Immunoglobulins Plus Corticosteroid May Improve Fever Course in MIS-C

Naïm Ouldali, MD, PhD

A new study demonstrated that methylprednisolone added to intravenous immunoglobulins (IVIG) was associated with a better course of fever in children with multisystem inflammatory syndrome (MIS-C).

A team, led by Naïm Ouldali, MD, PhD, Robert Debré University Hospital, University of Paris, conducted a retrospective cohort study in order to compare IVIG plus methylprednisolone and IVIG as initial therapy in MIS-C.

“Many children with MIS-C have received empirical treatment based on Kawasaki disease guidelines, with intravenous IVIG alone or combined with corticosteroids,” they wrote.

“In some studies, children have required second-line treatment, such as tumor necrosis factor inhibitor or interleukin 1 inhibitor, which underscores the importance of defining optimal initial therapy.”

Ouldali and colleagues noted that evidence for most effective therapies for MIS-C is still lacking.

IVIG and Methylprednisolone

The study cohort consisted of data on 111 children with MIS-C, which were drawn from a national surveillance system with propensity score-matched analysis.

As noted by the investigators, all cases with suspected MIS-C were reported to the French National Publish Health Agency.

The study began on April 1, 2020, with follow-up ending on January 6, 2021.

“The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure,” wrote Oudali and team.

“Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit,” they continued.

Of the entire evaluated population, 52% were female, and the median age was 8.6 years. Further, 5 children did not receive either treatment.

The team reported that 3 of 34 children (9%) in the IVIG plus methylprednisolone group did not respond to treatment.

However, as many as 37 of 72 (51%) of those in the IVIG only group did not respond to treatment.

Treatment with IVIG plus methylprednisolone—when compared with IVIG alone—was associated with a lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09-0.70]; P = .008).

Additionally, methylprednisolone used in conjunction with IVIG was significantly associated with a lower risk of use of second-line therapy (absolute risk difference, −0.22 [95% CI, −0.40 to −0.04]; OR, 0.19 [95% CI, 0.06-0.61]; P = .004).

A similar trend in lower risk for the combination treatment group was noted for hemodynamic support (absolute risk difference, −0.17 [95% CI, −0.34 to −0.004]; OR, 0.21 [95% CI, 0.06-0.76]) and acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, −0.18 [95% CI, −0.35 to −0.01]; OR, 0.20 [95% CI, 0.06-0.66]).

And finally, the combination therapy was associated with a shorter duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, −2.4 [95% CI, −4.0 to −0.7]).

MIS-C, Corticosteroids, and COVID-19

The results of the study thus indicate that corticosteroids may have a beneficial effect in children with MIS-C.

These findings may prove to be an essential consideration when treating pediatric patients with inflammation caused by SARS-CoV-2.

“Some recent preliminary mechanistic studies also suggested similarities between MIS-C and acute respiratory distress syndrome related to SARS-CoV-2 infection in adults,” the team wrote. “Corticosteroid use is currently one of the few validated therapeutics in severe respiratory adult forms of COVID-19.”

However, they acknowledged that additional studies are needed to better understand the mechanisms underlying a possible corticosteroid effect in MIS-C and in severe forms of COVID-19.

The study, “Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone with Course of Fever in Multisystem Inflammatory Syndrome in Children,” was published online in JAMA.