Rationale for use for monoclonal antibody and anti-cytokine therapy for multisystem inflammatory syndrome in children: A systematic review

Objective: To review systematically the rationale for choice and use of monoclonal antibody and anti-cytokine therapy in multisystem inflammatory syndrome in children. Study design: A systematic review was conducted using electronic databases (MEDLINE, Embase, Global Health, SCOPUS, and Web of Science) and preprint servers (MedRxiv and BioRxiv) between 01/01/2020 and 01/03/22. Studies were included if they had pediatric patients aged <21 years with multisystem inflammatory syndrome that had experienced the use of monoclonal antibodies and anti-cytokine therapy. Randomized controlled trials, cohort studies, case reports, case series and case-control studies were included. Results: Twenty observational studies with 726 patients were included. Anakinra, tocilizumab and infliximab were used in 9.9%, 6.9%, and 12.4% of the cases, respectively. The most common rationale for the initiation of emerging therapy for multisystem inflammatory syndrome in children was for patients who presented with severe disease or refractory to first line therapy. Infliximab tended to be used because of its precedence in managing intravenous immunoglobulin-resistant Kawasaki Disease. Conclusions: Use and choice of monoclonal antibody and anti-cytokine therapy seems to rely more on subjective clinician preferences than rigorous evidence-based studies. More studies exploring the exact pathogenesis of multisystem inflammatory syndrome in children are warranted to identify the key players of the cytokine storm that act as biological targets and their outcomes.