The combination of methylprednisolone and intravenous immunoglobulins works better than intravenous immunoglobulins alone for multisystem inflammatory syndrome in children (MIS-C), researchers say.
“I’m not sure it’s the best treatment because we have not studied every possible treatment,” François Angoulvant, MD, PhD, told this news organization, “but right now, it’s the standard of care.”
Dr. Angoulvant, a professor of pediatrics at University of Paris, and colleagues published a comparison of the two treatments in the Journal of the American Medical Association.
A small percentage of children infected with SARS-CoV-2 develop MIS-C about 2 to 4 weeks later. It is considered a separate disease entity from COVID-19 and is associated with persistent fever, digestive symptoms, rash, bilateral nonpurulent conjunctivitis, mucocutaneous inflammation signs, and frequent cardiovascular involvement. In more than 60% of cases, it leads to hemodynamic failure, with acute cardiac dysfunction.
Because MIS-C resembles Kawasaki disease, clinicians modeled their treatment on that condition and started with immunoglobulins alone, Dr. Angoulvant said.
Based on expert opinion, the National Health Service in the United Kingdom published a consensus statement in Sept. listing immunoglobulins alone as the first-line treatment.
But anecdotal reports have emerged that combining the immunoglobulins with a corticosteroid worked better. To investigate this possibility, Dr. Angoulvant and colleagues analyzed records of MIS-C cases in France, where physicians are required to report all suspected cases of MIS-C to the French National Public Health Agency.
Among the 181 cases they scrutinized, 111 fulfilled the World Health Organization criteria for MIS-C. Of these, the researchers were able to match 64 patients who had received immunoglobulins alone with 32 who had received the combined therapy and could be matched using propensity scores.
The researchers defined treatment failure as persistence of fever for 2 days after the start of therapy or recurrence of fever within a week. By this measure, the combination treatment failed in only 9% of cases while immunoglobulins alone failed in 38% of cases. The difference was statistically significant (P = .008). Most of those for whom these treatments failed received second-line treatments such as steroids or biological agents.
Patients treated with the combination therapy also had a lower risk of secondary acute left ventricular dysfunction (odds ratio, 0.20; 95% confidence interval, 0.06-0.66) and a lower risk of needing hemodynamic support (OR, 0.21; 95% CI, 0.06-0.76).
Those receiving the combination therapy spent a mean of 4 days in the pediatric intensive care unit compared with 6 days for those receiving immunoglobulins alone. (Difference in days, −2.4; 95% CI, −4.0 to −0.7; P = .005).
There are few drawbacks to the combination approach, Dr. Angoulvant said, as the side effects of corticosteroids are generally not severe and they can be anticipated because this class of medications has been used for many years.
The study raises the question of whether corticosteroids might work as well by themselves, but it could not be answered with this database as no one is using that approach in France, Dr. Angoulvant said. “I hope other teams around the world could bring us the answer.”
In the United States, most physicians appear to already be using the combination therapy, said David Teachey, MD, an associate professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia.
The reduction in time in pediatric intensive care and the reduced risk of cardiac dysfunction are important findings, he said.
This retrospective study falls short of the evidence provided by a randomized clinical trial, Dr. Teachey noted. But he acknowledged that few families would agree to participate in such a trial as they would have to take a chance that the sick children would receive a less effective therapy than what they would otherwise get. “It’s hard to [talk] about a therapy reduction,” he told this news organization.
Given that impediment, he agreed with Dr. Angoulvant that the current study and others like it may provide the best data available pointing to a treatment approach for MIS-C.
The study received an unrestricted grant from Pfizer. The French COVID-19 Paediatric Inflammation Consortium received an unrestricted grant from the Square Foundation (Grandir–Fonds de Solidarité pour L’Enfance). Dr. Angoulvant and Dr. Teachey have disclosed no relevant financial relationships.
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