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21-06-2021 | Rheumatology | News | Article

Editor's pick

Studies evaluate effectiveness of IVIG, glucocorticoids for MIS-C

Claire Barnard

medwireNews: Two real-world studies published in The New England Journal of Medicine draw conflicting conclusions on the effectiveness of treatment regimens involving intravenous immunoglobulin (IVIG) and glucocorticoids for the treatment of multisystem inflammatory disease in children (MIS-C).

“Since the sudden emergence of [MIS-C] in April 2020 as a novel and severe presentation of coronavirus disease 2019 (Covid-19), nearly 4000 cases of MIS-C and 35 deaths have been reported in the United States and many more internationally,” says Roberta DeBiasi (Children’s National Hospital and Research Institute, Washington, DC, USA) in an editorial accompanying publication of the studies.

She adds that while “experts [have] achieved consensus about diagnostic criteria and the need to induce rapid immunomodulation aimed at limiting the course of the illness,” consensus on “specific immunomodulatory therapies has been more elusive,” with treatment including IVIG, glucocorticoids, and biologics “in various combinations, depending on the treating center.”

In the first study, the Overcoming COVID-19 investigators analyzed data from 103 patients with MIS-C who were given initial treatment with IVIG plus glucocorticoids at one of 58 US hospitals between March and October 2020, and the same number of propensity score-matched patients who were initially treated with IVIG alone. Patients were aged a median of approximately 8 years, and more than three-quarters had no pre-existing conditions.

In all, 17% of patients in the combination therapy group and 31% of those given IVIG alone experienced the composite endpoint of cardiac dysfunction on or after day 2, translating into a significant 44% reduced risk with the combination.

When components of the composite endpoint were considered separately, rates of left ventricular dysfunction (8 vs 17%) and shock resulting in the use of vasopressors (13 vs 24%) were significantly lower in the IVIG plus glucocorticoids group compared with the IVIG only group. Rates of adjunctive therapy use were also significantly lower in the combination group (34 vs 70%).

On the other hand, Adrienne Randolph (Boston Children’s Hospital, Massachusetts, USA) and co-investigators report that rates of persistent or recurrent fever and length of stay in the intensive care unit “were not clearly lower” among patients given IVIG plus glucocorticoids versus IVIG alone.

They conclude: “Until published data that define best practices are available, these data provide clinicians with additional evidence to guide treatment for MIS-C.”

In contrast to the Overcoming COVID-19 results, the authors of the second study found “no evidence that recovery from MIS-C differed” after initial treatment with IVIG plus glucocorticoids or either therapy alone.

Michael Levin (Imperial College London, UK) and colleagues from the BATS group evaluated the outcomes of 614 children with confirmed or suspected MIS-C who were treated at 81 hospitals across 34 countries in June 2020–February 2021. Patients received initial treatment with IVIG (n=246), glucocorticoids (n=99), a combination of both (n=208), other immunomodulators (n=22), or no immune-modulatory treatment (n=39).

The team reports that rates of the composite outcome of inotropic support or mechanical ventilation on day 2 or later or death were not significantly different among patients treated with IVIG plus glucocorticoids versus IVIG alone, nor among those given glucocorticoids versus IVIG, in a weighted analysis. Rates of this outcome in the combination, IVIG-only, and glucocorticoid-only groups were 31.1%, 20.9%, and 20.5%, respectively.

Similarly, Levin and team say that rates of the second primary outcome – reduction in disease severity as measured on an ordinal scale – were comparable in the three groups, as was the time to reduction in disease activity.

Editorialist Roberta DeBiasi asks: “What are possible reasons for these apparently disparate results and what do they mean for clinicians who are treating a critically ill child with MIS-C?”

She points out that the Overcoming COVID-19 and BATS cohorts “represent different patient populations” that could influence the response to immunomodulation, and discusses the possibility that “the dysregulated hyperimmune response of MIS-C could vary or change” according to the strain of SARS-CoV-2, given the difference in timing between the two studies.

And DeBiasi adds that “[s]ystematic and comprehensive long-term follow-up” for cardiac and noncardiac outcomes is needed to understand the long-term impact of different immunomodulatory therapies in patients with MIS-C.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

21 June 2021: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.

N Engl J Med 2021; doi:10.1056/NEJMoa2102605
N Engl J Med 2021; doi:10.1056/NEJMoa2102968
N Engl J Med 2021; doi:10.1056/NEJMe2108276

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