INDIGO NATURALIS FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE REFRACTORY TO ADVANCED IMMUNOSUPPRESSIVE THERAPY

Abstract BACKGROUND Despite advances in immunosuppressive therapies, treatment-refractory inflammatory bowel disease (IBD) remains a major challenge. An annual loss of response occurs in 10–20% of patients receiving advanced therapies, and only 30–50% achieve clinical remission. This therapeutic ceiling highlights the necessity to explore novel therapy. At the same time, the use of complementary and alternative medicine (CAM) is prevalent in this population. Among these, Indigo Naturalis (IN), a traditional herbal supplement, has shown promise for inducing clinical response in ulcerative colitis (UC), a subtype of IBD. The objective of this pilot study is to examine the efficacy of IN in treating UC patients refractory to advanced therapy and explore potential cytokine pathways involved. METHODS We conducted a retrospective chart review of UC patients treated with IN at an academic center between 1/1/2023 and 5/1/2025. Demographics, disease phenotype, concomitant medications, prior advanced therapies, and IN dosing were abstracted from the medical records. Clinical response and remission were defined by standard criteria for the partial Mayo score (pMayo). Adverse events were documented. Cytokine analysis was performed on plasma using a commercial Proteome Human Cytokine Array kit. RESULTS 11 UC patients were started on IN (mean age 53.4 ± 16.7 years; 36% female). 9 patients had failed at least one advanced therapy, with 55% having been on 3 or more advanced therapies (Table 1). The median baseline pMayo was 5 with IQR 3. The IN dose ranges from 1-3 grams daily. 36% of patients took IN for over a year. Following IN initiation, either as monotherapy or adjunctive therapy, 8 of 11 patients (72.7%) achieved a clinical remission. 1 patient discontinued IN due to worsening abdominal pain, while 2 patients discontinued IN due to lack of benefit. Cytokine analysis was performed in 2 UC controls and 2 UC patients taking IN. Patients on IN had decreased signal intensity for both complement C5/C5a and CXCL11/I-TAC compared to controls. CONCLUSION The majority of patients with treatment-refractory UC experienced clinical improvement with IN, and treatment was well tolerated. These findings suggest that IN may represent a promising adjunctive therapy in refractory disease and warrant further investigation in larger clinical trials with mechanistic endpoints.