First Report®

American Academy of Pain Medicine (AAPM) 27th Annual Meeting

March 24-27, 2011 National Harbor, MD

Examining the Biomarkers and Management of Osteoarthritis

National Harbor, MD—Although there is no known cure for osteoarthritis (OA), there are several pharmacological and nonpharmacological treatments used to manage the disease and its symptoms. At the recent AAPM annual meeting, researchers discussed the various alternatives during a satellite symposium titled “Osteoarthritis: From Biomarkers to New Strategies for Pain Management.”

Affecting nearly 27 million adults, OA is the most common form of arthritis and the leading source of physical disability in the United States. It is associated with pain and loss of joint function. The disease is identified when physicians see structural abnormalities on plain radiographs and magnetic resonance images. Patients with OA may experience pain, stiffness, fatigue, and sleep disturbance that can limit physical function, cause physical disability, and reduce health-related quality of life.

Virginia Byers Kraus, MD, PhD, Professor of Medicine, Division of Rheumatology, Duke University Medical Center, Durham, NC, began the session by outlining the stages of OR: molecular, preradiographic, radiographic, and joint replacement. Dr. Kraus said that pain can occur in any of the stages, and that there is a need to better understand the stages and when and how to intervene.

According to Dr. Kraus, biomarkers may identify preradiographic OA or pain sensitivity and differentiate joint pain with or without structural degeneration. There are also biomarkers of drug metabolism that could predict efficacy and biomarkers that could predict short- and long-term pain outcomes.

Dr. Kraus cited a study that concluded that baseline C-reactive protein levels were associated with the changes in symptoms of knee OA, including pain (P < .01), function (P < .01), and score on the Western Ontario and McMaster Universities Arthritis Index (P < .01). She said that the source of pain in patients with OA may be found in the subchondral bone, periostium, synovium, ligaments, and joint capsule.

Because OA pain correlates with biomarkers that are indicative of structural degeneration and joint inflammation, Dr. Kraus suggested that biomarkers could help researchers understand the sources of joint pain and detection of early OA. However, to gain a better understanding of the biology and etiology of joint pain, Dr. Kraus said that researchers must assess intermediate phenotypes associated with causal pathways.

Marc C. Hochberg, MD, MPH, Professor of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, followed by indicating that treating knee OA is centered around reducing pain, maintaining or improving joint mobility, limiting functional impairment, and improving health-related quality of life. He noted that several organizations provide guidelines and recommendations to treat knee OA, including the Osteoarthritis Research Society International, the National Institute for Health and Clinical Excellence, the European League Against Rheumatism, and the American College of Rheumatology.

Pharmacological treatments for OA include acetaminophen (ACT), oral nonsteroidal anti-inflammatory drugs (NSAIDs), topical analgesics, intra-articular therapy, and duloxetine. Dr. Hochberg said that ACT is normally recommended for first-line treatment of OA because of its safety profile and superiority in efficacy as compared with placebo. However, studies have shown that ACT is associated with increased risk of hypertension, antiplatelet trialists’ collaboration cardiovascular events, perforations, ulcers and bleeds, and a decline in glomerular filtration rate. According to Dr. Hochberg, an updated meta-analysis from 2010 indicated that ACT had minimal effect on pain and no significant effect on function or stiffness (Zhang W, et al. Osteoarthritis Cartilage. 2010;18[4]:476-499).

After evidence indicated that ACT was the leading cause of drug-induced liver failure in the United States and that approximately 50% of the cases were due to unintentional overdoses, a U.S. Food and Drug Administration Advisory Committee suggested lowering the maximum individual dose from 1000 mg to 650 mg, ensuring patients could only get a 1000-mg dose through a prescription, eliminating prescription combination ACT products, and including a boxed warning on all ACT products. Dr. Hochberg said that because daily doses of ACT of less than 4000 mg are not effective, rheumatologists should consider not using ACT in patients with OA.

Dr. Hochberg then discussed nonselective NSAIDs and COX-2 selective inhibitors, which studies have shown to be superior in efficacy to ACT. Nonselective NSAIDs and COX-2 selective inhibitors have similar efficacy for pain relief. He also mentioned topical NSAIDs, intra-articular corticosteroids, intra-articular hyaluronates, and duloxetine. According to Dr. Hochberg, two 13-week, placebo-controlled randomized trials have shown duloxetine’s effectiveness for controlling pain and improving physical function. He recommended that duloxetine be used alone or as adjunctive therapy for patients taking ACT or oral or topical NSAIDs.

The next speaker, F. Michael Gloth III, MD, FACP, AGSF, Associate Professor of Medicine, Johns Hopkins University School of Medicine, and Adjunct Associate Professor, University of Maryland School of Medicine, Baltimore, then discussed the potential role of opioids in managing OA. He said that there is a lack of evidence for the long-term effectiveness of opioids intreating persistent, noncancer pain. He also noted that it is difficult to assess the clinical trial data of opioids for the treatment of long-term pain.

Dr. Gloth reviewed guidelines from the American Geriatrics Society (AGS) for opioid therapy in older patients with persistent pain. Among its recommendations, the AGS says that when using fixed-dose opioid combination agents in an analgesic regimen, patients should not exceed a maximum safe dose of ACT or NSAIDs. In addition, the AGS recommends that physicians consistently reassess patients who take opioid analgesics to track therapeutical goals, adverse effects, and safe and responsible medication use. Dr. Gloth described a Functional Pain Scale ranging from 0 (no pain) to 5 (intolerable pain that causes people to be unable to communicate) that can be used to assess if patients are improving.

When prescribing opioids, physicians should be cognizant of the risks associated with the drugs, according to Dr. Gloth. Although relatively few patients abuse opioids, Dr. Gloth said that the abuse correlates with genetic and environmental factors and that older adults with no history of substance abuse are at relatively low risk of becoming addicted. Several assessments can be used to assess potential opioid abuse, such as the Opioid Risk Tool, the Screener and Opioid Assessment for Patients with Pain, and the Current Opioid Misuse Measure.

This educational activity was jointly sponsored by the Postgraduate Institute for Medicine and Miller Medical Communications, LLC. This activity was supported by an educational grant from Endo Pharmaceuticals, Inc.