Treatment of osteoarthritis (OA) today primarily focuses on pain, which is the reason most patients seek help. While researchers are exploring new modalities in the hope of developing disease-modifying treatments, the current challenge is to manage the disease with treatments that have limited efficacy and considerable toxicity until the point when the patient requires a total joint replacement.
"I generally start treatment with something to help with the pain, and I teach them exercises. Muscle strengthening and conditioning seem very important in limiting pain and even improving pain. Analgesics and anti-inflammatories also help with that," said David T. Felson, MD, of Harvard Medical School in Boston.
"And I use injections a lot -- primarily corticosteroids. About two-thirds of patients respond to this," he told 乌鸦传媒.
The most recent recommendations on OA treatment from the American College of Rheumatology (ACR) suggest that initial pharmacologic approaches can include acetaminophen, topical and oral nonsteroidal anti-inflammatory drugs (NSAIDs), tramadol, and intra-articular corticosteroid injections. However, the guidelines advise that oral NSAIDs should not be used in patients with contraindications to these drugs and that prescribers should be aware of precautions and warnings.
NSAID Risks
"When drugs like Celebrex first came out, there was a sense that the anti-inflammatory drugs were pretty safe, but gradually we've come to know that all of these drugs have a heart warning, including the Cox 2 drugs," said Theodore Fields, MD, of the Hospital for Special Surgery in New York City. "They can cause high blood pressure, ankle swelling, and kidney dysfunction, and OA tends to develop in older people, who are more likely to have hypertension, kidney problems, and heart disease," he said in an interview. "In general, we're using them less than we did in the past," he added.
A study presented at this year's annual meeting of the ACR by Daniel Solomon, MD, of Brigham and Women's Hospital in Boston, addressed concerns about potential major NSAID toxicities, including cardiovascular and kidney events as well as clinically significant gastrointestinal events and death.
He and his colleagues analyzed outcomes from the trial, which compared the cardiovascular safety of celecoxib, naproxen, and ibuprofen in almost 25,000 patients. Patients recruited during the first 4 years of the study were used to derive a clinical risk score for major NSAID toxicities, and those enrolled during the last 5 years were used to validate the risk score.
In the derivation group, factors that were associated with toxicity risk included male sex (HR 1.51), history of cardiovascular disease (HR 1.94), age (HR 1.03 per year), hypertension (HR 1.29), diabetes (HR 1.42), smoking (HR 1.55), use of statins (HR 1.43), and aspirin use (HR 1.37).
The investigators then calculated 1-year risks for major toxicity and identified 5.8% whose 1-year risk was below 1%, 66.7% whose risk was 1% to 4%, and 26.6% whose 1-year risk was higher than 4%. "Elements of the score are easy to obtain and, if found to be externally valid, could help clinicians and patients determine risks and benefits of chronic NSAID use," Solomon and colleagues concluded.
Role of Surgery?
In another study presented at the ACR meeting, no differences were seen at 5 years between patients with OA knee pain and meniscal tears who were treated surgically and those managed with physical therapy (PT) alone.
Patients in the study, known as METEOR, were randomized to receive arthroscopic partial meniscectomy (n=164), were assigned to the PT group but crossed over to receive the surgery (n=68), or received PT alone (109). At 6 months, pain scores in the three groups declined from 40-50 to 20-25, and little change was subsequently seen during 5 years of follow-up, according to Jeffrey N. Katz, MD, of Brigham & Women's Hospital and Harvard University in Boston.
"For clinicians, these results suggest that patients with meniscal tear and osteoarthritic changes can be reassured that they are likely to experience improvement with either surgery or PT," Katz said during a plenary session at the meeting.
Knee pain from OA and meniscal tears are a frequent source of disability in middle-aged and older individuals, and 400,000 arthroscopic partial meniscectomies are performed for this indication each year in the U.S., he noted.
Yet several clinical trials have documented similar improvements among patients managed with PT compared with those undergoing surgery. The earlier trials, however, have been short in duration -- including the , published in 2013 in the New England Journal of Medicine.
In that publication, Katz and colleagues found that the mean improvement in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 6 months was 20.9 points (95% CI 17.9-23.9) for surgical patients and 18.5 (95% CI 15.6-21.5) in the PT group, for a nonsignificant difference of 2.4 points (95% CI -1.8 to 6.5).
Moreover, the likelihood of subsequently undergoing total knee replacement was higher (HR 5, 95% CI 1.2-21.8) for patients who received the surgery.
"We've definitely learned that arthroscopy is not a good tool for the patient with advanced OA where it's bone-on-bone," said Geoffrey H. Westrich, MD, research director of the Adult Reconstruction and Joint Replacement Service at the Hospital for Special Surgery in New York City.
"There are surgeons who are not arthritis specialists who are still doing these procedures, and I see two or three people who have had a failed arthroscopy. Sometimes the pain is worse than before the arthroscopy," Westrich told 乌鸦传媒.
"If arthroscopy is recommended in the setting of advanced arthritis where it's bone-on-bone, the patient should probably get a second opinion at a tertiary care referral center where a lot of arthritis-related surgery is done," he advised.
What About Methotrexate?
The slow-acting agent methotrexate is the cornerstone of treatment for rheumatoid arthritis and other inflammatory arthritides associated with synovitis. British researchers proposed that this drug might be helpful in alleviating pain in patients with OA, which also is characterized by synovitis.
In a study presented in a poster session at the ACR meeting, Philip G. Conaghan, MBBS, PhD, of Leeds University, reported that in a multicenter yearlong study known as PROMOTE, methotrexate plus usual care was associated with a significant reduction in OA knee pain at 6 months. Among 155 patients, pain scores averaged 5.1 for those randomized to methotrexate and 6.2 in those given placebo, for a treatment difference of -0.83 points (95% CI -1.55 to -0.10, P=0.025).
This was a standard effect size of 0.36, which was considered moderate but was smaller than thresholds considered clinically meaningful, Conaghan noted.
Knee stiffness measured on WOMAC also showed significant benefits, with an adjusted difference at 6 months between the groups of -0.60 (95% CI -1.18 to -0.01, P=0.045), as did WOMAC physical function, with a mean difference of -5.01 (95% CI -8.74 to -1.29, P=0.008).
"Further analyses will explore predictors of response to understand if patients with enhanced responses can be identified," Conaghan and co-authors concluded.
Central Pain
An additional factor that can complicate the management of OA is when patients develop a fibromyalgia-like central sensitization pattern. "Some people with chronic pain -- maybe 20% of OA patients -- develop central sensitization, and this changes the way your body processes pain," Fields explained. "They may feel pain in their whole leg or their whole body -- a secondary fibromyalgia. This often occurs among patients who have OA of the knee that keeps them from sleeping properly. That seems to set off the central sensitization," he said.
In those patients, treatment also has to address the wider pain syndrome, and typically involves the use of drugs such as duloxetine (Cymbalta) and gabapentin (Neurontin) that have central effects and are widely prescribed for fibromyalgia, he added.