One-year clinical efficacy and safety of indigo naturalis for active ulcerative colitis: a real-world prospective study

Abstract

Background/aims: Recent studies suggested a favorable effect of indigo naturalis (IN) in inducing remission for refractory ulcerative colitis (UC), however, the maintenance effect of IN for patients with UC remains unknown. Therefore, we conducted a prospective uncontrolled open-label study to analyze the efficacy and safety of IN for patients with UC.

Methods: Patients with moderate to severe active UC (clinical activity index [CAI] ≥ 8) took 2 g/day of IN for 52 weeks. CAI at weeks 0, 4, 8, and 52 and Mayo endoscopic subscore (MES) and Geboes score (GS) at weeks 0, 4, and 52 were assessed. Clinical remission (CAI ≤ 4), mucosal healing (MES ≤ 1), and histological healing (GS ≤ 1) rates at each assessment were evaluated. Overall adverse events (AEs) during study period were also evaluated. The impact of IN on mucosal microbial composition was assessed using 16S ribosomal RNA gene sequences.

Results: Thirty-three patients were enrolled. The rates of clinical remission at weeks 4, 8, and 52 were 67%, 76%, and 73%, respectively. The rates of mucosal healing at weeks 4 and 52 were 48% and 70%, respectively. AEs occurred in 17 patients (51.5%) during follow-up. Four patients (12.1%) showed severe AEs, among whom 3 manifested acute colitis. No significant alteration in the mucosal microbial composition was observed with IN treatment.

Conclusions: One-year treatment of moderate to severe UC with IN was effective. IN might be a promising therapeutic option for maintaining remission in UC, although the relatively high rate of AEs should be considered.

Keywords: Colitis, ulcerative; Indigo naturalis; Maintenance therapy; Qing-Dai.

Fig. 1.

The clinical response rate and clinical remission rate at weeks 4, 8, and 52 after initiation of indigo naturalis were calculated using non-responder imputation.

Fig. 2.

Indicates the week in which the patients achieved a new clinical remission. Thirty patients achieved clinical remission. Although most patients respond early to indigo naturalis treatment, some had delayed response.

Fig. 3.

Trends for clinical activity index (CAI) and C-reactive protein (CRP) scores. (A) CAI scores at weeks 0, 4, 8, and 52 after the initiation of indigo naturalis (IN). (B) CRP levels at weeks 0, 4, and 52 after the initiation of IN.

Fig. 4.

(A) The mucosal healing rate and the complete mucosal healing rate at weeks 4 and 52 were calculated using non-responder imputation. Histological healing was defined as Geboes score ≤1. (B) Mayo endoscopic subscores at weeks 0, 4, and 52 after the initiation of indigo naturalis (IN). (C) Geboes scores at weeks 0, 4, and 8 after the initiation of IN.

Fig. 5.

(A) Alpha diversity by the observed species index and (B) beta diversity by the metrics of weighted UniFrac were not significantly different before and after indigo naturalis treatment. The lines in the box are median and whiskers are interquartile range.