Introduction: Opioid-induced Constipation (OIC) has been a major cause of distress in patients treated with opioids for cancer pain. Numerous drugs have been studied so far to manage refractory OIC. Naloxegol (NKTR-118), a pegylated form of naloxone, and Naldemedine, a peripherally acting μ-opioid receptor antagonist (PAMORA), have shown to alleviate OIC without affecting central analgesia. We study here the efficacy and safety of Naloxegol and Naldemedine in the treatment of OIC - both in clinical trials and in real-world clinical practice.
Methods: We searched and screened a total of 397 articles from databases such as PubMed, Cochrane, Embase, and Web of Science. A total of 9 studies assessing the use of Naloxegol and Naldemedine in patients with cancer pain were included in our review. We extracted data related to response rate and adverse events. Patient assessment of constipation symptoms (PAC-SYM) and assessment of constipation quality of life (PAC-QOL) scales were also analyzed. STATA version 3.2 was used for data analysis.
Results: Of the 397 studies that were identified by our database search, 9 studies were found to be relevant and met the inclusion criteria. Five studies (three RCT and 2 observational), and four observational studies were included for the assessment of Naldemedine and Naloxegol efficacy respectively. A total of 953 OIC cancer patients were treated with Naldemedine, and the response rate for Spontaneous Bowel Movements (SBM) is 72 % (95 % CI, p = 0.004). A significant improvement in Quality-of-life scales such as PAC-SYM and PAC-QOL was also reported. A total of 570 patients from four observational studies treated with Naloxegol were included in our review. In all these studies there was a significant improvement in Bowel Function and Quality of Life after adding Naloxegol despite the poor performance status of the participant. The most common adverse events leading to drug discontinuation were diarrhea, and abdominal pain, dysesthesia.
Discussion: Our results suggest that Naloxegol and Naldemedine are safe and effective in the treatment of refractory OIC in cancer patients. This review is significant in terms of that it includes data from both clinical trials and observational studies. The lack of a control group and a placebo arm in Naloxegol studies warrants more research. However, the randomized control trials employing Naldemedine had an efficacious and safer profile than placebo which is promising in the treatment of OIC with cancer pain.
