Implementation Of Biosimilars Research Articles

Increasing Access to Effective Systemic Treatments in Patients with Moderate-to-Severe Psoriasis: Narrative Review.

Psoriasis is a chronic, immune-mediated inflammatory disease with a worldwide prevalence ranging between 0.51 and 11.43%. It results in a large clinical and social burden, with patients frequently suffering from reduced quality of life, psychologic distress and debilitating comorbidities. Biologic agents are used to establish and maintain disease control in patients with moderate-to-severe psoriasis and are essential to improving quality of life. However, a substantial proportion of patients have limited access to therapy due to economics, health policies and clinical considerations, which creates clinical unmet needs that disadvantage both patients and healthcare professionals. Biosimilars are a cost-effective alternative to off-patent biologic therapies, and there is mounting evidence to suggest they offer a valuable pharmacoeconomic strategy to lower healthcare costs in patients with psoriasis. Furthermore, the introduction of biosimilars can increase the number of patients able to receive biologics, allowing these patients to be treated earlier in the disease course, potentially modifying the course of their disease and reducing the risk of comorbidities. In time, the emergence of additional data, particularly those related to long-term safety, efficacy in extrapolated indications and the effects of switching, should reassure physicians and help overcome the final hurdles for a wider implementation of biosimilars. This review aims to provide an overview of current treatment approaches for patients with moderate-to-severe psoriasis in the biosimilars era and explores both the current challenges and potential opportunities to improve access to high-quality, effective treatments.

Preparing for the market entry of adalimumab biosimilars in the US in 2023: A primer for specialty pharmacists.

The impact of the market entry of adalimumab biosimilars on clinical practices and specialty pharmacies is explained. A roadmap is also provided for how pharmacists can successfully navigate this landscape. Biosimilars have previously been introduced as a mechanism to help curb biologic expenditures, with biosimilars undergoing an abbreviated regulatory approval process that focuses on biosimilarity and generating product competition. Adalimumab is currently the leading product in the biologics market, generating approximately $20 to $30 billion in sales worldwide consecutively from 2019 to 2021. Many adalimumab biosimilars are slated to enter the market in 2023 and become available for patient use. However, compared to other biosimilars, adalimumab biosimilars have several unique considerations, such as interchangeability and concentration, that will impact pharmacy practices and workflows. Because pharmacists embedded in clinical practices and specialty pharmacies will be significantly involved in the processes relating to adalimumab biosimilar implementation, adoption, and use, a primer on understanding the various adalimumab biosimilar products available and considerations surrounding these products with regard to workflow and patient use is critical. Several resources are also provided to help pharmacists successfully navigate the adalimumab biosimilar landscape. The biosimilar landscape continues to evolve, and 2023 will see the launch of several adalimumab biosimilar products, which vary with regard to formulation, concentration, and interchangeability status. Pharmacists are well positioned to educate providers and patients about this landscape and help implement an efficient workflow to support adalimumab biosimilar adoption and use.

A Framework for Evaluating the Implementation of Biosimilar Drugs.

The introduction of biosimilar drugs has significant effects on health care systems, and a variety of approaches are required to support acceptance, adoption, and use of these drugs. Literature exists on the enablers of, and barriers to, biosimilar implementation, but frameworks that support the evaluation of biosimilar implementation strategies are currently lacking. To develop an evaluation framework for assessing the effects of biosimilar implementation strategies on patients, clinicians, and publicly funded drug programs. The scope of the evaluation was determined by a pan-Canadian working group through the creation of a logic model of activities and expected outcomes associated with biosimilar implementation. Each component of the logic model was considered under the RE-AIM framework, which led to a set of evaluation questions and indicators. Feedback to inform the final framework was sought from stakeholders through focus group sessions and written responses. An evaluation framework was created that articulates evaluation questions and indicators across 5 priority areas: stakeholder engagement, patient experience, patient outcomes, clinician experience, and system sustainability and affordability. Stakeholder feedback was obtained through 9 focus group sessions with a total of 87 participants. Feedback was used to refine the framework on the basis of stakeholder priorities and feasibility. Through extensive stakeholder consultation, an evaluation framework was developed to measure and monitor the effects of biosimilar implementation on the 5 identified priority areas, as well as to inform future biosimilar implementations. This framework can be used as a starting point for evaluating the implementation of biosimilars across health care systems.

Biosimilar strategic implementation at a large health system.

This article highlights one health system's response to the market influx of biosimilars with the establishment of a process for formulary review and selection of preferred agents and support for therapeutic interchanges. Through assessment of available literature, insurance payor coverage, and manufacturer-anticipated approvals of biosimilars, a strategic stance was developed to guide biosimilar order preparation, review, adoption, and implementation. The electronic medical record (EMR) is prepared for biosimilar implementation at least 6 to 12 months ahead of anticipated formulary review. The review includes assessment of a class (reference product and available biosimilars) after at least 2 biosimilars become available. Key health-system departments and clinicians are enlisted to support review of clinical, safety, and economic implications. Implementation of a preferred product relies on standard education, formulary availability, and staff awareness to address any perceived patient safety concerns and gather provider support. The standard steps developed now apply to all future biosimilar reviews, adoption plans, and ongoing monitoring. Barriers evaluated include changes in payor coverage and challenges in preparation of the EMR for future biosimilars, meeting precertification team education needs, and providing operational support for pharmacy inventory. To date, use of 5 preferred biosimilar products has led to significant cost savings to the institution, and the process has been endorsed by providers. The institution's successes can be attributed to clear communication with stakeholders and the development of a deliberate process, led by a multidisciplinary leadership team, for managing formulary, safety, and operational barriers in a thoughtful and systematic manner.

Uptake of biosimilar trastuzumab in Denmark compared with other European countries: a comparative study and discussion of factors influencing implementation and uptake of biosimilars

PurposeThe aim of this study was to describe the implementation and uptake of biosimilar trastuzumab in Denmark compared with other European countries.MethodsEuropean data for usage of trastuzumab was supplied by IQVIA™, using the MIDAS® dataset. A comparison was performed based on market share estimated in sales volume. A separate comparison was undertaken between countries with a full two-fold switch between different biosimilars. Data was collected spanning the time from first registered sales of biosimilar trastuzumab until the 1st quarter of 2020.ResultsDenmark had the fastest and most thorough uptake of biosimilar trastuzumab compared with other EU countries. After 3 months, the market share of biosimilar trastuzumab had increased to 90% while the second fastest country had a 50% market share after 3 months. Only two other countries had undergone a full second switch between biosimilars, Hungary and Norway. All of the three countries made near complete switches between biosimilars while only Denmark had reduced the use of biooriginator below 10%.ConclusionThe implementation of biosimilar trastuzumab in Denmark was rapid and achieved high overall uptake compared with other EU countries. The switch from one biosimilar to another was also achieved quickly and thoroughly. We believe that the rapid dissemination of information and involvement of all stakeholders — administrators, pharmacies, prescribers, nurses, and patients — constitute the backbone of the Danish success. A similar strategy is recommend for biosimilar implementation in other countries.

Can biosimilar products be interchangeable? Pharmaceutical perspective in the implementation of biosimilars in oncology.

To evaluate the safety in the interchangeability of biosimilar products approved for cancer treatment from a pharmaceutical perspective. A literature review was carried out using the descriptors "Biosimilar", "Oncology Therapy", "Interchangeable drugs" and "Biological Products", in the Sciencedirect, MEDLINE, and CAPLUS databases. Fifty-one articles were selected, which addressed the importance of establishing standards that prove the efficacy and safety of biosimilars with reference products, as well as the growing interest of the pharmaceutical industry in the development of biosimilars and the impact on costs and changes in the perspective of the treatment of cancer patients. As they are large and complex molecules, it is impossible to obtain identical copies of their reference products, which generates conflicts and concerns on the part of the pharmaceutical class regarding the safety in the interchangeability of these products, highlighting the importance of pharmacovigilance in this process.

Navigating uncharted waters: Developing a standardized approach for evaluating and implementing biosimilar products at a comprehensive cancer center.

The processes for formulary implementation and electronic health record (EHR) integration of biosimilar products at a comprehensive cancer center are described. Implications for research protocols are also discussed. The existing literature focuses on practical considerations for formulary addition of biosimilar products, but there is a lack of guidance on how to implement the change, particularly within the EHR. Before building the ordering tools for biosimilars, the clinical and informatics teams should determine the role of biosimilars at the institution, identify drug-specific product characteristics that affect medication build, and characterize implications of future formulary changes or drug shortages. Leveraging an orderable record provides the ability to include logic that maps to multiple products and also allows for future implementation of changes within the medication record rather than requiring "swaps" at the treatment protocol level. The institutional review board should coordinate changes in affected research protocols and consent forms and work with principal investigators to amend protocols when necessary. Pharmacy leaders should develop processes to oversee inventory during the transition period and minimize the risk of errors. The development of a standardized approach for evaluating and implementing biosimilar products improves efficiency and collaboration among the various team members responsible for the products' integration into existing workflows, including implications for clinical research. Implementing biosimilars for agents used to treat cancer will pose new challenges and require additional considerations. Partial implementation of biosimilars continues to pose multiple challenges in the provision of patient care.

A narrative review of biosimilars: a continued journey from the scientific evidence to practice implementation.

Biologic agents have revolutionized the management of serious health conditions in the last two decades. The use of “targeted therapy” brings not only better progression free survivals and overall survivals, but also better toxicity profiles and quality of life benefits, compared to empirical palliative chemotherapy. However, given the high cost associated with biologic drugs and the sharp increases in biologic drug utilization, this drug category has significantly raised healthcare cost over the years. A similar phenomenon was previously experienced with branded simple chemical compound drugs, including chemotherapeutic agents, which was largely mitigated by the introduction of a generic approval pathway, decreasing the costs of the drugs, making them more affordable, given to the increase in competition among the drug makers. A similar opportunity presents years later with the completion of the full patent exclusivity period of many biologics. However, the ending of patent exclusivity, although enables more market competition, does not guarantee market penetration. Stakeholders, such as patients, providers and payers, must build trust and confidence in the science of biosimilars and the product specific studies leading to FDA approval in order to incorporate these products to practice and enable the biosimilar market at large to reach the potential to significantly contribute to reductions in drug cost. Dissemination of scientific and emerging biosimilar evidence is paramount in order to support stakeholder informed decision making and enable each to benefit from expanded treatment options. This paper describes the biosimilar development, approval process, and reviews a number of challenges with the marketing implementation of biosimilars.

Trastuzumab Biosimilars in the Therapy of Breast Cancer - "Real World" Experiences from four Bavarian University Breast Centres.

Introduction With the introduction of the first trastuzumab biosimilar in the summer of 2018, biosimilar antibodies for breast cancer have found their way into the area of gynaecological oncology. The switch of anti-human epidermal growth factor receptor 2 (HER2) therapy from the reference drug Herceptin ® to a biosimilar has presented challenges to the clinics. In addition to structural and organisational measures, training of employees as well as patient briefing and acceptance were major challenges. The study presented here records – within the context of quality assurance – how the switch to a trastuzumab biosimilar was implemented at four Bavarian university clinics in the Purchasing Association of Bavarian University Pharmacies. Materials/Methods Questionnaires on treatment figures and the switching process were sent to breast centres and pharmacies of four Bavarian university clinics between July and December 2019. The neoadjuvant, adjuvant and metastasised anti-HER2 therapy with trastuzumab with or without pertuzumab was recorded, evaluated and summarised. Results In the anti-HER2-therapy, trastuzumab was used intravenously (i. v.) and subcutaneously. Between July and December 2018, all four clinics in the Purchasing Association switched the i. v. trastuzumab therapy from the reference drug (Herceptin) to a biosimilar (for 2018: Kanjinti ® ). Over 200 patients were treated with trastuzumab i. v. in each of the two half-years of 2018 (before and after the switch). The spectrum of side effects and pCR rates under therapy with the biosimilar were comparable to the experiences made with the reference drug. Three out of four clinics provided training to employees and informed patients by means of a defined information leaflet. Patient acceptance was high. Summary The anti-HER2 therapy could be switched successfully and safely to trastuzumab biosimilars at the Bavarian university hospitals. This may serve as guideline for the further implementation of biosimilars. The structures necessary for this initial switching process have been prepared with trastuzumab as an example.

Biosimilars in the French and Polish System: Chosen Aspects of Reimbursement and Access

The EU approved the first biosimilar drug in 2006. By 2017, the EU had authorized the highest number of biosimilars worldwide, acquiring considerable experience in their use and safety. In May 2019, the European Medicines Agency (EMA) search engine showed 54 authorized biosimilars. Biosimilars reduce public expenditure; however, the discussion about their potential disadvantages is still ongoing. Each country adopts different regulations on the interchangeability, switching, and substitution of a reference medicine by its biosimilar, since the EMA does not regulate this issue. Additionally, each nation has a unique reimbursement system, which results in significant differences in patients’ access to biosimilars. The importance of securing a higher availability of these cheaper versions of biological drugs is well-recognized. The better the access to these biosimilars is, the lower the overall drug expenditure and need for rationing would be, and therefore the better treatment results. The aim of this paper is to compare selected aspects of reimbursement and access to the EMA authorized biosimilar medicines in two countries – France and Poland. The stated drug policy goal of both countries is to significantly improve biosimilar implementation in the coming years. The research is based on an analysis of four main sources: the EMA biosimilars database, the Polish reimbursement list published by the Polish Ministry of Health, and two French reimbursement databases published by the French Ministry of Health. An additional literature review was conducted. The expected results concentrate on differences in the number of reimbursed biosimilars, the average time between EMA authorization and country reimbursement decision date, and the availability of biosimilars registered outside of the centralized (EMA) procedure. These findings could identify areas of improvement and help with discussions on how to optimize the reach of biosimilars, as well as improve French-Polish collaboration on this matter.

The Efficacy, Safety, and Immunogenicity of Switching Between Reference Biopharmaceuticals and Biosimilars: A Systematic Review.

To date, no consensus exists among stakeholders about switching patients between reference biological products (RPs) and biosimilars, which may have been curbing the implementation of biosimilars in clinical practice. This study synthesizes the available data on switching and assesses whether switching patients from a RP to its biosimilar or vice versa affects efficacy, safety, or immunogenicity outcomes. A total of 178 studies, in which switch outcomes from a RP to a biosimilar were reported, was identified. Data were derived from both randomized controlled trials and real‐world evidence. Despite the limitations stemming from a lack of a robust design for most of the studies, the available switching data do not indicate that switching from a RP to a biosimilar is associated with any major efficacy, safety, or immunogenicity issues. Some open‐label and observational studies reported increased discontinuation rates after switching, which were mainly attributed to nocebo effects. Involvement of the prescriber in any decision to switch should remain and attention should be paid to the mitigation of a potential nocebo effect.

Proceedings of the biosimilars workshop at the International Symposium on Oncology Pharmacy Practice 2019.

The International Society of Oncology Pharmacy Practitioners organized a workshop to create learning opportunities on biosimilars in pharmacy practice on 10 October 2019. The topics that were covered included (i) the development and testing of biosimilars, (ii) the challenges of bringing biosimilars to market, and (iii) real-world data on patient safety and perceptions during biosimilar implementation. The development of biosimilars can take up to eight years and the extensiveness of the process depends on several factors, such as the complexity of the production process and regulatory requirements. Compared to generic products of small-molecule drugs, there is a higher barrier to market entry for biosimilars, explaining the small number of biosimilars in the market. Appraisal of biosimilars for inclusion in hospital formularies is also different from the review process of originator biologics, where the former is usually institution-led and has fewer restrictions on use. When several biosimilar products are available, factors that should be considered besides cost are licensed indications, supply chain confidence, clinical data, and product attributes. Real-world data have shown that biosimilars are well-tolerated and have safety data that are comparable to that of the originator product. Oncology pharmacists from the United Kingdom, Kenya, and Canada also presented their respective experiences with biosimilar use. Different countries at varying stages of biosimilar implementation faced distinct challenges. Nevertheless, resources to assist biosimilar implementation can potentially be shared between different regions. International Society of Oncology Pharmacy Practitioners is well-positioned to foster professional cooperation at an international level to drive biosimilar implementation.

A survey of global biosimilar implementation practice conducted by the International Society of Oncology Pharmacy Practitioners.

The International Society of Oncology Pharmacy Practitioners (ISOPP) Biosimilars Task Force was charged to develop educational activities and resources to assist members when implementing biosimilar medicines into their local practice. To facilitate the process, the task force conducted a survey in order to understand biosimilar implementation practice by ISOPP members across the world and the challenges that oncology pharmacists face when adopting biosimilars into their clinical practice. A cross-sectional survey was conducted between 20 April 2019 and 27 May 2019. Members of ISOPP and a number of national oncology pharmacy groups were invited to complete the survey. The survey contained 29 items and consisted of three sections: respondents’ demographics, respondents’ institutional practice relating to biosimilar implementation and post implementation practice at the respondents’ institutions. Descriptive statistics were utilized to analyze the survey results. A total of 265 ISOPP members were surveyed, with 50 members providing a response (response rate = 19%). In addition, 40 nonmembers participated in the survey, bringing the total to 90 respondents. The most common factors that influence the decision to implement use of a biosimilar as reported by respondents are medication costs/pricing (92%), available clinical data (73%), and product availability (63%). Respondents also commented on the barriers to biosimilar implementation at their institutions, which included a reluctance of prescribers to use biosimilars (due to the lack of familiarity or perceived inferiority), a reluctance to switch established patients from an originator to a biosimilar and the preferences of insurance companies or funding bodies. The results of this survey reinforce the need for greater education and training for health care professionals in the use of biosimilars, the importance of sharing good practice, and a need for standardization.

Lessons from International Experience with Biosimilar Implementation: An Application of the Diffusion of Innovations Model.

Although biosimilars offer cost savings in Canadian healthcare, uptake is low. We discuss the literature on international experiences with biosimilar adoption in the context of the Diffusion of Innovations model. We highlight potential challenges with biosimilar implementation and gaps in research needed to inform implementation efforts. We observe a lack of systematic description of implementation design and evaluation and a paucity of in-depth and engaged research to understand stakeholders' pragmatic considerations and the knowledge, messages and meanings that shape clinician and patient decisions to choose biosimilars.

A novel approach to support implementation of biosimilars within a UK tertiary hospital.

We analysed data collected prospectively in a hospital-based registry in a large NHS tertiary referral hospital in the UK. The registry was administered by the hospital's BSG, which considered requests for patients to remain on or revert to originator products. The registry contained prospectively collected data on patients switching therapy from an originator to a biosimilar. The data included clinical circumstances or rationale for each request, whether it was granted, and the results of clinical reviews at 3-6 months. In a 12-month period, we identified 1299 patients who could switch to the respective biosimilar and, of these, 1196 (92%) did so. Of the 260 patients taking infliximab, 250 (96%) switched to infliximab biosimilar; of the 390 patients taking etanercept 50 mg, 298 (76%) switched to etanercept 50 mg biosimilar; and of the 649 patients taking rituximab, 648 (99%) switched to rituximab biosimilar. The BSG received 39 applications: 12 (out of 39) applications were to remain on the originator and 27 (out of 39) were to switch back to the originator. Of the applications to remain on the originator 10 (out of 12) were approved. At 3-6 month review, 2 of these approvals reported continued efficacy, 3 switched to the biosimilar, 3 switched to an alternative therapy and 2 stopped treatment. Two (out of 10) applications were not approved, both applicants reported efficacy with the biosimilar at follow up. Of the 27 applications to switch back to the originator, 16 (out of 27) applications were approved. At 3-6 months, 9 (out of 16) applicants reported regain of efficacy, 6 (out of 16) reported cessation of reported adverse effects and 1 (out of 16) switched to alternative therapy. Eight (out of 27) applications were not approved, and, at point of follow up, 50% reported efficacy with the biosimilar and 50% had switched to an alternative therapy. Three (out of 27) applications were withdrawn by the clinical team as efficacy was achieved with the biosimilar. We have set up a system within a busy NHS clinical practice to successfully switch patients to biosimilars, and established a mechanism to guide decisions on continuing with or reverting back to the originator. Such a system could be of use more broadly within the NHS and other health care systems.

The nocebo effect challenges the non-medical infliximab switch in practice

BackgroundIn clinical practice, non-medical switching of biological medication may provoke nocebo effects due to unexplained deterioration of therapeutic benefits. Indication extrapolation, idiosyncratic reactions, and interchangeability remain challenged in clinical practice after biosimilar approval by the European Medicines Agency. The principle of “first do no harm” may be challenged in a patient when switching from originator to biosimilar biological.AimTo describe the 1-year results of a pragmatic study on infliximab biosimilar implementation in immune-mediated inflammatory disease patients on the basis of shared decision-making under effectiveness and safety monitoring.MethodsInflammatory bowel disease and rheumatology patients on infliximab originator were converted to infliximab biosimilar after providing informed consent. Nocebo response patients were monitored after switch back to originator. Linear mixed models were used to analyze continuous endpoints on effectiveness and laboratory outcomes to determine significance (P ≤ 0.05) of change over time after switching.ResultsAfter inviting 146 patients, a group of 125 patients enrolled in the project over time, respectively, 73 Crohn’s disease, 28 ulcerative colitis, nine rheumatoid arthritis, ten psoriatic arthritis, and five ankylosing spondylitis patients. No statistically significant changes in effectiveness and safety were observed in any of the indications after a median of 4 infusions in 9 months of study. An overall nocebo response of 12.8% was found among the patients during a minimal observation period of 6 months after the transition to biosimilar infliximab. The overall nocebo response rate did not differ between the studied indications.ConclusionsIn inflammatory bowel disease and rheumatological patients, similar effectiveness and safety were demonstrated on the transition into infliximab biosimilar. In our series, patient empowerment and registration of treatment outcomes delineated biosimilar transition, an approach that hypothetically could reduce nocebo response rates which are relevant to account for regarding biosimilar implementation.

Rheumatologists' Perceptions of Biosimilar Medicines Prescription: Findings from a French Web-Based Survey.

Healthcare cost savings are closely linked to prescribers' confidence in and acceptance of the prescription of biosimilar drugs. The aim of this study was to assess the knowledge, experience and opinions of hospital-based and office-based French rheumatologists with regard to biosimilar medicines and to identify the barriers to and possible options to promote their prescription. A web-based, self-administered survey was conducted among French rheumatologists from June 8 to August 2, 2015. A total of 116 rheumatologists responded to the survey. Many reported having little knowledge and a lack of available information about biosimilar drugs, especially office-based rheumatologists. 98.3% of the respondents had at least one question about biosimilars, and seven in ten raised issues regarding substitution, iatrogenic effects or cost savings that might be achievable. Only eight rheumatologists had already prescribed a biosimilar drug. The most common barriers reported were indication extrapolation and a lack of data about tolerability. Nine out of ten physicians thought that starting a treatment with a biosimilar drug in biologic treatment-naïve patients was possible. The rheumatologists' opinions were rather favorable towards the implementation of biosimilars, but a majority expressed a negative opinion about substitution by the pharmacist. Our survey gave a better appreciation of the concerns associated with biosimilar prescriptions. Targeted communication initiatives, deeper experience and availability of new clinical data may help to address the outstanding questions and should overcome the misunderstandings surrounding biosimilar drugs among rheumatologists.