Compared to treatment with intravenous immunoglobulins (IVIG) alone, treatment with IVIG plus methylprednisolone for multisystem inflammatory syndrome in children (MIS-C) may be associated with a more favorable fever course and less severe acute complications, according to study results published in Journal of the American Medical Association.

A combination of a wide range of clinical features elevated inflammatory markers, and evidence of COVID-19 among children and adolescents aged 0 to 19 years with a fever greater than 3 days was termed as MIS-C. This inflammatory syndrome can be associated with hemodynamic failure and death.

The objective of the current study was to compare IVIG alone vs a combination of IVIG and methylprednisolone for patients with MIS-C associated with COVID-19.

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The retrospective cohort study included 181 children with suspected MIS-C, of whom 111 fulfilled the World Health Organization (WHO) criteria for MIS-C. After excluding 5 patients from the study who did not receive IVIG or steroids and 10 patients who could not be matched, the primary analysis included 32 patients who received a combination of IVIG and methylprednisolone and 64 propensity score-matched children. 

Primary outcome of the study was treatment failure, defined as persistence of fever for 2 days after the start of therapy or recurrence of fever with a week.

The combination of IVIG and methylprednisolone vs IVIG alone was associated with a lower rate of treatment failure (9% vs 38%, respectively; odds ratio [OR], 0.25; 95% CI, 0.09-0.70; P =.008). In most cases of treatment failure, the patients received second-line treatments, such as steroids or biologic therapy. The combination of IVIG and methylprednisolone was also associated with a lower risk for secondary acute left ventricular dysfunction occurring after the initial therapy (OR, 0.20; 95% CI, 0.06-0.66) and hemodynamic support (OR, 0.21; 95% CI, 0.06-0.76).

Length of stay in the pediatric intensive care unit was significantly shorter for patients who received combination therapy vs IVIG alone (median, 4 vs 6 days, respectively; P =.005).

The study had several limitations, including the observational design, variation in steroid treatment route and dosage, variable fever duration before presenting to the hospital, and potential underascertainment.

“Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course,” the researchers concluded.

Disclosure: This clinical trial was supported by Pfizer. Please see the original reference for a full list of authors’ disclosures.


Ouldali N, Toubiana J, Antona D. Association of intravenous immunoglobulins plus methylprednisolone vs immunoglobulins alone with course of fever in multisystem inflammatory syndrome in children. JAMA. Published online February 1, 2021. doi:10.1001/jama.2021.0694