Yasuo Suzuki1, Toshiyuki Matsui, Hiroaki Ito, Toshifumi Ashida, Shiro Nakamura, Satoshi Motoya, Takayuki Matsumoto, Noriko Sato, Kunihiko Ozaki, Mamoru Watanabe, Toshifumi Hibi. 1. *Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Japan; †Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan; ‡Kinshukai Infusion Clinic, Osaka, Japan; §Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan; ||Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan; ¶Inflammatory Bowel Diseases Center, Sapporo-kosei General Hospital, Sapporo, Japan; **Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan; ††Mitsubishi Tanabe Pharma Corporation, Osaka, Japan; ‡‡Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan; and §§Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
Abstract
BACKGROUND: We aimed to clarify the efficacy, safety, and factors associated with remission on dose escalation in patients with Crohn's disease showing loss of response (LOR) to infliximab treatment of 5 mg/kg at 8-week intervals in a clinical trial. METHODS: Thirty-nine patients with LOR to 5 mg/kg infliximab therapy started treatment with 10 mg/kg per 8 weeks. LOR was defined as both a Crohn's Disease Activity Index of ≥175 at 8 weeks after infusion of 5 mg/kg infliximab and a Crohn's Disease Activity Index increase of ≥50 from 4 to 8 weeks after infusion. RESULTS: At week 8 after the first infusion of 10 mg/kg, median (95% confidence interval) reduction in Crohn's Disease Activity Index of 33 patients evaluated was 95.0 (70.0-134.0), meeting the primary endpoint. Remission rate at week 40 was 41% (16 of 39), with correlation noted between remission achievement and serum infliximab level (P = 0.036). Univariate analysis revealed that "infliximab trough level ≥1 µg/mL," "interleukin 6 level ≤2.41 pg/mL," and "albumin level ≥3.8 g/dL" before dose escalation were significantly associated with remission at week 40 (P = 0.017, P = 0.011, and P = 0.019, respectively), and these variables were correlated with each other (all: P < 0.001). The cutoff infliximab level for remission was 0.42 µg/mL in receiver operating characteristic curve analysis. No adverse events related to dose escalation were observed. CONCLUSIONS: Doubling the infliximab dose safely led to remission in patients with Crohn's disease with LOR to 5 mg/kg treatment. Remission was associated with pre-escalation levels of infliximab, interleukin 6, and albumin. Our findings suggest that dose escalation while maintaining a certain level of infliximab is important in achieving remission.
BACKGROUND: We aimed to clarify the efficacy, safety, and factors associated with remission on dose escalation in patients with Crohn's disease showing loss of response (LOR) to infliximab treatment of 5 mg/kg at 8-week intervals in a clinical trial. METHODS: Thirty-nine patients with LOR to 5 mg/kg infliximab therapy started treatment with 10 mg/kg per 8 weeks. LOR was defined as both a Crohn's Disease Activity Index of ≥175 at 8 weeks after infusion of 5 mg/kg infliximab and a Crohn's Disease Activity Index increase of ≥50 from 4 to 8 weeks after infusion. RESULTS: At week 8 after the first infusion of 10 mg/kg, median (95% confidence interval) reduction in Crohn's Disease Activity Index of 33 patients evaluated was 95.0 (70.0-134.0), meeting the primary endpoint. Remission rate at week 40 was 41% (16 of 39), with correlation noted between remission achievement and serum infliximab level (P = 0.036). Univariate analysis revealed that "infliximab trough level ≥1 µg/mL," "interleukin 6 level ≤2.41 pg/mL," and "albumin level ≥3.8 g/dL" before dose escalation were significantly associated with remission at week 40 (P = 0.017, P = 0.011, and P = 0.019, respectively), and these variables were correlated with each other (all: P < 0.001). The cutoff infliximab level for remission was 0.42 µg/mL in receiver operating characteristic curve analysis. No adverse events related to dose escalation were observed. CONCLUSIONS: Doubling the infliximab dose safely led to remission in patients with Crohn's disease with LOR to 5 mg/kg treatment. Remission was associated with pre-escalation levels of infliximab, interleukin 6, and albumin. Our findings suggest that dose escalation while maintaining a certain level of infliximab is important in achieving remission.
Authors: Adam Frymoyer; Daniël R Hoekman; Travis L Piester; Tim G de Meij; Thalia Z Hummel; Marc A Benninga; Angelika Kindermann; K T Park Journal: J Pediatr Gastroenterol Nutr Date: 2017-12 Impact factor: 2.839