Infliximab infusions proven safe, effective in paediatric patients with acute Kawasaki disease

A single infusion of infliximab effectively resolves fever in paediatric patients with acute Kawasaki disease (KD) refractory to conventional therapies, a Japan study performed in the real-world clinical setting has shown. In addition, it is well tolerated, with no new safety concerns seen.

Patients with acute KD in this multicentre, prospective, open-label, single-cohort, observational study received a single 5-mg/kg dose of infliximab. The researchers evaluated safety and effectiveness of infliximab infusions at 1 month and further observed live vaccine-related infections until 6 months from KD onset. Outcome measures included fever resolution rate, incidence of coronary artery lesions and change in coronary diameter Z scores.

All of the 291 patients with acute KD completed the study, of whom 12.4 percent and 3.1 percent reported adverse drug reactions (ADRs) and serious ADRs, respectively. No live vaccine-related infections were observed. [Pediatr Infect Dis J 2020;39:41-47]

Fever resolution rate within 48 hours following infliximab infusion was 77.4 percent (95 percent confidence interval, 71.1–82.9) in the 208 patients with effectiveness assessments. Median time until fever resolution stood at 16.6 hours.

No notable change was observed in the incidence (baseline: 10.9 percent; final observation point: 12.0 percent; maximum value, 14.6 percent) and severity of coronary artery lesions after infliximab administration.

“The results of this prospective postmarketing surveillance study in patients with acute KD refractory to conventional therapies in Japan demonstrated that a single infusion of infliximab was well tolerated and effective in fever resolution,” the researchers said. “No new safety concerns were reported.”

The safety profile of infliximab in this study was consistent with that of clinical studies from Japan, US and Korea in similar patient populations of KD treated with infliximab. [J Pediatr 2008;153:833-838; Korean Circ J 2010;40:334-338; Lancet 2014;383:1731-1738; Pediatr Infect Dis J 2016;35:457-459; J Pediatr 2018;195:115-120.e3; Sci Rep 2018;8:1994]

Furthermore, serious ADRs occurred more frequently (3/17; 17.6 percent) among infants who comprised only 5.8 percent of the patient population.

“Because of the limited number of infants with KD in this study, further studies are required to confirm this serious ADR incidence rate,” the researchers said. “Therefore, paediatricians should consider the overall risks and benefits of infliximab before treating infants.”

The present study had certain limitations. Because of its observational design, this study did not include a control or comparison group. Patient selection was also less stringent, particularly about previous and concomitant medications, since it was carried out in the real-world clinical setting. Moreover, race bias was not accounted for, and echocardiography assessment was not centralized.

“Overall, future prospective randomized studies are needed to determine the appropriate treatment for patients with refractory KD,” the researchers noted.

Infliximab was approved in 2015 for the treatment of patients with intravenous immunoglobulin-refractory KD in Japan, but there was limited real-world data on its usefulness for acute KD patients, according to the researchers.