More than 200 experts and specialists from across the autoimmune disease spectrum gathered at the recent 4th annual Interdisciplinary Autoimmune Summit (IAS), at the New York Marriott Marquis.
Figure 1_ Joel M. Gelfand, MD, MSCE
The event was co-chaired by Joel M. Gelfand, MD, MSCE, associate professor of dermatology and epidemiology, medical director, Dermatology Clinical Studies Unit, director, Psoriasis and Phototherapy Treatment Center, University of Pennsylvania, Perelman School of Medicine (Figure 1). At the meeting, specialists had the opportunity to discuss and debate the effectiveness of groundbreaking approaches to treating patients with immune-mediated inflammatory disease (IMID) and collaborate with fellow dermatologists, rheumatologists, gastroenterologists, immunologists, internists, and other health care professionals on patient care.
“There’s a growing realization that inflammatory diseases are not linked to any one organ system. So many specialties are involved, and each has insights,” explained Steven R. Feldman, MD, PhD, chief medical editor of The Dermatologist and professor of Dermatology, Pathology, and Public Health Sciences, Wake Forest University School of Medicine, in Winston-Salem, NC.
Collaboration is key in treating IMIDs such as psoriasis, psoriatic arthritis, rheumatoid arthritis, spondyloarthritis, and Crohn disease and colitis, because of many shared features, including common inflammatory pathways; comorbid risks; treatment response; care strategies toward achieving remission; risk of organ damage; and association with increased morbidity and mortality.
Microbiome Connection
Figure 2_ Keynote speaker Charles L. Raison, MD
Keynote speaker Charles L. Raison, MD, professor, School of Human Ecology and School of Medicine and Public Health, University of Wisconsin-Madison, shared his expertise on IMID and the microbial world (Figure 2).
Research on human-microbial interactions has increased sharply within the last decade. However, this new area of research is not part of formal education for most clinicians. He noted that clinicians dealing with disorders that the immune system is a significant contributor to are going to have to understand the human-microbial interactions. He provided an overview of microbiota and health across a range of disease states commonly treated by the attendees. The human microbiota consists of the 10-100 trillion symbiotic microbial cells harbored by each person, primarily bacteria in the gut. The human microbiome consists of the genes these cells harbor.1 The microbiome is defined as the collective genomes of the microbes (composed of bacteria, bacteriophage, fungi, protozoa, and viruses) that live inside and on the human body.2 He noted that these disorders are driven by the crosstalk between the microbial world and the human world. Understanding the science behind this will allow clinicians to master this new understanding of what these disease states are, he said (Figure 3).
Inflammatory bowel disease and irritable bowel syndrome appear to be connected to microbial interactions, said Dr Raison. However, links have been identified recently to other disorders, such as Parkinson disease, autism, depression, rheumatoid arthritis, and others.
“Auto immune conditions, while not unknown in prior times, have seen astounding explosion in the lifetimes of many of us,” he said. “Conditions like type 2 diabetes and multiple sclerosis have tripled in numbers in last 40 or 50 years. It is not just autoimmune conditions, it is also asthma and allergies. We are in the midst of this not-fully-recognized epidemic of immune dysregulation.”
Other factors such as nutrition, stress, inadequate sleep, and chronic inflammation play a role in immune dysregulation of modern people in industrialized societies. He discussed emerging potential microbial treatments based on human microbial interactions, including probiotics/prebiotics/synbiotics; fecal/microbiota transplant; and micro-organisms (ie, gut flora, saprophytic mycobacteria, and helminths).
“Something in the modern world is driving chronic inflammatory bias and immunodysregulation is manifesting in autoimmune conditions that is increasingly contributing to this very striking rise in psychiatric patients also,” Dr Raison said. “It looks like no small part of this problem derives from the fact that we have massively altered our relationships with the microbial (and macroscopic) world. About 20% of medicine is going to be about relationships—family therapies—and about how we deal with this microbial family. You see a lot of patterns and problems in the microbial world that you see in the human world that give rise to psychiatric conditions.”
Data increasingly suggest that manipulating the microbiome may hold promise for the treatment of a wide array of disease states. “However, much is yet to be learned,” he said. “Our relationships with the microbial world mirror our relationships with humans: cooperation, conflict, and deception.”
Article continues on page 2
{{pagebreak}}
Psoriatic Diseases
Dr Gelfand discussed new biologics to improve outcomes and quality of life for patients with psoriatic diseases in his presentation. The impact of psoriasis stretches wide and effects quality of life and also is linked to other health issues. “Psoriasis is a multifactorial disease,” he said, noting that genetics, immune dysfunction, environmental risk factors (such as obesity and smoking), and modifying factors/triggers (such as skin injury, infections, medications, depression, smoking, and alcohol) all play some role in the disease.
“Moderate-to-severe psoriasis is associated with serious impairment in health-related quality of life and a 5-year decrease in life expectancy,” he said noting that well established comorbidities of psoriasis include heart attack, stroke, cardiovascular death, metabolic syndrome, diabetes, psoriatic arthritis, mood disorders, Crohn disease, and t cell lymphoma.
In recent years, the need to improve the structure of psoriatic disease therapy, to define treatment goals, and to measure treatment outcomes by means of parameters of clinical severity and quality of life has intensified. Compared to traditional systemic treatments, current and emerging biologic agents offer the promise of improved disease management and potential reduction in associated comorbidities, along with new safety concerns in long-term psoriasis management, said Dr Gelfand.
“There has been a rapid expansion of treatment alternatives achieving greater efficacy and possibly improved safety in psoriasis and psoriatic arthritis. However, longer-term data are needed,” he added.
The session featured the Oculus Virtual Reality technology, which was used to illustrate the psoriasis pathophysiology and the mechanism of action of new and emerging biologics; psoriasis and psoriatic arthritis, and also psoriasis comorbidities.
Advances in understanding psoriasis pathophysiology have led to a broad spectrum of anti-psoriatic agents, including small molecules and biologics. Dr Gelfand discussed the complexity of immune cell interactions and signaling mechanisms in psoriatic and other immune-related diseases as the basis for newest targeted treatment approaches, including mechanisms underlying itch (a symptom affecting patient quality of life and work productivity), the role of inflammation in psoriatic and cardiovascular disease, and the mechanisms by which some targeted therapies provide more rapid responses and better patient outcomes. Dr Gelfand presented a complicated case study that demonstrated the need for an ever-evolving course of therapy.
He noted that an individualized patient centered approach to psoriatic diseases is needed. This often incorporates available targeted and biologic agents and other therapies in the treatment plan based on existing comorbidities and patient-reported benefits. “Treatment selection remains highly dependent on individual patient characteristics and preferences,” he concluded.
Understanding Biosimilar Complexities
Jonathan Kay, MD, professor of medicine, director of clinical research, rheumatology, University of Massachusetts Medical School, gave a comprehensive biosimilars overview in his talk, titled to Examining Biosimilars within the Immune Mediated Inflammatory Disorders (IMID) Landscape. “I define a biosimilar as a legitimate copy of a biopharmaceutical that no long is protected by patent, which has undergone rigorous analytical and clinical assessment, in comparison to its reference product; and been approved by a regulatory agency according to a specific pathway for biosimilar evaluation,” he said.
However, Dr Kay noted that the official regulatory definition varies depending on the country. In the US, FDA defines biosimilarity as “that the biologic product is highly similar to the reference product notwithstanding minor differences in clinically inactive components” and that “there are no clinically meaningful differences between the biologic product and the reference product in terms of the safety, purity, and potency of the product.”3
He also outlined potential differences in biosimilars vs the reference biologic and strategies to ensure safe and effective treatment. Depending on the country, varying terms are used to describe this category of drugs as well (Figure 4). He reviewed the current state of the biosimilar market across varying countries (Figures 5). Numerous additional biosimilars are in development to treat inflammatory diseases including adalimumab (13), etanercept (6), golimumab (1), infliximab (5), abatacept (2), tocilizumab (3), and rituximab (8).4
Figure 4. Depending on the country, varying terms are used to describe this category of drugs as well.
Figure 5. The current state of the biosimilar market across varying countries.
Dr Kay also discussed the manufacturing process of biosimilars and the US regulatory pathways for small-molecule drugs and biopharmaceuticals. He reviewed a list of biosimilar abbreviated biologics license applications filed with the FDA.
Other issues related to this category of drugs, such as switching vs substitution and pricing and varying insurance payer coverage, can make it confusing when evaluating treatment options. Dr Kay explained that a switch is equal to a transition. For example, a patient transitioned to a biosimilar after initial treatment with a bio-originator. Substitution equals interchange. “Biologics Price Competition Act of 2009 affords 1 year of exclusive marketing rights to the first biosimilar approved as being ‘interchangeable’ with the reference product. Interchange can be initiated without prescriber input,” he said.5
In many states legislation in is in various stages related to biologic medications and substitution of biosimilars.6
The potential risk to the individual of switching to a lower-cost biosimilar should be outweighed by the potential benefit to global society of expanding access to care for all, he said. “We should accept a lower cost biosimilar (as opposed to the reference product), so that medications are more widely available to all members of society,” Dr Kay added.
The potential benefits of lower-priced biosimilars should decrease the cost of treating patients; and biosimilars should be more readily available to patients who the bio-originator has been inaccessible. “Greater global access to effective biosimilars should reduce disability, morbidity, and mortality associated with inflammatory diseases,” he said.
“Biosimilar undergo a rigorous regulatory approval process with an abbreviated clinical package. With many biopharmaceuticals going off-patent in the near future, opportunity exists to expand patient access through availability biosimilar,” he concluded.
Next year’s meeting will be held at the Westin Boston Waterfront, in Boston, MA, from April 27-29, 2018. For more information, please visit https://interdisciplinaryautoimmunenetwork.com/
References
- Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449:804–810.
- Yang J. The Human Microbiome Project: Extending the definition of what constitutes a human. July 16, 2012. https://www.genome.gov/27549400/the-human-microbiome-project-extending-the-definition-of-what-constitutes-a-human/ Accessed March 28, 2017.
- US Food and Drug Administration. Guidance for Industry. Biosimilars: questions and answers regarding Biosimilars: questions and answers regarding implementation of Biologics Price Competition and Innovation Act of 2009. Department of Heath and Human Services, 2015.
- Dörner T, et al. Nat Rev Rheumatol. 2015; 11(12):713-724; (*As of December 2016.)
https://www.gabionline.net/Biosimilars/General/Biosimilars- of-adalimumab. https://www.gabionline.net/Biosimilars/General/Biosimilars-of-etanercept; https://www.gabionline.net/Biosimilars/General/Biosimilars-of-infliximab. https://www.gabionline.net/Biosimilars/General/Biosimilars-of-tocilizumab; https://www.gabionline.net/Biosimilars/General/Biosimilars-of-rituximab
5. FDA. Guidance Compliance Regulatory Information. https://www.fda.gov/downloads/Drugs/Guidance ComplianceRegulatoryInformation/UCM216146.pdf.
6. National Conference of State Legislatures. State laws and legislation related to biologic medications and substitution of biosimilars. https://www.ncsl.org/research/health/state-laws-and-legislation-related-to-biologic-medications-and-substitution-of-biosimilars.aspx. Accessed November 16, 2016.
More than 200 experts and specialists from across the autoimmune disease spectrum gathered at the recent 4th annual Interdisciplinary Autoimmune Summit (IAS), at the New York Marriott Marquis.
Figure 1_ Joel M. Gelfand, MD, MSCE
The event was co-chaired by Joel M. Gelfand, MD, MSCE, associate professor of dermatology and epidemiology, medical director, Dermatology Clinical Studies Unit, director, Psoriasis and Phototherapy Treatment Center, University of Pennsylvania, Perelman School of Medicine (Figure 1). At the meeting, specialists had the opportunity to discuss and debate the effectiveness of groundbreaking approaches to treating patients with immune-mediated inflammatory disease (IMID) and collaborate with fellow dermatologists, rheumatologists, gastroenterologists, immunologists, internists, and other health care professionals on patient care.
“There’s a growing realization that inflammatory diseases are not linked to any one organ system. So many specialties are involved, and each has insights,” explained Steven R. Feldman, MD, PhD, chief medical editor of The Dermatologist and professor of Dermatology, Pathology, and Public Health Sciences, Wake Forest University School of Medicine, in Winston-Salem, NC.
Collaboration is key in treating IMIDs such as psoriasis, psoriatic arthritis, rheumatoid arthritis, spondyloarthritis, and Crohn disease and colitis, because of many shared features, including common inflammatory pathways; comorbid risks; treatment response; care strategies toward achieving remission; risk of organ damage; and association with increased morbidity and mortality.
Microbiome Connection
Figure 2_ Keynote speaker Charles L. Raison, MD
Keynote speaker Charles L. Raison, MD, professor, School of Human Ecology and School of Medicine and Public Health, University of Wisconsin-Madison, shared his expertise on IMID and the microbial world (Figure 2).
Research on human-microbial interactions has increased sharply within the last decade. However, this new area of research is not part of formal education for most clinicians. He noted that clinicians dealing with disorders that the immune system is a significant contributor to are going to have to understand the human-microbial interactions. He provided an overview of microbiota and health across a range of disease states commonly treated by the attendees. The human microbiota consists of the 10-100 trillion symbiotic microbial cells harbored by each person, primarily bacteria in the gut. The human microbiome consists of the genes these cells harbor.1 The microbiome is defined as the collective genomes of the microbes (composed of bacteria, bacteriophage, fungi, protozoa, and viruses) that live inside and on the human body.2 He noted that these disorders are driven by the crosstalk between the microbial world and the human world. Understanding the science behind this will allow clinicians to master this new understanding of what these disease states are, he said (Figure 3).
Inflammatory bowel disease and irritable bowel syndrome appear to be connected to microbial interactions, said Dr Raison. However, links have been identified recently to other disorders, such as Parkinson disease, autism, depression, rheumatoid arthritis, and others.
“Auto immune conditions, while not unknown in prior times, have seen astounding explosion in the lifetimes of many of us,” he said. “Conditions like type 2 diabetes and multiple sclerosis have tripled in numbers in last 40 or 50 years. It is not just autoimmune conditions, it is also asthma and allergies. We are in the midst of this not-fully-recognized epidemic of immune dysregulation.”
Other factors such as nutrition, stress, inadequate sleep, and chronic inflammation play a role in immune dysregulation of modern people in industrialized societies. He discussed emerging potential microbial treatments based on human microbial interactions, including probiotics/prebiotics/synbiotics; fecal/microbiota transplant; and micro-organisms (ie, gut flora, saprophytic mycobacteria, and helminths).
“Something in the modern world is driving chronic inflammatory bias and immunodysregulation is manifesting in autoimmune conditions that is increasingly contributing to this very striking rise in psychiatric patients also,” Dr Raison said. “It looks like no small part of this problem derives from the fact that we have massively altered our relationships with the microbial (and macroscopic) world. About 20% of medicine is going to be about relationships—family therapies—and about how we deal with this microbial family. You see a lot of patterns and problems in the microbial world that you see in the human world that give rise to psychiatric conditions.”
Data increasingly suggest that manipulating the microbiome may hold promise for the treatment of a wide array of disease states. “However, much is yet to be learned,” he said. “Our relationships with the microbial world mirror our relationships with humans: cooperation, conflict, and deception.”
Article continues on page 2
{{pagebreak}}
Psoriatic Diseases
Dr Gelfand discussed new biologics to improve outcomes and quality of life for patients with psoriatic diseases in his presentation. The impact of psoriasis stretches wide and effects quality of life and also is linked to other health issues. “Psoriasis is a multifactorial disease,” he said, noting that genetics, immune dysfunction, environmental risk factors (such as obesity and smoking), and modifying factors/triggers (such as skin injury, infections, medications, depression, smoking, and alcohol) all play some role in the disease.
“Moderate-to-severe psoriasis is associated with serious impairment in health-related quality of life and a 5-year decrease in life expectancy,” he said noting that well established comorbidities of psoriasis include heart attack, stroke, cardiovascular death, metabolic syndrome, diabetes, psoriatic arthritis, mood disorders, Crohn disease, and t cell lymphoma.
In recent years, the need to improve the structure of psoriatic disease therapy, to define treatment goals, and to measure treatment outcomes by means of parameters of clinical severity and quality of life has intensified. Compared to traditional systemic treatments, current and emerging biologic agents offer the promise of improved disease management and potential reduction in associated comorbidities, along with new safety concerns in long-term psoriasis management, said Dr Gelfand.
“There has been a rapid expansion of treatment alternatives achieving greater efficacy and possibly improved safety in psoriasis and psoriatic arthritis. However, longer-term data are needed,” he added.
The session featured the Oculus Virtual Reality technology, which was used to illustrate the psoriasis pathophysiology and the mechanism of action of new and emerging biologics; psoriasis and psoriatic arthritis, and also psoriasis comorbidities.
Advances in understanding psoriasis pathophysiology have led to a broad spectrum of anti-psoriatic agents, including small molecules and biologics. Dr Gelfand discussed the complexity of immune cell interactions and signaling mechanisms in psoriatic and other immune-related diseases as the basis for newest targeted treatment approaches, including mechanisms underlying itch (a symptom affecting patient quality of life and work productivity), the role of inflammation in psoriatic and cardiovascular disease, and the mechanisms by which some targeted therapies provide more rapid responses and better patient outcomes. Dr Gelfand presented a complicated case study that demonstrated the need for an ever-evolving course of therapy.
He noted that an individualized patient centered approach to psoriatic diseases is needed. This often incorporates available targeted and biologic agents and other therapies in the treatment plan based on existing comorbidities and patient-reported benefits. “Treatment selection remains highly dependent on individual patient characteristics and preferences,” he concluded.
Understanding Biosimilar Complexities
Jonathan Kay, MD, professor of medicine, director of clinical research, rheumatology, University of Massachusetts Medical School, gave a comprehensive biosimilars overview in his talk, titled to Examining Biosimilars within the Immune Mediated Inflammatory Disorders (IMID) Landscape. “I define a biosimilar as a legitimate copy of a biopharmaceutical that no long is protected by patent, which has undergone rigorous analytical and clinical assessment, in comparison to its reference product; and been approved by a regulatory agency according to a specific pathway for biosimilar evaluation,” he said.
However, Dr Kay noted that the official regulatory definition varies depending on the country. In the US, FDA defines biosimilarity as “that the biologic product is highly similar to the reference product notwithstanding minor differences in clinically inactive components” and that “there are no clinically meaningful differences between the biologic product and the reference product in terms of the safety, purity, and potency of the product.”3
He also outlined potential differences in biosimilars vs the reference biologic and strategies to ensure safe and effective treatment. Depending on the country, varying terms are used to describe this category of drugs as well (Figure 4). He reviewed the current state of the biosimilar market across varying countries (Figures 5). Numerous additional biosimilars are in development to treat inflammatory diseases including adalimumab (13), etanercept (6), golimumab (1), infliximab (5), abatacept (2), tocilizumab (3), and rituximab (8).4
Figure 4. Depending on the country, varying terms are used to describe this category of drugs as well.
Figure 5. The current state of the biosimilar market across varying countries.
Dr Kay also discussed the manufacturing process of biosimilars and the US regulatory pathways for small-molecule drugs and biopharmaceuticals. He reviewed a list of biosimilar abbreviated biologics license applications filed with the FDA.
Other issues related to this category of drugs, such as switching vs substitution and pricing and varying insurance payer coverage, can make it confusing when evaluating treatment options. Dr Kay explained that a switch is equal to a transition. For example, a patient transitioned to a biosimilar after initial treatment with a bio-originator. Substitution equals interchange. “Biologics Price Competition Act of 2009 affords 1 year of exclusive marketing rights to the first biosimilar approved as being ‘interchangeable’ with the reference product. Interchange can be initiated without prescriber input,” he said.5
In many states legislation in is in various stages related to biologic medications and substitution of biosimilars.6
The potential risk to the individual of switching to a lower-cost biosimilar should be outweighed by the potential benefit to global society of expanding access to care for all, he said. “We should accept a lower cost biosimilar (as opposed to the reference product), so that medications are more widely available to all members of society,” Dr Kay added.
The potential benefits of lower-priced biosimilars should decrease the cost of treating patients; and biosimilars should be more readily available to patients who the bio-originator has been inaccessible. “Greater global access to effective biosimilars should reduce disability, morbidity, and mortality associated with inflammatory diseases,” he said.
“Biosimilar undergo a rigorous regulatory approval process with an abbreviated clinical package. With many biopharmaceuticals going off-patent in the near future, opportunity exists to expand patient access through availability biosimilar,” he concluded.
Next year’s meeting will be held at the Westin Boston Waterfront, in Boston, MA, from April 27-29, 2018. For more information, please visit https://interdisciplinaryautoimmunenetwork.com/
References
- Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449:804–810.
- Yang J. The Human Microbiome Project: Extending the definition of what constitutes a human. July 16, 2012. https://www.genome.gov/27549400/the-human-microbiome-project-extending-the-definition-of-what-constitutes-a-human/ Accessed March 28, 2017.
- US Food and Drug Administration. Guidance for Industry. Biosimilars: questions and answers regarding Biosimilars: questions and answers regarding implementation of Biologics Price Competition and Innovation Act of 2009. Department of Heath and Human Services, 2015.
- Dörner T, et al. Nat Rev Rheumatol. 2015; 11(12):713-724; (*As of December 2016.)
https://www.gabionline.net/Biosimilars/General/Biosimilars- of-adalimumab. https://www.gabionline.net/Biosimilars/General/Biosimilars-of-etanercept; https://www.gabionline.net/Biosimilars/General/Biosimilars-of-infliximab. https://www.gabionline.net/Biosimilars/General/Biosimilars-of-tocilizumab; https://www.gabionline.net/Biosimilars/General/Biosimilars-of-rituximab
5. FDA. Guidance Compliance Regulatory Information. https://www.fda.gov/downloads/Drugs/Guidance ComplianceRegulatoryInformation/UCM216146.pdf.
6. National Conference of State Legislatures. State laws and legislation related to biologic medications and substitution of biosimilars. https://www.ncsl.org/research/health/state-laws-and-legislation-related-to-biologic-medications-and-substitution-of-biosimilars.aspx. Accessed November 16, 2016.
More than 200 experts and specialists from across the autoimmune disease spectrum gathered at the recent 4th annual Interdisciplinary Autoimmune Summit (IAS), at the New York Marriott Marquis.
Figure 1_ Joel M. Gelfand, MD, MSCE
The event was co-chaired by Joel M. Gelfand, MD, MSCE, associate professor of dermatology and epidemiology, medical director, Dermatology Clinical Studies Unit, director, Psoriasis and Phototherapy Treatment Center, University of Pennsylvania, Perelman School of Medicine (Figure 1). At the meeting, specialists had the opportunity to discuss and debate the effectiveness of groundbreaking approaches to treating patients with immune-mediated inflammatory disease (IMID) and collaborate with fellow dermatologists, rheumatologists, gastroenterologists, immunologists, internists, and other health care professionals on patient care.
“There’s a growing realization that inflammatory diseases are not linked to any one organ system. So many specialties are involved, and each has insights,” explained Steven R. Feldman, MD, PhD, chief medical editor of The Dermatologist and professor of Dermatology, Pathology, and Public Health Sciences, Wake Forest University School of Medicine, in Winston-Salem, NC.
Collaboration is key in treating IMIDs such as psoriasis, psoriatic arthritis, rheumatoid arthritis, spondyloarthritis, and Crohn disease and colitis, because of many shared features, including common inflammatory pathways; comorbid risks; treatment response; care strategies toward achieving remission; risk of organ damage; and association with increased morbidity and mortality.
Microbiome Connection
Figure 2_ Keynote speaker Charles L. Raison, MD
Keynote speaker Charles L. Raison, MD, professor, School of Human Ecology and School of Medicine and Public Health, University of Wisconsin-Madison, shared his expertise on IMID and the microbial world (Figure 2).
Research on human-microbial interactions has increased sharply within the last decade. However, this new area of research is not part of formal education for most clinicians. He noted that clinicians dealing with disorders that the immune system is a significant contributor to are going to have to understand the human-microbial interactions. He provided an overview of microbiota and health across a range of disease states commonly treated by the attendees. The human microbiota consists of the 10-100 trillion symbiotic microbial cells harbored by each person, primarily bacteria in the gut. The human microbiome consists of the genes these cells harbor.1 The microbiome is defined as the collective genomes of the microbes (composed of bacteria, bacteriophage, fungi, protozoa, and viruses) that live inside and on the human body.2 He noted that these disorders are driven by the crosstalk between the microbial world and the human world. Understanding the science behind this will allow clinicians to master this new understanding of what these disease states are, he said (Figure 3).
Inflammatory bowel disease and irritable bowel syndrome appear to be connected to microbial interactions, said Dr Raison. However, links have been identified recently to other disorders, such as Parkinson disease, autism, depression, rheumatoid arthritis, and others.
“Auto immune conditions, while not unknown in prior times, have seen astounding explosion in the lifetimes of many of us,” he said. “Conditions like type 2 diabetes and multiple sclerosis have tripled in numbers in last 40 or 50 years. It is not just autoimmune conditions, it is also asthma and allergies. We are in the midst of this not-fully-recognized epidemic of immune dysregulation.”
Other factors such as nutrition, stress, inadequate sleep, and chronic inflammation play a role in immune dysregulation of modern people in industrialized societies. He discussed emerging potential microbial treatments based on human microbial interactions, including probiotics/prebiotics/synbiotics; fecal/microbiota transplant; and micro-organisms (ie, gut flora, saprophytic mycobacteria, and helminths).
“Something in the modern world is driving chronic inflammatory bias and immunodysregulation is manifesting in autoimmune conditions that is increasingly contributing to this very striking rise in psychiatric patients also,” Dr Raison said. “It looks like no small part of this problem derives from the fact that we have massively altered our relationships with the microbial (and macroscopic) world. About 20% of medicine is going to be about relationships—family therapies—and about how we deal with this microbial family. You see a lot of patterns and problems in the microbial world that you see in the human world that give rise to psychiatric conditions.”
Data increasingly suggest that manipulating the microbiome may hold promise for the treatment of a wide array of disease states. “However, much is yet to be learned,” he said. “Our relationships with the microbial world mirror our relationships with humans: cooperation, conflict, and deception.”
Article continues on page 2
{{pagebreak}}
Psoriatic Diseases
Dr Gelfand discussed new biologics to improve outcomes and quality of life for patients with psoriatic diseases in his presentation. The impact of psoriasis stretches wide and effects quality of life and also is linked to other health issues. “Psoriasis is a multifactorial disease,” he said, noting that genetics, immune dysfunction, environmental risk factors (such as obesity and smoking), and modifying factors/triggers (such as skin injury, infections, medications, depression, smoking, and alcohol) all play some role in the disease.
“Moderate-to-severe psoriasis is associated with serious impairment in health-related quality of life and a 5-year decrease in life expectancy,” he said noting that well established comorbidities of psoriasis include heart attack, stroke, cardiovascular death, metabolic syndrome, diabetes, psoriatic arthritis, mood disorders, Crohn disease, and t cell lymphoma.
In recent years, the need to improve the structure of psoriatic disease therapy, to define treatment goals, and to measure treatment outcomes by means of parameters of clinical severity and quality of life has intensified. Compared to traditional systemic treatments, current and emerging biologic agents offer the promise of improved disease management and potential reduction in associated comorbidities, along with new safety concerns in long-term psoriasis management, said Dr Gelfand.
“There has been a rapid expansion of treatment alternatives achieving greater efficacy and possibly improved safety in psoriasis and psoriatic arthritis. However, longer-term data are needed,” he added.
The session featured the Oculus Virtual Reality technology, which was used to illustrate the psoriasis pathophysiology and the mechanism of action of new and emerging biologics; psoriasis and psoriatic arthritis, and also psoriasis comorbidities.
Advances in understanding psoriasis pathophysiology have led to a broad spectrum of anti-psoriatic agents, including small molecules and biologics. Dr Gelfand discussed the complexity of immune cell interactions and signaling mechanisms in psoriatic and other immune-related diseases as the basis for newest targeted treatment approaches, including mechanisms underlying itch (a symptom affecting patient quality of life and work productivity), the role of inflammation in psoriatic and cardiovascular disease, and the mechanisms by which some targeted therapies provide more rapid responses and better patient outcomes. Dr Gelfand presented a complicated case study that demonstrated the need for an ever-evolving course of therapy.
He noted that an individualized patient centered approach to psoriatic diseases is needed. This often incorporates available targeted and biologic agents and other therapies in the treatment plan based on existing comorbidities and patient-reported benefits. “Treatment selection remains highly dependent on individual patient characteristics and preferences,” he concluded.
Understanding Biosimilar Complexities
Jonathan Kay, MD, professor of medicine, director of clinical research, rheumatology, University of Massachusetts Medical School, gave a comprehensive biosimilars overview in his talk, titled to Examining Biosimilars within the Immune Mediated Inflammatory Disorders (IMID) Landscape. “I define a biosimilar as a legitimate copy of a biopharmaceutical that no long is protected by patent, which has undergone rigorous analytical and clinical assessment, in comparison to its reference product; and been approved by a regulatory agency according to a specific pathway for biosimilar evaluation,” he said.
However, Dr Kay noted that the official regulatory definition varies depending on the country. In the US, FDA defines biosimilarity as “that the biologic product is highly similar to the reference product notwithstanding minor differences in clinically inactive components” and that “there are no clinically meaningful differences between the biologic product and the reference product in terms of the safety, purity, and potency of the product.”3
He also outlined potential differences in biosimilars vs the reference biologic and strategies to ensure safe and effective treatment. Depending on the country, varying terms are used to describe this category of drugs as well (Figure 4). He reviewed the current state of the biosimilar market across varying countries (Figures 5). Numerous additional biosimilars are in development to treat inflammatory diseases including adalimumab (13), etanercept (6), golimumab (1), infliximab (5), abatacept (2), tocilizumab (3), and rituximab (8).4
Figure 4. Depending on the country, varying terms are used to describe this category of drugs as well.
Figure 5. The current state of the biosimilar market across varying countries.
Dr Kay also discussed the manufacturing process of biosimilars and the US regulatory pathways for small-molecule drugs and biopharmaceuticals. He reviewed a list of biosimilar abbreviated biologics license applications filed with the FDA.
Other issues related to this category of drugs, such as switching vs substitution and pricing and varying insurance payer coverage, can make it confusing when evaluating treatment options. Dr Kay explained that a switch is equal to a transition. For example, a patient transitioned to a biosimilar after initial treatment with a bio-originator. Substitution equals interchange. “Biologics Price Competition Act of 2009 affords 1 year of exclusive marketing rights to the first biosimilar approved as being ‘interchangeable’ with the reference product. Interchange can be initiated without prescriber input,” he said.5
In many states legislation in is in various stages related to biologic medications and substitution of biosimilars.6
The potential risk to the individual of switching to a lower-cost biosimilar should be outweighed by the potential benefit to global society of expanding access to care for all, he said. “We should accept a lower cost biosimilar (as opposed to the reference product), so that medications are more widely available to all members of society,” Dr Kay added.
The potential benefits of lower-priced biosimilars should decrease the cost of treating patients; and biosimilars should be more readily available to patients who the bio-originator has been inaccessible. “Greater global access to effective biosimilars should reduce disability, morbidity, and mortality associated with inflammatory diseases,” he said.
“Biosimilar undergo a rigorous regulatory approval process with an abbreviated clinical package. With many biopharmaceuticals going off-patent in the near future, opportunity exists to expand patient access through availability biosimilar,” he concluded.
Next year’s meeting will be held at the Westin Boston Waterfront, in Boston, MA, from April 27-29, 2018. For more information, please visit https://interdisciplinaryautoimmunenetwork.com/
References
- Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449:804–810.
- Yang J. The Human Microbiome Project: Extending the definition of what constitutes a human. July 16, 2012. https://www.genome.gov/27549400/the-human-microbiome-project-extending-the-definition-of-what-constitutes-a-human/ Accessed March 28, 2017.
- US Food and Drug Administration. Guidance for Industry. Biosimilars: questions and answers regarding Biosimilars: questions and answers regarding implementation of Biologics Price Competition and Innovation Act of 2009. Department of Heath and Human Services, 2015.
- Dörner T, et al. Nat Rev Rheumatol. 2015; 11(12):713-724; (*As of December 2016.)
https://www.gabionline.net/Biosimilars/General/Biosimilars- of-adalimumab. https://www.gabionline.net/Biosimilars/General/Biosimilars-of-etanercept; https://www.gabionline.net/Biosimilars/General/Biosimilars-of-infliximab. https://www.gabionline.net/Biosimilars/General/Biosimilars-of-tocilizumab; https://www.gabionline.net/Biosimilars/General/Biosimilars-of-rituximab
5. FDA. Guidance Compliance Regulatory Information. https://www.fda.gov/downloads/Drugs/Guidance ComplianceRegulatoryInformation/UCM216146.pdf.
6. National Conference of State Legislatures. State laws and legislation related to biologic medications and substitution of biosimilars. https://www.ncsl.org/research/health/state-laws-and-legislation-related-to-biologic-medications-and-substitution-of-biosimilars.aspx. Accessed November 16, 2016.
