title: Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial.
abstract: OBJECTIVE
  Fusobacterium varium may contribute to ulcerative colitis (UC). We conducted a double-blind placebo-controlled multicenter trial to determine whether antibiotic combination therapy induces and/or maintains remission of active UC.
  
  
  METHODS
  Patients with chronic mild-to-severe relapsing UC were randomly assigned to oral amoxicillin 1500 mg/day, tetracycline 1500 mg/day, and metronidazole 750 mg/day, vs. placebo, for 2 weeks, and then followed up. The primary study end point was clinical response (Mayo score at 3 months after treatment completion) and secondary end points were clinical and endoscopic score improvements at 12 months. Anti-F. varium antibodies were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Treatment and placebo groups each had 105 subjects. At the primary end point, response rates were significantly greater with antibiotics than with placebo (44.8 vs. 22.8%, P=0.0011). Endoscopic scores significantly improved at 3 months (P=0.002 vs. placebo). Remission rates were 19.0% (antibiotics) vs. 15.8% (placebo) at 3 months (P=0.59). At the secondary end point, response rates were significantly greater with antibiotics than with placebo (49.5 vs. 21.8%, respectively, P<0.0001). Endoscopic scores were significantly improved at 12 months after antibiotic treatment (P=0.002 vs. placebo). Remission rates had improved to 26.7% with antibiotics vs. 14.9% for placebo, at 12 months (P=0.041). F. varium antibody titers decreased in responders but not in nonresponders, and more in the antibiotic than in the placebo group. More pretreatment steroid-dependent UC patients discontinued corticosteroids after treatment completion (6 months: 28.6 vs. 11.8%, respectively, P=0.046; 9 months: 34.7 vs. 13.7%, respectively, P=0.019; and 12 months: 34.7 vs. 13.7%, respectively, P=0.019). These effects were greater in the subanalysis of the active group (Mayo scores of 6-12) than in that of total cases (0-12). No serious drug-related toxicities occurred.
  
  
  CONCLUSIONS
  The 2-week triple antibiotic therapy produced improvement, remission, and steroid withdrawal in active UC more effectively than a placebo.
authors.affiliation: Department of Gastroenterology and Hepatology, Jikei University, Tokyo, Japan. ohkusa@jikei.ac.jp
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ohkusa
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kato
authors.forename: Shuichi
authors.initials: S
authors.lastname: Terao
authors.forename: Toshimi
authors.initials: T
authors.lastname: Chiba
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Mabe
authors.forename: Kazunari
authors.initials: K
authors.lastname: Murakami
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mizokami
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Akinori
authors.initials: A
authors.lastname: Yanaka
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamato
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Isao
authors.initials: I
authors.lastname: Okayasu
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
authors.forename: Hisao
authors.initials: H
authors.lastname: Tajiri
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Sato
mesh_terms: D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000658:Amoxicillin / Q000008:administration & dosage / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000382:microbiology*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D016099:Endoscopy, Gastrointestinal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005674:Fusobacterium Infections / Q000188:drug therapy* / Q000382:microbiology*; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D018709:Statistics, Nonparametric; D013752:Tetracycline / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D010919:Placebos; D008795:Metronidazole; D000658:Amoxicillin; D013752:Tetracycline