Rheumatoid Arthritis: Early Intervention and Treatment

Rheumatoid arthritis may be linked to genetic, environmental, hormonal, immunologic, and infectious factors.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects an estimated 1.5 million individuals in the United States.¹ It is characterized by severe pain, stiffness, inflammation, joint deformity, fatigue, and eventual loss of mobility, all of which can negatively impact one’s overall quality of life.¹ While the exact cause of RA is unknown, researchers are discovering growing evidence that the disease may be linked to genetic, environmental, hormonal, immunologic, and infectious factors.^1-4 Studies reveal that women are 2.5 to 3 times more likely to develop RA compared with men.^1,3,5 According to the American College of Rheumatology (ACR), an estimated 75% of those affected by RA are women.⁶ While RA can occur at any age, it typically occurs later in life, manifesting most commonly between the ages of 30 and 60 years.^1,3,6 Key facts and statistics about RA can be found in Online Table 1.^1-6

TABLE 1: FACTS ABOUT RA

• The exact cause of RA is unknown, although genetic, environmental, hormonal, immunologic, and infectious factors are thought to play a pivotal role.
• RA affects women 2.5 times more than men.
• The typical age of onset is between 30 and 60 years (average, 66.8 years).
• RA carries a high risk for disability and mortality and accounts for 22% of all deaths from arthritis and other rheumatic conditions.
• Symptoms typically begin in the small joints of the fingers, wrists, and feet.
• Joints on both sides of the body are usually affected; over time, joints may become deformed and mobility impaired.
• Left untreated, RA may cause damage to lung tissue and increase the risk for hardening of the arteries and spinal injury (if neck bones are affected).
• RA may cause rheumatoid vasculitis (inflammation of the blood vessels), which may result skin, nerve, heart, and brain issues.

^{RA = rheumatoid arthritis.Adapted from references 1-5.}

While a diagnosis of RA may be overwhelming and pose some concerns and challenges, results from various clinical studies have shown that early diagnosis and treatment may halt the joint damage associated with RA.^2,5 Pharmacists can assist patients with RA—especially newly diagnosed patients—not only by counseling them about their medications but also by directing them to available educational resources to help them manage and cope with this disease as effectively as possible.⁷

Over time and without early intervention, RA can worsen and have a negative impact on everyday life by making simple tasks cumbersome and affecting one’s ability to function. Some patients with RA also experience high levels of depression and anxiety, low self-esteem, and feelings of helplessness.^1,6,8 With the development of more effective therapies over the past 2 decades, patients with RA now have additional treatment options that may produce better clinical outcomes and enable them to lead more active lives; some patients may even achieve remission.⁷ Moreover, results of clinical studies reveal that intensive treatment of early RA can stop joint damage and improve overall quality of life.^6,7 Signs and Symptoms

The signs and symptoms associated with RA tend to manifest gradually and become additive over time (Online Table 2).^1,3,5 Symptom severity varies from patient to patient, with the hallmark characteristic being persistent synovitis (also known as symmetric polyarthritis).⁶ Synovitis typically develops gradually and symmetrically, often involving the joints of the hands, wrists, knees, or feet.^5-7 Patients also often complain of morning stiffness, and some develop rheumatoid nodules, which are lumps of tissue that form under the skin.^5-7

TABLE 2: SIGNS AND SYMPTOMS ASSOCIATED WITH RHEUMATOID ARTHRITIS

• Tender, warm, swollen joints
• Symmetric pattern of affected joints
• Inflammation often affecting the finger joints closest to the hand and wrist
• Inflammation sometimes affecting other joints, including the neck, shoulders, elbows, hips, knees, ankles, and feet
• Low-grade fever, fatigue, malaise, generalized stiffness, myalgia, or generalized arthralgia

^{Adapted from references 3, 5-7.}

Treating Rheumatoid Arthritis

There is no cure for RA, but recent years have brought new treatments that have greatly improved therapeutic outcomes for patients with the disease. Many experts believe that aggressive and early RA treatment may delay or decrease joint destruction.^2,6,7,9,10 In general, the goals of treatment include pain relief, reduced joint inflammation and damage, improved quality of life, and a better ability to perform everyday tasks.^2,6,7 Treatment is typically multipronged and involves pharmacologic therapy as well as nonpharmacologic measures such as adequate nutrition, physical therapy, emotional support, exercise, and rest. Studies have shown that exercise may benefit patients with RA by improving joint mobility and slowing loss of muscle mass. However, some patients may require surgery.

Various classes of pharmacologic agents are used to treat RA, including nonsteroidal anti-inflammatory drugs, corticosteroids, and disease-modifying antirheumatic drugs (DMARDs).^1,3,6,7 DMARDs are classified into 2 subtypes: nonbiologic and biologic. Nonbiologic DMARDs include hydroxychloroquine, azathioprine, sulfasalazine, methotrexate, leflunomide, and cyclosporine.^6,7,11,12 In October 2013, the FDA approved Otrexup, the first single-dose, selfadministered, disposable methotrexate subcutaneous autoinjector; this new drug is indicated for adults with severe, active RA who have not responded to or cannot tolerate first-line therapy.^11,13 Another category of pharmacologic agents approved for RA is a subset of DMARDs called biologic response modifiers, or biologics (Online Table 3).^11-34

TABLE 3: BIOLOGIC DMARD AGENTS USED TO TREAT RA

Drug Class

Agent

Comments

Common Adverse Effects

TNF inhibitors

· Etanercept (Enbrel)

· Infliximab (Remicade)

· Adalimumab (Humira)

· Certolizumab pegol (Cimzia)

· Golimumab (Simponi)

· Patients may experience fever, chills, body aches, and headache associated with the infusion of biologics.

· TNF inhibitors are administered either subcutaneously or intravenously depending on the agent and manufacturer recommendations.

· These agents are used as monotherapy or in conjunction with methotrexate.

· Patients should be tested for TB before starting therapy with TNF inhibitors. Patient should also talk to their primary health care provider before getting any live vaccines.

· Injection-site reaction

· Upper respiratory infection

· Pneumonia

· Urinary tract infection

· Skin infection

· Nausea

Selective T-cell costimulation modulator

Abatacept (Orencia)

· Abatacept is administered either subcutaneously or intravenously.

· Responses are typically observed within 3 months of therapy.

· As with other biological DMARDs, infections are increased in patients receiving abatacept.

· This agent may be used as monotherapy or with DMARDs other than TNF antagonists.

· Headache

· Dizziness

· Sore throat

· Cough

· Nausea

CD20-directed cytolytic antibody

Rituximab (Rituxan)

· Rituximab is administered intravenously.

· Patients should receive an intravenous corticosteroid 30 minutes before each infusion to reduce the incidence and severity of infusion reactions.

· Hives

· Itching

· Swelling

· Difficulty breathing

· Fever

· Chills

· Changes in blood pressure

IL-6 receptor antagonist

Tocilizumab (Actemra)

· Tocilizumab is administered via intravenous infusion or subcutaneous injection.

· It is indicated for the treatment of adult patients with moderate to severe RA who have had an inadequate response to one or more DMARDs.

· Upper respiratory tract infection

· Nasopharyngitis

· Headache

· Hypertension

· Increased alanine transaminase

Human recombinant IL-1 receptor antagonist

Anakinra (Kineret)

· Anakinra is administered subcutaneously.

· In clinical studies, some patients have experienced symptom improvement within 12 weeks after beginning treatment.

· Injection-site pain

· Erythema

· Itching

· Fever

· Nausea

^{DMARD = disease-modifying anti-rheumatic agent; IL = interleukin; RA = rheumatoid arthritis; TB = tuberculosis; TNF = tumor necrosis factor.Adapted from references 11-32.}

Many health care experts agree that early implementation of therapy with DMARDs is considered the standard of care in managing RA, with methotrexate being the first line of therapy for most patients.^6,7,11,12,14 Results from various studies reveal that initiating early therapy with these agents (<6 months after the onset of symptoms) helps not only to delay the progression of RA more effectively when compared with later treatment, but may also generate remission in more patients.^6,7,11,12 These results show that the use of DMARDs can slow or prevent disease progression, joint destruction, and subsequent loss of mobility and function.^6,11,14 In addition, researchers believe that proper use of DMARDs may also decrease or eliminate the need for other antiinflammatory or analgesic medications; however, until the full therapeutic effect of DMARDs takes effect, anti-inflammatory or analgesic medications may be warranted as supplemental therapy for pain and inflammation if no contraindications are present.^6,11,14

The FDA has also approved an oral agent in a new class of drugs known as janus kinase (JAK) inhibitors for the treatment of RA.³⁰ JAK inhibitors block janus kinase pathways, which are involved in the body’s immune system.^11,30-32 Tofacitinib (Xeljanz) is the first oral biologic DMARD approved in almost a decade.^14,31 It is indicated for adults with moderate to severe RA who have had an inadequate response to, or who may have been intolerant of, methotrexate.³¹ The FDA reports that the use of tofacitinib is associated with an increased risk for serious infections (including opportunistic infections), tuberculosis, cancers, and lymphoma.³¹ Xeljanz should not be initiated in patients who have an active infection, including a localized infection.³¹ It may be used as monotherapy or in conjunction with methotrexate or other nonbiologic DMARDs.³¹ It should not be used in combination with biologic DMARDs or potent immunosuppressants, such as azathioprine or cyclosporine.³¹

In 2012, the ACR published updated guidelines for treating and managing RA.¹⁵ These guidelines encourage physicians to individualize therapy and consider the risks and benefits of treatment for each patient.^7,14,29

Counseling Patients

Patients should have a clear understanding about their treatment plan and be encouraged to take an active role in their overall health. During counseling, they should be educated about their medications as well as nonpharmacologic measures to control or decrease common RA symptoms and flare-ups; these measures include hot and cold treatments, relaxation techniques, massage therapy, and exercise.³⁵ Patients should keep a current list of all medications they are taking, including OTC drugs, nutritional supplements, and alternative remedies; patients should also consult their primary care provider before taking any medications to avoid potential drug interactions or contraindications. In addition, patients should be encouraged to join support groups so that they can learn more about RA and how to cope with its physical and emotional aspects, as well as gain more insight into controlling this disease. Support groups may also provide patients with positive reinforcement and encouragement.

During counseling, patients should be reminded that they can improve their RA symptoms by managing their overall health, adhering to the prescribed medication regimen, getting sufficient rest when needed, staying active, and eating a balanced diet. Patients should be aware that aggressive and early treatment may significantly improve their condition and should be encouraged to discuss their treatment options with their primary health care provider.

Great strides have been made in the development of medications for RA. Today, in conjunction with rest, exercise, patient education, and support programs, patients with RA can effectively manage their condition and lead active lives. More than 400 clinical trials investigating RA are ongoing. For more information, visit https://clinicaltrials.gov/ct2/results?term=rheumatoid+arthritis&recr=Open.

TABLE 4: RESOURCES FOR PATIENTS WITH RHEUMATOID ARTHRITIS

• American College of Rheumatology: www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/ra.asp www.rheumatology.org/practice/clinical/guidelines/Singh_ACR_RA_GL_May_2012_AC-R.pdf
• Arthritis Foundation: www.arthritis.org
• National Institute of Arthritis and Musculoskeletal and Skin Diseases: www.niams.nih.gov/Health_Info/Rheumatic_Disease/rheumatoid_arthritis_ff.asp
• Rheumatology Research Foundation: www.rheumatology.org/Foundation

Ms. Terrie is a clinical pharmacist and medical writer based in Haymarket, Virginia.

References

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