Treatment Outcomes with Biosimilars: Be Aware of the Nocebo Effect

AbstractOver the years, biologic agents have proven their importance in the management of chronic autoimmune diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Biosimilars, which are biologic medicines, are highly similar to approved biologic medicines, and are comprehensively developed and rigorously tested to ensure efficacy and safety are similar to the reference product. A broader armamentarium of biosimilars is expected to improve patients’ access to safe and effective biologic medicines, thus offering benefits to healthcare systems around the globe. Here we consider the factors that may compromise the benefits of biosimilars being realized, including patient and physician perception of biosimilars, and an often overlooked factor, the nocebo effect, which is re-emerging with the widespread adoption of biosimilar medicines. We have also described a variety of strategies and recommendations that could help limit the nocebo effect. Funding: Biogen.

• Publication year

  2017

• Venue

  Rheumatology and Therapy

• Publication date

  2017-10-14

• Fields of study

  Medicine

• Identifiers
  DOI 10.1007/s40744-017-0085-zPMID 29032452PMCID 5696297
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase

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  2017cited by this paper
• Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4

  2017cited by this paper
• Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase.

  2017cited by this paper
• FRI0211 A descriptive analysis of real-world treatment patterns of innovator infliximab (REMICADE) and biosimilar infliximab in a treatment naÏve turkish rheumatologic disease population

  2017cited by this paper
• FRI0200 Higher acceptance and persistence rates after biosimilar transitioning in patients with a rheumatic disease after employing an enhanced communication strategy

  2017cited by this paper
• SAT0175 A descriptive analysis of real-world treatment patterns in a turkish rheumatology population that continued innovator infliximab (REMICADE) therapy or switched to biosimilar infliximab

  2017cited by this paper
• 225. SWITCHING TO BIOSIMILAR ETANERCEPT IN CLINICAL PRACTICE

  2017cited by this paper
• SAT0173 Switching from reference product etanercept to the biosimilar sb4 in a real-life setting: follow-up of 147 patients

  2017cited by this paper
• AB0377 Switching from bio-original etanercept to biosimilar etanercept sb4: patient acceptability and outcomes in the real world

  2017cited by this paper
• Update on biosimilars in rheumatology

  2017cited by this paper
• 210. SWITCHING TO BIOSIMILARS: AN EARLY CLINICAL REVIEW

  2017cited by this paper
• Switching Patients from Originator to Biosimilar Medications in Rheumatoid Arthritis: Limiting The ‘Nocebo’ Effect

  2017cited by this paper
• A nationwide non-medical switch from originator infliximab to biosimilar CT-P13 in 802 patients with inflammatory arthritis: 1-year clinical outcomes from the DANBIO registry

  2017cited by this paper
• The Placebo and Nocebo Phenomena: Their Clinical Management and Impact on Treatment Outcomes.

  2017cited by this paper
• Comparing the immunogenicity of the etanercept biosimilar SB4 with the innovator etanercept: another consideration

  2016cited by this paper
• The changing landscape of biosimilars in rheumatology

  2016cited by this paper
• Twelve‐Year Retention Rate of First‐Line Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: Real‐Life Data From a Local Registry

  2016cited by this paper
• A randomized phase l pharmacokinetic study comparing SB4 and etanercept reference product (Enbrel®) in healthy subjects

  2016cited by this paper
• Awareness, Knowledge, and Perceptions of Biosimilars Among Specialty Physicians

  2016cited by this paper
• Patient attitudes and understanding about biosimilars: an international cross-sectional survey

  2016influential reference
• THU0150 Long-Term Safety and Efficacy of SB4 (Etanercept Biosimilar) in Patients with Rheumatoid Arthritis: Comparison between Continuing SB4 and Switching from Etanercept Reference Product To SB4

  2016cited by this paper
• The nocebo effect of drugs

  2016cited by this paper
• Evaluation of the structural, physicochemical, and biological characteristics of SB4, a biosimilar of etanercept

  2016cited by this paper
• A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy

  2015cited by this paper
• Cross-immunogenicity: antibodies to infliximab in Remicade-treated patients with IBD similarly recognise the biosimilar Remsima

  2015cited by this paper
• Clinical effectiveness of CT-P13 (Infliximab biosimilar) used as a switch from Remicade (infliximab) in patients with established rheumatic disease. Report of clinical experience based on prospective observational data

  2015cited by this paper
• Patient-centred care in established rheumatoid arthritis.

  2015cited by this paper
• The nocebo effect: patient expectations and medication side effects

  2013cited by this paper
• The nocebo effect: A clinicians guide

  2013cited by this paper
• Motivational Interviewing: moving from why to how with autonomy support

  2012cited by this paper
• Placebo and nocebo responses in randomised controlled trials of drugs applying for approval for fibromyalgia syndrome treatment: systematic review and meta-analysis.

  2012cited by this paper
• To Tell the Truth, the Whole Truth, May Do Patients Harm: The Problem of the Nocebo Effect for Informed Consent

  2012cited by this paper
• A meta-analytic approach to estimating nocebo effects in neuropathic pain trials

  2012cited by this paper
• Nocebo phenomena in medicine: their relevance in everyday clinical practice.

  2012cited by this paper
• How expectations shape pain.

  2012cited by this paper
• Nocebo effects, patient-clinician communication, and therapeutic outcomes.

  2012cited by this paper
• The Effect of Treatment Expectation on Drug Efficacy: Imaging the Analgesic Benefit of the Opioid Remifentanil

  2011cited by this paper
• Supplementary Materials for The Effect of Treatment Expectation on Drug Efficacy: Imaging the Analgesic Benefit of the Opioid Remifentanil

  2011cited by this paper
• Nocebo is the enemy, not placebo. A meta-analysis of reported side effects after placebo treatment in headaches

  2011cited by this paper
• Insular Cortex Activity Is Associated with Effects of Negative Expectation on Nociceptive Long-Term Habituation

  2010cited by this paper
• The nocebo effect: a reason for patients' non-adherence to generic substitution?

  2010cited by this paper
• Gender and the nocebo response following conditioning and expectancy.

  2009cited by this paper
• Beliefs about medications: a questionnaire survey of people with rheumatoid arthritis.

  2005cited by this paper
• Nonspecific medication side effects and the nocebo phenomenon.

  2002influential reference
• Nocebos contribute to host of ills.

  1996cited by this paper
• Influence of the behaviour pattern on the nocebo response of healthy volunteers.

  1995cited by this paper

• Position statement of the Biotechnology Committee of the Brazilian Society of Rheumatology on the interchangeability of originator and biosimilar biologics in immune-mediated rheumatic diseases

  2026cites this paper
• Temporal Trends in the Prescription of Biosimilars and the Status of Switching from Original Biologics to Biosimilars at Individual and Institutional Levels in Japan

  2025cites this paper
• Accelerating Earlier Access to Anti-TNF-α Agents with Biosimilar Medicines in the Management of Inflammatory Bowel Disease

  2025influential citation
• What do the guidelines say about use of biosimilar insulin therapy? Simple practical considerations to guide clinicians in different patient subgroups—Sharing Canadian perspectives

  2025cites this paper
• Biosimilars in pediatric rheumatology: innovations, challenges, and opportunities

  2025cites this paper
• Counting the costs: a nationwide study on healthcare use following an adalimumab biosimilar switch in >1300 inflammatory arthritis patients

  2024cites this paper
• Identifying the psychological effects of nocebo education: results from two pre-registered experiments

  2024cites this paper
• The Nocebo Effect: A Bias in Clinical Practice—An Ethical Approach

  2024influential citation
• A randomised, crossover trial exploring the patient perspective and effectiveness of biosimilar adalimumab transition: IBD reference and biosimilar adalimumab cross over study (iBaSS)

  2024cites this paper
• An Overview of Biosimilars—Development, Quality, Regulatory Issues, and Management in Healthcare

  2024cites this paper
• Knowledge and Attitudes of Patients with Rheumatoid Diseases towards Biosimilars

  2024cites this paper
• An Educational Digital Tool to Improve the Implementation of Switching to a Biosimilar (Rapid Switch Trainer): Tool Development and Validation Study

  2024cites this paper
• Mitigating the Nocebo Effect in Biosimilar Use and Switching: A Systematic Review

  2024cites this paper
• The Nocebo Effect

  2023cites this paper
• Clinical Outcomes and Patient Experience of Biosimilar to Biosimilar Infliximab Switching in Patients with Inflammatory Bowel Disease: A Prospective, Single-Centre, Phase IV Interventional Study with a Nested Qualitative Study

  2023cites this paper
• The use of biosimilar insulins in 2023

  2023cites this paper
• Administrative Databases and Diagnostic Therapeutic and Assistance Paths -PDTA- in the Monitoring Treatment of Rheumatoid Arthritis: The Experience of ATS Pavia

  2023cites this paper
• Biosimilars in Pediatric IBD: Updated Considerations for Disease Management

  2022cites this paper
• Knowledge, Attitudes and Practice of Healthcare Providers, Healthcare Regulatory Practitioners and Patients Toward Biosimilars in China: Insights From a Nationwide Survey

  2022cites this paper
• Exploring the Reasons Behind the Substantial Discontinuation Rate Among Patients Taking CT-P13 in a Large Tertiary Hospital in Western Switzerland: A Retrospective Cohort Study Using Routinely Collected Medical Data

  2022cites this paper
• A review of biosimilars for rheumatoid arthritis.

  2022cites this paper
• The Sincerest Form of Flattery? Biosimilars in Inflammatory Bowel Disease.

  2022cites this paper
• Moving forward: Implementing health psychology research to improve patient acceptance of biosimilars.

  2022cites this paper
• An Introduction to Biosimilars for the Treatment of Retinal Diseases: A Narrative Review

  2022cites this paper
• Using family-centered communication to optimize patient-provider-companion encounters about changing to biosimilars: A randomized controlled trial.

  2022cites this paper
• Patient perspectives of successful adalimumab biosimilar transitioning in Crohn’s disease: an interview study

  2022cites this paper
• BTT_A_367032 57..66

  2022cites this paper
• Impact of switching to infliximab biosimilars on treatment patterns among US veterans receiving innovator infliximab

  2022cites this paper
• A Systematic Review on Infliximab Biosimilar SB2: From Pre-Clinical Data to Real-World Evidence

  2021cites this paper
• Systematic review and meta-analysis of biosimilar for the treatment of rheumatoid arthritis informing the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

  2021cites this paper
• Switching and Discontinuation Patterns Among Patients Stable on Originator Infliximab Who Switched to an Infliximab Biosimilar or Remained on Originator Infliximab

  2021cites this paper
• Maintaining Clinical Freedom Whilst Achieving Value in Biologics Prescribing: An Integrated Cross-Specialty Consensus of UK Dermatologists, Rheumatologists and Gastroenterologists

  2021cites this paper
• The impact of biosimilar insulins on the diabetes landscape.

  2021cites this paper
• Effects of Patients’ Expectation in Dermatology: Evidence from Experimental and Clinical Placebo Studies and Implications for Dermatologic Practice and Research

  2021cites this paper
• Biosimilars in Inflammatory Bowel Diseases: General Concepts and Clinical Implications

  2021cites this paper
• Informing Patients about Biosimilar Medicines: The Role of European Patient Associations

  2021cites this paper
• A bio-what? Medical companions’ perceptions towards biosimilars and information needs in rheumatology

  2021cites this paper
• The Psychological Risks Associated With the Non-medical Switch From Biologics to Biosimilars

  2021cites this paper
• Monitoring the transition of patients on biologics in rheumatoid arthritis: Consensus guidance for pharmacists

  2021cites this paper
• Increasing and dampening the nocebo response following medicine-taking: A randomised controlled trial.

  2021cites this paper
• Efficacy and Safety of Etanercept Biosimilars Compared With the Originator for Treatment of Juvenile Arthritis: A Prospective Observational Study

  2021cites this paper
• The mode of delivery and content of communication strategies used in mandatory and non-mandatory biosimilar transitions: a systematic review with meta-analysis

  2021cites this paper
• Biosimilars in chronic inflammatory diseases: facts and remaining questions 5 years after their introduction in Europe

  2021cites this paper
• Optimizing Use of Biologic Medicines Using a Quality Use of Medicines Approach

  2020cites this paper
• Effects of Message Framing on Patients’ Perceptions and Willingness to Change to a Biosimilar in a Hypothetical Drug Switch

  2020cites this paper
• Biologika und Biosimilars

  2020cites this paper
• The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases

  2020cites this paper
• Patterns of Tumor Necrosis Factor Inhibitor (TNFi) Biosimilar Use Across United States Rheumatology Practices

  2020cites this paper
• Disease modifying drugs for rheumatological diseases: a brief history of everything.

  2020cites this paper
• Patients’ beliefs and behaviours are associated with perceptions of safety and concerns in a hypothetical biosimilar switch

  2020cites this paper
• Biosimilars in pediatric rheumatology and their introduction into routine care.

  2020cites this paper
• Clinical Practice of Adalimumab and Infliximab Biosimilar Treatment in Adult Patients With Crohn’s Disease

  2020cites this paper
• New Treatments in Rheumatology: Biosimilars

  2020cites this paper
• Real-world observational study of biosimilars in inflammatory arthritis treatment: a systematic literature review

  2020cites this paper
• Nocebo effect and biosimilars in inflammatory bowel diseases: what’s new and what’s next?

  2020cites this paper
• BIOSIMILAR THE NEW ERA OF THERAPTIC SCIENCE

  2020cites this paper
• Switching to Biosimilar SDZ-ADL in Patients with Moderate-to-Severe Active Rheumatoid Arthritis: 48-Week Efficacy, Safety and Immunogenicity Results From the Phase III, Randomized, Double-Blind ADMYRA Study

  2020cites this paper
• When symptoms become side effects: Development of the side effect attribution scale (SEAS).

  2020cites this paper
• Biosimilarity and Interchangeability of Biologic Drugs‐General Principles, Biophysical Tests, and Clinical Requirements to Demonstrate Biosimilarity

  2020cites this paper
• Information et perception des patients au sujet des biosimilaires en rhumatologie

  2019cites this paper
• Nocebo in Biosimilars and Generics in Neurology: A Systematic Review

  2019cites this paper
• Anti-TNF biosimilars in Crohn’s Disease: a patient-centric interdisciplinary approach

  2019cites this paper
• No Reason to Feel Sick? Nocebo Responses in the Placebo Arms of Experimental Endotoxemia Studies

  2019cites this paper
• Real-Life Tolerability and Effectiveness of Adalimumab Biosimilar in Rheumatoid Arthritis: ASPIRE Registry Data

  2019cites this paper
• It is not just the drugs that matter: the nocebo effect

  2019cites this paper
• Era of biosimilars in rheumatology: reshaping the healthcare environment

  2019cites this paper
• Biosimilar medicines: Impact, opportunities and strategies. Twelve years of experience in Europe

  2019cites this paper
• Switching to biosimilars: current perspectives in immune-mediated inflammatory diseases

  2019cites this paper
• Effectiveness of etanercept biosimilar SB4 in maintaining low disease activity in patients with psoriatic arthritis switched from etanercept originator: an open-label one year study

  2019cites this paper
• Systemic rheumatic diseases: From biological agents to small molecules.

  2019cites this paper
• Consensus report: clinical recommendations for the prevention and management of the nocebo effect in biosimilar‐treated IBD patients

  2019cites this paper
• Biosimilars for inflammatory bowel disease: how can healthcare professionals help address patients’ concerns?

  2019cites this paper
• Biosimilar medicines: impact, opportunities and strategies. Twelve years of experience in Europe.

  2019cites this paper
• Patients' information and perspectives on biosimilars in rheumatology: A French nation-wide survey.

  2019cites this paper
• The IBD Pathway: From a Patient Perspective

  2019cites this paper
• Drug Discontinuation in Studies Including a Switch From an Originator to a Biosimilar Monoclonal Antibody: A Systematic Literature Review.

  2019cites this paper
• Optimising Patient Management in Rheumatoid Arthritis: Can We Live Up to Patient Expectations?

  2019cites this paper
• [Biosimilars in France, to understand the stakes in order to use them well].

  2019cites this paper
• Biological and synthetic target DMARDs in psoriatic arthritis.

  2019cites this paper
• Biosimilars in the management of chronic inflammatory diseases: The Dutch experience

  2019cites this paper
• Optimising Patient Management in Rheumatoid Arthritis: Can We Live Up to Patient Expectations?

  2019cites this paper
• Acceptance rate and sociological factors involved in the switch from originator to biosimilar etanercept (SB4).

  2019cites this paper
• The Clinical Implications of Nocebo Effects for Biosimilar Therapy

  2019cites this paper
• A brief overview of biosimilars and factors limiting their uptake

  2019cites this paper
• [Interchangeability of biological products in the Brazilian Unified National Health System (SUS): the main regulatory challenges].

  2019cites this paper
• Patient satisfaction survey: substitution of reference etanercept with a biosimilar product

  2019cites this paper
• The Breakthrough of Biosimilars: A Twist in the Narrative of Biological Therapy

  2019cites this paper
• Does a mandatory non-medical switch from originator to biosimilar etanercept lead to increase in healthcare use and costs? A Danish register-based study of patients with inflammatory arthritis

  2019cites this paper
• Real-World Evidence on Etanercept Biosimilar SB4 in Etanercept-Naïve or Switching Patients: A Systematic Review

  2019cites this paper
• Nurses are Critical in Aiding Patients Transitioning to Biosimilars in Inflammatory Bowel Disease: Education and Communication Strategies

  2018cites this paper
• Mental health, fatigue and function are associated with increased risk of disease flare following TNF inhibitor tapering in patients with rheumatoid arthritis: an exploratory analysis of data from the Optimizing TNF Tapering in RA (OPTTIRA) trial

  2018cites this paper
• Biosimilars and patient care

  2018cites this paper
• Biosimilars und Patientenversorgung

  2018cites this paper
• Talking to patients about biosimilars.

  2018cites this paper
• Les biosimilaires en rhumatologie : de la prescription à l’acceptation

  2018cites this paper
• Non-pharmacological Effects in Switching Medication: The Nocebo Effect in Switching from Originator to Biosimilar Agent

  2018cites this paper
• The Biosimilar Nocebo Effect? A Systematic Review of Double-Blinded Versus Open-Label Studies

  2018cites this paper
• Response to: ‘Switching from the bio-originators to biosimilar: is it premature to recommend this procedure?’ by Cantini and Benucci

  2018cites this paper
• Biosimilars: An opportunity. Position statement of the French Rheumatology Society (SFR) and Inflammatory Rheumatic Disease Club (CRI).

  2018cites this paper
• Regulation of biosimilar medicines and current perspectives on interchangeability and policy

  2018cites this paper