IV immunoglobulin plus methylprednisolone linked to better fever course in MIS-C
Treatment with IV immunoglobulin plus methylprednisolone resulted in a more favorable fever course — and fewer complications — in children with COVID-19-related multisystem inflammatory syndrome than IV immunoglobulins alone.
“In April 2020, severe systemic hyperinflammatory disease was reported in children in Europe and the United States, occurring 2 to 4 weeks after SARS-CoV-2 infection,” François Angoulvant, MD, PhD, of Necker–Enfants Malades Hospital and the University of Paris, told Healio Rheumatology. “This novel entity, named Multisystem Inflammatory Syndrome in Children (MIS-C) is associated with a wide range of clinical features including persistent fever, digestive symptoms, rash, bilateral non-purulent conjunctivitis, muco-cutaneous inflammation signs and frequent cardiovascular involvement.”
“Many children with MIS-C have received empirical treatment based on Kawasaki disease guidelines, with intravenous immunoglobulin (IVIG) alone or combined with corticosteroids,” he added. “In the absence of evidence, a British Delphi consensus study proposed treating MIS-C with IVIG as initial therapy. However, this was based on expert advice, and no comparative study supported their conclusions. Overall, in the midst of a worldwide SARS-CoV-2 infection surge, MIS-C treatment driven by evidence-based medicine is still lacking and is urgently needed.”
To compare IVIG plus methylprednisolone to IVIG alone as an initial therapy for MIS-C, Angoulvant and colleagues conducted a retrospective cohort study using data from the French National Public Health Agency. In all, the researchers included 111 cases meeting the WHO definition of MIS-C in their analysis. Among the included patients, 34 received IVIG plus methylprednisolone and 72 were treated with IVIG alone. Five children did not receive either therapy. The study began April 1, 2020, with a follow-up period ending Jan. 6.
The primary outcome was persistence of fever 2 days after the introduction of initial therapy, or recrudescence of fever within 7 days, the latter of which as defined as treatment failure. Secondary outcomes included the use of a second-line therapy, hemodynamic support, acute left ventricular dysfunction following first-line therapy, and length of stay in a pediatric intensive care unit. The researchers’ primary analysis included propensity score matching with a minimum caliper of 0.1.
According to the researchers, 9% of children who received IVIG plus methylprednisolone failed to respond to treatment, compared with 51% of the IVIG monotherapy group. In all, initial therapy with IVIG plus methylprednisolone was associated with a lower risk for treatment failure, compared with IVIG alone, with an absolute risk difference of –0.28 (95% CI, –0.48 to –0.08) and an odds ratio of 0.25 (95% CI, 0.09-0.7).
In addition, IVIG plus methylprednisolone significantly associated with a lower risk for using a second-line therapy, compared with IVIG monotherapy, with an absolute risk difference of –0.22 (95% CI, –0.4 to –0.04) and an odds ratio of 0.19 (95% CI, 0.06-0.61).
The combination therapy group also demonstrated significantly lower risks for hemodynamic support, with an absolute risk difference of –0.17 (95% CI, –0.34 to –0.004) and an odds ratio of 0.21 (95% CI, 0.06-0.76); acute left ventricular dysfunction occurring after initial therapy, with absolute risk difference of –0.18 (95% CI, –0.35 to –0.01) and an odds ratio of 0.2 (95% CI, 0.06-0.66); and a longer pediatric intensive care unit duration, with a median stay of 4 versus 6 days, respectively (difference in days = –2.4 ; 95% CI, –4 to –0.7).
“Reducing the risk of these life-threatening acute complications is of critical interest,” Angoulvant said. “Our study provides evidence-based data showing the superiority of IVIG plus methylprednisolone vs. IVIG alone to treat MIS-C. Our findings should rapidly drive new guidelines to consider this therapeutic option as first-line therapy for MIS-C.”