Canadian Rheumatology Association (CRA): Conference and Annual Meeting

Primary angiitis of the central nervous system in children, which encompasses a spectrum of progressive and nonprogressive large- and small-vessel inflammatory brain diseases, has been linked in recent years to a range of neurologic conditions, such as refractory status epilepticus, movement disorders, severe cognitive dysfunction, optic neuritis, and psychiatric symptoms in previously healthy children, according to Dr. Susanne Benseler, director of the Childhood CNS Vasculitis Program at the Hospital for Sick Children in Toronto.

Although an accurate, timely diagnosis is essential for optimizing neurologic outcomes in this reversible disease, overlapping clinical features with noninflammatory brain conditions – such as vasoconstrictive disorders and neuronal antibody–associated conditions – can complicate the diagnosis and lead to treatment delays, as well as potentially devastating consequences, Dr. Benseler said at the joint annual meeting of the Canadian Rheumatology Association and the Mexican Congress of Rheumatology.

In this column, Dr. Benseler answers questions about the management of primary angiitis of the central nervous system in children (cPACNS) and offers a diagnostic algorithm that allows for rapid evaluation and initiation of targeted therapy.

QUESTION: What is the incidence of cPACNS in the general population?

Dr. Benseler: Primary central nervous system vasculitis in children includes progressive and nonprogressive, angiography-positive, large-vessel vasculitis, small-vessel vasculitis, and most recently, primary CNS venulitis. Because it has only recently been described in case reports and case series, the true incidence of cPACNS remains unknown, but as recognition of the condition increases, so does the number of cases that are diagnosed and treated appropriately. For example, we currently have no idea how many kids presenting with status epilepticus have CNS vasculitis. We can assume that the number is large, however, because once we began looking for vasculitis in these children, we have been diagnosing it in case after case.

QUESTION: What are some of the risk factors for the development of the disease?

Dr. Benseler: Primary childhood CNS vasculitis develops in heretofore perfectly healthy children. Preceding viral illness may play a role. However, no true risk factors have been identified so far. It does not run in families, and it does not reflect any "weakness" of the immune system. It is the exact opposite.

QUESTION: How is cPACNS diagnosed, and what are some of the more pressing diagnostic challenges?

Dr. Benseler: The diagnosis is based on an algorithm of clinical features, including the presence of newly acquired neurologic deficits and/or psychiatric symptoms; such serum inflammatory markers as C-reactive protein, erythrocyte sedimentation rate, and von Willebrand’s factor antigen; the absence of neuronal autoantibodies in the cerebrospinal fluid; evidence of ischemic or inflammatory parenchymal disease on MRI; and evidence of CNS vascular disease on angiography or brain biopsy (Curr. Opin. Rheumatol. 2010;22: 590-7). At the same time, causes of secondary vasculitis, noninflammatory vasculopathies, and nonvasculitic inflammatory brain diseases have to be excluded.

QUESTION: Should elective brain biopsies be done routinely in patients with suspected cPACNS, or is there a specific subgroup of children in whom the procedure is most appropriate?

Dr. Benseler: Following the diagnostic algorithm, brain biopsies should be considered in children in whom the treating physician has a strong clinical suspicion of an inflammatory brain disease in the absence of vasculitis on angiography.

QUESTION: You have noted that the spectrum of the disease in children comprises progressive and nonprogressive forms. Are there differences that are apparent at diagnosis that might help clinicians distinguish between the two forms, and how would this affect management?

Dr. Benseler: We have reported the clinical, laboratory, and imaging characteristics of both subtypes. Children with nonprogressive disease present with strokes in the absence of significant inflammatory markers. The vascular wall of the distal internal carotid artery and/or proximal middle cerebral artery and/or anterior cerebral artery are inflamed and thickened on gadolinium-enhanced MRI angiography. The lumen is narrowed, causing ischemic strokes in the vascular territory, which typically includes the basal ganglia. These kids are started on antithrombotic therapy in addition to a 3-month course of high-dose corticosteroids.

In contrast, children with progressive CNS vasculitis present with additional diffuse deficits, and have evidence of inflammatory markers and angiographic abnormalities affecting multiple vessel segments, including the distal vessels. Children are diagnosed based on their angiographic appearance and are treated with the same protocol that we have reported for small-vessel vasculitis, which includes 6 months of cyclophosphamide, monthly pulses plus high-dose steroids, followed by 18 months of mycophenolate maintenance therapy with tapering doses of steroids (Lancet Neurol. 2010;9:1078-84).

QUESTION: What are some of the key management considerations for cPACNS?

Dr. Benseler: The management of CNS vasculitis has multiple components, including drug theory for inflammation; symptom therapy, such as antiseizure medications, selective serotonin reuptake inhibitors, and other drugs; supportive medications, such as vitamin D and pneumocystis jiroveci pneumonia prophylaxis; rehabilitation; family support; and school-adjustment counseling.

Dr. Benseler is also associate professor of pediatrics in the division of rheumatology and an associate scientist in Child Health Evaluative Sciences in the Research Institute at the University of Toronto. She has no conflicts of interest to disclose.

Primary angiitis of the central nervous system in children, which encompasses a spectrum of progressive and nonprogressive large- and small-vessel inflammatory brain diseases, has been linked in recent years to a range of neurologic conditions, such as refractory status epilepticus, movement disorders, severe cognitive dysfunction, optic neuritis, and psychiatric symptoms in previously healthy children, according to Dr. Susanne Benseler, director of the Childhood CNS Vasculitis Program at the Hospital for Sick Children in Toronto.

Although an accurate, timely diagnosis is essential for optimizing neurologic outcomes in this reversible disease, overlapping clinical features with noninflammatory brain conditions – such as vasoconstrictive disorders and neuronal antibody–associated conditions – can complicate the diagnosis and lead to treatment delays, as well as potentially devastating consequences, Dr. Benseler said at the joint annual meeting of the Canadian Rheumatology Association and the Mexican Congress of Rheumatology.

In this column, Dr. Benseler answers questions about the management of primary angiitis of the central nervous system in children (cPACNS) and offers a diagnostic algorithm that allows for rapid evaluation and initiation of targeted therapy.

QUESTION: What is the incidence of cPACNS in the general population?

Dr. Benseler: Primary central nervous system vasculitis in children includes progressive and nonprogressive, angiography-positive, large-vessel vasculitis, small-vessel vasculitis, and most recently, primary CNS venulitis. Because it has only recently been described in case reports and case series, the true incidence of cPACNS remains unknown, but as recognition of the condition increases, so does the number of cases that are diagnosed and treated appropriately. For example, we currently have no idea how many kids presenting with status epilepticus have CNS vasculitis. We can assume that the number is large, however, because once we began looking for vasculitis in these children, we have been diagnosing it in case after case.

QUESTION: What are some of the risk factors for the development of the disease?

Dr. Benseler: Primary childhood CNS vasculitis develops in heretofore perfectly healthy children. Preceding viral illness may play a role. However, no true risk factors have been identified so far. It does not run in families, and it does not reflect any "weakness" of the immune system. It is the exact opposite.

QUESTION: How is cPACNS diagnosed, and what are some of the more pressing diagnostic challenges?

Dr. Benseler: The diagnosis is based on an algorithm of clinical features, including the presence of newly acquired neurologic deficits and/or psychiatric symptoms; such serum inflammatory markers as C-reactive protein, erythrocyte sedimentation rate, and von Willebrand’s factor antigen; the absence of neuronal autoantibodies in the cerebrospinal fluid; evidence of ischemic or inflammatory parenchymal disease on MRI; and evidence of CNS vascular disease on angiography or brain biopsy (Curr. Opin. Rheumatol. 2010;22: 590-7). At the same time, causes of secondary vasculitis, noninflammatory vasculopathies, and nonvasculitic inflammatory brain diseases have to be excluded.

QUESTION: Should elective brain biopsies be done routinely in patients with suspected cPACNS, or is there a specific subgroup of children in whom the procedure is most appropriate?

Dr. Benseler: Following the diagnostic algorithm, brain biopsies should be considered in children in whom the treating physician has a strong clinical suspicion of an inflammatory brain disease in the absence of vasculitis on angiography.

QUESTION: You have noted that the spectrum of the disease in children comprises progressive and nonprogressive forms. Are there differences that are apparent at diagnosis that might help clinicians distinguish between the two forms, and how would this affect management?

Dr. Benseler: We have reported the clinical, laboratory, and imaging characteristics of both subtypes. Children with nonprogressive disease present with strokes in the absence of significant inflammatory markers. The vascular wall of the distal internal carotid artery and/or proximal middle cerebral artery and/or anterior cerebral artery are inflamed and thickened on gadolinium-enhanced MRI angiography. The lumen is narrowed, causing ischemic strokes in the vascular territory, which typically includes the basal ganglia. These kids are started on antithrombotic therapy in addition to a 3-month course of high-dose corticosteroids.

In contrast, children with progressive CNS vasculitis present with additional diffuse deficits, and have evidence of inflammatory markers and angiographic abnormalities affecting multiple vessel segments, including the distal vessels. Children are diagnosed based on their angiographic appearance and are treated with the same protocol that we have reported for small-vessel vasculitis, which includes 6 months of cyclophosphamide, monthly pulses plus high-dose steroids, followed by 18 months of mycophenolate maintenance therapy with tapering doses of steroids (Lancet Neurol. 2010;9:1078-84).

QUESTION: What are some of the key management considerations for cPACNS?

Dr. Benseler: The management of CNS vasculitis has multiple components, including drug theory for inflammation; symptom therapy, such as antiseizure medications, selective serotonin reuptake inhibitors, and other drugs; supportive medications, such as vitamin D and pneumocystis jiroveci pneumonia prophylaxis; rehabilitation; family support; and school-adjustment counseling.

Dr. Benseler is also associate professor of pediatrics in the division of rheumatology and an associate scientist in Child Health Evaluative Sciences in the Research Institute at the University of Toronto. She has no conflicts of interest to disclose.

Primary angiitis of the central nervous system in children, which encompasses a spectrum of progressive and nonprogressive large- and small-vessel inflammatory brain diseases, has been linked in recent years to a range of neurologic conditions, such as refractory status epilepticus, movement disorders, severe cognitive dysfunction, optic neuritis, and psychiatric symptoms in previously healthy children, according to Dr. Susanne Benseler, director of the Childhood CNS Vasculitis Program at the Hospital for Sick Children in Toronto.

Although an accurate, timely diagnosis is essential for optimizing neurologic outcomes in this reversible disease, overlapping clinical features with noninflammatory brain conditions – such as vasoconstrictive disorders and neuronal antibody–associated conditions – can complicate the diagnosis and lead to treatment delays, as well as potentially devastating consequences, Dr. Benseler said at the joint annual meeting of the Canadian Rheumatology Association and the Mexican Congress of Rheumatology.

In this column, Dr. Benseler answers questions about the management of primary angiitis of the central nervous system in children (cPACNS) and offers a diagnostic algorithm that allows for rapid evaluation and initiation of targeted therapy.

QUESTION: What is the incidence of cPACNS in the general population?

Dr. Benseler: Primary central nervous system vasculitis in children includes progressive and nonprogressive, angiography-positive, large-vessel vasculitis, small-vessel vasculitis, and most recently, primary CNS venulitis. Because it has only recently been described in case reports and case series, the true incidence of cPACNS remains unknown, but as recognition of the condition increases, so does the number of cases that are diagnosed and treated appropriately. For example, we currently have no idea how many kids presenting with status epilepticus have CNS vasculitis. We can assume that the number is large, however, because once we began looking for vasculitis in these children, we have been diagnosing it in case after case.

QUESTION: What are some of the risk factors for the development of the disease?

Dr. Benseler: Primary childhood CNS vasculitis develops in heretofore perfectly healthy children. Preceding viral illness may play a role. However, no true risk factors have been identified so far. It does not run in families, and it does not reflect any "weakness" of the immune system. It is the exact opposite.

QUESTION: How is cPACNS diagnosed, and what are some of the more pressing diagnostic challenges?

Dr. Benseler: The diagnosis is based on an algorithm of clinical features, including the presence of newly acquired neurologic deficits and/or psychiatric symptoms; such serum inflammatory markers as C-reactive protein, erythrocyte sedimentation rate, and von Willebrand’s factor antigen; the absence of neuronal autoantibodies in the cerebrospinal fluid; evidence of ischemic or inflammatory parenchymal disease on MRI; and evidence of CNS vascular disease on angiography or brain biopsy (Curr. Opin. Rheumatol. 2010;22: 590-7). At the same time, causes of secondary vasculitis, noninflammatory vasculopathies, and nonvasculitic inflammatory brain diseases have to be excluded.

QUESTION: Should elective brain biopsies be done routinely in patients with suspected cPACNS, or is there a specific subgroup of children in whom the procedure is most appropriate?

Dr. Benseler: Following the diagnostic algorithm, brain biopsies should be considered in children in whom the treating physician has a strong clinical suspicion of an inflammatory brain disease in the absence of vasculitis on angiography.

QUESTION: You have noted that the spectrum of the disease in children comprises progressive and nonprogressive forms. Are there differences that are apparent at diagnosis that might help clinicians distinguish between the two forms, and how would this affect management?

Dr. Benseler: We have reported the clinical, laboratory, and imaging characteristics of both subtypes. Children with nonprogressive disease present with strokes in the absence of significant inflammatory markers. The vascular wall of the distal internal carotid artery and/or proximal middle cerebral artery and/or anterior cerebral artery are inflamed and thickened on gadolinium-enhanced MRI angiography. The lumen is narrowed, causing ischemic strokes in the vascular territory, which typically includes the basal ganglia. These kids are started on antithrombotic therapy in addition to a 3-month course of high-dose corticosteroids.

In contrast, children with progressive CNS vasculitis present with additional diffuse deficits, and have evidence of inflammatory markers and angiographic abnormalities affecting multiple vessel segments, including the distal vessels. Children are diagnosed based on their angiographic appearance and are treated with the same protocol that we have reported for small-vessel vasculitis, which includes 6 months of cyclophosphamide, monthly pulses plus high-dose steroids, followed by 18 months of mycophenolate maintenance therapy with tapering doses of steroids (Lancet Neurol. 2010;9:1078-84).

QUESTION: What are some of the key management considerations for cPACNS?

Dr. Benseler: The management of CNS vasculitis has multiple components, including drug theory for inflammation; symptom therapy, such as antiseizure medications, selective serotonin reuptake inhibitors, and other drugs; supportive medications, such as vitamin D and pneumocystis jiroveci pneumonia prophylaxis; rehabilitation; family support; and school-adjustment counseling.

Dr. Benseler is also associate professor of pediatrics in the division of rheumatology and an associate scientist in Child Health Evaluative Sciences in the Research Institute at the University of Toronto. She has no conflicts of interest to disclose.

Primary angiitis of the central nervous system in children, which encompasses a spectrum of progressive and nonprogressive large- and small-vessel inflammatory brain diseases, has been linked in recent years to a range of neurologic conditions, such as refractory status epilepticus, movement disorders, severe cognitive dysfunction, optic neuritis, and psychiatric symptoms in previously healthy children, according to Dr. Susanne Benseler, director of the Childhood CNS Vasculitis Program at the Hospital for Sick Children in Toronto.

Although an accurate, timely diagnosis is essential for optimizing neurologic outcomes in this reversible disease, overlapping clinical features with noninflammatory brain conditions – such as vasoconstrictive disorders and neuronal antibody–associated conditions – can complicate the diagnosis and lead to treatment delays, as well as potentially devastating consequences, Dr. Benseler said at the joint annual meeting of the Canadian Rheumatology Association and the Mexican Congress of Rheumatology.

In this column, Dr. Benseler answers questions about the management of primary angiitis of the central nervous system in children (cPACNS) and offers a diagnostic algorithm that allows for rapid evaluation and initiation of targeted therapy.

QUESTION: What is the incidence of cPACNS in the general population?

Dr. Benseler: Primary central nervous system vasculitis in children includes progressive and nonprogressive, angiography-positive, large-vessel vasculitis, small-vessel vasculitis, and most recently, primary CNS venulitis. Because it has only recently been described in case reports and case series, the true incidence of cPACNS remains unknown, but as recognition of the condition increases, so does the number of cases that are diagnosed and treated appropriately. For example, we currently have no idea how many kids presenting with status epilepticus have CNS vasculitis. We can assume that the number is large, however, because once we began looking for vasculitis in these children, we have been diagnosing it in case after case.

QUESTION: What are some of the risk factors for the development of the disease?

Dr. Benseler: Primary childhood CNS vasculitis develops in heretofore perfectly healthy children. Preceding viral illness may play a role. However, no true risk factors have been identified so far. It does not run in families, and it does not reflect any "weakness" of the immune system. It is the exact opposite.

QUESTION: How is cPACNS diagnosed, and what are some of the more pressing diagnostic challenges?

Dr. Benseler: The diagnosis is based on an algorithm of clinical features, including the presence of newly acquired neurologic deficits and/or psychiatric symptoms; such serum inflammatory markers as C-reactive protein, erythrocyte sedimentation rate, and von Willebrand’s factor antigen; the absence of neuronal autoantibodies in the cerebrospinal fluid; evidence of ischemic or inflammatory parenchymal disease on MRI; and evidence of CNS vascular disease on angiography or brain biopsy (Curr. Opin. Rheumatol. 2010;22: 590-7). At the same time, causes of secondary vasculitis, noninflammatory vasculopathies, and nonvasculitic inflammatory brain diseases have to be excluded.

QUESTION: Should elective brain biopsies be done routinely in patients with suspected cPACNS, or is there a specific subgroup of children in whom the procedure is most appropriate?

Dr. Benseler: Following the diagnostic algorithm, brain biopsies should be considered in children in whom the treating physician has a strong clinical suspicion of an inflammatory brain disease in the absence of vasculitis on angiography.

QUESTION: You have noted that the spectrum of the disease in children comprises progressive and nonprogressive forms. Are there differences that are apparent at diagnosis that might help clinicians distinguish between the two forms, and how would this affect management?

Dr. Benseler: We have reported the clinical, laboratory, and imaging characteristics of both subtypes. Children with nonprogressive disease present with strokes in the absence of significant inflammatory markers. The vascular wall of the distal internal carotid artery and/or proximal middle cerebral artery and/or anterior cerebral artery are inflamed and thickened on gadolinium-enhanced MRI angiography. The lumen is narrowed, causing ischemic strokes in the vascular territory, which typically includes the basal ganglia. These kids are started on antithrombotic therapy in addition to a 3-month course of high-dose corticosteroids.

In contrast, children with progressive CNS vasculitis present with additional diffuse deficits, and have evidence of inflammatory markers and angiographic abnormalities affecting multiple vessel segments, including the distal vessels. Children are diagnosed based on their angiographic appearance and are treated with the same protocol that we have reported for small-vessel vasculitis, which includes 6 months of cyclophosphamide, monthly pulses plus high-dose steroids, followed by 18 months of mycophenolate maintenance therapy with tapering doses of steroids (Lancet Neurol. 2010;9:1078-84).

QUESTION: What are some of the key management considerations for cPACNS?

Dr. Benseler: The management of CNS vasculitis has multiple components, including drug theory for inflammation; symptom therapy, such as antiseizure medications, selective serotonin reuptake inhibitors, and other drugs; supportive medications, such as vitamin D and pneumocystis jiroveci pneumonia prophylaxis; rehabilitation; family support; and school-adjustment counseling.

This column, "Ask the Expert," regularly appears in Rheumatology News, an Elsevier publication. Dr. Benseler is also associate professor of pediatrics in the division of rheumatology and an associate scientist in Child Health Evaluative Sciences in the Research Institute at the University of Toronto. She has no conflicts of interest to disclose.

Primary angiitis of the central nervous system in children, which encompasses a spectrum of progressive and nonprogressive large- and small-vessel inflammatory brain diseases, has been linked in recent years to a range of neurologic conditions, such as refractory status epilepticus, movement disorders, severe cognitive dysfunction, optic neuritis, and psychiatric symptoms in previously healthy children, according to Dr. Susanne Benseler, director of the Childhood CNS Vasculitis Program at the Hospital for Sick Children in Toronto.

Although an accurate, timely diagnosis is essential for optimizing neurologic outcomes in this reversible disease, overlapping clinical features with noninflammatory brain conditions – such as vasoconstrictive disorders and neuronal antibody–associated conditions – can complicate the diagnosis and lead to treatment delays, as well as potentially devastating consequences, Dr. Benseler said at the joint annual meeting of the Canadian Rheumatology Association and the Mexican Congress of Rheumatology.

In this column, Dr. Benseler answers questions about the management of primary angiitis of the central nervous system in children (cPACNS) and offers a diagnostic algorithm that allows for rapid evaluation and initiation of targeted therapy.

QUESTION: What is the incidence of cPACNS in the general population?

Dr. Benseler: Primary central nervous system vasculitis in children includes progressive and nonprogressive, angiography-positive, large-vessel vasculitis, small-vessel vasculitis, and most recently, primary CNS venulitis. Because it has only recently been described in case reports and case series, the true incidence of cPACNS remains unknown, but as recognition of the condition increases, so does the number of cases that are diagnosed and treated appropriately. For example, we currently have no idea how many kids presenting with status epilepticus have CNS vasculitis. We can assume that the number is large, however, because once we began looking for vasculitis in these children, we have been diagnosing it in case after case.

QUESTION: What are some of the risk factors for the development of the disease?

Dr. Benseler: Primary childhood CNS vasculitis develops in heretofore perfectly healthy children. Preceding viral illness may play a role. However, no true risk factors have been identified so far. It does not run in families, and it does not reflect any "weakness" of the immune system. It is the exact opposite.

QUESTION: How is cPACNS diagnosed, and what are some of the more pressing diagnostic challenges?

Dr. Benseler: The diagnosis is based on an algorithm of clinical features, including the presence of newly acquired neurologic deficits and/or psychiatric symptoms; such serum inflammatory markers as C-reactive protein, erythrocyte sedimentation rate, and von Willebrand’s factor antigen; the absence of neuronal autoantibodies in the cerebrospinal fluid; evidence of ischemic or inflammatory parenchymal disease on MRI; and evidence of CNS vascular disease on angiography or brain biopsy (Curr. Opin. Rheumatol. 2010;22: 590-7). At the same time, causes of secondary vasculitis, noninflammatory vasculopathies, and nonvasculitic inflammatory brain diseases have to be excluded.

QUESTION: Should elective brain biopsies be done routinely in patients with suspected cPACNS, or is there a specific subgroup of children in whom the procedure is most appropriate?

Dr. Benseler: Following the diagnostic algorithm, brain biopsies should be considered in children in whom the treating physician has a strong clinical suspicion of an inflammatory brain disease in the absence of vasculitis on angiography.

QUESTION: You have noted that the spectrum of the disease in children comprises progressive and nonprogressive forms. Are there differences that are apparent at diagnosis that might help clinicians distinguish between the two forms, and how would this affect management?

Dr. Benseler: We have reported the clinical, laboratory, and imaging characteristics of both subtypes. Children with nonprogressive disease present with strokes in the absence of significant inflammatory markers. The vascular wall of the distal internal carotid artery and/or proximal middle cerebral artery and/or anterior cerebral artery are inflamed and thickened on gadolinium-enhanced MRI angiography. The lumen is narrowed, causing ischemic strokes in the vascular territory, which typically includes the basal ganglia. These kids are started on antithrombotic therapy in addition to a 3-month course of high-dose corticosteroids.

In contrast, children with progressive CNS vasculitis present with additional diffuse deficits, and have evidence of inflammatory markers and angiographic abnormalities affecting multiple vessel segments, including the distal vessels. Children are diagnosed based on their angiographic appearance and are treated with the same protocol that we have reported for small-vessel vasculitis, which includes 6 months of cyclophosphamide, monthly pulses plus high-dose steroids, followed by 18 months of mycophenolate maintenance therapy with tapering doses of steroids (Lancet Neurol. 2010;9:1078-84).

QUESTION: What are some of the key management considerations for cPACNS?

Dr. Benseler: The management of CNS vasculitis has multiple components, including drug theory for inflammation; symptom therapy, such as antiseizure medications, selective serotonin reuptake inhibitors, and other drugs; supportive medications, such as vitamin D and pneumocystis jiroveci pneumonia prophylaxis; rehabilitation; family support; and school-adjustment counseling.

This column, "Ask the Expert," regularly appears in Rheumatology News, an Elsevier publication. Dr. Benseler is also associate professor of pediatrics in the division of rheumatology and an associate scientist in Child Health Evaluative Sciences in the Research Institute at the University of Toronto. She has no conflicts of interest to disclose.

Primary angiitis of the central nervous system in children, which encompasses a spectrum of progressive and nonprogressive large- and small-vessel inflammatory brain diseases, has been linked in recent years to a range of neurologic conditions, such as refractory status epilepticus, movement disorders, severe cognitive dysfunction, optic neuritis, and psychiatric symptoms in previously healthy children, according to Dr. Susanne Benseler, director of the Childhood CNS Vasculitis Program at the Hospital for Sick Children in Toronto.

Although an accurate, timely diagnosis is essential for optimizing neurologic outcomes in this reversible disease, overlapping clinical features with noninflammatory brain conditions – such as vasoconstrictive disorders and neuronal antibody–associated conditions – can complicate the diagnosis and lead to treatment delays, as well as potentially devastating consequences, Dr. Benseler said at the joint annual meeting of the Canadian Rheumatology Association and the Mexican Congress of Rheumatology.

In this column, Dr. Benseler answers questions about the management of primary angiitis of the central nervous system in children (cPACNS) and offers a diagnostic algorithm that allows for rapid evaluation and initiation of targeted therapy.

QUESTION: What is the incidence of cPACNS in the general population?

Dr. Benseler: Primary central nervous system vasculitis in children includes progressive and nonprogressive, angiography-positive, large-vessel vasculitis, small-vessel vasculitis, and most recently, primary CNS venulitis. Because it has only recently been described in case reports and case series, the true incidence of cPACNS remains unknown, but as recognition of the condition increases, so does the number of cases that are diagnosed and treated appropriately. For example, we currently have no idea how many kids presenting with status epilepticus have CNS vasculitis. We can assume that the number is large, however, because once we began looking for vasculitis in these children, we have been diagnosing it in case after case.

QUESTION: What are some of the risk factors for the development of the disease?

Dr. Benseler: Primary childhood CNS vasculitis develops in heretofore perfectly healthy children. Preceding viral illness may play a role. However, no true risk factors have been identified so far. It does not run in families, and it does not reflect any "weakness" of the immune system. It is the exact opposite.

QUESTION: How is cPACNS diagnosed, and what are some of the more pressing diagnostic challenges?

Dr. Benseler: The diagnosis is based on an algorithm of clinical features, including the presence of newly acquired neurologic deficits and/or psychiatric symptoms; such serum inflammatory markers as C-reactive protein, erythrocyte sedimentation rate, and von Willebrand’s factor antigen; the absence of neuronal autoantibodies in the cerebrospinal fluid; evidence of ischemic or inflammatory parenchymal disease on MRI; and evidence of CNS vascular disease on angiography or brain biopsy (Curr. Opin. Rheumatol. 2010;22: 590-7). At the same time, causes of secondary vasculitis, noninflammatory vasculopathies, and nonvasculitic inflammatory brain diseases have to be excluded.

QUESTION: Should elective brain biopsies be done routinely in patients with suspected cPACNS, or is there a specific subgroup of children in whom the procedure is most appropriate?

Dr. Benseler: Following the diagnostic algorithm, brain biopsies should be considered in children in whom the treating physician has a strong clinical suspicion of an inflammatory brain disease in the absence of vasculitis on angiography.

QUESTION: You have noted that the spectrum of the disease in children comprises progressive and nonprogressive forms. Are there differences that are apparent at diagnosis that might help clinicians distinguish between the two forms, and how would this affect management?

Dr. Benseler: We have reported the clinical, laboratory, and imaging characteristics of both subtypes. Children with nonprogressive disease present with strokes in the absence of significant inflammatory markers. The vascular wall of the distal internal carotid artery and/or proximal middle cerebral artery and/or anterior cerebral artery are inflamed and thickened on gadolinium-enhanced MRI angiography. The lumen is narrowed, causing ischemic strokes in the vascular territory, which typically includes the basal ganglia. These kids are started on antithrombotic therapy in addition to a 3-month course of high-dose corticosteroids.

In contrast, children with progressive CNS vasculitis present with additional diffuse deficits, and have evidence of inflammatory markers and angiographic abnormalities affecting multiple vessel segments, including the distal vessels. Children are diagnosed based on their angiographic appearance and are treated with the same protocol that we have reported for small-vessel vasculitis, which includes 6 months of cyclophosphamide, monthly pulses plus high-dose steroids, followed by 18 months of mycophenolate maintenance therapy with tapering doses of steroids (Lancet Neurol. 2010;9:1078-84).

QUESTION: What are some of the key management considerations for cPACNS?

Dr. Benseler: The management of CNS vasculitis has multiple components, including drug theory for inflammation; symptom therapy, such as antiseizure medications, selective serotonin reuptake inhibitors, and other drugs; supportive medications, such as vitamin D and pneumocystis jiroveci pneumonia prophylaxis; rehabilitation; family support; and school-adjustment counseling.

This column, "Ask the Expert," regularly appears in Rheumatology News, an Elsevier publication. Dr. Benseler is also associate professor of pediatrics in the division of rheumatology and an associate scientist in Child Health Evaluative Sciences in the Research Institute at the University of Toronto. She has no conflicts of interest to disclose.

CANCÚN, MEXICO – Most ankylosing spondylitis patients who have elevated disease activity and inflammatory back pain that is not controlled with conventional therapy have been shown to respond to anti–tumor necrosis factor therapy, according to findings from a recent study.

Importantly, "disease activity will most likely not result in improvement," Dr. Nathan Vastesaeger reported at the annual meeting of the Canadian Rheumatology Association. As such, "the treating physician should consider a defined trial period with a TNF inhibitor if disease activity is not controlled with conventional therapy," he said.

Specifically, patient age, peripheral enthesitis measure, C-reactive protein (CRP) level, functionality, and human leukocyte antigen B27 (HLA-B27) genotype are also associated with the likelihood that a patient with ankylosing spondylitis (AS) will respond to anti-TNF treatment, reported Dr. Vastesaeger.

The findings are based on analysis of data, separately and combined, from two randomized controlled trials to model the probability of achieving response or remission after initiating anti-TNF therapy or continuing conventional therapy with NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), or corticosteroids for AS, said Dr. Vastesaeger of Schering-Plough.

The two studies included in the analysis were the ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial and the GO-RAISE (Golimumab – A Randomized Study in Ankylosing Spondylitis Subjects of a Novel Anti-TNF mAB Injection Given Every Four Weeks) trial.

The two studies combined comprised 479 AS patients treated with anti-TNF drugs and 156 AS patients treated with placebo and continued conventional therapy. All of the patients included in the analysis had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of at least 4 and spinal pain assessment scores of at least 4, Dr. Vastesaeger reported.

The prediction model incorporated patient age, enthesitis score, CRP level, Bath AS Functional Index (BASFI) score, and HLA-B27 genotype. The mean age of the patients included in the analysis was 39.5 years, and the mean BASFI, CRP, and enthesitis measures were 5.4, 2.1, and 2.4, respectively.

For the ASSERT, GO-RAISE, and combined data, the area under the ROC curve for 50% improvement in BASDAI score (BASDAI50) at 12 weeks was 82%, 75%, and 77%, respectively, and for Assessment in AS (ASAS) partial remission at 24 weeks was 80%, 77%, and 78%, according to Dr. Vastesaeger. When the data were categorized by age (40 years or younger vs. older than 40 years), enthesitis score (0 vs. greater than 0), CRP level (0.6 mg/dL or less, greater than 0.6-2 mg/dL, and greater than 2 mg/dL), and BASFI score (4.5 or less, greater than 4.5-6.5, and greater than 6.5), "the area under the curve of the combined data set prediction model was 80% for [BASDAI50] response and 77% for [ASAS] partial remission," Dr. Vastesaeger reported. "This suggests a good prediction model according to the academic point system."

In a matrix model designed to represent increasing proportion of BASDAI50 response and ASAS partial remission with respect to baseline characteristics, "only 2% of patients who did not have BASDAI50 response at week 12 had ASAS partial remission at week 24," said Dr. Vastesaeger.

The development of the matrix model was reported by Dr. Vastesaeger and his colleagues online March 14 in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 March 14 [doi:10.1136/ard.2010.147744]).

On the basis of the model, the investigators determined that patients younger than 40 years and those without enthesitis, in particular, demonstrated the highest likelihood of responding to TNF inhibition, and that these variables, along with CRP, functionality, and HLA-B27 status, are useful in the assessment of probable treatment response. The model, as an adjunct to expert opinion, "may help clinicians choose more appropriate therapies for patients in daily practice and may also help improve patient selection and protocol design for clinical studies," Dr. Vastesaeger concluded.

Dr. Vastesaeger is an employee of Schering-Plough. He reported having no conflicts of interest with respect to this presentation.

CANCÚN, MEXICO – Most ankylosing spondylitis patients who have elevated disease activity and inflammatory back pain that is not controlled with conventional therapy have been shown to respond to anti–tumor necrosis factor therapy, according to findings from a recent study.

Importantly, "disease activity will most likely not result in improvement," Dr. Nathan Vastesaeger reported at the annual meeting of the Canadian Rheumatology Association. As such, "the treating physician should consider a defined trial period with a TNF inhibitor if disease activity is not controlled with conventional therapy," he said.

Specifically, patient age, peripheral enthesitis measure, C-reactive protein (CRP) level, functionality, and human leukocyte antigen B27 (HLA-B27) genotype are also associated with the likelihood that a patient with ankylosing spondylitis (AS) will respond to anti-TNF treatment, reported Dr. Vastesaeger.

The findings are based on analysis of data, separately and combined, from two randomized controlled trials to model the probability of achieving response or remission after initiating anti-TNF therapy or continuing conventional therapy with NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), or corticosteroids for AS, said Dr. Vastesaeger of Schering-Plough.

The two studies included in the analysis were the ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial and the GO-RAISE (Golimumab – A Randomized Study in Ankylosing Spondylitis Subjects of a Novel Anti-TNF mAB Injection Given Every Four Weeks) trial.

The two studies combined comprised 479 AS patients treated with anti-TNF drugs and 156 AS patients treated with placebo and continued conventional therapy. All of the patients included in the analysis had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of at least 4 and spinal pain assessment scores of at least 4, Dr. Vastesaeger reported.

The prediction model incorporated patient age, enthesitis score, CRP level, Bath AS Functional Index (BASFI) score, and HLA-B27 genotype. The mean age of the patients included in the analysis was 39.5 years, and the mean BASFI, CRP, and enthesitis measures were 5.4, 2.1, and 2.4, respectively.

For the ASSERT, GO-RAISE, and combined data, the area under the ROC curve for 50% improvement in BASDAI score (BASDAI50) at 12 weeks was 82%, 75%, and 77%, respectively, and for Assessment in AS (ASAS) partial remission at 24 weeks was 80%, 77%, and 78%, according to Dr. Vastesaeger. When the data were categorized by age (40 years or younger vs. older than 40 years), enthesitis score (0 vs. greater than 0), CRP level (0.6 mg/dL or less, greater than 0.6-2 mg/dL, and greater than 2 mg/dL), and BASFI score (4.5 or less, greater than 4.5-6.5, and greater than 6.5), "the area under the curve of the combined data set prediction model was 80% for [BASDAI50] response and 77% for [ASAS] partial remission," Dr. Vastesaeger reported. "This suggests a good prediction model according to the academic point system."

In a matrix model designed to represent increasing proportion of BASDAI50 response and ASAS partial remission with respect to baseline characteristics, "only 2% of patients who did not have BASDAI50 response at week 12 had ASAS partial remission at week 24," said Dr. Vastesaeger.

The development of the matrix model was reported by Dr. Vastesaeger and his colleagues online March 14 in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 March 14 [doi:10.1136/ard.2010.147744]).

On the basis of the model, the investigators determined that patients younger than 40 years and those without enthesitis, in particular, demonstrated the highest likelihood of responding to TNF inhibition, and that these variables, along with CRP, functionality, and HLA-B27 status, are useful in the assessment of probable treatment response. The model, as an adjunct to expert opinion, "may help clinicians choose more appropriate therapies for patients in daily practice and may also help improve patient selection and protocol design for clinical studies," Dr. Vastesaeger concluded.

Dr. Vastesaeger is an employee of Schering-Plough. He reported having no conflicts of interest with respect to this presentation.

CANCÚN, MEXICO – Most ankylosing spondylitis patients who have elevated disease activity and inflammatory back pain that is not controlled with conventional therapy have been shown to respond to anti–tumor necrosis factor therapy, according to findings from a recent study.

Importantly, "disease activity will most likely not result in improvement," Dr. Nathan Vastesaeger reported at the annual meeting of the Canadian Rheumatology Association. As such, "the treating physician should consider a defined trial period with a TNF inhibitor if disease activity is not controlled with conventional therapy," he said.

Specifically, patient age, peripheral enthesitis measure, C-reactive protein (CRP) level, functionality, and human leukocyte antigen B27 (HLA-B27) genotype are also associated with the likelihood that a patient with ankylosing spondylitis (AS) will respond to anti-TNF treatment, reported Dr. Vastesaeger.

The findings are based on analysis of data, separately and combined, from two randomized controlled trials to model the probability of achieving response or remission after initiating anti-TNF therapy or continuing conventional therapy with NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), or corticosteroids for AS, said Dr. Vastesaeger of Schering-Plough.

The two studies included in the analysis were the ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial and the GO-RAISE (Golimumab – A Randomized Study in Ankylosing Spondylitis Subjects of a Novel Anti-TNF mAB Injection Given Every Four Weeks) trial.

The two studies combined comprised 479 AS patients treated with anti-TNF drugs and 156 AS patients treated with placebo and continued conventional therapy. All of the patients included in the analysis had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of at least 4 and spinal pain assessment scores of at least 4, Dr. Vastesaeger reported.

The prediction model incorporated patient age, enthesitis score, CRP level, Bath AS Functional Index (BASFI) score, and HLA-B27 genotype. The mean age of the patients included in the analysis was 39.5 years, and the mean BASFI, CRP, and enthesitis measures were 5.4, 2.1, and 2.4, respectively.

For the ASSERT, GO-RAISE, and combined data, the area under the ROC curve for 50% improvement in BASDAI score (BASDAI50) at 12 weeks was 82%, 75%, and 77%, respectively, and for Assessment in AS (ASAS) partial remission at 24 weeks was 80%, 77%, and 78%, according to Dr. Vastesaeger. When the data were categorized by age (40 years or younger vs. older than 40 years), enthesitis score (0 vs. greater than 0), CRP level (0.6 mg/dL or less, greater than 0.6-2 mg/dL, and greater than 2 mg/dL), and BASFI score (4.5 or less, greater than 4.5-6.5, and greater than 6.5), "the area under the curve of the combined data set prediction model was 80% for [BASDAI50] response and 77% for [ASAS] partial remission," Dr. Vastesaeger reported. "This suggests a good prediction model according to the academic point system."

In a matrix model designed to represent increasing proportion of BASDAI50 response and ASAS partial remission with respect to baseline characteristics, "only 2% of patients who did not have BASDAI50 response at week 12 had ASAS partial remission at week 24," said Dr. Vastesaeger.

The development of the matrix model was reported by Dr. Vastesaeger and his colleagues online March 14 in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 March 14 [doi:10.1136/ard.2010.147744]).

On the basis of the model, the investigators determined that patients younger than 40 years and those without enthesitis, in particular, demonstrated the highest likelihood of responding to TNF inhibition, and that these variables, along with CRP, functionality, and HLA-B27 status, are useful in the assessment of probable treatment response. The model, as an adjunct to expert opinion, "may help clinicians choose more appropriate therapies for patients in daily practice and may also help improve patient selection and protocol design for clinical studies," Dr. Vastesaeger concluded.

Dr. Vastesaeger is an employee of Schering-Plough. He reported having no conflicts of interest with respect to this presentation.

CANCÚN, MEXICO – Most ankylosing spondylitis patients who have elevated disease activity and inflammatory back pain that is not controlled with conventional therapy have been shown to respond to anti–tumor necrosis factor therapy, according to findings from a recent study.

Importantly, "disease activity will most likely not result in improvement," Dr. Nathan Vastesaeger reported at the annual meeting of the Canadian Rheumatology Association. As such, "the treating physician should consider a defined trial period with a TNF inhibitor if disease activity is not controlled with conventional therapy," he said.

Specifically, patient age, peripheral enthesitis measure, C-reactive protein (CRP) level, functionality, and human leukocyte antigen B27 (HLA-B27) genotype are also associated with the likelihood that a patient with ankylosing spondylitis (AS) will respond to anti-TNF treatment, reported Dr. Vastesaeger.

The findings are based on analysis of data, separately and combined, from two randomized controlled trials to model the probability of achieving response or remission after initiating anti-TNF therapy or continuing conventional therapy with NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), or corticosteroids for AS, said Dr. Vastesaeger of Schering-Plough.

The two studies included in the analysis were the ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial and the GO-RAISE (Golimumab – A Randomized Study in Ankylosing Spondylitis Subjects of a Novel Anti-TNF mAB Injection Given Every Four Weeks) trial.

The two studies combined comprised 479 AS patients treated with anti-TNF drugs and 156 AS patients treated with placebo and continued conventional therapy. All of the patients included in the analysis had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of at least 4 and spinal pain assessment scores of at least 4, Dr. Vastesaeger reported.

The prediction model incorporated patient age, enthesitis score, CRP level, Bath AS Functional Index (BASFI) score, and HLA-B27 genotype. The mean age of the patients included in the analysis was 39.5 years, and the mean BASFI, CRP, and enthesitis measures were 5.4, 2.1, and 2.4, respectively.

For the ASSERT, GO-RAISE, and combined data, the area under the ROC curve for 50% improvement in BASDAI score (BASDAI50) at 12 weeks was 82%, 75%, and 77%, respectively, and for Assessment in AS (ASAS) partial remission at 24 weeks was 80%, 77%, and 78%, according to Dr. Vastesaeger. When the data were categorized by age (40 years or younger vs. older than 40 years), enthesitis score (0 vs. greater than 0), CRP level (0.6 mg/dL or less, greater than 0.6-2 mg/dL, and greater than 2 mg/dL), and BASFI score (4.5 or less, greater than 4.5-6.5, and greater than 6.5), "the area under the curve of the combined data set prediction model was 80% for [BASDAI50] response and 77% for [ASAS] partial remission," Dr. Vastesaeger reported. "This suggests a good prediction model according to the academic point system."

In a matrix model designed to represent increasing proportion of BASDAI50 response and ASAS partial remission with respect to baseline characteristics, "only 2% of patients who did not have BASDAI50 response at week 12 had ASAS partial remission at week 24," said Dr. Vastesaeger.

The development of the matrix model was reported by Dr. Vastesaeger and his colleagues online March 14 in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 March 14 [doi:10.1136/ard.2010.147744]).

On the basis of the model, the investigators determined that patients younger than 40 years and those without enthesitis, in particular, demonstrated the highest likelihood of responding to TNF inhibition, and that these variables, along with CRP, functionality, and HLA-B27 status, are useful in the assessment of probable treatment response. The model, as an adjunct to expert opinion, "may help clinicians choose more appropriate therapies for patients in daily practice and may also help improve patient selection and protocol design for clinical studies," Dr. Vastesaeger concluded.

Dr. Vastesaeger is an employee of Schering-Plough. He reported having no conflicts of interest with respect to this presentation.

CANCÚN, MEXICO – Most ankylosing spondylitis patients who have elevated disease activity and inflammatory back pain that is not controlled with conventional therapy have been shown to respond to anti–tumor necrosis factor therapy, according to findings from a recent study.

Importantly, "disease activity will most likely not result in improvement," Dr. Nathan Vastesaeger reported at the annual meeting of the Canadian Rheumatology Association. As such, "the treating physician should consider a defined trial period with a TNF inhibitor if disease activity is not controlled with conventional therapy," he said.

Specifically, patient age, peripheral enthesitis measure, C-reactive protein (CRP) level, functionality, and human leukocyte antigen B27 (HLA-B27) genotype are also associated with the likelihood that a patient with ankylosing spondylitis (AS) will respond to anti-TNF treatment, reported Dr. Vastesaeger.

The findings are based on analysis of data, separately and combined, from two randomized controlled trials to model the probability of achieving response or remission after initiating anti-TNF therapy or continuing conventional therapy with NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), or corticosteroids for AS, said Dr. Vastesaeger of Schering-Plough.

The two studies included in the analysis were the ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial and the GO-RAISE (Golimumab – A Randomized Study in Ankylosing Spondylitis Subjects of a Novel Anti-TNF mAB Injection Given Every Four Weeks) trial.

The two studies combined comprised 479 AS patients treated with anti-TNF drugs and 156 AS patients treated with placebo and continued conventional therapy. All of the patients included in the analysis had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of at least 4 and spinal pain assessment scores of at least 4, Dr. Vastesaeger reported.

The prediction model incorporated patient age, enthesitis score, CRP level, Bath AS Functional Index (BASFI) score, and HLA-B27 genotype. The mean age of the patients included in the analysis was 39.5 years, and the mean BASFI, CRP, and enthesitis measures were 5.4, 2.1, and 2.4, respectively.

For the ASSERT, GO-RAISE, and combined data, the area under the ROC curve for 50% improvement in BASDAI score (BASDAI50) at 12 weeks was 82%, 75%, and 77%, respectively, and for Assessment in AS (ASAS) partial remission at 24 weeks was 80%, 77%, and 78%, according to Dr. Vastesaeger. When the data were categorized by age (40 years or younger vs. older than 40 years), enthesitis score (0 vs. greater than 0), CRP level (0.6 mg/dL or less, greater than 0.6-2 mg/dL, and greater than 2 mg/dL), and BASFI score (4.5 or less, greater than 4.5-6.5, and greater than 6.5), "the area under the curve of the combined data set prediction model was 80% for [BASDAI50] response and 77% for [ASAS] partial remission," Dr. Vastesaeger reported. "This suggests a good prediction model according to the academic point system."

In a matrix model designed to represent increasing proportion of BASDAI50 response and ASAS partial remission with respect to baseline characteristics, "only 2% of patients who did not have BASDAI50 response at week 12 had ASAS partial remission at week 24," said Dr. Vastesaeger.

The development of the matrix model was reported by Dr. Vastesaeger and his colleagues online March 14 in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 March 14 [doi:10.1136/ard.2010.147744]).

On the basis of the model, the investigators determined that patients younger than 40 years and those without enthesitis, in particular, demonstrated the highest likelihood of responding to TNF inhibition, and that these variables, along with CRP, functionality, and HLA-B27 status, are useful in the assessment of probable treatment response. The model, as an adjunct to expert opinion, "may help clinicians choose more appropriate therapies for patients in daily practice and may also help improve patient selection and protocol design for clinical studies," Dr. Vastesaeger concluded.

Dr. Vastesaeger is an employee of Schering-Plough. He reported having no conflicts of interest with respect to this presentation.

CANCÚN, MEXICO – Most ankylosing spondylitis patients who have elevated disease activity and inflammatory back pain that is not controlled with conventional therapy have been shown to respond to anti–tumor necrosis factor therapy, according to findings from a recent study.

Importantly, "disease activity will most likely not result in improvement," Dr. Nathan Vastesaeger reported at the annual meeting of the Canadian Rheumatology Association. As such, "the treating physician should consider a defined trial period with a TNF inhibitor if disease activity is not controlled with conventional therapy," he said.

Specifically, patient age, peripheral enthesitis measure, C-reactive protein (CRP) level, functionality, and human leukocyte antigen B27 (HLA-B27) genotype are also associated with the likelihood that a patient with ankylosing spondylitis (AS) will respond to anti-TNF treatment, reported Dr. Vastesaeger.

The findings are based on analysis of data, separately and combined, from two randomized controlled trials to model the probability of achieving response or remission after initiating anti-TNF therapy or continuing conventional therapy with NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), or corticosteroids for AS, said Dr. Vastesaeger of Schering-Plough.

The two studies included in the analysis were the ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial and the GO-RAISE (Golimumab – A Randomized Study in Ankylosing Spondylitis Subjects of a Novel Anti-TNF mAB Injection Given Every Four Weeks) trial.

The two studies combined comprised 479 AS patients treated with anti-TNF drugs and 156 AS patients treated with placebo and continued conventional therapy. All of the patients included in the analysis had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of at least 4 and spinal pain assessment scores of at least 4, Dr. Vastesaeger reported.

The prediction model incorporated patient age, enthesitis score, CRP level, Bath AS Functional Index (BASFI) score, and HLA-B27 genotype. The mean age of the patients included in the analysis was 39.5 years, and the mean BASFI, CRP, and enthesitis measures were 5.4, 2.1, and 2.4, respectively.

For the ASSERT, GO-RAISE, and combined data, the area under the ROC curve for 50% improvement in BASDAI score (BASDAI50) at 12 weeks was 82%, 75%, and 77%, respectively, and for Assessment in AS (ASAS) partial remission at 24 weeks was 80%, 77%, and 78%, according to Dr. Vastesaeger. When the data were categorized by age (40 years or younger vs. older than 40 years), enthesitis score (0 vs. greater than 0), CRP level (0.6 mg/dL or less, greater than 0.6-2 mg/dL, and greater than 2 mg/dL), and BASFI score (4.5 or less, greater than 4.5-6.5, and greater than 6.5), "the area under the curve of the combined data set prediction model was 80% for [BASDAI50] response and 77% for [ASAS] partial remission," Dr. Vastesaeger reported. "This suggests a good prediction model according to the academic point system."

In a matrix model designed to represent increasing proportion of BASDAI50 response and ASAS partial remission with respect to baseline characteristics, "only 2% of patients who did not have BASDAI50 response at week 12 had ASAS partial remission at week 24," said Dr. Vastesaeger.

The development of the matrix model was reported by Dr. Vastesaeger and his colleagues online March 14 in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 March 14 [doi:10.1136/ard.2010.147744]).

On the basis of the model, the investigators determined that patients younger than 40 years and those without enthesitis, in particular, demonstrated the highest likelihood of responding to TNF inhibition, and that these variables, along with CRP, functionality, and HLA-B27 status, are useful in the assessment of probable treatment response. The model, as an adjunct to expert opinion, "may help clinicians choose more appropriate therapies for patients in daily practice and may also help improve patient selection and protocol design for clinical studies," Dr. Vastesaeger concluded.

Dr. Vastesaeger is an employee of Schering-Plough. He reported having no conflicts of interest with respect to this presentation.

CANCUN, MEXICO – Most patients with early rheumatoid arthritis do not have radiographic progression within the first 2 years of the disease, a study has shown.

Additionally, the risk of continuous radiographic progression during this period can be predicted using certain baseline indicators of disease activity, Maggie Hong Chen reported at the meeting.

An analysis of data from the Study of New-Onset Rheumatoid Arthritis (SONORA) cohort using the original Sharp method to score radiographic progression over 2 years identified the following four patterns among the 529 early arthritis patients included in the investigation: never progressed, progressed at year 1 only; progressed at year 2 only, and progressed at both year 1 and year 2, said Ms. Chen, a research fellow in the University Health Network Research Institute of the University of Toronto. For the analysis, radiographic progression was defined as a change in total Sharp score of at least 3.5 within a year, she noted.

Of the 529 patients – all of whom were diagnosed with early rheumatoid arthritis based on symptom duration of 3-12 months and who had hand radiographs obtained at baseline, 1 year, and 2 years – 457 patients (86%) had no progression, Ms. Chen reported. Progression at year 1, year 2, and both years 1 and 2 was observed in 18 patients (3.4%), 40 patients (7.6%), and 14 (2.6%), respectively, she said.

The investigators evaluated multiple potential clinical indicators of progression, including baseline Sharp score, baseline levels of C-reactive protein (CRP), answers to the Health Assessment Questionnaire (HAQ), swollen joint count, disease duration, anticyclic citrullinated peptide (anti-CCP) antibody status, gender, rheumatoid factor (RF) status, and smoking history. Of these, "baseline Sharp score was a statistically significant indicator of whether the subject would progress within the 2-year period," Ms. Chen stated, noting that, in the no-progression group, the mean baseline Sharp score was 4.06, compared with 9.33 in the 1-year progression group, 8.28 in the 2-year progression group, and 14.0 among the patients with progression both years.

Significant differences were also observed between the patterns for CRP score, baseline HAQ, swollen joint count, and anti-CCP positive status, said Ms. Chen. "Subjects who had no radiographic progression within the 2-year period were younger with a lower swollen joint count, a lower disease activity score [DAS], and lower CRP. They were also negative for anti-CCP and RF at baseline," she said.

The findings provide insight into the patterns and characteristics of radiographic damage in early rheumatoid arthritis, "and they may also contribute to clinical decision making," said Ms. Chen. The identified indicators can help rheumatologists identify patients at highest risk of continuous radiographic progression and manage them accordingly, potentially with more aggressive therapy if warranted, she said.

Ms. Chen had no financial conflicts of interest to disclose.

CANCUN, MEXICO – Most patients with early rheumatoid arthritis do not have radiographic progression within the first 2 years of the disease, a study has shown.

Additionally, the risk of continuous radiographic progression during this period can be predicted using certain baseline indicators of disease activity, Maggie Hong Chen reported at the meeting.

An analysis of data from the Study of New-Onset Rheumatoid Arthritis (SONORA) cohort using the original Sharp method to score radiographic progression over 2 years identified the following four patterns among the 529 early arthritis patients included in the investigation: never progressed, progressed at year 1 only; progressed at year 2 only, and progressed at both year 1 and year 2, said Ms. Chen, a research fellow in the University Health Network Research Institute of the University of Toronto. For the analysis, radiographic progression was defined as a change in total Sharp score of at least 3.5 within a year, she noted.

Of the 529 patients – all of whom were diagnosed with early rheumatoid arthritis based on symptom duration of 3-12 months and who had hand radiographs obtained at baseline, 1 year, and 2 years – 457 patients (86%) had no progression, Ms. Chen reported. Progression at year 1, year 2, and both years 1 and 2 was observed in 18 patients (3.4%), 40 patients (7.6%), and 14 (2.6%), respectively, she said.

The investigators evaluated multiple potential clinical indicators of progression, including baseline Sharp score, baseline levels of C-reactive protein (CRP), answers to the Health Assessment Questionnaire (HAQ), swollen joint count, disease duration, anticyclic citrullinated peptide (anti-CCP) antibody status, gender, rheumatoid factor (RF) status, and smoking history. Of these, "baseline Sharp score was a statistically significant indicator of whether the subject would progress within the 2-year period," Ms. Chen stated, noting that, in the no-progression group, the mean baseline Sharp score was 4.06, compared with 9.33 in the 1-year progression group, 8.28 in the 2-year progression group, and 14.0 among the patients with progression both years.

Significant differences were also observed between the patterns for CRP score, baseline HAQ, swollen joint count, and anti-CCP positive status, said Ms. Chen. "Subjects who had no radiographic progression within the 2-year period were younger with a lower swollen joint count, a lower disease activity score [DAS], and lower CRP. They were also negative for anti-CCP and RF at baseline," she said.

The findings provide insight into the patterns and characteristics of radiographic damage in early rheumatoid arthritis, "and they may also contribute to clinical decision making," said Ms. Chen. The identified indicators can help rheumatologists identify patients at highest risk of continuous radiographic progression and manage them accordingly, potentially with more aggressive therapy if warranted, she said.

Ms. Chen had no financial conflicts of interest to disclose.

CANCUN, MEXICO – Most patients with early rheumatoid arthritis do not have radiographic progression within the first 2 years of the disease, a study has shown.

Additionally, the risk of continuous radiographic progression during this period can be predicted using certain baseline indicators of disease activity, Maggie Hong Chen reported at the meeting.

An analysis of data from the Study of New-Onset Rheumatoid Arthritis (SONORA) cohort using the original Sharp method to score radiographic progression over 2 years identified the following four patterns among the 529 early arthritis patients included in the investigation: never progressed, progressed at year 1 only; progressed at year 2 only, and progressed at both year 1 and year 2, said Ms. Chen, a research fellow in the University Health Network Research Institute of the University of Toronto. For the analysis, radiographic progression was defined as a change in total Sharp score of at least 3.5 within a year, she noted.

Of the 529 patients – all of whom were diagnosed with early rheumatoid arthritis based on symptom duration of 3-12 months and who had hand radiographs obtained at baseline, 1 year, and 2 years – 457 patients (86%) had no progression, Ms. Chen reported. Progression at year 1, year 2, and both years 1 and 2 was observed in 18 patients (3.4%), 40 patients (7.6%), and 14 (2.6%), respectively, she said.

The investigators evaluated multiple potential clinical indicators of progression, including baseline Sharp score, baseline levels of C-reactive protein (CRP), answers to the Health Assessment Questionnaire (HAQ), swollen joint count, disease duration, anticyclic citrullinated peptide (anti-CCP) antibody status, gender, rheumatoid factor (RF) status, and smoking history. Of these, "baseline Sharp score was a statistically significant indicator of whether the subject would progress within the 2-year period," Ms. Chen stated, noting that, in the no-progression group, the mean baseline Sharp score was 4.06, compared with 9.33 in the 1-year progression group, 8.28 in the 2-year progression group, and 14.0 among the patients with progression both years.

Significant differences were also observed between the patterns for CRP score, baseline HAQ, swollen joint count, and anti-CCP positive status, said Ms. Chen. "Subjects who had no radiographic progression within the 2-year period were younger with a lower swollen joint count, a lower disease activity score [DAS], and lower CRP. They were also negative for anti-CCP and RF at baseline," she said.

The findings provide insight into the patterns and characteristics of radiographic damage in early rheumatoid arthritis, "and they may also contribute to clinical decision making," said Ms. Chen. The identified indicators can help rheumatologists identify patients at highest risk of continuous radiographic progression and manage them accordingly, potentially with more aggressive therapy if warranted, she said.

Ms. Chen had no financial conflicts of interest to disclose.

CANCUN, MEXICO – Most patients with early rheumatoid arthritis do not have radiographic progression within the first 2 years of the disease, a study has shown.

Additionally, the risk of continuous radiographic progression during this period can be predicted using certain baseline indicators of disease activity, Maggie Hong Chen reported at the meeting.

An analysis of data from the Study of New-Onset Rheumatoid Arthritis (SONORA) cohort using the original Sharp method to score radiographic progression over 2 years identified the following four patterns among the 529 early arthritis patients included in the investigation: never progressed, progressed at year 1 only; progressed at year 2 only, and progressed at both year 1 and year 2, said Ms. Chen, a research fellow in the University Health Network Research Institute of the University of Toronto. For the analysis, radiographic progression was defined as a change in total Sharp score of at least 3.5 within a year, she noted.

Of the 529 patients – all of whom were diagnosed with early rheumatoid arthritis based on symptom duration of 3-12 months and who had hand radiographs obtained at baseline, 1 year, and 2 years – 457 patients (86%) had no progression, Ms. Chen reported. Progression at year 1, year 2, and both years 1 and 2 was observed in 18 patients (3.4%), 40 patients (7.6%), and 14 (2.6%), respectively, she said.

The investigators evaluated multiple potential clinical indicators of progression, including baseline Sharp score, baseline levels of C-reactive protein (CRP), answers to the Health Assessment Questionnaire (HAQ), swollen joint count, disease duration, anticyclic citrullinated peptide (anti-CCP) antibody status, gender, rheumatoid factor (RF) status, and smoking history. Of these, "baseline Sharp score was a statistically significant indicator of whether the subject would progress within the 2-year period," Ms. Chen stated, noting that, in the no-progression group, the mean baseline Sharp score was 4.06, compared with 9.33 in the 1-year progression group, 8.28 in the 2-year progression group, and 14.0 among the patients with progression both years.

Significant differences were also observed between the patterns for CRP score, baseline HAQ, swollen joint count, and anti-CCP positive status, said Ms. Chen. "Subjects who had no radiographic progression within the 2-year period were younger with a lower swollen joint count, a lower disease activity score [DAS], and lower CRP. They were also negative for anti-CCP and RF at baseline," she said.

The findings provide insight into the patterns and characteristics of radiographic damage in early rheumatoid arthritis, "and they may also contribute to clinical decision making," said Ms. Chen. The identified indicators can help rheumatologists identify patients at highest risk of continuous radiographic progression and manage them accordingly, potentially with more aggressive therapy if warranted, she said.

Ms. Chen had no financial conflicts of interest to disclose.

CANCUN, MEXICO – Most patients with early rheumatoid arthritis do not have radiographic progression within the first 2 years of the disease, a study has shown.

Additionally, the risk of continuous radiographic progression during this period can be predicted using certain baseline indicators of disease activity, Maggie Hong Chen reported at the meeting.

An analysis of data from the Study of New-Onset Rheumatoid Arthritis (SONORA) cohort using the original Sharp method to score radiographic progression over 2 years identified the following four patterns among the 529 early arthritis patients included in the investigation: never progressed, progressed at year 1 only; progressed at year 2 only, and progressed at both year 1 and year 2, said Ms. Chen, a research fellow in the University Health Network Research Institute of the University of Toronto. For the analysis, radiographic progression was defined as a change in total Sharp score of at least 3.5 within a year, she noted.

Of the 529 patients – all of whom were diagnosed with early rheumatoid arthritis based on symptom duration of 3-12 months and who had hand radiographs obtained at baseline, 1 year, and 2 years – 457 patients (86%) had no progression, Ms. Chen reported. Progression at year 1, year 2, and both years 1 and 2 was observed in 18 patients (3.4%), 40 patients (7.6%), and 14 (2.6%), respectively, she said.

The investigators evaluated multiple potential clinical indicators of progression, including baseline Sharp score, baseline levels of C-reactive protein (CRP), answers to the Health Assessment Questionnaire (HAQ), swollen joint count, disease duration, anticyclic citrullinated peptide (anti-CCP) antibody status, gender, rheumatoid factor (RF) status, and smoking history. Of these, "baseline Sharp score was a statistically significant indicator of whether the subject would progress within the 2-year period," Ms. Chen stated, noting that, in the no-progression group, the mean baseline Sharp score was 4.06, compared with 9.33 in the 1-year progression group, 8.28 in the 2-year progression group, and 14.0 among the patients with progression both years.

Significant differences were also observed between the patterns for CRP score, baseline HAQ, swollen joint count, and anti-CCP positive status, said Ms. Chen. "Subjects who had no radiographic progression within the 2-year period were younger with a lower swollen joint count, a lower disease activity score [DAS], and lower CRP. They were also negative for anti-CCP and RF at baseline," she said.

The findings provide insight into the patterns and characteristics of radiographic damage in early rheumatoid arthritis, "and they may also contribute to clinical decision making," said Ms. Chen. The identified indicators can help rheumatologists identify patients at highest risk of continuous radiographic progression and manage them accordingly, potentially with more aggressive therapy if warranted, she said.

Ms. Chen had no financial conflicts of interest to disclose.

CANCUN, MEXICO – Most patients with early rheumatoid arthritis do not have radiographic progression within the first 2 years of the disease, a study has shown.

Additionally, the risk of continuous radiographic progression during this period can be predicted using certain baseline indicators of disease activity, Maggie Hong Chen reported at the meeting.

An analysis of data from the Study of New-Onset Rheumatoid Arthritis (SONORA) cohort using the original Sharp method to score radiographic progression over 2 years identified the following four patterns among the 529 early arthritis patients included in the investigation: never progressed, progressed at year 1 only; progressed at year 2 only, and progressed at both year 1 and year 2, said Ms. Chen, a research fellow in the University Health Network Research Institute of the University of Toronto. For the analysis, radiographic progression was defined as a change in total Sharp score of at least 3.5 within a year, she noted.

Of the 529 patients – all of whom were diagnosed with early rheumatoid arthritis based on symptom duration of 3-12 months and who had hand radiographs obtained at baseline, 1 year, and 2 years – 457 patients (86%) had no progression, Ms. Chen reported. Progression at year 1, year 2, and both years 1 and 2 was observed in 18 patients (3.4%), 40 patients (7.6%), and 14 (2.6%), respectively, she said.

The investigators evaluated multiple potential clinical indicators of progression, including baseline Sharp score, baseline levels of C-reactive protein (CRP), answers to the Health Assessment Questionnaire (HAQ), swollen joint count, disease duration, anticyclic citrullinated peptide (anti-CCP) antibody status, gender, rheumatoid factor (RF) status, and smoking history. Of these, "baseline Sharp score was a statistically significant indicator of whether the subject would progress within the 2-year period," Ms. Chen stated, noting that, in the no-progression group, the mean baseline Sharp score was 4.06, compared with 9.33 in the 1-year progression group, 8.28 in the 2-year progression group, and 14.0 among the patients with progression both years.

Significant differences were also observed between the patterns for CRP score, baseline HAQ, swollen joint count, and anti-CCP positive status, said Ms. Chen. "Subjects who had no radiographic progression within the 2-year period were younger with a lower swollen joint count, a lower disease activity score [DAS], and lower CRP. They were also negative for anti-CCP and RF at baseline," she said.

The findings provide insight into the patterns and characteristics of radiographic damage in early rheumatoid arthritis, "and they may also contribute to clinical decision making," said Ms. Chen. The identified indicators can help rheumatologists identify patients at highest risk of continuous radiographic progression and manage them accordingly, potentially with more aggressive therapy if warranted, she said.

Ms. Chen had no financial conflicts of interest to disclose.