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Effect of Linaclotide in Treatment of Constipation-predominant Irritable Bowel Syndrome (IBS-C): A Systematic Review and Meta-analysis


Atluri, Dileep MD, MRCP1; Falck-Ytter, Yngve MD2; Chandar, Apoorva MBBS, MA, MPH2; Bharucha, Adil MBBS, MD3

American Journal of Gastroenterology: October 2013 - Volume 108 - Issue - p S567–S568

1. University Hospitals of Cleveland, Cleveland, OH;

2. Veterans Affairs, Cleveland, OH;

3. Mayo Clinic, Rochester, MN.

Purpose: Constipation-predominant irritable bowel syndrome (IBS-C) is a commonly encountered condition in clinical setting with few effective treatment options. Recent randomized controlled trials (RCTs) suggest that linaclotide may improve IBS-C symptoms. We systematically reviewed the available evidence and conducted meta-analysis to evaluate the efficacy and safety of linaclotide in treatment of IBS-C.

Methods: We searched the following database resources: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, SCOPUS, CINAHL, and gastroenterology conference proceedings and abstracts. Study eligibility criteria: RCTs comparing linaclotide with placebo in adult patients with study period of at least 12 weeks. Study appraisal and synthesis methods: Articles were independently assessed by two investigators. Standardized forms were used for blinded duplicate data extraction of study participants, quality, methods, and outcomes, including adequate relief of IBS-C symptoms and adverse events from eligible articles.

Results: Of 110 identified citations, 3 RCTs enrolling 1,773 patients met the inclusion criteria. The metaanalysis revealed that in comparison to placebo, fewer patients on linaclotide failed to achieve adequate IBS symptom relief (RR=0.73; 95% CI 0.65-0.82). Diarrhea was the most common side effect. Incidence of diarrhea leading to discontinuation of treatment was significantly higher in the linaclotide group (3 RCTs; 1,773 patients; RR=14.75; 95% CI 4.04-53.81). The quality of evidence was moderate for adequate relief response and high for significant diarrhea.

Conclusion: Few studies were available at the time of this analysis. All the included studies involved highly selective patient population, which limits generalizability. Conclusions: Linaclotide appears to be moderately effective in providing adequate relief of IBS-C symptoms with diarrhea being the major side effect. Further studies are needed to evaluate efficacy and safety of linaclotide with longer treatment periods.



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