Psoriasis

MIAMI – Children with psoriasis have a significantly greater risk of developing a psychiatric disorder than those without psoriasis, according to findings from a large, retrospective, case-control study.

Nationally representative health plan data for 7,404 children with psoriasis under age 18 years found that 5.1% were diagnosed with or treated for a psychiatric disorder after health plan enrollment, compared with 4.1% of 37,020 controls. Psoriasis patients were particularly more likely to be diagnosed with depression (3%) or anxiety (1.8%), compared with controls (2.4% and 1.4%, respectively), Carol Bao, Ph.D., reported during a poster discussion session at the annual meeting of the American Academy of Dermatology.

For children with psoriasis, the estimated hazard ratio for developing any psychiatric disorder was 1.25, for developing depression was 1.23, and for developing anxiety was 1.32, said Dr. Bao, a senior manager at Abbott Laboratories, Chicago.

The investigators also looked at prescriptions for psychotropic medications in assessing risk for development of psychiatric disorders. Prescriptions can be a marker for a diagnosis in cases where the prescribing physician may be hesitant to refer the patient or make a diagnosis, Dr. Bao explained, noting that this helped correct for possible underestimation of the development of psychiatric disorders and provided a risk estimate range.

When both diagnoses and prescriptions were considered, psoriasis patients had 25%-47% greater risk of developing a psychiatric disorder, 23%-62% greater risk of developing depression, and 32%-250% greater risk of developing anxiety, compared with controls, she said.

Patients included in the study had a mean age of 11.4 years. They were selected from a database of health plan participants who were enrolled in a plan at least 6 months before and after the first psoriasis diagnosis date (the index date), and who were followed from the index date until they were first diagnosed with any psychiatric disorder or were prescribed a drug used for the treatment of a psychiatric disorder. Any plan participant with a pre-enrollment psychiatric diagnosis or prescription was excluded.

Controls were matched to patients based on age, sex, and index date.

The findings of an increased risk of developing psychiatric disorders in case patients remained significant after controlling for age, sex, health plan, region of residence, and comorbidities, Dr. Bao noted.

The study is limited by the potential for coding and reporting errors in the data used and by lack of information on the severity of the psychiatric disorders. However, the findings do suggest that the psychiatric impact of psoriasis on children must be addressed because of the potential for both short-and long-term adverse effects.

"If we put these data in perspective, the development of psychiatric disorders at a young age can have a great impact in future adult life," she said.

Abbott Laboratories sponsored the study.

MIAMI – Children with psoriasis have a significantly greater risk of developing a psychiatric disorder than those without psoriasis, according to findings from a large, retrospective, case-control study.

Nationally representative health plan data for 7,404 children with psoriasis under age 18 years found that 5.1% were diagnosed with or treated for a psychiatric disorder after health plan enrollment, compared with 4.1% of 37,020 controls. Psoriasis patients were particularly more likely to be diagnosed with depression (3%) or anxiety (1.8%), compared with controls (2.4% and 1.4%, respectively), Carol Bao, Ph.D., reported during a poster discussion session at the annual meeting of the American Academy of Dermatology.

For children with psoriasis, the estimated hazard ratio for developing any psychiatric disorder was 1.25, for developing depression was 1.23, and for developing anxiety was 1.32, said Dr. Bao, a senior manager at Abbott Laboratories, Chicago.

The investigators also looked at prescriptions for psychotropic medications in assessing risk for development of psychiatric disorders. Prescriptions can be a marker for a diagnosis in cases where the prescribing physician may be hesitant to refer the patient or make a diagnosis, Dr. Bao explained, noting that this helped correct for possible underestimation of the development of psychiatric disorders and provided a risk estimate range.

When both diagnoses and prescriptions were considered, psoriasis patients had 25%-47% greater risk of developing a psychiatric disorder, 23%-62% greater risk of developing depression, and 32%-250% greater risk of developing anxiety, compared with controls, she said.

Patients included in the study had a mean age of 11.4 years. They were selected from a database of health plan participants who were enrolled in a plan at least 6 months before and after the first psoriasis diagnosis date (the index date), and who were followed from the index date until they were first diagnosed with any psychiatric disorder or were prescribed a drug used for the treatment of a psychiatric disorder. Any plan participant with a pre-enrollment psychiatric diagnosis or prescription was excluded.

Controls were matched to patients based on age, sex, and index date.

The findings of an increased risk of developing psychiatric disorders in case patients remained significant after controlling for age, sex, health plan, region of residence, and comorbidities, Dr. Bao noted.

The study is limited by the potential for coding and reporting errors in the data used and by lack of information on the severity of the psychiatric disorders. However, the findings do suggest that the psychiatric impact of psoriasis on children must be addressed because of the potential for both short-and long-term adverse effects.

"If we put these data in perspective, the development of psychiatric disorders at a young age can have a great impact in future adult life," she said.

Abbott Laboratories sponsored the study.

MIAMI – Children with psoriasis have a significantly greater risk of developing a psychiatric disorder than those without psoriasis, according to findings from a large, retrospective, case-control study.

Nationally representative health plan data for 7,404 children with psoriasis under age 18 years found that 5.1% were diagnosed with or treated for a psychiatric disorder after health plan enrollment, compared with 4.1% of 37,020 controls. Psoriasis patients were particularly more likely to be diagnosed with depression (3%) or anxiety (1.8%), compared with controls (2.4% and 1.4%, respectively), Carol Bao, Ph.D., reported during a poster discussion session at the annual meeting of the American Academy of Dermatology.

For children with psoriasis, the estimated hazard ratio for developing any psychiatric disorder was 1.25, for developing depression was 1.23, and for developing anxiety was 1.32, said Dr. Bao, a senior manager at Abbott Laboratories, Chicago.

The investigators also looked at prescriptions for psychotropic medications in assessing risk for development of psychiatric disorders. Prescriptions can be a marker for a diagnosis in cases where the prescribing physician may be hesitant to refer the patient or make a diagnosis, Dr. Bao explained, noting that this helped correct for possible underestimation of the development of psychiatric disorders and provided a risk estimate range.

When both diagnoses and prescriptions were considered, psoriasis patients had 25%-47% greater risk of developing a psychiatric disorder, 23%-62% greater risk of developing depression, and 32%-250% greater risk of developing anxiety, compared with controls, she said.

Patients included in the study had a mean age of 11.4 years. They were selected from a database of health plan participants who were enrolled in a plan at least 6 months before and after the first psoriasis diagnosis date (the index date), and who were followed from the index date until they were first diagnosed with any psychiatric disorder or were prescribed a drug used for the treatment of a psychiatric disorder. Any plan participant with a pre-enrollment psychiatric diagnosis or prescription was excluded.

Controls were matched to patients based on age, sex, and index date.

The findings of an increased risk of developing psychiatric disorders in case patients remained significant after controlling for age, sex, health plan, region of residence, and comorbidities, Dr. Bao noted.

The study is limited by the potential for coding and reporting errors in the data used and by lack of information on the severity of the psychiatric disorders. However, the findings do suggest that the psychiatric impact of psoriasis on children must be addressed because of the potential for both short-and long-term adverse effects.

"If we put these data in perspective, the development of psychiatric disorders at a young age can have a great impact in future adult life," she said.

Abbott Laboratories sponsored the study.

MIAMI – Treatment with ustekinumab significantly improved sexual function in patients with moderate to severe psoriasis, according to a secondary analysis of phase III study data.

"It has become really clear that psoriasis has an influence on sexual function in our patients," Dr. Lyn Guenther said during a poster discussion session at the annual meeting of the American Academy of Dermatology.

There is, however, a paucity of published data--with only a few researchers quantifying sexual function and none examining possible benefits of medical treatment in this patient population.

To find out if ustekinumab could improve sexual function, Dr. Guenther and her colleagues assessed quality-of-life data from the phase III PHOENIX I (Lancet 2008;371:1665-74) and PHOENIX II (Lancet 2008;371:1675-84) trials.

At baseline, 23% of the combined 1,996 study patients reported that psoriasis affected their sexual function. Impaired function was defined by a patient response of "very much" or "a lot" of sexual difficulties related to their skin disease on the Dermatology Life Quality Index (DLQI). All participants had moderate to severe psoriasis and 69% were men. By gender, 28% of women and 21% of men reported impaired sexual function.

DLQI scores range from 0 to 30. Mean DLQI patient score at baseline was 12, "indicating a very large negative effect on patients' lives," said Dr. Guenther, professor of dermatology at the University of Western Ontario, London.

The mean Psoriasis Area and Severity Index (PASI) score was a "fairly significant" 20, she said, and mean percentage of body surface area affected by psoriasis was 26%.

Worse sexual dysfunction was significantly associated with increased psoriasis disease severity. As an example, 54% of the women with a PASI score greater than 30 reported a significant impact of their condition on sexuality. "At each of the PASI severity cut-off points, it's almost a linear increase," Dr. Guenther said.

"Can we make a difference?" she asked. After 12 weeks, the percentage of patients who reported sexual function impairment dropped from 23% to 3% in both ustekinumab dosage groups, with no change observed in the control group. "It was surprising to me to see how quickly we could improve the impairment," she said.

Similarly, at week 12, DLQI scores in the treatment groups decreased by a mean of 9.1 points, versus a 0.5-point decrease in controls, a statistically significant difference.

A meeting attendee asked if there was a difference between men and women in terms of improvement. Dr. Guenther replied no, that "they each improved dramatically."

The PHOENIX I and II trial investigators randomized 1,334 patients to ustekinumab (45 mg or 90 mg) at weeks 0, 4, and every 12 weeks thereafter. They also randomized another 662 patients to placebo at weeks 0 and 4, with crossover to ustekinumab (45 mg or 90 mg) at week 12. Placebo patients who crossed over to ustekinumab experienced similar benefits. "The lessening of the sexual dysfunction continued to week 24," Dr. Guenther said.

The mechanism of action for improved sexual function is unknown, but patients treated with ustekinumab might experience less fatigue and more hope about their condition improving, she suggested.

"Why these people have [sexual function] problems is not clear. Future trials will be done to identify the reasons," Dr. Guenther said. She added that further research using validated sexual dysfunction instruments is warranted.

Dr. Guenther was a consultant for Johnson & Johnson, sponsor of the study. Ustekinumab (Stelara) is manufactured by Centocor Ortho Biotech, a wholly-owned subsidiary of Johnson & Johnson.

MIAMI – Treatment with ustekinumab significantly improved sexual function in patients with moderate to severe psoriasis, according to a secondary analysis of phase III study data.

"It has become really clear that psoriasis has an influence on sexual function in our patients," Dr. Lyn Guenther said during a poster discussion session at the annual meeting of the American Academy of Dermatology.

There is, however, a paucity of published data--with only a few researchers quantifying sexual function and none examining possible benefits of medical treatment in this patient population.

To find out if ustekinumab could improve sexual function, Dr. Guenther and her colleagues assessed quality-of-life data from the phase III PHOENIX I (Lancet 2008;371:1665-74) and PHOENIX II (Lancet 2008;371:1675-84) trials.

At baseline, 23% of the combined 1,996 study patients reported that psoriasis affected their sexual function. Impaired function was defined by a patient response of "very much" or "a lot" of sexual difficulties related to their skin disease on the Dermatology Life Quality Index (DLQI). All participants had moderate to severe psoriasis and 69% were men. By gender, 28% of women and 21% of men reported impaired sexual function.

DLQI scores range from 0 to 30. Mean DLQI patient score at baseline was 12, "indicating a very large negative effect on patients' lives," said Dr. Guenther, professor of dermatology at the University of Western Ontario, London.

The mean Psoriasis Area and Severity Index (PASI) score was a "fairly significant" 20, she said, and mean percentage of body surface area affected by psoriasis was 26%.

Worse sexual dysfunction was significantly associated with increased psoriasis disease severity. As an example, 54% of the women with a PASI score greater than 30 reported a significant impact of their condition on sexuality. "At each of the PASI severity cut-off points, it's almost a linear increase," Dr. Guenther said.

"Can we make a difference?" she asked. After 12 weeks, the percentage of patients who reported sexual function impairment dropped from 23% to 3% in both ustekinumab dosage groups, with no change observed in the control group. "It was surprising to me to see how quickly we could improve the impairment," she said.

Similarly, at week 12, DLQI scores in the treatment groups decreased by a mean of 9.1 points, versus a 0.5-point decrease in controls, a statistically significant difference.

A meeting attendee asked if there was a difference between men and women in terms of improvement. Dr. Guenther replied no, that "they each improved dramatically."

The PHOENIX I and II trial investigators randomized 1,334 patients to ustekinumab (45 mg or 90 mg) at weeks 0, 4, and every 12 weeks thereafter. They also randomized another 662 patients to placebo at weeks 0 and 4, with crossover to ustekinumab (45 mg or 90 mg) at week 12. Placebo patients who crossed over to ustekinumab experienced similar benefits. "The lessening of the sexual dysfunction continued to week 24," Dr. Guenther said.

The mechanism of action for improved sexual function is unknown, but patients treated with ustekinumab might experience less fatigue and more hope about their condition improving, she suggested.

"Why these people have [sexual function] problems is not clear. Future trials will be done to identify the reasons," Dr. Guenther said. She added that further research using validated sexual dysfunction instruments is warranted.

Dr. Guenther was a consultant for Johnson & Johnson, sponsor of the study. Ustekinumab (Stelara) is manufactured by Centocor Ortho Biotech, a wholly-owned subsidiary of Johnson & Johnson.

MIAMI – Treatment with ustekinumab significantly improved sexual function in patients with moderate to severe psoriasis, according to a secondary analysis of phase III study data.

"It has become really clear that psoriasis has an influence on sexual function in our patients," Dr. Lyn Guenther said during a poster discussion session at the annual meeting of the American Academy of Dermatology.

There is, however, a paucity of published data--with only a few researchers quantifying sexual function and none examining possible benefits of medical treatment in this patient population.

To find out if ustekinumab could improve sexual function, Dr. Guenther and her colleagues assessed quality-of-life data from the phase III PHOENIX I (Lancet 2008;371:1665-74) and PHOENIX II (Lancet 2008;371:1675-84) trials.

At baseline, 23% of the combined 1,996 study patients reported that psoriasis affected their sexual function. Impaired function was defined by a patient response of "very much" or "a lot" of sexual difficulties related to their skin disease on the Dermatology Life Quality Index (DLQI). All participants had moderate to severe psoriasis and 69% were men. By gender, 28% of women and 21% of men reported impaired sexual function.

DLQI scores range from 0 to 30. Mean DLQI patient score at baseline was 12, "indicating a very large negative effect on patients' lives," said Dr. Guenther, professor of dermatology at the University of Western Ontario, London.

The mean Psoriasis Area and Severity Index (PASI) score was a "fairly significant" 20, she said, and mean percentage of body surface area affected by psoriasis was 26%.

Worse sexual dysfunction was significantly associated with increased psoriasis disease severity. As an example, 54% of the women with a PASI score greater than 30 reported a significant impact of their condition on sexuality. "At each of the PASI severity cut-off points, it's almost a linear increase," Dr. Guenther said.

"Can we make a difference?" she asked. After 12 weeks, the percentage of patients who reported sexual function impairment dropped from 23% to 3% in both ustekinumab dosage groups, with no change observed in the control group. "It was surprising to me to see how quickly we could improve the impairment," she said.

Similarly, at week 12, DLQI scores in the treatment groups decreased by a mean of 9.1 points, versus a 0.5-point decrease in controls, a statistically significant difference.

A meeting attendee asked if there was a difference between men and women in terms of improvement. Dr. Guenther replied no, that "they each improved dramatically."

The PHOENIX I and II trial investigators randomized 1,334 patients to ustekinumab (45 mg or 90 mg) at weeks 0, 4, and every 12 weeks thereafter. They also randomized another 662 patients to placebo at weeks 0 and 4, with crossover to ustekinumab (45 mg or 90 mg) at week 12. Placebo patients who crossed over to ustekinumab experienced similar benefits. "The lessening of the sexual dysfunction continued to week 24," Dr. Guenther said.

The mechanism of action for improved sexual function is unknown, but patients treated with ustekinumab might experience less fatigue and more hope about their condition improving, she suggested.

"Why these people have [sexual function] problems is not clear. Future trials will be done to identify the reasons," Dr. Guenther said. She added that further research using validated sexual dysfunction instruments is warranted.

Dr. Guenther was a consultant for Johnson & Johnson, sponsor of the study. Ustekinumab (Stelara) is manufactured by Centocor Ortho Biotech, a wholly-owned subsidiary of Johnson & Johnson.

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.

Miami — Etanercept therapy in children and adolescents with moderate to severe plaque psoriasis remained safe, well tolerated, and efficacious in the first 96 weeks of a 5-year open-label extension study, Dr. Richard Langley reported at the annual meeting of the American Academy of Dermatology.

The multicenter study, designed to evaluate long-term safety and efficacy of the immunosuppressant drug in the pediatric population, followed an initial 48-week randomized controlled trial reported in 2008 (N. Engl. J. Med. 2008;358:241-51). Read our story here.

Of 211 patients aged 4-17 years included in the initial trial, 182 (86%) completed that trial or achieved Psoriasis Area Severity Index (PASI) of 50 or better on or after week 12 with no adverse events, and thus were eligible and agreed to participate in the extension study. Of these, most (80%) reported at least one adverse event by week 96 of the extension study, but only three reported a total of five serious adverse events, none of which were infectious or deemed attributable to etanercept, Dr. Langley, director of research in the division of clinical dermatology and cutaneous science at Dalhousie University, Halifax, N.S., said during a poster discussion session.

The most common adverse events were upper respiratory tract infections in 25% of patients, nasopharyngitis in 17%, streptococcal pharyngitis in 13%, headache in 12%, and sinusitis in 11%. Serious adverse events were anxiety in one patient, intestinal obstruction in one patient, and abdominal pain, dehydration, and elective abortion all in one patient, Dr. Langley said, stressing that no opportunistic infections or malignancies occurred, which is particularly important to consider when evaluating the safety of an immunosuppressive agent.

Only two patients in the extension phase withdrew due to adverse events, and neither of these (Crohn’s disease in one, and sinusitis in one) were considered to be due to etanercept. Other patients did withdraw, however, most often due to consent withdrawal (19 patients) and loss to follow-up (14 patients); 140 patients completed 96 weeks of the extension study, and most (89%) of these achieved PASI of 50 or better (relative to baseline in the initial 48-week trial), including 30% who achieved PASI of 90 or better.

The mean PASI improvement was about 70%, and static Physician Global Assessment scores of 0 or 1 (clear or almost clear) were achieved in 47% of patients.

Treatment in both the initial and extension phases of the trial involved once-weekly subcutaneous injection of 0.8 mg/kg of etanercept, with a maximum dose of 50 mg/kg. Patients were also allowed to use standard topical treatments.

The conclusion at this stage of the trial is that etanercept is acceptably safe in this population at 96 weeks, Dr. Langley said, adding that this is the longest extension in a randomized controlled trial of patients receiving etanercept. No new adverse events or serious adverse events were seen, compared with the initial research.

“We believe this supports the continued study [of etanercept] and we will continue to follow these patients up to 5 years for infections and major adverse events,” he said.

Dr. Langley disclosed that he was an adviser and investigator for Amgen, and he has received grants and honoraria from Amgen. This trial was funded by Immunex Corp., a wholly-owned subsidiary of Amgen. Amgen and Wyeth Pharmaceuticals Inc. (now a part of Pfizer) together market Enbrel (etanercept).

Miami — Etanercept therapy in children and adolescents with moderate to severe plaque psoriasis remained safe, well tolerated, and efficacious in the first 96 weeks of a 5-year open-label extension study, Dr. Richard Langley reported at the annual meeting of the American Academy of Dermatology.

The multicenter study, designed to evaluate long-term safety and efficacy of the immunosuppressant drug in the pediatric population, followed an initial 48-week randomized controlled trial reported in 2008 (N. Engl. J. Med. 2008;358:241-51). Read our story here.

Of 211 patients aged 4-17 years included in the initial trial, 182 (86%) completed that trial or achieved Psoriasis Area Severity Index (PASI) of 50 or better on or after week 12 with no adverse events, and thus were eligible and agreed to participate in the extension study. Of these, most (80%) reported at least one adverse event by week 96 of the extension study, but only three reported a total of five serious adverse events, none of which were infectious or deemed attributable to etanercept, Dr. Langley, director of research in the division of clinical dermatology and cutaneous science at Dalhousie University, Halifax, N.S., said during a poster discussion session.

The most common adverse events were upper respiratory tract infections in 25% of patients, nasopharyngitis in 17%, streptococcal pharyngitis in 13%, headache in 12%, and sinusitis in 11%. Serious adverse events were anxiety in one patient, intestinal obstruction in one patient, and abdominal pain, dehydration, and elective abortion all in one patient, Dr. Langley said, stressing that no opportunistic infections or malignancies occurred, which is particularly important to consider when evaluating the safety of an immunosuppressive agent.

Only two patients in the extension phase withdrew due to adverse events, and neither of these (Crohn’s disease in one, and sinusitis in one) were considered to be due to etanercept. Other patients did withdraw, however, most often due to consent withdrawal (19 patients) and loss to follow-up (14 patients); 140 patients completed 96 weeks of the extension study, and most (89%) of these achieved PASI of 50 or better (relative to baseline in the initial 48-week trial), including 30% who achieved PASI of 90 or better.

The mean PASI improvement was about 70%, and static Physician Global Assessment scores of 0 or 1 (clear or almost clear) were achieved in 47% of patients.

Treatment in both the initial and extension phases of the trial involved once-weekly subcutaneous injection of 0.8 mg/kg of etanercept, with a maximum dose of 50 mg/kg. Patients were also allowed to use standard topical treatments.

The conclusion at this stage of the trial is that etanercept is acceptably safe in this population at 96 weeks, Dr. Langley said, adding that this is the longest extension in a randomized controlled trial of patients receiving etanercept. No new adverse events or serious adverse events were seen, compared with the initial research.

“We believe this supports the continued study [of etanercept] and we will continue to follow these patients up to 5 years for infections and major adverse events,” he said.

Dr. Langley disclosed that he was an adviser and investigator for Amgen, and he has received grants and honoraria from Amgen. This trial was funded by Immunex Corp., a wholly-owned subsidiary of Amgen. Amgen and Wyeth Pharmaceuticals Inc. (now a part of Pfizer) together market Enbrel (etanercept).

Miami — Etanercept therapy in children and adolescents with moderate to severe plaque psoriasis remained safe, well tolerated, and efficacious in the first 96 weeks of a 5-year open-label extension study, Dr. Richard Langley reported at the annual meeting of the American Academy of Dermatology.

The multicenter study, designed to evaluate long-term safety and efficacy of the immunosuppressant drug in the pediatric population, followed an initial 48-week randomized controlled trial reported in 2008 (N. Engl. J. Med. 2008;358:241-51). Read our story here.

Of 211 patients aged 4-17 years included in the initial trial, 182 (86%) completed that trial or achieved Psoriasis Area Severity Index (PASI) of 50 or better on or after week 12 with no adverse events, and thus were eligible and agreed to participate in the extension study. Of these, most (80%) reported at least one adverse event by week 96 of the extension study, but only three reported a total of five serious adverse events, none of which were infectious or deemed attributable to etanercept, Dr. Langley, director of research in the division of clinical dermatology and cutaneous science at Dalhousie University, Halifax, N.S., said during a poster discussion session.

The most common adverse events were upper respiratory tract infections in 25% of patients, nasopharyngitis in 17%, streptococcal pharyngitis in 13%, headache in 12%, and sinusitis in 11%. Serious adverse events were anxiety in one patient, intestinal obstruction in one patient, and abdominal pain, dehydration, and elective abortion all in one patient, Dr. Langley said, stressing that no opportunistic infections or malignancies occurred, which is particularly important to consider when evaluating the safety of an immunosuppressive agent.

Only two patients in the extension phase withdrew due to adverse events, and neither of these (Crohn’s disease in one, and sinusitis in one) were considered to be due to etanercept. Other patients did withdraw, however, most often due to consent withdrawal (19 patients) and loss to follow-up (14 patients); 140 patients completed 96 weeks of the extension study, and most (89%) of these achieved PASI of 50 or better (relative to baseline in the initial 48-week trial), including 30% who achieved PASI of 90 or better.

The mean PASI improvement was about 70%, and static Physician Global Assessment scores of 0 or 1 (clear or almost clear) were achieved in 47% of patients.

Treatment in both the initial and extension phases of the trial involved once-weekly subcutaneous injection of 0.8 mg/kg of etanercept, with a maximum dose of 50 mg/kg. Patients were also allowed to use standard topical treatments.

The conclusion at this stage of the trial is that etanercept is acceptably safe in this population at 96 weeks, Dr. Langley said, adding that this is the longest extension in a randomized controlled trial of patients receiving etanercept. No new adverse events or serious adverse events were seen, compared with the initial research.

“We believe this supports the continued study [of etanercept] and we will continue to follow these patients up to 5 years for infections and major adverse events,” he said.

Dr. Langley disclosed that he was an adviser and investigator for Amgen, and he has received grants and honoraria from Amgen. This trial was funded by Immunex Corp., a wholly-owned subsidiary of Amgen. Amgen and Wyeth Pharmaceuticals Inc. (now a part of Pfizer) together market Enbrel (etanercept).

Montreal – Injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a study presented at the annual meeting of the Canadian Rheumatology Association.

“All we're talking about here is an association; we can't infer causation,” said the study’s principal investigator, Dr. Dafna Gladman, in an interview.

Previous, less rigorous studies have suggested the association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto and deputy director of the Centre for Prognosis Studies in the Rheumatic Diseases in that city.

“This study supports that notion – that environmental factors are important – but we think genetic factors are also involved,” as well as immunologic factors, she said, explaining that at most, 30% of psoriasis patients go on to develop PsA.

Her study, which was presented as a poster at the meeting, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone, in order to identify risk factors for progression to PsA.

Men accounted for a similar percentage of both groups (46% in the PsA group and 44% in the controls). The mean age of participants in each group was similar (45 years and 48 years, respectively) as was the mean duration of psoriasis (17.5 years and 18.5 years, respectively). The mean duration of PsA was 3 years.

A questionnaire was administered to all patients to assess their environmental exposure over the past 10 years, including occupational trauma, infection, immunization, smoking status and history, and psychological stress.

Univariate and multivariate logistic regression analysis was used to determine the odds ratio of each exposure prior to the diagnosis of PsA.

“We actually examined all the patients with psoriasis to make sure they didn’t have psoriatic arthritis,” she said.

Univariate analysis revealed that a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an OR of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8.

And the third-highest risk factor was any injury requiring medical attention (OR, 2.43).

Multivariate analysis revealed that injuries requiring medical attention but excluding fracture and motor vehicle accident (OR, 2.3; P = .03), occupations requiring the lifting of heavy loads (OR, 2.7; P = .002), and severe infection requiring hospitalization (OR, 10.6; P = .03) were significantly associated with progression from psoriasis to PsA.

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” said Dr. Gladman. “And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress; in fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis.”

After the multifactorial analysis, smoking appeared to be associated with decreased risk, she added. Current smoking had an OR of 0.4 (P = .01), and past smoking had an OR of 0.5 (P = .04).

Dr. Gladman said that the findings are too preliminary to inform clinical recommendations at this time, but psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it’s the only factor, we don’t know, because there are also genetic factors involved. It’s quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.”

She said that the next step should be to look at genetic and environmental factors and see if they are independent or not.

Dr. Gladman declared no conflicts of interest.

Montreal – Injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a study presented at the annual meeting of the Canadian Rheumatology Association.

“All we're talking about here is an association; we can't infer causation,” said the study’s principal investigator, Dr. Dafna Gladman, in an interview.

Previous, less rigorous studies have suggested the association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto and deputy director of the Centre for Prognosis Studies in the Rheumatic Diseases in that city.

“This study supports that notion – that environmental factors are important – but we think genetic factors are also involved,” as well as immunologic factors, she said, explaining that at most, 30% of psoriasis patients go on to develop PsA.

Her study, which was presented as a poster at the meeting, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone, in order to identify risk factors for progression to PsA.

Men accounted for a similar percentage of both groups (46% in the PsA group and 44% in the controls). The mean age of participants in each group was similar (45 years and 48 years, respectively) as was the mean duration of psoriasis (17.5 years and 18.5 years, respectively). The mean duration of PsA was 3 years.

A questionnaire was administered to all patients to assess their environmental exposure over the past 10 years, including occupational trauma, infection, immunization, smoking status and history, and psychological stress.

Univariate and multivariate logistic regression analysis was used to determine the odds ratio of each exposure prior to the diagnosis of PsA.

“We actually examined all the patients with psoriasis to make sure they didn’t have psoriatic arthritis,” she said.

Univariate analysis revealed that a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an OR of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8.

And the third-highest risk factor was any injury requiring medical attention (OR, 2.43).

Multivariate analysis revealed that injuries requiring medical attention but excluding fracture and motor vehicle accident (OR, 2.3; P = .03), occupations requiring the lifting of heavy loads (OR, 2.7; P = .002), and severe infection requiring hospitalization (OR, 10.6; P = .03) were significantly associated with progression from psoriasis to PsA.

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” said Dr. Gladman. “And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress; in fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis.”

After the multifactorial analysis, smoking appeared to be associated with decreased risk, she added. Current smoking had an OR of 0.4 (P = .01), and past smoking had an OR of 0.5 (P = .04).

Dr. Gladman said that the findings are too preliminary to inform clinical recommendations at this time, but psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it’s the only factor, we don’t know, because there are also genetic factors involved. It’s quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.”

She said that the next step should be to look at genetic and environmental factors and see if they are independent or not.

Dr. Gladman declared no conflicts of interest.

Montreal – Injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a study presented at the annual meeting of the Canadian Rheumatology Association.

“All we're talking about here is an association; we can't infer causation,” said the study’s principal investigator, Dr. Dafna Gladman, in an interview.

Previous, less rigorous studies have suggested the association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto and deputy director of the Centre for Prognosis Studies in the Rheumatic Diseases in that city.

“This study supports that notion – that environmental factors are important – but we think genetic factors are also involved,” as well as immunologic factors, she said, explaining that at most, 30% of psoriasis patients go on to develop PsA.

Her study, which was presented as a poster at the meeting, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone, in order to identify risk factors for progression to PsA.

Men accounted for a similar percentage of both groups (46% in the PsA group and 44% in the controls). The mean age of participants in each group was similar (45 years and 48 years, respectively) as was the mean duration of psoriasis (17.5 years and 18.5 years, respectively). The mean duration of PsA was 3 years.

A questionnaire was administered to all patients to assess their environmental exposure over the past 10 years, including occupational trauma, infection, immunization, smoking status and history, and psychological stress.

Univariate and multivariate logistic regression analysis was used to determine the odds ratio of each exposure prior to the diagnosis of PsA.

“We actually examined all the patients with psoriasis to make sure they didn’t have psoriatic arthritis,” she said.

Univariate analysis revealed that a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an OR of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8.

And the third-highest risk factor was any injury requiring medical attention (OR, 2.43).

Multivariate analysis revealed that injuries requiring medical attention but excluding fracture and motor vehicle accident (OR, 2.3; P = .03), occupations requiring the lifting of heavy loads (OR, 2.7; P = .002), and severe infection requiring hospitalization (OR, 10.6; P = .03) were significantly associated with progression from psoriasis to PsA.

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” said Dr. Gladman. “And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress; in fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis.”

After the multifactorial analysis, smoking appeared to be associated with decreased risk, she added. Current smoking had an OR of 0.4 (P = .01), and past smoking had an OR of 0.5 (P = .04).

Dr. Gladman said that the findings are too preliminary to inform clinical recommendations at this time, but psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it’s the only factor, we don’t know, because there are also genetic factors involved. It’s quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.”

She said that the next step should be to look at genetic and environmental factors and see if they are independent or not.

Dr. Gladman declared no conflicts of interest.

Psoriasis vulgaris is a multifactorial heritable disease characterized by severe inflammation resulting in poorly differentiated, hyperproliferative keratinocytes. Recent advances in genetic analyses have implicated components regulating the interleukin (IL)-23 and nuclear factor-B pathways as risk factors for psoriasis. These inflammatory pathways exhibit increased activity in skin lesions, and promote secretion of various cytokines, such as IL-17 and IL-22. Unrestrained, the activated inflammatory cytokine network in psoriasis may trigger a vicious cycle of inflammation and cellular proliferation that ultimately results in lesion formation. These advances in genetic analyses, together with the progress made in targeted biological therapy, pave the path to tailor treatment on the basis of an individual’s genetic and immunologic profile.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis vulgaris is a multifactorial heritable disease characterized by severe inflammation resulting in poorly differentiated, hyperproliferative keratinocytes. Recent advances in genetic analyses have implicated components regulating the interleukin (IL)-23 and nuclear factor-B pathways as risk factors for psoriasis. These inflammatory pathways exhibit increased activity in skin lesions, and promote secretion of various cytokines, such as IL-17 and IL-22. Unrestrained, the activated inflammatory cytokine network in psoriasis may trigger a vicious cycle of inflammation and cellular proliferation that ultimately results in lesion formation. These advances in genetic analyses, together with the progress made in targeted biological therapy, pave the path to tailor treatment on the basis of an individual’s genetic and immunologic profile.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis vulgaris is a multifactorial heritable disease characterized by severe inflammation resulting in poorly differentiated, hyperproliferative keratinocytes. Recent advances in genetic analyses have implicated components regulating the interleukin (IL)-23 and nuclear factor-B pathways as risk factors for psoriasis. These inflammatory pathways exhibit increased activity in skin lesions, and promote secretion of various cytokines, such as IL-17 and IL-22. Unrestrained, the activated inflammatory cytokine network in psoriasis may trigger a vicious cycle of inflammation and cellular proliferation that ultimately results in lesion formation. These advances in genetic analyses, together with the progress made in targeted biological therapy, pave the path to tailor treatment on the basis of an individual’s genetic and immunologic profile.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is a chronic inflammatory disorder that affects approximately 2% of the general population. Numerous studies have evaluated the increased prevalence of comorbid diseases and risk factors in psoriatic patients, including obesity, metabolic syndrome, cardiovascular disease, psoriatic arthritis, autoimmune disease, psychiatric illness, liver disease, smoking, malignancy, chronic obstructive pulmonary disease, sleep apnea, and alcohol abuse. Insight into the overlapping pathogenesis of these comorbidities of psoriasis highlights the importance of immune-mediated mechanisms in these disease states. Psoriasis, with its comorbidities, must be approached in a multidisciplinary manner to effectively and comprehensively understand, manage, and treat those with this complex disorder.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is a chronic inflammatory disorder that affects approximately 2% of the general population. Numerous studies have evaluated the increased prevalence of comorbid diseases and risk factors in psoriatic patients, including obesity, metabolic syndrome, cardiovascular disease, psoriatic arthritis, autoimmune disease, psychiatric illness, liver disease, smoking, malignancy, chronic obstructive pulmonary disease, sleep apnea, and alcohol abuse. Insight into the overlapping pathogenesis of these comorbidities of psoriasis highlights the importance of immune-mediated mechanisms in these disease states. Psoriasis, with its comorbidities, must be approached in a multidisciplinary manner to effectively and comprehensively understand, manage, and treat those with this complex disorder.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is a chronic inflammatory disorder that affects approximately 2% of the general population. Numerous studies have evaluated the increased prevalence of comorbid diseases and risk factors in psoriatic patients, including obesity, metabolic syndrome, cardiovascular disease, psoriatic arthritis, autoimmune disease, psychiatric illness, liver disease, smoking, malignancy, chronic obstructive pulmonary disease, sleep apnea, and alcohol abuse. Insight into the overlapping pathogenesis of these comorbidities of psoriasis highlights the importance of immune-mediated mechanisms in these disease states. Psoriasis, with its comorbidities, must be approached in a multidisciplinary manner to effectively and comprehensively understand, manage, and treat those with this complex disorder.

*For a PDF of the full article, click on the link to the left of this introduction.

Efalizumab was approved for moderate to severe psoriasis in 2003 based on studies in approximately 2700 patients, of whom only 218 were exposed to the drug for more than 1 year. In 2009, after more than 46,000 patients were exposed to efalizumab, the drug was withdrawn from the market after 3 confirmed and 1 suspected case of progressive multifocal leukoencephalopathy (PML) were spontaneously reported. As PML is very rare, it is extremely unlikely that the 4 reported cases were due to chance and given that PML occurs primarily in patients who are immunosuppressed, the association is likely causal. The identification of PML as a serious, but statistically rare risk of efalizumab demonstrates the strengths and weaknesses of the current drug approval and pharmacovigilance processes for fully measuring the safety of a drug. Patients and clinicians need to be aware of the relative completeness and limitations of existing safety data of a drug when selecting a treatment.

*For a PDF of the full article, click on the link to the left of this introduction.

Efalizumab was approved for moderate to severe psoriasis in 2003 based on studies in approximately 2700 patients, of whom only 218 were exposed to the drug for more than 1 year. In 2009, after more than 46,000 patients were exposed to efalizumab, the drug was withdrawn from the market after 3 confirmed and 1 suspected case of progressive multifocal leukoencephalopathy (PML) were spontaneously reported. As PML is very rare, it is extremely unlikely that the 4 reported cases were due to chance and given that PML occurs primarily in patients who are immunosuppressed, the association is likely causal. The identification of PML as a serious, but statistically rare risk of efalizumab demonstrates the strengths and weaknesses of the current drug approval and pharmacovigilance processes for fully measuring the safety of a drug. Patients and clinicians need to be aware of the relative completeness and limitations of existing safety data of a drug when selecting a treatment.

*For a PDF of the full article, click on the link to the left of this introduction.

Efalizumab was approved for moderate to severe psoriasis in 2003 based on studies in approximately 2700 patients, of whom only 218 were exposed to the drug for more than 1 year. In 2009, after more than 46,000 patients were exposed to efalizumab, the drug was withdrawn from the market after 3 confirmed and 1 suspected case of progressive multifocal leukoencephalopathy (PML) were spontaneously reported. As PML is very rare, it is extremely unlikely that the 4 reported cases were due to chance and given that PML occurs primarily in patients who are immunosuppressed, the association is likely causal. The identification of PML as a serious, but statistically rare risk of efalizumab demonstrates the strengths and weaknesses of the current drug approval and pharmacovigilance processes for fully measuring the safety of a drug. Patients and clinicians need to be aware of the relative completeness and limitations of existing safety data of a drug when selecting a treatment.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is a chronic inflammatory disease that is not uncommon in children and adolescents. While exact prevalence rates of pediatric psoriasis have not been determined, 30% to 40% of adults with psoriasis report onset of their signs and symptoms before age 16.1-4 Although the diagnosis of pediatric psoriasis remains predominantly clinical, its presentation varies in clinical course, distribution, and morphology. The management of psoriasis in children ranges from topical medications for mild and moderate disease to the use of systemic immunomodulatory agents for more severe disease. None of the systemic medications, including methotrexate, cyclosporine, and biological agents, such as etanercept, infliximab, adalimumab, and ustekinumab have specific indication by the United States Food and Drug Administration (FDA) for pediatric psoriasis. The pediatric dermatologic literature has limited studies in which investigators
examine the use of these therapies, unlike the corresponding adult literature. Subsequently, experts rely on unpublished clinical experience and studies of these systemic medications for other pediatric conditions, such as those published in the rheumatologic, transplant, oncological, and gastroenterologic literature. In this article, we discuss the systemic treatment options for pediatric  psoriasis, including drug mechanism of action and associated risks and benefits of treatment, to aid dermatologists in treating psoriasis in this special population.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is a chronic inflammatory disease that is not uncommon in children and adolescents. While exact prevalence rates of pediatric psoriasis have not been determined, 30% to 40% of adults with psoriasis report onset of their signs and symptoms before age 16.1-4 Although the diagnosis of pediatric psoriasis remains predominantly clinical, its presentation varies in clinical course, distribution, and morphology. The management of psoriasis in children ranges from topical medications for mild and moderate disease to the use of systemic immunomodulatory agents for more severe disease. None of the systemic medications, including methotrexate, cyclosporine, and biological agents, such as etanercept, infliximab, adalimumab, and ustekinumab have specific indication by the United States Food and Drug Administration (FDA) for pediatric psoriasis. The pediatric dermatologic literature has limited studies in which investigators
examine the use of these therapies, unlike the corresponding adult literature. Subsequently, experts rely on unpublished clinical experience and studies of these systemic medications for other pediatric conditions, such as those published in the rheumatologic, transplant, oncological, and gastroenterologic literature. In this article, we discuss the systemic treatment options for pediatric  psoriasis, including drug mechanism of action and associated risks and benefits of treatment, to aid dermatologists in treating psoriasis in this special population.

*For a PDF of the full article, click on the link to the left of this introduction.

Psoriasis is a chronic inflammatory disease that is not uncommon in children and adolescents. While exact prevalence rates of pediatric psoriasis have not been determined, 30% to 40% of adults with psoriasis report onset of their signs and symptoms before age 16.1-4 Although the diagnosis of pediatric psoriasis remains predominantly clinical, its presentation varies in clinical course, distribution, and morphology. The management of psoriasis in children ranges from topical medications for mild and moderate disease to the use of systemic immunomodulatory agents for more severe disease. None of the systemic medications, including methotrexate, cyclosporine, and biological agents, such as etanercept, infliximab, adalimumab, and ustekinumab have specific indication by the United States Food and Drug Administration (FDA) for pediatric psoriasis. The pediatric dermatologic literature has limited studies in which investigators
examine the use of these therapies, unlike the corresponding adult literature. Subsequently, experts rely on unpublished clinical experience and studies of these systemic medications for other pediatric conditions, such as those published in the rheumatologic, transplant, oncological, and gastroenterologic literature. In this article, we discuss the systemic treatment options for pediatric  psoriasis, including drug mechanism of action and associated risks and benefits of treatment, to aid dermatologists in treating psoriasis in this special population.

*For a PDF of the full article, click on the link to the left of this introduction.

The development of biologics has dramatically altered the treatment of moderate-to-severe psoriasis while also introducing new standards of care for therapeutic monitoring. Currently, the biologics approved by the US Food and Drug Administration are divided into 3 classes: T-cell modulators, tumor necrosis factor- inhibitors, and interleukin-12/23 inhibitors. Although the US Food and Drug Administration has established recommendations for pre- and peri-treatment screening evaluations, much of the evidence comes from clinical trials evaluating the short-term safety and efficacy of each medication, rather than longterm data, or studies that summarize either the appropriateness or feasibility of screening. Instead of following a blanket algorithm, providers must understand the evidence as it relates to each medication to determine which tests are appropriate for any specific patient. This chapter summarizes the current body of evidence and recommends a practical approach for monitoring psoriasis patients who are receiving biologic therapies.

*For a PDF of the full article, click on the link to the left of this introduction.

The development of biologics has dramatically altered the treatment of moderate-to-severe psoriasis while also introducing new standards of care for therapeutic monitoring. Currently, the biologics approved by the US Food and Drug Administration are divided into 3 classes: T-cell modulators, tumor necrosis factor- inhibitors, and interleukin-12/23 inhibitors. Although the US Food and Drug Administration has established recommendations for pre- and peri-treatment screening evaluations, much of the evidence comes from clinical trials evaluating the short-term safety and efficacy of each medication, rather than longterm data, or studies that summarize either the appropriateness or feasibility of screening. Instead of following a blanket algorithm, providers must understand the evidence as it relates to each medication to determine which tests are appropriate for any specific patient. This chapter summarizes the current body of evidence and recommends a practical approach for monitoring psoriasis patients who are receiving biologic therapies.

*For a PDF of the full article, click on the link to the left of this introduction.

The development of biologics has dramatically altered the treatment of moderate-to-severe psoriasis while also introducing new standards of care for therapeutic monitoring. Currently, the biologics approved by the US Food and Drug Administration are divided into 3 classes: T-cell modulators, tumor necrosis factor- inhibitors, and interleukin-12/23 inhibitors. Although the US Food and Drug Administration has established recommendations for pre- and peri-treatment screening evaluations, much of the evidence comes from clinical trials evaluating the short-term safety and efficacy of each medication, rather than longterm data, or studies that summarize either the appropriateness or feasibility of screening. Instead of following a blanket algorithm, providers must understand the evidence as it relates to each medication to determine which tests are appropriate for any specific patient. This chapter summarizes the current body of evidence and recommends a practical approach for monitoring psoriasis patients who are receiving biologic therapies.

*For a PDF of the full article, click on the link to the left of this introduction.