Biologic therapies have been cited as promising developments in the treatment of rheumatoid arthritis. With this in mind, the panelists for this Q&A discussion offer their insights on baseline diagnostic testing for patients who may be candidates for these medications. The panelists also emphasize the importance of patient education on these agents and offer a closer look at new drugs that may emerge in the future.

Q: What types of tests do you obtain prior to initiating biologic therapy?

A: Alan Kivitz, MD, usually obtains a complete blood cell count (CBC), chemistry panel, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and purified protein derivative (PPD). Dr. Kivitz notes that baseline tests have been evolving over the years. More recently, he has added testing for Hepatitis B and C in this patient population.
       Nathan Wei, MD, concurs. He adds that his practice performs annual PPD testing for patients who are being treated with biologics.
       “While biologic therapies have revolutionized our approach to RA and have allowed us to get patients into remission and slow down disease progression, they have also presented rheumatologists with challenges as far as monitoring for safety issues,” points out Dr. Wei.
       Dr. Wei notes that the role of the Quantiferon gold test for assessing tuberculosis risk remains unclear.

Q: How do you counsel your patients before starting them on biologic therapy?

A: Dr. Kivitz says one should obviously tailor the discussion to the individual patient. While he always discusses the higher risk of infection with biologics, Dr. Kivitz says he tries to put this into perspective for his patients. He provides them with literature on the biologic therapies and notes this is a springboard for further discussion at their next visit.
       “For most patients, the decision (to try a biological therapy) is not made at one visit,” explains Dr. Kivitz. “The discussion about potential toxicities is an ongoing item with most visits.”

Q: What new breakthroughs in RA medication do you see emerging in the next three to five years?

A: “Over the next three to five years, I expect to see the approval of tocilizumab, certolizumab pegol and golimumab,” predicts Roy Fleischmann, MD.
       Tocilizumab, a monoclonal antibody to the IL6 receptor, will have a once-a-month IV dosing, according to Dr. Fleischmann. By the time tocilizumab (Actemra, Roche) receives FDA approval, Dr. Fleischmann believes the research will show the agent is effective as a monotherapy, in combination with methotrexate, in combination with other DMARDs and in patients who have previously failed anti-TNF drugs.
       Dr. Fleischmann says the safety profile of tocilizumab is not yet clear but it may be different than that of the anti-TNF agents.
       He also cites the potential of certolizumab pegol (Cimzia, UCB). Dr. Fleischmann says this agent may receive approval for treating patients who have had an incomplete response to methotrexate, and may garner approval as a monotherapy as well. He suggests this therapy may have key advantages over other ant-TNF medications.
       “The qow subcutaneous injection may burn less than the other subcutaneous anti-TNF drugs and appears to have maximal effect (ACR 20, ACR 50 and ACR 70 responses) within three to four months, which is faster than the other anti-TNF medications,” explains Dr. Fleischmann.
       Dr. Fleischmann also predicts that golimumab (Centocor) will be approved for the indications of early RA, ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in those who have had an incomplete response to methotrexate and patients who have failed DMARDs and anti-TNF drugs. He says the medication will likely be prescribed as a monthly subcutaneous injection or intravenous infusion. Dr. Fleischmann believes the agent will have a similar safety profile and efficacy as infliximab (Remicade, Centocor).
       He adds that several B-cell therapies may be approved for the treatment of RA in the next couple of years. Dr. Fleischmann cites agents such as ocrelizumab (Genentech), a human antibody to B cells that is similar to rituximab (Rituxan, Genentech), and the anti-CD20 therapy ofatumumab (Genmab). He also asserts that TRU-015, a Trubion anti-CD20 agent still in development, may eventually be approved as well.
       Dr. Fleischmann adds that several oral agents (including an anti-JAK3 kinase drug) are currently in development.

Pertinent Pearls In Diagnosing And Treating RA

- Q: What little known or possibly overlooked pearls can you share that might help clinicians treating RA? A: Ron Rapoport, MD, says there is insidious onset of the disease in 70 percent of patients with RA. He emphasizes that the cervical spine is affected in 20 to 50 percent of patients with RA. Dr. Wei concurs. When it comes to patients with RA and neck pain, Dr. Wei encourages clinicians to obtain flexion and extension films of the neck along with a magnetic resonance imaging (MRI) scan to look for evidence of erosion of the odontoid or significant subluxation. Drs. Rapoport and Wei point out that thrombocytosis may correlate with disease activity. In his clinical experience, Dr. Wei says thrombocytosis often correlates with an elevated ESR and CRP. Dr. Rapoport says the differential diagnosis of rheumatoid nodules includes tophaceous gout, amyloid, sarcoid and xanthoma formation. He adds that diseases other than RA that are associated with a positive rheumatoid factor include hepatitis C (40 percent), Sjogren’s syndrome (70 percent), systemic lupus erythematosus (20 percent), subacute bacterial endocarditis and other chronic infections. Dr. Wei adds that leprosy and sarcoidosis may also be associated with a positive rheumatoid factor.

       Dr. Kivitz is Director of the Altoona Arthritis Research Center in Altoona, Pa.

       Dr. Rapoport works in a private practice in Fall River, Mass.

       Dr. Fleischmann is a Clinical Professor of Medicine at the University of Texas Southwestern Medical Center and is the Co-Medical Director of the Metroplex Clinical Research Center in Dallas, Tx. Dr. Fleischmann has been a clinical investigator of RA therapies for over 30 years.

       Dr. Wei is a board-certified rheumatologist. He is the Clinical Director of the Arthritis and Osteoporosis Center in Frederick, Md.