The long term efficacy and safety of adjuvant opioids in older persons with rheumatoid arthritis

s The Journal of Pain S79 (412) The long term efficacy and safety of adjuvant opioids in older persons with rheumatoid arthritis S Albano-aluquin, N Elmagboul, and S Maclary; Penn State University College of Medicine, Hershey, PA We retrospectively assessed the long termefficacy and safety of opioids in older personswith rheumatoid arthritis(RA.We included RA patients aged$60 years who received opioids based on moderate-severe numerical pain scores (NPS 010 scale) of$5. Efficacymeasures at immediate and last follow-upswere$30% improvement in pain (NPS30), $0.22 improvement in physical function by health assessment questionnaire (HAQ-DI) and $50% improvement in clinical disease activity index (CDAI50). Safety outcomes include discontinuations from serious events and abnormalities in creatinine/transaminases and reports of misuse/diversion. Of 20 patients, 16 (80%) were women. Mean age was 69.9 6 5.1 years and disease duration 10.6 6 8.6 years. Mean baseline scores were 7.2 6 2.1 for NPS(0-10),1.19 6 0.8 for HAQ-DI(0-3)and 25.8 6 12.6 for CDAI(0-76). Five patients (25%) received Schedule II short-acting morphine, oxycodone 6 acetaminophen, 1(5%)got Schedule II long-acting morphine, oxycodone or fentanyl plus Schedule III/IV-hydrocodone, tramadol or codeine, 3 (15%) received Schedule II long-acting plus short-acting and 11 (55%) received Schedule III/IV only. 16(80%) patients received a total daily dose of #120 mg morphine equivalents while 4 (20%)had $120 mg. At 1)immediate (mean 4 6 2 months) and 2)last (Median 11 months; range 6-71) follow-ups, NPS30 was achieved in 8/19 (42%) and 9/19 (47%), HAQ-DI 0.22 in 4/15 (27%) and 5/14 (46%) and CDAI50 in 1/19 (5.2%) and 1/18 (5.5%) respectively. Oxycodone achieved NPS30 in 5/7 (71.4%) patients . One serious event of intestinal obstruction in a diabetic on fentanyl-oxycodone regimen was noted. Misuse, diversion or creatinine/transaminase abnormalities were not detected. Responders had worse baseline pain versus non-responders(8.6 6 1.8 vs. 6.2 6 1.8;p=.008). In this older RA cohort, opioidsparticularly oxycodone-effectively improved pain and physical function. (413) Acute pain control challenges with suboxone therapy in a patient with compartment syndrome secondary to McArdle’s Disease: a case report G Chang Chien, Z McCormick, S Chu, and P Joseph; Rehabilitation Institute of Chicago, Chicago, IL A 50-year-old male with a history of McArdle’s disease complicated by 2 prior episodes of rhabdomyolysis and opioid dependence on Suboxone , presented to the Emergency Department (ED) with severe bilateral anterior thigh pain. On exam, his quadriceps were tender to palpation and he demonstrated 2/5 weakness of hip flexion, knee flexion and extension, ankle dorsi and plantar flexion. Over the following 8 hours, he was given a total of 12mg of IV push dilaudid without pain relief. Subsequently, patient controlled analgesic (PCA) of dilaudid was started at 0.5mg PRN q15min without basal medication, which only decreased the patient’s pain level from 10/10 to 8/10 intensity. His serum creatinine kinase (CK) levelwas 17,213 (baseline for patient), and hewas admitted for pain control. Subsequent CK was elevated at 198,688, and his compartment pressures were found to be greater than 90 mmHg. The patient underwent emergent bilateral thigh and left calf fasciotomies. Post-operatively he recovered full strength and sensation, but pain control remained a challenge. His dilaudid PCA was increased to 0.8mg PRN q15min with a basal rate of 0.5mg/hr, resulting in stable pain score of 3/10. He was successfully discharged with hydrocodone/acetaminophen for pain control. Clinicians should be aware that Suboxone is being increasingly prescribed for pain management. Treating acute pain in a patient taking Suboxone requires knowledge of the drugs pharmacokinetic profile. The active ingredient buprenorphine is a partial agonist with high affinity for the mu receptor. This results in competitive inhibition of co-administered opioid, requiring higher doses of opioids for analgesic effect. If Suboxone is discontinued to treat acute pain with other opiates, patients must be monitored for overdose. Patients on Suboxone therapy are at high risk for under-medication due to deficits in provider knowledge, compounded by opiophobia, and negative attitudes toward patients with opioid dependence. (414) A multicenter, 12-month, open-label, single-arm, safety study of oxycodone hydrochloride and naltrexone hydrochloride extended-release capsules (ALO-02) in patients with moderate to severe chronic non-cancer pain B Setnik, S Arora, M Drass, J Hudson, R Clemmer, P Meisner, G Pixton, and K Sommerville; Pfizer Inc., Cary, NC ALO-02 is an investigational analgesic that consists of pellets of extended-release oxycodone hydrochloride that surrounds a sequestered core of naltrexone hydrochloride (12% naltrexone), and is designed to discourage common methods of tampering associated with prescription opioid misuse and abuse. When used as directed, the naltrexone core remains sequestered and patients receive oxycodone in an extended-release manner. When the pellets are crushed, the naltrexone is released and is designed to counteract the effects of oxycodone. The primary objective of this study was to evaluate the longterm safety of ALO-02 administered for up to 12months. Thiswas amulticenter, open-label, single-arm study in adult patients withmoderate-to-severe chronic non-cancer pain. After initiating study drug, doses could be adjusted upward or downward; the total daily dose range was 20-160mg oxycodone. The primary endpoints were the number and type of adverse events (AEs) and adverse reactions (AEs assessed by the investigator as treatment-related). Of the 395 patients enrolled in the study, all received study drug (safety population). A total of 193 (48.9%) patients received ALO-02 for $181 days and 105 (26.6%) patients for $361 days. A total of 237 (60.0%) patients discontinued, similar to other long-term opioid trials. The most common treatment-emergent AEs were nausea (25.3%), constipation (21.3%), vomiting (13.9%), and headache (11.6%). The most common adverse reactions were constipation (18.0%), nausea (14.9%), somnolence (8.4%), fatigue (6.8%), dizziness (5.6%), and vomiting (5.1%). Themost common treatment-emergent serious AEswere acutemyocardial infarction, non-cardiac chest pain, pneumonia, convulsion, and nephrolithiasis (0.5% patients per serious AE). The most common AEs leading to discontinuation were nausea (4.6%) and constipation (2.5%). AEs observed during treatment with ALO-02 for up to 1 year for moderate-to-severe chronic non-cancer pain were consistent with AEs commonly associated with chronic opioid treatment. Sponsored by Pfizer Inc. (415) Analgesia during long-term lubiprostone therapy in patients with opioid-induced constipation and chronic, non-cancer pain: results from a phase 3, open-label clinical trial T Joswick, E Spierings, E Lindner, F Woldegeorgis, and R Ueno; Multiple sites Opioid use is usually associated with opioid-induced constipation (OIC). The primary objective of this 9-month extension study was to evaluate the longterm safety of open-label lubiprostone 24 mcg, a locally acting chloride channel (ClC-2) activator, twice daily in adults (N=439) with chronic non-cancer pain and OIC. Consistent treatment with a full-agonist opioid was required during the study. OIC was defined as <3 spontaneous bowel movements (SBMs)/ week, of which $25% were hard to very hard consistency, incompletely evacuated, and/or associated with moderate or worse straining, during the 2week baseline period. Mean Brief Pain Inventory-Short Form scores remained stable throughout the 9-month treatment period. Mean morphine-equivalent daily dose was similar to baseline at months 1, 2, 3, 4, 5, and 9 (P$.18), but statistically significantly increased at months 6, 7, and 8 (by 2.6% [P=.013], 3.5% [P=.031], and 3.6% [P=.035], respectively). During the study, 27.3% of patients reported a treatment-related adverse event (AE), most commonly nausea, diarrhea, and flatulence (7.1%, 4.8%, and 2.1%, respectively). No drug-related serious AEs were reported. Six (1.4%) and 5 (1.1%) patients withdrew because of nausea and diarrhea, respectively; 3 cases of nausea and 2 cases of diarrhea were severe. Reliance on rescue medication decreased from 33.3% to 18.6% of patients from months 1 to 9. Mean weekly SBM frequencies increased from 1.4 at baseline to$4.9 at later months (all P<.001). Straining, stool consistency, constipation severity, abdominal bloating, abdominal discomfort, and bowel habit irregularity all statistically significantly improved from baseline (P<.001, all months). Lubiprostone treatment did not appear to effect opioidinduced analgesia, was well-tolerated, and improved symptoms and signs of OIC overall in this 9-month, open-label study. Supported by Sucampo Pharma Americas and Takeda Pharmaceuticals USA.