Introduction
Biologicals -in this context mostly drugs that are recombinant
therapeutic proteins, monoclonal antibodies (mAb), fusion proteins and
conjugates- have entered many therapeutic areas in the last couple of
decades.
The pharmacokinetic characteristics of such drugs differ in several
aspects from the traditional small molecule drugs. The route of
administration is frequently intravenous (iv) only, occasionally
formulations for subcutaneous (sc) administration are available and may
introduce a source of variation in bioavailability. Still, the most
important factor giving rise to variability within and between patients,
is the elimination of biological drugs. The question is whether this
leads to variations of a proportion suggesting that individualization of
dosing is warranted. Currently, for most of the established therapies
with biologicals, the dosage regimens are typically one recommended dose
for all adults -or in some cases dose adjusted to bodyweight or body
surface area.
In organ transplantation there are only a limited number of biologicals
with immunosuppression after transplantation as the labelled indication.
A few more may have labels relevant for treatment of conditions related
to transplantation or the underlying disease. A number of biological
drugs, however, are used off label on various indications in organ
transplant recipients. Hopefully, in many cases it will serve the
patient well, but unless this transforms into formal clinical studies of
the new indication, it is difficult to aggregate experience with dosing
versus response and toxicity and to optimize the treatment further by
implementing therapeutic drug monitoring (TDM). Following a period of
very few drugs reaching approval for the use in transplant recipients,
there is currently a resurgence and a number of biologicals are in
clinical testing, mostly for desensitization and treatment of antibody
mediated rejections, but also for some other specific indications.
Examples of such drugs are listed alongside drugs with approved
indications in Table 1.