The Relationship Between Opioid Dose and Opioid-Induced Constipation in Japanese Patients With Cancer Pain: A Post Hoc Analysis of a Prospective Observational Cohort Study.

INTRODUCTION

This is a post hoc analysis of the multicenter, prospective, observational cohort study of Opioid-Induced Constipation in patients with cancer pain in Japan (OIC‑J) study (UMIN000025864), which investigated the incidence of opioid-induced constipation (OIC) in patients with cancer. The objective of the present study was to explore the relationship between opioid dose and the development of OIC.

METHODS

Patients of either sex, aged ≥20 years, with cancer pain and an Eastern Cooperative Oncology Group performance status (ECOG PS) score of two or less, and who had no pre‑existing constipation and required initiation of strong opioid analgesics were included. Patients who started laxatives on the same day of opioid initiation were considered to have "prophylactic use of laxatives" and were excluded. The relationship between daily opioid dose (oral morphine milligram equivalent; MME) and OIC incidence was assessed, along with Bowel Function Index (BFI) scores.

RESULTS

A total of 100 patients without prophylactic laxative use were included. Although none of the patients had constipation before opioid initiation, 66% developed OIC within two weeks of opioid initiation. Daily opioid dose was compared between the OIC group (n=66) and the non-OIC group (n=34) to determine whether opioid use differed based on the presence or absence of OIC. The mean±standard deviation daily opioid dose was higher in the OIC group (22.5±15.7 MME/day) than in the non-OIC group (17.8±13.0 MME/day), although the difference was not statistically significant (=0.1380). When assessing the trend between opioid dose and OIC incidence, the proportion of patients developing OIC increased numerically with higher opioid doses from 54.2% (95% confidence interval [CI]: 32.8‑74.5) at ≤10 mg/day to 80.8% (95% CI: 44.4-97.5) at >40-80 mg/day. In the multivariate logistic regression analysis, the odds ratio for daily opioid dose (per 10 mg) was 1.339 (95% CI: 0.949-1.890), indicating a trend toward increased OIC incidence with higher opioid doses; however, this was not a statistically significant factor associated with OIC incidence (=0.096). Furthermore, no correlation was observed between opioid dose and BFI score (=0.258).

CONCLUSIONS

This post hoc analysis reported that OIC incidence is not significantly dependent on opioid dose. The high incidence of OIC even in patients with cancer receiving low-dose opioids highlights the need to manage OIC proactively, regardless of the opioid dose.