The Clinical Implications of Nocebo Effects for Biosimilar Therapy

Abstract

Nocebo effects encompass negative responses to inert interventions in the research setting and negative outcomes with active treatments in the clinical research or practice settings, including new or worsening symptoms and adverse events, stemming from patients' negative expectations and not the pharmacologic action of the treatment itself. Numerous personality, psychosocial, neurobiological, and contextual/environmental factors contribute to the development of nocebo effects, which can impair quality of life and reduce adherence to treatment. Biologics are effective agents widely used in autoimmune disease, but their high cost may limit access for patients. Biosimilar products have gained regulatory approval based on quality, safety, and efficacy comparable to that of originator biologics in rigorous study programs. In this review, we identified gaps in patients' and healthcare professionals' awareness, understanding, and perceptions of biosimilars that may result in negative expectations and nocebo effects, and may diminish their acceptance and clinical benefits. We also examined features of nocebo effects with biosimilar treatment that inform research and clinical practices. Namely, when biosimilars are introduced to patients as possible treatment options, we recommend adoption of nocebo-reducing strategies to avoid negative expectations, including delivery of balanced information on risk-benefit profiles, framing information to focus on positive attributes, and promoting shared decision-making processes along with patient empowerment. Healthcare professionals confident in their knowledge of biosimilars and aware of bias-inducing factors may help reduce the risk of nocebo effects and improve patients' adherence in proposing biosimilars as treatment for autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease.

Continuous effectiveness and safety after a hospital-wide switch to adalimumab biosimilar: an observational study in rheumatoid arthritis patients

“…The way information is conveyed in case of a potential switch can also contribute to a nocebo effect [33]. By avoiding negative associations, one can keep the nocebo effect as small as possible [34]. However, the development of negative associations cannot be fully controlled and can always in uence the outcomes to some extent.…”

Informing Patients about Biosimilar Medicines: The Role of European Patient Associations

“…Several studies have already shown that it is crucial to positively formulate the message about biosimilars towards patients. An empathic and positive communication (including positive framing) or attitude increase the acceptance to switch and reduce the development of nocebo effects after transitioning to a biosimilar [54][55][56][57][58]. An open and positive communication, emphasizing the equalities and not the differences between the reference product and its biosimilar, should be the norm when talking to patients.…”

“…Some patients will naturally be more concerned about their treatment and ask for more information. While other patients trust their physician completely and will express no further concerns about biosimilars [55,60,64]. However, many patients will be somewhere between these two extremes of the spectrum, highlighting the importance of tailored communication.…”

“…European regulatory agencies and national competent authorities have a supporting role in disseminating unbiased information about biosimilars in general [55,66,91]. However, room for improvement was recently pointed out for European national competent authorities to disseminate biosimilar information to the public [92].…”

Biosimilars are becoming indispensable in the management of multiple diseases although concerns still exist

“…We have seen a growing increase in the utilisation of biosimilars across countries as a result of ongoing initiatives, and this is likely to continue 39,49-52 enhanced by advice concerning additional initiatives that could be instigated to enhance their use if needed 53 . Education of physicians and patients regarding biosimilars is very important given the nocebo effect in practice else saving goals will not be achieved 54,55 . Such initiatives are likely to grow given the number of biological medicines likely to lose their patent in the near future and the need to enhance the use of biological medicines across countries to improve patient care 56 .…”