The following article is a part of conference coverage from the American College of Gastroenterology 2021 Annual Meeting , held from October 22 to 27, 2021. The team at Gastroenterology Advisor will be reporting on the latest news and research conducted by leading experts in gastroenterology. Check back for more from ACG 2021.
Among patients with opioid-induced constipation (OIC) and an extreme symptom burden, naloxegol was associated with clinical improvements in multiple bowel parameters, according to research presented at the American College of Gastroenterology (ACG) 2021 Annual Meeting, held from October 22 to 27, 2021, in Las Vegas, Nevada and virtually.
Investigators sought to determine whether naloxegol, a peripherally acting mu-opioid receptor antagonist (PAMORA) that targets the gastrointestinal (GI) tract, could improve symptom outcomes in patients with extreme OIC. Naloxegol was previously shown to be effective for treating OIC in adults with chronic noncancer-related pain in 2 phase 3 trials (KODIAC 4/5).
The researchers pooled data from the 2 trials. They defined extreme OIC as <1 spontaneous bowel movement (SBM) and ˂1 complete SBM (sense of complete evacuation) (CSBM) per week. A total of 380 participants (28.4% of the full cohort) met the definition of extreme OIC and were included in the analysis.
SBM and CSBM frequency were obtained from the patients’ daily reports. The study authors assessed the changes from baseline with use of mixed-model repeated-measures models with fixed effects for baseline dependent variables, baseline laxative response, treatment, treatment-time interaction, and random effects for study center.
A total of 115 participants received naloxegol 12.5 mg, 137 received naloxegol 25 mg, and 128 received placebo.
Patients with extreme OIC had statistically significant and clinically relevant OIC symptom improvements that favored both naloxegol doses compared with placebo (P <.05 for all assessments) for weeks 1 to 12. Rapid symptom improvement regarding frequency of SBM, CSBM, and percentage of days with a CSBM was significantly increased in patients who received naloxegol compared with the placebo group. The improvements occurred within the first week (P <.05 for 12.5 mg/25 mg) and continued throughout treatment.
Regarding the number of SBM per week, the adjusted mean difference vs placebo was 1.12 for naloxegol 12.5 mg and 1.08 for naloxegol 25 mg. For number of CSBM per week, the adjusted mean difference vs placebo was 0.66 for naloxegol 12.5 mg and 0.61 for naloxegol 25 mg. For percentage of days per week with a CSBM, the adjusted mean difference vs placebo was 10.07 for naloxegol 12.5 mg and 9.20 for naloxegol 25 mg.
Patients who received placebo, naloxegol 12.5 mg, and naloxegol 25 mg had similar rates of GI adverse events (GI AEs) — abdominal pain (7.0%, 9.6%, 10.9%), diarrhea (3.1%, 4.3%, 5.8%), and nausea (3.1%, 10.4%, 6.6%, respectively).
The GI AEs that led to discontinuation were low in the placebo, naloxegol 12.5-mg group, and naloxegol 25-mg group — abdominal pain (1.6%, 0.9%, 2.2%), diarrhea (0%, 0.9%, 2.2%), and nausea (0%, 1.7%, 0.7%, respectively).
“Consistent with the therapeutic effects observed in the overall phase 3 data, in a cohort of OIC patients with an extreme symptom burden at baseline, potentially representing the highest need population, naloxegol yielded significant, sustained, and clinically relevant improvements in multiple bowel parameters,” the investigators concluded.
Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
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Brenner DM, Chey WD, Adler J, et al. Naloxegol achieved rapid and sustained improvement of opioid-induced constipation (OIC) symptoms in patients with extreme OIC: a pooled analysis of two pivotal phase 3 trials. Presented at: ACG 2021 Annual Meeting; October 22-27, 2021; Las Vegas, NV and virtual. Abstract P0397.