Clinical Quick Reference Monthly Newsletter/ November & December 2023 - New Test For RA Patients
Clinical Quick Reference Guides - Concept Review RA/PrismRA
This reference guide will review concepts related to Rheumatoid Arthritis and the PrismRA test.
What Is RA?
Rheumatoid arthritis (RA) is a systemic autoimmune disease. Approximately 1.3 million Americans suffer from RA. The condition is characterized by an inflammatory arthritis with extra-articular involvement. It is a chronic disorder, linked to a combination of genetic and environmental factors. RA primarily targets the synovial joints.
How Do We Know A Patient Has RA?
Because of the progressive nature of rheumatoid arthritis, early diagnosis and care are key to avoiding complications. In addition to clinical signs and symptoms, several tests help providers reach a diagnosis. Rheumatoid factor (RF) has been very useful in the diagnosis of RA. While RF may be indicative, it can lack necessary specificity. High rates of false positive RF were found in other connective tissue diseases, namely SLE and Sjogren’s syndrome.
Anti-cyclic citrullinated peptide (CCP) detection is one of the best markers introduced for diagnosis of RA. Sensitivity of the assay is similar to RF, however the specificity is superior.
Autoimmune? Synovial Joints? What’s Going On In Rheumatoid Arthritis?
Autoimmune conditions occur when aberrant immune responses cause the patient’s system to attack functional tissues as if they were foreign invaders. Synovial joints, also known as diarthroses, are joints that a freely mobile. They are considered the main functional joints of the human body.
Rheumatoid arthritis usually begins with smaller peripheral joints being affected. Clinicians note that the joint involvement in RA is generally symmetric. If left untreated, RA can progress to include the proximal joints as well.
Over time, chronic inflammation leads to destruction of involved joints, loss of cartilage, and bone erosion. Remember that when left untreated, rheumatoid arthritis is a progressive disease with morbidity and increased mortality. RA is a major risk factor for cardiovascular disease, severe infections and lymphoma.
“Early” Vs. “Established”
RA with a symptom duration of fewer than six months is defined as early RA. When the condition and symptoms are present for more than six months, it is defined as established RA.
It is interesting to note that autoantibodies will appear before the onset of clinical arthritis. Autoimmunity begins at the molecular and cellular levels far ahead of the clinical phase. This is often referred to as pre-symptomatic (or pre-clinical) rheumatoid arthritis.
A New Test?
A new blood test, called “PrismRA,” may help providers determine which therapies are best for patients with rheumatoid arthritis.
According to the clinicians and researchers that developed the PrismRA test, it is the first clinically validated RA test able to accurately predict treatment response. Their hope is that patients will receive the best treatment for their condition from the start.
The researchers found that the first line of biologic treatment RA patients are most often prescribed is an anti-inflammatory drug from the tumor necrosis factor inhibitor (TNFi) family. (Infliximab and adalimumab are two of several TNFis approved by the FDA). They also found that the success rate after six months of TNFI treatment for RA was only 30%. That meant the majority of patients with RA would be unable to successfully curb disease progression.
Eventually, the researchers were able to gain access to the TNFi response rates for hundreds of RA patients as well as baseline blood data. They analyzed genetic material from blood biomarkers and used machine learning algorithms to determine which patients would benefit from TNFis based on the data. In addition, they recruited and studied roughly 700 RA patients for a prospective trial to examine the PrismRA test's clinical value. This helped to validate the results.
According to their findings, patients who received PrismRA testing were three times more likely to have remission than those who had not taken the PrismRA biomarker test.
Learn more about how the PrismRA test works here:
TNFi’s (Tumor Necrosis Factor (TNF) Inhibitors)
One of the earliest histopathologic findings notable in rheumatoid arthritis is new synovial blood vessel growth. This process leads to transmigration of both lymphocytes and polymorphonuclear leukocytes into the synovial fluid.
Angiogenesis (blood vessel formation where new vessels will emerge from existing vessels) is required to support the highly catabolic synovium. It is spurred by proinflammatory cytokines such as tumor necrosis factor (TNF).
In the early phase of the disease, this infusion of inflammatory cells into the synovial membrane will lead to the proliferation of monocytes and a thickening of the synovial membrane. Small villous projections follow, these jut out into the joint space.
TNF inhibitors are medications that work to inhibit inflammation. They are prescribed worldwide in the treatment of inflammatory conditions.
Note:
Tumor necrosis factor is a protein in your body that causes inflammation.
FDA Approved TNF Inhibitors
The TNF inhibitors approved by the FDA are:
- infliximab,
- adalimumab,
- etanercept,
- golimumab, and
- certrolizumab.
These therapies may be used on their own, or combined with other medications such as:
- prednisone,
- methotrexate,
- hydroxychloroquine,
- leflunomide or
- sulfasalazine.
Taking A TNFi
There are two main ways patients receive TNF inhibitors therapies: self-injections and infusions.
Self-injections involve using a very small needle to deliver the medication just under the skin of the thigh or abdomen. Self-administered TNF-inhibitors can be given on a weekly, biweekly, or monthly basis. Infusions, on the other hand, are given in healthcare facilities over a period of several hours every 4-8 weeks.
Most patients feel better after receiving 2-3 doses, but it can take up to 3 months for the full effects to be felt.
TNFi Side Effects
The most common side effect seen with the injectable TNFi drugs are skin reactions. These are most commonly referred to as “injection site reactions.” Such reactions can last up to a week.
Infliximab, which is only available as an intravenous infusion, may rarely cause a severe allergic reaction. The symptoms of this reaction involve swelling of the lips, difficulty breathing and low blood pressure.
The most significant side effects for all of the TNF inhibitors is an increased risk for all types of infections, including tuberculosis (TB) and fungal infections. Some of the infections can be severe.
TNF inhibitors also increase the risk of certain types of skin cancer. Health care professionals need to remind their patients that using sun protection is recommended.
TNF inhibitors have been associated, rarely, with multiple sclerosis. They have also been known to worsen heart failure.
Medical Terminology
Getting to know these terms will help reinforce the above material.
Angiogenesis - blood vessel formation in which new vessels emerge from existing vessels
Autoantibodies - antibodies produced by the immune system directed against one or more of the individual's own proteins
Histopathologic – the microscopic examination of tissue
Rheumatoid arthritis (RA) – systemic autoimmune disease
Synovial joints (diarthroses) - joints that a freely mobile
TNF (Tumor necrosis factor) - protein capable of causing inflammation
Anatomy & Physiology
Rheumatoid Arthritis Nodules
RA nodules are firm subcutaneous lumps. These nodules appear in up to 20% of patients with the condition. Rheumatoid arthritis nodules tend to form close to affected joints. These “lumps” are composed of fibrin and inflammatory cells.
Clinicians are more likely to find the nodules on overexposed joints like the fingers and elbows. However, they can also be found in areas like the back of the heel.
Other Tests To Know
Sed Rate - Erythrocyte sedimentation rate (ESR) A blood test that helps indicate the amount of inflammation in a persons body by measures how fast red blood cells cling together and settle to the bottom of a tube over the course of an hour.
C-reactive protein (CRP) – is also a measure of inflammation. This protein is produced by the liver when there is inflammation anywhere in the body. The higher the inflammation, the greater the elevation in CRP.
MBDA test (Vectra DA) - developed by a biotechnology company to look at the chemical factors in the body that drive rheumatoid arthritis activity. It checks 12 proteins, hormones and growth factors to give the provider a single disease activity score
Helpful video:
Disclaimer: The above study guide represents study materials, always seek and follow the advice of your medical provider for any acute or chronic medical issues or questions.
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Resources:
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