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Eluxadoline: a Treatment for IBS with Diarrhoea in Adults

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Eluxadoline: a Treatment for IBS with Diarrhoea in Adults ■ NEW PRODUCT Eluxadoline: a treatment for IBS with diarrhoea in adults STEVE CHAPLIN Eluxadoline (Truberzi) KEY POINTS is an oral mixed opioid- receptor agonist/ ■ Eluxadoline is an opioid-receptor agonist/antagonist with low systemic absorption antagonist licensed for ■ It is licensed for the treatment of irritable bowel syndrome with diarrhoea in the treatment of irritable adults and is recommended by NICE as a second-line agent bowel syndrome with ■ The recommended dosage is 75–100mg orally twice daily diarrhoea in adults. ■ In clinical trials, response rates were 27%–31% with eluxadoline and 19.5% with placebo after 26 weeks’ treatment This article examines its ■ Common adverse effects include constipation, nausea and abdominal pain properties, efficacy in ■ Pancreatitis and sphincter of Oddi spasm were uncommon adverse events clinical trials and side- ■ Treatment with eluxadoline costs £88.20 per month. effects. he initial management of irritable locally within the gastrointestinal tract, Tbowel syndrome (IBS) entails dietary slowing gastrointestinal transit, reducing and lifestyle change and treatment with urgency and improving stool consistency; antispasmodic agents.1 For people with its abuse potential is low. IBS and diarrhoea, loperamide is the anti- Eluxadoline is licensed for the treat- motility agent of first choice, adjusting the ment of IBS with diarrhoea in adults. The dose to achieve optimum stool consist- recommended dosage is 100mg twice ency. If this is unsatisfactory, treatment daily (reduced to 75mg twice daily if with a low-dose tricyclic antidepressant poorly tolerated). Treatment should be should be considered, with an SSRI a initiated at the lower dose in older people further option if this is unsuccessful. (over 65 years) and increased to 100mg Referral for cognitive behavioural ther- twice daily if well tolerated but not suf- apy, hypnotherapy and/or psychological ficiently effective. It is not known what therapy should be considered for people effect renal impairment has on the dis- with refractory IBS when drug treatment is position of eluxadoline but none is antic- unsuccessful after 12 months. ipated because renal excretion is only a NICE has now recommended eluxa- minor route of elimination. doline (Truberzi) as an option for treating Eluxadoline is contraindicated in irritable bowel syndrome with diarrhoea in patients with impaired hepatic function, adults when other drug treatments have those with pancreatitis or risk factors failed, are contraindicated or not tolerated. for it, patients with biliary duct obstruc- Treatment may be initiated only in sec- tion or sphincter of Oddi dysfunction, ondary care and should be stopped if no patients without a gall bladder, those improvement is evident after four weeks.2 with a history of severe constipation or gastro intestinal obstruction, and patients Mode of action and indications being treated with ciclosporin and other Eluxadoline is an agonist at mu and potent inhibitors of the membrane trans- kappa opioid receptors and an antag- port protein OATP1B1. Clinically signifi- onist at delta opioid receptors. It is cant drug interactions may occur with taken orally but has very low systemic high-dose statins, angiotensin II-receptor absorption due to low bioavailability and blockers and some CYP3A4 substrates first-pass metabolism. It therefore acts (eg pimozide, quinidine, nifedipine). 44 ❚ Prescriber October 2017 prescriber.co.uk Eluxadoline l NEW PRODUCT ■ Efficacy Eluxadoline has been evaluated in two 50 12 weeks phase 3 trials (IBS-3001 and IBS-3002) 26 weeks involving a total of 2425 patients ran- 40 domised to receive placebo or treatment with 75 or 100mg eluxadoline twice daily.3 Eligible patients had IBS with 30 diarrhoea of at least moderate severity with at least mild pain. Loperamide was 20 permitted as rescue medication but was Response rate (%) rarely used in any treatment group. 10 The primary endpoint was the pro- portion of patients who had a composite response at 12 or 26 weeks (defined as 0 recording on ≥50% of days: a reduction placebo eluxadoline eluxadoline of ≥30% from average baseline score for 75mg bd 100mg bd worst abdominal pain and, on the same days, a stool-consistency score of <5 Figure 1. Response rates (primary efficacy endpoint; see main text for definition) after 12 on the Bristol Stool Form (BSF) scale of and 26 weeks’ treatment with eluxadoline 75mg or 100mg twice daily or placebo (pooled 3 0–7). If the patient did not have a bowel data from IBS-3001 and IBS-3002 trials) movement on the day of assessment, a frequency and urgency. Eluxadoline was sphincter of Oddi spasm (one and seven response for that day was defined as an associated with greater improvement in cases respectively) were reported with improvement of ≥30% in the score for the abdominal pain and, at the higher dose, eluxadoline but not with placebo. worst abdominal pain. reduced bloating. Significantly more At baseline, the study population patients reported adequate symptom relief References reported moderate abdominal pain and with eluxadoline (53%–60%) than placebo 1. National Institute for Health and Care bloating (mean symptom score approxi- (44%–49%). Mean IBS-related quality of life Excellence. Irritable bowel syndrome in adults: mately 6/10 for each, with 0 indicating scores increased significantly more with diagnosis and management. CG61. February no symptoms and 10 the worst imagi- eluxadoline than with placebo. 2008 (updated April 2017). Available from: https://www.nice.org.uk/guidance/cg61 nable symptoms) and diarrhoea (mean 2. National Institute for Health and Care score over 6/7 on the BSF scale). Adverse effects Excellence. Eluxadoline for treating irritable Patients averaged three to four episodes Adverse events, recorded for 26–52 bowel syndrome with diarrhoea. TA471. August of urgency and five bowel movements per weeks’ treatment in the phase 3 trials, 2017. Available from: https://www.nice.org. day. About one-third of patients discon- were not consistently more frequent with uk/guidance/ta471 tinued study participation early, evenly the higher dose of eluxadoline. The most 3. Lembo AJ, et al. Eluxadoline for irritable divided between the treatment arms; frequently reported events were con- bowel syndrome with diarrhea. N Engl J Med adverse effects accounted for about 24% stipation (8% with eluxadoline vs 2.5% 2016;374:242–53. of withdrawals from eluxadoline treat- with placebo), nausea (7.7% vs 5.1%) 4. European Medicines Agency. Truberzi Public ment and 13% from placebo.4 and abdominal pain (6.5% vs 4.1%).3 Assessment Report. July 2016. Response rates were significantly In pooled studies, 1%– 2% of patients higher with eluxadoline than placebo after taking eluxadoline reported somno- Declaration of interests 12 and 26 weeks (p<0.001) (see Figure lence compared with 0.3% taking pla- None to declare. 1).3 A response was evident within the first cebo, but absolute numbers were small. week of treatment and was associated Pancreatitis (two cases at the lower dose Steve Chaplin is a medical writer with improved stool consistency and less of eluxadoline, three at the higher) and specialising in therapeutics prescriber.co.uk Prescriber October 2017 ❚ 45.
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