Note: The following is adapted from an interview given by Daniel Furst, M.D., with Susan L. Smith, MN, Ph.D, Director MedscapeCME.

     Bioengineered molecules, also known as biologic agents or biologic response modifiers, target specific immune cell subpopulations involved in the development of disease or conditions resulting from disease. They represent an important breakthrough in the treatment of some chronic inflammatory diseases, including autoimmune diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis. Tumor necrosis factor (TNF)-alpha inhibitors, first licensed for clinical use in 1998, are one class of biologic agents.

     Currently five TNF inhibitors are approved for use in the United States--adalimumab, golimumab, infliximab, natalizumab, and etanercept. They suppress the activity of TNF-alpha, a proinflammatory cytokine that is important in the human immune response to infections. (Cytokines include interleukins, some interferons, and tumor necrosis factor.)

     As holds true with all medications, TNF inhibitors have both positive and negative aspects; and, therefore, patients and all clinicians who treat patients taking TNF inhibitors must be knowledgeable about the potential benefits as well as the risk of adverse effects, particularly infection.

     Considering these agents in the case of rheumatoid arthritis (RA), biologics as a class--and TNF inhibitors in particular-- have changed the landscape of RA treatment. In the opinion of many, this stride forward is as important as the discovery of steroids in the 1950s, which completely changed the treatment of RA.

     Like all immunosuppressants and immunomodulating therapies, TNF inhibitors increase the risk of infections. Many--maybe most--RA patients are already on methotrexate which, by itself, is associated with an approximate twofold increase in the risk for infection. Since rheumatoid arthritis itself is associated with an increased risk for infection, the addition of a TNF inhibitor increases the risk for serious infections by approximately fourfold to fivefold.

     Regarding general infections, such as bronchitis or bladder infection, the risk is significantly greater compared with patients on methotrexate alone. Approximately 30 to 40 percent of patients get these kinds of infections. They are mild although sometimes they do require oral antibiotics. Generally the incidence of viral infections is not increased in patients on TNF inhibitors, with the rare exception of herpes zoster infections.

     Patients do need to tell any other health care providers that they are taking these medications. If they feel that they have a standard "cold," they generally do not need to see a physician immediately. However, if they have more than mild symptoms, i.e., fever and feeling ill, they should seek medical attention because there is a possibility that they could have a bacterial infection. If they go to an emergency department, they should tell the physician that they are on immunosuppressants and immunomodulators. Emergency medicine physicians should be able to take it from there.

     As to vaccinations, TNF inhibitors potentially decrease the efficacy of protein-based vaccines that are T-cell dependent, such as those for hepatitis B virus, viral influenza A and B, human papilloma virus, and tetanus. For example, controlled studies of hepatitis B virus vaccine in patients on etanercept showed that the efficacy is decreased by about 10 to 20 percent relative to the efficacy in patients taking methotrexate.

     This is also likely to be true for the influenza vaccine. The average efficacy is approximately 95 percent in the general population but decreases to 80 to 85 percent in patients taking TNF inhibitors. The bottom line is that one would expect about a 10 to 15 percent lower efficacy rate for protein-based vaccines in patients taking TNF inhibitors versus methotrexate. However, one would not expect a decrease in efficacy for the carbohydrate-based vaccines, such as the pneumococcal vaccines.

     Live vaccines should not be given to patients on TNF inhibitors; and the recommendation, in general, is to administer any vaccines before initiating TNF inhibitor therapy. This, of course, is not always possible for the influenza vaccines which are administered seasonally.

     Some other drug-related effects of TNF inhibitors need to be considered. For example, there's growing evidence that the risk of activated latent tuberculosis is increased, particularly with the use of the monoclonal antibody TNF inhibitors. Thus, all patients taking TNF inhibitors should be screened for tuberculosis, including possible chest x-rays.

     Furthermore, patients on TNF inhibitors are at increased risk for opportunistic infections, e.g., fungal infections, blastomycosis, coccidiomycosis, and, especially in certain areas, histoplasmosis. Physicians need to be aware of environmental risk factors in patients being treated with immunosuppressants and immunomodulators.

     Patients may experience rashes and the outside possibility of abnormalities in liver functions tests although patients experiencing these side effects are nearly always on other drugs as well. Also, there may be a very rare possibility of white blood cell or platelet count abnormalities and malignancies. There is an approximate threefold increased risk for lymphoma, particularly non-Hodgkin's lymphoma, in patients taking TNF inhibitors. However, no evidence exists that TNF inhibitors increase the risk for other solid tumors, with the possible exception of nonmelanotic basal cell carcinomas of the skin which are not usually serious.

     Daniel E. Furst, M.D., rheumatologist and researcher, comments, "I can't emphasize enough how important these drugs have been to patients. Previously, we did not even talk about remission. Now, although there is a lot of controversy about what remission actually means, by some definitions about 30 to 50 percent of patients taking these drugs go into remission. This was unheard of 15 years ago. These drugs are having a very positive effect, and you can't tell one from another in this respect."

     Limited resources are available to help patients, usually the truly indigent, with the very considerable cost of these drugs. Dr. Furst says, "I feel strongly that the cost of these drugs can and should be decreased."

     Dr. Furst is the Carl M. Pearson Professor of Rheumatology, David Geffen School of Medicine at the University of California at Los Angeles (UCLA) and Director of Therapeutic Research, UCLA, Los Angeles, California.

--Source: Adapted from "What Every Patient Taking Tumor Necrosis Factor-Alpha Inhibitors Needs to Know," Daniel E. Furst, M.D., August 5, 2009