UNDERUSE OF NALDEMEDINE IN OPIOID-TREATED PATIENTS: ITALIAN REAL-WORLD EVIDENCE

A. Ungar¹, A. Cuomo², F. Radaelli³, S. Calabria⁴, M. Leogrande⁴, M. Capacci⁵, M. Torrini⁶, L. Degli Esposti⁴ | ¹Head division of Geriatrics and Intensive Care Unit, Università di Firenze, Italy; ²IRCCS Istituto Nazionale Tumori Fondazione, Napoli, Italy; ³UOC di Gastroenterologia, Ospedale Valduce, Como, Italy; ⁴CliCon S.r.l. Società Benefit, Bologna, Italy; ⁵SOD Geriatria per l'Alta Intensità e Cardiologia Geriatrica, AOU Careggi e Università degli Studi di Firenze, Italy; ⁶Geriatrics Unit for High Care Complexity, Università di Firenze, Italy

Background. Chronic opioids represent a therapeutic option for cancer/non-cancer pain. About 50% of non-cancer opioid-treated patients experience opioid-induced constipation (OIC), which is more common among elderly and women (1). In Italy, naldemedine is reimbursed for refractory OIC (2). This Italian real-world analysis aimed to describe the health status of patients in chronic use of opioids and new users of naldemedine.
Methods. This retrospective observational analysis of Italian administrative databases covering ~9 million inhabitants care within the Italian National health Service (INHS), identified adults receiving ≥2 opioid prescriptions (ATC code N02A) during the inclusion period (01/01/2022-31/12/2024). Moreover, adults receiving ≥1 naldemedine prescription (ATC code A06AH05) from its reimbursement (2) to the end of follow-up (01/05/2020-31/12/2025) were identified. Index-date was the first opioid or naldemedine dispensation date, respectively. Baseline characteristics were described (age, sex, comorbidity burden by means of Charlson Comorbidity Index – CCI, and comorbidities of interest). For naldemedine users, analyses were made for patients with/without active cancer, based on ≥1 of the following criteria within 5 years before the index-date: in-hospital primary/secondary diagnosis (ICD-9-CM codes: 140-209, 235-239); ≥1 dispensation of ATC code L01; exemption code 048. Naldemedine treated patients were also assessed among the total chronic opioid users.
Results. Among 7.8 million adult inhabitants, 4.3% (N=335,671) were chronic opioid users. The mean age was 71±14.2 years, and 64.3% were female. The baseline comorbidity burden was low (mean CCI 0.8±1.3), with less than one quarter affected by chronic obstructive airway diseases (23.0%), diabetes (22.6%) and cancer. Among chronic opioid users, 2.2% (N=7451) received naldemedine. Among adult inhabitants, 0.1% (N=10,090) received naldemedine: 56.8% (N=5741) had active cancer, the mean age was 68.7±12.6 (vs 71.1±15.5 without cancer), 47.6% were females (vs 59.5%), mean CCI was high (3.2±2.8 vs 0.7±0.9), while more frequent comorbidities were observed in lower proportions compared to patients without active cancer (chronic obstructive airway diseases 27.6% vs 29.0%, diabetes 21.7% vs 21.9% and depression/mood disorders 17.2% vs 28.9%).
Conclusions. Patients receiving opioids reimbursed by the INHS are underestimated, but their health status results in line with expectations. Among them, a substantial underuse of naldemedine is observed. Overall, a substantial use of naldemedine in patients with cancer is observed, limiting this specific therapeutic option to a very small proportion of the potential population eligible for the drug. These patients are prescribed when they are in a condition of significant frailty, characterized by the coexistence of chronic diseases and a high average age, highlighting the need for early management of both cancer-related pain and OIC. A call-to-action appears to be urgent for non-oncologist through educational programs that would increase awareness and expertise on OIC.