Therapeutic Research

Abstract

Background：Linaclotide is used for treatment of irritable bowel syndrome with constipation（IBS‒C）and chronic constipation（CC）in Japan. However, factors affecting the efficacy and safety of linaclotide, including occurrence of diarrhea, have not been identified. Object：To determine whether patient baseline characteristics affect the occurrence of diarrhea and spontaneous bowel movement（SBM）frequency, to assess stool form（Bristol stool form scale, BSFS）over time, and to assess changes in diarrhea symptoms with dose reduction, in Japanese patients with IBS‒C or CC treated with linaclotide. Method：Retrospective pooled analysis of individual data from two randomized placebo‒controlled studies with open‒label extensions of once‒daily linaclotide 0.5 mg （52‒56 weeks）. Results：Among patients administered linaclotide at least once （randomized and/or extension phase）, baseline characteristics did not differ between patients with（n＝75） or without（n＝425）diarrhea. Diarrhea was well controlled by dose reduction or temporary discontinuation；most patients continued linaclotide with dose reduction. Among patients administered linoclotide during both randomized and extension phases（n＝256）, there were no differences in adjusted mean of change from baseline to Week 4 in weekly SBM frequency between subgroups（eg, male vs female, body mass index＜25 vs ≧25 kg/m2）. Over 12 weeks of treatment, the number of patients with diarrhea（BSFS：6, 7）did not increase and approximately 70％ of patients maintained good defecation status. Conclusion：Linaclotide can be used for long‒term treatment of constipation in patients with IBS‒C or CC, with dose adjustment as needed, regardless of patient characteristics.