Rifaximin superior to lactulose as monotherapy for preventing overt HE recurrence

Secondary prophylaxis with rifaximin monotherapy is significantly more efficacious than lactulose monotherapy in preventing the recurrence of overt hepatic encephalopathy (HE) and is well tolerated in patients with cirrhosis who are in overt HE remission, suggests a post hoc analysis of two randomized trials presented at EASL 2024.

During up to 6 months of treatment, significantly fewer patients treated with rifaximin experienced an overt HE episode vs those treated with lactulose (23.2 percent vs 49 percent), with a number needed to treat of 4 (p<0.0001). Receiving rifaximin monotherapy was associated with a 60 percent reduction in the risk of a breakthrough overt HE event vs lactulose monotherapy (hazard ratio, 0.40, 95 percent confidence interval, 0.26–0.62; p<0.001).

The safety profile also favoured rifaximin, with a lower incidence of ≥1 drug-related adverse event (AE) reported in patients treated with rifaximin vs those treated with lactulose (6.4 percent vs 24.1 percent), as well as less frequent reporting of ≥1 serious AE in the former group (35.2 percent vs 41.4 percent). [EASL 2024, poster FRI-069]

“Our data suggest rifaximin monotherapy could be a viable management option for reducing the risk of overt HE recurrence in appropriate patients.” said Professor Jasmohan Bajaj, a gastroenterologist at the Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University in Richmond, Virginia, US.

Pooling data from a phase III and a phase IV trial

Rifaximin is typically offered as an add-on therapy to lactulose when additional episodes occur despite secondary prophylaxis with lactulose monotherapy. The present findings were derived from pooling data from studies RFHE3001 and RFHE4044 to determine whether rifaximin monotherapy can serve as an alternative management strategy to lactulose monotherapy

Study RFHE3001 was a phase III, randomized, double-blind, placebo-controlled trial in patients with ≥2 episodes of overt HE within the 6 months preceding the screening visit. While the trial evaluated the efficacy of rifaximin 550 mg twice daily versus placebo, concomitant administration of lactulose was permitted in both arms (used by 91.3 percent at baseline). [N Engl J Med 2010;362:1071-1081]

Study RFHE4044 was a phase IV, randomized, open-label, active-controlled trial in patients with ≥1 episode of overt HE within the 6 months preceding the screening visit. The study compared rifaximin monotherapy with rifaximin plus lactulose.

Accordingly, the current analysis (n=270) compared patients who received rifaximin without concomitant lactulose from studies RFHE3001 and RFHE4044 with those who received lactulose plus placebo from study RFHE3001.