Article Text
Abstract
It is nearly inevitable that when we administer foreign (even humanised) proteins intravenously or subcutaneously to a person, that said person will develop antibodies to that (foreign) protein. This happens to most of our patients when we administer biologicals; depending on the sensitivity of our methods, we can measure these anti-bodies easily or not at all. These antibodies start becoming a problem when they are actually binding the administered biological, thus making the active drug less available for its targeted function. We can evaluate this by measuring the actual drug-level, so called trough level. Numerous reports have been published, showing that there is indeed a negative correlation between e.g. anti-tumor necrosis factor (TNF) drug antibodies and the efficacy of anti TNF in the treatment of RA. It has also been shown that adding methotrexate (MTX) to the anti-TNF treatment improves its efficacy and reduces the level of anti-drug antibodies. Probably only 10 mg MTX weekly would be enough to obtain this effect.
So what do I do as a clinician when I observe that a patient, who originally did very well, loses response to her biological? Do I measure possible anti-drug antibodies? No, the consequences are zero: When the patient is not responding to the given drug anymore, I need to adapt the treatment; the drug she is using is not effective anymore, so we should change. Would the presence of anti-drug antibodies influence my decision? No, there is no cross-reactivity to other biologicals (even from the same class of action), except to its biosimilar (underscoring that it is a real biosimilar!). In case there is doubt whether a patient is actually using the biological we could better measure the drug-trough level; but –in my practice- this question seldom arises in patients with active arthritis, being treated with a biological.
Measuring drug-trough levels is a completely other item, and perhaps more relevant. Biologicals are in general given in a standard fixed dosage, while there are clear differences in patients characteristics, that could influence bioavailability of the biological. In addition when the disease is more active, it could be that more biological is needed to temper the inflammation compared to low disease activity, where perhaps a lower dosage would be more than effective. To guide physician and patient in personalizing and optimizing treatment with biologicals measuring drug-trough levels might be helpful. Different studies have been performed trying to use through level of the drug in adapting the dosage, and even in predicting possibility to stop the drug treatment. This area is still being evaluated and it is too early to make firm statements, but with a look at cost-effectiveness this will certainly become relevant.
Coming back to the original question: do I use anti-drug antibodies in my daily practice to guide treatment: no, it doesn't influence my decisions. Will I use in the future drug trough levels to guide treatment decisions: this could well be, but it is too early to make a final decision yet.
Disclosure of Interest None declared