IVIG, Steroids for Multisystem Inflammatory Syndrome in Children Have Varying Outcomes

Despite an apparent benefit of intravenous immunoglobulin (IVIG) on early discharge, the likelihood of needing second-line treatment was 3 times higher in patients who initiated treatment with IVIG alone.

The use of intravenous immunoglobulin (IVIG), steroids, and their combination in multisystem inflammatory syndrome in children (MIS-C) may have varying outcomes, according to a study published in the European Journal of Pediatrics.

Researchers had previously established that steroids combined with IVIG might reduce the need for hemodynamic support and the duration of fever in MIS-C, but the certainty of this evidence was low. Very little data exist regarding optimal treatments for MIS-C, which is characterized by the dysregulated response of the immune system after SARS-CoV-2 infection, according to the study authors.

To better understand optimal treatments, investigators assessed children with MIS-C who were enrolled prospectively in the Epidemiological Study of COVID-19 in Children of the Spanish Society of Pediatrics (EPICO-AEP). Participants were diagnosed between March 1, 2020, and June 1, 2021.

IVIG dose was 2 g/kg and steroids were 1 to 2 mg/kg/day of methylprednisolone or its equivalent. Patients were discharged after clinical stability and fever resolution and researchers defined 3 transitions: initiation of treatment to hospital discharge (t1); initiation of treatment to second-line therapy (t2); and second-line therapy to hospital discharge (t3). For each transition, researchers estimated the time-to-event probability (discharge or second-line therapy) according to treatment initiation therapy (IVIG, steroids, or both).

Overall, 150 children with MIS-C were enrolled and only patients initially treated with steroids, IVIG, or a combination of the 2 were analyzed. In total, 62.1% of patients were admitted to a pediatric intensive care unit (PICU), 34.1% in the first period and 65.9% in the second period.

According to the study, 22.7% of patients were initially treated with steroids alone, 21.9% with IVIG alone, and 55.3% with IVIG plus steroids. Thirty-four of the 132 patients needed second-line treatment over time: 30% who had received steroids previously; 41.4% who had received IVIG; and 17.8% who had received both.

Additionally, 53% had persistent fever after 2 days of treatment. Of those, 61.4% did not receive a second-line treatment despite persistent fever and 67.4% were initially treated with IVIG plus steroids. In all these cases, fever resolved without additional treatment after 48 hours. Three patient deaths were reported (2.2%).

The probability of discharge and of needing second-line treatment was different according to treatment initiation. The probability of early discharge was 61% higher for patients who initiated treatment with IVIG than for those initiating with IVIG plus steroids, whereas no significant differences were observed between patients initiating with steroids versus IVIG plus steroids.

Despite this apparent benefit of IVIG on early discharge, the likelihood of needing second-line treatment was 3 times higher in patients who initiated treatment with IVIG than on those initiated with IVIG plus steroids. This was not observed in children who started treatment on steroids.

Patients treated with steroids or IVIG plus steroids had a similar probability of persistent fever after treatment initiation and patients treated with IVIG alone had a higher probability of persistent fever. When comparing patients treated initially with IVIG or steroids, those treated with IVIG had a 4 times greater probability of persistent fever after treatment initiation.

Based on these findings, the researchers concluded that each treatment has its own pros and cons according to different outcomes. Therefore, it is also important to consider the availability of each product and economic factors. The authors noted that clinical trials should thoroughly evaluate the efficacy and safety of the available treatments in short- and long-term outcomes.

REFERENCE

Tagarro A, Dominguez-Rodriguez S, Mesa J, et al. Treatments for multi-system inflammatory syndrome in children—discharge, fever, and second-line therapies. Eur J Pediatr. 2022 Oct. 25: 1-6. doi:10.1007/s00431-022-04649-8.