Treating Musculoskeletal Pain

San Antonio—More than 1.7 billion people have musculoskeletal conditions, making the diseases the second largest cause of disability, with the fourth largest impact on overall health in the world. In the United States, more than 30% of adults are affected, and the diseases account for approximately $950 billion in annual direct and indirect costs. Most are treated with nonsteroidal anti-inflammatory drugs (NSAIDs), which can be effective but also have side effects.

James W. Atchison, DO, medical director at the Rehabilitation Institute of Chicago, defined musculoskeletal disorders as conditions affecting the nerves, tendons, joints, and supporting structures. Examples of the conditions include osteoarthritis, rheumatoid arthritis (RA), back and neck pain, osteoporosis, and tendinitis.

At the AMCP meeting, Dr. Atchison joined other speakers during a satellite symposium titled New Approaches and Treatment Considerations in Mild-to-Moderate Musculoskeletal Pain. Iroko Pharmaceuticals, LLC supported the session with educational grants. Dr. Atchison said musculoskeletal conditions can be acute or chronic, localized or widespread, and can be associated with a variety of signs and symptoms, such as pain, tenderness, weakness, stiffness, and a limited range of motion. There are numerous ways to diagnosis the conditions, according to Dr. Atchison.

He said healthcare professionals should first ask patients about the onset, duration, and location of the conditions and see if they had taken previous treatments. Patients who have experienced trauma, had a history of cancer, unexplained weight loss, or unexplained fever, and are >70 years of age are particularly susceptible to having musculoskeletal conditions.

Patients should also undergo a physical exam that includes a visual inspection, motor exam, sensory exam, and an evaluation of them standing, sitting, and in supine position. In addition, they should have their pain assessed using methods, such as the Visual Analogue Scale, the Numeric Rating Scale, the Brief Pain Inventory, the McGill Pain Questionnaire, and the Pain Disability Index. 

Nonpharmacologic therapies for musculoskeletal conditions include exercise, acupuncture, physical therapy, relaxation techniques, and dietary supplements. Pharmacologic treatments include opioids, acetaminophen, NSAIDs, corticosteroids, antidepressants, anticonvulsants, and skeletal muscle relaxants.

Dr. Atchison mentioned the World Health Organization (WHO) Pain Relief Ladder that indicates the drugs to take for different levels of pain:

• For mild pain, the WHO suggests a nonopioid such an NSAID with or without adjuvant analgesics

• For moderate pain, the WHO recommends a weak opioid such as codeine with or without a nonopioid and an adjuvant analgesic

• For severe pain, the WHO suggests a strong opioid such as morphine with or without a nonopioid and an adjuvant analgesic

NSAIDs as a Treatment Option

Christopher Herndon, PharmD, associate professor at Southern Illinois University Edwardsville, said approximately 23 million people use over-the-counter NSAIDs on a regular basis in oral and topical forms. In 2012, there were 98 million NSAID prescriptions filled, and most were prescribed for chronic pain. The most commonly used NSAID in the United States was ibuprofen, while diclofenac was the most common NSAID worldwide.

NSAIDs are also commonly indicated for headaches, neck pain, low back pain, osteoarthritis, RA, dysmenorrhea, and gout, according to Dr. Herndon. He added that all NSAIDs inhibit the cyclooxygenase (COX) 1 and 2 enzymes.

Dr. Herndon recommended that patients only use 1 NSAID at the lowest dose and for the shortest time possible. He said prescribers should balance the benefits and risks of NSAIDs and tailor the therapies for individuals. Several organizations have guidelines for NSAIDs, including the American Academy of Orthopaedic Surgeons, American College of Rheumatology, American Geriatrics Society, European League Against Rheumatism, Osteoarthritis Research Society International, and National Institute for Health and Clinical Excellence. The guidelines all suggest using oral or topical NSAIDs or acetaminophen for first-line therapy.

Considerations for NSAID Therapy

NSAIDs are associated with safety concerns, according to Dr. Herndon. Some people taking NSAIDs, particularly those with multiple risk factors and a history of previous complicated ulcers, have gastrointestinal issues, such as ulcers, bleeding, perforation, and obstructions. Dr. Herndon said NSAIDs also have been shown to have an increased risk of cardiovascular disease (CVD), vascular events, and blood pressure and a worsening of heart failure.

A meta-analysis of 754 trials involving more than 350,000 patients found that NSAIDs and selective COX-2 inhibitors increased the risk of cardiovascular events, gastrointestinal bleeding, and heart-failure related hospitalizations [Lancet. 2013;382(9894):769-779]. The authors concluded that the vascular risks of high-dose diclofenac and ibuprofren are comparable with COX-2 inhibitors, but high-dose naproxen has less vascular risk than other NSAIDs.

Renal events are also possible with people taking NSAIDs, particularly those with risk factors such as an advanced age, congestive heart failure, diabetes, hypertension, concurrent use of diuretics, and a family history of renal events. Meanwhile, Dr. Herndon said liver damage has been found in patients taking NSAIDs, especially those who are >50 years of age, female, have autoimmune disease, and are also using hepatotoxic drugs.

Dr. Atchison mentioned the American Heart Association (AHA)’s approach to managing musculoskeletal symptoms in patients with known CVD or at risk of ischemic heart disease begins with treatments having the lowest reported risk of cardiovascular events. Non–COX-2 selective NSAIDs such as ibuprofen, naproxen, and indomethacin are to be used first. If those aren’t effective, healthcare professionals should prescribe NSAIDs with some COX-2 activity such as diclofenac or piroxicam and then a COX-2 selective NSAID such as celecoxib or meloxicam. The AHA considers naproxen the safest NSAID, according to Dr. Atchison.

Dr. Atchison said NSAIDs cost between $4 and $300 per month, with naproxen being the cheapest option. He added that pharmacoeconomic evaluations have found that NSAIDs plus a gastroprotective agent are the most cost effective options considering adverse events, although the results are not always consistent. In addition, COX-2 inhibitors can be effective for patients with high gastrointestinal risk, but they should also receive gastroprotective agents. Topical NSAIDs or fixed combination formulations may be beneficial, too, although Dr. Atchison said the results are not well established.

Numerous companies are developing nanoformulations of NSAIDs with the goals of improving tolerability, maintaining effectiveness, and lowering the dosage of the drugs. In October, the FDA approved diclofenac capsules for treating mild-to-moderate acute pain at a dosage 20% lower than the previously available versions of diclofenac. The FDA also accepted new drug applications for indomethacin for acute pain and diclofenac for osteoarthritis pain. Nanoformulations of meloxicam and naproxen are in late-stage trials for osteoarthritis pain.

Dr. Herndon said that the nanoformulations of NSAIDs have been well tolerated for up to 12 weeks in clinical trials, although there is no data on long-term safety.