Updated Rheumatoid Arthritis Fact Sheet 2018

What is rheumatoid arthritis?

Rheumatoid arthritis (RA) is an inflammatory disease affecting the joints, the connections between bones. Unlike the more common osteoarthritis, which is due to wear and tear on the joints, RA is an autoimmune disorder, which occur when the immune system, the body’s defense against infection, starts attacking healthy tissue. In RA, this leads to inflammation in the lining of the joints (called the synovial membranes ), causing pain, swelling, stiffness, and, if not treated early and properly, damage and loss of function. Progression of the disease often results in deformities of the affected joints.


RA usually starts by affecting the small joints in the fingers, toes, and wrists. It usually affects both the left and the right side at the same time. (Other types of arthritis, such as OA, tend to first affect larger joints, like the knees or hips. And they may affect one side much more than the other.)


As the disease progresses the elbows, shoulders, knees, hips, and cervical spine (the neck portion of the spinal cord) can also be involved.
Inflammation can also affect other organs, including the heart, lungs, and eyes. RA is a chronic illness, with no known cure. The main treatment options include drug therapies to control symptoms and slow joint damage, and lifestyle changes to make living and coping with the pain of the disorder easier.


RA is found in roughly 1% of the US population, most commonly in those between the ages of 40 and 60. It occurs in both genders, but women are three times more likely to be affected. A similar disorder, juvenile rheumatoid arthritis (also known as juvenile idiopathic arthritis) can be found in children under the age of 16.

Risk Factors


The cause of rheumatoid arthritis (RA) is unknown, but some risk factors have been identified, including:


Gender - women are three times more likely than men to be diagnosed
Genetics - RA is not an inherited disease.

However, people with specific variants of human leukocyte antigen (HLA) genes are more likely to develop RA than people with other gene variants. Many individuals who carry HLA genes never develop RA. This suggests that additional factors (a trigger) must be necessary for a person to develop the condition. Some possibilities include:

- Infection by a virus or bacteria
- A history of smoking (smoking may also increase the severity of RA)
- A stressful life event in the months leading up to diagnosis 

Diagnosis of Rheumatoid Arthritis

Early-stage rheumatoid arthritis (RA can be difficult to diagnose, as the symptoms are similar to other forms of arthritis. Because RA cannot be diagnosed using a single test, a definitive diagnosis may not be made immediately. The longer the symptoms are experienced, the more likely it is that RA is the correct diagnosis. RA is diagnosed through a multi-step process including a medical history and physical examination, blood tests, and x-rays of the affected joints.

The medical history and physical exam will look for symptoms that have lasted for longer than six weeks, including morning stiffness lasting longer than one hour and pain and/or swelling in at least three joints in both of the hands or wrists. The exam will also measure reflexes and muscle strength.Blood tests will also be performed measuring all of the following:

  • Rheumatic factor (RF) – an antibody called RF is present in the blood of 70-80% of people with RA. However, RF is also found in people with other types of rheumatic disease and in a small number of healthy individuals.
  • Anti-cyclic citrullinated peptide (anti-CCP) / protein antibody (ACPA) – blood tests for antibodies to CCP / ACPA are more specific than RF for diagnosing RA. Anti-ACPA antibody tests may be positive very early in the course of disease. The test is positive in most patients with RA.
  • Erythrocyte sedimentation rate (ESR) – a blood test that indirectly measures how much inflammation is in the body. People with RA tend to have an elevated ESR, which indicates the presence of an inflammatory process in the body.
  • C-reactive protein (CRP) – a protein produced by the liver in response to inflammation or infection. Elevated levels are often seen in RA due to the inflammation associated with the disease.
  • X-rays of the hands, wrists, and feet are taken, both to check for current damage to the joints and to use as a baseline to compare to future x-rays, in order to measure disease progression.

Symptoms and Disease Progression
 
Rheumatoid arthritis (RA) is a progressive disease, and early symptoms may be so mild that they go unnoticed, such as fatigue, low-grade fever, and tingling or numbness in the hands. Other symptoms begin gradually and include:

  • Painful, red, and swollen joints
  • Morning stiffness lasting longer than 1 hour
  • Pain in the same joints on both sides of the body
  • Rheumatoid nodules , firm lumps of tissue under the skin

The joints in the feet, hands, and wrists are generally the first to be involved. In the early stages, RA typically affects small joints, especially the joints at the base of the fingers, the joints in the middle of the fingers, and the joints at the base of the toes. Patients may experience pain when squeezing their hands, may lose grip strength, may have trouble bending the wrists backwards, or may experience pain when putting weight onto different parts of the feet. As the disease progresses, other joints may become involved, including the elbows, shoulders, ankles, knees, hips, and cervical spine (the neck area). In roughly 30% of patients, the cricoarytenoid joint, which is near the windpipe, may also be involved, leading to hoarseness and difficulty breathing.

Patients with RA experience multiple symptoms beyond joint pain, or extra-articular symptoms. These are due to inflammation, and can include:

  • Inflammation of the tissue lining the chest cavity and surrounding the heart (pericarditis), a cause of chest pain or difficulty breathing
    Inflammation of the lung that is not due to infection may cause shortness of breath and a dry cough.
  • Problems with nerve function, a cause of numbness or tingling
  • Inflammation of the eye, a cause of pain and vision difficulties
  • Enlargement of the spleen, can reduce the number of healthy red blood cells, platelets and white cells thereby increasing the risk of infections and bleeding.
  • Sjogren's syndrome , a cause of dry mouth and eyes
  • Inflammation of the blood vessels (vasculitis)
  • Anemia

Progression of the disease varies for each patient. Many show a typical, or “classic,” RA, in which the disease progresses consistently over time, while others display a “palindromic” rheumatism, where the symptoms are episodic. These patients can experience joint pain and swelling for hours or days, followed by days or months symptom-free.

The times when a disease is active and symptomatic are known as flares, and times when the symptoms have abated are known as remission. While disease activity in terms of flares and remissions can vary among patients, all will experience irreversible joint damage, particularly if not properly treated with medication. The structural damage can cause pain, deformity, and functional difficulties that will persist even during periods of remission.


Stages of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a progressive disease, characterized by periods of flares and periods of reduced activity. In most patients with RA, the severity of symptoms fluctuates for weeks or months. It is generally impossible to predict the course of disease in a particular individual [see our video in the Conversations submenu). The goal of therapy is to increase the periods of remission and to limit the damage during periods of disease activity.
 
RA can be grossly categorised into three stages based on progressively worse symptoms of inflammation and damage. 

Mildly active

  • Fewer than 5 inflamed joints
  • Mildly elevated or normal ESR and CRP
  • No symptoms beyond joints
  • No evidence of joint damage

Moderately to severely active

  • At least 5 inflamed joints
  • Elevated ESR and CRP
  • Positive RF and anti-CCP
  • Evidence of joint damage

End-stage

  • Disease has not responded to treatment
  • Pain, loss of function, decreased activity
  • Joint damage
  • Nerve damage
  • Organ involvement (heart, lungs)
  • Elevated ESR and CRP

 

Complications of rheumatoid arthritis

Rheumatoid arthritis (RA) is associated with multiple complications and raises the risk for a number of other disorders. These include:

  • Osteoporosis - A condition that weakens the bones and makes them more prone to fracture. RA itself, along with some medications used for treating it (such as corticosteroids) can increase the risk of osteoporosis.
 
  • Carpal tunnel syndrome - A condition caused by the compression of the median nerve in the wrist (the nerve that serves most of the hand and fingers), which can cause pain and numbness in the hand. In RA this can be due to inflammation involving the wrist and compressing the nerve.
  • Heart disease - RA can increase the risk of hardened and blocked arteries (including those that nourish the heart itself), as well as inflammation of the sac that encloses the heart.
  • Lung disease - People with RA have an increased risk of inflammation and scarring of the lung tissues, which can lead to progressive shortness of breath.

Treatments for Rheumatoid Arthritis

As there is no cure for Rheumatoid arthritis (RA), the main focus of treatment is to reduce pain and inflammation, and to limit the amount of joint damage. Treatments should be decided by a rheumatologist, a doctor that specializes in treating the many forms of arthritis, and should be tailored to the individual patient.

Treatments will include a combination of the following:

  • Drug therapy
  • Physical therapy
  • Patient education and counselling
  • Lifestyle modifications

 
State of the Art Research on Rheumatoid Arthritis

While biologic TNF-inhibitors are very effective at reducing the inflammation and joint damage associated with Rheumatoid arthritis (RA), these drugs can be very expensive, limiting their use to patients who can afford them. Newer choices, known as biosimilars, are on offer at a lower cost.  A biosimilar is a drug which is similar to a biological drug already in use, but which differs in minor ways due to production differences. Biological drugs are made from living cells, and it is not possible to perfectly replicate the manufacturing process in another laboratory using different cells. Therefore, before a biosimilar can be used in treatment it must be proven to be as safe and effective as the drug it is mimicking. The function of a biosimilar TNF-inhibitor must be the same as the TNF-inhibitor already available, which means it must undergo significant clinical testing to prove its safety and efficacy.

Biosimilars, such as CT-P13, which mimics infliximab (Remicade), are currently being tested. CT-P13 has already been shown to be as safe and as effective as infliximab (Remicade) in the short-term, and studies of its long-term efficacy are underway. Janus kinase (JAK) inhibitors , such as tofacitinib (Xeljanz), are the newest non-biologic therapy on the market. JAK is an enzyme that signals the body to start an inflammatory response. JAK inhibitors block the signaling pathway, decreasing inflammation. Tofacitinib is useful for patients with moderately to severely active rheumatoid arthritis, and can be taken on its own or in combination with another DMARD. Studies have shown that 75% of patients using tofacitinib experienced a 20% reduction in their symptoms, a third had about 70% reduction, and 17.9% achieved remission. It should not be taken with a biologic drug, such as the TNF-inhibitors. JAK inhibitors have been associated with decreased white blood cell levels, which increases the risk of infection, as well as high blood pressure and high cholesterol levels. Tofacitinib is currently available for use, though the long-term effectiveness is still under research. Other JAK inhibitors currently being studied are baricitnib, VX-509, and BLPG0634.

Compound 20 is a new therapy currently being studied, which affects the T cells. T cells are lymphocytes, cells that have a variety of roles in the immune response. Conventional T cells are involved in initiating an immune response, while regulatory T cells inhibit the immune response once it has already started. Compound 20 has been found in animal studies to have two actions that may regulate RA: it inhibits the conventional T cells, while at the same time increases the activity and effectiveness of the regulatory T cells, restoring the activity of these T cells to normal levels and helping to calm the autoimmune response. This therapy is currently undergoing clinical trials.

Other possible drug therapies currently under research in animals include atsttrin, ascorbyl palmitate, and BH3. Atsttrin is a protein that has been engineered to inhibit certain forms of tumor necrosis factor (TNF). This protein can slow the inflammatory response, but does not decrease the overall immune system as do current TNF-inhibitors, therefore patients would not be as susceptible to infection. Ascorbyl palmitate is a gel injected directly at the joints involved in rheumatoid arthritis. The gel holds a medication that is released only when inflammation is occurring, and only at the site of the joint, unlike systemic treatments which can affect the entire body. BH3 is a molecule developed to mimic the protein Bim. Bim removes cells in the body that do not belong, such as, in RA, the extra immune cells that are produced to attack the joints. BH3 has been shown to improve symptoms in mice with RA, and even blocks RA from developing when given to healthy mice.

These therapies could prove to be important developments in RA treatment; however, they are all still under preliminary research, and must undergo clinical testing in humans.

It is very important that you give your body the best chance to manage the disease:

  • Exercise regularly
  • Eat moderately with an emphasis on fruit and vegetables
  • Keep a positive attitude
  • Keep your friends close
  • Occupy your time