Introduction

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that primarily affects the joints. The worldwide prevalence of RA has been estimated as 0.24% based upon the Global Burden of Disease 2010 Study. Prevalence rates in the US and Northern Europe are somewhat higher, with estimates between 0.5% and 1% and the annual incidence of RA in these areas is estimated at around 40 per 100,000 persons. RA affects women, in whom incidence and prevalence rates of RA are twice as high as in men, with the lifetime risk of developing RA at 3.6% in women compared to only 1.7% in men.¹

Overview

The development and progression of RA involve many pathways. B cell-derived autoantibodies and proinflammatory cytokines play a pivotal role. Such autoimmunity is dependent on a constant T cell–initiated immune response. The constant co-stimulation required for T-cell activation comes from a variety of sources—such as B cells, dendritic cells, and macrophages—through feedback loops that are crucial for disease perpetuation.²

As RA disease progresses, permanent structural damage and functional impairment can occur. Such outcomes include irreversible bone erosion, cartilage degradation, synovitis, pain, and other joint-related abnormalities.³

RA is associated with autoantibodies that target various molecules including modified self-epitopes and proinflammatory cytokines. The identification of these novel autoantibodies has enhanced diagnostic precision which has led to updated classification criteria that can facilitate both the recognition and analysis of the disease early in its course.⁴

Signs & Symptoms

Signs and symptoms of RA may include:⁵

• Painful, stiff, tender, or swollen joints, often with symmetrical joint swelling
• Prolonged feeling of stiffness in the morning and after inactivity
• Fever, fatigue, and loss of appetite

RA patients may experience periods of increased symptoms called flares—which can last for days or months—that alternate with periods of relative remission during which swelling and pain diminish. Initial bone loss can occur before clinical disease onset. After the onset of disease, the proximal interphalangeal, metacarpophalangeal, and metatarsophalangeal joints are involved most frequently.^5,6

The underlying systemic inflammation in RA patients can also give rise to extra-articular manifestations of disease, including:⁵

• Rheumatoid nodules⁷
  • Subcutaneous rheumatoid nodules eventually develop in up to 30% of patients, usually at sites of pressure and chronic irritation
  • Visceral nodules—such as pulmonary nodules, which require a biopsy to distinguish them from pulmonary nodules of other etiologies—are usually asymptomatic and occur in severe RA
• Vasculitis that can cause leg ulcers or mononeuritis multiplex
• Lung manifestations, such as pleural effusion, pulmonary infiltrates, or fibrosis
• Cardiovascular manifestations, such as pericardial effusion, pericarditis, or myocarditis
• Amyloidosis and lymphoma⁴

Typical changes of rheumatoid arthritis of the hands with prominent metacarpophalangeal osteopenia, erosions very marked within the carpus and radiocarpal/ulnocarpal joints.

Risk Factors

Although the exact cause of RA is unknown, several risk factors can increase the risk of developing RA. They include:⁸

• Age. RA can start at any age, but the chance of developing RA increases with age, and happens most frequently among adults in their sixties.
• Sex. Women are afflicted with RA about two-to-three times more than men.
• Genetics/inherited traits. People who have inherited certain genes, like HLA (human leukocyte antigen) class II genotypes, may have their arthritis exacerbated. In fact, the risk of RA may be highest when carriers of these genes are exposed to environmental factors that are also known to induce RA.
• Obesity. Being obese has been shown to increase the risk of developing RA. Studies examining the role of obesity also found that the heavier a person was, the more at risk they were of developing RA.
• Smoking. Several studies show a correlation between cigarette smoking and increased risk of developing RA, and smoking can also make the disease worse.

Disease & Clinical Trial Tools

It is important to assess disease activity in the follow-up of patients with RA. Clinical indicators employed in the assessment of RA activity use both individual variables (eg, swollen joint counts and acute phase reactant measurements) and composite indices for disease activity assessment. In addition, definitions of remission and criteria for clinically significant responses also use these indicators. Although several of these assessment tools were generated for use in clinical trials,⁹ many have been adopted and are frequently used in clinical practice.⁴

• ACR
• DAS28
• SDAI
• CDAI

American College of Rheumatology (ACR) Response Criteria

The American College of Rheumatology (ACR) response criteria is a composite measure used to determine the effectiveness of RA medications and treatments in clinical trials. ACR20, ACR50 and ACR70 reflect the extent of improvement in disease activity, as shown in the table on the right.²

Download ACR

Disease Activity Score 28 (DAS28)

To optimize care, the Disease Activity Score 28 (DAS28) measures disease activity in RA and tracks results over time.

Assessments of tender joint count (TJC) and swollen joint count (SJC) in the specified joints are combined with erythrocyte sedimentation rate (ESR) or C-reactive protein, and global health (GH) assessments to produce a DAS28 score, which correlates with the extent of disease activity.¹⁰

Download DAS28

Simplified Disease Activity Index (SDAI)

The easy to calculate Simplified Disease Activity Index (SDAI) is a useful tool for the routine clinical assessment of RA disease activity. To calculate SDAI, add the TJC28 (tender joint count using 28-joint counts), SJC28 (swollen joint count using 28-joint counts), patient global assessment of disease activity (PGA), evaluator global assessment of disease activity (EGA), and C-reactive protein (CRP) levels.¹¹

Download SDAI

Clinical Disease Activity Index (CDAI)

The Clinical Disease Activity Index (CDAI) can be assessed using only variables that can be immediately evaluated, making it a useful tool to evaluate RA disease activity. To calculate CDAI, add the TJC28 (tender joint count using 28-joint counts), SJC28 (swollen joint count using 28-joint counts), patient global assessment of disease activity (PGA), and evaluator global assessment of disease activity (EGA).²

Download CDAI