title: Circulating Interleukin 6 and Albumin, and Infliximab Levels Are Good Predictors of Recovering Efficacy After Dose Escalation Infliximab Therapy in Patients with Loss of Response to Treatment for Crohn's Disease: A Prospective Clinical Trial.
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.
authors.affiliation: *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.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Matsui
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ito
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ashida
authors.forename: Shiro
authors.initials: S
authors.lastname: Nakamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Motoya
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Ozaki
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000328:Adult; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D000069285:Infliximab / Q000008:administration & dosage* / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D011446:Prospective Studies; D012372:ROC Curve; D012074:Remission Induction / Q000379:methods*; D012709:Serum Albumin / Q000032:analysis; D055815:Young Adult
chemical_list: D005765:Gastrointestinal Agents; D015850:Interleukin-6; D012709:Serum Albumin; D000069285:Infliximab