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Biosimilars is FDA approved for the treatment of rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis (JIA), psoriatic arthritis (PA), ankylosing spondylitis (AS), plaque psoriasis (PsO), inflammatory bowel disease (IBD): adult Crohn disease (CD), ulcerative colitis (UC), granulomatosis with polyangiitis (GPA) (Wegener granulomatosis), microscopic polyangiitis (MPA), type 1 diabetes mellitus (DM), non-squamous non-small cell lung cancer, metastatic colorectal cancer, metastatic renal cell carcinoma, glioblastoma, recurrent or metastatic cervical cancer, HER2 (human epidermal growth factor receptor 2) associated breast cancer, and HER2 associated gastric (metastatic) or gastroesophageal junction adenocarcinoma, chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL). Biosimilars are biotherapeutic agents similar to their respective original biologic product (reference product). This activity will highlight the mechanism of action, adverse event profile, and other key factors pertinent to interprofessional team members in managing patients with inflammatory diseases and the use of biosimilars. Objectives: Identify the mechanism of action of all biosimilars. Identify the indications for the use of biosimilars. Identify the issues of concern that exist for biosimilars. Summarize interprofessional team strategies for improving care coordination and communication to advance biosimilars use in treating patients with inflammatory diseases and improve outcomes. Access free multiple choice questions on this topic.

Biosimilars are biological agents that are highly analogous to their reference products currently approved and licensed by the U.S. Food and Drug Administration (FDA). Biosimilars possess no differences in their safety, purity, potency, or effectiveness compared to their respective reference biologic agents. The abbreviated licensure pathway 351(k) for biosimilars or agents interchangeable with FDA-approved biological agents (reference product) was formed by Congress by The Biologics Price Competition and Innovation Act (BPCI Act) of 2009.[1] Biosimilars aim to increase the number of biologics available at more inexpensive costs when compared to their reference products, further increasing patient access to more treatment options.[2] Similar to biologics or reference products, biosimilars are expected to meet the FDA's meticulous approval criteria, ensuring the reliability of the agent's safety, efficacy, quality, and effectiveness.[3] The FDA approval process for biosimilars is based on data proving its prominent similarity and correlation to an already FDA-approved biologic agent (reference product) and its indications for use. No clinically meaningful differences among the biosimilar and its respective reference agent should exist.[3] Differences exist in the regulatory provisions for the original biologic agent (reference product) and a biosimilar as the biosimilars obtain approval from FDA by their abbreviated approval pathway.[4] Biosimilars seeking FDA approval must include data assessments demonstrating the agent's similarity to a reference product acquired from analytical investigations, animal studies, and clinical studies. Added data and analyses of the biosimilars immunogenicity, pharmacokinetics, pharmacodynamics, and data discussing the indication(s) the reference product is licensed and approved for use are also included.[5]

Similar to biologics or reference products, biosimilars are expected to meet the FDA's meticulous approval criteria, ensuring the reliability of the agent's safety, efficacy, quality, and effectiveness.[3] The FDA approval process for biosimilars is based on data proving its prominent similarity and correlation to an already FDA-approved biologic agent (reference product) and its indications for use. No clinically meaningful differences among the biosimilar and its respective reference agent should exist.[3] Differences exist in the regulatory provisions for the original biologic agent (reference product) and a biosimilar as the biosimilars obtain approval from FDA by their abbreviated approval pathway.[4] Biosimilars seeking FDA approval must include data assessments demonstrating the agent's similarity to a reference product acquired from analytical investigations, animal studies, and clinical studies. Added data and analyses of the biosimilars immunogenicity, pharmacokinetics, pharmacodynamics, and data discussing the indication(s) the reference product is licensed and approved for use are also included.[5] To date, ten biological agents: bevacizumab, etanercept, epoetin-alfa, trastuzumab, adalimumab, pegfilgrastim, filgrastim, infliximab, rituximab, and insulin glargine, have been used as reference products for the approval of 30 biosimilar agents. Biosimilars can be used in the management of various inflammatory and autoimmune diseases. Ailments such as rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis (JIA), psoriatic arthritis (PA), ankylosing spondylitis (AS), plaque psoriasis (PsO), inflammatory bowel disease (IBD): adult Crohn disease (CD), ulcerative colitis (UC), granulomatosis with polyangiitis (GPA) (Wegener granulomatosis), microscopic polyangiitis (MPA), and type 1 diabetes mellitus (DM). Filgrastim-sndz, a biosimilar of the reference product "filgrastim," was the first-ever biosimilar to receive FDA approval in March 2015 and is characterized as a leukocyte growth factor indicated to reduce infections caused by febrile neutropenia in the neutropenic and immunosuppressed subjects.

To date, ten biological agents: bevacizumab, etanercept, epoetin-alfa, trastuzumab, adalimumab, pegfilgrastim, filgrastim, infliximab, rituximab, and insulin glargine, have been used as reference products for the approval of 30 biosimilar agents. Biosimilars can be used in the management of various inflammatory and autoimmune diseases. Ailments such as rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis (JIA), psoriatic arthritis (PA), ankylosing spondylitis (AS), plaque psoriasis (PsO), inflammatory bowel disease (IBD): adult Crohn disease (CD), ulcerative colitis (UC), granulomatosis with polyangiitis (GPA) (Wegener granulomatosis), microscopic polyangiitis (MPA), and type 1 diabetes mellitus (DM). Filgrastim-sndz, a biosimilar of the reference product "filgrastim," was the first-ever biosimilar to receive FDA approval in March 2015 and is characterized as a leukocyte growth factor indicated to reduce infections caused by febrile neutropenia in the neutropenic and immunosuppressed subjects. Other indications of biosimilars alongside inflammatory diseases include management for specific malignancies and secondary causes of anemia. In September 2017, bevacizumab-awwb was the first biosimilar that was granted FDA approval for certain cancers. A few months later, in December 2017, biosimilar trastuzumab-dkst was also granted FDA approval for specific malignancies. Cancers indicative of biosimilar therapy include non-squamous non-small cell lung cancer, metastatic colorectal cancer, metastatic renal cell carcinoma, glioblastoma, recurrent or metastatic cervical cancer, HER2 (human epidermal growth factor receptor 2) associated breast cancer, and HER2 associated gastric (metastatic) or gastroesophageal junction adenocarcinoma, chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL). To date, new biosimilars are currently still being FDA approved, with the latest approval coming on July 28, 2021, for biosimilar agent insulin glargine-yfgn, a long-acting insulin agent indicated for pediatric type 1 diabetes mellitus (DM) and adult patients with DM type 1 and DM type 2.

Other indications of biosimilars alongside inflammatory diseases include management for specific malignancies and secondary causes of anemia. In September 2017, bevacizumab-awwb was the first biosimilar that was granted FDA approval for certain cancers. A few months later, in December 2017, biosimilar trastuzumab-dkst was also granted FDA approval for specific malignancies. Cancers indicative of biosimilar therapy include non-squamous non-small cell lung cancer, metastatic colorectal cancer, metastatic renal cell carcinoma, glioblastoma, recurrent or metastatic cervical cancer, HER2 (human epidermal growth factor receptor 2) associated breast cancer, and HER2 associated gastric (metastatic) or gastroesophageal junction adenocarcinoma, chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL). To date, new biosimilars are currently still being FDA approved, with the latest approval coming on July 28, 2021, for biosimilar agent insulin glargine-yfgn, a long-acting insulin agent indicated for pediatric type 1 diabetes mellitus (DM) and adult patients with DM type 1 and DM type 2. Biosimilars agent insulin glargine-yfgn is the first insulin biosimilar agent to receive FDA approval and is also the first interchangeable agent in the class of biosimilar agents. Interchangeable products are biosimilars that meet additional criteria specified by the Biologics Price Competition and Innovation Act during the assessment and testing of the agent during its FDA approval process.[6] Data is required demonstrating clinical results as its respective reference product in any subject treated with the interchangeable products.[6] Data on the interchangeable products substituted with their reference product in terms of safety and efficacy of alternating back and forth have been assessed and evaluated by the FDA prior to their approval. Once an interchangeable product has been approved, it may be interchanged for their reference product without requiring additional consulting from the prescribing clinician or healthcare professional.[7][8] Table 1: Summarizes all FDA approved biosimilars

As the development of biosimilars agents has progressed over the years, awareness in subspecialty practices encountering high incidence and prevalence of inflammatory diseases such as rheumatology, dermatology, and gastroenterology is also expanding.[4] Other specialties such as oncology and endocrinology have now also introduced biotherapeutics.[4] However, a gap in knowledge and confusion of biosimilars may exist in non-subspecialty practices, particularly with primary care clinicians (PCP). While PCP's are up to date on the more conventional original biologic treatments, many may not have gained familiarity and experience with the more current biosimilar innovative therapeutics, which in turn are more inexpensive, further increasing medication acquisition and compliance improving disease outcomes and the quality of life. [4] The American journal of managed care (AJMC) discussed insights on biologics and biosimilars for inflammatory diseases. In the United States (US), fewer than 1% of dispensed prescribed medications consist of biological agents; however, the biologic agents value over one-fourth of all prescription costs in the US. The knowledge and awareness of biosimilars in specialty practices such as rheumatology and gastroenterology have increased in recent years due to the advocacy from respective specialty associations.[22] The preliminary approvals for biosimilars use for inflammatory diseases in medicine were issued for rheumatologic conditions. One of the gaps in knowledge for biosimilars use in medicine comes from when the FDA is making a governing action versus when a biosimilar is ultimately FDA-approved and available for use. Biosimilars have been prevalent in Europe, Japan, and South Korea for over a decade, but their availability in the US was delayed due to the necessity of regulations dictating their pathway to market. The Biologics Price Competition and Innovation Act was implemented in 2009, and since the initial FDA approval was granted for biosimilar "filgrastim-sndz " in March 2015. To date, more biosimilars are being approved and marketed, with the latest approval coming on July 28, 2021, for biosimilar agent insulin glargine-yfgn. The proposed predictions for reducing costs vary from $54 billion to $250 billion within the midst of the 2020s onwards.[4][23]

Biosimilars have been prevalent in Europe, Japan, and South Korea for over a decade, but their availability in the US was delayed due to the necessity of regulations dictating their pathway to market. The Biologics Price Competition and Innovation Act was implemented in 2009, and since the initial FDA approval was granted for biosimilar "filgrastim-sndz " in March 2015. To date, more biosimilars are being approved and marketed, with the latest approval coming on July 28, 2021, for biosimilar agent insulin glargine-yfgn. The proposed predictions for reducing costs vary from $54 billion to $250 billion within the midst of the 2020s onwards.[4][23] For the cost-saving potential and improved patient access to agents for treating inflammatory diseases, recognition of biosimilars as safe and efficacious agents by patients, primary care clinicians, specialists, and other healthcare professionals is warranted to achieve market share.[23] The recognition of biosimilars as safe alternative agents to biologics may be subdued by education on the meticulous approval criteria required of biosimilars imposed by the FDA for prescribing clinicians and healthcare professionals.[4][24] Several original biologics will be nearing closings of their patents, and prospective producers of biosimilars are anticipated and the importance of regulative criteria ensuring their safety and effectiveness in managing inflammatory diseases. More than 70% of biologic agents' costs were accumulated from biologics with lapsed patents, which would soon be off-patent.[4]

Several original biologics will be nearing closings of their patents, and prospective producers of biosimilars are anticipated and the importance of regulative criteria ensuring their safety and effectiveness in managing inflammatory diseases. More than 70% of biologic agents' costs were accumulated from biologics with lapsed patents, which would soon be off-patent.[4] When producing and developing biosimilars, their primary structure and sequence of amino acids are identical to their respective reference products.[24] The minor variations may occur in the biosimilar tertiary or quarternary structure, with no meaningful clinical differences compared to the original biologics and treating inflammatory diseases.[4] Moreover, biosimilars also possess no discrepancies in safety, purity, efficacy, and potency compared to the original biologics.[4][24] Evidence-based impacts with biosimilars in clinical practice have been limited due to their legal matters and availability. Clinical and desired patient outcomes with biosimilars and choosing them over a conventional biologic for inflammatory diseases vary from specialty to specialty and on a case-by-case basis, depending on the individual and type of disease course.[24] Some patients may have a more silent disease course, while others may be in remission. Clinicians may feel more comfortable with the standard of care and prescribe a biological agent due to successful patient outcomes.[24]  Immunogenicity should also be considered when prescribing immunotherapeutics in a clinical setting, as it may also affect desired patient results. When treating inflammatory diseases, a patient-centered approach should be regarded when considering the use of biosimilars. Biosimilars are deemed to be more affordable when compared to original biologics improving access to treatment options. When prescribing biosimilars, cost efficiency for the patient should be considered as it may only be more economical to the provider and payer but not so much to the patient.[22] As some subjects may be paying a certain amount of co-pay for conventional biologics, it is not assured the patients will receive a reduced rate if treated with a biosimilar.[22]

When treating inflammatory diseases, a patient-centered approach should be regarded when considering the use of biosimilars. Biosimilars are deemed to be more affordable when compared to original biologics improving access to treatment options. When prescribing biosimilars, cost efficiency for the patient should be considered as it may only be more economical to the provider and payer but not so much to the patient.[22] As some subjects may be paying a certain amount of co-pay for conventional biologics, it is not assured the patients will receive a reduced rate if treated with a biosimilar.[22] Patients may also feel comfortable continuing care with the original biologic initiated if they are already being treated compared to subjects with newly diagnosed inflammatory diseases, who may feel more open to a biosimilar.[24][22] An open-ended discussion and patient-centered approach between provider and patients regarding biosimilars, treatment options, and patient outcomes should be discussed. Biosimilars ultimately demonstrate similarity to original biologics based on their characteristics of safety, efficacy, potency, tolerability but do not share similar cost considerations. Cost and prescribing considerations can ultimately make biosimilars the choice of biotherapeutics when prescribing biologics for inflammatory diseases.[24][22] Barriers that need to be considered when prescribing biosimilars are patients not responding to the switch in medications or receiving no cost benefits due to their managed care plans.[23] The cost and prescribing considerations are a predominant focus of biosimilars in the US, as decreasing costs will improve patient access to biotherapeutics.[24][22] Cost variability for biosimilars may also affect their presence and use on the US market. Competition from other biopharmaceuticals such as price drops, incentives, and reimbursements from existing biologics may narrow the price gap between original biologics and biosimilars.[23]

Barriers that need to be considered when prescribing biosimilars are patients not responding to the switch in medications or receiving no cost benefits due to their managed care plans.[23] The cost and prescribing considerations are a predominant focus of biosimilars in the US, as decreasing costs will improve patient access to biotherapeutics.[24][22] Cost variability for biosimilars may also affect their presence and use on the US market. Competition from other biopharmaceuticals such as price drops, incentives, and reimbursements from existing biologics may narrow the price gap between original biologics and biosimilars.[23] Challenges clinicians may face when discussing biosimilars with patients for inflammatory diseases are medication switches in subjects with disease states already in remission. Patients may not want to risk replacing an already established agent that has demonstrated desired patient outcomes and disease stability with another agent similar to the primary medication for cost benefits.[24][22] Patient education and information on biosimilars are crucial for subjects already managed with biotherapeutics for inflammatory diseases. A better knowledge of biosimilars can overcome barriers in treatment.[22][4] Clinician awareness for biosimilars use for inflammatory disease in clinical practice is gradually increasing through clinician programs through their respective specialty programs.[22] A greater understanding of the benefits, risks, similarities, safety, efficacy, costs, and prescribing considerations of biosimilars compared to the original biologics can aid clinicians to make informed decisions when utilizing and discussing biosimilars with their patients.[4][22] The future for biosimilars use in inflammatory disease in the US is gaining positive traction.[22] To date, there are currently 30 FDA-approved biosimilars agents referenced from 10 original biologics since its very first approval in 2015. When looking at the current state of biosimilars in the European Union (EU), European Medicines Agency (EMA) has approved 65 biosimilars for the use of various diseases. The US FDA regulatory pathway of biosimilars is ordinarily alike of EMA with some variations.[25]

The future for biosimilars use in inflammatory disease in the US is gaining positive traction.[22] To date, there are currently 30 FDA-approved biosimilars agents referenced from 10 original biologics since its very first approval in 2015. When looking at the current state of biosimilars in the European Union (EU), European Medicines Agency (EMA) has approved 65 biosimilars for the use of various diseases. The US FDA regulatory pathway of biosimilars is ordinarily alike of EMA with some variations.[25] The EMA has served as a lead for setting regulatory pathways for biosimilars and their approvals as the first-ever biosimilar received approval in 2006 by the EMA.[25] Biosimilar agents approved for use in the EU include insulin, growth hormone, heparin/ low-molecular-weight heparin (LMWH), interferons, and monoclonal antibody products.[25][24][4] The FDA recently approved its first insulin biosimilar and first-ever interchangeable products. As advancements in technology and scientific methodology progress, biosimilars' development and regulatory conditions are also destined to improve.[25][4][23][24][26][22]

Biosimilars are biological agents that are highly analogous to their reference products currently approved and licensed by the U.S. Food and Drug Administration (FDA). Biosimilars can be used in various inflammatory and autoimmune diseases such as rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, plaque psoriasis, inflammatory bowel disease: adult Crohn disease, ulcerative colitis, granulomatosis with polyangiitis (Wegener granulomatosis), microscopic and polyangiitis (MPA). With the latest advancements in biosimilars agents, it is now also indicated for use in specific malignancies, anemia, and diabetes mellitus—patients suffering from such conditions prompt care and oversight from an interprofessional team of healthcare professionals. The interprofessional team should consist of a primary care clinician, specialists such as a rheumatologist, gastroenterologist, dermatologist, oncologist, and endocrinologist, alongside mid-level practitioners, nurses, a physical therapist (PT), and a pharmacist. Efficient care and communication within the interprofessional healthcare team concerning patients suffering from such ailments receiving biosimilars can improve patient access to biotherapeutics, resulting in clinical improvements, decreased disease progression, and a greater quality of life. Prescribing clinicians and the healthcare team should be up to date with the latest guidelines, advancements, and latest FDA-approved indications for biosimilar use. Although FDA-approved biosimilars have extrapolated indications of their original biologic agents, some FDA labels of biosimilars do not designate all indications of their reference products and may potentially be considered off-label use.[4] Healthcare professionals should also review the difference between biosimilars and interchangeable biosimilars and thoroughly educate their patients being managed with such agents.[4]

Prescribing clinicians and the healthcare team should be up to date with the latest guidelines, advancements, and latest FDA-approved indications for biosimilar use. Although FDA-approved biosimilars have extrapolated indications of their original biologic agents, some FDA labels of biosimilars do not designate all indications of their reference products and may potentially be considered off-label use.[4] Healthcare professionals should also review the difference between biosimilars and interchangeable biosimilars and thoroughly educate their patients being managed with such agents.[4] Patients should be educated on biosimilars and their comparison to original biologics and reassured that FDA biosimilars possess no clinically meaningful differences in terms of their safety, purity, potency, or effectiveness compared to their respective reference biologic agents. The healthcare team should also advise patients about the potential adverse effects while receiving treatment as similar adverse effects are anticipated as the reference products. Immunogenicity should also be discussed when prescribing immunotherapeutics in a clinical setting, as it may also alter desired patient results. Additional educational material on biosimilars can be provided to patients from the FDA website. Clinicians can expand their knowledge base and awareness of advances in biosimilars and their use in specialty practices from their respective specialty associations. Additional information can also be attained from the FDA website. The cost-saving potential of biosimilars should be taken into account and analyzed for the best treatment options for the patients. Biosimilars use in a clinical setting should be patient-focused and beneficial to the patient and not limited to provider and managed care plans. A thorough, open-ended discussion on biosimilars use for therapy between the interprofessional team, primarily the PCP and specialists, and their patients, is crucial as education on treatment with biotherapeutics in the management of inflammatory diseases can further increase medication trust and compliance and better clinician-patient rapport.