the researchers said evaluating clinical outcomes in patients with MIS-C could provide insight into the efficacy of various immunomodulatory therapies. To investigate this, the team assessed patterns of immunomodulatory medication use in patients MIS-C.

The analysis included 596 patients with MIS-C who were admitted to 58 hospitals between March 15 and October 31, 2020. Of those, 87% received at least one immunomodulatory treatment during their hospitalization.

The patients had a median age of 8.7 years, 42% were female, 35% were Black and non-Hispanic, 34% were Hispanic or Latino, and 75% had no preexisting conditions and had not been taking any prescription medications. More than half (55%) had involvement of 5 or more organ systems, 38% met complete or incomplete criteria for Kawasaki disease, 74% were admitted to the intensive care unit, and 2% ultimately died.

Among the 518 patients who received immunomodulatory therapies during their hospitalization, 17% were treated with IVIG alone; 47% received IVIG and glucocorticoids; 21% received IVIG, glucocorticoids, and a biologic; and 16% received other treatments. Methylprednisolone was the most commonly prescribed glucocorticoid, and the most common initial treatments given on day 0 were IVIG alone and IVIG plus glucocorticoids.

According to the study authors, patients who received immunomodulating treatments at any time during their hospital stay had severe illness with notable treatment heterogeneity. They noted that treatment patterns changed over time, with most immunomodulatory agents given early after hospitalization and in rapid succession.

The 107 patients who received IVIG, glucocorticoids, and biologic therapies had the highest illness severity based on multiple indicators of critical illness. Of the 501 patients for whom at least 1 echocardiogram was obtained during their hospitalization, coronary-artery aneurysms were documented in 64, and 212 had left ventricular dysfunction during their hospitalization.

When analyzing the impact of various treatments given on day 0, the researchers found that initial therapy with IVIG plus glucocorticoids was associated with a lower risk of cardiovascular dysfunction compared to IVIG alone (20% vs 24%). They also found lower risks of each of the components of the composite outcome: left ventricular dysfunction occurred in 8% and 15% of the patients, respectively, and shock resulting in vasopressor use occurred in 16% and 20% of patients, respectively.

Based on these findings, the authors said initial treatment with IVIG and glucocorticoids can lower the risk of serious short-term outcomes in patients with MIS-C, including new or persistent cardiovascular dysfunction 2 or more days later. The ongoing spread of SARS-CoV-2 may result in more outbreaks of MIS-C, so they urged further research to examine the generalizability of their findings.

REFERENCE

Son MBF, Murray N, Friedman K, Young C, et al. Multisystem inflammatory syndrome in children—Initial therapy and outcomes. New England Journal of Medicine. July 1, 2021. Accessed July 16, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2102605