Real-world Safety and Effectiveness of Infliximab in Pediatric Patients With Acute Kawasaki Disease

Abstract

Background: In 2015, infliximab was approved for the treatment of patients with intravenous immunoglobulin-refractory Kawasaki disease (KD) in Japan. However, limited real-world data exist on the usefulness of infliximab for acute KD patients. We conducted a postmarketing surveillance study in patients with acute KD refractory to conventional therapies to evaluate the safety (including any live vaccine-related infections) and the effectiveness of infliximab. Methods: This was a multicenter, prospective, open-label, single-cohort, observational study in patients with acute KD refractory to conventional therapy who were prescribed a single 5 mg/kg dose of infliximab. Safety and effectiveness of infliximab were evaluated at 1 month, and live vaccine-related infections were further observed until 6 months from KD onset. Effectiveness assessments included fever resolution rate, the incidence of coronary artery lesions and change in coronary diameter Z scores. Results: A total of 291 patients were enrolled, and all patients completed the study. Adverse drug reactions and serious adverse drug reactions were reported in 12.4% and 3.1% of patients, respectively. Live vaccine-related infections were not observed. In the 208 patients with effectiveness assessments, the fever resolution rate within 48 hours after infliximab infusion was 77.4% (95% confidence interval: 71.1–82.9). Median time until fever resolution was 16.6 hours. After infliximab administration, the incidence (at baseline: 10.9%; at the final observation point: 12.0%; maximum value: 14.6%) and severity of coronary artery lesions did not change notably. Conclusions: In this study, Infliximab for patients with acute KD refractory to conventional therapies was well tolerated and effective.

COVID‐19 and multisystem inflammatory syndrome in children: A systematic review and meta‐analysis

“…Tocilizumab, an IL‐6 receptor antagonist, and Anakinra, an IL‐1 receptor antagonist, have been used for the treatment of severe COVID‐19 in adults, although safety and efficacy has been controversial 51–54 . Infliximab, an anti‐human tumor necrosis factor‐α (TNF‐α) monoclonal antibody, is effective against several inflammatory diseases including KD thus maybe an interesting agent in the MIS‐C population 55,56 . Furthermore, remdesivir, which is a nucleoside analogue that inhibits viral RNA polymerases, has been shown to be associated with the clinical improvement in adults with COVID‐19 57–59 .…”

Increased Pentraxin 3 Levels Correlate With IVIG Responsiveness and Coronary Artery Aneurysm Formation in Kawasaki Disease

“…Prediction of CAL risk has become an important issue in KD because of recent advances in the therapeutic strategies available, such as prednisolone therapy ( 15) or treatment with a tumor necrosis factor-alpha antagonist (23), advances that enable stratification of the initial treatment for the patients with a high level of predicted risk. Thus, we carried out this collateral analysis to ascertain the diagnostic accuracy of PTX3, NT-proBNP and Presepsin in detecting CAL before the initial IVIG treatment.…”

Infliximab versus second intravenous immunoglobulin for treatment of resistant Kawasaki disease in the USA (KIDCARE): a randomised, multicentre comparative effectiveness trial

“…21 In an open-label, observational study from Japan of infliximab (5 mg/kg) for IVIG resistance, 291 patients were enrolled. 22 The majority had already received a second IVIG dose or other therapies and the authors concluded that the safety profile was excellent. Three small, random ised clinical trials of second IVIG versus infliximab (5 mg/kg) enrolling between 24 to 43 subjects have been reported from the USA, 7 Korea, 23 and Japan.…”