In the debut of our “Rheumatoid Arthritis” Q&A column, the expert panelists take a closer look at whether the blood test for rheumatoid factor (RF) can be beneficial in diagnosing rheumatoid arthritis (RA). They also discuss the evolution of methotrexate as a first-line treatment therapy. Without further delay, here is what the panelists had to say.

Q: When the diagnosis of rheumatoid arthritis (RA) is less than clear, won't the blood test for rheumatoid factor (RF) give me the answer I need?
A: All of the panelists agree that the blood test for RF can aid in the diagnosis of RA but is not diagnostic in and of itself. They concur that RA is primarily a clinical diagnosis.

When evaluating patients with rheumatoid arthritis, Dr. Peck says they may have decreased grip strength or may have trouble making a fist.

Brian Peck, MD, says the diagnosis of RA should be based upon typical findings in the patient history and physical examination. Typical history findings include reports of morning stiffness, increased stiffness after prolonged immobility and reports of symmetrical swelling of the small joints of the hands and feet, according to Dr. Peck. Eric Gall, MD, concurs. In addition to the swelling of the small joints, Dr. Gall says RA patients usually have synovitis, involvement of other joints and systemic symptoms.

When examining patients with RA, Dr. Peck says clinicians will also typically note warmth of the affected joints with evidence of soft tissue swelling. It is also generally easier to detect effusions in the knees than in the small joints, according to Dr. Peck. He adds that RA patients may have decreased grip strength or may even have difficulty making a fist at all.

In regard to the rheumatoid factor, Antonio P. Giannelli, MsA, PA-C says it is a measurement of an antibody against human IgG that is usually detected by the latex agglutination technique or the newer nephelometry technique. Giannelli notes that RF is produced when chronic immune stimulation is present.

When it comes to patients with the aforementioned clinical symptoms of RA, Dr. Gall says a positive RF, particularly in a higher titer, offers another bit of clinical evidence to help make the RA diagnosis. The higher the titer, it is more likely the patient has RA, according to Dr. Gall. He also notes that RA patients who have a positive RF have a poorer prognosis than patients who are seronegative. Giannelli concurs. He points out that patients with RA and a positive RF generally tend to have a more aggressive disease, particularly when it comes to joint inflammation and destruction, and a higher incidence of extraarticular manifestations such as iritis or RA lung.

However, Dr. Gall notes that in terms of diagnosing RA, the sensitivity and specificity of the RF test ranges between 70 to 80 percent. All the panelists agree that patients may have a positive blood test for RF with other disease states such as hepatitis, bacterial endocarditis and some lymphoproliferative disorders. Dr. Gall emphasizes that a positive RF is common among patients with chronic infection or chronic fibrotic disease of the lung, liver and other organs.

Additionally, Dr. Gall points out that elderly patients “often have positive RF … without having apparent disease.” In the overall population, between three to five percent of individuals with positive RF have no associated disease, according to Dr. Gall. Dr. Peck says greater than five percent of individuals “without any kind of arthritis” exhibit a positive RF.

In Dr. Peck's experience, many individuals with a clear clinical diagnosis of RA have a negative test for RF. These patients with seronegative RA often develop another disease state such as psoriatic arthritis or gout, according to Giannelli.

When it comes to seronegative patients whom you suspect of having RA, Giannelli recommends the lab test anti-CCP (cyclic citrullinated peptide) antibody. He says this test is “highly specific for RA.” Dr. Gall adds that the clinical use of this test is increasing among specialists who treat this disease.

Q: When should methotrexate be used to treat suspected RA?
A: Methotrexate is considered the gold standard in treating RA, according to the panelists. Dr. Gall says one should not use the drug in “suspected RA” and Giannelli adds that one may start using methotrexate “as soon as the diagnosis of RA is made,” provided there are no contraindications such as hepatitis.

As Drs. Gall and Peck point out, the use of disease-modifying agents such as methotrexate has evolved over the years. Originally, Dr. Gall notes that gold, methotrexate and other disease modifying agents were used only after clinicians had failed to get results with less toxic and less aggressive treatments. However, knowing that significant joint destruction and disability can occur “very early, even in the first months and years of disease,” Dr. Peck says clinicians are now treating RA earlier and more aggressively. Dr. Gall concurs, noting that early use of drugs such as methotrexate can prevent disease progression and erosions in joint destruction, and lead to better outcomes.

Giannelli notes that methotrexate is one of several disease modifying antirheumatic drugs (DMARDs), which one can prescribe to suppress joint inflammation. The advent of biologic therapy, such as tumor necrosis alpha-inhibitors, has begun to challenge methotrexate as the drug of first choice in treating RA, according to Dr. Gall. He says the biologic agents are “effective, relatively safe and often have dramatic effects on patients with RA.” However, Dr. Gall concedes the biologic agents are far more expensive than methotrexate and notes the long-term safety data are just becoming available for the biologic agents.

Giannelli says he often uses methotrexate in conjunction with antiinflammatories and biologic agents but notes that it “can take several weeks to become effective.” Dr. Gall counters that biologic agents are often more effective when one combines them with methotrexate.

While one may consider the use of other DMARDs, Dr. Peck says methotrexate is usually the best choice due to its efficacy and ease of administration. He notes that one can administer the drug PO, IM, SQ or even IV in doses of five to 25 mg once a week. Dr. Peck points out that parenteral dosing is usually more effective than PO administration due to more complete absorption and fewer gastrointestinal side effects. Although many clinicians administer methotrexate PO from the beginning of therapy, Dr. Peck says some begin dosing it parenterally and switch to the PO route once the treatment has been established.

Dr. Peck advises checking CBC, U/A, kidney and liver functions prior to initiating treatment with methotrexate. When using the drug, Giannelli says one must monitor liver function tests and CBC routinely to guard against hepatotoxicity and neutropenia. On the other hand, Dr. Peck recommends checking these monthly for the first two or three months and less frequently afterward. Dr. Peck says it is okay if liver functions rise slightly but if the trend continues, one should lower or temporaily suspend methotrexate pending further monitoring of the aforementioned tests.

One should not use methotrexate to treat patients who have any possibility of becoming pregnant and in those who have liver disease, according to Dr. Gall. He says there are a number of other relative contraindications to the drug. Dr. Gall adds that clinicians must tell patients to avoid consuming alcohol during the treatment course.

Brian Peck, MD, is an Assistant Clinical Professor of Medicine at the Yale University School of Medicine, and is an Adjunct Clinical Professor of Medicine within the Physician Assistant Program at Quinnipac University in New Haven, Ct. He is the Medical Director of the Arthritis Center of Connecticut in Waterbury, Ct.

Eric Gall, MD, is a Professor and Chairman of the Department of Medicine at the Chicago Medical School within the Rosalind Franklin University of Medicine and Science in Chicago. He is a Fellow of the American College of Rheumatology and is a Master of the American College of Physicians.

Antonio Giannelli, MsA, PA-C, is a physician assistant with Associated IM Specialists, Rheumatology in Battle Creek, Mich. He is a Clinical Instructor within the Department of Internal Medicine at Michigan State University. He is also a board member of the Society of Physician Assistants in Rheumatology.