17th March 2017

Long-term data

A 24-month, open-label maintenance (OLM) 1 study of rifaximin-α 550mg twice daily in patients with recurrent HE who participated to the pivotal RCT 2 or in newly enrolled patients.

OBJECTIVE: to examine the long-term effect (up to 30 months) of rifaximin-α use on safety, survival and hospitalisations.

Safety and hospitalisations data were compared between the group receiving rifaximin-α in the OLM and the groups receiving rifaximin-α or placebo in the RCT.

Rates of HE-related hospitalisations in the OLM study 1 compared with the historical rates in the placebo and rifaximin-α arms in the RCT 2

Adapted from Mullen et al. 2014

Long-term safety 1

Adverse event (AE) rates did not increase over the long-term 1 , compared with those observed in pivotal RCT. 2

During long-term rifaximin-α treatment:

  • AE rates did not increase compared with those observed in the rifaximin-α or placebo arm in the pivotal RCT
  • No new serious AEs emerged
  • Mortality rate was similar to that observed in the placebo arm of the pivotal RCT and no deaths were attributed to rifaximin-α
  • Infection rates were lower than those reported in the rifaximin-α or placebo arm in the pivotal RCT
  • Incidence of gastrointestinal-related AEs was significantly higher with rifaximin-α plus lactulose (N=352) compared with rifaximin-α alone (N=40) (69.6% vs 47.5%; p<0.001)
  • Six patients treated with rifaximin-α developed C difficile infection: 2 in the RCT and 4 in the OLM (event rate 0.012)

UKE-HEP-XIF-2000014   DOP: June 2020


* Optional use of lactulose (~90% patients in 'All rifaximin-α' group received concomitant lactulose).

References

  1. TARGAXAN® Summary of Product Characteristics. Available at: http://www.medicines.org.uk/emc/medicine/27427
  2. NICE. Costing report: Implementing the NICE guidance on rifaximin for preventing episodes of overt hepatic encephalopathy (TA337). Available at: https:// www.nice.org.uk/guidance/ta337/resources/costing-report-428453677

References

  1. Mullen KD, et al. Clin Gastroenterol Hepatol 2014;12(8):1390-97
  2. Bass NM, et al. N Engl J Med 2010;362(12):1071-81