AMSTERDAM — None of the commonly used pharmacotherapies for pain relief in knee osteoarthritis offer clinically meaningful benefit, said Dr. R. Andrew Moore at a satellite symposium held in conjunction with the annual European Congress of Rheumatology.
“The reality is that the evidence shows the therapies we have at the moment are working statistically but not necessarily being as effective as we'd want. … There's a whole series of interventions in osteoarthritis where there isn't much evidence of useful efficacy,” commented Dr. Moore, professor of health sciences at the University of Wales Swansea.
A new metaanalysis conducted by investigators at the University of Bergen, Norway, included more than 14,000 patients with knee osteoarthritis in 63 randomized, placebo-controlled clinical trials evaluating oral and topical NSAIDs, acetaminophen, intraarticular corticosteroid injections, opioids, glucosamine sulfate, and chondroitin sulfate.
These therapies have received the highest level of recommendation in current European League Against Rheumatism guidelines for the management of knee osteoarthritis, noted Dr. Moore. Yet the metaanalysis showed that pain-relief benefits, compared with those of placebo, were limited to the first 2–3 weeks of treatment and were so small as to be below the minimal patient-defined threshold for clinically perceptible improvement.
“In view of the widespread use of pharmacological agents in [knee osteoarthritis] management, a discussion is needed to clarify if the limited benefits and considerable costs can justify current recommendations,” according to the Norwegian investigators (Eur. J. Pain 2006 May 6;DOI:10.1016/j.ejpain.2006.02.013).
The investigators found, for example, that the maximum efficacy of oral NSAIDs or opioids in patients with moderate to severe pain corresponded to a 10-mm greater reduction than with placebo on a 100-mm visual analog scale. Yet prior studies by other investigators have shown that knee osteoarthritis patients define a mean 19.9-mm reduction as the minimal clinically important improvement, and that a shift from “unchanged” to “slight improvement” in pain requires a mean 12.3-mm decrease.
The best performances among the studied treatments came from topical NSAIDs and steroid injections; however, neither offered meaningful pain relief after the first month.
Dr. Moore noted that the “disappointing” findings of the new metaanalysis were entirely in keeping with the results of a study he and his colleagues presented at the EULAR congress. It involved 19,163 participants in 15 randomized osteoarthritis trials in the Pfizer Clinical Trials Registry evaluating various traditional NSAIDs and cyclooxygenase-2 inhibitors.
“The best we could do was get 60% of patients to have a 10-mm improvement on the pain visual analog scale, which isn't by any means a high threshold. That means 40% did not even achieve that low end point,” Dr. Moore said at the satellite symposium sponsored by CombinatoRx Inc.
Chronic pain management, he stressed, is an exceedingly challenging matter.
“The one great success we've had in pain has been in cancer pain, where the WHO [World Health Organization] pain ladder has really made an enormous difference over the past 25 years,” Dr. Moore asserted. “It's an overall package of care. Nobody yet has tried doing all this in a systematic way in other chronic painful conditions.”
The results of the two large metaanalyses fit well with the clinical experience of discerning physicians, according to Dr. Tore K. Kvien. “I don't mean that NSAIDs don't work in osteoarthritis. The data just show they're not as effective as we usually believe,” noted the professor of rheumatology at the University of Oslo, Norway, and immediate past president of EULAR.
Shown are marked narrowing of the knee's medial compartment (left) and narrowing of the lateral compartment (right). ©American College of Rheumatology
Survey Says: 40% of Patients Find Pain Management Doesn't Work
It's not just the randomized trials that are saying current drug therapies for osteoarthritis don't bring clinically meaningful pain relief—patients and their physicians have been registering the same complaint as well.
A recent major survey of chronic pain including more than 46,000 adult respondents in 15 European countries concluded 1 in 5 people experience pain of moderate to severe intensity that's present every day or nearly every day for at least 6 months, according to Dr. Moore.
Osteoarthritis is a leading cause of this chronic pain, he added.
Two thirds of survey respondents with chronic pain were taking prescription medications for it. Overall, 40% characterized their pain management as inadequate and 60% had visited their physician about their pain 2–9 times in the past 6 months. Also, 19% had lost their job, and another 13% had changed work because of their pain (Eur. J. Pain 2006;10:287–333).
Investigators at Frenchay Hospital in Bristol, England, conducted a face-to-face survey with 504 British primary care physicians. Of those, 81% indicated that fewer than half of their affected patients experienced optimal control of chronic non-cancer-related pain symptoms, Dr. Moore said at the satellite symposium sponsored by CombinatoRx Inc.