Objectives: To examine the efficacy and safety of lubiprostone for the treatment of opioid-induced constipation (OIC) in patients by opioid class received. Design: Data were pooled from three phase III, randomized, double-blind, placebo-controlled studies. Subjects/Setting: Adults with chronic noncancer pain receiving opioid therapy for 30 or more days and diagnosed with OIC. Methods: Overall mean change from baseline in spontaneous bowel movement (SBM) frequency, overall treatment response (≥1 SBM/week improvement over baseline SBM frequency in all treatment weeks with available data and ≥3 SBMs/week for ≥9 of the 12 weeks of treatment), and OIC-related symptoms were examined in patients taking opioids. Data were pooled and analyzed by opioid group. Results: In patients receiving phenanthrene opioids (e.g., oxycodone; N = 1,159), lubiprostone significantly increased overall mean changes in SBM frequency from baseline (P = 0.0001), increased overall response rate (P = 0.0024), and improved OIC symptoms (P ≤ 0.0229) vs placebo. Patients receiving phenylpiperidine opioids (e.g., fentanyl; N = 137) had significant improvement in SBM frequency (P = 0.0129) and favorable trends in response rates (21.4% vs 9.8%; P = 0.0723) and OIC symptoms vs placebo. Efficacy was not observed in overall analyses of patients receiving diphenylheptane opioids (e.g., methadone), although an increase in SBM frequency was observed in patients who received a morphine-equivalent daily dose of 200 or fewer mg, suggesting a dose-dependent negative interference of this opioid class on lubiprostone effects. For all groups, the lubiprostone adverse event profile was similar; the most common treatment-emergent adverse events were nausea and diarrhea. Conclusions: In patients using commonly prescribed opioids, lubiprostone is effective and generally well tolerated for the treatment of OIC.
RCT Entities:
Objectives: To examine the efficacy and safety of lubiprostone for the treatment of opioid-induced constipation (OIC) in patients by opioid class received. Design: Data were pooled from three phase III, randomized, double-blind, placebo-controlled studies. Subjects/Setting: Adults with chronic noncancer pain receiving opioid therapy for 30 or more days and diagnosed with OIC. Methods: Overall mean change from baseline in spontaneous bowel movement (SBM) frequency, overall treatment response (≥1 SBM/week improvement over baseline SBM frequency in all treatment weeks with available data and ≥3 SBMs/week for ≥9 of the 12 weeks of treatment), and OIC-related symptoms were examined in patients taking opioids. Data were pooled and analyzed by opioid group. Results: In patients receiving phenanthrene opioids (e.g., oxycodone; N = 1,159), lubiprostone significantly increased overall mean changes in SBM frequency from baseline (P = 0.0001), increased overall response rate (P = 0.0024), and improved OIC symptoms (P ≤ 0.0229) vs placebo. Patients receiving phenylpiperidine opioids (e.g., fentanyl; N = 137) had significant improvement in SBM frequency (P = 0.0129) and favorable trends in response rates (21.4% vs 9.8%; P = 0.0723) and OIC symptoms vs placebo. Efficacy was not observed in overall analyses of patients receiving diphenylheptane opioids (e.g., methadone), although an increase in SBM frequency was observed in patients who received a morphine-equivalent daily dose of 200 or fewer mg, suggesting a dose-dependent negative interference of this opioid class on lubiprostone effects. For all groups, the lubiprostone adverse event profile was similar; the most common treatment-emergent adverse events were nausea and diarrhea. Conclusions: In patients using commonly prescribed opioids, lubiprostone is effective and generally well tolerated for the treatment of OIC.