IVIG Compared With IVIG Plus Infliximab in Multisystem Inflammatory Syndrome in Children

Cole, Lyndsey D; Osborne, Christina; Silveira, Lori; Rao, Suchitra; Lockwood, Justin; Kunkel, Megan; Miyagami, Taiju; Heizer, Heather; Anderson, Marsha S.; Jone, Pei‐Ni; Dominguez, Samuel R.

doi:10.1542/peds.2021-052702

Cited by 23 publications

(23 citation statements)

References 29 publications

(38 reference statements)

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“…Most patients with MIS-C have been treated with intravenous immunoglobulin (IVIG), alone or in combination with glucocorticoids ( 10 – 12 ). In severe or refractory cases, particularly when myocarditis was present, biologic response modifiers, particularly tumor necrosis factor or interleukin-1 inhibitors, were given ( 13 , 14 ). However, despite the publication of various therapeutic recommendations ( 15 – 17 ) the treatment of MIS-C remains empirical and little information is available about the effectiveness of proposed strategies.…”

Section: Introductionmentioning

confidence: 99%

Timely Recognition and Early Multi-Step Antinflammatory Therapy May Prevent ICU Admission of Patients With MIS-C: Proposal for a Severity Score

et al. 2021

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In this observational study, we report the clinical, therapeutics and outcome features of 23 patients with multisystem inflammatory syndrome (MIS-C) who have been treated in Gaslini Children Hospital (Genoa, Italy) with a multistep antinflammatory treatment protocol, based on disease severity at admission. Patients were initially assigned to four severity classes on admission and treated accordingly. The therapeutic options ranged from IV immunoglobulin alone to a combination of IVIG plus pulses of methylprednisolone plus anakinra for patients with marked cardiac function impairment or signs of macrophage activation syndrome, with rapid treatment escalation in case of inadequate therapeutic response. With the application of this therapeutic strategy, no patient required admission to Intensive Care Unit (ICU) or invasive mechanical ventilation, and no inotropic drugs administration was required. Early aggressive treatment of MIS-C, with therapeutic interventions modulated based on the severity of clinical manifestations may help to prevent the progression of the inflammatory process and to avoid the need of admission to the ICU. A timely intervention with anti-IL-1 blockers can play a pivotal role in very severe patients that are at risk to have an incomplete response to immunoglobulins and steroids.

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Section: Introductionmentioning

confidence: 99%

Timely Recognition and Early Multi-Step Antinflammatory Therapy May Prevent ICU Admission of Patients With MIS-C: Proposal for a Severity Score

et al. 2021

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“…Almost 15–20% patients with MIS-C were treated with biopharmaceuticals, including IL-1R, IL-6, and TNF-α antagonist [ [6] , [7] , [8] , [9] ] as second-line therapies subsequent to IVIG. As in previous reports [ 33 , 34 ], the patient who was refractory to IVIG therapy responded to infliximab, which has been used successfully to treat IVIG refractory KD, without adverse effects.…”

Section: Discussionmentioning

confidence: 55%

“…TNF-α appears to play a key role in the pathogenesis of both KD and MIS-C [29,30]. Indeed, infliximab which is a chimeric monoclonal antibody that binds TNF-α and inhibits its downstream proinflammatory effects, has been successfully used to treat IVIG refractory KD [31] and MIS-C [32,33]. Cole, et al [32] reported that patients with severe MIS-C had better J o u r n a l P r e -p r o o f outcomes when they were initially treated with IVIG plus infliximab compared with IVIG alone.…”

Section: Hyperferritinemia In This Case Was Distinct From Previously Reported Mis-c Cases Inmentioning

confidence: 99%

“…Cole, et al [32] reported that patients with severe MIS-C had better J o u r n a l P r e -p r o o f outcomes when they were initially treated with IVIG plus infliximab compared with IVIG alone. Abdel-Haq, et al [33] reported that patients with severe MIS-C who required critical care had higher serum ferritin levels and required second-line infliximab therapy. Therefore, we hypothesize that early intervention with adjunctive infliximab for MIS-C patients with hyperferritinemia, such as this case, may induce more rapid resolution of inflammation and improve outcome.…”

Section: Hyperferritinemia In This Case Was Distinct From Previously Reported Mis-c Cases Inmentioning

confidence: 99%

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Infliximab treatment for refractory COVID-19-associated multisystem inflammatory syndrome in a Japanese child

Yamaguchi

Takasawa

Irabu

et al. 2022

Journal of Infection and Chemotherapy

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Patients with multisystem inflammatory syndrome in children (MIS-C) can develop clinical features resembling Kawasaki disease (KD). A full picture of MIS-C in East Asia which has higher incidence of KD than other regions remains unclear. We report on a 15-year-old Japanese boy with refractory MIS-C who was successfully treated with infliximab. A Japanese boy who was diagnosed with coronavirus disease 2019 (COVID-19) before a month developed MIS-C with fulfilling six principal symptoms of KD. Laboratory data showed extreme hyperferritinemia (11,404 ng/mL), besides lymphopenia and thrombocytopenia. The patient was refractory to initial therapy with intravenous immunoglobulin (IVIG; 2 g/kg), aspirin, and prednisolone. He was therefore administered a second IVIG (2 g/kg) and infliximab (5 mg/kg) on days 7 and 8 from the onset of fever, respectively, which resulted in an improvement of clinical symptoms. Only four Japanese cases with MIS-C were reported and all of them were responsive to IVIG. The hyperferritinemia in this case was distinctive from previously reported MIS-C cases in Japan and other cohorts and may be associated with refractoriness to IVIG therapy. Marked elevation of circulating ferritin levels is known to be induced by tumor necrosis factor-α, which plays a key role in the pathogenesis of both KD and MIS-C. Thus, for MIS-C patients with hyperferritinemia, early intervention with adjunctive infliximab may induce a more rapid resolution of inflammation and improve outcome. Because MIS-C may be heterogeneous with respect to immunopathology, genetic background, clinical phenotypes and response to therapies, optimized treatment strategies according to immunopathogenesis are required.

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“…With the widespread occurrence of MIS-C, there is a need for affordable treatment. Anti-inflammatory drugs other than GCS are not commonly used in children-the majority of pediatricians are not accustomed to ordering them [25]. As the disease is acute, children with MIS-C are treated in general hospitals, not only in rheumatology departments.…”

Section: Discussionmentioning

confidence: 99%

The Role of Glucocorticoids in the Treatment of Multisystem Inflammatory Syndrome (MIS-C)—Data from POLISH MIS-C Registry

et al. 2022

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Background: Multisystem inflammatory syndrome (MIS-C) is a condition related to COVID-19. It’s most significant feature is cardiac involvement. Methods: We have analyzed data from 42 hospitals in the Polish MIS-C Registry. To compare the effect of GCS on fever, we formed two groups: the first treated with IVIG and the second treated with IVIG+GCS. Results: There were 111 boys and 56 girls; the mean age was 8.57 years. All the patients were treated with IVIG: 76 patients with IVIG only, and 91 patients with IVIG+GCS. There were no statistically significant differences between the groups regarding age, gender, BMI, or inflammatory markers. Methylprednisolone was the most common drug (80%). Echocardiographic abnormalities on admission were more prevalent in the IVIG+GCS group. Mean time from IVIG infusion to subsidence of fever was 1.1 days, and 1.5 for those in the IVIG+GCS group. Conclusions: GCS are commonly used in the treatment of MIS-C patients in Poland. Various GCS regimens are used, from a single dose to a month-long therapy. Children with lower lymphocyte levels and cardiac abnormalities on an echocardiographic examination performed on admission were more likely to receive GCS+IVIG. The effect of GCS is difficult to access as patients were not randomly assigned to receive the treatment.

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IVIG Compared With IVIG Plus Infliximab in Multisystem Inflammatory Syndrome in Children

Cited by 23 publications

References 29 publications

Timely Recognition and Early Multi-Step Antinflammatory Therapy May Prevent ICU Admission of Patients With MIS-C: Proposal for a Severity Score

Timely Recognition and Early Multi-Step Antinflammatory Therapy May Prevent ICU Admission of Patients With MIS-C: Proposal for a Severity Score

Infliximab treatment for refractory COVID-19-associated multisystem inflammatory syndrome in a Japanese child

The Role of Glucocorticoids in the Treatment of Multisystem Inflammatory Syndrome (MIS-C)—Data from POLISH MIS-C Registry

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