Naldemedine Improved Bowel Function in Patients With Opioid-Induced Constipation Compared With Placebo

Compared with placebo, naldemedine improves bowel function in patients with opioid-induced constipation while preserving analgesia, according to results from a meta-analysis published in BMJ Supportive and Palliative Care.

Researchers searched PubMed, the Cochrane Library, and ClinicalTrials for randomized controlled trials that compared the effectiveness of naldemedine with that of placebo in patients with opioid-induced constipation.

In order to satisfy the study’s inclusion criteria, enrolled patients had to receive chronic pain treatment and demonstrate signs and symptoms of opioid-induced constipation. Opioid-induced constipation was defined as fewer than 3 spontaneous bowel movements (SBMs) per week despite routine use of laxatives and the presence of straining, feeling of incomplete evacuation, and/or hard or small stools in at least 25% of bowel movements. In total, 6 trials that enrolled 2769 patients were included.

Primary outcomes of the analysis included the number of treatment responders, as well as mean changes in spontaneous bowel movements (SBMs), complete SBMs, and SBMs without straining per week compared with baseline. The secondary outcome was the measurement of pain intensity using the 11-point Numerical Rating Scale after week 1 and week 2 of treatment.

Participants treated with naldemedine had a significantly greater response to treatment (OR=2.48; 95% CI, 2.02-3.06; P <.00001), SBMs (mean difference (MD)=1.45; 95% CI, 1.14-1.76; P <.00001), complete SBMs (MD=0.89; 95% CI, 0.62-1.17; P <.00001) and SBMs without straining (MD=0.89; 95% CI, 0.61-1.17; P<.00001). Moreover, 74.0% of patients with cancer responded to the naldemedine treatment while only 52.3% of individuals without cancer responded to treatment. There was no significant difference in numeric pain rating scales after weeks 1 and 2 of treatment.

Limitations of the study include clinical diversity based on the differences in study protocols, follow-up times, and patient cohorts. Moreover, sponsorship bias may have been present in some of the studies analyzed, which may have influenced results.

“Naldemedine appears to be one of the most efficient [peripherally acting μ-opioid receptor antagonists], especially among patients with cancer,” the authors noted. “However, whether and for what kind of patients naldemedine should be used as the treatment of first choice needs further evaluation, mainly due to the absence of head-to-head analysis and limited data on patients with cancer. OIC affects the quality of life negatively and appears to be a psychosocial risk factor. Therefore, new and more targeted therapy options for this patient collective are needed,” they concluded.