Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial.
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.
Ohkusa
Toshifumi
T
Department of Gastroenterology and Hepatology, Jikei University, Tokyo, Japan. ohkusa@jikei.ac.jp
Kato
Kimitoshi
K
Terao
Shuichi
S
Chiba
Toshimi
T
Mabe
Katsuhiro
K
Murakami
Kazunari
K
Mizokami
Yuji
Y
Sugiyama
Toshiro
T
Yanaka
Akinori
A
Takeuchi
Yoshiaki
Y
Yamato
Shigeru
S
Yokoyama
Tetsuji
T
Okayasu
Isao
I
Watanabe
Sumio
S
Tajiri
Hisao
H
Sato
Nobuhiro
N
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
D000305:Adrenal Cortex Hormones; D010919:Placebos; D008795:Metronidazole; D000658:Amoxicillin; D013752:Tetracycline