Vpliv sodelovanja bolnikov pri zdravljenju z dimetilfumaratom na zdravstvene izide pri multipli sklerozi

Jožef, Maj (author), Rot, Uroš (mentor), Kos, Mitja (comentor)

Sodelovanje pri zdravljenju z zdravili je neoptimalno pri več kot 50 % bolnikov z multiplo sklerozo (MS). Nesodelovanje je povezano s slabšimi zdravstvenimi in ekonomskimi izidi bolezni. Dimetilfumarat (DMF) je najpogosteje predpisano peroralno imunomodulirajoče (IMT) zdravilo proti MS v Sloveniji. Najpogostejši neželeni učinki so prehodne gastrointestinalne motnje. V doktorski disertaciji smo izvedli dve vsebinsko povezani retrospektivni in eno prospektivno kohortno raziskavo, v katere smo vključili celokupno 299 bolnikov z MS na terapiji z DMF. Sodelovanje pri zdravljenju smo ovrednotili na osnovi mere deleža razpoložljivih dni (angl. Proportion od Days Covered, PDC). Analizirali smo vpliv sodelovanja na pojavnost zagonov, napredovanja prizadetosti in radiološke aktivnosti v klinični praksi. V okviru prospektivne raziskave smo v kohorti 40 bolnikov izvedli kriterijsko veljavnost vprašalnika za vrednotenje sodelovanja MARS-5 z razponom točk med 5-25. Povprečna vrednost mere PDC je znašala 0,94. Delež bolnikov nad pragom 90% je bil 82%. Po dveh letih je na terapiji z DMF vztrajalo 77% bolnikov. Bolniki, stari vsaj 30 let so imeli manjše tveganje za prekinitev zdravljenja (HR = 0,493, P = 0,0013). Višja starost in primarna monoterapija sta bila pomembna napovedna dejavnika boljšega sodelovanja oz. vztrajanja. Slabše sodelovanje je bilo značilno povezano z večjim tveganjem za radiološko aktivnost bolezni (OR 1,25, P = 0,038). Pri vrednotenju vprašalnika MARS-5 smo v 6-mesečnem opazovalnem oknu povprečno beležili več kot 23 točk. Delež bolnikov nad pragom dobrega sodelovanja 24 točk je bil 60%. Ugotovili smo značilno povezavo z utežno mero PDC, validirano kvantitativno radiološko aktivnostjo in splošnimi predsodki do zdravil. Rezultati raziskav so pokazali visoko stopnjo sodelovanja in vztrajanja pri zdravljenju ter vpliv slabšega sodelovanja na radiološko napredovanje bolezni. MARS-5 se je potrdil kot zanesljiv in veljaven vprašalnik za vrednotenje sodelovanje pri zdravljenju z zdravili in napovedi predsodkov do zdravil pri bolnikih z MS. Sodelovanje in vztrajanje pri zdravljenju predstavljata uporabna nadomestna kazalnika stabilnega poteka MS v klinični praksi.

• Language: Slovenian
• Keywords: multipla skleroza, farmakoterapija, dimetilfumarat, sodelovanje pri zdravljenju z zdravili, zdravstveni izidi
• Work type: Doctoral dissertation
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-153161
• Publication date in RUL: 20.12.2023

Secondary language

• Language: English
• Title: Impact of medication adherence on health outcomes in patients with multiple sclerosis treated with dimethyl fumarate

Abstract

Medication adherence (MA) is nonoptimal in more than 50% of persons with multiple sclerosis (PwMS). Nonadherence is related to lower health and economic outcomes. Dimethyl fumarate (DMF) is the most frequently prescribed oral disease-modifying (DMT) medication in Slovenia. The most common adverse effects are temporal gastrointestinal disturbances. In the thesis, we performed two intuitively related retrospective and one prospective cohort study that included altogether 299 Slovenian PwMS treated with DMF. MA was evaluated by Proportion of Days Covered (PDC) measure. We analyzed the impact of MA on relapse occurrence, disability, and radiological progression in clinical settings. In the prospective study, we established the criterion validity of the MARS-5 questionnaire with a range of 5-25 points for MA assessment in 40 PwMS. The mean PDC value was 0.94. A total of 82% of patients were highly adherent upon a 90% threshold. After two years of treatment, 77% of patients were found to be persistent. Patients, aged 30 and above had a lower risk for nonpersistence (HR = 0.493, P = 0.0013). Among cofounders, older age and treatment-naivety were related to higher MA. Lower adherence was significantly associated with higher brain MRI activity (OR 1.25, P = 0.038). The mean MARS-5 score in the 6-month observation window was high (23 points). Sixty percent of patients were highly adherent, based on the 24-point threshold. MARS-5 score was significantly associated with weighted PDC measure, validated quanitfied brain MRI activity, and general treatment concerns. Our studies showed high MA and MP rates and the impact of lower adherence on brain MRI activity progression. The MARS-5 questionnaire was found to be valid and reliable for estimating MA and predicting general treatment concerns in PwMS. MA and MP are useful surrogate markers for a stable MS disease course in clinical settings.

• Keywords: Multiple sclerosis, Pharmacotherapy, Dimethyl fumarate, Medication adherence, Health outcomes