Guidelines on the use of etanercept for juvenile idiopathic arthritis in Japan

Abstract

Etanercept is a dimeric fusion protein consisting of the extracellular domain of human tumor necrosis factor receptor II (TNFR II, molecular weight 75 kDa) coupled to the Fc region of human immunoglobulin (IgG1). It is produced by recombinant DNA technology by first introducing the gene into Chinese hamster ovarian cells and then purifying the protein from the culture supernatant. The mechanism of action of etanercept consists of binding to serum TNF-α and lymphotoxin (LT)-α (TNF-β), which prevents TNF-α and LT-α from binding to the TNF-α receptor on the plasma membrane of the target cell. Etanercept is currently approved for treating adult rheumatoid arthritis (RA) in more than 70 countries worldwide. In Japan, it was approved for this target group in January 2005. The USA and Europe were the first to approve entanercept for use in treating juvenile idiopathic arthritis (JIA), initially for the treatment of active polyarticular JIA in patients not responding to disease-modifying antirheumatic drugs (USA in May 1999, followed by the EU in February 2000). Thereafter, the drug received approval for the treatment of JIA in many other countries. In Japan, children who have been diagnosed and treated according to Yokota et al. (Mod Rheumatol 17:353–363, 2007), but who have responded poorly to treatment must move onto the next stage of treatment. Such treatments include biological drugs, which, however, should be used with strict adhesion to the indications and exclusion criteria and should be used, for the time being, only by physicians trained on how to use them. In Japan, etanercept was approved in July 2009 for use in children. Although this drug has brought about a revolutionary advance in the treatment of JIA, it is our task to maximize its therapeutic effects and minimize its toxic effects. The guidelines presented here define the indications, exclusion criteria, usage, and evaluation criteria of etanercept for the treatment of polyarticular JIA.

Appendices

Appendix 1

Diagnostic and classification criteria for juvenile idiopathic arthritis by ILAR [11]

Appendix 2

JIA core set (ACR Pedi)

The JIA core set is used to objectively assess response to treatment in patients with JIA. This method is used to make an overall evaluation using not only clinical and laboratory test findings, such as arthritis and erythrocyte sedimentation rate, but the Childhood Health Assessment Questionnaire (CHAQ) and the physician’s global assessment (visual analog scale) as well.

Variables included in the core set are presented below. Each of the following variables is scored.

• a) Physician’s global assessment

• b) Global assessment by patient or patient’s legal guardian

• c) Number of joints with active arthritis (joints with swelling not due to deformity, or joints with limited motion with pain or tenderness)

• d) Number of joints with limitation of motion with pain or tenderness

• e) CHAQ assessed by patient or patient’s legal guardian

• f) Erythrocyte sedimentation rate

Evaluation method: the score for each variable above is calculated to determine disease activity, and any change in the score from the baseline value is used for evaluation purposes.

Reference:

Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A. Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum. 1997; 40:1202–9

Appendix 3

Appraisal Committee Members of the Pediatric Rheumatology Association of Japan

Dr. Yukoh Aihara, Department of Pediatrics, Yokohama City University Medical Center; Dr. Kunihiko Akagi, Division of Infection, Immunology and Rheumatology, Kanagawa Children’s Medical Center; Dr. Kazunaga Agematsu, Department of Infectious Immunology, Graduate School of Medicine, Shinshu University; Professor Tadashi Ariga, Department of Pediatrics, Hokkaido University School of Medicine; Dr. Yasuji Inamo, Department of General Pediatrics, Nihon University Nerima-Hikarigaoka Hospital; Dr. Hiroyuki Imanaka, Department of Pediatrics, Faculty of Medicine, Kagoshima University; Dr. Naomi Iwata, Department of Infection and Immunology, Aichi Children’s Health and Medical Center; Dr. Tsutomu Ohishi, Division of Infection, immunology and Allergy, Saitama Childrens Medical Center; Dr. Hiroshi Kawai, Department of Infectious Diseases and Rheumatology, Nagano Children’s Hospital; Dr. Toshiyuki Kitoh, Department of Pediatrics, Aichi Medical University; Dr. Noriko Kinjyo, Department of Child Health and Welfare, Faculty of Medicine, University of the Ryukyus; Professor Yoichi Kohno, Department of Pediatrics, Graduate School of Medicine, Chiba University; Dr. Yukio Sakiyama, Department of Pediatrics, Youtei Clinic, Dr. Osamu Tatsuzawa, Division of Infectious Diseases and Rheumatology, National Center for Child Health and Development; Dr. Takeshi Noma, Department of Pediatrics, Graduate School of Medical Science, Kitasato University; Dr. Yukihiko Fujita, Department of Pediatrics, Nihon University Itabashi Hospital; Dr. Motoharu Maeda, Department of Pediatrics, Kyorin University School of Medicine; Dr. Kenji Masunaga, Division of Infectious Diseases Department of Infectious Medicine, Kurume University School of Medicine; Dr. Tadashi Matsubayashi, Department of Pediatrics, Seirei Hamamatsu General Hospital; Dr. Mari Miyoshi, Department of Infectious Diseases and Rheumatology, Hyogo Prefectural Kobe Children’s Hospital; Dr. Noriyuki Wada, Department of Pediatrics, Jikei University School of Medicine; Dr. Yasuyuki Wada, Department of Pediatrics, Kashiwa Hospital, Jikei University School of Medicine; Dr. Nobuo Watanabe, Kyorin University School of Medicine; Dr. Masashi Hokonohara, Kagoshima University; Dr. Masahiko Ohkuni, Nihon University