Introduction
Ulcerative colitis (UC) is a chronic inflammatory bowel disease. The long-term maintenance of the disease is an important key of the treatment, as patients experience repetitive exacerbation. Dysbiosis of the gut microbiota is observed among UC patients and modifying their gut microbiota is recently attracting attention as one of the therapeutic targets. In our past study, Fusobacterium varium was observed on the mucosa of UC patients with high frequency. Based on this, we developed an antibiotic combination therapy (ATM therapy), which was expected to have sensitivity to F. varium. The regimen of our prior studies showed decent effectiveness for induction and maintenance on active UC patients.
Aims & Methods
In this study, we aim to investigate the long-term effectiveness of ATM therapy on a larger cohort.
A prospective open-label trial was undertaken. Patients were eligible if they were 18 years of age or above, and had an established diagnosis of UC based on endoscopic, clinical and histological feature. Exclusion criteria were penicillin allergy, administration of antibiotics agents within 2 weeks of study entry, ongoing biologic therapy, pregnancy, cancer and other serious comorbid illness. Patients who had stool pathogens were also excluded. A combination of oral amoxicillin (1500mg), tetracycline (1500mg) and metronidazole (750mg) was administered to patients daily for 2 weeks in addition to their conventional medication. Clinical assessment was performed using the Mayo score before treatment and at 0, 3, 6, 9 and 12 months. Endoscopic evaluation was performed using the Mayo score before treatment and at 3 and 12 months. The primary endpoint was the response rate at 3 months after the completion of ATM therapy. The secondary endpoints were the remission rate at 3 months, both remission and response rate at completion and 1 year after the ATM therapy. All adverse events were recorded.
Results
The data from 311 active UC patients were analysed. The compliance rate was 95.7%. The response rate and remission rate were 75.2% and 30.9% at completion, 62.7% and 29.6% at 3 months, 35.4% and 24.4% at 12 months, respectively. In the patient group with severe disease activity, the response rate tended to be high and was statistically higher at 6 months (p=0.0299). Regarding steroid dependent, resistant and disease extent, the response rate showed no statistical difference at any follow-up points. Adverse events were reported in 60.8% of participants. The most frequent adverse events were diarrhea (19.0%) and fever (14.8%). No life-threatening adverse event was observed and all the symptoms disappeared immediately after the discontinuation or the completement of the therapy.
Conclusion
2 weeks administration of ATM therapy induces response and remission of UC and maintains the symptom for long-term. The ATM therapy would be considered as one of the easy and convenient therapeutic choices for both induction and maintenance of the disease.
