IVIG plus infliximab lessens need for additional therapy in MIS-C

Initial treatment with intravenous immunoglobulin (IVIG) plus infliximab resulted in less additional therapy in multisystem inflammatory syndrome in children (MIS-C) compared with IVIG alone, according to a recent study.

Using Research Electronic Data Capture tools hosted at the University of Colorado, Colorado, US, the researchers identified 72 children diagnosed with and treated for MIS-C based on CDC* criteria between April 1, 2020 and February 28, 2021. Participants were divided into two groups according to their initial therapy regimen with either IVIG 2 g/kg (maximum of 70 g) for 10–12 or 20–24 hours, depending on cardiac function and patient fluid status, plus infliximab 10 mg/kg (n=52, median age 9 years), or IVIG alone (n=20, median age 8 years). [Pediatrics 2021;148:e2021052702]

Twenty-nine patients required additional therapy after their initial treatment. The need for additional therapy was lower among those who received IVIG plus infliximab than IVIG alone (31.0 percent vs 65.0 percent; p=0.01).

The IVIG plus infliximab group also had a shorter duration of ICU stay than the IVIG alone group (median 1.8 vs 3.3 days; p=0.001).

Fewer patients on IVIG plus infliximab developed new or worsened left ventricle (LV) dysfunction (4.0 percent vs 20.0 percent; p=0.05) or required new vasoactive medication after 24 hours of treatment initiation (4.0 percent vs 15.0 percent; p=0.13) than those on IVIG alone.

Notably, those treated with IVIG plus infliximab compared with IVIG alone achieved a more rapid improvement in C-reactive protein (CRP) levels at ≥24 hours (median -46.0 percent vs 0.0 percent; p<0.001) and at ≥48 hours after treatment initiation (median -70.0 percent vs -5.0 percent; p<0.001).

“This suggests that a targeted antitumour necrosis factor approach is effective in reducing the inflammatory response represented by CRP, which is largely reflective of elevations in interleukin 6 (IL-6) levels, [and usually most patients with MIS-C have elevated IL-6 levels],” the researchers noted.

The rates of hospital admission, number of days to fever resolution, duration of vasoactive medication, or need for diuretics were comparable between the two treatment groups.

“In April 2020, MIS-C was first described in reports of children presenting with a severe multisystem hyperinflammatory illness temporally associated with preceding SARS-CoV-2 infection or exposure,” said the researchers. [Lancet 2020;395:1771-1778; BMJ 2020;369:m2094]

“Given the reported similarity in MIS-C to Kawasaki disease (KD), the approach to [the] treatment of MIS-C has been similar to treatment of KD … At our institution, high-risk patients with KD are routinely treated with IVIG plus infliximab, which has been shown to reduce [the] need for additional therapy and decrease treatment duration,” the researchers noted.

“[In conclusion,] patients with MIS-C initially treated with IVIG plus infliximab … were less likely to require additional therapy [compared with IVIG alone. Results also showed improvement in several outcomes, including] decreased ICU length of stay, decreased development of LV dysfunction, and more rapid decline in CRP levels,” said the researchers.

“[However,] potential risks of giving both IVIG and infliximab vs IVIG alone are unknown and should be specifically explored in further studies,” the researchers noted. “[Therefore,] future randomized controlled trials are necessary to confirm these findings and [also] to compare initial therapy with IVIG alone, IVIG plus infliximab, and IVIG plus corticosteroids.”