Therapeutic drug monitoring is a tool for personalizing patients' pharmacotherapy

On November 22, 2024, the next meeting of the Council on Personalized Medicine under the Presidium of the Russian Academy of Sciences (Chairman - Academician of the Russian Academy of Sciences E.V. Shlyakhto, Scientific Secretary - Academician of the Russian Academy of Sciences A.O. Konradi) was held online. The study was organized by the group on pharmacokinetics and personalized pharmacotherapy of the Council (head of the group - Academician of the Russian Academy of Sciences D.A. Sychev, Secretary - Doctor of Medical Sciences, Associate Professor K.B. Mirzaev). The meeting was devoted to therapeutic drug monitoring (TDM) as a scientifically based tool for personalizing pharmacotherapy for patients with various diseases, including socially significant and widespread ones. The following reports were heard and discussed:

• "Therapeutic drug monitoring—a tool for personalized pharmacotherapy of patients" (authors: Academician of the Russian Academy of Sciences D.A. Sychev, Doctor of Medicine, Professor T.V. Vavilova, A.V. Karasev, Doctor of Medicine, Associate Professor K.B. Mirzaev);
• "Drug monitoring in immunosuppressive therapy in the aspect of personalized medicine" (author - Doctor of Medicine, Associate Professor N.V. Borovkova);
• "Therapeutic drug monitoring of antiepileptic drugs: current status and prospects" (authors: Doctor of Medicine, Professor N.A. Schneider, Doctor of Medicine, Associate Professor D.V. Dmitrienko);
• "Therapeutic drug monitoring as a modern approach to increasing the effectiveness of pharmacotherapy for patients in critical conditions" (author - MD, Professor S.K. Zyryanov).

The discussion was attended by the following: Academician of the Russian Academy of Sciences A.O. Konradi, Academician of the Russian Academy of Sciences D.A. Sychev, Corresponding Member of the Russian Academy of Sciences T.V. Priputnevich, Corresponding Member of the Russian Academy of Sciences D.A. Kudlai, MD, Professor T.V. Vavilova, MD, Professor V.A. Baturin, A.V. Karasev.The transition to personalized medicine through the rational use of drugs is a priority outlined in the Strategy for Scientific and Technological Development of Russia, adopted in February 2024. The meeting participants noted that this approach will improve the expected outcomes of people in our country in accordance with the National Development Goals of Russia, signed in May by President V.V. Putin is increasing the effectiveness and safety of pharmacotherapy for patients with diseases that make significant contributions to morbidity and mortality. Earlier, pharmacogenetic testing was discussed at council meetings as an "a priori" (before prescribing a drug to a patient) technology for personalized pharmacotherapy for patients. At the same time, TDM (monitoring the concentration of drugs in biological fluids) is a "posterior" (i.e., against the background of the use of a drug in a patient) technology for personalizing pharmacotherapy. At the same time, TDM is especially important when using drugs with a narrow therapeutic range (a small difference between the minimum effective and maximum concentrations), for which the effectiveness and/or development of adverse reactions directly depends on the concentration of the drug in the blood. At the same time, based on the results of TDM, the "presence" of the drug in the patient's blood in the therapeutic range is assessed, which will ensure the effectiveness of the treatment. In addition, the results of TDM allow an objective assessment of the patient's adherence to drug treatment (whether the patient takes the drug or not, whether he or she uses it "correctly"). TDM provides information for the physician for personalized correction of the patient's pharmacotherapy: changing the dosage regimen and storing the drug. Currently, data have accumulated on the evidence base of the effectiveness (randomized clinical trials (RCTs) have been conducted, there are meta-analyses and systematic reviews) of TDM for a number of drugs widely used in clinical practice (immunosuppressants in transplantology, antiepileptic drugs, psychotropic drugs, some antimicrobial drugs, digoxin, etc.), while TDM of some drugs has already been included in domestic clinical guidelines. Other drugs were also discussed in terms of the prospects for the development and study of TDM (direct oral anticoagulants, antiretroviral drugs, anti-tuberculosis drugs, methotrexate, etc.). Experts expressed the opinion that TDM is especially necessary for patients at risk for developing adverse reactions (premature infants, elderly patients with polymorbidity and polypharmacy, liver and kidney dysfunction, patients who are carriers of "pharmacogenetic" markers, etc.). TDM can be useful when changing a patient’s name to another within the same international nonproprietary name, which is especially important in the context of import substitution. The meeting participants discussed the situation with the availability of TDM methods (ELISA, HPLC), the development of new methods for detecting drug concentrations in biological fluids, including "indirect" ones (for example, anti-Xa activity and anti-IIa activity for determining the concentration of drugs in biological fluids, etc.). It should be noted that the labor function as "personalization of patient pharmacotherapy based on the results of pharmacogenetic testing and therapeutic drug monitoring" is regulated in the professional standard of a physician - clinical pharmacologist. At the same time, the results of a survey of 317 physicians clinical pharmacologists of medical organizations from various regions of Russia were presented and discussed at the meeting. It turned out that slightly more than 20% of patients use TDM to personalize patient pharmacotherapy, whereas 70% do not use TDM but believe that it is necessary. Physicians and clinical pharmacologists consider the following obstacles to the implementation of TDM: lack of payment for TDM through the compulsory medical insurance channel (67% of respondents), high cost of TDM (60% of respondents), lack of knowledge about TDM (35% of respondentand lacklack of mention of TDM in clinical guidelines (30.7% of respondents). The resolution of the meeting reflects the need to expand scientific research in the field of developing new TDM methods, assessing its effectiveness in various categories of patients with common diseases, accumulating an "evidence base" for TDM (new RCTs, RWD / RWE studies), "links" between pharmacogenetic testing and, an, and conducting pharmacoeconomic studies. The need to incorporate TDM and indications for its use in clinical guidelines, standards, laboratory reference books, payment for TDM through the compulsory medical insurance channel, etc., was also unanimously noted. A mandatory component of the implementation of TDM is the formation of relevant competencies in doctors, which requires the development of an appropriate educational module in educational programs for residency and professional retraining, primarily for doctors—clinical pharmacologists and doctors of clinical laboratory diagnostics, as well as for other "related" specialists (therapists, general practitioners, neurologists, psychiatrists, cardiologists, resuscitators, infectious disease specialists, etc.), as well as advanced training programs was unanimously noted.

Editor-in-chief
Dmitry Sychev

MD, professor, academician of the Russian Academy of Sciences, head of the department of clinical pharmacology and therapy, rector of the Federal State Budgetary Educational Institution of Higher Professional Education "Russian Medical Academy of Continuous Professional Education", Moscow, Russian Federation