Psychometric evaluation of the 5-item Medication Adherence Report Scale questionnaire in persons with multiple sclerosis.

The 5-item Medication Adherence Report Scale (MARS-5) is a reliable and valid questionnaire for evaluating adherence in patients with asthma, hypertension, and diabetes. Validity has not been determined in multiple sclerosis (MS). We aimed to establish criterion validity and reliability of the MARS-5 in persons with MS (PwMS). Our prospective study included PwMS on dimethyl fumarate (DMF). PwMS self-completed the MARS-5 on the same day before baseline and follow-up brain magnetic resonance imaging (MRI) 3 and 9 months after treatment initiation and were graded as highly and medium adherent upon the 24-cut-off score, established by receiver operator curve analysis. Health outcomes were represented by relapse occurrence from the 1st DMF dispense till follow-up brain MRI and radiological progression (new T2 MRI lesions and quantitative analysis) between baseline and follow-up MRI. Criterion validity was established by association with the Proportion of Days Covered (PDC), new T2 MRI lesions, and Beliefs in Medicines questionnaire (BMQ). The reliability evaluation included internal consistency and the test-retest method. We included 40 PwMS (age 37.6 ± 9.9 years, 75% women), 34 were treatment-naive. No relapses were seen during the follow-up period but quantitative MRI analysis showed new T2 lesions in 6 PwMS. The mean (SD) MARS-5 score was 23.1 (2.5), with 24 PwMS graded as highly adherent. The higher MARS-5 score was associated with higher PDC (b = 0.027, P<0.001, 95% CI: (0.0134-0.0403)) and lower medication concerns (b = -1.25, P<0.001, 95% CI: (-1.93-(-0,579)). Lower adherence was associated with increased number (P = 0.00148) and total volume of new T2 MRI lesions (P = 0.00149). The questionnaire showed acceptable internal consistency (Cronbach α = 0.72) and moderate test-retest reliability (r = 0.62, P < 0.0001, 95% CI: 0.33-0.79). The MARS-5 was found to be valid and reliable for estimating medication adherence and predicting medication concerns in persons with MS.

Medication persistence among people with multiple sclerosis in Slovenia treated with dimethyl fumarate.

Objective: Multiple sclerosis is a chronic, demyelinating inflammatory disease of the central nervous system. Medication persistence is defined as an interval between the initiation and last dose of the applied medication and presents a useful surrogate marker of a stable disease course. This observational study aimed to evaluate medication persistence and discontinuation reasons in Slovenian people with multiple sclerosis treated with dimethyl fumarate.Methods: Our retrospective cohort study evaluated people with relapsing-remitting multiple sclerosis treated with dimethyl fumarate as an initial monotherapy or switched from injectable disease-modifying therapy medication between 2014 and 2021. Medication dispenses were extracted from the Slovenian National Institute of Public Health Outpatient Medication Database. The medication persistence criterion was based on the treatment gap. Patients exceeding a 60-day gap were considered nonpersistent. The median time to discontinuation was assessed using survival analyses. Considering discontinuation reasons, patients were further divided into safety and inefficacy groups. Due to the high probability of adverse effects, patients exceeding a 60-day gap were included in the safety group, but definite discontinuation reason remains unknown. The impact of covariates was evaluated by Cox regression.Results: A total of 269 patients were included (183 women, mean age 37 years). During the 7-year follow-up period, 123 (45.7%) patients discontinued treatment. The median time to discontinuation was 5.6 years. After 1, 2, and 5 years of treatment, 84%, 77%, and 57% of patients were found to be persistent, respectively. All patients older than 30 years (p = 0.0013) and among them, those in the inefficacy group (p = 0.037) were more likely to be persistent.Conclusions: The results of our study proved a high persistence rate among our patients. The most frequent discontinuation reason was gastrointestinal adverse effects. Medication persistence requires interventions in younger patients with an unstable disease course.

Medication adherence and health outcomes in persons with multiple sclerosis treated with dimethyl fumarate.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that particularly affects people in their 30s. Oral disease-modifying therapy (DMT) offers a simple dosage form, good efficacy and safety. Dimethyl fumarate (DMF) is a frequently prescribed oral DMT medication worldwide. The aim of this study was to evaluate the impact of medication adherence on health outcomes in Slovenian persons with MS treated with DMF. METHODS: Our retrospective cohort study included persons with relapsing-remitting MS on DMF treatment. The medication adherence was evaluated by AdhereR software package using the proportion of days covered (PDC) measure. The threshold was set at 90%. Health outcomes after treatment initiation were represented by relapse occurrence, disability progression and occurrence of active (new T2 and T1/Gadolinium (Gd) enhancing) lesions between first two outpatient visits and first two brain magnetic resonance imaging (MRI), respectively. For each health outcome a separate multivariable regression model was built. RESULTS: The study included 164 patients. Their mean age (SD) was 36.7 (8.8) years, and the majority of patients were women (114 or 70%). Eighty-one patients were treatment naive. The mean (SD) PDC value was 0.942 (0.08) and 82% of patients were considered adherent above the 90% threshold. Older age (OR 1.06 per one year, P = 0.017, 95% CI (1.01-1.11)) and treatment naivety (OR 3.93, P = 0.004, 95% CI (1.64-10.4)) were related to higher adherence. In the 6-year follow-up period after DMF treatment initiation, 33 patients experienced a relapse. Among those, 19 required an emergency visit. Sixteen patients had a 1-point disability progression on the Expanded Disability Status Scale (EDSS) score between two consecutive outpatient visits. Thirty-seven patients were found to have active lesions between first and second brain MRI. Medication adherence showed no impact on relapse occurrence or disability progression. Lower medication adherence (10% lower PDC) was associated with higher occurrence of active lesions (OR 1.25, P=0.038, 95% CI: 1.01-1.56). Higher disability prior to DMF initiation was related to a higher risk for relapse occurrence and EDSS progression. CONCLUSION: Our study showed high medication adherence among Slovenian persons with relapse-remitting MS on DMF treatment. Higher adherence was associated with lower incidence of the radiological progression of MS. Interventions for improving medication adherence should be intended for younger patients with higher disability prior treatment with DMF and those switching from alternative DMTs.

[Current clinical evidence on topiramate pharmacokinetics]. / Savremena klinicka iskustva o farmakokinetici topiramata.

Topiramate is biochemically classified as a fructopyranose sulphamate. Discovered as early as 1979, during middle 1980's it was approved in many countries for the treatment of epilepsies and migraine prevention. More recently, in the experimental stage, possible new indications have been disclosed: treatment of obesity, bipolar disorder, also cessation of smoking, neuropathic pain, cerebral pseudotumour, bulimia, periventricular leucomalatia in preterm infants and alcohol addiction. Most epileptologists consider it to be the first choice antiepileptic drug in severe pharmacoresistant epilepsies. A substantial corpus of evidence in paediatric population has been accumulated that confirms its efficiency in the treatment of generalised tonic-clonic seizures, Lenox-Gestaut syndrome, partial, absence and combined seizures. Having a unique monosaccharide chemical structure among other anticonvulsant drugs, characterizes it with special pharmacokinetic features. This substance exhibits a low interindividual variability in plasma levels and hence it features predictable pharmacokinetics. A steady state plasma concentration of topiramate increases linearly with higher dosages. Serum protein binding is approximately 15%, and biologic half-life in healthy volunteers is considered to range from 20 to 30 hours. Mean expected distribution volume rates from 0.55-0.8 l/kg, and accordingly, the drug shows a low and saturable binding capacity toward erythrocytes. It has not been present at the market for a sufficiently long time that would enable us to speak about a significant accumulation of data on its metabolism based on post-registration 4th stage clinical trials. For this purpose, we have done a literature review in order to summarise so far reported experience on topiramate pharmacokinetics in patients and healthy adults. Deeper understanding of its pharmacokinetic profile could enable a better technological design of the produced drug and the choice of the adequate route of its administration, and accordingly a more rational treatment of severe epilepsies resistant to other drugs.