Clinical efficacy of adalimumab in Crohn’s disease: a real practice observational study in Japan

BMC Gastroenterology, Jul 2016

Background There are few reports of the efficacy of adalimumab (ADA) for clinical remission and preventing postoperative recurrence in Crohn's disease (CD) in Asian real practice settings. We conducted a Japanese multicenter retrospective observational study. Methods We evaluated patients with CD who were treated with ADA at 11 medical institutions in Japan to investigate the clinical efficacy of remission up to 52 weeks and the associated factors to achieve remission with a CD Activity Index (CDAI) < 150. The effects of preventing postoperative recurrence were also evaluated. Results In 62 patients, the remission rates were 33.9, 74.2, 75.8, 77.4, and 66.1 % at 0, 4, 12, 26, and 52 weeks, respectively. Although 10 patients discontinued treatment due to primary nonresponse, secondary nonresponse, or adverse events, the ongoing treatment rate at 52 weeks was 83.9 %. Comparison of remission and non-remission on univariate analysis identified colonic type and baseline CDAI value as significant associated factors (P < 0.05). In 16 patients who received ADA to prevent postoperative recurrence, the clinical remission maintenance rate was 93.8 % and the mucosal healing rate was 64.3 % during a mean postoperative follow-up period of 32.3 months. Conclusions ADA effectively induced remission and prevented postoperative recurrence in patients with CD in a real practice setting.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

http://www.biomedcentral.com/content/pdf/s12876-016-0501-9.pdf

Clinical efficacy of adalimumab in Crohn’s disease: a real practice observational study in Japan

Takeshima et al. BMC Gastroenterology Clinical efficacy of adalimumab in Crohn's disease: a real practice observational study in Japan Fuminao Takeshima 0 Daisuke Yoshikawa 2 Syuntaro Higashi 1 Tomohito Morisaki 6 Hidetoshi Oda 5 Maho Ikeda 4 Haruhisa Machida 3 Kayoko Matsushima 0 Hitomi Minami 0 Yuko Akazawa 0 Naoyuki Yamaguchi 0 Ken Ohnita 0 Hajime Isomoto 0 Masato Ueno 7 Kazuhiko Nakao 0 0 Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University Hospital , 1-7-1 Sakamoto, Nagasaki City, Nagasaki 852-8501 , Japan 1 Department of Gastroenterology, National Hospital Organization Nagasaki Medical Center , 2-1001-1 Kubara, Ohmura City, Nagasaki 856-8562 , Japan 2 Department of Gastroenterology and Hepatology, Sasebo City General Hospital , 9-3 Hirase-cho, Sasebo City, Nagasaki 857-8511 , Japan 3 Department of Internal Medicine, Shunkaikai Inoue Hospital , 6-12 Takara-machi, Nagasaki City, Nagasaki 850-0045 , Japan 4 Department of Internal Medicine, Kouseikai Hospital , 1-3-12 Hayama, Nagasaki City, Nagasaki 852-8053 , Japan 5 Department of Gastroenterology and Hepatology, Sasebo Chuo Hospital , 15 Yamato-cho, Sasebo City, Nagasaki 857-1195 , Japan 6 Department of Gastroenterology and Hepatology, National Hospital Organization Ureshino Medical Center , 2436 Ureshino-cho, Ureshino City, Saga 843-0393 , Japan 7 Integrated Marketing Department, Eisai Co., Ltd. , 13-1 Nishigoken-cho, Shinjuku-ku, Tokyo 162-0812 , Japan Background: There are few reports of the efficacy of adalimumab (ADA) for clinical remission and preventing postoperative recurrence in Crohn's disease (CD) in Asian real practice settings. We conducted a Japanese multicenter retrospective observational study. Methods: We evaluated patients with CD who were treated with ADA at 11 medical institutions in Japan to investigate the clinical efficacy of remission up to 52 weeks and the associated factors to achieve remission with a CD Activity Index (CDAI) < 150. The effects of preventing postoperative recurrence were also evaluated. Results: In 62 patients, the remission rates were 33.9, 74.2, 75.8, 77.4, and 66.1 % at 0, 4, 12, 26, and 52 weeks, respectively. Although 10 patients discontinued treatment due to primary nonresponse, secondary nonresponse, or adverse events, the ongoing treatment rate at 52 weeks was 83.9 %. Comparison of remission and non-remission on univariate analysis identified colonic type and baseline CDAI value as significant associated factors (P < 0.05). In 16 patients who received ADA to prevent postoperative recurrence, the clinical remission maintenance rate was 93.8 % and the mucosal healing rate was 64.3 % during a mean postoperative follow-up period of 32.3 months. Conclusions: ADA effectively induced remission and prevented postoperative recurrence in patients with CD in a real practice setting. Adalimumab; Crohn's disease; Preventing postoperative recurrence; Japanese patients; Real practice Background Crohn's disease (CD), an inflammatory bowel disease (IBD), is an intractable disease of unknown etiology [ 1 ]. CD is progressive and markedly impairs patient quality of life due to its associated symptoms such as diarrhea, abdominal pain, fever, and surgery [ 2–4 ]. Although there is currently no cure for CD, the inflammatory cytokine tumor necrosis factor-α (TNF-α) is involved in clinical condition [ 5 ], against which anti-TNF-α monoclonal antibody (anti-TNF-α antibody) is highly effective [ 6, 7 ]. For the treatment of CD, infliximab (IFX), a chimeric antibody and infusion drug, first appeared as an antiTNF-α antibody, followed by adalimumab (ADA), a fully humanized antibody and subcutaneous drug. IFX and ADA were highly effective in large-scale studies and have already been widely used worldwide [ 8–15 ]. Although the clinical features of CD in Asia is relatively similar to that of North America or Europe, there are some differences such as a higher prevalence of males and ileo-colonic type, less familial clustering, extra-intestinal manifestations, and surgical rates. As for genetics, nucleotide oligomerization domain-2 (NOD2) variants and autophagy-related 16-like 1(ATG16L1) variants, which have been firmly associated with CD in the West have not been detected in the patients with CD in Asia [ 16 ]. Taking account of these differences, the data from Asia is important in spite of the numerous data from West. However, ADA received approval later in Asian countries including Japan than in the Europe and US; therefore, there are limited reports on its efficacy in Asian real practice settings [ 17–20 ]. Watanabe et al. reported that clinical remission rate at week 4 in the induction therapy was 33.3 %. Seventy percentage of patients achieved decrease in CDAI ≥ 70 points and the rest was unresponsive at week 4 in the induction therapy [17]. Furthermore, intestinal resection is commonly required in patients with CD and often leads to repeated surgery; thus (...truncated)


This is a preview of a remote PDF: http://www.biomedcentral.com/content/pdf/s12876-016-0501-9.pdf

Fuminao Takeshima, Daisuke Yoshikawa, Syuntaro Higashi, Tomohito Morisaki, Hidetoshi Oda, Maho Ikeda, Haruhisa Machida, Kayoko Matsushima, Hitomi Minami, Yuko Akazawa, Naoyuki Yamaguchi, Ken Ohnita, Hajime Isomoto, Masato Ueno, Kazuhiko Nakao. Clinical efficacy of adalimumab in Crohn’s disease: a real practice observational study in Japan, BMC Gastroenterology, 2016, pp. 82, 16, DOI: 10.1186/s12876-016-0501-9