title: Monoclonal antibody therapy for Kawasaki disease: a protocol for systematic reviews and meta-analysis.
abstract: BACKGROUND
  Kawasaki disease (KD) is a form of self-limiting vasculitis that causes coronary artery abnormality in children. Based on reports of elevated plasma level of cytokines such as tumor necrosis factor-α in KD patients, clinical trials of monoclonal antibodies that block cytokine cascades have been conducted. However, the studies have revealed contradictory results. The objective of this study is to examine the effectiveness of treatment with monoclonal antibodies for KD patients.
  
  
  METHODS
  Relevant randomized controlled trials (RCTs), cluster RCTs, quasi-RCTs, cross-over trials, and any observational studies (e.g., cohort studies, case-control studies, case series, and case reports) will be included to summarize available evidence both qualitatively and quantitatively. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and ICUSHI will be searched. We will assess coronary artery and treatment outcomes of the interventions. Two authors will independently screen studies for inclusion and consulting with a third author where necessary to resolve discrepancies. The risk of bias of included studies will be assessed using the Cochrane Collaboration risk of bias tool and quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Meta-analysis of the included studies will be conducted using fixed effects or random effects models depending on the degree of between-study heterogeneity. Results will be presented using risk ratios with 95 % confidence interval (CI) for dichotomous outcomes and standardized mean differences with 95 % CI for continuous outcomes.
  
  
  CONCLUSIONS
  This systematic review and meta-analysis protocol does not require ethical approval. We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals.
  
  
  BACKGROUND
  PROSPERO CRD42016033079 .
authors.affiliation: Division of Pediatric Emergency Medicine, Tokyo Metropolitan Children's Hospital, 2-8-29, Musasidai, Fuchu-shi, Tokyo, 183-8561, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nomura
authors.affiliation: Department of Pediatrics, Kawakita General Hospital, 1-7-3, Asagaya-kita, Suginami-ku, Tokyo, 166-0001, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Department of Health Policy, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Ota
authors.affiliation: Division of Cardiology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ono
authors.affiliation: Department of General Pediatrics and Interdisciplinary Medicine, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ishiguro
authors.affiliation: Division of Clinical Research Planning, Department of Development Strategy, Center for Clinical Research and Development, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan. torukoba@nifty.com.
authors.forename: Tohru
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006801:Humans; D015201:Meta-Analysis as Topic; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy*; D012107:Research Design; D000078202:Systematic Reviews as Topic
chemical_list: D000911:Antibodies, Monoclonal
keywords: Coronary artery abnormality; Kawasaki disease; Meta-analysis; Monoclonal antibody agents; Systematic review