Prolonged-release oxycodone/naloxone in opioid-naïve patients - subgroup analysis of a prospective observational study.

OBJECTIVE: Prolonged-release oxycodone/naloxone (OXN PR) showed improved gastrointestinal tolerability and equivalent analgesic efficacy compared to oxycodone alone in patients with non-cancer pain or cancer pain. This is the first dataset to demonstrate its effectiveness and safety compared to other strong opioids in opioid-naïve patients. METHODS: This is a subgroup analysis of a 4- to 6-week multicenter, observational study. A total of 162 opioid-naïve patients with moderate-to-severe pain of varying etiologies received either OXN PR or other strong opioids (control group). Documented parameters include pain relief (numeric rating scale), bowel function (Bowel Function Index [BFI]), pain-related functional impairment (Brief Pain Inventory Short Form), quality of life (QoL; EuroQol EQ-5D-3L) and a global therapy assessment. RESULTS: OXN group patients experienced a substantial clinically important reduction in mean pain intensity of 51.4%, compared to a 28.6% reduction in control patients. Although the BFI remained in the reference range in both groups, there was a difference between BFI changes during treatment in favor of OXN PR. The superior effectiveness of OXN PR was paralleled by greater improvements of pain interference and QoL and fewer adverse drug reactions compared to other strong opioids. CONCLUSION: The favorable outcomes under real-life conditions suggest that OXN PR provides a valuable option for treatment of moderate-to-severe pain without using weak opioids first.

Prolonged-release oxycodone/naloxone in the treatment of neuropathic pain - results from a large observational study.

OBJECTIVES: Opioids have shown consistent efficacy in neuropathic pain, but opioid-induced bowel dysfunction is a relevant problem. In controlled clinical trials, a fixed-dose combination of prolonged-release (PR) oxycodone/PR naloxone was superior to oxycodone alone in bowel function, while providing effective analgesia. The present report is an analysis of its efficacy and safety in a subgroup of patients with severe chronic neuropathic pain who were treated in a large observational study under real-life conditions. RESEARCH DESIGN AND METHODS: Dosed according to pain severity, 1488 patients with chronic severe neuropathic pain received PR oxycodone/PR naloxone for up to 4 weeks. Variables included pain severity, patient-reported bowel function (Bowel Function Index; BFI) and quality of life. RESULTS: During treatment with PR oxycodone/PR naloxone, mean pain intensity decreased in opioid-naive and opioid-pretreated patients. After 4 weeks on treatment, mean BFI scores were reduced from 41.6 ± 31.6 at the initiation visit to 16.5 ± 19.6 (p < 0.001), reflecting normal bowel function. Quality of life was improved by 47%. CONCLUSIONS: Treatment of severe neuropathic pain with PR oxycodone/PR naloxone provided effective analgesia with the added benefit of favorable effects on bowel function and quality of life.

A randomized, placebo-controlled phase 3 trial (Study SB-767905/012) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain.

UNLABELLED: Gastrointestinal (GI) side effects are common with opioid medication, and constipation affects ∼40% of patients. Such symptoms considerably impair patients' quality of life. Alvimopan is an orally administered, systemically available, peripherally acting mu-opioid receptor (PAM-OR) antagonist approved in the US for short-term, in-hospital management of postoperative ileus in patients undergoing bowel resection. This double-blind, placebo-controlled trial was conducted as part of a recently discontinued clinical program, in which alvimopan was being developed for opioid-induced constipation (OIC). Patients (N = 518) receiving opioids for non-cancer pain were randomized to receive alvimopan .5 mg once daily, alvimopan .5 mg twice daily, or placebo for 12 weeks. The primary efficacy endpoint was the proportion of patients experiencing ≥ 3 spontaneous bowel movements (SBMs; bowel movements with no laxative use in the previous 24 hours) per week over the treatment period and an average increase from baseline of ≥ 1 SBM per week. A significantly greater proportion of patients in the alvimopan .5 mg twice-daily group met the primary endpoint compared with placebo (72% versus 48%, P < .001). Treatment with alvimopan twice daily improved a number of other symptoms compared with placebo and reduced the requirement for rescue laxative use. The opioid-induced bowel dysfunction Symptoms Improvement Scale (SIS) responder rate was 40.4% in the alvimopan .5 mg twice daily group, versus 18.6% with placebo (P < .001). In general, alvimopan .5 mg once daily produced qualitatively similar but numerically smaller responses than twice-daily treatment. Active treatment did not increase the requirement for opioid medication or increase average pain intensity scores. Over the 12-week treatment period, alvimopan appeared to be well tolerated. PERSPECTIVE: These results demonstrate the potential for a PAM-OR antagonist to improve the symptoms of OIC without antagonizing opioid analgesia.

Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain.

UNLABELLED: This randomized, double-blind, placebo- and active-controlled, parallel-group study was designed to demonstrate the superiority of oxycodone in combination with naloxone in a prolonged release (PR) formulation over placebo with respect to analgesic efficacy. The active control group was included for sensitivity and safety analyses, and furthermore to compare the analgesic efficacy and bowel function of oxycodone PR/naloxone PR with oxycodone PR alone. The analgesic efficacy was measured as the time from the initial dose of study medication to multiple pain events (ie, inadequate analgesia) in patients with moderate to severe chronic low back pain. The full analysis population consisted of 463 patients. The times to recurrent pain events were significantly longer in the oxycodone PR/naloxone PR group compared with placebo (P < .0001-.0003); oxycodone PR/naloxone PR reduced the risk of pain events by 42% (P < .0001; full analysis population). The appearance of pain events was comparable for oxycodone PR/naloxone PR versus oxycodone PR, confirming that the addition of naloxone PR to oxycodone PR in a combination tablet did not negatively affect analgesic efficacy of the opioid. Furthermore, oxycodone PR/naloxone PR offers benefits in terms of an improvement in bowel function. In a therapeutic area of great unmet need, therefore, the combination tablet of oxycodone PR/naloxone PR offers patients effective analgesia while improving opioid-induced bowel dysfunction. Taken together with the observation that the safety profile of oxycodone PR/naloxone PR is consistent with that expected from other opioid analgesics except opioid-induced constipation, these findings indicate that the addition of naloxone to oxycodone in a PR combination tablet offers improved tolerability. Oxycodone PR/naloxone PR is therefore a promising new treatment approach for the management of chronic pain. PERSPECTIVE: This study evaluated the analgesic efficacy and safety of the combination of oxycodone PR/naloxone PR in chronic nonmalignant pain. Opioids are often reduced in dosage or even discontinued as a result of impaired bowel function, leading to insufficient pain treatment. Not only does oxycodone PR/naloxone PR demonstrate analgesic efficacy comparable with oxycodone PR, but it also improves opioid-induced bowel dysfunction, and may therefore improve the acceptability of long-term opioid treatment for chronic pain.

Adjustment to chronic pain in back pain patients classified according to the motivational stages of chronic pain management.

UNLABELLED: According to Prochaska's transtheoretical model, the Freiburg Questionnaire stages of chronic pain management (FQ-STAPM) were used to classify chronic back patients into 4 distinct motivational stages. The FQ-STAMP was completed by 163 chronic back pain patients. Pain chronicity was measured by the Mainz Pain Staging System; pain intensity was measured by the numeric rating scale. Healthcare system expenses were considered as number of consulted physicians, number of stays in hospital, and number of rehabilitation programs. As psychometric tests, the lower pain disability index (PDI), the Hospital Anxiety and Depression Scale (HADS), and a quality of life score (SF36) were used. Patients were in the following motivational stages: precontemplation in 30%, preparation in 19%, action in 30%, maintenance in 21%. The intensity of pain in the precontemplation stage patients was significantly higher compared to patients in the maintenance stage. A lower pain chronicity was related to a significantly higher motivation. Moreover, there was a significant increase in healthcare system expenses by the lesser motivated patients. Patients in the maintenance stage used significantly less opioids than patients in the precontemplation stage. The higher motivated patients had a significantly lower PDI, a significantly lower HADS, and a significantly higher quality of life compared to less motivated patients. PERSPECTIVE: The study indicates that the FQ-STAPM might be a useful tool to classify chronic back pain patients and to work out a strategy together with the patient relevant to the outcome of pain management among chronic back pain patients.