Efficacy and Safety of Lubiprostone in Patients with Chronic Constipation

Abstract

In patients with chronic constipation, lubiprostone produced a bowel movement in the majority of individuals within 24 h of initial dosing, with sustained improvement in frequency as well as other constipation symptoms over 4 weeks of treatment.

Effective Constipation Treatment Changes More Than Bowel Frequency: A Systematic Review and Meta-Analysis

“…22 Despite the different impact on colorectal sensatory mechanisms, 19,[21][22][23] linaclotide, lubiprostone and tegaserod similarly alleviated chronic pain ratings in IBS-C and constipation. [9][10][11][24][25][26] The relationship between improved bowel patterns and decreased discomfort, as highlighted by our meta-analysis, does not establish an underlying mechanism, but fits into a larger context of past experimental and clinical data. As mentioned above, loperamide reduced bowel frequency in healthy volunteers to a degree sufficient to trigger symptoms consistent with IBS-C. 29 While few comparative effectiveness analyses of active agents are available, the limited evidence does not support superiority of more recently developed agents with polyethylene glycol (PEG) being either superior or equivalent to tegaserod.…”

“…Of the articles included in the analysis, 16 focused on chronic constipation, 11,[24][25][26][32][33][34][35][36][37][38][39][40][41][42] 11 enrolled patients with IBS-C, 27,43-51 with one also including patients with mixed bowel patterns. 48 One study did not differentiate IBS-C from constipation.…”

“…The researchers often included authors who participated in the formulation of these very criteria and/or led trials examining drug effects on constipation or IBS-C in separate studies with similar methodology, at times operationally defining IBS-C by a pain intensity of 3 or more on a 5-point scale. 24,25,63,[76][77][78] We recognize that other factors, such as pain frequency or impact on quality of life, were not measured and may define differences in those with constipation compared to IBS-C. While our meta-analysis cannot truly address conceptual issues about disease mechanisms or manifestations, the findings are consistent with prospective cohort studies that show a substantial overlap between constipation and IBS-C. 1,3,4 Prospective studies will have to determine whether and to what degree these diseases are truly distinct or whether they primarily differ based on a potentially shifting focus and emphasis on symptoms associated with constipation.…”

“…22 Despite the different impact on colorectal sensatory mechanisms, 19,[21][22][23] linaclotide, lubiprostone and tegaserod alleviated chronic pain ratings in IBS-C and constipation. [9][10][11][24][25][26] Interestingly, two studies compared the effects of tegaserod with polyethylene glycol (PEG), which acts as an osmotic laxative and should thus not directly affect sensory mechanisms or pain. However, the simple laxative was either superior to or demonstrated an equivalent effect to tegaserod.…”

ThePAC‐SYMquestionnaire for chronic constipation: defining the minimal important difference

“…As such, the questionnaire is increasingly being used as a patient‐reported outcome measure in clinical trials of constipation. Over 18 clinical studies have used the PAC‐SYM, since its validation in 1999: 14 of these have been reported since 2010 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Moreover, these trials have examined a range of interventions including sacral nerve stimulation,20 lifestyle changes19 and pharmacological agents 6, 11…”