Burden of OA-associated pain

Osteoarthritis-associated pain

Pain associated with osteoarthritis is significant and requires an alternative management approach

Osteoarthritis (OA) is the most common form of arthritis, estimated to affect 302 million people worldwide¹. The knees, hips and hands are the most commonly affected joints; knee and hip osteoarthritis rank highly as global causes of disability (eleventh highest) and chronic pain among older adults^1-3. OA may also lead to increased risk of all-cause mortality and the incidence of OA continues to rise due to both the ageing population and increased prevalence of obesity⁴.

OA is a heterogeneous condition involving the whole joint. Pathology includes structural alteration of cartilage, subchondral bone, ligaments, capsule, periarticular muscles and synovial inflammation which leads to pain, stiffness, swelling and loss of function^1,5.

As OA is a progressive disorder with varying degrees of severity it requires long-term management over the disease course. As there is no disease-modifying treatment for OA, treatment is largely based on symptom relief. Reducing the pain associated with OA can reduce the impact of OA on the patient's mobility and quality of life⁴. Pain is therefore the major driver of clinical decision making in OA⁶.

What does OA look like?

Patients with OA can experience⁶:

• morning stiffness
• reduced range of movement
• crepitus
• joint instability
• swelling
• muscle weakness
• fatigue
• pain-related psychological distress.

The pain associated with knee OA is typically intermittent and associated with weight-bearing. However, when pain becomes more severe, more frequent or unpredictable (e.g. during a 'flare') patients more often classify their pain as unacceptable⁶. Everybody experiences pain differently, which justifies a personalised approach to OA management.

Let’s meet our patient ‘Marie’. How does knee osteoarthritis affect her daily life?

Note: this is a theoretical case for educational purposes only. Marie has had osteoarthritis (OA) for a number of years and so we review her treatment and comment on how she might have been treated differently using the current guideline recommendations. At the bottom of the page, you will have the opportunity to complete a short quiz based on this case study.

Initial clinical presentation

• Female, 55 years old, obese (BMI 34 kg/m²)
• 3-year history of progressively worsening pain in both knees
• Knees stiff for about 20 minutes first thing in the morning and for a few minutes after getting up from a chair during the day
• Difficulty walking >30 minutes because of pain and swelling (limits recreational walking with friends)
• Symptoms exacerbated by kneeling, squatting or descending stairs (limits gardening and housework)
• Sitting, resting and reclining relieve pain, but becomes stiff if in one position for too long

• Symptoms worse on humid or cold days

Her increasing pain led Marie to see her doctor who referred her to a specialist for evaluation.

Physical examination

Physical examination of the lower extremities revealed:

• Mildly antalgic gait (limp to avoid pain) and passive range of motion of both knees indicated palpable crepitus (grating or crunching)
• Unable to flex or extend knees completely:
  • maximum flexion <120° ( normal maximum flexion is 140–150°, physically active OA patient commonly has a maximum flexion <130°)
  • 8° loss of extension (<10° loss in severe OA)
  • patellar facet tenderness, tenderness over the joint line and patellofemoral crepitus (common in patients with knee OA), moderate warmth and soft-tissue swelling, patellar tilt and moderately severe decreased patellar glide (medially and laterally)
  • medial pseudolaxity (symmetric instability)

Examination of Marie’s hands revealed:

• Enlargement of some of the proximal interphalangeal joints (Bouchard’s nodes) and some of the distal interphalangeal joints (Heberden’s nodes)
• Squaring at the bases of both thumbs at the carpometacarpal joints (feet demonstrated similar deformities, with enlargement and reduced dorsiflexion of the first metatarsophalangeal joints)

Because of the prevalence of atherosclerosis in the older population, a thorough neurovascular examination was performed but there were no signs of neurovascular compromise (distal pulses and sensation intact, no evidence of cyanosis, clubbing or oedema).

Marie’s hip and back were also examined thoroughly to rule out any contribution to the knee symptoms. She had full range of motion (ROM) of the lumbosacral region, and all motions were pain-free. Her hip examination showed decreased internal ROM, but motions were pain-free and symmetric indicating that neither hips nor back was contributing to her symptoms.

Radiographic exam

Radiographs showed osteophytes (a), joint space narrowing (b) and subchondral bone sclerosis (c) in both of her knees. This confirmed the diagnosis of moderate bilateral knee osteoarthritis.

Linear pain scales overused in osteoarthritis

Traditional linear pain assessment scales are sometimes overused in osteoarthritis and may not be fit-for-purpose in assessing patient QoL in the real world

Accurate pain assessment is the foundation of optimal management⁷. However, because pain is highly subjective, assessing severity can be difficult. Indeed, healthcare professionals (HCPs) and patients frequently differ in their perception of pain severity associated with a condition or extent of tissue damage⁸. In a study comparing patient–physician discordance in global assessment of patients with osteoarthritis  (OA) (n = 243) versus patients with rheumatoid arthritis (RA) (n = 216), patients with OA were more likely to be discordant with their rheumatologists than patients with RA with the most important explanatory variable for discordance being higher levels of pain⁹.

Traditionally visual analogue scales (VAS) are used to assess pain. Patients are asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance (mm) on the 10 cm line between the ‘no pain’ anchor and the ‘pain as bad as it could be’ extreme¹⁰. A score of more than 30 mm on the 10 cm scale suggests moderate pain¹¹ (Figure 1).

Figure 1. Interpreting the visual analogue pain score (Adapted^11,12)

Any outcome worse than mild pain is unacceptable and usually indicates analgesic or treatment failure¹². OA guidelines describe a number of pain scales (including VAS) that can be used to assess levels of pain for knee and hip OA, and are listed in hierarchical order, as developed by the American College of Rheumatology (ACR)¹:

1. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (Likert/100mm) or Knee Injury and Osteoarthritis Outcome Score (KOOS) or Hip Disability and Osteoarthritis Outcome Score (HOOS)
2. Pain during activity (VAS)
3. Pain during walking (VAS)
4. Global knee pain (VAS)
5. Pain at rest (VAS)
6. SF-36 (bodily pain subscale)
7. Health Assessment Questionnaire (HAQ, pain subscale), Lequesne algofunctional index (pain subscale), Arthritis Impact Measurement Scale (AIMS, pain subscale), Knee-Specific Pain Scale (KSPS), McGill Pain Questionnaire (pain intensity)
8. Pain at night (VAS), pain during activity (Numerical Rating Scale, NRS), pain on walking (NRS), number of painful days (days)

In both clinical trials and clinical practice, outcome assessments have traditionally been limited to evaluation of pain intensity. In reality, patients may experience more pain, have many comorbidities and use their pain treatments intermittently¹³. This often results in inadequate pain relief, which is explored further in the next page.

Current osteoarthritis treatments often ineffective

Current osteoarthritis pain treatments are often ineffective, which may lead to treatment escalation and use of controlled drugs associated with more serious side effects

An observational study in patients with knee osteoarthritis (OA) suggests that inadequate pain relief (IPR) is highly prevalent. Following a year of physician-prescribed treatment, 54% of patients reported IPR (moderate-to-severe pain)¹³. This suggests that currently prescribed pain treatments for knee OA are not meeting the needs of the majority of patients¹³.

Current osteoarthritis treatments

Figure 2 shows the 2019 Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) treatment algorithm for knee OA, which recommends a combination of non-pharmacological and pharmacological treatment approaches⁴. There are similar recommendations for hand, knee and hip OA¹, and it is notable that the majority of treatments are only weakly recommended.

Figure 2. ESCEO stepwise treatment algorithm for knee osteoarthritis (Adapted⁴). COX-2, cyclooxygenase-2; CS, chondroitin sulphate; CV, cardiovascular; GI, gastrointestinal; GS, glucosamine sulphate; IA, intra-articular; NSAID, non-steroidal anti-inflammatory drug; PPI, proton pump inhibitor; SYSADOA, symptomatic slow-acting drugs in osteoarthritis; OA, osteoarthritis.

Pharmacological treatment approaches for osteoarthritis pain

Paracetamol

The ESCEO working group gives a weak recommendation for the use of paracetamol and that it should not be used on a regular basis as long-term background pharmacological therapy for the management of knee OA⁴. This is based on questionable efficacy (minimal analgesic effect size of 0.14 [95% confidence interval 0.05–0.22], essentially no detectable clinical effect and no significant effect on stiffness and physical function in patients with knee OA) and confirmed safety issues (gastrointestinal, cardiovascular, hepatic and renal side effects)⁴.

ESCEO does give a weak recommendation that paracetamol (≤3 g/day) may be used as short-term rescue analgesia only, when given in addition to symptomatic slow-acting drugs for OA (SYSADOAs, glucosamine, chondroitin, diacerein and avocado soybean unsaponifiables)⁴ .

Non-steroidal anti-inflammatory drugs (NSAIDs)

ESCEO recommends NSAIDs as Step 2 therapy, either intermittently or for longer cycles but based on the patient risk profile⁴. Oral NSAIDs have a small-to-moderate effect on pain relief in OA, with analgesic effect size ranging between 0.35 (95% credibility index 0.31–0.40) for OA-approved daily doses of celecoxib 200 mg/day, and 0.57 (95% credibility index 0.45–0.69) or 0.58 (95% credibility index 0.43–0.74) for maximally approved daily doses of diclofenac 150 mg/day or etoricoxib 60 mg/day⁴.  Cyclooxygenase-2 (COX-2)-selective, partially selective, or non-selective NSAIDs (nsNSAIDs) are all similarly effective in controlling pain⁴ but have different risk profiles. While all NSAIDs are associated with increased risk of acute kidney injury, meta-analyses have shown that all nsNSAIDs and COX-2 inhibitors have the potential for both gastrointestinal and cardiovascular toxicity⁴. 

Intra-articular interventions

Intra-articular corticosteroids are more effective than intra-articular hyaluronic acid (IAHA) in the short-term (2–4 weeks) and are weakly recommended by ESCEO⁴. Corticosteroids elicit immunosuppressive and anti-inflammatory effects through direct action on nuclear receptors that interfere with the inflammatory cascade at multiple levels¹⁴. Hyaluronic acid is a natural glycosaminoglycan secreted into the synovial fluid, which provides viscous lubrication, shock-absorbing properties and, possibly, direct anti-inflammatory and antioxidant functions¹⁴. While trial results are variable, IAHA or corticosteroids should be considered in patients for whom NSAIDs are contraindicated or who remain symptomatic despite use of NSAIDs⁴. There is good evidence for the effectiveness of IAHA from clinical trials, meta-analyses and real-life experience. For example, in a network meta-analysis, IAHA had a measured analgesic effect size of 0.34 on pain (95% credibility index 0.26–0.42) when compared with placebo at 3 months and superior efficacy to oral NSAIDs⁴.

Duloxetine

Duloxetine is a selective serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressant not widely used in Europe, but ESCEO give it a weak recommendation as an alternative to weak opioids in Step 3 of the algorithm⁴. The antidepressant duloxetine has been used in chronic pain syndromes and there is some evidence for an effect in OA (particularly in patients with pain from central sensitisation), but with a high incidence of side effects (dizziness, falls)⁴.

Opioids

It is noteworthy that classical oral or transdermal opioids are only recommended for severely symptomatic patients in whom surgery is either contraindicated or refused, and are effectively the last pharmacological resort⁴. This is because only small-to-moderate positive effects on OA pain and function have been demonstrated, with an increased risk of side effects¹⁵. Indeed, other guidelines strongly recommend against the use of opioids³.

Opioid addiction avoidable

Opioids offer only small benefits in terms of pain and function in osteoarthritis (OA) and do not improve quality of life or depression¹⁶

There are a number of consensus and position statements that recommend against the use of opioid pain medication for the treatment of OA (American Association of Orthopaedic Surgeons [AAOS]¹⁷; American Association of Hand and Knee Surgeons [AAHKS]¹⁸). Despite these recommendations, nearly 27% of patients with OA still receive opioids and benzodiazepines, with about 36% of such individuals demonstrating at least one risk factor for prescription misuse (the most prevalent being ‘early refill’ and a history of receiving ≥3 prescriptions in the previous month), according to data from a large US health care system¹⁹.

Opioid overuse in OA has also been reported in Europe. In a 12-month study in 751,579 residents in Sweden, 23.7% patients with OA were prescribed opioids [95% confidence intervals 23.3–24.2], which was twofold higher than for individuals without knee or hip OA. Similarly, patients with OA were more likely to have an incident opioid dispensation, particularly for strong opioids (incidence rate ratio: 2.6 [95% confidence interval 2.5-2.7])²⁰.

These studies highlight that patients with knee and hip OA constitute a group of patients with a worryingly high use of opioids despite recent international concerns about the devastating potential for chemical dependency posed by opioid medications³.

Socioeconomic burden of osteoarthritis

The socioeconomic burden associated with osteoarthritis pain is significant and underestimated

What is the economic burden of osteoarthritis (OA)? Given its high prevalence, OA incurs substantial health and societal costs, both directly (clinician visits, treatments, surgery) and indirectly (impaired work productivity and early retirement)³.

The costs associated with OA can be particularly significant for the elderly, who face potential loss of independence and a requirement for help with activities of daily living. While estimating costs is difficult, the US Bone and Joint Initiative (USBJI) has highlighted the enormous economic impact of OA in their 2018 Burden of Musculoskeletal Diseases report²¹:

• In 2008–14, per-person medical costs attributed to OA averaged $11,052 per-year
• In 2008–14, annual all-cause costs (both direct and indirect) attributed to OA and allied disorders averaged $486.4 billion nationally
• In 2013, there were 20.78 million ambulatory care visits and ~2.95 million inpatient hospitalisations for patients with OA and associated disorders

In Europe a 2013 review estimated that²²:

• the average total annual cost of OA per patient in Europe ranged from €1,330 to €10,452
• when considering only direct medical costs, the annual cost of OA ranged from €534 to €1,788
• in active patients, the indirect costs were much higher than the direct costs

Figure 3. Direct and indirect costs of knee osteoarthritis in Italy. Based on a sample of 254 patients with a mean age of 65 years. Total cost per year = €2,170. Direct costs are represented in green and indirect costs in blue (Adapted²³).

As the increasing populations of developed nations age, and obesity increases over the coming decades, the need for better understanding of osteoarthritis and for improved therapeutic alternatives will continue to grow²²

References

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