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OROS hydromorphone ER failed to achieve statistical significance for the primary endpoint using the prespecified imputation method (BOCF), likely due to the high discontinuation rate associated with the fixed-dose design. When data were analyzed according to an alternate method of imputation (LOCF), OROS hydromorphone ER demonstrated statistically significant improvements in pain, stiffness, and physical function.

A randomized, 4-week, double-blind trial followed by an open-label extension trial assessed the efficacy and safety of a once-daily, extended-release morphine formulation (Avinza (previously referred to as Morphelan)) in 295 patients with chronic, moderate-to-severe osteoarthritis pain who had failed to obtain adequate pain relief with NSAIDs and acetaminophen. Participants received one of four treatments: Avinza 30 mg once daily (QAM or QPM), MS Contin(R) 15 mg twice daily, or placebo twice daily. Patients (n =181) received Avinza QAM or QPM during the 26-week open-label extension trial and could increase their dose to optimize pain control. Avinza and MS Contin reduced pain and improved several sleep measures versus placebo. Analgesic efficacy was comparable between Avinza and MS Contin; however, Avinza QAM demonstrated greater improvements in overall quality of sleep. The most common adverse events were constipation and nausea. The majority of AEs occurred at a similar incidence among the active treatment groups.

IntroductionAlthough synthetic and biologic disease-modifying antirheumatic drugs are available, many patients with rheumatoid arthritis have a difficult-to-control disease and need other treatment options. Repository corticotropin injection (RCI) may alleviate symptoms and exacerbations in patients with refractory disease.MethodsNine patients with refractory rheumatoid arthritis were included in this study. Patients were maintained on their baseline therapies with a minimum of 7.5 mg prednisone daily. RCI was given daily at 40 U for 7 days. Patients who had an adequate disease response were given 40 U twice weekly through Week 12. For patients who had inadequate disease response, the dose was increased to 80 U daily for 7 days, followed by 80 U twice weekly through Week 12.ResultsThe primary endpoint was >1.2 point reduction in the Disease Activity Score 28 using C-reactive protein (DAS28-CRP) at Week 12. Secondary endpoints were improvements in Health Assessment Questionnaire-Disease Index and Functional Assessment of Chronic Illness Therapy scores. Six of the nine patients met the primary endpoint. The average change in DAS28-CRP from baseline to Week 12 was numerically greater with 40 U than with 80 U RCI. Functional Assessment of Chronic Illness Therapy and Health Assessment Questionnaire-Disease Index improved as early as Week 1, and the improvements remained throughout treatment.ConclusionThere was no association between cortisol levels and low-dose RCI response. No serious adverse events occurred. RCI produced a clinically meaningful reduction in markers of disease activity, improved health-related quality of life, and a favorable safety profile. The response rate to RCI was substantial and shows promise in this difficult-to-treat population.

The short-term management of pain is one of the conditions that most frequently confront physicians in the clinic. Our dilemma is choosing the most effective treatment that is associated with few side effects.There is a general consensus among physicians that the treatment of pain is inadequate.1 In addition, many physicians are concerned about the side effects of both opioid and non-opioid analgesics. Prescribing opioid agents carries the physician into an environment in which legal and societal pressures exist, and these pressures discourage the liberal use of opioids. This scenario may explain in part why the most frequently prescribed treatment for pain is nonsteroidal anti-inflammatory drugs (NSAIDs). 2Used for the management of several different symptoms and numerous conditions, NSAIDs continue to be among the most frequently prescribed medications. Approximately 100 million prescriptions for this class of drugs are written each year. While their benefits are unquestionable, physicians generally recognize that the use of NSAIDs is associated with a number of important side effects, including gastrointestinal (GI) and renal toxicity.NSAIDs function via a number of different mechanisms. However, the mechanism that may be the most frequently discussed, and perhaps the one associated with the greatest number of potential side effects, involves the inhibition of prostaglandin biosynthesis, described by Vane in 1971. 3The inhibition of prostaglandin biosynthesis in the periphery and the abrogation of nociception are effective methods of diminishing pain perception. However, the prudent use of NSAIDs requires cognizance of potential side effects. Clinical experience suggests that, although complications can occur early in the course of treatment, they are more likely to occur with chronic use.Gastrointestinal toxicity is the most frequently encountered side effect associated with NSAIDs and presents considerable concern. Approximately one half of all hospital admissions for a bleeding ulcer are attributed to the use of NSAIDs, aspirin, or the two taken in combination during the week prior to admission. 4 A survey of Tennessee Medicaid patients who were hospitalized with GI complications showed that patients who used NSAIDs had approximately a fourfold greater risk for developing GI hemorrhage or peptic ulcer disease than patients not taking NSAIDs.5 Serious GI events, according to the FDA, occur in as many as 2% to 4% of patients per year who are taking continuous NSAID therapy for rheumatoid arthritis. The relative risk of gastric ulcer (4.725), duodenal ulcer (1.1 to 1.6), bleeding (3.8), perforation, and death are all increased by NSAID use when such patients are compared to those who do not take these products. In 1989, patients with rheumatoid arthritis had approximately 20,000 hospitalizations per year with an estimated cost of $10,000 per stay. 6 Some currently available NSAIDs that are more COX-2 selective, such as etodolac and nabumetone, may be associated with less risk of GI toxicity. 7 Newer agents su...