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In the June 15, 2008 issue of Arthritis Care & Research, the American College of Rheumatology (ACR) published updated guidelines on the use of nonbiologic disease-modifying anti-rheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA). The guidelines also provide recommendations for the use of biologic agents for the first time. The ACR recommendations are the culmination of a systematic review of evidence that updates guidelines that were previously released in 2002. They were developed for specialists who are familiar with assessing RA activity and disease severity.

Assessing DMARD Therapies

The ACR recommendations provide evidence-based suggestions for when to initiate biologic and nonbiologic DMARDs. Recommendations should be based on the level of disease activity, duration of RA, and factors that pertain to prognosis. Nonbiologic DMARD combinations recommended in the guidelines and used most commonly include methotrexate plus hydroxycholoroquine, methotrexate plus sulfasalazine, methotrexate plus leflunomide, sulfasalazine plus hydroxychloroquine, and sulfasalazine plus hydroxychloroquine followed by methotrexate. Monotherapy with either methotrexate or leflunomide, however, is recommended as initial therapy for most patients with RA for all disease durations and degrees of disease activity.

Biologic therapies have assumed a significant role in the treatment of RA, particularly for patients with severe RA and high disease activity after failure of nonbiologic DMARDs. The updated guidelines recommend appropriate times to consider biologics and provide safety considerations that should be recognized when using these therapies. Biologic DMARDs are separated according to disease duration (less than 6 months and 6 months or longer). Patients with early RA and only low or moderate disease activity are not considered candidates for biologic therapy. Anti-TNFá-agents (notably etanercept, infliximab, or adalimumab) are recommended for patients with early RA for 3 months or less and those with high disease activity who have never received DMARDs. These agents are also recommended for patients with an intermediate or longer duration of RA but who have failed to respond to methotrexate.

Safety & Surveillance

A number of potential contraindications are specified in the updated recommendations based on the unique profiles of the available therapies. Contraindications to nonbiologic and biologic DMARDs may include infectious disease and/or pneumonitis, as well as hematologic, oncologic, cardiac, liver, renal, and neurologic contraindications. Pregnancy and breast-feeding contraindications are also clarified. Specifically, leflunomide, methotrexate, and biologic agents should not be initiated or resumed in the presence of active bacterial infection, tuberculosis (TB), herpes zoster, or hepatitis B and C.

TB monitoring has been a safety concern associated with biologic therapy use. When considering biologic DMARDs, potential risk factors for TB should be assessed and a TB skin test conducted. All of the therapies used in RA necessitate attention to safety; patients should be seen at least three or four times a year to assess their efficacy in disease activity and to monitor for possible therapeutic toxicity. When starting or resuming DMARDs, conduct baseline tests of complete blood counts, liver transaminase, and creatinine levels. In those receiving methotrexate, leflunomide, or sulfasalazine, these tests should be repeated every 2 to 4 weeks for 3 months for new treatment or dose escalation. Hopefully, physicians will find that the updated ACR guidelines will serve as a valuable reference and guide.

Kenneth G. Saag, MD, MSc has indicated to Physician’s Weekly that he has received consultant fees (less than $10,000 each) from Roche, UCB, Nitec, and Amgen. He has also received research support from Abbott, Amgen, Centecor, Roche, and Wyeth.