Clinical use: pain associated with osteoarthritis
• Osteoarthritis is a progressive disease. Symptoms can include severe pain and loss of function.
• Opioids are effective analgesics, although the magnitude of the effect may be small.
• On the basis of the available evidence, widespread use of strong opioids cannot be recommended.
• With careful patient selection, however, certain patients may derive analgesic and functional benefit.
Osteoarthritis can be a progressive disease of synovial joints. It is characterized by destruction of articular surfaces and remodelling of subchondral bone. Osteoarthritis is the result of a disturbance of the normal balance between cartilage production and loss. Cartilage breakdown, the result of the actions of proteolytic enzymes such as the matrix metalloproteinases, is accompanied by an increase in the activity of chondrocytes attempting tissue repair.
The most commonly affected joints are the interphalangeal joints of the hand, the knees, hips, and the facet joints of the cervical and lumbar spine. Usual symptoms include pain, swelling, stiffness, and loss of function.
The diagnosis of osteoarthritis is made on a combination of clinical features and radiographic evidence. X-rays have to be interpreted with some caution, however, as considerable pathological changes may occur before radiographs become abnormal, and furthermore, much osteoarthritis seen on X-rays may be completely asymptomatic.
Some osteoarthritis, of the hip or knee for example, responds well to operative treatment. When symptoms are the result of osteoarthritis in joints not amenable to surgery, or where patient comorbidities preclude surgery, treatment is palliative. Opioids can be a part of successful symptomatic management.
Much of the evidence regarding the symptomatic treatment of chronic back pain, presented in Chapter 7, has relevance in osteoarthritis. There is incomplete crossover, however, as osteoarthritis pain refers to pain arising from the damaged articular surfaces, whereas back pain can arise not only from the synovial joints of the spine, but also discs, spinal nerves, paraspinal muscles, and other spinal structures.
Osteoarthritis is an age-related condition. When considering prescribing strong opioids to elderly patients, it is vital to assess the balance of benefits and adverse effects carefully, on a patient-by-patient basis.
8.2 Evidence for effectiveness of opioids in the treatment of osteoarthritis pain
There have been a number of trials specifically addressing the opioid responsiveness of osteoarthritis pain. One trial randomized 107 patients with persistent moderate to severe pain uncontrolled with standard therapy (non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol and/or short acting opioids) to either controlled release oxycodone or placebo. Over the study period of 90 days, those patients taking the active drug reported statistically significant reductions in pain intensity, and improved measures of physical functioning. The magnitude of these improvements, however, was small (in the case of pain intensity, approximately 1 point on an 11 point scale), although patients reported much higher levels of satisfaction with medication when taking the opioid compared to the placebo. Another study randomized patients to receive transdermal fentanyl or placebo. Although this study demonstrated a small improvement in mean pain scores at 1–3 weeks, this was not sustained past 4 weeks. A measurement of physical function, the WOMAC (Western Ontario and McMaster Universities Osteoarthritis) index improved. The drug manufacturers, who funded the trial, were involved in the study design and statistical analysis.
A recent meta-analysis of randomized-placebo controlled trials of pharmacotherapeutic interventions in osteoarthritic knee pain identified five trials where the active drug was a strong opioid and one trial where the active drug was codeine. The pooled data from 1057 patients showed that, over the short term, there was a statistically significant reduction in pain. The magnitude of that analgesic effect, however, was only 10.5 mm on a 0–100 mm visual analogue scale (VAS). The applicability of these findings, however, is limited by the fact that the authors failed to distinguish between opioids and made no assessment as to the appropriateness of the opioid doses used in the included trials.
The use of tramadol in osteoarthritic pain has been the subject of a recent Cochrane review. Eleven trials were identified, all of which were of good methodological quality. The pooled data indicate that whilst there is good evidence that tramadol is an effective analgesic in osteoarthritis, the magnitude of that effect is small, corresponding to 12.5 mm on a VAS. The number-needed-to-harm (NNTH—the number of patients needed to be treated for one to suffer an adverse effect) for minor adverse effects was similar to the number-needed-to-benefit, although the NNTH is significantly reduced if there is a slow upwards dose titration during the initial phase of treatment. The use of tramadol also confers a small beneficial effect on function, equivalent to 0.32 points on the 0–10 WOMAC (Western Ontario and McMaster Universities Osteoarthritis) index of function.
There is good evidence that strong opioids, including tramadol, have analgesic efficacy in osteoarthritic pain. The magnitude of this benefit, however, is small and the number-needed-to-treat high (around 6). Little is known about the long-term effectiveness of opioids in improving analgesia or function. Given that the patient population with osteo-arthritis are predominantly the elderly, in whom opioid side-effects can be expected to be more severe, a careful assessment needs to be made of the potential benefits and risks prior to starting a trial of strong opioids.
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