Healthcare resource use and costs of opioid-induced constipation among non-cancer and cancer patients on opioid therapy: A nationwide register-based cohort study in Denmark.

Background And Aim: Opioid analgesics are often effective for pain management, but may cause constipation. The aim of this study was to determine healthcare resource use and costs in non-cancer and cancer patients with opioid-induced constipation (OIC).

Methods: This was a nationwide register-based cohort study including patients ≥18 years of age initiating ≥4 weeks opioid therapy (1998-2012) in Denmark. A measure of OIC was constructed based on data from Danish national health registries, and defined as ≥1 diagnosis of constipation, diverticulitis, mega colon, ileus/subileus, abdominal pain/acute abdomen or haemorrhoids and/or ≥2 subsequent prescription issues of laxatives. Total healthcare resource utilization and costs (including pharmacy dispense, inpatient-, outpatient-, emergency room- and primary care) were estimated according to OIC status, opioid treatment dosage and length, gender, age, marital status, and comorbidities using Generalised Linear Model.

Results: We identified 97169 eligible opioid users (77568 non-cancer and 19601 patients with a cancer diagnosis). Among non-cancer patients, 15% were classified with OIC, 10% had previous constipation, and 75% were without OIC. Patients characteristics of non-cancer OIC patients showed a higher frequency of strong opioid treatment (69% versus 41%), long-term opioid treatment (1189 days versus 584 days), advanced age (73 years versus 61 years), and cardiovascular disease (31% versus 19%) compared to those without OIC (P<0.001 for all comparisons). Non-cancer patients with OIC had 34% higher total healthcare costs compared to those without OIC (P<0.001) after adjusting for age, gender, opioid usage, marital status and comorbidities. Among cancer patients, 35% were classified with OIC, 14% had previous constipation, and 51% were without OIC. A higher proportion of cancer patients with OIC were continuous opioid users (85% versus 83%) and strong opioid users (97% versus 85%), compared to those without OIC (P<0.001 for both comparisons). Further, the mean number of days on opioids were higher for cancer patients with versus without OIC (329 days versus 238 days, P<0.001). Total healthcare costs were 25% higher for cancer patients with versus without OIC (P<0.001) after adjusting for age, gender, opioid usage, marital status and comorbidities.

Conclusions: The results of this nationwide study based on real life data suggested that both non-cancer patients and cancer patients suffering from opioid-induced constipation (OIC) may have higher healthcare resource utilization and higher associated costs compared to those without OIC.

Implications: Reducing the number of OIC patients has potential cost savings for the health care system. Special attention should be on patients at potential high risk of OIC, such as strong and long-term opioid treatment, advanced age, and concomitant cardiovascular disease.