Tumor necrosis factor-Î± antagonists used to treat autoimmune diseases such as rheumatoid arthritis may pose less risk of serious infection than previously thought, a new study suggests.
Tumor necrosis factor (TNF)-α antagonists used to treat autoimmune diseases may pose less risk of serious infection than previously thought, suggests a study published online last week in the Journal of the American Medical Association.
TNF plays an important role in host defense and tumor surveillance, so there has been ongoing concern that TNF-α antagonists may leave patients vulnerable to infection. Indeed, as an editorial accompanying the study notes, previous randomized controlled trials of anti-TNF therapies have reported results ranging from no increased risk of serious infection to a greater than fourfold increased risk compared with nonbiologic therapies.
For the current study, researchers led by Carlos G. Grijalva, MD, of Vanderbilt University assembled retrospective cohorts, spanning from 1998-2007, of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, psoriatic arthritis, or ankylosing spondylitis. The data was combined from Kaiser Permanente California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid, and national Medicaid/Medicare. The study cohorts included 10,484 RA, 2,323 IBD, and 3,215 psoriasis/spodyloarthropathies matched pairs using TNF-α antagonists and comparator medications. The main outcome measure of the study was infections requiring hospitalization during the first 12 months after starting treatment.
Among all the patients included in the study, there were 1,172 serious infections. Among RA patients, serious infection rates were 8.16 per 100 person-years for TNF-α antagonists and 7.78 per 100 person-years for comparator regimens. For IBD patients, serious infection rates were 10.91 (TNF-α antagonists) and 9.60 (comparator regimens) per 100 person-years. For psoriasis/spondyloarthropathy patients, they were 5.41 (TNF-α antagonists) and 5.37 (comparator regimens) per 100 person-years. Among RA patients, infliximab was associated with a significant increase in serious infections compared with other TNF-α antagonists etanercept and adalimumab.
Based on these results, the researchers concluded that treatment of patients suffering from autoimmune diseases with TNF-α antagonists was not associated with an increased risk of hospitalization due to serious infection compared with nonbiologic treatments.
The editorial accompanying the study notes that in previous studies, a coherent pattern has seemed to emerge from the data suggesting that an initially high rate of infection with anti-TNF therapy declines over time, apparently due to “changes in glucocorticoid use, improvements in disease severity, and a depletion of susceptible patients (whereby high-risk patients have their infections early and discontinue treatment, thus leaving a cohort that is at lower risk of infections).”
The current study, by contrast, finds no change in infection rate over time. It is possible that the discrepancy with previous studies is due to the rate of infection in the comparator group, which was much higher than in other studies. (This higher rate may be due to the fact that those in the current study were underserved, vulnerable patients of the sort usually not included in clinical trials.) The study’s results may also have been influenced by selection of which patient would receive which type of treatment. (The researchers attempted to match patients in the two groups with similar risk of serious infection, though they were limited by available information in so doing.)
The editorial concludes as follows: “Conflicting findings between large pharmacoepidemiology studies are to be expected, and exploring reasons for discrepant results can yield helpful insights. From existing knowledge plus this recent study by Grijalva et al, one conclusion is that when compared with ongoing nonbiologic DMARD [disease-modifying antirheumatic drug] use, infection rates are increased in patients who started treatment with anti-TNF agents. However, this study suggests that serious infection risk may be no higher in those initiating anti-TNF therapy than in those starting a new DMARD, perhaps in combination with methotrexate. These intriguing findings need replication in other studies. Nevertheless, the report by Grijalva et al raises important questions about the comparative safety of immunosuppressant and biologic therapy and may prompt a reevaluation of anti-TNF safety.”