Biologic therapies- silver bullets that target the immune system abnormalities in rheumatoid arthritis (RA) patients- have revolutionized the treatment of this disease. It is now possible to put patients with RA into remission.

However, as with all therapies there are potential downsides. One of the risks that has been written extensively about is infections, particularly with TNF-α inhibitors. Examples of these drugs include Enbrel, Humira, and Remicade.

A recent study supports the notion that infections are not only increased in incidence but also are responsible for more hospitalizations in patients with rheumatoid arthritis.

Among patients with rheumatoid arthritis, treatment with tumor necrosis factor (TNF) antagonists is associated with a "small to moderate" increase in risk of hospitalization with infection. (Askling J, et al. Ann Rheum Dis 2007;66:1339-1344).

The authors state, "These findings add to the emerging evidence to suggest that anti-TNF treatment is indeed associated with an increased risk of infections," and they add, "since... closer monitoring for infections may be difficult to achieve in clinical practice, an increased awareness and increased patient information of this potential side effect of treatment may be indicated."

The investigators studied a total of 45,000 RA patients obtained from the Swedish Biologics Register and other national Swedish registers to determine the outcome, relative risks, and predictors of hospitalization with an infection in patients with rheumatoid arthritis.

They found that treatment with a first TNF inhibitor was associated with a significant 43% increased risk of hospitalization with infection during the first year of treatment. Infection risk during the second year and thereafter was not significantly increased.

The relative risk for infection was two times higher during treatment with a second TNF inhibitor, the researchers note.

Using additional data, other risk factors identified as being significant predictors for infection with TNF inhibitor treatment were older age, higher Health Assessment Questionnaire (HAQ) score, and disease-modifying anti-rheumatic drug (DMARD) treatment other than methotrexate.

When infections were assessed by type, only respiratory infection showed a slightly significant increase in relative risk in association with TNF antagonist treatment.

It is unclear so far as to whether the risk is due to one of the TNF inhibitor drugs more than another.

These findings, as well as other observational trials, mirror what was seen in the clinical trials that led to approval by the FDA for the treatment of RA.

Patients who are prospective candidates for this type of treatment need to be warned about this potential side effect.

In addition, they should be monitored carefully. In the future, it may be possible to identify high risk patients ahead of time so that other therapies might be offered instead of anti-TNF drugs.