Question: What causes the lull in effectiveness reported by some patients using Enbrel?
Some patients report a lull in effectiveness after using Enbrel for a couple of months. The patients who experience this can feel disappointed because they want the initial dramatic improvement to last forever. Is the lull in effectiveness real or perceived and what might be the cause?
Answer:
Of the three TNF (tumor necrosis factor) blockers (Enbrel, Remicade, and Humira), Enbrel seems to work the fastest, possibly due to its shorter half life or its mechanism of action (i.e. as a soluble TNF receptor for the TNF molecule). I spoke with the company (that maunfactures Enbrel). They cannot say why the lull in effectiveness which some patients report happens, but suspect that when a patient is exposed to Enbrel, they have a high level of TNF in their blood that contributes to a poor feeling of malaise, fatigue and pain. Initial lowering of the TNF level will sometimes bring a dramatic feeling of well being that levels out over time. It is not felt to be related to antibody production to Enbrel.
Enbrel is a fusion protien, not a monoclonal antibody. Remicade and Humira are both monoclonal antibodies. Because Remicade contains a mouse protein, neutralizing antibodies against the mouse (foreign) component commonly develop and decrease the drugs effectiveness. In addition, resuming Remicade after a prolonged period of time may increase the risk of infusion reaction due to the antibodies. The effect of these antibodies can be diminished by combining Methotrexate with Remicade as well as increasing the dose of Remicade. Humira is a fully humanized monoclonal antibody so the neutralzing antibodies are not an issue.
Answer provided by Scott J. Zashin, M.D., clinical assistant professor at University of Texas Southwestern Medical School, Divion of Rheumatology, in Dallas, Texas. Dr. Zashin is also an attending physician at Presbyterian Hospitals of Dallas and Plano. He is a fellow of the American College of Physicians and the American College of Rheumatology and a member of the American Medical Association. Dr. Zashin is author of Arthritis Without Pain - The Miracle Of Anti-TNF Blockers. The book is a must-have for anyone on one of the biologic drugs (Enbrel, Remicade, Humira) or considering the biologic drugs. Read my review of the book.More Arthritis Q&A