But new research from the University of Alabama at Birmingham Center for Education and Research on Therapeutics reveals that a class of biologics called tumor necrosis factor antagonists, or TNF inhibitors, may only minimally increase risk compared to more traditional therapies.
The infection risk for TNF therapy is similar to comparative non-biologic drugs and probably less than higher doses of glucocorticoids such as prednisone, more commonly used to treat autoimmune diseases, according to findings published online Nov. 6, 2011, in the Journal of the American Medical Association.
The multi-institutional study, part of the federally funded Safety Assessment of Biologic Therapy project, analyzed more than 16,000 patients with autoimmune diseases — rheumatoid arthritis, inflammatory bowel disease and psoriasis, psoriatic arthritis or ankylosing spondylitis — drawn from four national health-plan databases.
“The majority of the study subjects could be classified as high-risk individuals — older, sicker and of lower socio-economic status than the general population,” said Jeffrey Curtis, M.D., M.S., MPH, associate professor of medicine in the UAB Division of Clinical Immunology and Rheumatology and the senior investigator of the study.
Biologics, including TNF inhibitors, have been used to treat autoimmune diseases for 13 years. Curtis’s group studied three of the most commonly used TNF inhibitors: infliximab, adalimumab and etanercept. TNF inhibitors are monoclonal antibodies or fusion proteins that bind and inhibit TNF, which is a family of cytokines, or signaling molecules, that play a role in inflammation.
Curtis’ group looked at hospitalization for common bacterial infections seen in those with autoimmune diseases including pneumonia, cellulitis, sepsis and kidney/urinary tract infections. They identified 1,172 serious infections in their study population. Rheumatoid arthritis patients receiving TNF inhibitors had an infection hospitalization rate of 8.16 per 100 person-years, as opposed to 7.78 per 100 for patients on comparative non-biologic medications. Patients with inflammatory bowel disease had a hospitalization rate of 10.91 against 9.60 for controls and patients with psoriasis had infection rates of 5.41 opposed to 5.37.
“Our findings indicate that TNF antagonists present comparable infection risk to the most commonly used non-biologic immunosuppressive medications, even in a vulnerable, high-risk population,” said Curtis.
The only exception was among rheumatoid arthritis patients receiving one particular TNF inhibitor, infliximab, for which the serious infection rate was 25 percent greater than those receiving non-biologics.
“Since the onset of their use, there has been controversy whether these drugs increase the risk of infection,” said Curtis. “Our findings should provide some reassurance to clinicians and patients, especially high-risk patients. Biologics are not without risk, but the risk is reasonable and manageable, given the benefit of the drugs for most people.” Curtis said these findings, coupled with the known risks of long-term steroid use, suggest that more aggressive efforts to wean autoimmune patients off steroids is warranted.
Of note, more rare types of infections, such as opportunistic infections, were not included in this analysis and are the focus of another SABER study led by Curtis and his colleagues.
The research team included other investigators from UAB, along with researchers from Vanderbilt University, the Birmingham Veterans Affairs Medical Center, Oregon Health and Science University, Kaiser Permanente, U.S. Food and Drug Administration, Brigham and Women’s Hospital and Harvard University and the University of Pennsylvania.