A new study has found that combining immunoglobulin and glucocorticoids is an effective treatment for Multisystem Inflammatory Syndrome in Children (MIS-C), a rare but severe illness associated with SARS-CoV-2 infection.MIS-C is a hyperinflammatory condition that affects children and can cause severe symptoms, including fever, abdominal pain, rash, and cardiac dysfunction.
The illness has emerged as a serious concern worldwide, with cases reported in countries across the globe. Researchers from the National Institutes of Health (NIH) conducted a clinical trial to evaluate the efficacy of treatment options for MIS-C. The study included 614 children with MIS-C who were randomly assigned to receive either immunoglobulin, glucocorticoids, or a combination of both.
According to The Lancet Rheumatology, pediatric inflammatory multisystem syndrome (TIMSS), also known as MIS-C, was identified in April 2020 as an unusual but deadly post-infectious illness affecting children. Due to a lack of evidence from randomized controlled trials, the treatment guidelines for the newly diagnosed condition were developed by clinical consensus in numerous countries.
Based on the similarity between MIS-C and Kawasaki disease, for which intravenous immunoglobulin is the established treatment, national and international guidelines have recommended intravenous immunoglobulin as the initial treatment, with the addition of glucocorticoids or other immunomodulatory agents or both, for patients with severe illness.
No randomized controlled trials (RCTs) have compared treatments for MIS-C. Still, several observational studies using propensity score methods have suggested combining intravenous immunoglobulin and glucocorticoids is associated with improved cardiac outcomes, and RCTs are currently being conducted.
The Best Available Treatment Study (BATS) was launched in May 2020, shortly after MIS-C was found, to gather and analyze data systematically regarding the medicines chosen by individual pediatricians and provide evidence for treatment recommendations.
Given the urgent need for data to support treatment decisions, an analysis of the first 614 patients recruited in BATS was provided in July 2021. The findings of 15 patients treated with intravenous immunoglobulin alone, glucocorticoids alone, or a combination of the two were identical. However, this might be attributed to the small size of the study’s sample.
The study’s primary outcomes were requirements for inotropic support, ventilation on day two or later, or death, as well as the rate of improvement on the ordinal severity scale. The researchers found no significant differences in these outcomes among the treatment groups.
However, there was a non-significant trend towards a slower rate of improvement in patients treated with glucocorticoids alone compared to those treated with IVIG alone. Still, this comparison was limited to those with less severe illnesses at presentation. The study found no significant difference in coronary artery aneurysm outcomes between the primary treatment groups, with resolution in most patients.
A secondary analysis that compared glucocorticoids alone with combined IVIG plus glucocorticoids showed no significant difference in the requirements for inotropic support, ventilation on day two or later, or death. However, there was a faster time to improve for those treated with IVIG plus glucocorticoids, and lower rates of treatment escalation and lower rates of fever on day 2 in patients treated with IVIG plus glucocorticoids.
The researchers note that the potential incremental benefits of IVIG plus glucocorticoids to reduce the severity of illness and accelerate the resolution of fever must be balanced against the potential side effects of combination therapy. They suggest that in resource-limited settings, primary treatment with glucocorticoids alone is a safe alternative to IVIG alone or combined with glucocorticoids.
IVIG is reserved for patients who do not improve with glucocorticoids alone. In countries where the cost of IVIG is less prohibitive, initial treatment with a single agent may be preferable, with the addition of a second agent only in those who do not improve.
Overall, the study provides important insights into treating MIS-C in children and suggests that glucocorticoids alone may be a safe alternative to IVIG alone or combined with glucocorticoids, especially in resource-limited settings.