Baseline Characteristics Associated With Response to Lubiprostone Treatment in Patients With Opioid-Induced Constipation

Abstract

Introduction: Lubiprostone, a ClC-2 chloride channel activator, is indicated for the treatment of opioidinduced constipation (OIC) in adults with chronic non-cancer pain. Straining, stool consistency, and constipation severity at baseline (BL) were examined to determine clinical characteristics that might be associated with treatment response to lubiprostone. Methods: Data were pooled from three 12-week, randomized, placebo-controlled, double-blind studies of lubiprostone (24 mcg twice daily) in patients ≥18 years old with OIC treated with non-methadone opioids for chronic non-cancer pain. Overall responders had ≥1 additional spontaneous bowel movement (SBM) compared with BL each week that data were available and ≥3 SBMs/week for ≥9 weeks. Differences in SBM response rates between patients treated with lubiprostone or placebo were analyzed by the Cochran-Mantel-Haenszel test, stratified by pooled site. Median values for changes from BL in SBM frequency were analyzed between groups using the Wilcoxon rank sum test. Results: With lubiprostone treatment vs placebo, patients with moderate or worse straining for ≥25% of SBMs at BL had higher treatment response rates (23.7% vs 17.2%; P=0.013) and higher median increases from BL in SBM frequency (2.3 vs 1.8; P=0.003), respectively. Patients with severe or very severe straining at BL likewise experienced significantly higher treatment response rates (Figure 1) and median changes in SBM frequency (Figure 2) with lubiprostone. Treatment response rates (24.1% vs 17.7%; P=0.034) and median increases in SBMs from baseline (2.4 vs 1.8; P < 0.001) were higher with lubiprostone treatment vs placebo, respectively, in patients with hard or very hard stool consistency for ≥25% of SBMs at BL; change in SBM frequency was significantly higher in patients with very hard stool consistency at BL who were treated with lubiprostone(Figure 2). Patients with absent/normal constipation severity at BL had higher treatment response rates with lubiprostone vs placebo (25.5% vs 16.8%; P=0.006; Figure 1), whereas significant increases in SBM frequency occurred with lubiprostone treatment in patients with absent/normal and severe constipation at BL (Figure 1).Figure 1Figure 2Conclusion: More severe straining, harder stool consistency, and less severe constipation at BL were associated with treatment response to lubiprostone.