Treatment with indigo naturalis (IN) is effective in treating ulcerative colitis (UC) and inducing clinical response and mucosal healing, even in patients with steroid-dependent disease or anti–TNF-α refractoriness, according to a study published in the Journal of Gastroenterology.

Various treatments have been developed and allow most patients with UC to achieve mucosal healing. However, some patients with intractable uncontrolled UC eventually require a colectomy; thus, a treatment with a novel mechanism of action against UC is required.

In this post hoc subanalysis, researchers analyzed the dataset from the INDIGO study, a multicenter, randomized, double-blind clinical trial examining the efficacy and safety of IN for inducing clinical response in patients with active UC (N=86). Patients were randomized to receive IN (0.5, 1.0, or 2.0 g/daily) or placebo for 8 weeks. The primary end point was defined as the difference in clinical response and the rate of mucosal healing in refractory vs nonrefractory patients. Refractory patients were categorized by the presence of steroid-dependent disease, previous use of anti–TNF-α, concomitant use of thiopurine at baseline, and a Mayo endoscopic score of 9 to 11 at baseline.

Related Articles

The rate of clinical response was 77.8% in patients with steroid-dependent disease (95% CI, 70.9-84.7), 77.5% in patients with previous use of anti–TNF-α (95% CI, 68.4-86.6), 70.8% in patients with concomitant use of thiopurine (95% CI, 61.5-80.1), and 76.7% in patients with a Mayo endoscopic score of 9-11 (95% CI, 69.0-84.4). None of the participants in the placebo group achieved clinical response at week 8 with steroid-dependent disease (P <.001), previous use of anti-TNF-α (P =.004), concomitant use of thiopurine (P =.016), or a Mayo endoscopic score of 9 to 11 (P <.001). In the IN group, the rate of mucosal healing was significantly higher than was seen in the placebo group for patients with steroid-dependent disease (50% vs 0%, P =.009) and Mayo score of 9-11 (42.9% vs 0%; P =.002). For patients receiving IN, the median fecal calprotectin level at week 8 significantly decreased in patients with steroid-dependent disease (from 1654.5 mg/kg at baseline to 105.0 mg/kg at week 8, P <.001) and in patients with previous use of anti–TNF-α (from 2999.0 mg/kg at baseline to 193.0 mg/kg at week 8; P =.004).

Limitations of this study included assessing endoscopic scores without viewing video clips from the endoscopic procedures. Also, the efficacy of IN may be inferior in patients with previous use of anti–TNF-α compared with patients with no previous use of anti-TNF-α, although the rate of mucosal healing was not significantly different between these cohorts. Nevertheless, short-term use of IN with rigorous monitoring is considered acceptable to balance the efficacy and adverse effects of IN.

The researchers demonstrated that 8 weeks of treatment with IN is effective in inducing clinical response and mucosal healing, even in patients with steroid-dependent disease or anti–TNF-α refractoriness. “Although herbal medicine has not been shown to be comparable to traditional medicine, IN can be used in patients who prefer to use herbal medicine or in patients who have experienced adverse effects from conventional treatments, such as corticosteroids, immunosuppressants, or biologics,” the researchers concluded. “At present, IN should be mainly used in cases of refractory or intolerance to conventional medicines for UC, in consideration of the adverse effects by IN.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Naganuma M, Sugimoto S, Fukuda T, et al. Indigo naturalis is effective even in treatment-refractory patients with ulcerative colitis: a post hoc analysis from the INDIGO study [published online September 16, 2019]. J Gastroenterol. doi: 10.1007/s00535-019-01625-2