臨床外科60巻7号

2005年07月発行

特集 炎症性腸疾患―治療における最近の進歩

クローン病の内科的治療―抗TNF-α抗体の使用法と問題点

著者： 矢田親一朗¹ 松本主之¹ 飯田三雄¹

所属機関： ¹九州大学大学院医学研究院病態機能内科学分野

ページ範囲：P.877 - P.882

文献概要

要旨：クローン病の病態には消化管粘膜における免疫異常が関与し，なかでもTNF-αを介した炎症性サイトカインの発現が重要な役割を担っている．近年，TNF-αをターゲットとした治療薬が開発され，クローン病にも応用されている．キメラ型抗TNF-α抗体infliximabは欧米において有効性が確認され，わが国でもクローン病に対する投与が行われている．しかし，栄養療法を中心とするわが国のクローン病の治療指針における本剤の位置づけはいまだ確立されていない．一方，ヒト型抗TNF-α抗体CDP571や完全ヒト型抗TNF-α抗体adalimumab，あるいはPEG化フラグメント抗体CDP870のクローン病に対する効果はinfliximabを凌駕するものではない．わが国では，今後TNF-α抗体療法の維持療法としての位置づけを検証する必要がある．

参考文献

1）Targan SR, Hanauer SB, van Deventer SJ, et al：A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N Engl J Med 337：1029-1035, 1997

2）Sandborn WJ, Feagan BG, Radford-Smith G, et al：CDP571, a humanised monoclonal antibody to tumour necrosis factor alpha, for moderate to severe Crohn's disease：a randomised, double blind, placebo controlled trial. Gut 53：1485-1493, 2004

3）Sandborn WJ, Hanauer S, Loftus EV, et al：An open-label study of the human anti-TNF monoclonal antibody adalimumab in subjects with prior loss of response or intolerance to infliximab for Crohn's disease. Am J Gastroenterol 99：1984-1989, 2004

4）Papadakis KA, Shaye OA, Vasiliauskas EA, et al：Safety and efficacy of adalimumab（D2E7）in Crohn's disease patients with an attenuated response to infliximab. Am J Gastroenterol 100：75-79, 2005

5）Winter TA, Wright J, Ghosh S, et al：Intravenous CDP870, a PEGylated Fab'fragment of a humanized antitumour necrosis factor antibody in patients with moderate-to-severe Crohn's disease：an exploratory study. Aliment Pharmacol Ther 20：1337-1346, 2004

6）Sandborn WJ, Hanauer SB, Katz S, et al：Etanercept for active Crohn's disease：a randomized, double-blind, placebo-controlled trial. Gastronterology 121：1088-1094, 2001

7）Asakura H, Yao T, Matsui T, et al：Efficacy of treatment with chimeric monoclonal antibody（Infliximab）to tumor necrosis factor-alpha for Crohn's disease in Japan：evaluation by rapid turnover proteins, and radiologic and endoscopic findings. J Gastroenterol Hepatol 16：763-769, 2001

8）D'haens GR, Deventer S, Van Hogezand R, et al：Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease：A European multicenter trial. Gastroenterology 116：1029-1034, 1999

9）Baert FJ, D'haens GR, Peeters M, et al：Tumor necrosis factor alpha antibody（infliximab）therapy profoundly down-regulates the inflammation in Crohn's ileocolitis. Gastroenterology 116：22-28, 1999

10）Hanauer SB, Feagan BG, Lichtenstein GR, et al：Maintenance infliximab for Crohn's disease：the ACCENTⅠrandomised trial. Lancet 359：1541-1549, 2002

11）Present DH, Rutgeerts P, Targan SR, et al：Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 340：1398-1405, 1999

12）Sands BE, Anderson FH, Bernstein CN, et al：Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med 26：934-936, 2003

13）Sands BE, Blank MA, Patel K, et al：Long-term treatment of rectovaginal fistulas in Crohn's disease：response to infliximab in the ACCENTⅡStudy. Clin Gastroenterol Hepatol 2：912-920, 2004

14）Regueiro M, Mardini H：Treatment of perianal fistulizing Crohn's disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement. Inflamm Bowel Dis 9：98-103, 2003

15）Parsi MA, Achkar JP, Richardson S, et al：Predictors of response to infliximab in patients with Crohn's disease. Gastroenterology 123：707-713, 2002

16）Kinney T, Rawlins M, Kozarek R, et al：Immunomodulators and“on demand”therapy with infliximab in Crohn's disease：clinical experience with 400 infusions. Am J Gastroenterol 98：608-612, 2003

17）松本主之，矢田親一朗，中村昌太郎，他：Crohn病長期経過例における抗TNF-α抗体療法の効果．胃と腸39：171-184，2004

18）Matsumoto T, Iida M, Kohgo Y, et al：Therapeutic efficacy of infliximab on active Crohn's disease under nutritional therapy. Scand J Gastroenterol（in press）

19）Colombel JF, Loftus EV, Tremaine WJ, et al：The safety profile of infliximab in patients with Crohn's disease：the Mayo Clinic experience in 500 patients. Gastroenterology 126：19-31, 2004

20）Keane J, Gersho S, Pharm D, et al：Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 345：1098-1104, 2001

21）Charles NB, James FB, Erich K, et al：Cancer risk in patients with inflammatory bowel disease. Cancer 91：854-862, 2001

22）Katz JA, Antoni C, Keenan GF, et al：Outcome of pregnancy in women receiving infliximab for the treatment of Crohn's disease and rheumatoid arthritis. Am J Gastroenterol 99：2385-2392, 2004