Glucocorticoids Alone Noninferior to Combination Therapy in Children With MIS-C

Initial treatment with glucocorticoids may be a safe and cost-effective alternative to immunoglobulin or combined therapy for multisystem inflammatory syndrome in children (MIS-C), according to study findings published in The Lancet.

Researchers conducted a propensity-weighted cohort study to compare the safety and efficacy of treatments for MIS-C.

Patients with MIS-C were placed in 3 cohorts: intravenous immunoglobulin alone, glucocorticoids alone, or intravenous immunoglobulin plus glucocorticoids. Longitudinal data included presenting features, demographics, laboratory findings, immunomodulatory and supportive treatments. In addition, duration of hospital stay, the need for organ support, and health status at the time of discharge were also recorded.

Primary outcomes included the need for inotropic or ventilator support on or after day 2, or death, and time to improvement on clinical severity scale. Secondary outcomes were immunomodulator escalation, coronary artery aneurysm occurrence, increase in cardiorespiratory supportive therapy after day 0, and therapeutic complications. 

A total of 2009 children (median age, 8.0 years; 59.8% boys) with MIS-C were included in the study.

No significant difference was found between treatment with glucocorticoids alone and intravenous immunoglobulin plus glucocorticoids; however, researchers noted a faster time to improvement for the combination-therapy group (hazard ratio [HR], 1.25; 95% CI, 1.05-1.48). Faster time to improvement was seen from days 5 to 7 of treatment and among patients who did not require intensive support at baseline. Moreover, the escalation of primary therapy and persistence of fever from day 2 was more common in patients who received treatment with glucocorticoids alone vs intravenous immunoglobulin plus glucocorticoids. 

Compared with patients who received intravenous immunoglobulin plus glucocorticoid therapy, those who did not receive immunomodulator therapy had substantially less derangement in laboratory markers of inflammation and organ dysfunction.

With regard to the first primary outcome (inotropic support or ventilation on day 2 or later, or death), the odds ratio for patients who received treatment with intravenous immunoglobulin plus glucocorticoids or glucocorticoids alone compared with intravenous immunoglobulins alone was 1.09 (95% CI, 0.75-1.58) and 0.93 (0.58-1.47), respectively. 

With regard to the second primary outcome (time to improvement on clinical severity scale), there was a slower improvement among those who received glucocorticoids alone compared with those who received immunoglobulin alone (HR, 0.84).

A subgroup analysis among children with severe disease compared with those who did not require intensive care showed that there was slower improvement among those receiving glucocorticoids alone compared with immunoglobulins alone (HR, 1.06; 95% CI, 0.75-1.49; P =.75). 

Regarding secondary outcomes in patients with reported echocardiograms, of 1918 patients, 236 (12.3%) had a coronary artery aneurysm at any time. Of note, most cases resolved during follow-up (n=182; 92.9%), with similar rates among all primary treatment groups. No statistical significance was found in incidence of coronary artery aneurysms between patients who received intravenous immunoglobulin vs those who received glucocorticoids alone. 

Limitations of the study included the exclusion of a large randomized controlled trial for definitive data, as well as selection bias from the voluntary inclusion of data, as it may not have been comprehensive of all cases of MIS-C from each site. 

“We did not find significant differences in outcome between treatment with glucocorticoids or intravenous immunoglobulin as single agents or between the single- agent and dual-agent primary treatments,” the study authors noted.

“Our findings suggest that glucocorticoids are not inferior to intravenous immunoglobulin or intravenous immunoglobulin plus glucocorticoids as primary treatment of MIS-C, and their wide availability and lower cost would support their choice as initial treatment for MIS-C,” they concluded.