Report, Summit Address the State of Autoimmune Diseases

Washington – Think globally, but act locally. The political mantra is perfectly suited to describe the necessary approach to not only improving the diagnosis and management of autoimmune diseases, but also to curing and eventually preventing them altogether, Dr. Noel R. Rose said at a meeting on autoimmune diseases organized by the American Autoimmune Related Diseases Association.

“In addition to looking at each autoimmune disease as an important topic that merits medical attention and research emphasis, we have to look at the common problems of autoimmune diseases,” said Dr. Rose, director of the Johns Hopkins Autoimmune Disease Research Center in Baltimore. Identifying the shared features will likely provide clues to the causes, and ultimately to the cures, he said.

Additionally, when considered collectively as a family of diseases rather than multiple individual disorders, the scope of the public health impact of autoimmune conditions cannot be ignored, said Dr. Rose, alluding to data presented in a briefing report released at the meeting. The report contains an estimate that autoimmune diseases are responsible for more than $100 billion annually in direct health care costs. “We now realize the magnitude of the problem. Conservatively, we’re talking about at least about 80 diseases – although the number of diseases in which autoimmunity plays a significant role could probably be almost double that – and at least 20 million people who are affected,” he said. Despite being such a major public health threat, “it is obvious that the attention given to autoimmune diseases is not nearly proportional to the magnitude of the problem,” Dr. Rose said.

Some of the research, development, and management deficits are highlighted in the AARDA publication, titled “A Briefing Report on Autoimmune Disease and AARDA: Past, Present and Future.” The report contains an assessment of autoimmune diseases, including the most recent data on incidence, prevalence, and etiology. Current and pipeline therapies and trends in research funding are also discussed in the report. For example, most of the currently available therapies target fewer than 10% of the unique autoimmune or autoimmune-related diseases, and new drug development programs only target approximately 30%, according to the report, which will be made available through the AARDA website.

The report also identifies inconsistencies in incidence and prevalence data for autoimmune diseases individually and collectively. The analysis suggests that the actual annual direct and indirect costs of autoimmune diseases likely far exceed the $100 billion estimate. The costs associated with the seven major autoimmune diseases – Crohn’s disease, ulcerative colitis, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, and scleroderma – are estimated to be about $50 billion.

The value of taking a global, collective view of autoimmune diseases is particularly obvious in the research and development setting, said Dr. Rose. The drug development process can take from 7-10 years and the current pipeline lacks drug candidates for more than 70% of the known autoimmune diseases. In light of those hard facts, the most promise for broad application is likely to come from research programs that look for commonalities among groups of autoimmune diseases, he said.

Toward this end, the National Institutes of Health sponsors a range of basic translational and clinical research efforts focusing on autoimmune diseases. The basic research endeavors – the identification of new targets for drugs that could go into development and the discovery of pathways for cells and networks that might be targets for future development, for example – are especially important, Dr. Daniel Rotrosen said at the summit. “That kind of research is tremendously valuable in autoimmune diseases, perhaps more than other diseases, because of the shared underlying mechanisms between the various conditions. If we learn about a pathway that’s important in multiple sclerosis, it may also be important in lupus and 5 or 10 other autoimmune diseases.”

Although clinical trials consume significantly less of the NIH research funding overall, there are some dedicated clinical research networks at the National Institute of Allergy and Infectious Diseases (NIAID), including the Immune Tolerance Network, as well as nine Autoimmune Centers of Excellence across the country. Another research focus is a stem cell transplantation program that is looking at bone marrow transplantation for systemic sclerosis and multiple sclerosis. Another effort involves predominantly preclinical autoimmune disease prevention centers focusing on cutting-edge bench and animal research that is intended to lead prevention strategies later on in clinical studies, reported Dr. Rotrosen, director of the Division of Allergy, Immunology, and Transplantation (DAIT) at NIAID.

“Currently we have approximately 25-30 clinical trials going on in autoimmune diseases, about one-third of which are in type 1 diabetes, one-third for rheumatologic disease and one-third for other conditions,” Dr. Rotrosen stated, noting that clinical trials in this arena are notoriously difficult. In particular, “the complexity and chronicity of autoimmune diseases present many challenges clinically,” he said. “Often, patients go undiagnosed for years, so by the time subjects come into the trials, they have a history of years of established disease that is hard to arrest or reverse at that point. As a result, new therapies are often being tested in late-stage disease, usually after patients have gone through multiple therapy failures, where the chances for successful outcomes are not as good as they would have been with earlier intervention.”

There are also numerous program and operational challenges associated with subject recruitment. “Once you define eligibility criteria for a particular trial, it may turn out that because of prior therapy or disease stage, the number of patients at a given site is too small to power a study. This is especially true with the less common diseases,” Dr. Rotrosen explained. “In such cases, we have to do multisite studies, recruiting patients from around the country, and sometimes we have to go overseas, which introduces regulatory barriers and financial constraints.”

To alleviate some of the challenges, the NIAID provides support for multidisciplinary clinical research networks in order to help facilitate long-term, multisite clinical trials, said Dr. Rotrosen said. In autoimmune disease research, this helps investigators explore the mechanisms of disease progression and get a sense of the impact of therapies over time. “This is especially important with relapsing and remitting diseases. Stable support over time is critical in order to see improvement against this background,” he said. Additionally, the NIAID offers generous support for mechanistic studies and biomarker discovery, “which hopefully will lead to earlier, more accurate diagnoses, and will allow us to stratify subjects based on stage of disease, family history, genetic background, and so forth, so we can ultimately simplify trial designs and make them shorter and less costly.”

Dr. Rose and Dr. Rotrosen did not report conflicts of interest related to their presentations.

Washington – Think globally, but act locally. The political mantra is perfectly suited to describe the necessary approach to not only improving the diagnosis and management of autoimmune diseases, but also to curing and eventually preventing them altogether, Dr. Noel R. Rose said at a meeting on autoimmune diseases organized by the American Autoimmune Related Diseases Association.

“In addition to looking at each autoimmune disease as an important topic that merits medical attention and research emphasis, we have to look at the common problems of autoimmune diseases,” said Dr. Rose, director of the Johns Hopkins Autoimmune Disease Research Center in Baltimore. Identifying the shared features will likely provide clues to the causes, and ultimately to the cures, he said.

Additionally, when considered collectively as a family of diseases rather than multiple individual disorders, the scope of the public health impact of autoimmune conditions cannot be ignored, said Dr. Rose, alluding to data presented in a briefing report released at the meeting. The report contains an estimate that autoimmune diseases are responsible for more than $100 billion annually in direct health care costs. “We now realize the magnitude of the problem. Conservatively, we’re talking about at least about 80 diseases – although the number of diseases in which autoimmunity plays a significant role could probably be almost double that – and at least 20 million people who are affected,” he said. Despite being such a major public health threat, “it is obvious that the attention given to autoimmune diseases is not nearly proportional to the magnitude of the problem,” Dr. Rose said.

Some of the research, development, and management deficits are highlighted in the AARDA publication, titled “A Briefing Report on Autoimmune Disease and AARDA: Past, Present and Future.” The report contains an assessment of autoimmune diseases, including the most recent data on incidence, prevalence, and etiology. Current and pipeline therapies and trends in research funding are also discussed in the report. For example, most of the currently available therapies target fewer than 10% of the unique autoimmune or autoimmune-related diseases, and new drug development programs only target approximately 30%, according to the report, which will be made available through the AARDA website.

The report also identifies inconsistencies in incidence and prevalence data for autoimmune diseases individually and collectively. The analysis suggests that the actual annual direct and indirect costs of autoimmune diseases likely far exceed the $100 billion estimate. The costs associated with the seven major autoimmune diseases – Crohn’s disease, ulcerative colitis, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, and scleroderma – are estimated to be about $50 billion.

The value of taking a global, collective view of autoimmune diseases is particularly obvious in the research and development setting, said Dr. Rose. The drug development process can take from 7-10 years and the current pipeline lacks drug candidates for more than 70% of the known autoimmune diseases. In light of those hard facts, the most promise for broad application is likely to come from research programs that look for commonalities among groups of autoimmune diseases, he said.

Toward this end, the National Institutes of Health sponsors a range of basic translational and clinical research efforts focusing on autoimmune diseases. The basic research endeavors – the identification of new targets for drugs that could go into development and the discovery of pathways for cells and networks that might be targets for future development, for example – are especially important, Dr. Daniel Rotrosen said at the summit. “That kind of research is tremendously valuable in autoimmune diseases, perhaps more than other diseases, because of the shared underlying mechanisms between the various conditions. If we learn about a pathway that’s important in multiple sclerosis, it may also be important in lupus and 5 or 10 other autoimmune diseases.”

Although clinical trials consume significantly less of the NIH research funding overall, there are some dedicated clinical research networks at the National Institute of Allergy and Infectious Diseases (NIAID), including the Immune Tolerance Network, as well as nine Autoimmune Centers of Excellence across the country. Another research focus is a stem cell transplantation program that is looking at bone marrow transplantation for systemic sclerosis and multiple sclerosis. Another effort involves predominantly preclinical autoimmune disease prevention centers focusing on cutting-edge bench and animal research that is intended to lead prevention strategies later on in clinical studies, reported Dr. Rotrosen, director of the Division of Allergy, Immunology, and Transplantation (DAIT) at NIAID.

“Currently we have approximately 25-30 clinical trials going on in autoimmune diseases, about one-third of which are in type 1 diabetes, one-third for rheumatologic disease and one-third for other conditions,” Dr. Rotrosen stated, noting that clinical trials in this arena are notoriously difficult. In particular, “the complexity and chronicity of autoimmune diseases present many challenges clinically,” he said. “Often, patients go undiagnosed for years, so by the time subjects come into the trials, they have a history of years of established disease that is hard to arrest or reverse at that point. As a result, new therapies are often being tested in late-stage disease, usually after patients have gone through multiple therapy failures, where the chances for successful outcomes are not as good as they would have been with earlier intervention.”

There are also numerous program and operational challenges associated with subject recruitment. “Once you define eligibility criteria for a particular trial, it may turn out that because of prior therapy or disease stage, the number of patients at a given site is too small to power a study. This is especially true with the less common diseases,” Dr. Rotrosen explained. “In such cases, we have to do multisite studies, recruiting patients from around the country, and sometimes we have to go overseas, which introduces regulatory barriers and financial constraints.”

To alleviate some of the challenges, the NIAID provides support for multidisciplinary clinical research networks in order to help facilitate long-term, multisite clinical trials, said Dr. Rotrosen said. In autoimmune disease research, this helps investigators explore the mechanisms of disease progression and get a sense of the impact of therapies over time. “This is especially important with relapsing and remitting diseases. Stable support over time is critical in order to see improvement against this background,” he said. Additionally, the NIAID offers generous support for mechanistic studies and biomarker discovery, “which hopefully will lead to earlier, more accurate diagnoses, and will allow us to stratify subjects based on stage of disease, family history, genetic background, and so forth, so we can ultimately simplify trial designs and make them shorter and less costly.”

Dr. Rose and Dr. Rotrosen did not report conflicts of interest related to their presentations.

Washington – Think globally, but act locally. The political mantra is perfectly suited to describe the necessary approach to not only improving the diagnosis and management of autoimmune diseases, but also to curing and eventually preventing them altogether, Dr. Noel R. Rose said at a meeting on autoimmune diseases organized by the American Autoimmune Related Diseases Association.

“In addition to looking at each autoimmune disease as an important topic that merits medical attention and research emphasis, we have to look at the common problems of autoimmune diseases,” said Dr. Rose, director of the Johns Hopkins Autoimmune Disease Research Center in Baltimore. Identifying the shared features will likely provide clues to the causes, and ultimately to the cures, he said.

Additionally, when considered collectively as a family of diseases rather than multiple individual disorders, the scope of the public health impact of autoimmune conditions cannot be ignored, said Dr. Rose, alluding to data presented in a briefing report released at the meeting. The report contains an estimate that autoimmune diseases are responsible for more than $100 billion annually in direct health care costs. “We now realize the magnitude of the problem. Conservatively, we’re talking about at least about 80 diseases – although the number of diseases in which autoimmunity plays a significant role could probably be almost double that – and at least 20 million people who are affected,” he said. Despite being such a major public health threat, “it is obvious that the attention given to autoimmune diseases is not nearly proportional to the magnitude of the problem,” Dr. Rose said.

Some of the research, development, and management deficits are highlighted in the AARDA publication, titled “A Briefing Report on Autoimmune Disease and AARDA: Past, Present and Future.” The report contains an assessment of autoimmune diseases, including the most recent data on incidence, prevalence, and etiology. Current and pipeline therapies and trends in research funding are also discussed in the report. For example, most of the currently available therapies target fewer than 10% of the unique autoimmune or autoimmune-related diseases, and new drug development programs only target approximately 30%, according to the report, which will be made available through the AARDA website.

The report also identifies inconsistencies in incidence and prevalence data for autoimmune diseases individually and collectively. The analysis suggests that the actual annual direct and indirect costs of autoimmune diseases likely far exceed the $100 billion estimate. The costs associated with the seven major autoimmune diseases – Crohn’s disease, ulcerative colitis, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, and scleroderma – are estimated to be about $50 billion.

The value of taking a global, collective view of autoimmune diseases is particularly obvious in the research and development setting, said Dr. Rose. The drug development process can take from 7-10 years and the current pipeline lacks drug candidates for more than 70% of the known autoimmune diseases. In light of those hard facts, the most promise for broad application is likely to come from research programs that look for commonalities among groups of autoimmune diseases, he said.

Toward this end, the National Institutes of Health sponsors a range of basic translational and clinical research efforts focusing on autoimmune diseases. The basic research endeavors – the identification of new targets for drugs that could go into development and the discovery of pathways for cells and networks that might be targets for future development, for example – are especially important, Dr. Daniel Rotrosen said at the summit. “That kind of research is tremendously valuable in autoimmune diseases, perhaps more than other diseases, because of the shared underlying mechanisms between the various conditions. If we learn about a pathway that’s important in multiple sclerosis, it may also be important in lupus and 5 or 10 other autoimmune diseases.”

Although clinical trials consume significantly less of the NIH research funding overall, there are some dedicated clinical research networks at the National Institute of Allergy and Infectious Diseases (NIAID), including the Immune Tolerance Network, as well as nine Autoimmune Centers of Excellence across the country. Another research focus is a stem cell transplantation program that is looking at bone marrow transplantation for systemic sclerosis and multiple sclerosis. Another effort involves predominantly preclinical autoimmune disease prevention centers focusing on cutting-edge bench and animal research that is intended to lead prevention strategies later on in clinical studies, reported Dr. Rotrosen, director of the Division of Allergy, Immunology, and Transplantation (DAIT) at NIAID.

“Currently we have approximately 25-30 clinical trials going on in autoimmune diseases, about one-third of which are in type 1 diabetes, one-third for rheumatologic disease and one-third for other conditions,” Dr. Rotrosen stated, noting that clinical trials in this arena are notoriously difficult. In particular, “the complexity and chronicity of autoimmune diseases present many challenges clinically,” he said. “Often, patients go undiagnosed for years, so by the time subjects come into the trials, they have a history of years of established disease that is hard to arrest or reverse at that point. As a result, new therapies are often being tested in late-stage disease, usually after patients have gone through multiple therapy failures, where the chances for successful outcomes are not as good as they would have been with earlier intervention.”

There are also numerous program and operational challenges associated with subject recruitment. “Once you define eligibility criteria for a particular trial, it may turn out that because of prior therapy or disease stage, the number of patients at a given site is too small to power a study. This is especially true with the less common diseases,” Dr. Rotrosen explained. “In such cases, we have to do multisite studies, recruiting patients from around the country, and sometimes we have to go overseas, which introduces regulatory barriers and financial constraints.”

To alleviate some of the challenges, the NIAID provides support for multidisciplinary clinical research networks in order to help facilitate long-term, multisite clinical trials, said Dr. Rotrosen said. In autoimmune disease research, this helps investigators explore the mechanisms of disease progression and get a sense of the impact of therapies over time. “This is especially important with relapsing and remitting diseases. Stable support over time is critical in order to see improvement against this background,” he said. Additionally, the NIAID offers generous support for mechanistic studies and biomarker discovery, “which hopefully will lead to earlier, more accurate diagnoses, and will allow us to stratify subjects based on stage of disease, family history, genetic background, and so forth, so we can ultimately simplify trial designs and make them shorter and less costly.”

Dr. Rose and Dr. Rotrosen did not report conflicts of interest related to their presentations.