Therapeutic Monitoring of Drugs Used in the Treatment of Multiple Sclerosis

Summary

The main goal of multiple sclerosis (MS) treatment is to prevent further relapses of the disease and the progression of neurological deficit. Although MS cannot yet be cured, early control of symptoms and reduction of disease progression is associated with a longer time to disability and improve long-term treatment outcomes. Currently, MS is treated using a multidisciplinary approach, which consists of treatment with so-called "disease-modifying drugs" ("DMDs"), symptomatic therapy of individual symptoms, lifestyle adjustments, psychological support, and rehabilitation interventions. According to the latest results, treatment with "DMDs" can reduce the annual incidence of relapses by 29-68% compared to placebo or an active comparator. Thus, as can be seen, even this group of modern drugs does not completely compensate for MS in many patients. For this reason, there is a need to use certain parameters to best assess the effectiveness of individual treatments in specific patients with MS in routine clinical practice. Therapeutic drug monitoring (TDM) is a specific method of clinical pharmacology that has long been used to monitor therapy for a variety of diseases by measuring drug concentrations in body fluids (plasma, serum, whole blood, cerebrospinal fluid, breast milk) with subsequent interpretation by clinical pharmacologist and acceptance by the clinician. The groups of drugs for which TDM is routinely performed include selected groups of antibiotics (aminoglycosides, vancomycin, beta-lactams), immunosuppressants, digoxin, and especially drugs used in neurology and psychiatry (antiepileptics and psychotropic drugs). As far as "DMDs" is concerned, the first data on the possibility of using TDM in the therapy of MS have already appeared in the professional literature, but these are so far rare and completely insufficient. In addition, individual drugs differ not only in efficacy but also in dose, dosing schedule, and safety profile. The development of new analytical methods to determine serum or whole blood "DMDs" concentrations, together with the objectification of the relationship between measured concentrations to the patient's clinical condition and the possibility of objectifying patient adherence to treatment, could therefore significantly help individualize the dosage of "DMDs" in each individual patient.

Conditions

• Multiple Sclerosis

Interventions

DIAGNOSTIC_TEST

Measurement of concentrations of orally-used DMDs

For effectiveness - the measured concentrations of orally used "DMDs" will be correlated with the clinical condition of patients with MS (usual clinical examinations such as physical assessment of clinical condition, evaluation of EDSS scale, MSQOL-54 quality of life questionnaire, and routine magnetic resonance imaging of the brain once a year). At the same time, the relationship between the measured concentrations of orally used "DMDs" and the concentrations of other biomarkers of MS, such as signs of axonal (so-called plasma neurofilament light chain - "pNfL") and glial (so-called chitinase 3-like 1 - "CHI3L1") damage, will be analyzed. concentrations of selected cytokines, concentrations of CD4 + and CD8 + T-lymphocytes, and the results of a genetic examination of drug transporters, again with an effect on the clinical condition of the patient.

DIAGNOSTIC_TEST

Genetic testing

One blood tube will be taken for genetic testing for the duration of the study, again with standard and routine single injections before taking the drug.

DIAGNOSTIC_TEST

Parameters for routine use of DMDs

For safety - the usual parameters for routine use of "DMDs" will be monitored (blood count, liver tests, renal function, etc. according to the specifics of individual drugs).

OTHER

Side effects of orally used DMDs

For tolerability - possible side effects of orally used "DMDs" will be monitored and the effect of genetic testing of drug transporters will be analyzed.

Sponsors & Collaborators

• University of Ostrava

  collaborator OTHER

• University Hospital Ostrava

  lead OTHER

Principal Investigators

• Ivana Kacířová, Assoc. Prof.,MD,PhD · University Hospital Ostrava

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-06-30

Primary Completion

2025-11-30

Completion

2026-05-31

Countries

• Czechia

Study Locations