An update on efficacy and safety considerations for the latest drugs used to treat irritable bowel syndrome

ABSTRACT

Introduction

Irritable bowel syndrome (IBS), globally affecting 11.2% of the population and imposing a direct annual cost of $1.7bn-$10bn in the US, is one of the today’s major therapeutic challenges. Therefore, there is urgent need to address this issue through reviewing the tolerability and efficacy of available medications.

Areas covered

Over the past decade, related experiments were cited through Clinicaltrials.gov, PubMed, WHO ICTRP, and Cochrane library. Pharmacological parameters of approved medications available in the USFDA, EMA, TGA and PMDA were also stated.

Expert opinion

Anti-spasmodics are used as the first-line treatment in pain-predominant IBS and IBS-D, among which calcium channel blockers and neurokinin-type 2 receptor antagonists seem to replace anti-cholinergic drugs. As second-line treatments, rifaximin is considered to be the best for IBS-D though it has lower efficacy than alosetron and eluxadoline. For IBS-C, linaclotide is the most effective and the safest second-line therapy, following laxatives/fibers, which may be replaced by tenapanor, in the future. When moderate to severe IBS is associated with severe pain or comorbid psychological disorders, gut-brain neuromodulators could also be prescribed. Regarding all this, there is still a paramount need to conduct careful clinical studies on efficacy, safety and cost-effectiveness of current approved and non-approved treatments.

KEYWORDS:

• Diarrhea-predominant irritable bowel syndrome (IBS-D)
• constipation-predominant irritable bowel syndrome (IBS-C)
• metabolic and toxicological considerations
• new drugs
• expert opinion
• clinical trials

Article highlights

• Given the high prevalence of IBS accompanied by several comorbidities and reduced QOL, it is of high value to establish IBS management upon prescribing more effective drugs with the least side effects, which is the main focus of this article.

• Currently, antispasmodics are considered as the first-line treatment for managing pain-predominant IBS, among which calcium channel blockers and NK2 receptor antagonists seem to replace anti-cholinergic drugs in the future.

• Alosetron, ramosetron, eluxadoline, mebeverine, and rifaximin have been approved for IBS-D with the first being the most effective and the latter being the most cost-effective and the safest treatment.

• For IBS-C, linaclotide is now the second-line treatment following laxatives/fibers, with the highest efficacy, safety, and cost-effectiveness amidst all, including lubiprostone, plecanatide, tegaserod, and tenapanor. Albeit, tenapanor, with increased efficiency, may also become a second-line treatment in the future.

• Gut-brain neuromodulators, including TCAs, SSRIs, and SNRIs could be prescribed when there is severe pain or comorbid psychological disorder in moderate to severe IBS; however, there are conflicting results on their efficacy, and most of them do not have acceptable safety profile.

• There are several under evaluation candidates for both IBS-C and IBS-D, the safety and efficacy of which are fully discussed in this review; however, further large-scale and well-designed studies are required.

• The pharmacological properties of most of the recent approved treatments are not well understood and require further investigation. This is more emphasized about tenapanor, ramosetron, linaclotide, and plecanatide.

Acknowledgments

The Iran National Science Foundation (INSF) is acknowledged for the general Seat Award directed to the corresponding author.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.