Rifaximin effective in treatment unresponsive IBS-D

Patients with irritable bowel syndrome with diarrhoea (IBS-D) who have not responded to other medications may benefit from rifaximin, post hoc analyses of the TARGET 3* trial showed.

“Two-week courses of rifaximin were efficacious in improving abdominal pain, stool consistency, and bloating in adults with prior IBS medication use,” said the authors whose study was presented as a poster at DDW 2020.

“Rifaximin appears to be an effective treatment in patients unresponsive to other IBS-D therapies,” they said. 

Study participants were adults with IBS-D and mean daily abdominal pain and bloating scores of ≥3 and Bristol Stool Scale type 6 or 7 stool consistency for ≥2 days/week who previously received other treatments for IBS-D.

The trial was divided into an open-label and double-blind phase. During the open-label phase, 1,258 participants received rifaximin 550 mg TID for 2 weeks followed by a 4-week follow-up period. Patients with symptom relapse during the 18-week treatment-free observation phase were then randomized 1:1 (n=185 in each group) to receive rifaximin at the same dose or placebo for 2 weeks followed by 4-week follow-up and then a 6-week treatment-free period. Regardless of response, they received retreatment with the same dose of rifaximin or placebo for 2 weeks followed by a 4-week follow-up.

In the double-blind phase, response was significantly greater among rifaximin compared with placebo recipients for the composite of abdominal pain plus stool consistency (40.0 percent vs 23.2 percent; p<0.001). This improved response was evident when the two components were assessed separately (60.0 percent vs 40.5 percent; p<0.001 [abdominal pain] and 50.3 percent vs 34.6 percent; p=0.002 [stool consistency]). There was also a significantly greater response to bloating with rifaximin vs placebo (53.5 percent vs 40.5 percent; p=0.01). [DDW 2020, abstract Mo1329 – 2020]

The researchers also noted a greater likelihood of sustained response** with rifaximin vs placebo for the composite of abdominal pain plus stool consistency (16.8 percent vs 6.5 percent; p<0.001) as well as for each component (34.1 percent vs 16.8 percent; p<0.0001 [abdominal pain] and 22.7 percent vs 14.1 percent; p=0.03 [stool consistency]).

Response greater with rifaximin regardless of colonoscopy timing

In an analysis of the phase III TARGET 1 and 2*** trials, patients with IBS-D were randomized to receive rifaximin 550 mg TID or placebo for 2 weeks followed by a 10-week treatment-free follow-up period. Response was stratified according to timing of colonoscopy – ≤60 days (n=408 and 431 rifaximin and placebo recipients, respectively) or >60 days (n=215 and 203, respectively) before the first dose. [DDW 2020, abstract Mo1338 – 2020]

There was a greater response with rifaximin compared with placebo with regard to a composite of pain and stool consistency regardless of whether colonoscopy was performed ≤60 days (46.6 percent vs 39.4 percent; p=0.04) or >60 days (46.5 percent vs 33.0 percent; p=0.005) before the first dose. The findings remained significant when the composite components were assessed separately.

Responder rate difference between rifaximin and placebo did not significantly differ according to timing of colonoscopy (eg, 7.1 percent [≤60 days] vs 13.5 percent [>60 days]; p=0.27 for the composite of pain and stool consistency).

“In this pooled analysis, a 2-week course of rifaximin in adults with IBS-D had significantly greater efficacy vs placebo regardless of whether colonoscopy occurred ≤60 or >60 days before start of treatment,” the researchers said.

They noted that the treatment differences between rifaximin and placebo were greater in the >60 days group, which may be at least partially attributable to “re-establishment of IBS-related gut microbiota dysbiosis,” though further study is required to establish this hypothesis.