Systematic Review of Adverse Events of IL-1 and IL-6 Inhibitor Use in Pediatrics

Abstract

Objective: Two, relatively new and potent, classes of biologicals are interleukin-6 (IL-6) and interleukin-1 (IL-1) inhibitors. As the use of these biologicals in children is more recent, the nature and incidence of adverse effects in the pediatric population are less well known. We systematically reviewed the available literature to elucidate the risks of IL-1 and IL-6 inhibitor use in the pediatric population.

Methods: A systematic literature search was conducted including English-language clinical studies of children who received IL-1 or IL-6 inhibitors for therapeutic purposes. Abstracts and full-text screening of manuscripts were carried out by 2 independent reviewers, based on predefined eligibility criteria. Any conflicts between the 2 reviewers were resolved by a third reviewer. Data extracted included characteristics such as intervention (drug, dose, method of administration, frequency), adverse events, and frequency of adverse events.

Results: A total of 2707 studies were screened and 38 studies were selected for inclusion. Of these 38 studies, 9 involved canakinumab, 12 involved anakinra, 2 involved rilonacept, 15 involved tocilizumab, and 1 involved an unspecified recombinant IL-6 antagonist. The most common adverse events included infection, local injection site reactions, headache, fever, arthralgia, and rash. There were 557 serious adverse events reported in 2208 patients (rate = 25%).

Conclusions: Risks of biological use should be considered alongside the immunosuppressive benefits when prescribing IL-1 and IL-6 inhibitors in the pediatric population. Few data were available on long-term follow-up of these patients.

Keywords: biological therapy; child; drug-related side effects and adverse reactions; interleukin 1 receptor antagonist protein; interleukin-1; interleukin-6; pediatrics.

Figure.

PRISMA diagram outlining study screening process.