The nocebo effect: a clinical challenge in the era of biosimilars

Abstract

The nocebo effect is defined as a negative effect of a pharmacological or non-pharmacological medical treatment that is induced by patients' expectations, and that is unrelated to the physiological action of the treatment. The nocebo effect is an important clinical challenge in the current era of biosimilars. Areas covered: This review aims to answer five key questions about the nocebo effect, namely to reveal its definition, pathophysiology, clinical relevance, contributing factors, and management. Expert commentary: The nocebo effect lowers patients' quality of life and negatively affects treatment adherence rates in biosimilar-treated patients. It may negatively impact on the cost-savings of biosimilars. Health-care providers in charge of biosimilar-treated patients need to be aware of the nocebo effect and adopt strategies to minimize it. They have to be well-informed and confident about the existing evidence about biosimilars. A good patient-physician relationship will improve patients' acceptance of biosimilars, and limits the risk of inappropriate negative bias and the nocebo effect.

Consensus report: clinical recommendations for the prevention and management of the nocebo effect in biosimilar‐treated IBD patients

“…Although data about the nocebo effect and its impact in biosimilar‐treated IBD patients remain scarce, research in many other fields, such as depression, neuropathic pain perception, and primary headache, supports the influence of negative expectations on the occurrence of adverse symptoms, and consequently on patients' well‐being and adherence. However only supported by indirect evidence, the nocebo effect can also lead to unnecessary cessation of biologic treatment, thereby altering IBD patients' outcomes in clinical practice and in clinical trials . The consensus group expressed concerns that the nocebo effect may also negatively impact on the cost‐savings of biosimilars, while the main objective of implementing biosimilars in IBD is economically driven .…”

“…Three members of the consensus group (LP, SD, LPB) conducted an extended literature search for relevant manuscripts on the nocebo effect in PubMed/MEDLINE, EMBASE (Excerpta Medica Database) and Cochrane CENTRAL from database inception up to July 2018. Detailed search strategy and results of this literature review were published previously . Randomised controlled trials specifically examining the nocebo effect in biosimilar‐treated IBD patients were lacking.…”

“…The nocebo effect is defined as a negative effect of a pharmacological or nonpharmacological medical treatment that is induced by patients' expectations, and that is unrelated to the physiological action of the treatment . It has been recognised as an important clinical challenge in the current era of biosimilars, since it can lower patients' quality of life and negatively affect treatment adherence rates . Evidence that the nocebo effect might indeed lead to unnecessary cessation of biologic treatment is mainly indirectly derived from open‐label observational studies, because double‐blinded trials are less susceptible to the nocebo effect .…”

The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases

“…Patients may experience nocebo effects (worsening or incitement of symptoms that are induced by a negative attitude toward an intervention) [172] that are only perceptible to the patient [173] and may impact on quality of life, treatment adherence, and the cost-saving potential of biosimilars [172,174]. In a study of 100 patients with RA, AS, or psoriatic arthritis, 89% initially accepted a nonmedical switch from reference infliximab to CT-P13 [175].…”

Who is afraid of biosimilars? Openness to biosimilars in an Australian cohort of patients with rheumatoid arthritis

“…Moreover, our cross‐sectional study does not account for the nocebo effect, where patients experience higher rates of a negative health effect due to the negative expectations of a treatment. Patients that initially accept biosimilars may refuse them later due to the nocebo effect as well as the potential social desirability bias. Real‐world data from the Danish registry suggest that patients who switched back from biosimilar to bio‐originator etanercept were due to changes in disease activity and adverse effects that were subjective rather than objective .…”