Treating Osteoarthritis: A Review of NSAIDs and COX–2 Inhibitors

Contents

• Introduction
• The Epidemiology of Osteoarthritis
• Pathophysiology of Osteoarthritis*
• Clinical Investigation and Diagnosis*
• Treating Osteoarthritis*
• Pharmacologic Therapy for Osteoarthritis*
• Treating Osteoarthritis: The Non-steroidal Anti-inflammatory Drugs*
• Differentiating Non-steroidal Anti-inflammatory Drugs: Efficacy and Safety*
• Case Study 1*
• Case Study 2*
• Case Study 3*
• Summary*
• References*
• Additional Information*

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Learning Objectives

After completing this activity, participants will be able to:

• Discuss the relative benefits of acetaminophen and NSAIDs (including the COX-2s) for the treatment of pain associated with osteoarthritis
• Identify the class of medications known as NSAIDs and COX-2s along with the similarities and differences between the various agents in the class
• Understand the mechanisms of action of NSAIDs and COX-2 inhibitors, and how these mechanisms affect gastrointestinal and cardiovascular risk

Introduction

Osteoarthritis (OA) is the most common form of arthritis and the most common joint disorder worldwide.1-3 The disease is typified by the breakdown and loss of cartilage in joints, leading to chronic pain and reduced functioning. Despite its prevalence and impact, OA is a disease without a cure. Unlike other forms of arthritis, such as rheumatoid arthritis, no disease-modifying therapies for OA currently exist. Instead, treatment relies upon non-pharmacological interventions, analgesics, and, for many patients, long-term use of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs provide relief of OA symptoms for many patients, but carry the potential for adverse gastrointestinal (GI) and cardiovascular events. Given the diverse population of patients with OA, selecting an appropriate treatment plan can be a clinical challenge. This activity describes the pathophysiology of OA, and illustrates an approach to treatment through the use of case studies of typical patients.

The Epidemiology of Osteoarthritis

Osteoarthritis is extremely common, affecting approximately 21 million Americans.4 Radiographic evidence of OA is present in the majority of people by age 65, and in over 80% of those over 75.² However, not all people with radiographic OA report symptoms; in fact, 60% of patients with radiographic OA of the knee have no symptoms.⁵Estimates of the prevalence of symptomatic OA vary. Once source cites that approximately 11% of people >64 years of age had symptomatic OA of the knee, the most common site of OA pain.^2,4 The National Health and Nutrition Examination Survey (NHANES) reported that 21% of respondents at least 60 years of age had significant knee pain on most days, most likely due to OA.^3,4 It has been estimated that 6% of people age 30 or older have both frequent symptomatic knee pain and radiographic evidence of OA.^1,6

The prevalence of osteoarthritis is expected to grow as the US population ages. In one projection, arthritic disorders will affect approximately 18% of Americans by the year 2020, translating to 60 million individuals.^7,8 Such data highlight the importance of accurate recognition and appropriate treatment of OA.

It appears that OA is most commonly caused by mechanical factors that occur within the joint within the background of systemic susceptibility. Factors that influence susceptibility include age and gender; nutritional deficiencies and metabolic imbalances may also play a role.¹ Epidemiological studies have also documented a significant hereditary influence on the risk of OA, although very few specific genes have yet been identified.⁹ Mechanical factors that may play a role in the development of OA include joint misalignment, muscle weakness, or changes in the structural integrity of the joint.¹

Age is a major risk factor for OA. In one community-based survey, the incidence and prevalence of OA increased 2- to 10-fold from 30 to 65 years of age.^10,11 The role of gender is more complicated. In people younger than 50 years of age, OA in most joints is more common in men than women. After the age of 50, more women are affected at most joints than men, although studies have reported that hip OA remains more common in men.^11,12 Overall, because of its strong association with age, OA affects far more women than men.

The typical presentation of OA includes joint pain, often accompanied by stiffness, swelling, and reduced range of motion. The joints affected most often are the knees, feet, hands, hips, and spine, but OA can occur in any joint.⁴ Chronic joint pain is very common among older people. One study reported that one-quarter of individuals over the age of 55 had an episode of persistent knee pain during a one-year period; one-sixth of these patients sought medical treatment.¹³ Unfortunately, pain in older patients may often be inadequately assessed or inappropriately treated, suggesting an important unmet medical need.^14-16

The impact of OA is tremendous. Joint pain and stiffness can restrict mobility and overall functioning, and lead to reduced quality of life. Due to its prevalence and associated disability, OA accounts for more difficulty with walking and climbing and descending stairs than any other disease.¹⁷ It is also the most common cause of impaired mobility among Americans over the age of 65, and is the leading reason for total hip and knee arthroplasty.^11,18 The direct and indirect costs of OA are staggering. Some estimates of the total cost of arthritis, of which OA is the most common form, exceed 2% of the gross domestic product.¹⁹

In both primary and secondary OA, conditions within the joint may act in the context of genetic susceptibility to initiate the disease process.

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