OROS Hydromorphone ER: No Sustained Efficacy for Osteoarthritis Pain vs. Placebo
HONOLULU, HI—A randomized, placebo-controlled, double-blind study evaluating OROS hydromorphone ER for reducing moderate-to-severe osteoarthritis (OA) pain showed that though the treatment is effective in treating chronic OA, it failed to demonstrate sustained efficacy vs. placebo + rescue medication, “perhaps due to higher use of rescue medication in the latter group,” investigators concluded during a presentation at the American Pain Society's 31st Annual Scientific Meeting.
During a 1–4 week conversion/titration phase, Martin Hale, MD, of Gold Coast Research, Weston, FL, and colleagues converted opioid-tolerant patients to OROS hydromorphone ER at approximately 75% of the daily equianalgesic dose of their previous opioid dosage (5:1 morphine:hydromorphone), using dosages of OROS hydromorphone ER 8–48mg/day; max 64g/day.
Of the 334 patients who entered conversion/titration, 100 were randomized during the 12-week double-blind phase to maintain OROS hydromorphone ER at their stable dose and 100 to placebo plus rescue medication, in which OROS hydromorphone ER doses were tapered on Days 1–14 to discontinuation (blind was maintained). In the latter group, immediate-release hydromorphone 2–16mg/day was provided as rescue medication. Patients requiring a weekly mean of >2 rescue medication tablets/day during any 7-day period starting on Day 15 of the double-blind phase were withdrawn from the study as treatment failure. Mean stable dose of OROS hydromorphone ER at the start of the double-blind phase was 31mg/day and 32mg/day in the OROR hydromorphone ER and placebo groups, respectively.
Mean pain intensity numerical rating scale score change from baseline to Week 12 was the primary outcome measure. Secondary endpoints included Western Ontario and McMaster Universities OA Index (WOMAC) pain, stiffness, and physical function subscales, as well as Patient Global Assessment (PGA).
The investigators found that mean pain intensity (SD) decreased >50% from 6.9 (1.48) at screening to 3.0 (0.95) at the end of conversion/titration. During double-blind treatment, reductions in pain intensity were generally maintained in both treatment groups (mean [SE], 3.6 [0.2] at Week 12 for both groups), with no significant differences between treatment groups. However, the study design failed to demonstrate a greater efficacy of OROS hydromorphone against placebo. This could be attributed to significantly more rescue medication being used in those receiving placebo compared with than those receiving OROS hydromorphone ER (mean [SE], 1.5 [0.1] vs 1.1 [0.1]; P=0.006), the inability to titrate doses to >64mg/day, the imputation scheme for missing data, and the small sample size Additionally, differences between groups were not significant for any of the WOMAC subscales or PGA.
Of the 338 patients who entered the conversion and titration phase, 58.3% experienced and adverse event. Commonly reported adverse events during conversion/titration were constipation (17.5%); nausea, (15.7%); and somnolence (8.3%). In the double-blind treatment phase, constipation (20.0%) nausea (14.0%) and vomiting (9.0%) occurred more frequently in patients receiving OROS hydromorphone ER.