今日の臨床サポート

若年性特発性関節炎(小児科)

著者: 佐藤智 埼玉県立小児医療センター 感染免疫・アレルギー科

監修: 渡辺博 帝京大学老人保健センター

著者校正/監修レビュー済:2021/02/10
参考ガイドライン:
  1. 日本リウマチ学会:若年性特発性関節炎 初期診療の手引き2015
患者向け説明資料

概要・推奨   

  1. JIAの定義・分類は、国際リウマチ学会(International League of Associations for Rheumatology、ILAR)による分類案が用いられる(推奨度2)。
  1. 関節MRIは、進行中の滑膜炎を最も鋭敏に検出する画像検査法であり、JIAの診断、重症度評価、治療モニタリング等に有用である(推奨度2)。
  1. 全身型JIAの診断は臨床症状と除外診断で行われる。ILAR分類では関節炎と発熱が両方揃っていることを重視しており、特に関節症状がなく全身性炎症所見のみがみられる場合には、鑑別診断はしばしば困難である(推奨度2)。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧に
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
佐藤智 : 未申告[2021年]
監修:渡辺博 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 若年性特発性関節炎(JIA)とは、16歳未満の小児に発症する原因不明の慢性関節炎である。
  1. 2001年の国際分類[1]では、表に示すように7亜型に分類されている。発症から6カ月間の経過で亜型分類を行う。
  1. 関節炎は少なくとも6週間持続することが必要で、他の疾患を除外して診断される。
  1. 全身型は、2週間以上持続する発熱(うち3日間は連続する)と1カ所以上の関節炎、リウマトイド疹(搔痒を伴わない紅斑)を主徴とし、しばしば関節外症状(リンパ節腫脹、肝脾腫、心膜炎)を伴う。
  1. 少関節型は、4カ所以下の関節炎で、6歳以下の女児に多い。関節予後はよいが、抗核抗体陽性例は虹彩毛様体炎の合併率が高い。
  1. 多関節型は、5カ所以上の関節炎で、リウマチ因子(RF)が陽性か陰性かによってさらに分類される。
  1. RF陽性多関節型は、HLA-DR4陽性の年長女児に多く、成人の関節リウマチが小児期に発症したものと考えられる。早期に骨・関節障害を生じ、関節予後が悪い例が多い。
  1. RF陰性多関節型は、女児に多いがどの年齢にもみられる。関節予後はさまざまである。
  1. 付着部炎関連関節炎は、主に下肢の少関節炎でHLA-B27陽性の年長男児に多い。足底筋膜の踵骨への付着部やアキレス腱の踵骨への付着部が好発部位である。
  1. 検査所見は、赤沈亢進やCRP陽性などの非特異的炎症反応を呈する。欧米ではRF陽性は少数であるが、わが国では比較的RF陽性例を認める。抗核抗体も必ずしも陽性にならない。骨関節X線では早期病変を検出できず、MRIもしくは関節エコー検査による滑膜炎の検出が最も鋭敏である。
 
JIA患者の膝関節Gd造影MRI像

輝度の高い滑膜が炎症を反映している。

 
RF陽性多関節型JIA女児における単純X線像の変化

a:発症時。b:4年後のX線像。十分量のステロイド治療を行っていたにもかかわらず、DIP・PIP・MP関節の軟骨の消失を伴う破壊性変化、手根骨の破壊と癒合がみられる。

 
  1. 有病率・発症率:報告により差があるものの、わが国における有病率は10人/10万人の小児、発症率は1人/10万人の小児と推定されている[2]
  1. 男女比は全体で男:女=1:2~3とされているが、病型により異なる。全身型は男女比ほぼ1:1である。
  1. 全身型若年性特発性関節炎は、指定難病であり、重症例などは、申請し認定されると保険料の自己負担分の一部が公費負担として助成される。([平成27年1月施行])
  1.  難病法に基づく医療費助成制度 
 
  1. JIAの定義・分類は、国際リウマチ学会(International League of Associations for Rheumatology、ILAR)による分類案が用いられる(推奨度2、OG)。
  1. 小児の慢性関節炎については用語や分類方法について複数の基準が用いられてきた。1970年代にはAmerican College of Rheumatology(ACR)によるJuvenile Rheumatoid Arthritis(JRA)の分類、およびEuropean League Against Rheumatism(EULAR)によりJuvenile Chronic Arthritis(JCA)の分類が提案され、前者は主に米国や日本、後者は主に欧州で用いられた。
  1. これらの分類基準間の不一致から生じる混乱に対し、ILARによって新たな分類案が作成され、疾患名もJIAと改められた[3]。この分類案では、JIAの一般的な定義として「16歳未満に発症し、他の疾患が除外された、6週間以上持続する関節炎」と記載され、7つのカテゴリーそれぞれに定義がつけられている。このうち乾癬関節炎と付着部関連関節炎は背景となる疾患(すなわち乾癬、付着部炎)が存在する「症候性関節炎」であり、本稿では診断、治療に関する記述を省略した。従来のACRやEULARの分類で診断していた患者をILAR分類で改めて分類すると、どのカテゴリーにも入らない、あるいは複数のカテゴリーに入るため“undifferentiated”とされる症例が多いという報告がみられており、これに対して2001年の改訂版では、乾癬の診断における皮膚科医の関与やHLA-27関連疾患の家族歴の扱い等が改められている[1]
 
  1. 関節MRIは、進行中の滑膜炎を最も鋭敏に検出する画像検査法であり、JIAの診断、重症度評価、治療モニタリング等に有用である(推奨度2、O)。
  1. JIAにおいて病態の中心になるのは滑膜の炎症であり、MRIは他の方法に比べ卓越した感度で滑膜炎を検出することができる。肥厚した滑膜はT1強調画像で低信号に描出され、またT2強調画像では、活動性の高い滑膜炎は高信号で描出される。関節液との区別がつきにくい場合、造影剤を用いることでより鮮明となる。<図表>
  1. 骨髄浮腫(柱状骨内部にみられる、境界不鮮明な水分含有量の多い部位)は、成人の関節リウマチではびらん性関節破壊の予測因子になることが示されている。この変化はMRIでのみ捉えることが可能である。骨のびらん性変化や軟骨の破壊性変化も容易に捉えることができるなど、JIAの画像検査においてMRIには多くの利点がある。欠点としては高価である、長時間かかるため小児では鎮静が必要である、造影剤アレルギーのリスク、1回につき1つの関節しか評価できない――などの点が挙げられる[4]
問診・診察のポイント  
関節の診察:
  1. 関節症状を訴える患者を診察する際、それが関節炎であるかどうか、罹患関節は何カ所か、固定性か移動性か、を明らかにする必要がある。

今なら12か月分の料金で14ヶ月利用できます(個人契約、期間限定キャンペーン)

11月30日(火)までにお申込みいただくと、
通常12ヵ月の使用期間が2ヶ月延長となり、14ヵ月ご利用いただけるようになります。

詳しくはクリック
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Ross E Petty, Taunton R Southwood, Prudence Manners, John Baum, David N Glass, Jose Goldenberg, Xiaohu He, Jose Maldonado-Cocco, Javier Orozco-Alcala, Anne-Marie Prieur, Maria E Suarez-Almazor, Patricia Woo, International League of Associations for Rheumatology
雑誌名: J Rheumatol. 2004 Feb;31(2):390-2.
Abstract/Text
PMID 14760812  J Rheumatol. 2004 Feb;31(2):390-2.
著者: R E Petty, T R Southwood, J Baum, E Bhettay, D N Glass, P Manners, J Maldonado-Cocco, M Suarez-Almazor, J Orozco-Alcala, A M Prieur
雑誌名: J Rheumatol. 1998 Oct;25(10):1991-4.
Abstract/Text
PMID 9779856  J Rheumatol. 1998 Oct;25(10):1991-4.
著者: Maria Beatrice Damasio, Clara Malattia, Alberto Martini, Paolo Tomà
雑誌名: Pediatr Radiol. 2010 Jun;40(6):985-98. doi: 10.1007/s00247-010-1612-z. Epub 2010 Apr 30.
Abstract/Text Juvenile idiopathic arthritis (JIA) represents a group of heterogeneous diseases characterized by a chronic inflammatory process primarily targeting the synovial membrane. A persistent synovitis is associated with an increased risk of osteocartilaginous damage.With the advent of effective structure-modifying treatment for JIA, it may be possible to significantly reduce or even completely prevent structural damage and associated functional disability. The trend towards early suppression of inflammation, in order to prevent erosive disease, shifts the emphasis away from conventional radiographic detectable structural damage to the slightest traces of early joint damage, and drives the need for alternative imaging techniques more sensitive in detecting early signs of disease activity and damage. In this regard MRI and US are playing an increasing role in the evaluation of arthritic joints.This article will review the key aspects of the current status and recent important advances of imaging techniques available to investigate the child with rheumatic disease, briefly discussing conventional radiography, and particularly focusing on MRI and US. In this era of advancing imaging technology, knowledge of the relative values of available imaging techniques is necessary to optimize the management of children with JIA.

PMID 20432018  Pediatr Radiol. 2010 Jun;40(6):985-98. doi: 10.1007/s00・・・
著者: K Martin, E G Davies, J S Axford
雑誌名: Ann Rheum Dis. 1994 Jul;53(7):429-33.
Abstract/Text We have described a child with systemic onset juvenile chronic arthritis who presented initially with fever of unknown origin. Treatment of a presumed infection led to a severe allergic response with Stevens-Johnson syndrome, renal failure and DIC. This reaction obscured the features of the underlying disease and delayed the diagnosis.

PMID 7944613  Ann Rheum Dis. 1994 Jul;53(7):429-33.
著者: R Mouy, J L Stephan, P Pillet, E Haddad, P Hubert, A M Prieur
雑誌名: J Pediatr. 1996 Nov;129(5):750-4.
Abstract/Text OBJECTIVES: To evaluate the efficacy of cyclosporine A in the treatment of macrophage activation syndrome (MAS) occurring in children with juvenile arthritis.
STUDY DESIGN: MAS developed in two boys and three girls with systemic juvenile arthritis (four) and polyarticular juvenile arthritis (one). In three children whose condition was life-threatening, increased parenteral administration of corticosteroids failed to improve their condition; therefore cyclosporine A (2 to 5 mg/kg per day) was added. In two other patients with less severe clinical manifestations, cyclosporine A alone (2 to 8 mg/kg per day) was given.
RESULTS: After the introduction of cyclosporine A, rapid improvement was obtained in all patients and apyrexia occurred within 24 to 48 hours. The biologic abnormalities disappeared more slowly (up to 5 weeks for liver enzymes).
CONCLUSIONS: These observations underline the usefulness of cyclosporine A in this complication. The use of this drug may circumvent the need for increased doses of corticosteroids in some patients. The mechanism of action of cyclosporine A remains speculative, but these results indicate indirectly that T-helper lymphocytes may play a role in the pathogenesis of MAS.

PMID 8917244  J Pediatr. 1996 Nov;129(5):750-4.
著者: E H Giannini, G D Cawkwell
雑誌名: Pediatr Clin North Am. 1995 Oct;42(5):1099-125.
Abstract/Text Rheumatology made its debut as a legitimate subspecialty of pediatrics sometime in the 1940s in Europe, and in the 1970s in North America. Therapy of juvenile rheumatoid arthritis has evolved from salicylates and gold injections to newer, less toxic nonsteroidal anti-inflammatory drugs and methotrexate. Corticosteroids remain as important drugs when life-threatening complications or blinding iridocyclitis develop. Immune response modifiers and gene therapies offer considerable potential for eventually halting or curing the disease but have yet to make a substantial impact on therapy. Methods for the correct conduct and interpretation of data from clinical trials are discussed.

PMID 7567188  Pediatr Clin North Am. 1995 Oct;42(5):1099-125.
著者: Philip J Hashkes, Ronald M Laxer
雑誌名: JAMA. 2005 Oct 5;294(13):1671-84. doi: 10.1001/jama.294.13.1671.
Abstract/Text CONTEXT: The treatment of juvenile idiopathic arthritis (JIA) has changed markedly in the last 15 years. Many children with JIA are not treated by pediatric rheumatologists.
OBJECTIVE: To review the best evidence for the treatment of JIA.
DATA SOURCES: English-language trials of JIA between 1966 and 2005 were searched using MEDLINE, EMBASE, the Cochrane database, and abstracts from recent rheumatology and pediatric scientific meetings.
STUDY SELECTION: Randomized controlled trials and open studies including at least 10 patients for medications without controlled trials.
DATA EXTRACTION: For studies after 1997, the American College of Rheumatology Pediatric 30 outcome measure was used to define patients as responders. For older studies, the primary response outcome measure defined by the authors was used.
DATA SYNTHESIS: Thirty-four controlled studies were identified. Nonsteroidal anti-inflammatory drugs are effective only for a minority of patients, mainly those with oligoarthritis. Intra-articular corticosteroid injections are very effective for oligoarthritis. Methotrexate is effective for the treatment of extended oligoarthritis and polyarthritis and less effective for systemic arthritis. Sulfasalazine and leflunomide may be alternatives to methotrexate. Antitumor necrosis factor medications are highly effective for polyarticular course JIA not responsive to methotrexate but are less effective in systemic arthritis. There is a lack of evidence for the optimal treatment of systemic and enthesitis-related arthritis.
CONCLUSIONS: Despite many advances in the treatment of JIA, there is still a lack of evidence for treatment of several disease subtypes. The treatment plan needs to be individualized based on the JIA subtype.

PMID 16204667  JAMA. 2005 Oct 5;294(13):1671-84. doi: 10.1001/jama.294・・・
著者: A O Adebajo, M A Hall
雑誌名: Br J Rheumatol. 1998 Nov;37(11):1240-2.
Abstract/Text An open prospective study using i.v. methylprednisolone in children with juvenile chronic arthritis (JCA) who had had a systemic exacerbation of disease is described. Eighteen children aged from 3 to 14 yr and 9 months (mean 9.7 yr) were treated. Ten patients (55%) had a loss of all systemic features 1 month after the pulse, and eight (45%) had a reduction in the active joint count. At this time, five of the patients on oral prednisolone had achieved a reduction in dosage. Also at 1 month, a reduction in erythrocyte sedimentation rate was observed in 11 patients (61%) and of C-reactive protein in 11 of 16 (72%). Altogether, 13 patients (72%) had a good response, while a further three (16%) went into remission. Our conclusions are that pulse methylprednisolone provides good short-term benefit in patients with systemic-onset JCA; no serious side-effects were noted. Further long-term studies are warranted.

PMID 9851278  Br J Rheumatol. 1998 Nov;37(11):1240-2.
著者: Philip Kahn
雑誌名: Bull NYU Hosp Jt Dis. 2011;69(3):264-76.
Abstract/Text Juvenile idiopathic arthritis (JIA) consists of a collection of all forms of chronic arthritis in childhood with no apparent cause. JIA is the most common rheumatic disease in children and may result in significant pain, joint deformity, and growth impairment, with persistence of active arthritis into adulthood. The extra-articular features of JIA, such as anterior uveitis or macrophage activation syndrome, are often the greater focus of therapy. Prior to the mid 1990s, the therapeutic armamentarium for JIA was more limited, utilizing non-specific agents, many with significant adverse effects. In the current era of target-specific biologic therapy, it is possible to better tailor therapy for patients. Through continued translational research and clinical trials, the biology mediating disease is better understood, and there is the hope of safer, more effective medicine and potential cure. This review will outline the clinical features of JIA as well as provide the latest updates in current and future pharmacotherapy.

PMID 22035441  Bull NYU Hosp Jt Dis. 2011;69(3):264-76.
著者: E H Giannini, J T Cassidy, E J Brewer, A Shaikov, A Maximov, N Kuzmina
雑誌名: Semin Arthritis Rheum. 1993 Aug;23(1):34-46.
Abstract/Text Results from three randomized placebo-controlled trials were combined in a meta-analysis to compare the clinical utility of four advanced drug therapy agents used to treat juvenile rheumatoid arthritis (JRA): D-penicillamine (10 mg/kg/d), hydroxychloroquine (6 mg/kg/d), auranofin (oral gold, 0.15 to 0.20 mg/kg/d), and two low dose levels of methotrexate [5MTX, 5 mg/M2/wk; 10MTX, 10 mg/M2/wk]. A total of 520 children with JRA were enrolled into these trials. Only 10MTX resulted in significantly greater improvement than placebo in variables that assess effectiveness: physician's global assessment, a composite index, and erythrocyte sedimentation rate. Treatment effect sizes were the largest in the 10MTX group for all articular disease indices. The short-term safety profiles were similar across all treatment groups. It is concluded that the current trend among pediatric rheumatologists to use oral methotrexate as the first advanced drug therapy in JRA is appropriate and that the minimum effective dose is 10 mg/M2/wk.

PMID 8235664  Semin Arthritis Rheum. 1993 Aug;23(1):34-46.
著者: E H Giannini, E J Brewer, N Kuzmina, A Shaikov, A Maximov, I Vorontsov, C W Fink, A J Newman, J T Cassidy, L S Zemel
雑誌名: N Engl J Med. 1992 Apr 16;326(16):1043-9. doi: 10.1056/NEJM199204163261602.
Abstract/Text BACKGROUND: The antimetabolite methotrexate has been shown in placebo-controlled trials to be effective in adults with rheumatoid arthritis. Methotrexate may also be effective in children with resistant juvenile rheumatoid arthritis, but the supporting data are from uncontrolled trials.
METHODS: Centers in the United States and the Soviet Union participated in this randomized, controlled, double-blind trial designed to evaluate the effectiveness and safety of orally administered methotrexate. Patients received one of the following treatments each week for six months: 10 mg of methotrexate per square meter of body-surface area (low dose), 5 mg of methotrexate per square meter (very low dose), or placebo. The use of prednisone (less than or equal to 10 mg per day) and two nonsteroidal antiinflammatory drugs was also allowed.
RESULTS: The 127 children (mean age, 10.1 years) had a mean duration of disease of 5.1 years; 114 qualified for the analysis of efficacy. According to a composite index of several response variables, 63 percent of the children who received low-dose methotrexate improved, as compared with 32 percent of those in the very-low-dose group and 36 percent of those in the placebo group (P = 0.013). As compared with the placebo group, the low-dose group also had significantly larger mean reductions from base line in the number of joints with pain on motion (-11.0 vs. -7.1), the pain-severity score (-19 vs. -11.5), the number of joints with limited motion (-5.4 vs. -0.7), and the erythrocyte sedimentation rate (-19.0 vs. -6 mm per hour). In the methotrexate groups only three children had the drug discontinued because of mild-to-moderate side effects; none had severe toxicity.
CONCLUSIONS: Methotrexate given weekly in low doses is an effective treatment for children with resistant juvenile rheumatoid arthritis, and at least in the short term this regimen is safe.

PMID 1549149  N Engl J Med. 1992 Apr 16;326(16):1043-9. doi: 10.1056/・・・
著者: Masaaki Mori, Takuya Naruto, Tomoyuki Imagawa, Takuji Murata, Syuji Takei, Minako Tomiita, Yasuhiko Itoh, Satoshi Fujikawa, Shumpei Yokota
雑誌名: Mod Rheumatol. 2009;19(1):1-11. doi: 10.1007/s10165-008-0123-3. Epub 2008 Sep 25.
Abstract/Text Methotrexate (MTX), the primary treatment for the articular-type juvenile idiopathic arthritis (JIA), is effective and brings about radiological improvement. Patient compliance is good, and it is recognized that its known side effects, namely, disruption of liver function and induction of pulmonary lesions, are unlikely to be severe at the low MTX doses that are administered. In Japan, MTX was granted approval in 1999 by the then Ministry of Health and Welfare specifically for treating rheumatoid arthritis in adult patients, allowing it be generally used in medical institutions for patients having National Health Insurance. However, in the pediatric field, its use outside the indications has so far been unavoidable, and has been left to the discretion of the physician. Finally, at the present conference, expansion of the indications of MTX for JIA was approved in Japan. It is noteworthy that this expansion of indications was achieved without requiring clinical trials on children sponsored by the pharmaceutical company: it was achieved rather by collecting necessary information through ongoing efforts (including collection and analysis of information about approval status in foreign countries, adequate evidence from the literature, implementation of a clinical use survey in Japan, etc.). It also merits attention that the maximum dose (10 mg/m2) was set on the basis of pharmacokinetic data from children, rather than relying on the dosing method and dose for adults.

PMID 18815725  Mod Rheumatol. 2009;19(1):1-11. doi: 10.1007/s10165-008・・・
著者: F Halle, A M Prieur
雑誌名: Clin Exp Rheumatol. 1991 May-Jun;9(3):297-302.
Abstract/Text Methotrexate therapy was evaluated in 30 children with juvenile chronic arthritis according to the type of onset. The systemic form seemed less responsive than the ANA positive form with a polyarticular course or polyarticular onset. The clinical improvement, particularly in the ANA positive polyarticular course was confirmed by a significant decrease in the values of the ESR. Side effects occurred in 12 patients and consisted of gastrointestinal upset, mouth ulcers, slight leucopenia and elevated transaminases. They led to discontinuation of the treatment in only one child. Concomitant therapy could be stopped in 50% of the patients with an ANA positive polyarticular course, but remained necessary in the two other groups. These results indicate a differential effect of MTX therapy according to the type of JCA.

PMID 1879091  Clin Exp Rheumatol. 1991 May-Jun;9(3):297-302.
著者: Timothy Beukelman, Nivedita M Patkar, Kenneth G Saag, Sue Tolleson-Rinehart, Randy Q Cron, Esi Morgan DeWitt, Norman T Ilowite, Yukiko Kimura, Ronald M Laxer, Daniel J Lovell, Alberto Martini, C Egla Rabinovich, Nicolino Ruperto
雑誌名: Arthritis Care Res (Hoboken). 2011 Apr;63(4):465-82. doi: 10.1002/acr.20460.
Abstract/Text
PMID 21452260  Arthritis Care Res (Hoboken). 2011 Apr;63(4):465-82. do・・・
著者: D J Lovell, E H Giannini, A Reiff, G D Cawkwell, E D Silverman, J J Nocton, L D Stein, A Gedalia, N T Ilowite, C A Wallace, J Whitmore, B K Finck
雑誌名: N Engl J Med. 2000 Mar 16;342(11):763-9. doi: 10.1056/NEJM200003163421103.
Abstract/Text BACKGROUND: We evaluated the safety and efficacy of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein, in children with polyarticular juvenile rheumatoid arthritis who did not tolerate or had an inadequate response to methotrexate.
METHODS: Patients 4 to 17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to three months in the initial, open-label part of a multicenter trial. Those who responded to treatment then entered a double-blind study and were randomly assigned to receive either placebo or etanercept for four months or until a flare of the disease occurred. A response was defined as an improvement of 30 percent or more in at least three of six indicators of disease activity, with no more than one indicator worsening by more than 30 percent.
RESULTS: At the end of the open-label study, 51 of the 69 patients (74 percent) had had responses to etanercept treatment. In the double-blind study, 21 of the 26 patients who received placebo (81 percent) withdrew because of disease flare, as compared with 7 of the 25 patients who received etanercept (28 percent) (P=0.003). The median time to disease flare with placebo was 28 days, as compared with more than 116 days with etanercept (P<0.001). In the double-blind study, there were no significant differences between the two treatment groups in the frequency of adverse events.
CONCLUSIONS: Treatment with etanercept leads to significant improvement in patients with active polyarticular juvenile rheumatoid arthritis. Etanercept is well tolerated by pediatric patients.

PMID 10717011  N Engl J Med. 2000 Mar 16;342(11):763-9. doi: 10.1056/N・・・
著者: Masaaki Mori, Syuji Takei, Tomoyuki Imagawa, Hiroyuki Imanaka, Nobuaki Maeno, Rumiko Kurosawa, Yoshifumi Kawano, Shumpei Yokota
雑誌名: Mod Rheumatol. 2005;15(6):397-404. doi: 10.1007/s10165-005-0431-9.
Abstract/Text We examined and evaluated the pharmacokinetics, efficacy, and safety of etanercept in patients with methotrexate (MTX)-refractory polyarticular juvenile idiopathic arthritis (JIA) in Japan. All MTX-refractory polyarticular JIA patients 4-17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to 3 months in the open-label, prospective, and multicenter trial. A response was defined as an improvement of 30%, 50%, 70%, or more from baseline in at least three of six indicators of disease activity, with no more than one indicator worsening by more than 30% from baseline (30%, 50%, or 70% definition of improvement, respectively), and disease activity score (DAS28) by EULAR (European League Against Rheumatism) response criteria. At the end of the 12-week study, 20 of the 22 patients (90.9%) had responses with both 30% and 50% definition of improvement after etanercept treatment. To our surprise, 15 of 22 patients (68.2%) had a response with 70% definition of improvement. Moreover, in DAS28, eight patients were evaluated as having a good response and there were no patients with a poor response to etanercept. Treatment had to be stopped in one patient who developed joint contracture during the study period, but there were no significant adverse events in the other patients. In conclusion, treatment with etanercept leads to significant improvement in patients with active polyarticular JIA in Japan. Etanercept is well tolerated by pediatric patients as well as adults.

PMID 17029102  Mod Rheumatol. 2005;15(6):397-404. doi: 10.1007/s10165-・・・
著者: Tomoyuki Imagawa, Shumpei Yokota, Masaaki Mori, Takako Miyamae, Syuji Takei, Hiroyuki Imanaka, Yasuhito Nerome, Naomi Iwata, Takuji Murata, Mari Miyoshi, Norihiro Nishimoto, Tadamitsu Kishimoto
雑誌名: Mod Rheumatol. 2012 Feb;22(1):109-15. doi: 10.1007/s10165-011-0481-0. Epub 2011 Jun 12.
Abstract/Text We evaluated the safety and efficacy of tocilizumab in polyarticular-course juvenile idiopathic arthritis (pJIA) with polyarticular or oligoarticular onset. Patients received 8 mg/kg tocilizumab every 4 weeks in the open-label studies: initial study (to week 12) and then an extension study (at least 48 weeks). Nineteen patients intractable to conventional methotrexate therapy were enrolled. Seventeen patients had polyarticular-onset pJIA; two had oligoarticular-onset pJIA. Mean age was 11.6 years; mean disease duration 5.3 years. American College of Rheumatology Pediatric (ACR Pedi) 30, 50, 70, and 90 response rates, respectively, were 94.7%, 94.7%, 57.9%, and 10.5% at week 12, and 100%, 94.1%, 88.2%, and 64.7% at week 48. Mean disease activity score (DAS28) remained below the remission level (2.6) from week 24. Administration was discontinued in two patients during the extension study because the ACR Pedi 50 response was judged insufficient (one patient) and antitocilizumab antibodies developed (one patient). Adverse events were generally mild, and the four serious adverse events resolved spontaneously or with treatment. In conclusion, tocilizumab showed early and sustained efficacy and tolerability for treating intractable pJIA, which suggests that it is a promising new treatment for this disease.

PMID 21667343  Mod Rheumatol. 2012 Feb;22(1):109-15. doi: 10.1007/s101・・・
著者: Shumpei Yokota, Tomoyuki Imagawa, Masaaki Mori, Takako Miyamae, Yukoh Aihara, Shuji Takei, Naomi Iwata, Hiroaki Umebayashi, Takuji Murata, Mari Miyoshi, Minako Tomiita, Norihiro Nishimoto, Tadamitsu Kishimoto
雑誌名: Lancet. 2008 Mar 22;371(9617):998-1006. doi: 10.1016/S0140-6736(08)60454-7.
Abstract/Text BACKGROUND: Systemic-onset juvenile idiopathic arthritis does not always respond to available treatments, including antitumour necrosis factor agents. We investigated the efficacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder.
METHODS: 56 children (aged 2-19 years) with disease refractory to conventional treatment were given three doses of tocilizumab 8 mg/kg every 2 weeks during a 6-week open-label lead-in phase. Patients achieving an American College of Rheumatology Pediatric (ACR Pedi) 30 response and a C-reactive protein concentration (CRP) of less than 5 mg/L were randomly assigned to receive placebo or to continue tocilizumab treatment for 12 weeks or until withdrawal for rescue medication in a double-blind phase. The primary endpoint of the double-blind phase was an ACR Pedi 30 response and CRP concentration of less than 15 mg/L. Patients responding to tocilizumab and needing further treatment were enrolled in an open-label extension phase for at least 48 weeks. The analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, numbers NCT00144599 (for the open-label lead-in and double-blind phases) and NCT00144612 (for the open-label extension phase).
FINDINGS: At the end of the open-label lead-in phase, ACR Pedi 30, 50, and 70 responses were achieved by 51 (91%), 48 (86%), and 38 (68%) patients, respectively. 43 patients continued to the double-blind phase and were included in the efficacy analysis. Four (17%) of 23 patients in the placebo group maintained an ACR Pedi 30 response and a CRP concentration of less than 15 mg/L compared with 16 (80%) of 20 in the tocilizumab group (p<0.0001). By week 48 of the open-label extension phase, ACR Pedi 30, 50, and 70 responses were achieved by 47 (98%), 45 (94%), and 43 (90%) of 48 patients, respectively. Serious adverse events were anaphylactoid reaction, gastrointestinal haemorrhage, bronchitis, and gastroenteritis.
INTERPRETATION: Tocilizumab is effective in children with systemic-onset juvenile idiopathic arthritis. It might therefore be a suitable treatment in the control of this disorder, which has so far been difficult to manage.

PMID 18358927  Lancet. 2008 Mar 22;371(9617):998-1006. doi: 10.1016/S0・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから