Treatment journey in rheumatoid arthritis with biosimilars: from better access to good disease control through cost savings and prevention of nocebo effects.

Early diagnosis and treatment of rheumatoid arthritis (RA) are of critical importance to halt the progression of the disease. Optimal use of advanced imaging techniques or biomarkers may facilitate early diagnosis of RA. Even though many disease-modifying anti-rheumatic drugs (DMARDs) are available for RA treatment, biological DMARDs (bDMARDs) offer expanding therapeutic options and good outcomes in patients with RA who do not have a sufficient response to conventional synthetic DMARDs. However, high costs of bDMARDs have limited patient access to optimised disease management and increased the cost burden for healthcare systems. The advent of biosimilars led to significant cost savings driven by price competition among the reference products, which could be beneficial for healthcare systems. Healthcare provider (HCP)-patient communication and informed shared decision-making are crucial to prevent the occurrence of a nocebo effect, which results from negative perceptions that patients may have and could lead to less effective outcomes. Research has demonstrated that effective communication between HCPs and patients utilising positive framing can improve acceptance by patients to be initiated on or switched to a biosimilar and can help to integrate biosimilars into routine clinical practice to maximise benefits for patients with RA.

European Stakeholder Learnings Regarding Biosimilars: Part II-Improving Biosimilar Use in Clinical Practice.

BACKGROUND: Despite the benefits biosimilars offer in terms of cost savings and patient access, healthcare professionals and patients have been reluctant to use them. Next to insufficient understanding of and trust in biosimilars, healthcare professionals and patients have questions about switching and the nocebo effect when using biosimilars in clinical practice. In addition, clear motivation to use biosimilars may be lacking among these stakeholders. OBJECTIVE: This study aims to provide recommendations on how to improve biosimilar use on both a clinical and a practical level based on insights from healthcare professionals (physicians, hospital pharmacists, nurses), patients (or their representatives), and regulators across Europe. METHODS: We conducted 44 semi-structured interviews with experts from five stakeholder groups across Europe: physicians, hospital pharmacists, nurses, regulators, and patients/representatives. Interviews were transcribed ad verbatim and transcripts analysed according to the thematic framework method. RESULTS: Based on the insights and considerations of the experts interviewed, we identified a number of recommendations to improve the use of biosimilars in clinical practice. Regarding switch implementation, the experts voiced support for the following actions: (1) disseminate evidence from and experience with (multiple) switching; (2) provide clear, one-voice regulatory guidance about the interchangeability of biosimilars and their reference product; (3) apply a multi-stakeholder implementation and communication protocol to guide switching in clinical practice; (4) apply a pragmatic approach when taking switch decisions; and (5) avoid mandated switching, allowing stakeholder communication and alignment. When discussing approaches to increase the willingness of stakeholders to use biosimilars, we concluded that actions should be centred on (1) communicating the benefits provided by biosimilars and the introduction of market competition, (2) increasing awareness among stakeholders about medicine prices and their societal responsibility to use medicines in a cost-effective manner, (3) transparent reporting about the allocation of savings, (4) sharing biosimilar usage data among hospitals and prescribers to allow peer-to-peer benchmarking, and (5) applying a balanced combination of tangible and non-tangible incentives that can be tailored to offset the time and effort expended by stakeholders when switching to a biosimilar. CONCLUSIONS: This study proposes a number of strategic, practical, and overarching recommendations to support healthcare professionals and inform decision makers to improve the clinical use of biosimilars and the willingness of stakeholders to use them. The proposed solutions to fully realise the potential of biosimilars for healthcare systems and patients include developing practical switch guidance, being transparent about the gains from biosimilar use (and how savings are allocated), and developing a combination of non-tangible and tangible incentives for involved stakeholders.

Multidisciplinary management of the nocebo effect in biosimilar-treated IBD patients: Results of a workshop from the NOCE-BIO consensus group.

The high cost of biological drugs for patients with inflammatory bowel disease (IBD) considerably impacts on health-care budgets. Since the patent of biological products expired, cheaper biosimilars have entered the market. Available data coming from real-world cohorts and clinical trials indicate that the efficacy and safety of biosimilars is comparable to that of the originator drugs. Treating IBD patients with a biosimilar may be complicated by the risk of the nocebo effect, a negative effect of a pharmacological or non-pharmacological treatment, induced by patients's expectations and unrelated to the physiological action of the treatment. The nocebo effect can negatively affect treatment outcomes and hamper the cost-savings of biosimilars. Reducing the nocebo effect requires a multidisciplinary effort of all health-care providers in charge of biosimilar-treated IBD patients. The aim of the review is to reflect the key messages of an international workshop on this topic, including viewpoints from the perspective of physicians, nurses, psychologists, pharmacists and patients.

Sensitive Skin Syndrome: An Update.

Sensitive skin syndrome is a widely reported complaint but a diagnostic challenge because of its subjective symptoms and lack of clearly visible manifestations. Epidemiological studies have shown the prevalence of sensitive skin to be as high as 60-70% among women and 50-60% among men. Patients with this syndrome usually have unpleasant sensations when exposed to physical, thermal, or chemical stimuli that normally cause no provocation on healthy skin. Recent studies and newly accepted position papers have provided a more in-depth understanding and consensus of its underlying pathophysiology, associations, diagnosis, and treatment. Since no clinical studies have been conducted about specific treatment protocols, patients with this condition should be provided with personalized skin management. Given this updated knowledge, our review offers an approach to sensitive skin syndrome, with differential diagnoses, and interventions targeting its pathophysiology.

The nocebo effect as a source of bias in the assessment of treatment effects.

The term nocebo effect refers to the harmful outcomes that result from people's negative beliefs, anticipations, or experiences related to the treatment rather than the pharmacological properties of the treatment. These outcomes may include a worsening of symptoms, a lack of expected improvement, or adverse events, and they may occur after the active treatment and the placebo that is supposed to imitate it.  The nocebo effect is always unwanted and may distort estimates of treatment effectiveness and safety; moreover, it may cause discontinuation of therapy or withdrawal from a trial. The nocebo effect may be unintentionally evoked by the explanations given by healthcare professionals during a clinical consultation or consent procedures, or by information from other patients, the media, or the Internet. Moreover, it may be a consequence of previous bad experiences with the treatment, through learning and conditioning, and the conditioning may happen without patients' conscious awareness. In trial settings, a study design, for example lack of blinding, may introduce bias from the nocebo effect. Unlike the placebo effect, which is usually taken into consideration while interpreting treatment outcomes and controlled for in clinical trials, the nocebo effect is under-recognised by clinical researchers and clinicians. This is worrying, because the nocebo phenomenon is common and may have potentially negative consequences for the results of clinical treatment and trials. It is therefore important that doctors and medical researchers consider any potential nocebo effect while assessing the treatment effect and try to minimise it through careful choice and phrasing of treatment-related information given to patients.

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

INTRODUCTION: 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.

Is there a nocebo response that results from disease awareness campaigns and advertising in Australia, and can this effect be mitigated?

Direct-to-consumer advertising is banned in Australia, and instead pharmaceutical companies use disease awareness campaigns as a strategy to raise public awareness of conditions for which the company produces a treatment. This practice has been justified by promoting individual autonomy and public health, but it has attracted criticism regarding medicalisation of normal health and ageing, and exaggeration of the severity of the condition in question, imbalanced reporting of risks and benefits, and damaging the patient-clinician relationship. While there are benefits of disease awareness promotion, there is another possible adverse consequence that has not yet been rigorously considered: the possibility of inducing a nocebo response via the campaign. We will discuss the creation of a nocebo response in this context.

Interactions between brain and spinal cord mediate value effects in nocebo hyperalgesia.

Value information about a drug, such as the price tag, can strongly affect its therapeutic effect. We discovered that value information influences adverse treatment outcomes in humans even in the absence of an active substance. Labeling an inert treatment as expensive medication led to stronger nocebo hyperalgesia than labeling it as cheap medication. This effect was mediated by neural interactions between cortex, brainstem, and spinal cord. In particular, activity in the prefrontal cortex mediated the effect of value on nocebo hyperalgesia. Value furthermore modulated coupling between prefrontal areas, brainstem, and spinal cord, which might represent a flexible mechanism through which higher-cognitive representations, such as value, can modulate early pain processing.

Nocebo and the potential harm of 'high risk' labelling: a scoping review.

AIMS: A discussion of the existence, prevalence and characteristics of the nocebo effect in health care. BACKGROUND: There is increasing but inconsistent evidence for nocebo effects (the opposite of placebo). Causal mechanisms are believed to be similar to placebo (negative effects result from suggestions of negative clinical outcomes). Risk screening in health care may produce this unintended effect through labelling some patients as high risk. Given health care's almost universal coverage this potentially affects many people. DESIGN: Discussion paper following a scoping review of the existence and frequency of nocebo. DATA SOURCES: Literature databases (PsycINFO, MEDLINE, CCTR, CINAHL and EMBASE) searched from inception dates to 2013. IMPLICATIONS FOR NURSING: Significant empirical evidence indicates that negative beliefs may impact on health outcomes (incidence estimates range from 3-27%). The nocebo effect, rooted in the complex interplay between physiological functioning and social factors, appears significantly more common among women and where prior negative knowledge or expectations exist. Pre-existing psychological characteristics (anxiety, neuroses, panic disorder or pessimism) exacerbate it. CONCLUSION: While the placebo effect is well documented, there has been no systematic attempt to synthesize primary empirical research on the role of nocebo. It is possible that nocebo outcomes may be preventable through careful consideration of information provision and the prior identification of potentially high risk individuals. This paper summarizes the scale and importance of the nocebo effect, its distribution according to a range of social and clinical variables and its known relation to psychological precursors. It identifies important gaps in the research literature.