Abstract
Background
Biosimilar therapies represent a key strategy to improve sustainability and access to high-cost biologic treatments in multiple sclerosis (MS). Despite robust evidence supporting their efficacy and safety, patient resistance to biosimilar use and switching persists, often driven by informational gaps, patients’ health literacy processes, and nocebo-related mechanisms. While healthcare professionals play a central role in patient education, the specific contribution of nursing professionals, particularly MS nurses, remains underexplored. This study aimed to evaluate knowledge, attitudes, trust, and informational experiences related to biosimilars among individuals with MS, with particular attention to the perceived informational role of nurses.
Methods
An observational, multicenter, cross-sectional study was conducted across Italy. Adult individuals with MS were recruited through the Italian Network of Multiple Sclerosis Nurses. A theory-informed questionnaire was developed to operationalize the four health literacy domains (access, understand, appraise, apply) in the context of biosimilar therapies. Descriptive analyses were performed to evaluate response patterns across domains.
Results
Ninety-nine participants were included. Awareness of biosimilars was low, with over 60% reporting no prior knowledge, indicating limitations in the access domain. Comprehension-related items showed relatively low agreement regarding feeling adequately informed, suggesting gaps in the understand domain. Trust in healthcare professionals was high, perceived informational completeness was lower, and many participants reported seeking additional information independently, reflecting tension within the appraise domain. Willingness to switch to or initiate biosimilars was moderately positive and strongly influenced by professional recommendations, particularly from physicians and nurses.
Conclusions
Biosimilar acceptance in MS appears to be shaped more by difference in health literacy processes than by negative attitudes. MS nurses play a pivotal role in addressing these gaps, supporting informed understanding, reducing uncertainty, and guiding therapeutic decision-making. Strengthening nurse-led communication strategies may enhance patient confidence and promote informed, shared decision-making regarding biosimilar therapies.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12912-026-04660-6.
Keywords: Multiple sclerosis, Biosimilars, Health literacy, Nurses, Shared decision-making
Background
The increasing use of biologic therapies has substantially improved clinical outcomes in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system [1, 2]. However, the high cost of biologic drugs remains a major barrier to equitable access [3]. In this context, biosimilars have been introduced as a strategic solution to enhance sustainability while maintaining comparable efficacy, safety, and quality to originator biologics through rigorous regulatory approval processes [2]. The recent availability of biosimilar natalizumab [4], a highly effective therapy for relapsing forms of MS, exemplifies this opportunity [5]. Despite robust clinical evidence supporting biosimilar equivalence, resistance to biosimilar use and switching persists among patients with MS [2], a phenomenon commonly referred to as the nocebo effect [6]. Previous studies consistently indicate that such resistance is not driven by clinical outcomes, but rather by cognitive and informational factors, including limited knowledge, misconceptions about the regulatory approval process, and low trust in biosimilar therapies [7, 8]. These findings align with the health literacy framework, which conceptualizes patients’ engagement with healthcare decisions as a multidimensional process. Health literacy includes four interrelated competencies: the ability to access, understand, appraise, and apply health information to make informed decisions [9]. In this context, access refers to patients’ exposure to and access to relevant information about biosimilar therapies; understand refers to comprehension of concepts such as clinical equivalence and therapeutic implications; appraise involves critical evaluation of benefits and risks, including the development of trust in the therapy and in the healthcare system; apply refers to the integration of this information into personal therapeutic decisions, including acceptance or resistance to switching. Within this framework, patients’ treatment acceptance and satisfaction are not isolated but the result of a dynamic process. Patients must access reliable information, understand its meaning, critically appraise its relevance, and apply this information to their personal treatment decisions [9]. Limitations in any of these dimensions may contribute to misinterpretation of information, increasing uncertainty and susceptibility to nocebo-related responses. In contrast, adequate health literacy supports informed acceptance, treatment satisfaction, and shared decision-making with healthcare professionals [9, 10]. Healthcare professionals, particularly physicians and MS nurses, play a central role in shaping patients’ health literacy process. Nurses are often the primary point of contact during treatment initiation, switching, and follow-up, and can facilitate access to reliable information, promote comprehension, support critical appraisal, and guide the application of information to individual treatment choices [11–14]. Through structured and tailored communication strategies, nursing professionals may therefore mitigate misinformation and reduce nocebo-related responses.
However, although several studies have explored isolated aspects of patient perceptions toward biosimilars [15], important gaps remain in the current literature. The role of nursing professionals, particularly MS nurses, in shaping patients’ knowledge, attitudes, trust, and informational experiences regarding biosimilar therapies remains underexplored. Despite their central role in patient education, treatment counselling, and ongoing therapeutic support, nurses’ impact on biosimilar acceptance and satisfaction has not been examined in depth. This gap in literature limits a comprehensive understanding of their contribution within MS care. The absence of a structured assessment of how nursing communication shapes patients’ informational processes, it remains difficult to design targeted, nurse-led educational interventions aimed at improving informed decision-making and patient-centered care in the context of biosimilar use in MS. Within the health literacy framework, patients’ engagement with biosimilar therapies can be conceptualized across four interrelated dimensions: the ability to access, understand, appraise, and apply information. This framework offers a structured perspective to analyze how nursing communication influences the patient’s decision-making process regarding treatment. Therefore, the primary aim of this study was to evaluate knowledge, attitudes, trust, and informational experiences related to biosimilar drugs among individuals with MS, with particular attention to the perceived informational role of nursing professionals. This study also included a preliminary field test of a newly developed, theory-informed questionnaire designed to measure health literacy in the MS context, to enable descriptive assessment and inform future refinement and validation studies.
Methods
Study design
An observational, multicenter, cross-sectional study was conducted from March to May 2025 across Italy. To ensure comprehensive and accurate reporting of the research process, the STrengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were followed [16].
Participants
The study was conducted through the Italian Network of Multiple Sclerosis Nurses, involving multiple healthcare facilities across Italian regions. A convenience sampling approach with consecutive recruitment was used across the participating centers. Ten specialized MS nurses identified eligible patients from their daily clinical caseloads to ensure they met the predefined inclusion and exclusion criteria. The group of potential participants, estimated at around 200, was based on the nurses’ active caseloads during the recruitment. On average, each nurse reported about 20 patients who fulfilled the eligibility criteria and were likely to attend routine follow-up visits during the study period. All eligible patients attending scheduled appointments during this period were consecutively invited to participate. Inclusion criteria for patient recruitment were: (1) a confirmed MS diagnosis according to the 2017 McDonald criteria [17], (2) a minimum age of 18 years, (3) a diagnosis made at least one year before enrollment, (4) a voluntary agreement to participate by signing the informed consent form, (5) absence of a severe cognitive impairment that could compromise the ability to understand and complete the questionnaire, and (6) full completion of the data collection instruments. Patients were excluded if they did not meet these criteria, refused to sign the informed consent, or failed to complete the questionnaire.
Description of the questionnaire
Questionnaire development – items generation
The questionnaire used in this study was developed as a theory-informed instrument, based on the health literacy framework [9], to explore knowledge, attitudes, trust, and informational experiences related to biosimilar drugs in people with MS, as no disease-specific instrument addressing these dimensions was available. Item generation was conducted by an interdisciplinary research team including MS nurses, neurologists, and researchers with expertise in health literacy and quantitative research methodology. An initial pool of 27 items was drafted by an interdisciplinary research team composed of MS nurses and neurologists to reflect the essential elements of each health literacy domain (access, understand, appraise, and apply), based on current literature on biosimilars, regulatory guidance from the European Medicines Agency, and established conceptual models of health literacy. Particular attention was given to clarity of wording and accessibility of language to ensure comprehensibility for individuals with varying educational backgrounds. Items were formulated in patient-accessible language and structured with Likert-type response options.
Qualitative refinement of the questionnaire
To improve clarity and relevance, a qualitative refinement phase was carried out. Two focus groups, one with six healthcare professionals, including three MS nurses and three neurologists and one with eight patients with MS, were conducted. Focus groups with professionals were conducted through semi-structured interviews, allowing participants to give feedback on item relevance, clarity, and overall comprehensibility. Instead, focus groups with patients, using a think-aloud method, aligned with the four health literacy domains, help patients assess item comprehension, interpretability, and response processes. Feedback from focus groups with healthcare professionals was examined and organized into themes highlighting areas requiring revision, such as conceptual overlap, ambiguous wording, and relevance to the clinical setting. The research team discussed the suggested modifications until consensus was reached. Overall, four items were removed, and minor revisions were made to improve wording and reduce redundancy. The final questionnaire consisted of 23 items. Finally, feedback from patients’ interviews confirmed clarity and readability of all included items, therefore no further changes or revision were applied to the instrument.
Final version of the questionnaire and pilot implementation
Following qualitative refinement, a pre-test of the questionnaire was conducted with a small group of patients from the target population. This phase verified the instrument’s clarity and usability before its implementation in the cross-sectional study. Subsequently, it was employed to assess descriptive response patterns in the real-world clinical setting. The items of the final questionnaire were organized into five sections (Supplementary Table 1). (I) The first section collected sociodemographic data, including gender, age, age group, region of residence, marital status, educational level, and employment status (5 items). (II) The second section explored the health literacy domain “access”, assessing patients’ information sources, exposure to biosimilar-related information and the accessibility of communication pathways within the healthcare setting. Specifically, this section assessed whether participants had ever heard about biosimilar drugs (Q6 – Awareness); where they first heard about biosimilars (Q7 – First source of information); whether healthcare professionals had provided information on biosimilars and through which channels (multiple responses allowed) (Q8 and Q9); which healthcare professional first provided information on biosimilars (Q10); and the type of information provided by healthcare professionals regarding biosimilar drugs (Q11). Within this section, items Q6–Q8 were dichotomous. Items Q7, Q9, Q10, and Q11 were evaluated by multiple-choice variables. (III) The third section evaluated the health literacy domain “understand”, through items evaluating perceived knowledge, and comprehension of information related to biosimilar drugs. Statements addressed perceived differences between biosimilars and originator biologics (Q12), perceived sustainability and safety of biosimilars (Q13), perceived safety equivalence (Q14), perception of being adequately informed (Q15). (IV) The fourth section assessed the health literacy domain “appraise”, with items designed to measure critical evaluation of information and trust. Statements explored confidence in biosimilar safety (Q16), adequacy and completeness of information provided (Q17), trust in such information (Q18), and the need for independent search for additional information (Q19). (V) The fifth section evaluated the health literacy domain “apply”, through items examining integration of information into therapeutic decisions. This section included items related to willingness to switch to a biosimilar (Q20), acceptance of a biosimilar for treatment initiation (Q21), influence of the nurse advice on treatment decisions (Q22), and influence of the physician advice on treatment choice (Q23). Items (Q14–Q21) were rated on a 5-point Likert scale, ranging from “strongly disagree” to “strongly agree”, while items Q22 and Q23 were measured using a 5-point scale ranging from “Not at all” to “In a decisive way”.
Sample size estimation
Given the descriptive and exploratory nature of this study, no formal psychometric validation procedures were performed. Similarly, no priori sample size calculation was performed. Recruitment was guided by feasibility within participating centers within the national nursing network and based on consecutive enrolment during routine clinical care.
Statistical analysis
Descriptive statistics were computed for all variables. Categorical variables were summarized using frequencies and percentages. Likert-type items were described by reporting the distribution of responses across categories. Given the theory-informed, explorative and descriptive aim of the instrument, analyses focused on describing response patterns within the four health literacy domains (access, understand, appraise, apply).
Results
Study subjects
A total of 99 patients completed the questionnaire, yielding a response rate of 49.5%. The sample was predominantly female (71.7%), with 2.0% not reporting gender, and a mean age of 44.3 years (SD = 11). Sociodemographic characteristics are reported in Table 1. Participants were mainly aged 31–45 years (41.4%) and 46–54 years (28.3%). Most respondents were married or cohabited (62.6%). Regarding employment status, 61.6% were employed, 18.2% were unemployed, 16.2% were retired, and 4.0% were students. The educational level was generally high, with 47.5% holding a university degree and 2.0% a doctoral degree, while 36.4% had completed upper secondary education; lower educational levels were less represented. Participants were mainly residents of Southern and Central Italy, with the largest proportion living in Puglia (46.5%), followed by Lazio (11.1%) and Sardegna (9.1%), while other regions were represented to a lesser extent.
Table 1.
Sociodemographic Variables (N = 99)
| Variable | n | % |
|---|---|---|
| Gender | ||
| Female | 71 | 71.7 |
| Male | 26 | 26.3 |
| Not reported | 2 | 2.0 |
| Age group (years) | ||
| 18–30 | 11 | 11.1 |
| 31–45 | 41 | 41.4 |
| 46–54 | 28 | 28.3 |
| ≥ 55 | 19 | 19.2 |
| Marital status | ||
| Single | 30 | 30.3 |
| Separated/Divorced | 6 | 6.1 |
| Married/Cohabiting | 62 | 62.6 |
| Widowed | 1 | 1.0 |
| Employment status | ||
| Employed | 61 | 61.6 |
| Unemployed | 18 | 18.2 |
| Retired | 16 | 16.2 |
| Student | 4 | 4.0 |
| Educational level | ||
| Primary school | 1 | 1.0 |
| Lower secondary school | 13 | 13.1 |
| Upper secondary school | 36 | 36.4 |
| University degree | 47 | 47.5 |
| PhD | 2 | 2.0 |
| Region of residence | ||
| Puglia | 46 | 46.5 |
| Lazio | 11 | 11.1 |
| Sardegna | 9 | 9.1 |
| Lombardia | 5 | 5.1 |
| Basilicata | 5 | 5.1 |
| Veneto | 4 | 4.0 |
| Toscana | 4 | 4.0 |
| Emilia-Romagna | 3 | 3.0 |
| Piemonte | 3 | 3.0 |
| Sicilia | 3 | 3.0 |
| Campania | 2 | 2.0 |
| Liguria | 2 | 2.0 |
| Trentino-Alto Adige | 1 | 1.0 |
| Calabria | 1 | 1.0 |
Access: knowledge, information sources, and professional advice
Regarding prior exposure to information on biosimilar medicines before initiating treatment with a biosimilar, 37.4% of participants reported having previously heard about biosimilars, whereas 62.6% had not. Most participants reported receiving information from healthcare professionals, while a small proportion reported receiving no information (5.1%). Among those, the first source of information was most frequently a healthcare professional, particularly a physician (52.5%) or a nurse (36.4%), whereas pharmacists (3.0%) and other sources (8.1%) were reported less frequently. Information was mainly delivered through verbal explanation (91.5%), while printed material (2.1%) and structured educational sessions (1.1%) were rarely used.
With respect to the content of information received, participants most frequently reported receiving information on treatment effectiveness (40.4%), followed by mechanism of action (16%) and potential side effects (9.6%). Information on safety was less frequently reported (2.1%) when considered as a single topic; however, a substantial proportion of respondents indicated receiving combined information covering multiple aspects, including effectiveness, safety, mechanism of action, and side effects (31.9%), highlighting variability in the depth and breadth of informational experiences (Table 2).
Table 2.
ACCESS: Knowledge, Information Sources, and Professional Advice (Q6-Q10)
| Items | n | % |
|---|---|---|
| Q6. Had you ever heard about biosimilar drugs before starting treatment with a biosimilar? | ||
| Yes | 37 | 37.4 |
| No | 62 | 62.6 |
| Q7. Have you ever received information about biosimilar drugs from healthcare professionals? | ||
| Yes | 94 | 94.9 |
| No | 5 | 5.1 |
| Q8. Apart from healthcare professionals, which other sources have provided you with information about biosimilar drugs? | ||
| Internet | 69 | 69.7 |
| Other patients | 25 | 25.3 |
| Patient association (AISM) | 5 | 5.1 |
| Q9. Through which main channel did healthcare professionals provide information? * | ||
| Verbal explanation | 86 | 91.5 |
| Printed material | 2 | 2.1 |
| Educational sessions | 1 | 1.1 |
| No response | 5 | 5.3 |
| Q10. Who first provided you with information about biosimilars? | ||
| Physician | 52 | 52.5 |
| Nurse | 36 | 36.4 |
| Pharmacist | 3 | 3.0 |
| Other | 8 | 8.1 |
| Q11. What information were you provided about biosimilar drugs? * | ||
| Effectiveness | 38 | 40.4 |
| Mechanism of action | 15 | 16.0 |
| Side effects | 9 | 9.6 |
| Safety | 2 | 2.1 |
| All of the above | 30 | 31.9 |
* Frequencies and percentages are calculated among participants who responded “Yes” to Q7 (n = 94)
Understand: informational experience
Overall, responses tended to cluster around the neutral score, with a median of 3 across all items, indicating a moderate level of agreement. Perceived difference between biosimilars and originator products yielded a mean value close to neutrality (M = 3.07, SD = 0.84), with nearly half of participants selecting the neutral option (48.5%), while 28.3% agreed, and only a small proportion strongly agreed (2.0%). Moderate agreement was also observed regarding the perceived sustainability of biosimilars (M = 3.31, SD = 0.80), although most respondents remained neutral (56.6%), while 28.3% agreed that biosimilars are more sustainable than originator biologics. A similar pattern emerged for perceived safety equivalence (M = 3.28, SD = 0.80), with 56.6% reporting a neutral position and 34.4% expressing agreement or strong agreement.
The perceived level of being adequately informed was lower (M = 2.68, SD = 1.04), indicating potential gaps in patients’ perceived comprehension of biosimilar-related information; 38.4% of participants disagreed or strongly disagreed with the statement, whereas only 21.2% agreed or strongly agreed that they felt adequately informed (Table 3).
Table 3.
Understand: Informational Experience (Q12-Q15)
| Item | Response | n | % |
|---|---|---|---|
| Q12. Biosimilar drugs are different from originator (reference) biologic drugs | Strongly disagree | 4 | 4.0 |
| Disagree | 17 | 17.2 | |
| Neither agree nor disagree | 48 | 48.5 | |
| Agree | 28 | 28.3 | |
| Strongly agree | 2 | 2.0 | |
| Q13. Biosimilar drugs are more sustainable than originator biologic drugs. | Strongly disagree | 3 | 3.0 |
| Disagree | 5 | 5.1 | |
| Neither agree nor disagree | 56 | 56.6 | |
| Agree | 28 | 28.3 | |
| Strongly agree | 7 | 7.1 | |
| Q14. Biosimilar drugs are as safe as originator biologic drugs | Strongly disagree | 3 | 3.0 |
| Disagree | 6 | 6.1 | |
| Neither agree nor disagree | 56 | 56.6 | |
| Agree | 28 | 28.3 | |
| Strongly agree | 6 | 6.1 | |
| Q15. I feel adequately informed about biosimilar drugs | Strongly disagree | 18 | 18.2 |
| Disagree | 20 | 20.2 | |
| Neither agree nor disagree | 40 | 40.4 | |
| Agree | 20 | 20.2 | |
| Strongly agree | 1 | 1.0 |
Appraise: critical evaluation and trust
Items exploring evaluative processes and trust revealed heterogeneous patterns. Confidence in biosimilar safety showed moderate agreement (M = 3.17, SD = 0.90), although more than half of participants adopted a neutral position (52.5%), while 32.4% reported agreement or strong agreement. Trust in healthcare professionals’ information was relatively high (M = 3.29, SD = 0.94), with 42.5% of respondents agreeing or strongly agreeing that they trust the information provided, although 43.4% remained neutral. In contrast, agreement regarding the completeness of information was lower (M = 2.83, SD = 1.06); notably, 35.3% of participants disagreed or strongly disagreed that healthcare professionals had provided all the useful information about biosimilars, while only 30.3% agreed. The item assessing the need to seek additional information beyond what was provided by healthcare professionals yielded a mean value above neutrality (M = 3.31, SD = 0.88), with 45.4% of respondents reporting that they searched for additional information independently (Table 4).
Table 4.
Appraise domain (Q16–Q19): critical evaluation and trust
| Item | Response | n | % |
|---|---|---|---|
| Q16. I would feel confident, in terms of safety, using a biosimilar instead of an originator biologic drug | Strongly disagree | 6 | 6.1 |
| Disagree | 9 | 9.1 | |
| Neither agree nor disagree | 52 | 52.5 | |
| Agree | 26 | 26.3 | |
| Strongly agree | 6 | 6.1 | |
| Q17. Healthcare professionals have provided me with all the useful information about biosimilar drugs. | Strongly disagree | 14 | 14.1 |
| Disagree | 21 | 21.2 | |
| Neither agree nor disagree | 34 | 34.3 | |
| Agree | 28 | 28.3 | |
| Strongly agree | 2 | 2.0 | |
| Q18. I trust the information provided by healthcare professionals regarding biosimilar drugs. | Strongly disagree | 6 | 6.1 |
| Disagree | 8 | 8.1 | |
| Neither agree nor disagree | 43 | 43.4 | |
| Agree | 35 | 35.4 | |
| Strongly agree | 7 | 7.1 | |
| Q19. I needed to search for additional information beyond what was provided by healthcare professionals | Strongly disagree | 5 | 5.1 |
| Disagree | 8 | 8.1 | |
| Neither agree nor disagree | 41 | 41.4 | |
| Agree | 41 | 41.4 | |
| Strongly agree | 4 | 4.0 |
Apply: decision-making application
Behavioral intention items showed generally positive trends. Participants reported moderate agreement with willingness to switch to a biosimilar if recommended by their physician (M = 3.30, SD = 0.86), although half of the respondents adopted a neutral position (50.5%), while 38.4% expressed agreement or strong agreement. A slightly stronger pattern was observed regarding acceptance of biosimilars from the first treatment cycle (M = 3.42, SD = 0.82), with nearly half of participants reporting agreement or strong agreement (49.5%), whereas 39.4% remained neutral.
The influence of healthcare professionals on treatment choices was rated as high. Specifically, the advice of nurses was perceived as determinant or very influential by 82.8% of participants (in a decisive way = 60.6%; much = 22.2%), whereas only 10.1% reported little or no influence (slightly = 6.1%; not at all = 4.0%). Similarly, the advice of physicians was considered determinant or very influential by 92.9% of respondents (in a decisive way = 69.7%; much = 23.2%), confirming the central role of both professional figures in therapeutic decision-making related to biosimilars (Table 5).
Table 5.
– Apply: decision-making application
| Item | Response | n | % |
|---|---|---|---|
| Q20. I would be willing to switch from an originator biologic drug to a biosimilar if recommended by my physician. | Strongly disagree | 4 | 4.0 |
| Disagree | 7 | 7.1 | |
| Neither agree nor disagree | 50 | 50.5 | |
| Agree | 31 | 31.3 | |
| Strongly agree | 7 | 7.1 | |
| Q21. I would be willing to use a biosimilar if my physician recommended it from the first treatment cycle. | Strongly disagree | 2 | 2.0 |
| Disagree | 9 | 9.1 | |
| Neither agree nor disagree | 39 | 39.4 | |
| Agree | 43 | 43.4 | |
| Strongly agree | 6 | 6.1 | |
| Q22. How much does the nurse’s advice influence your treatment choices, including biosimilars? | Strongly | 60 | 60.6 |
| Very much | 22 | 22.2 | |
| Moderately | 7 | 7.1 | |
| Slightly | 6 | 6.1 | |
| Not at all | 4 | 4.0 | |
| How much does your physician’s advice influence your treatment choices, including biosimilars? | Strongly | 69 | 69.7 |
| Very much | 23 | 23.2 | |
| Moderately | 2 | 2.0 | |
| Slightly | 4 | 4.0 | |
| Not at all | 1 | 1.0 |
Discussion
The present study aims to evaluate knowledge, attitudes, trust, and informational experiences related to biosimilar drugs among individuals with MS, with particular attention to the perceived informational role of nursing professionals. The secondary aim was to describe the application of a newly developed, theory-informed questionnaire designed to operationalize the four domains of the health literacy framework (access, understand, appraise, and apply) in the context of biosimilars in MS.
Limited access to biosimilar information
One of the most striking findings in the access domain was that over 60% of participants reported having never heard of biosimilars, despite being under active treatment with these agents. This limitation in the access domain influences the downstream process, as patients must first encounter structured, comprehensible information before they can meaningfully evaluate or accept a therapeutic option. The overall low level of awareness suggested that systematic informational pathways regarding biosimilars may not yet be fully integrated into routine MS care. Importantly, this finding does not necessarily reflect resistance to biosimilar therapies but highlights potential informational gaps at the initial stage of the health literacy process.
Indeed, this lack of awareness aligns with previous studies showing that patients often fail to differentiate between generics, biologics, and biosimilars [18]. A global survey confirmed that familiarity with biosimilars is limited among patients, pharmacists, and physicians, with substantial variation across countries and healthcare systems [15].
Uncertain understanding of biosimilar information
Items assessing understand of the domain showed moderate but not robust endorsement, with participants reporting relatively low agreement with feeling adequately informed. Even when receiving information, the partial understanding may generate uncertainty without necessarily leading to negative attitudes [9, 19]. These findings suggest that many participants adopted a neutral position when evaluating key aspects of biosimilars, including perceived differences from originator biologics, sustainability, and safety equivalence. This pattern may reflect uncertainty or limited familiarity with biosimilar-related information, rather than clearly formed opinions. In particular, the relatively low mean score and high proportion of disagreement observed for the item assessing perceived adequacy of information indicate that a substantial proportion of patients do not feel sufficiently informed about biosimilars. Together, these results highlight potential gaps in patients’ informational experience and suggest that improving the clarity and completeness of communication about biosimilars may represent an important target for patient education and shared decision-making in clinical practice.
Appraisal marked by trust but informational gaps
Trust in healthcare professionals was relatively high and confidence in biosimilar safety showed moderate endorsement. However, the perceived completeness of information was lower. This coexistence of trust and insufficient information suggests a tension in the appraisal process. Patients appear to consider healthcare professionals credible yet still perceive that their informational needs are not fully satisfied. This gap may reflect time constraints during consultations, variability in communication approaches, or the absence of tailored educational interventions [11] and may drive independent information-seeking behaviors, potentially exposing patients to inconsistent or inaccurate sources and increasing vulnerability to nocebo-related responses. In this context, healthcare professionals should ensure that communication is sufficiently comprehensive, tailored, and responsive to patients’ concerns. These findings suggest that, despite relatively high trust in healthcare professionals, respondents perceived gaps in the quantity or clarity of information provided.
Application influenced by healthcare professionals
The most impactful and trusted source of information on biosimilars remained healthcare professionals, particularly physicians and nurses. The apply domain revealed a clinically relevant finding. Willingness to switch to or initiate treatment with a biosimilar was moderately positive, particularly when recommended by a physician. Moreover, both nurses and physicians were perceived as highly influential in treatment decision-making, indicating that therapeutic application is strongly mediated by professional advice. Acceptance of biosimilars may be conditional and influenced by contextual and informational factors rather than driven by autonomous pharmacological evaluation [20]. In this vein the healthcare professional-patient interaction is central to improving informed acceptance of biosimilars. However, it is important to note that the items assessing the influence of healthcare professionals specifically referred to treatment decisions related to biosimilar therapies. Nevertheless, this study did not directly assess negative attitudes toward biosimilars. Therefore, the potential contribution of attitudinal factors alongside health literacy processes should be interpreted with caution. Future research should further explore the role of attitudes and beliefs in shaping patients’ acceptance of biosimilar therapies. These findings are consistent with earlier work showing that trust in healthcare providers and the quality of interpersonal communication are key determinants of therapeutic adherence [21], and that patients’ openness to biosimilars is strongly mediated by trust in healthcare professionals rather than by autonomous evaluation of pharmacological equivalence [22]. These results highlight the central role of healthcare professionals in supporting informed decision-making and facilitating the integration of biosimilars into routine clinical practice.
The role of healthcare professionals in biosimilar communication
Structured and proactive communication about biosimilars is central for their inclusion in therapeutic pathways. While online sources provide accessibility, they also carry the risk of misinformation. Thus, interventions that empower healthcare professionals to deliver clear, consistent, and evidence-based messages are essential. The decisive influence of physicians in treatment decisions observed in our study confirms their primary role in shaping patient choices. Our results also highlight the substantial impact of nurses, who influence patients’ knowledge and perceived treatment effectiveness. This is a crucial finding, given that the role of nurses in biosimilar education has been less frequently addressed in literature than that of prescribing physicians.
MS nurses are uniquely positioned to support patients in managing complex therapies and address informational gaps, reinforce key messages, and adapt communication to patients’ literacy levels and concerns, due to their frequent and repeated contact, continuity of care, and expertise in patient education [23, 24]. Nurse-led interventions have been shown to improve health literacy, adherence, and satisfaction in chronic diseases such as diabetes, rheumatoid arthritis, and hypertension [25–27].
Within MS care, where new treatment regimens such as biosimilars are complex, and adherence is vital to clinical outcomes, nurses can act as mediators between biomedical information and patients’ experience, tailoring communication to the individual’s level of understanding and emotional readiness.
This is consistent with the growing recognition of nurse-led clinics as effective and cost-efficient models of care in chronic disease management [28]. Evidence suggests that when nurses are empowered to deliver structured education, patients demonstrate improved trust, adherence, and self-management capacity [29]. Our findings strongly support the integration of such approaches into MS care, particularly with respect to biosimilars, where patient skepticism and lack of familiarity remain major barriers.
Taking together, these findings suggest that gaps within health literacy processes may contribute to patterns of biosimilar acceptance in MS. Strengthening nurse-led education and communication may therefore represent a promising strategy to enhance patients’ understanding, reduce uncertainty, and support informed, confident decision-making regarding biosimilar therapies.
Strengths and limitations
This study addresses an underexplored topic in MS by applying a theory-informed health literacy framework to interpret patients’ perceptions of informational experiences regarding biosimilars, with specific attention to the nursing role. Moreover, multicenter design and consecutive recruitment within routine clinical practice enhance the ecological validity of the findings, reflecting real-world nursing care settings. However, some limitations must be acknowledged. First, the cross-sectional design precludes causal inferences. Second, the relatively small sample size and convenience sampling strategy may limit generalizability within the participating centers. In particular, the sample was predominantly female and highly educated, which may have influenced the reported perceptions of health literacy. Third, all measures were self-reported, which may introduce recall and response bias. Participants rated nurses’ advice as determinant or very influential. However, this finding should be interpreted with caution, as respondents may have considered general treatment advice rather than biosimilar-specific counselling. Moreover, the results of this study should be interpreted considering its exploratory and descriptive nature, which shows how health literacy may affect patients’ perceptions and decision-making regarding biosimilars and highlights nursing professionals as important facilitators within this informational pathway. However, these results outline only hypotheses that warrant further exploration in future studies and therefore do not permit drawing conclusions about the specific contribution of attitudinal versus informational determinants in shaping acceptance of biosimilar therapies. Finally, the questionnaire used in this study represents the preliminary field application of a newly developed, theory-informed instrument. Although item development was grounded in conceptual modelling and qualitative refinement, formal psychometric validation, including reliability and construct validity, was not performed. Accordingly, the findings should be interpreted as exploratory and descriptive.
Moreover, the study did not directly evaluate the effects of structured nurse-led educational interventions. Future research should include larger samples to enable comprehensive psychometric evaluation, also examine measurement stability across demographic and educational subgroups, and confirm the generalizability of the findings across MS populations.
Conclusions
This study provides exploratory insights into patterns of biosimilar acceptance in MS, suggesting that health literacy processes may play a relevant role in shaping patients’ perceptions and therapeutic decision-making rather than by entrenched negative attitudes. Within this framework, the study underscores the pivotal role of nures as key facilitators of patient education and informed therapeutic decision-making. Optimizing health literacy processes in routine MS care may therefore represent a strategic pathway to improving biosimilar acceptance while promoting patient-centered and sustainable healthcare delivery.
Electronic Supplementary Material
Below is the link to the electronic supplementary material.
Acknowledgements
Editorial support was provided by Jacqueline Bersano, PhD, on behalf of Health Publishing & Services Srl. This support was funded by Sandoz according to Good Publication Practices.
Abbreviations
- MS
Multiple sclerosis
- STROBE
STrengthening the Reporting of Observational Studies in Epidemiology
Author contributions
Francesco Pastore, Giancarlo Cicolini: Conceptualization, Methodology, Analysis, Investigation, Supervision, Writing - Original Draft, Writing - Review & Editing.Barbara Foratefano, Emanuela Domenicone, Simona De Summa: Methodology, Analysis, Investigation, Writing - Original Draft, Writing - Review & Editing.Dania Comparcini, Valentina Simonetti: Conceptualization, Analysis, Supervision, Writing - Original Draft, Writing - Review & Editing.All authors approved the final version for the submission.
Funding
This work received no funding.
Data availability
The datasets supporting the conclusions of this article are included within the article (and its additional file).
Declarations
Ethics approval and consent to participate
According to the provisions of the Italian Medicines Agency (AIFA), as outlined in Determine Pres. n. 425/2024, this study was classified as a non-interventional observational study involving an anonymous survey, and therefore did not require prior ethical committee approval. This classification was formally confirmed by the Ethics Committee of Bari, which stated in a communication dated March 25, 2025, that no ethical opinion was needed for the study to be conducted. All participants received comprehensive information about the study’s objectives, procedures, and data management protocols. Participation was entirely voluntary and based on the provision of written informed consent. The questionnaire was fully anonymous, and to safeguard privacy, completed questionnaires were sealed in envelopes by participants and deposited into a designated collection box. Personal identifiers were stored separately from survey data, ensuring complete anonymity. All procedures concerning data collection, handling, and storage were carried out in accordance with national legal requirements and the General Data Protection Regulation (GDPR) (European Parliament & Council of the European Union, 2018). All data were stored on a secure, password-protected platform accessible exclusively to the principal investigator. A trained research nurse was responsible for the individual recruitment of participants and for verifying the fulfillment of the inclusion criteria. Participants who agreed to take part in the study were provided with comprehensive information regarding the study’s objectives and procedures, and informed that participation was entirely voluntary and anonymous.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Francesco Pastore and Giancarlo Cicolini contributed equally to this work.
Dania Comparcini and Valentina Simonetti equally contributed to project leadership.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets supporting the conclusions of this article are included within the article (and its additional file).