One-year efficacy and safety of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: KYONAL study.

OBJECTIVES: Naloxegol is a peripherally acting µ-opioid receptor antagonist (PAMORA) for treatment of opioid-induced constipation (OIC). The main objective was to analyse the long-term efficacy, quality of life (QOL) and safety of naloxegol in patients with cancer in a real-world study. METHODS: This one-year prospective study included patients older than 18 years, with active oncological disease who were under treatment with opioids for pain control and Karnofsky≥50 and OIC with inadequate response to treatment with laxative (s). All the patients received treatment with naloxegol according to clinical criteria. The main efficacy objectives were measured by the patient assessment of constipation QOL questionnaire (PAC-QOL), the PAC symptoms (PAC-SYM), the response rate at day 15, and months 1-3-6-12, and global QOL (EuroQoL-5D-5L). RESULTS: A total of 126 patients (58.7% males) with a mean age of 61.5 years (95% CI 59.4 to 63.7) were included. PAC-SYM and PAC-QOL total score and all their dimensions improved from baseline (p<0.0001). At 12 months, 77.8% of the patients were responders to naloxegol treatment. Global QOL was conserved from baseline. A total of 28 adverse reactions, mainly gastrointestinal were observed in 15.1% of the patients (19/126), being 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) appeared the first 15 days of treatment. CONCLUSION: The results of this first long-term and real-world-data study in patients with cancer, showed the sustained efficacy and safety of naloxegol for the treatment of OIC in this group of patients.

Efficacy of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: a 3-month follow-up analysis.

OBJECTIVES: Opioid-induced constipation (OIC) can affect up to 63% of all patients with cancer. The objectives of this study were to assess quality of life as well as efficacy and safety of naloxegol, in patients with cancer with OIC. METHODS: An observational study was made of a cohort of patients with cancer and with OIC exhibiting an inadequate response to laxatives and treated with naloxegol. The sample consisted of adult outpatients with a Karnofsky performance status score ≥50. The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) and the Patient Assessment of Constipation Symptoms (PAC-SYM) were applied for 3 months. RESULTS: A total of 126 patients (58.2% males) with a mean age of 61.3 years (range 34-89) were included. Clinically relevant improvements (>0.5 points) were recorded in the PAC-QOL and PAC-SYM questionnaires (p<0.0001) from 15 days of treatment. The number of days a week with complete spontaneous bowel movements increased significantly (p<0.0001) from 2.4 to 4.6 on day 15, 4.7 after 1 month and 5 after 3 months. Pain control significantly improved (p<0.0001) during follow-up. A total of 13.5% of the patients (17/126) presented some gastrointestinal adverse reaction, mostly of mild (62.5%) or moderate intensity (25%). CONCLUSIONS: Clinically relevant improvements in OIC-related quality of life, number of bowel movements and constipation-related symptoms were recorded as early as after 15 days of treatment with naloxegol in patients with cancer and OIC, with a good safety profile.

Antagonistas periféricos de los receptores opioides Mu en el tratamiento del estreñimiento inducido por opioides: revisión / Peripheral acting Mu opioid receptor antagonists in the treatment of the opioid-induced constipation: review

El estreñimiento inducido por opioides (EIO) constituye un problema clínico emergente que empeora la calidad de vida de los pacientes que requieren el uso de opioides para el manejo del dolor. Diferentes fármacos se han comercializado como antagonistas de los receptores opioides Mu periféricos, conocidos con el nombre de Peripheral Acting Mu Opioid Receptor Antagonists o PAMORA (metilnaltrexona, alvimopam y más recientemente naloxegol), que permiten la antagonización de los efectos periféricos de los opioides sin interferir en su efecto analgésico. Tanto metilnaltrexona como naloxegol han sido aprobados para el tratamiento del EIO, mientras que alvimopan está aprobado para la recuperación gastrointestinal después de resección intestinal con anastomosis primaria. Todos ellos han mostrado su eficacia clínica, pero es debatido el papel que han de tener en la estrategia global del manejo del EIO. Se revisa la información disponible sobre los PAMORA y se propone estrategia de uso clínico

The opioid induced constipation (OIC) is an emerging clinical problems that worsen the patients' quality of life requiring opioids for their pain relief. Many drugs have been launched as Peripheral Acting Mu Opioid Receptor Antagonists o PAMORAs (metylnaltrexone, alvimopam and more recently naloxegol), which antagonize the peripheral effects of opioids without affecting the opioids analgesia. Metylnaltrenone and naloxegol have been licensed for the treatment of CIO, meanwhile alvimopam is approved for the recovery of postoperative ileus after major abdominal surgery. All PAMORAs have shown clinical efficacy but is a matter of debate wich should be their role in the manangement of the CIO. The available information about PAMORAs is reviewed and informed strategy on the use of these drugs is proposed