The impact of abdominal pain on global measures in patients with chronic idiopathic constipation, before and after treatment with linaclotide: a pooled analysis of two randomised, double-blind, placebo-controlled, phase 3 trials

BackgroundFew clinical trials in chronic idiopathic constipation (CIC) patients have evaluated abdominal symptom severity and whether CIC patients with abdominal symptoms respond similarly to patients with limited abdominal symptoms. AimsTo examine abdominal symptom severity and relationships between symptoms and global measures at baseline; compare linaclotide's effect on symptoms in subpopulations with more or less abdominal pain; and assess relationships between symptom improvement and global measures in these two subpopulations. MethodsIn two phase 3 trials, patients meeting modified Rome II CIC criteria were assigned to linaclotide 145g, 290g, or placebo once daily. Patients rated abdominal and bowel symptoms daily during 2-week pre-treatment and 12-week treatment periods. Linaclotide's effect on symptoms and global measures [constipation severity, health-related quality of life (HRQOL), treatment satisfaction] and their inter-relationships were assessed in post hoc analyses of abdominal pain subpopulations. ResultsOf 1271 CIC patients, 23%, 32%, and 43% reported moderate-to-severe abdominal pain, discomfort, and bloating, respectively, during baseline. In more-severe abdominal pain patients, abdominal symptoms were more strongly correlated than bowel symptoms with global measures, but in less-severeabdominal pain patients, abdominal and bowel symptoms were similarly correlated with global measures, at baseline and post-treatment. Linaclotide significantly improved all symptoms and global measures in both subpopulations. ConclusionsWhen abdominal pain is present in CIC, abdominal and not bowel symptoms may drive patient assessments of constipation severity, HRQOL, and treatment satisfaction. Linaclotide (145g and 290g) is an effective treatment for both abdominal and bowel symptoms, even in CIC patients with more severe abdominal pain at baseline. (Clinicaltrials.gov: NCT00765882, NCT00730015).