Efficacy and tolerability of once-daily OROS® hydromorphone and twice-daily extended-release oxycodone in patients with chronic, moderate to severe osteoarthritis pain:: Results of a 6-week, randomized, open-label, noninferiority analysis

Objective: This study compared the efficacy and tolerability of a once-daily controlled-release formulation of hydromorphone (OROS (R) hydromorphone, Janssen-Cilag, Beerse, Belgium) and twice-daily extended-release (ER) oxycodone in patients with chronic, moderate to severe osteoarthritis (OA) pain. OROS hydromorphone is currently available only in Europe. Methods: Adults who met American College of Rheumatology clinical criteria for OA of the knee or hip with moderate to severe mean daily pain intensity despite chronic use of stable doses of NSAIDs or other nonsteroidal, nonopiold therapies were eligible for participation in this randomized, open-label study. The study consisted of a 14-day dose-titration and stabilization phase and a 28-day maintenance phase. OROS hydromorphone and ER oxycodone were initiated at dosages of 8 mg QD and 10 mg BID, respectively. Patients maintained diaries in which they rated their pain (from 0 = none to 3 = severe) and pain relief (from 0 = no relief to 4 = complete relief). Other assessments completed every 14 days included patient and investigator global evaluations of treatment effectiveness (scale from 1 = poor to 5 = excellent), the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, and the Medical Outcomes Study (MOS) Sleep Scale. Adverse events (whether observed by study personnel, identified in response to questioning, or spontaneously reported) and vital signs were monitored throughout the study. The primary efficacy measures were the mean pain relief score at end point and the time from initiation of treatment to the third day of moderate to complete pain relief, as reported in the patient diary. Noninferiority analyses were conducted on all primary and secondary efficacy variables. Results: One hundred thirty-eight patients (71 OROS hydromorphone, 67 ER oxycodone) received treatment (safety population), and 83 (60.1%) completed the study. Data from 124 patients were included in the efficacy analyses; the majority of these patients were white (85.5%) and female (69.4%), with a mean age of 63.6 years. The most commonly affected joint was the knee (79.8 %). At end point, the OROS hydromorphone group had a mean pain relief score of 2.3 (median, 2.0) and the ER oxycodone group had a mean pain relief score of 2.3 (median, 2.3) (95% CI, -0.30 to infinity). The mean time to the third day of moderate to complete pain relief was 6.2 days (median, 4.0) in the OROS hydromorphone group and 5.5 days (median, 5.0) in the ER oxycodone group (95% CI, -0.31 to infinity). Mean pain intensity decreased from baseline to end point by 0.6 point in the OROS hydromorphone group and by 0.4 point in the ER oxycodone group. Mean scores on the patient global evaluation improved by a respective 1.2 and 1.0 points (median, 1 in both groups). Approximately two thirds of patients in each group (67.2% and 66.7%) rated the overall effectiveness of treatment as good to excellent at end point. There were no statistically significant differences between groups in total WOMAC scores at end point, and similar improvements from baseline in the WOMAC physical function, stiffness, and pain scales were observed in both groups. Whereas MOS sleep outcomes scores improved from baseline in both groups, OROS hydromorphone was associated with a significantly greater improvement on the MOS Sleep Problems Index I compared with ER oxycodone (P < 0.045). Adverse events were comparable in both groups; the most frequently reported adverse events were nausea (35.2% and 29.9%), constipation (29.6% and 25.4%), somnolence (25.4% and 17.9%), vomiting (16.9% and 11.9%), and dizziness (14.1% and 22.4%). Adverse events led to study discontinuation in 35.2% (25/71) of patients in the OROS hydromorphone group and 32.8 % (22/6 7) in the ER oxycodone group. Discontinuations due to adverse events during the titration phase were numerically greater in the OROS hydromorphone group (29.6% [21/71]) than in the ER oxycodone group (19.4% [13/67]). Only 1 serious adverse event (diarrhea in a patient receiving OROS hydromorphone) was considered possibly related to study drug. Conclusions: Once-daily OROS hydromorphone and twice-daily ER oxycodone provided similar pain relief in these patients with OA of the knee or hip. The tolerability profiles of the 2 agents were similar.