Introduction: The purpose was to assess the level of medication adherence (MA) and related factors among individuals with multiple sclerosis (MS) in Bulgaria.

Materials and methods: A prospective one-year study was conducted among 54 patients with MS diagnosed, treated, and monitored in Clinic of Neurology, University Hospital “Alexandrovska”, Sofia in 2022/2023. Clinical data, patients reported outcomes, patients’ characteristics such as age, gender and reduced work capacity, and other data were collected to define the predictors of non-adherence to medicines. MA level was assessed through a free Morisky–Green 4-item questionnaire.

Results: Мost of the observed patients were rated with high and moderate adherence to MS therapy (n = 44; 81.48%). The remaining 18.52% of the patients with poor adherence to therapy were women. There was no statistical basis for asserting differences in adherence levels among the various factors considered.

Conclusion: The current study demonstrates the importance of MA assessment and provides insights into MA among patients with MS in Bulgaria. Still, there are low-adherent patients, and the responsible factors should be further investigated.

medication adherence, Morisky, multiple sclerosis, neurology

More than 2,8 million people suffer from multiple sclerosis (MS) worldwide (Soiza et al. 2018; Magyari and Sorensen 2020; Aslam et al. 2022). Every day about 300 people receive a diagnosis of multiple sclerosis and every five minutes someone in the world is diagnosed with MS. Europe has the highest prevalence rate of MS of all WHO regions, with approximately 133 per 100 000 people affected. It is assumed that the number of MS patients in Bulgaria is about 5 000 (Smart MS) (Magyari and Sorensen 2020).

Until now, a definitive cure for MS remains elusive, underscoring the complex nature of this autoimmune condition (Soiza et al. 2018; Kołtuniuk and Chojdak-łukasiewicz 2022). The treatment is based on an interdisciplinary approach (Feinstein et al. 2015; Axisa and Hafler 2016; Doshi and Chataway 2016; Baldassari and Fox 2018; Izquierdo et al. 2019; Villoslada and Steinman 2020). The primary objective is to slow down disease progression and reduce the long-term patients’ disability. Treatment approaches vary based on the specific course of the disease, whether the disease is in relapse phase or in remission. Treatment is generally divided into 3 main categories: management of relapses, disease-modifying therapy and symptomatic management (Milanov 2023). Improving patients’ quality of life and slowing their progression need good cooperation between patients and medical professionals and the key to effective therapy is good adherence and compliance by the patient. Non-adherence to disease-modifying therapies (DMTs) is associated with higher rates of relapse and risk of disease progression (Cunningham et al. 2010; Rolnick et al. 2013; Soiza et al. 2018; Kołtuniuk and Chojdak-łukasiewicz 2022; Kołtuniuk et al. 2022).

Medication adherence refers to how well a patient follows the recommended dosing schedule, including timing and dosage. Persistence, on the other hand, measures the duration of time in which a patient continues to take the medication from the start to the end of their treatment. Discontinuation refers to stopping of medication, which can be initiated either by the healthcare provider or the patients themselves (Mardan et al. 2021).

Suboptimal medication adherence can be intentional or unintentional. Intentional suboptimal adherence is when patients knowingly deviate from the prescribed regimen due to reasons such as perceiving the medication as ineffective, concerns about the cost, experiencing unwanted side effects or injection side reactions for injectable medications. Unintentional suboptimal adherence is primarily attributed to forgetfulness and can be influenced by factors like physical disabilities, cognitive impairments, or depression, which are often presented in patients with multiple sclerosis (Mardan et al. 2021).

It was still questionable whether the oral DMTs might offer better adherence to injectable ones, but recent studies suggest that real-world adherence and persistence with both once- and twice-daily oral maintenance DMTs (fingolimod, dimethyl fumarate, and teriflunomide) may be like self-injectable DMTs. Despite the proven effectiveness of these therapies, many patients with MS still struggle with adherence to their treatment plans (Cutter et al. 2019).

The aim of this study is to assess adherence to therapy of patients with multiple sclerosis in Bulgaria.

There is a lack of studies that assess in detail medication adherence in patients with multiple sclerosis in Bulgaria. To the best of our knowledge, this is the first study in Bulgaria focused on medication adherence and the factors leading to non-adherence in patients with multiple sclerosis. The study was performed in a real-world clinical setting by using the most commonly measure of adherence to therapy used both in research and medical practice capacities. Considering that multiple sclerosis is a chronic autoimmune disease with a treatment primarily focused on symptoms management and slowing disease progression, MA is critical to be assessed and improved.

There are a lot of validated and specific questionnaires and other methods for measuring medical adherence in patients with multiple sclerosis. In the current study we applied four-item Morisky Green Levine Medication Adherence test as a validated choice for measuring adherence to therapy in multiple sclerosis and many other chronic diseases (Fernandez-Lazaro et al. 2019; Fayet et al. 2020; Qiao et al. 2020).

The results showed that most patients had high or moderate adherence to MS therapy, with only 18.52% exhibiting poor adherence. Factors such as gender, therapy effectiveness, coexisting diseases, type of therapy, age, and reduced work capacity were assessed for their association with medication adherence. The conducted logistic regression analysis shows that low levels of medication adherence were primarily observed in women, individuals who believed therapy was more effective, and patients treated with moderately effective medications, although these patterns did not show significant statistical differences. On the other hand, patients with an EDSS score below 2.0 were 70% less likely to adhere to therapy. Patients with reduced work capacity and those aged 18–40 had approximately three times higher odds of showing better adherence. However, there is no statistically significant evidence to confirm variations in adherence levels among the factors studied.

There are various studies published regarding adherence to therapy in patients with multiple sclerosis. A cross-sectional study evaluated MS patients’ adherence in Latin America using the multiple sclerosis treatment adherence questionnaire (MS-TAQ). The authors found that the prevalence of non-adherence was similar to others previously reported. The study reported 78.1% overall adherence (79.7% in Argentina and 76% Ecuador, p = 0.23) and results are close to those in our study (84.18%). The authors found that patients using infusion therapies significantly more often belonged to the adherent group (Alonso et al. 2022). Another study used IMS Health World Data Adjudicated Claims – US and measured the adherence by medication possession ratio (MRI). The results showed that male sex and age older than 18–34 years are significantly associated with a higher likelihood of adherence. While in our study, we reported only female with poor adherence to therapy, and those with the highest odds of adherence were patients between 18–40 years of age (Munsell et al. 2017). There is a lack of available studies evaluating therapy adherence in individuals with multiple sclerosis in Bulgaria. In contrast to other areas such as Ontario, patients with multiple sclerosis in Bulgaria demonstrate high adherence to therapy. A retrospective cohort study evaluated poor adherence to disease-modifying drugs in patients with multiple sclerosis in Ontario which is compatible with previously reported rates of adherence in this region (Wong et al. 2011). Our research establishes a connection between the severity of disability and adherence to therapy, indicating that individuals with a lower EDSS score are more assessed patients with primary progressive multiple sclerosis and did not incorporate individuals with secondary progressive MS, unlike other studies. A German study revealed that the main reasons for nonadherence are adverse events, a physician’s recommendation, lack of treatment effect, dependence on a wheelchair and a secondary progressive MS (Twork et al. 2007). We did not incorporate the influence of adverse drug reactions on adherence in our study, unlike other studies that have explored this aspect. In Saudi Arabia 598 adult MS patients were recruited and their medication adherence was assessed using the Arabic version of the eight-item Morisky Medication Adherence Scale (MMAS-8). The authors revealed that the medication adherence among MS patients in Saudi Arabia is low due to changing prescribed drugs because of presence of attack, substandard response to treatment or adverse events (Alhazzani et al. 2019). The Moriyski’s green test is widely used, and numerous studies have been conducted to assess therapy adherence among patients with various diseases using this test (Gutie et al. 2016; Parente et al. 2020; Lara-morales et al. 2022; Portela et al. 2022; Dinkova et al. 2023; Kamusheva et al. 2023). Therapeutic adherence in 120 Spanish patients with MS under interferon b-1a was assessed with Morisky-Green test and with the percentage of doses received and the results showed that 68% of the patients are adhered to the treatment. Relying solely on one method for assessing medication adherence (Morisky Green Levine Medication Adherence) in our study yields elevated results in Bulgaria compared to Spain (Fernández et al. 2012).

Various factors influence the level of medication adherence. Some studies found that males and older patients have better treatment adherence. People with higher education are more likely to be less adherent than patients who did not go to college or finish their degree. Longer disease duration and insufficient information about the condition and treatments are associated with non-adherence. Mostly the higher EDSS score has a negative effect on treatment adherence but there are studies which prove otherwise. Psychological and behavioral problems such as memory loss, forgetfulness, and depression are associated with poorer treatment adherence. Commonly reported reasons for non-adherence are problems with administration and the occurrence of adverse events. Many studies have revealed that adherent patients have a better quality of life (Mékiès et al. 2018; Buja et al. 2021; Kołtuniuk et al. 2022; Soria et al. 2023).

Adherence to therapy is essential for an effective treatment, especially when a patient is dealing with a chronic disease like multiple sclerosis (Pagès-Puigdemont et al. 2016; Losi et al. 2021; Burnier 2023). Also, it is extremely important to assess the level of treatment satisfaction because patients who are more satisfied adhere to the treatment plan better (Haase et al. 2016; Jacobs et al. 2017). All healthcare professionals should provide the necessary knowledge about a patient’s disease and risks and encourage him to adhere to the treatment regimen. Therefore, the additional training of medical professionals and patients, as well as the introduction оf new technologies for monitoring patients’ adherence are of utmost importance.

Multiple sclerosis is a complex neurological disorder that requires a multifaceted approach to treatment and management. Correct management is essential for ensuring high adherence to therapy in individuals diagnosed with multiple sclerosis (Milanov 2023).

The research contributes to our understanding of medication adherence in the context of multiple sclerosis in Bulgaria, offering a foundation for future studies to delve deeper into the intricacies of patient behavior and treatment outcomes. These insights are essential for healthcare practitioners and policymakers aiming to optimize therapeutic interventions and improve patient outcomes in the management of multiple sclerosis. It is crucial to persist in research in this field and create approaches to assist patients in their efforts to adhere more effectively to their multiple sclerosis treatment regimens. This will ultimately enhance their quality of life and slow the progression of the disease. Such measures could encompass individualized education, addressing psychological and cognitive aspects, and delivering information customized to the patient’s disease duration and lifestyle.

This research was funded by the Bulgarian National Science Fund project 739/25.02.2022, “Evaluation of the compliance and adherence to therapy in case of socially important diseases with high degree of non-adherence” with contract number No. KP-06-KOCT/6/14.06.2022.