Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis.

BACKGROUND: Indigo naturalis (IN) consists of ligands for the aryl hydrocarbon receptor and exhibits anti-inflammatory effects. Previously, we demonstrated that an 8-week treatment with oral IN is effective in inducing a clinical response in patients with ulcerative colitis (UC). Some UC patients with proctitis are refractory to topical mesalamine or corticosteroids and therefore require an alternative topical treatment. OBJECTIVES: We aimed to prospectively evaluate the safety and efficacy of IN suppositories in UC patients. METHOD: We performed an open-label, single-center, prospective pilot study from February 2018 to October 2018. A total of 10 patients with active UC, who had moderate to severe inflammation from the rectum to the sigmoid colon, were enrolled. The patients received a daily dose of 50 mg IN suppository for 4 weeks. The primary endpoint was safety at week 4. RESULTS: Although 1 patient experienced anal pain, no serious adverse events were observed. At week 4, the rates of clinical remission and mucosal healing were 30 and 40%, respectively. Mayo rectal bleeding subscores significantly improved after treatment (1.80 ± 0.13 vs. 0.90 ± 0.28; p = 0.009). Approximately 80% of the patients with a baseline Mayo endoscopic subscore in the rectum (r-MES) of 2 achieved mucosal healing, but those with a baseline r-MES of 3 did not. CONCLUSIONS: We found that 4 weeks of IN suppository can be tolerated by UC patients, but its efficacy was limited by the severity of the disease. Further investigation will be needed in order to confirm the optimum dose of IN suppository for patients with UC.

Clinical Efficacy and Safety of Oral Qing-Dai in Patients with Ulcerative Colitis: A Single-Center Open-Label Prospective Study.

BACKGROUND/AIMS: Chinese herbal medicine Qing-Dai (also known as indigo naturalis) has been used to treat various inflammatory conditions. However, not much has been studied about the use of oral Qing-Dai in the treatment for ulcerative colitis (UC) patients. Studies exploring alternative treatments for UC are of considerable interest. In this study, we aimed at prospectively evaluating the safety and efficacy of Qing-Dai for UC patients. METHODS: The open-label, prospective pilot study was conducted at Keio University Hospital. A total of 20 patients with moderate UC activity were enrolled. Oral Qing-Dai in capsule form was taken twice a day (daily dose, 2 g) for 8 weeks. RESULTS: At week 8, the rates of clinical response, clinical remission, and mucosal healing were 72, 33, and 61%, respectively. The clinical and endoscopic scores, CRP levels, and fecal occult blood results were also significantly improved. We observed 2 patients with mild liver dysfunction; 1 patient discontinued due to infectious colitis and 1 patient discontinued due to mild nausea. CONCLUSION: This is the first prospective study indicating that oral Qing-Dai is effective for inducing remission in patients with moderate UC activity and can be tolerated. Thus, Qing-Dai may be considered an alternative treatment for patients, although further investigation is warranted.

Moderate dietary temperance effectively prevents relapse of Crohn disease: a prospective study of patients in remission.

The authors examined the influence of diet (dietary fat intake and dietary temperance) on relapse of patients with Crohn disease. A 1-year prospective study of 76 patients with Crohn disease was conducted. The criterion for eligibility was a Crohn Disease Activity Index score of 150 or lower for at least 1 month. The primary end point was defined as the relapse-free interval from the baseline until the first relapse. Fat intake was assessed using a validated diet history questionnaire. The degree of dietary temperance was assessed using a single-item nominal scale. The Cox proportional hazards model was used to evaluate the influence of diet. Crohn disease relapse was seen in 25 patients (33%), and 47 patients (62%) remained in continuous remission. A decreased ratio of n-6 polyunsaturated fatty acid (PUFA) to n-3PUFA (odds ratio = .38; p = .005) was associated with a poor prognosis. Dietary temperance also was significantly associated with prognosis (p = .014). More moderate dietary temperance decreased the risk of relapse (odds ratio = .22; p = .006). Effective prevention of relapse for Crohn disease patients might be achieved through moderate dietary temperance, particularly when the disease condition is unstable.

Granulocytapheresis is useful as an alternative therapy in patients with steroid-refractory or -dependent ulcerative colitis.

BACKGROUND: Recently, granulocyte and monocyte adsorption apheresis (GCAP) has been shown to be safe and effective for active ulcerative colitis (UC). We analyzed the safety and efficacy of GCAP (G-1 Adacolumn) in patients with steroid-refractory and -dependent UC. G-1 Adacolumn is filled with cellulose acetate carriers that selectively adsorb granulocytes and monocytes/macrophages. METHODS: Forty-four patients with UC were treated with GCAP. These patients received 5 apheresis sessions over 4 weeks. Twenty patients had steroid-refractory UC (group 1) and 10 had steroid-dependent UC (group 2). Fourteen patients who did not want readministration of steroids were treated with GCAP at the time of relapse, just after discontinuation of steroid therapy (group 3). RESULTS: Of 44 patients treated with GCAP, 24 (55%) obtained remission (CAI < or = 4), 9 (20%) showed a clinical response, and 11 (25%) remained unchanged. Only 2 of 10 patients (20%) with severe steroid-refractory UC (CAI > or = 12) achieved remission, whereas 7 of 10 patients (70%) with moderate steroid-refractory UC achieved remission (p < 0.05). The dose of corticosteroids was tapered in 9 of 10 (90%) patients with steroid-dependent UC after GCAP therapy. Twelve (86%) of 14 patients in group 3 showed an improvement in symptoms and could avoid re-administration of steroids after GCAP. No severe adverse effects occurred. CONCLUSIONS: The findings of this study suggest that GCAP may be a useful alternative therapy for patients with moderate steroid-refractory or -dependent UC, although cyclosporin A or colectomy is necessary in patients with severe UC. GCAP may also be useful for avoiding re-administration of steroids at the time of relapse. Randomized, controlled clinical trials are needed to confirm these findings.