Infection risk and combination therapy benefits highlight conference

Tumor necrosis factor a (TNF-a) antagonists and biologic agents do not increase the risk of infection in persons who have rheumatoid arthritis (RA) significantly more than methotrexate (MTX) and other disease-modifying antirheumatic drugs (DMARDs), according to research findings presented recently at the American College of Rheumatology (ACR) Annual Scientif- ic Meeting in Philadelphia. Researchers compared the risk of infection associated with biologic therapies with that of DMARDs used alone by reviewing information on 18,305 patients with RA. The overall risk of serious infection was not increased with TNF-a therapy or with anakinra, abatacept, or rituximab. Nonmedication-related factors associated with infections included age, RA clinical disease activity index, measures of physical function, duration of RA, lung disease, and previous infection.

In another study, TNF-a therapy for severe RA appeared to increase a patient’s risk of septic arthritis. The condition occurred twice as frequently in patients with RA who were receiving TNF-α therapy as in patients who were not.

The results of a third study showed that the use of prednisone, especially in high doses, increases the chances that an infection will occur in a person with RA. If a patient requires a combination of a TNF-a inhibitor, DMARDs, and corticosteroids, the researchers noted, he or she and the rheumatologist should be vigilant about the possibility of infection, especially in the presence of comorbid conditions.

Several studies addressed the effectiveness of combination therapy. A combination of MTX with sulfasalazine (SSZ) and hydroxychloroquine (HCQ) used initially may be effective in controlling RA. Researchers investigated the benefit of taking a combination of 3 oral DMARDs (MTX, SSZ, and HCQ) or a combination of 1 DMARD (MTX) and a TNF-a inhibitor (etanercept) in persons with RA and the benefit of starting with combination therapy compared with “step-up” therapy. At 6 months, combination therapy led to better responses than initial treatment with MTX alone. During the second year, however, there were no differences in the average levels of Disease Activity Score 28 between patients randomized to etanercept or triple DMARD therapy, regardless of whether they received immediate combination treatment or initial therapy with MTX and a step-up.

Combination therapy with infliximab and MTX shows promise for children who have polyarticular juvenile idiopathic arthritis. In 1 study, 68% of patients had achieved remission at 54 weeks.

Other rheumatologic study findings reported at the ACR meeting include the following:
•Cigarette smoking leads to RA, to less successful treatment of patients with RA, and to disease activity and damage in patients with systemic lupus erythematosus (SLE).
•Patients who have both SLE and depression may experience additional health problems. In 1 study, 27% of women with SLE had meaningful symptoms of depression and 63% had atherosclerosis; women with SLE who were depressed had nearly a 4-fold risk for atherosclerosis. In another study, living in poverty, having traditional cardiovascular risk or disease, and SLE disease activity were found to be significant predictors of depression.
•Patients who are receiving TNF-a therapy for RA may be at increased risk for nonmelanoma skin cancer. An increased risk was identified in veterans who are receiving TNF-a therapy for RA.

For more information on these and other research findings, visit the ACR Web site at http://www. rheumatology.org. Or, contact the organization at ACR, 2200 Lake Boulevard NE, Atlanta, GA 30319-5312; telephone: (404) 633-3777; fax: (404) 633-1870. n