American Academy of Pain Medicine 2010 Annual Meeting

Safety and Efficacy of Topical Diclofenac Sodium 1% Gel in Seniors and Younger Patients with Hand Osteoarthritis

San Antonio, TX—Roy D. Altman, MD, University of California-Los Angeles, and colleagues examined the safety and efficacy of diclofenac sodium 1% gel (DSG) in patients age < 65 and ≥ 65 years with hand osteoarthritis (OA). Results, presented at the annual AAPM meeting, revealed that DSG was effective and generally well tolerated for hand OA, regardless of patient age.

Three hundred eighty-five adults with radiographically verified hand OA were randomized to double-blind treatment with DSG (n=198) or placebo (n=187), 2 g to each hand 4 times daily for 8 weeks. OA pain intensity (100-mm visual analog scale), Australian/Canadian Osteoarthritis Hand Index (AUSCAN) score, and global rating of disease (GRD) at 4 and 6 weeks were the primary outcomes. Efficacy outcomes were compared by patient age (< 65 yr vs ≥ 65 yr) using analysis of variance (ANOVA). Researchers recorded all adverse events (AEs).

Participants randomized to DSG experienced improvements relative to baseline at weeks 4 and 6, in OA pain intensity (42%, 46%), total AUSCAN score (35%, 38%), and GRD (36%, 40%). These improvements were significantly superior to those experienced by patients randomized to placebo for OA pain intensity and total AUSCAN score (P ≤ 0.02) at weeks 4 and 6, but for GRD only at week 6 (P = 0.02). Efficacy differences (DSG vs placebo) between patients age < 65 years (DSG, n=109; placebo n=100) versus ≥ 65 years (DSG, n=89; placebo n=87) were not statistically significant. Application-site reactions were more common with DSG versus placebo for patients age < 65 years (4% vs 1%) and ≥ 65 years (5% vs 3%). Researchers reported that no gastrointestinal bleeding or serious treatment-related AEs occurred.

Funding was provided by Endo Pharmaceuticals Inc.
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Changes in Opioid Use and Economic Outcomes Among Diabetic Peripheral Neuropathic Pain Patients Treated with Duloxetine Versus Other Therapies

San Antonio, TX—Patients with continuous duloxetine-treated diabetic peripheral neuropathic pain (DPNP) appeared to have reduced opioid use and lower overall healthcare costs, as concluded in an abstract presented at the annual AAPM meeting. This exploratory analysis by Kimberly Fraser, BA, Abt Bio-Pharma Solutions, Inc, Lexington, MA, and colleagues examined changes in opioid use and healthcare costs among commercially-insured patients with DPNP who initiated duloxetine versus other standard of care (SOC) medications (tricyclic antidepressants, venlafaxine, gabapentin, pregabalin).

Administrative claims data were analyzed for patients with DPNP age 18-64 years who initiated duloxetine or SOC between 3/1/2005 and 12/31/2005.

Initiation was defined as no pill coverage in the previous 90 days for the same medication. All patients had opioids dispensed in the prior 90 days. Medication possession ratio (MPR) measured medication compliance. Participants were classified as either “continuous” (MPR ≥ 80%) users or “non-continuous” (MPR < 80%) users. Over the 12 months pre- and post-index periods, total opioid days, number of opioid prescriptions dispensed, and cumulative morphine equivalents were examined. In order to assess the changes (pre-index minus post-index) in opioid use (total, short-acting vs long-acting) and healthcare costs, multivariate regressions were performed.

One thousand two hundred eighty-one patients were identified (98 duloxetine continuous users, 243 duloxetine non-continuous users, 195 SOC continuous users, and 745 SOC non-continuous users). Results showed that duloxetine non-continuous and SOC (continuous and non-continuous) patients had significantly less reduction on total opioid days (-24.4, -23.7, -18.5, respectively, all P < 0.05) and short-acting hydrocodone use (days, prescriptions, and cumulative morphine equivalents) than duloxetine continuous patients, controlling for demographic and clinical characteristics. In addition, duloxetine non-continuous patients experienced $12,729 (P < 0.05) more total healthcare costs as compared to duloxetine continuous patients.

Funding for this project was provided by Eli Lilly and Company.
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Assessment for Opioid-Withdrawal Syndrome in Patients with Chronic Moderate-to-Severe Pain Taking ALO-01 (Morphine Sulfate and Naltrexone Hydrochloride) ER Capsules

San Antonio, TX—Pellets in ALO-01 (morphine sulfate and naltrexone hydrochloride) extended-release capsules (EMBEDA™), which are indicated for treatment of chronic moderate-to-severe pain, contain sequestered naltrexone designed for release to mitigate morphine-induced effects if tampered by crushing. In persons taking ALO-01 as intended (whole), trace amounts of naltrexone were found in a small proportion of plasma samples in early-phase single- and multiple-dose trials.

Two phase III trials, therefore, included assessments to determine whether any patients taking ALO-01 for chronic moderate-to-severe pain experienced opioid-withdrawal syndrome. Results, presented at the annual AAPM meeting, suggest that sequestered naltrexone in ALO-01 taken as directed does not increase risk of opioid withdrawal in patients with chronic moderate-to-severe pain.

Institutional review boards approved the protocol, informed-consent, and recruitment materials before trial initiation. Trial A (N=547): after dose titration, patients (n=344) were randomized to 12-weeks maintenance on ALO-01 or placebo (2-wk taper). Trial B: patients (n=465) took ALO-01 open-label for 12-months. The Clinical Opiate Withdrawal Scale (COWS: 0-48, mild [5-12]; moderate [13-24]; moderately severe [25-36]; severe [> 36]) evaluated opioid withdrawal.

Researchers from King Pharmaceuticals, Inc. found that no patients in either trial taking ALO-01 as directed experienced COWS consistent with moderate or greater withdrawal. In Trial A, one patient after 5-weeks titration had COWS of 16 (moderate withdrawal) after taking fewer doses than instructed; one patient during maintenance had a score of 28 (moderately severe) after abruptly stopping medication. Three patients during taper-to-placebo had scores 13, 23, and 23 (moderate withdrawal). In Trial B, a small proportion of patients had COWS consistent with mild withdrawal at week 4 (n=16, 4.8%) to month 6 (n=3, 1.4%). Five patients had COWS of 13-23, consistent with moderate withdrawal; all did not take medication as directed per study protocol.

Research was supported by King Pharmaceuticals, Inc.
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Poster

IV Acetaminophen Produces a Clinically Meaningful Pain Response and Opioid-Sparing Effect After Major Orthopedic Surgery: Pooled Data from Three Randomized, Placebo-Controlled Trials

San Antonio, TX—Intravenous (IV) acetaminophen has been used as the foundation of multimodal analgesia for years in Europe, and is currently under review by the FDA. Results from three randomized, double-blind, placebo-controlled studies (total N=231) evaluating the efficacy of IV acetaminophen 1 g after major orthopedic surgery (total hip or knee arthroplasty) were analyzed in order to assess the clinical relevance of the efficacy responses and the degree of opioid-sparing effects. See above table for three trials.

Analgesic efficacy was assessed by evaluating onset of effect, peak effects, and duration of effect. Onset was rapid in all three studies with a significant difference favoring IV acetaminophen over placebo by the end of the 15-minute infusion for many of the end points. Peak analgesic effect was highly statistically significant versus placebo in all studies (P < 0.001) for pain relief and pain intensity. The duration of analgesic effect was 4-6 hours across the studies.

IV acetaminophen caused significant opioid sparing (consumption reduction) across these studies. In study RC 210 3 002, mean IV morphine consumption was significantly reduced by 46% during the first 6 hours and 33% over 24 hours. Evaluating the first dosing period in studies 136-01-03 and 136-02-03, the mean opioid consumption was significantly reduced by 53% over 6 hours and by 63% over 4 hours, respectively. Across the studies, 13-50% of patients did not require any rescue opioid whatsoever during the first dosing period.

The three trials were sponsored by Bristol-Myers-Squibb Company, and funding for the poster was received from Cadence Pharmaceuticals.