Clinical and Pharmacokinetic Factors Associated With Adalimumab-Induced Mucosal Healing in Patients With Crohn’s Disease
Authors: Kenji Watanabe, Takayuki Matsumoto, Tadakazu Hisamatsu, Hiroshi Nakase, Satoshi Motoya, Naoki Yoshimura, Tetsuya Ishida, Shingo Kato, Tomoo Nakagawa, Motohiro Esaki, Masakazu Nagahori, Toshiyuki Matsui, Yuji Naito, Takanori Kanai, Yasuo Suzuki, Masanori Nojima, Mamoru Watanabe, Toshifumi Hibi, Akira Andoh, Toshifumi Ashida, Katsuya Endo, Yutaka Endo, Motohiro Esaki, Hiroshi Fujita, Mikihiro Fujiya, Ken Haruma, Toshifumi Hibi, Sakiko Hiraoka, Ichiro Hirata, Tadakazu Hisamatsu, Yutaka Honda, Hideki Iijima, Bunei Iizuka, Kentaro Ikeya, Takuya Inoue, Syuji Inoue, Tetsuya Ishida, Yo Ishiguro, Shyunji Ishihara, Hiroaki Ito, Ryuichi Iwakiri, Takashi Kagaya, Takanori Kanai, Hiroshi Kashida, Shingo Kato, Jun Kato, Takehiko Katsurada, Fukunori Kinjyo, Kiyonori Kobayashi, Mayumi Kodama, Reiko Kunisaki, Koichi Kurahara, Takafumi Kurokami, Lee Kyouwon, Koichiro Matsuda, Kazuhiro Matsueda, Toshiyuki Matsui, Takayuki Matsumoto, Keiichi Mitsuyama, Yuji Mizokami, Satoshi Motoya, Yuji Naito, Tomoo Nakagawa, Shiro Nakamura, Hiroshi Nakase, Masanori Nojima, Masafumi Nomura, Atsuhiro Ogawa, Kazuichi Okazaki, Kazuaki Otsuka, Hirotake Sakuraba, Masayuki Saruta, Makoto Sasaki, Takayuki Shirai, Tomoaki Suga, Kazuhito Sugimura, Toshiro Sugiyama, Yasuo Suzuki, Fuminao Takeshima, Hiroyuki Tamaki, Shinji Tanaka, Satoshi Tanida, Keiichi Tominaga, Taku Tomizawa, Kenji Watababe, Mamoru Watanabe, Kenji Watanabe, Syojiro Yamamoto, Masaki Yamashita, Atsushi Yoshida, Naoki Yoshimura
Journal: Clinical Gastroenterology and Hepatology (2017)

Background & AimsWe previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn's disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants.MethodsWe compared simple endoscopic scores for CD between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation.ResultsThe odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.04–4.32) but not at Week 52 (OR, 1.50; 95% CI, 0.77–2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95% CI, 0.72–0.90) and at Week 52 (OR, 0.91; 95% CI, 0.84–0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95% CI, 1.14–1.58; P for trend = .001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 (P < .001).ConclusionsIn a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146. We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn's disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. We compared simple endoscopic scores for CD between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation. The odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.04–4.32) but not at Week 52 (OR, 1.50; 95% CI, 0.77–2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95% CI, 0.72–0.90) and at Week 52 (OR, 0.91; 95% CI, 0.84–0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95% CI, 1.14–1.58; P for trend = .001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 (P < .001). In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146.