Jožef Maj, Locatelli Igor, Brecl Jakob Gregor, Rot Uroš, Kos Mitja
University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, Ljubljana 1000, Slovenia; University Medical Centre Ljubljana, Division of Neurology, Multiple Sclerosis Centre, Zaloška cesta 2, Ljubljana 1000, Slovenia.
University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, Ljubljana 1000, Slovenia.
Mult Scler Relat Disord. 2023 Apr;72:104615. doi: 10.1016/j.msard.2023.104615. Epub 2023 Mar 15.
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.
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.
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.
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.
多发性硬化症（MS）是一种中枢神经系统的慢性炎症性疾病，尤其影响30多岁的人群。口服疾病修正疗法（DMT）具有剂型简单、疗效和安全性良好的特点。富马酸二甲酯（DMF）是全球常用的口服DMT药物。本研究的目的是评估用药依从性对斯洛文尼亚接受DMF治疗的MS患者健康结局的影响。
我们的回顾性队列研究纳入了接受DMF治疗的复发缓解型MS患者。使用AdhereR软件包通过覆盖天数比例（PDC）测量来评估用药依从性。阈值设定为90%。治疗开始后的健康结局分别通过在前两次门诊就诊和前两次脑部磁共振成像（MRI）之间复发的发生、残疾进展以及活动性（新的T2和T1/钆（Gd）增强）病灶的出现来体现。针对每个健康结局建立了一个单独的多变量回归模型。
该研究纳入了164例患者。他们的平均年龄（标准差）为36.7（8.8）岁，大多数患者为女性（114例或70%）。81例患者为初治患者。平均（标准差）PDC值为0.942（0.08），82%的患者被认为依从性高于90%的阈值。年龄较大（每增加一岁，OR为1.06，P = 0.017，95%置信区间（1.01 - 1.11））和初治状态（OR为3.93，P = 0.004，95%置信区间（1.64 - 10.4））与更高的依从性相关。在DMF治疗开始后的6年随访期内，33例患者经历了复发。其中，19例需要急诊就诊。16例患者在连续两次门诊就诊之间的扩展残疾状态量表（EDSS）评分上有1分的残疾进展。37例患者在首次和第二次脑部MRI之间被发现有活动性病灶。用药依从性对复发的发生或残疾进展没有影响。较低的用药依从性（PDC低10%）与活动性病灶的更高发生率相关（OR为1.25，P = 0.038，95%置信区间：1.01 - 1.56）。DMF开始治疗前较高的残疾程度与复发发生和EDSS进展的较高风险相关。
我们的研究表明，斯洛文尼亚接受DMF治疗的复发缓解型MS患者用药依从性较高。更高的依从性与MS放射学进展的较低发生率相关。改善用药依从性的干预措施应针对DMF治疗前残疾程度较高的年轻患者以及从其他DMT转换过来的患者。
