ORIGINAL ARTICLE Retrieval of Serum Infliximab Level by Shortening the Maintenance Infusion Interval Is Correlated with Clinical Efficacy in Crohn’s Disease Toshifumi Hibi, MD, PhD, 1 Atsushi Sakuraba, MD, 1 Mamoru Watanabe, MD, PhD, 2 Satoshi Motoya, MD, PhD, 3 Hiroaki Ito, MD, PhD, 4 Kenta Motegi, MD, 5 Yoshitaka Kinouchi, MD, PhD, 6 Masakazu Takazoe, MD, 7 Yasuo Suzuki, MD, PhD, 8 Takayuki Matsumoto, MD, PhD, 9 Kazuhiko Kawakami, MD, 10 Takayuki Matsumoto, MD, PhD, 11 Ichiro Hirata, MD, PhD, 12 Shinji Tanaka, MD, PhD, 13 Toshifumi Ashida, MD, PhD, 14 and Toshiyuki Matsui, MD, PhD 15 Background: Infliximab has shown beneficial effects in the treatment of Crohn’s disease (CD). The aim of this study was to assess 1) the clin- ical efficacy of shortening the infusion interval from 8 to 4 weeks when patients had shown loss of response during maintenance therapy, and 2) the association between the serum trough level and clinical efficacy. Methods: This was an open-label prospective multicenter study. Infliximab was administered at 5 mg/kg to patients with active CD at weeks 0, 2, and 6. Week 10 responders received infliximab every 8 weeks thereafter. In those with loss of response after week 14 the interval was switched to every 4 weeks. Co-primary endpoints were the rate of patients achieving clinical response and remission at week 54. Serum level of infliximab was measured at each visit. Results: Fifty-seven patients who responded to induction treatment received maintenance therapy after week 14. Thirty-seven patients continued at the 8-week interval and 20 patients were switched to a 4-week interval. The overall clinical response and remission rates at week 54 were 82.5% and 61.4%, respectively. For those with loss of response, treatment at the 4-week interval resulted in clinical response and remission rates of 83.3% (15/18) and 55.6% (10/18), respectively, at week 54. A correlation between clinical efficacy and serum trough level was found (P < 0.01, overall). Conclusions: A treatment strategy with an option of shortening the dosing interval of infliximab retrieves its trough level and may be useful for maintaining its efficacy. (Inflamm Bowel Dis 2012;18:1480–1487) Key Words: Crohn’s disease, infliximab, maintenance, serum level, dosing interval C rohn’s disease (CD) is an inflammatory bowel disease (IBD) that is characterized by inflammation at various sites in the gastrointestinal tract, often resulting in compli- cations such as stenosis and fistula that requires surgery. 1 Therefore, maintaining a prolonged remission is an impor- tant issue in the treatment of CD. 2 The pathogenesis of CD remains unclear, but inflam- matory cytokines 3 including tumor necrosis factor (TNF)-a has been suggested to play an important role. 4–6 Infliximab, an antihuman TNF-a monoclonal antibody, binds to human TNF-a, neutralizing its bioactivity and inducing apoptosis of TNF-a-producing cells. 7 Clinical studies have Received for publication July 18, 2011; Accepted August 1, 2011. From the 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 2 Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan, 3 Inflammatory Bowel Diseases Center, Sapporo-kosei General Hospital, Sapporo, Japan, 4 Department of Molecular Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan, 5 Department of Gastroenterology, Gunma Prefectural Cancer Center, Ota, Gunma, Japan, 6 Health Administration Center, Center for the Advancement of Higher Education, Tohoku University, Sendai, Japan, 7 Inflammatory Bowel Diseases Center, Social Insurance Central General Hospital, Tokyo, Japan, 8 Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Japan, 9 Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan, 10 Matsuda Hospital Colo-Proctological Institute, Shizuoka, Japan, 11 Department of Lower Gastroenterology, Hyogo College of Medicine, Hyogo, Japan, 12 Department of Gastroenterology, Fujita Health University, Aichi, Japan, 13 Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan, 14 Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan, 15 Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan. Reprints: Toshifumi Hibi, MD, PhD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan (e-mail: thibi@sc.itc.keio.ac.jp). Copyright V C 2011 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.21886 Published online 10 October 2011 in Wiley Online Library (wileyonlinelibrary.com). Inflamm Bowel Dis  Volume 18, Number 8, August 2012 1480