Paediatric Rheumatology European Society Congress (PReS)

The 82 reported cases of Blau syndrome in the 6-year-old international registry are likely far from the entire catalog of affected children.

To be included in the registry, cases must involve the mutations in the nucleotide oligomerization domain 2 (NOD2) gene, a gene that is also involved in Crohn’s disease, according to Dr. Carlos Rosé, who maintains the registry along with his colleagues Tammy Martin, Ph.D., of the Casey Eye Institute at Oregon Health and Science University, Portland, and Dr. Carine Wouters of the Catholic University of Leuven (Belgium). An additional 100-plus patients have symptoms related to those seen in Blau patients, but do not have the NOD2 mutation.

Most clinicians "have never seen a case of Blau syndrome, or think they haven’t," said immunologist Dr. Martin, who with Dr. Rosé documented that Blau syndrome could occur sporadically through a germline mutation (J. Rheumatol. 2005;32:373-5).

Long believed to be strictly familial, Blau syndrome has been found to emerge sporadically from de novo mutations as well; such cases have sometimes been classified as early-onset sarcoidosis.

Blau – whether familial or sporadic – is by all measures rare. Dr. Martin said that she has introduced Blau families to one another, helping them share information, because "chances are that wherever they live, no one in their local community has Blau." Even Wikipedia’s Blau syndrome entry is classified as a "stub" awaiting further elaboration. Epidemiologic data on Blau are scarce, and are limited mostly to Denmark, although the disease occurs all around the world.

But new information on Blau is emerging rapidly, thanks in large part to the international registry. At the 18th European Pediatric Rheumatology Congress this fall in Bruges, Belgium, Dr. Rosé of the Alfred I. duPont Hospital for Children in Wilmington, Del. updated physicians on the newly expanded phenotype for Blau, which he published, along with Dr. Martin and Dr. Wouters in September (Curr. Opin. Rheumatol. 2011;23:411-8).

The international registry, established in 2005, has revealed that a substantial minority – up to one-third – of pediatric Blau patients also have systemic disease, which can include vasculitis; renal, hepatic, or lung involvement; and severe hypertension.

Clinical presentations in the registry vary broadly, from a girl in India with cardiomyopathy and aortoarteritis to a boy in Argentina with severe renal involvement. Fever is also now seen as a characteristic of Blau flare-ups. Little of this was known 6 years ago, according to Dr. Rosé.

But the registry also points to some consistencies, which should be heartening to pediatric rheumatologists who are presented with a possible Blau case. The triad of skin, joint, and eye involvement that was first described by pediatric nephrologist Edward Blau is still considered valid, although "it is a triad over time," which makes it less diagnostically helpful, Dr. Rosé said. For example, an ichthyosis-like rash in infancy may be a consistent feature of Blau, but it is also transient, and without a biopsy it will resemble common childhood rashes.

Rather, "bogginess of joints, familial history of the same phenotype, eye disease, and negative antinuclear antibodies [ANA] are the four bullets that should raise suspicion," Dr. Rosé said, noting that eye disease in juvenile idiopathic arthritis (JIA) is usually accompanied by positive ANA.

An unexplained fever – one that is "not periodic or hectic, [like those] you see in the autoinflammatory diseases" – should also be considered in the context of possible Blau, according to Dr. Rosé.

Dr. Rosé, who currently treats children in two unrelated families with Blau, has found that the inflammatory symptoms can be managed with infliximab, which is a TNF (tumor necrosis factor) inhibitor, and that other symptoms such as hypertension can generally be controlled with appropriate drugs. Infliximab is the most commonly used medication worldwide for Blau, he said.

Thalidomide, which targets a different signaling pathway than does a TNF inhibitor, was recently used by a Japanese team to treat Blau patients successfully (Arthritis Rheum. 2010;62:250-7). Dr. Rosé said he would be hesitant to try it, however, and didn’t know of clinicians outside Japan who had. "We’re a little nervous using thalidomide in children," he said.

Of all the Blau symptoms, uveitis is "by far the most problematic" to manage, said Dr. Rosé, who estimates that 60% of Blau patients will end up with eye disease.

Dr. Martin explained that the uveitis that occurs in Blau (compared with that in JIA and other rheumatic disorders) is typically "more severe, bilateral, and generally it involves the back of the eye," in addition to the front. Unlike JIA, the uveitis in Blau will not resolve spontaneously, which is why frequent monitoring is essential. And because it involves a different part of the eye, it cannot easily be treated with steroid drops.

Dr. Rosé said that he uses "a lot of oral prednisone" to combat uveitis in his Blau patients, and recommends that all Blau patients undergo a slit-lamp examination every 3 months. Although oral steroids are "not a solution," he said, "sometimes they are the only thing you can offer."

Dr. Martin has been studying an unusual family of uveitis patients and looking for clues to solve some of the many genetic mysteries Blau presents.

Asked to consult on a family with severe bilateral uveitis with onset in early adulthood instead of childhood and no arthritis or other symptoms of Blau, Dr. Martin subsequently found that the family has an NOD2 mutation that is slightly different from the mutation seen in most Blau cases.

Another family in the registry has incomplete penetrance; the father of an affected and mutation-positive child carried the same NOD2 mutation but never developed the disease (Arthritis Rheum. 2009:60:1804-6). "There’s some genetic or environmental modifier that’s quenching that NOD2 mutation," she said.

Finding it will entail deeper investigations into the NOD2 mutations, and other mutations that may produce Blau-like pathology. The 100-plus patients in the international registry who have Blau-like symptoms but lack NOD2 mutations may in fact have other, yet-undescribed syndromes that further genetic work may reveal.

"We’re finding so many new mutations," Dr. Martin said, as well as new sorts of disease within the registry. One small group in the registry presented atypical for Blau and had infantile panniculitis, along with fever, uveitis, and systemic granulomatous inflammation (J. Pediatr. 2007;151:707-9).

The finding suggests, Dr. Martin said, that the registry contains unknown diseases that are not truly Blau syndrome but that may be identified through genotyping, which "is starting to get cheap enough that we can do it for a reasonable amount of money."

The genetics, Dr. Martin said, are "helping us find that Blau," – whatever it is, and however it is ultimately defined – "may not be as rare as we thought."

At the same conference, Kevin Foley, Ph.D., a researcher at GlaxoSmithKline, presented new data on Blau biomarkers (Pediatric Rheumatology 2011, 9 [suppl. 1]:O25), which may prove helpful in developing agents targeting the NOD2 signaling pathway.

GlaxoSmithKline is investigating a medication – currently in preclinical testing – that inhibits RIP-2, one of the proteins involved in NOD2 signaling. The company is also funding a prospective cohort study, led by Dr. Rosé, that aims to describe the natural history of Blau from infancy and to isolate additional biomarkers of inflammation driven by hyperactive RIP-2.

John Bertin, Ph.D., head of GlaxoSmithKline’s pattern recognition receptor discovery unit, said in an interview that he hopes the Blau cohort "will provide information that will enable us to determine the feasibility of performing a clinical study in this patient population."

And because hyperactive RIP-2 signaling drives proinflammatory cytokine production in Crohn’s and ulcerative colitis, Dr. Bertin said, a RIP-2 inhibitor could offer promise treating those diseases as well.

Dr. Martin reported having no relevant financial disclosures. Dr. Rosé has an unrestricted grant to study Blau syndrome funded by GlaxoSmithKline and administered by the University of Leuven. Dr. Bertin and Dr. Foley are employees of GlaxoSmithKline.

The 82 reported cases of Blau syndrome in the 6-year-old international registry are likely far from the entire catalog of affected children.

To be included in the registry, cases must involve the mutations in the nucleotide oligomerization domain 2 (NOD2) gene, a gene that is also involved in Crohn’s disease, according to Dr. Carlos Rosé, who maintains the registry along with his colleagues Tammy Martin, Ph.D., of the Casey Eye Institute at Oregon Health and Science University, Portland, and Dr. Carine Wouters of the Catholic University of Leuven (Belgium). An additional 100-plus patients have symptoms related to those seen in Blau patients, but do not have the NOD2 mutation.

Most clinicians "have never seen a case of Blau syndrome, or think they haven’t," said immunologist Dr. Martin, who with Dr. Rosé documented that Blau syndrome could occur sporadically through a germline mutation (J. Rheumatol. 2005;32:373-5).

Long believed to be strictly familial, Blau syndrome has been found to emerge sporadically from de novo mutations as well; such cases have sometimes been classified as early-onset sarcoidosis.

Blau – whether familial or sporadic – is by all measures rare. Dr. Martin said that she has introduced Blau families to one another, helping them share information, because "chances are that wherever they live, no one in their local community has Blau." Even Wikipedia’s Blau syndrome entry is classified as a "stub" awaiting further elaboration. Epidemiologic data on Blau are scarce, and are limited mostly to Denmark, although the disease occurs all around the world.

But new information on Blau is emerging rapidly, thanks in large part to the international registry. At the 18th European Pediatric Rheumatology Congress this fall in Bruges, Belgium, Dr. Rosé of the Alfred I. duPont Hospital for Children in Wilmington, Del. updated physicians on the newly expanded phenotype for Blau, which he published, along with Dr. Martin and Dr. Wouters in September (Curr. Opin. Rheumatol. 2011;23:411-8).

The international registry, established in 2005, has revealed that a substantial minority – up to one-third – of pediatric Blau patients also have systemic disease, which can include vasculitis; renal, hepatic, or lung involvement; and severe hypertension.

Clinical presentations in the registry vary broadly, from a girl in India with cardiomyopathy and aortoarteritis to a boy in Argentina with severe renal involvement. Fever is also now seen as a characteristic of Blau flare-ups. Little of this was known 6 years ago, according to Dr. Rosé.

But the registry also points to some consistencies, which should be heartening to pediatric rheumatologists who are presented with a possible Blau case. The triad of skin, joint, and eye involvement that was first described by pediatric nephrologist Edward Blau is still considered valid, although "it is a triad over time," which makes it less diagnostically helpful, Dr. Rosé said. For example, an ichthyosis-like rash in infancy may be a consistent feature of Blau, but it is also transient, and without a biopsy it will resemble common childhood rashes.

Rather, "bogginess of joints, familial history of the same phenotype, eye disease, and negative antinuclear antibodies [ANA] are the four bullets that should raise suspicion," Dr. Rosé said, noting that eye disease in juvenile idiopathic arthritis (JIA) is usually accompanied by positive ANA.

An unexplained fever – one that is "not periodic or hectic, [like those] you see in the autoinflammatory diseases" – should also be considered in the context of possible Blau, according to Dr. Rosé.

Dr. Rosé, who currently treats children in two unrelated families with Blau, has found that the inflammatory symptoms can be managed with infliximab, which is a TNF (tumor necrosis factor) inhibitor, and that other symptoms such as hypertension can generally be controlled with appropriate drugs. Infliximab is the most commonly used medication worldwide for Blau, he said.

Thalidomide, which targets a different signaling pathway than does a TNF inhibitor, was recently used by a Japanese team to treat Blau patients successfully (Arthritis Rheum. 2010;62:250-7). Dr. Rosé said he would be hesitant to try it, however, and didn’t know of clinicians outside Japan who had. "We’re a little nervous using thalidomide in children," he said.

Of all the Blau symptoms, uveitis is "by far the most problematic" to manage, said Dr. Rosé, who estimates that 60% of Blau patients will end up with eye disease.

Dr. Martin explained that the uveitis that occurs in Blau (compared with that in JIA and other rheumatic disorders) is typically "more severe, bilateral, and generally it involves the back of the eye," in addition to the front. Unlike JIA, the uveitis in Blau will not resolve spontaneously, which is why frequent monitoring is essential. And because it involves a different part of the eye, it cannot easily be treated with steroid drops.

Dr. Rosé said that he uses "a lot of oral prednisone" to combat uveitis in his Blau patients, and recommends that all Blau patients undergo a slit-lamp examination every 3 months. Although oral steroids are "not a solution," he said, "sometimes they are the only thing you can offer."

Dr. Martin has been studying an unusual family of uveitis patients and looking for clues to solve some of the many genetic mysteries Blau presents.

Asked to consult on a family with severe bilateral uveitis with onset in early adulthood instead of childhood and no arthritis or other symptoms of Blau, Dr. Martin subsequently found that the family has an NOD2 mutation that is slightly different from the mutation seen in most Blau cases.

Another family in the registry has incomplete penetrance; the father of an affected and mutation-positive child carried the same NOD2 mutation but never developed the disease (Arthritis Rheum. 2009:60:1804-6). "There’s some genetic or environmental modifier that’s quenching that NOD2 mutation," she said.

Finding it will entail deeper investigations into the NOD2 mutations, and other mutations that may produce Blau-like pathology. The 100-plus patients in the international registry who have Blau-like symptoms but lack NOD2 mutations may in fact have other, yet-undescribed syndromes that further genetic work may reveal.

"We’re finding so many new mutations," Dr. Martin said, as well as new sorts of disease within the registry. One small group in the registry presented atypical for Blau and had infantile panniculitis, along with fever, uveitis, and systemic granulomatous inflammation (J. Pediatr. 2007;151:707-9).

The finding suggests, Dr. Martin said, that the registry contains unknown diseases that are not truly Blau syndrome but that may be identified through genotyping, which "is starting to get cheap enough that we can do it for a reasonable amount of money."

The genetics, Dr. Martin said, are "helping us find that Blau," – whatever it is, and however it is ultimately defined – "may not be as rare as we thought."

At the same conference, Kevin Foley, Ph.D., a researcher at GlaxoSmithKline, presented new data on Blau biomarkers (Pediatric Rheumatology 2011, 9 [suppl. 1]:O25), which may prove helpful in developing agents targeting the NOD2 signaling pathway.

GlaxoSmithKline is investigating a medication – currently in preclinical testing – that inhibits RIP-2, one of the proteins involved in NOD2 signaling. The company is also funding a prospective cohort study, led by Dr. Rosé, that aims to describe the natural history of Blau from infancy and to isolate additional biomarkers of inflammation driven by hyperactive RIP-2.

John Bertin, Ph.D., head of GlaxoSmithKline’s pattern recognition receptor discovery unit, said in an interview that he hopes the Blau cohort "will provide information that will enable us to determine the feasibility of performing a clinical study in this patient population."

And because hyperactive RIP-2 signaling drives proinflammatory cytokine production in Crohn’s and ulcerative colitis, Dr. Bertin said, a RIP-2 inhibitor could offer promise treating those diseases as well.

Dr. Martin reported having no relevant financial disclosures. Dr. Rosé has an unrestricted grant to study Blau syndrome funded by GlaxoSmithKline and administered by the University of Leuven. Dr. Bertin and Dr. Foley are employees of GlaxoSmithKline.

The 82 reported cases of Blau syndrome in the 6-year-old international registry are likely far from the entire catalog of affected children.

To be included in the registry, cases must involve the mutations in the nucleotide oligomerization domain 2 (NOD2) gene, a gene that is also involved in Crohn’s disease, according to Dr. Carlos Rosé, who maintains the registry along with his colleagues Tammy Martin, Ph.D., of the Casey Eye Institute at Oregon Health and Science University, Portland, and Dr. Carine Wouters of the Catholic University of Leuven (Belgium). An additional 100-plus patients have symptoms related to those seen in Blau patients, but do not have the NOD2 mutation.

Most clinicians "have never seen a case of Blau syndrome, or think they haven’t," said immunologist Dr. Martin, who with Dr. Rosé documented that Blau syndrome could occur sporadically through a germline mutation (J. Rheumatol. 2005;32:373-5).

Long believed to be strictly familial, Blau syndrome has been found to emerge sporadically from de novo mutations as well; such cases have sometimes been classified as early-onset sarcoidosis.

Blau – whether familial or sporadic – is by all measures rare. Dr. Martin said that she has introduced Blau families to one another, helping them share information, because "chances are that wherever they live, no one in their local community has Blau." Even Wikipedia’s Blau syndrome entry is classified as a "stub" awaiting further elaboration. Epidemiologic data on Blau are scarce, and are limited mostly to Denmark, although the disease occurs all around the world.

But new information on Blau is emerging rapidly, thanks in large part to the international registry. At the 18th European Pediatric Rheumatology Congress this fall in Bruges, Belgium, Dr. Rosé of the Alfred I. duPont Hospital for Children in Wilmington, Del. updated physicians on the newly expanded phenotype for Blau, which he published, along with Dr. Martin and Dr. Wouters in September (Curr. Opin. Rheumatol. 2011;23:411-8).

The international registry, established in 2005, has revealed that a substantial minority – up to one-third – of pediatric Blau patients also have systemic disease, which can include vasculitis; renal, hepatic, or lung involvement; and severe hypertension.

Clinical presentations in the registry vary broadly, from a girl in India with cardiomyopathy and aortoarteritis to a boy in Argentina with severe renal involvement. Fever is also now seen as a characteristic of Blau flare-ups. Little of this was known 6 years ago, according to Dr. Rosé.

But the registry also points to some consistencies, which should be heartening to pediatric rheumatologists who are presented with a possible Blau case. The triad of skin, joint, and eye involvement that was first described by pediatric nephrologist Edward Blau is still considered valid, although "it is a triad over time," which makes it less diagnostically helpful, Dr. Rosé said. For example, an ichthyosis-like rash in infancy may be a consistent feature of Blau, but it is also transient, and without a biopsy it will resemble common childhood rashes.

Rather, "bogginess of joints, familial history of the same phenotype, eye disease, and negative antinuclear antibodies [ANA] are the four bullets that should raise suspicion," Dr. Rosé said, noting that eye disease in juvenile idiopathic arthritis (JIA) is usually accompanied by positive ANA.

An unexplained fever – one that is "not periodic or hectic, [like those] you see in the autoinflammatory diseases" – should also be considered in the context of possible Blau, according to Dr. Rosé.

Dr. Rosé, who currently treats children in two unrelated families with Blau, has found that the inflammatory symptoms can be managed with infliximab, which is a TNF (tumor necrosis factor) inhibitor, and that other symptoms such as hypertension can generally be controlled with appropriate drugs. Infliximab is the most commonly used medication worldwide for Blau, he said.

Thalidomide, which targets a different signaling pathway than does a TNF inhibitor, was recently used by a Japanese team to treat Blau patients successfully (Arthritis Rheum. 2010;62:250-7). Dr. Rosé said he would be hesitant to try it, however, and didn’t know of clinicians outside Japan who had. "We’re a little nervous using thalidomide in children," he said.

Of all the Blau symptoms, uveitis is "by far the most problematic" to manage, said Dr. Rosé, who estimates that 60% of Blau patients will end up with eye disease.

Dr. Martin explained that the uveitis that occurs in Blau (compared with that in JIA and other rheumatic disorders) is typically "more severe, bilateral, and generally it involves the back of the eye," in addition to the front. Unlike JIA, the uveitis in Blau will not resolve spontaneously, which is why frequent monitoring is essential. And because it involves a different part of the eye, it cannot easily be treated with steroid drops.

Dr. Rosé said that he uses "a lot of oral prednisone" to combat uveitis in his Blau patients, and recommends that all Blau patients undergo a slit-lamp examination every 3 months. Although oral steroids are "not a solution," he said, "sometimes they are the only thing you can offer."

Dr. Martin has been studying an unusual family of uveitis patients and looking for clues to solve some of the many genetic mysteries Blau presents.

Asked to consult on a family with severe bilateral uveitis with onset in early adulthood instead of childhood and no arthritis or other symptoms of Blau, Dr. Martin subsequently found that the family has an NOD2 mutation that is slightly different from the mutation seen in most Blau cases.

Another family in the registry has incomplete penetrance; the father of an affected and mutation-positive child carried the same NOD2 mutation but never developed the disease (Arthritis Rheum. 2009:60:1804-6). "There’s some genetic or environmental modifier that’s quenching that NOD2 mutation," she said.

Finding it will entail deeper investigations into the NOD2 mutations, and other mutations that may produce Blau-like pathology. The 100-plus patients in the international registry who have Blau-like symptoms but lack NOD2 mutations may in fact have other, yet-undescribed syndromes that further genetic work may reveal.

"We’re finding so many new mutations," Dr. Martin said, as well as new sorts of disease within the registry. One small group in the registry presented atypical for Blau and had infantile panniculitis, along with fever, uveitis, and systemic granulomatous inflammation (J. Pediatr. 2007;151:707-9).

The finding suggests, Dr. Martin said, that the registry contains unknown diseases that are not truly Blau syndrome but that may be identified through genotyping, which "is starting to get cheap enough that we can do it for a reasonable amount of money."

The genetics, Dr. Martin said, are "helping us find that Blau," – whatever it is, and however it is ultimately defined – "may not be as rare as we thought."

At the same conference, Kevin Foley, Ph.D., a researcher at GlaxoSmithKline, presented new data on Blau biomarkers (Pediatric Rheumatology 2011, 9 [suppl. 1]:O25), which may prove helpful in developing agents targeting the NOD2 signaling pathway.

GlaxoSmithKline is investigating a medication – currently in preclinical testing – that inhibits RIP-2, one of the proteins involved in NOD2 signaling. The company is also funding a prospective cohort study, led by Dr. Rosé, that aims to describe the natural history of Blau from infancy and to isolate additional biomarkers of inflammation driven by hyperactive RIP-2.

John Bertin, Ph.D., head of GlaxoSmithKline’s pattern recognition receptor discovery unit, said in an interview that he hopes the Blau cohort "will provide information that will enable us to determine the feasibility of performing a clinical study in this patient population."

And because hyperactive RIP-2 signaling drives proinflammatory cytokine production in Crohn’s and ulcerative colitis, Dr. Bertin said, a RIP-2 inhibitor could offer promise treating those diseases as well.

Dr. Martin reported having no relevant financial disclosures. Dr. Rosé has an unrestricted grant to study Blau syndrome funded by GlaxoSmithKline and administered by the University of Leuven. Dr. Bertin and Dr. Foley are employees of GlaxoSmithKline.

BRUGES, BELGIUM – Should children whose juvenile idiopathic arthritis has been diagnosed by ultrasound be treated as aggressively as those whose disease is diagnosed clinically?

Researchers presenting last week at the Pediatric Rheumatology European Society Congress in Bruges, Belgium, offered both cautious and enthusiastic perspectives on musculoskeletal ultrasound, the use of which has become ubiquitous in pediatric rheumatology.

Dr. Silvia Magni-Manzoni, of Fondazione San Matteo in Pavia, Italy, presented results from a recent Europe-wide survey that showed that ultrasound is now being used by more than 90% of pediatric rheumatologists in their practices, with 40% of them using the technology personally (Pediatr. Rheumatol. 2011;9[suppl. 1]:P47), according to Dr. Magni-Manzoni, who conducted the survey with her associates.

Their 10-question survey of nearly 400 pediatric rheumatologists achieved a 24% response rate, with answers from 37 countries. The investigators collected information about current use in daily practice, the clinical relevance of ultrasound, and areas for prospective development. Nearly three-quarters of respondents said that ultrasound allowed for the immediate improving of diagnosis of joint and soft tissue disease, and 70% said they considered ultrasound important for diagnosis, therapy monitoring, and research.

However, Dr. Magni-Manzoni further cautioned about using ultrasound to predict the course of disease and make treatment recommendations in juvenile idiopathic arthritis (JIA).

Ultrasound diagnoses have led to the reclassification of JIA patients’ disease subtypes; for example, patients considered by clinical exam to be oligoarthritic have been reclassified as polyarthritic after ultrasound. "Clinical and ultrasound examinations show different sensitivity in detecting synovitis, especially for peripheral joints," she noted.

Last fall, Dr. Magni-Manzoni presented findings at the annual meeting of the American College of Rheumatology that showed how pronounced the discrepancy between clinical and ultrasound-detected synovitis can be. Looking at 28 consecutive JIA patients (Arthritis Rheum. 2010;62[suppl. 10]:2220) determined by clinical exam to be in remission, Dr. Magni-Manzoni and colleagues found synovial hyperplasia in 75% of these patients following immediate referral for ultrasound examination.

But the decision to treat earlier or more aggressively in patients with ultrasound-detected symptoms depends on whether the ultrasound-detected synovitis, joint diffusion, or synovial hyperplasia will ultimately translate into disease flares, she said.

Dr. Magni-Manzoni said that her team has been exploring the question, following 39 consecutive JIA patients who had been diagnosed at baseline with clinically inactive disease, but after a separate ultrasound exam immediately afterward were found to have subclinical symptoms.

After 2 years’ follow up, Dr. Magni-Manzoni and colleagues found that subclinical, ultrasound-detected synovial symptoms were not predictive of disease flares. More than 60% of the study subjects still had clinically inactive disease, even though three-quarters of them had ultrasound-detected synovial hyperplasia, and two-thirds had joint diffusion, at baseline.

In a separate presentation in at the pediatric rheumatology congress, Dr. Athimalaipet V. Ramanan discussed his data showing that ultrasound can be used successfully in specific applications in JIA. Used as a visual guide, ultrasound can produce accurate and effective temporomandibular joint injections as evidenced from a small study (n = 39).

The study involved children with JIA that was complicated by temporomandibular joint (TMJ) involvement. TMJ arthritis symptoms resolved in 92% of children within 2 months after ultrasound-guided corticosteroid injection. However, Dr. Ramanan, of the Bristol Royal Hospital for Children in Bristol, U.K., also noted his group had not found ultrasound helpful in diagnosis (Pediatr. Rheumatol. 2011;9[suppl. 1]:P122).

Noting that data presented by other investigators at the congress showed that blind TMJ injections in children with JIA were as successful as ones that were guided radiologically, Dr. Ramanan told the congress that despite lingering uncertainties, "We think the possibility of problems will be a lot lower with guided rather than blind injections."

Dr. Magni-Manzoni told the congress that she agreed that ultrasound-guided joint injections, such as those investigated by Dr. Ramanan and colleagues, were "very useful" in clinical practice. She expressed the need for more guidelines and for better knowledge of ultrasound anatomy in healthy children as reference. "Ultrasound reference values are not known in healthy children," she said.

While ultrasound has considerable advantages for the pediatric rheumatologist, Dr. Magni-Manzoni said, "there are some challenges." Ultrasound is not sensitive in helping identify disease in all joints, such as TMJ, she pointed out; the quality of imaging depends on the type of machine used and the operator’s technique; and operators require constant practice.

Dr. Magni-Manzoni and Dr. Ramanan each reported that they had no disclosures related to their findings.

BRUGES, BELGIUM – Should children whose juvenile idiopathic arthritis has been diagnosed by ultrasound be treated as aggressively as those whose disease is diagnosed clinically?

Researchers presenting last week at the Pediatric Rheumatology European Society Congress in Bruges, Belgium, offered both cautious and enthusiastic perspectives on musculoskeletal ultrasound, the use of which has become ubiquitous in pediatric rheumatology.

Dr. Silvia Magni-Manzoni, of Fondazione San Matteo in Pavia, Italy, presented results from a recent Europe-wide survey that showed that ultrasound is now being used by more than 90% of pediatric rheumatologists in their practices, with 40% of them using the technology personally (Pediatr. Rheumatol. 2011;9[suppl. 1]:P47), according to Dr. Magni-Manzoni, who conducted the survey with her associates.

Their 10-question survey of nearly 400 pediatric rheumatologists achieved a 24% response rate, with answers from 37 countries. The investigators collected information about current use in daily practice, the clinical relevance of ultrasound, and areas for prospective development. Nearly three-quarters of respondents said that ultrasound allowed for the immediate improving of diagnosis of joint and soft tissue disease, and 70% said they considered ultrasound important for diagnosis, therapy monitoring, and research.

However, Dr. Magni-Manzoni further cautioned about using ultrasound to predict the course of disease and make treatment recommendations in juvenile idiopathic arthritis (JIA).

Ultrasound diagnoses have led to the reclassification of JIA patients’ disease subtypes; for example, patients considered by clinical exam to be oligoarthritic have been reclassified as polyarthritic after ultrasound. "Clinical and ultrasound examinations show different sensitivity in detecting synovitis, especially for peripheral joints," she noted.

Last fall, Dr. Magni-Manzoni presented findings at the annual meeting of the American College of Rheumatology that showed how pronounced the discrepancy between clinical and ultrasound-detected synovitis can be. Looking at 28 consecutive JIA patients (Arthritis Rheum. 2010;62[suppl. 10]:2220) determined by clinical exam to be in remission, Dr. Magni-Manzoni and colleagues found synovial hyperplasia in 75% of these patients following immediate referral for ultrasound examination.

But the decision to treat earlier or more aggressively in patients with ultrasound-detected symptoms depends on whether the ultrasound-detected synovitis, joint diffusion, or synovial hyperplasia will ultimately translate into disease flares, she said.

Dr. Magni-Manzoni said that her team has been exploring the question, following 39 consecutive JIA patients who had been diagnosed at baseline with clinically inactive disease, but after a separate ultrasound exam immediately afterward were found to have subclinical symptoms.

After 2 years’ follow up, Dr. Magni-Manzoni and colleagues found that subclinical, ultrasound-detected synovial symptoms were not predictive of disease flares. More than 60% of the study subjects still had clinically inactive disease, even though three-quarters of them had ultrasound-detected synovial hyperplasia, and two-thirds had joint diffusion, at baseline.

In a separate presentation in at the pediatric rheumatology congress, Dr. Athimalaipet V. Ramanan discussed his data showing that ultrasound can be used successfully in specific applications in JIA. Used as a visual guide, ultrasound can produce accurate and effective temporomandibular joint injections as evidenced from a small study (n = 39).

The study involved children with JIA that was complicated by temporomandibular joint (TMJ) involvement. TMJ arthritis symptoms resolved in 92% of children within 2 months after ultrasound-guided corticosteroid injection. However, Dr. Ramanan, of the Bristol Royal Hospital for Children in Bristol, U.K., also noted his group had not found ultrasound helpful in diagnosis (Pediatr. Rheumatol. 2011;9[suppl. 1]:P122).

Noting that data presented by other investigators at the congress showed that blind TMJ injections in children with JIA were as successful as ones that were guided radiologically, Dr. Ramanan told the congress that despite lingering uncertainties, "We think the possibility of problems will be a lot lower with guided rather than blind injections."

Dr. Magni-Manzoni told the congress that she agreed that ultrasound-guided joint injections, such as those investigated by Dr. Ramanan and colleagues, were "very useful" in clinical practice. She expressed the need for more guidelines and for better knowledge of ultrasound anatomy in healthy children as reference. "Ultrasound reference values are not known in healthy children," she said.

While ultrasound has considerable advantages for the pediatric rheumatologist, Dr. Magni-Manzoni said, "there are some challenges." Ultrasound is not sensitive in helping identify disease in all joints, such as TMJ, she pointed out; the quality of imaging depends on the type of machine used and the operator’s technique; and operators require constant practice.

Dr. Magni-Manzoni and Dr. Ramanan each reported that they had no disclosures related to their findings.

BRUGES, BELGIUM – Should children whose juvenile idiopathic arthritis has been diagnosed by ultrasound be treated as aggressively as those whose disease is diagnosed clinically?

Researchers presenting last week at the Pediatric Rheumatology European Society Congress in Bruges, Belgium, offered both cautious and enthusiastic perspectives on musculoskeletal ultrasound, the use of which has become ubiquitous in pediatric rheumatology.

Dr. Silvia Magni-Manzoni, of Fondazione San Matteo in Pavia, Italy, presented results from a recent Europe-wide survey that showed that ultrasound is now being used by more than 90% of pediatric rheumatologists in their practices, with 40% of them using the technology personally (Pediatr. Rheumatol. 2011;9[suppl. 1]:P47), according to Dr. Magni-Manzoni, who conducted the survey with her associates.

Their 10-question survey of nearly 400 pediatric rheumatologists achieved a 24% response rate, with answers from 37 countries. The investigators collected information about current use in daily practice, the clinical relevance of ultrasound, and areas for prospective development. Nearly three-quarters of respondents said that ultrasound allowed for the immediate improving of diagnosis of joint and soft tissue disease, and 70% said they considered ultrasound important for diagnosis, therapy monitoring, and research.

However, Dr. Magni-Manzoni further cautioned about using ultrasound to predict the course of disease and make treatment recommendations in juvenile idiopathic arthritis (JIA).

Ultrasound diagnoses have led to the reclassification of JIA patients’ disease subtypes; for example, patients considered by clinical exam to be oligoarthritic have been reclassified as polyarthritic after ultrasound. "Clinical and ultrasound examinations show different sensitivity in detecting synovitis, especially for peripheral joints," she noted.

Last fall, Dr. Magni-Manzoni presented findings at the annual meeting of the American College of Rheumatology that showed how pronounced the discrepancy between clinical and ultrasound-detected synovitis can be. Looking at 28 consecutive JIA patients (Arthritis Rheum. 2010;62[suppl. 10]:2220) determined by clinical exam to be in remission, Dr. Magni-Manzoni and colleagues found synovial hyperplasia in 75% of these patients following immediate referral for ultrasound examination.

But the decision to treat earlier or more aggressively in patients with ultrasound-detected symptoms depends on whether the ultrasound-detected synovitis, joint diffusion, or synovial hyperplasia will ultimately translate into disease flares, she said.

Dr. Magni-Manzoni said that her team has been exploring the question, following 39 consecutive JIA patients who had been diagnosed at baseline with clinically inactive disease, but after a separate ultrasound exam immediately afterward were found to have subclinical symptoms.

After 2 years’ follow up, Dr. Magni-Manzoni and colleagues found that subclinical, ultrasound-detected synovial symptoms were not predictive of disease flares. More than 60% of the study subjects still had clinically inactive disease, even though three-quarters of them had ultrasound-detected synovial hyperplasia, and two-thirds had joint diffusion, at baseline.

In a separate presentation in at the pediatric rheumatology congress, Dr. Athimalaipet V. Ramanan discussed his data showing that ultrasound can be used successfully in specific applications in JIA. Used as a visual guide, ultrasound can produce accurate and effective temporomandibular joint injections as evidenced from a small study (n = 39).

The study involved children with JIA that was complicated by temporomandibular joint (TMJ) involvement. TMJ arthritis symptoms resolved in 92% of children within 2 months after ultrasound-guided corticosteroid injection. However, Dr. Ramanan, of the Bristol Royal Hospital for Children in Bristol, U.K., also noted his group had not found ultrasound helpful in diagnosis (Pediatr. Rheumatol. 2011;9[suppl. 1]:P122).

Noting that data presented by other investigators at the congress showed that blind TMJ injections in children with JIA were as successful as ones that were guided radiologically, Dr. Ramanan told the congress that despite lingering uncertainties, "We think the possibility of problems will be a lot lower with guided rather than blind injections."

Dr. Magni-Manzoni told the congress that she agreed that ultrasound-guided joint injections, such as those investigated by Dr. Ramanan and colleagues, were "very useful" in clinical practice. She expressed the need for more guidelines and for better knowledge of ultrasound anatomy in healthy children as reference. "Ultrasound reference values are not known in healthy children," she said.

While ultrasound has considerable advantages for the pediatric rheumatologist, Dr. Magni-Manzoni said, "there are some challenges." Ultrasound is not sensitive in helping identify disease in all joints, such as TMJ, she pointed out; the quality of imaging depends on the type of machine used and the operator’s technique; and operators require constant practice.

Dr. Magni-Manzoni and Dr. Ramanan each reported that they had no disclosures related to their findings.

BRUGES, BELGIUM – Blood levels of an inflammatory protein have been found to be strongly predictive of how well a child with juvenile idiopathic arthritis will do on methotrexate, U.K. researchers have learned.

Children with higher serum levels of myeloid-related protein 8/14 (MRP8/14) were seen to respond considerably better.

The MRP8/14 findings came from Sparks CHARMS (Childhood Arthritis Response to Medication Study), which used a cohort of previously untreated children with juvenile idiopathic arthritis (JIA) (n = 109) to assess predictors of success with methotrexate. The findings represent a step toward the "ambitious goal of personalized medicine for JIA," said Halima Moncrieffe, Ph.D., of University College London (Pediatr. Rheum. 2011;9[Suppl. 1]:O10), who presented the data on MRP8/14. Using a blood sample, clinicians might be able to know "whether or not, when a child walks in, is methotrexate going to be appropriate," she noted.

Dr. Moncrieffe noted that serum MRP8/14 is "relatively easy to measure" and that samples do not require cold storage, making laboratory transport and processing easier. High levels of MRP8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an ACR score of 50 or higher at 6 months on methotrexate, the researchers found, with likelihood of achieving ACR 50 or better seen increasing with every 500 ng/ml serum increase.

Of patients with MRP8/14 levels above 3,000 ng/ml at baseline, 96% went on to achieve an ACR 50 or higher response to methotrexate. High serum levels were predictive of methotrexate success regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.

Investigator Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam presented data on clinical indicators of treatment success or failure with etanercept in a cohort of JIA patients (Pediatr. Rheum. 2011;9[Suppl 1]:O28). Ongoing research is examining the usefulness of baseline MRP levels as response predictors, she noted.

Dr. Otten and colleagues enrolled 262 patients who had never been prescribed a biological agent to control their disease before starting etanercept. The patients had been enrolled as the Dutch Arthritis and Biologicals in Children register, which has since 1999 kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.

They then collected baseline clinical data using the physician’s global assessment of disease activity and children’s health assessment questionnaire scores. The investigators’ goal was to identify clinical predictors of poor response to etanercept and which clinical characteristics might be predictive of adverse events during treatment. However, the study failed to show any significant associations for adverse effects.

"It has been proven that etanercept is highly effective in juvenile idiopathic arthritis, and under current treatment strategies inactive disease seems to be a realistic treatment goal," Dr. Otten said at the conference. "However, a still-substantial proportion of patients do not reach the goal of inactive disease."

About a third of the patients in Dr. Otten and colleagues’ study (32%, n = 85) reached clinically inactive disease after 15 months on etanercept. Another third had an ACR 50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR 50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.

Children who began treatment with etanercept before trying disease-modifying anti-rheumatic drugs (DMARDs) saw more improvement than those who had been on them previously, the investigators learned. The finding that children who had taken fewer DMARDS did better was "really important," as it indicated "the earlier and more aggressively we treat, the better the patients get," she said.

Girls and children with systemic-onset JIA were more likely to fare poorly on etanercept, Dr. Otten and her colleagues found. However, about a quarter of children with systemic onset were able to achieve inactive disease after 15 months of treatment.

Dr. Moncrieffe’s study was sponsored by Sparks-UK, the Big Lottery Fund, Arthritis Research U.K., and the Great Ormond Street Hospital Children’s Charity. University College London has filed a patent relating to methods for predicting effectiveness of drug treatment for arthritis. Dr Moncrieffe is an inventor on this patent application.

Some funding for the study came from Abbott and Pfizer, Dr. Otten disclosed.

BRUGES, BELGIUM – Blood levels of an inflammatory protein have been found to be strongly predictive of how well a child with juvenile idiopathic arthritis will do on methotrexate, U.K. researchers have learned.

Children with higher serum levels of myeloid-related protein 8/14 (MRP8/14) were seen to respond considerably better.

The MRP8/14 findings came from Sparks CHARMS (Childhood Arthritis Response to Medication Study), which used a cohort of previously untreated children with juvenile idiopathic arthritis (JIA) (n = 109) to assess predictors of success with methotrexate. The findings represent a step toward the "ambitious goal of personalized medicine for JIA," said Halima Moncrieffe, Ph.D., of University College London (Pediatr. Rheum. 2011;9[Suppl. 1]:O10), who presented the data on MRP8/14. Using a blood sample, clinicians might be able to know "whether or not, when a child walks in, is methotrexate going to be appropriate," she noted.

Dr. Moncrieffe noted that serum MRP8/14 is "relatively easy to measure" and that samples do not require cold storage, making laboratory transport and processing easier. High levels of MRP8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an ACR score of 50 or higher at 6 months on methotrexate, the researchers found, with likelihood of achieving ACR 50 or better seen increasing with every 500 ng/ml serum increase.

Of patients with MRP8/14 levels above 3,000 ng/ml at baseline, 96% went on to achieve an ACR 50 or higher response to methotrexate. High serum levels were predictive of methotrexate success regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.

Investigator Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam presented data on clinical indicators of treatment success or failure with etanercept in a cohort of JIA patients (Pediatr. Rheum. 2011;9[Suppl 1]:O28). Ongoing research is examining the usefulness of baseline MRP levels as response predictors, she noted.

Dr. Otten and colleagues enrolled 262 patients who had never been prescribed a biological agent to control their disease before starting etanercept. The patients had been enrolled as the Dutch Arthritis and Biologicals in Children register, which has since 1999 kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.

They then collected baseline clinical data using the physician’s global assessment of disease activity and children’s health assessment questionnaire scores. The investigators’ goal was to identify clinical predictors of poor response to etanercept and which clinical characteristics might be predictive of adverse events during treatment. However, the study failed to show any significant associations for adverse effects.

"It has been proven that etanercept is highly effective in juvenile idiopathic arthritis, and under current treatment strategies inactive disease seems to be a realistic treatment goal," Dr. Otten said at the conference. "However, a still-substantial proportion of patients do not reach the goal of inactive disease."

About a third of the patients in Dr. Otten and colleagues’ study (32%, n = 85) reached clinically inactive disease after 15 months on etanercept. Another third had an ACR 50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR 50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.

Children who began treatment with etanercept before trying disease-modifying anti-rheumatic drugs (DMARDs) saw more improvement than those who had been on them previously, the investigators learned. The finding that children who had taken fewer DMARDS did better was "really important," as it indicated "the earlier and more aggressively we treat, the better the patients get," she said.

Girls and children with systemic-onset JIA were more likely to fare poorly on etanercept, Dr. Otten and her colleagues found. However, about a quarter of children with systemic onset were able to achieve inactive disease after 15 months of treatment.

Dr. Moncrieffe’s study was sponsored by Sparks-UK, the Big Lottery Fund, Arthritis Research U.K., and the Great Ormond Street Hospital Children’s Charity. University College London has filed a patent relating to methods for predicting effectiveness of drug treatment for arthritis. Dr Moncrieffe is an inventor on this patent application.

Some funding for the study came from Abbott and Pfizer, Dr. Otten disclosed.

BRUGES, BELGIUM – Blood levels of an inflammatory protein have been found to be strongly predictive of how well a child with juvenile idiopathic arthritis will do on methotrexate, U.K. researchers have learned.

Children with higher serum levels of myeloid-related protein 8/14 (MRP8/14) were seen to respond considerably better.

The MRP8/14 findings came from Sparks CHARMS (Childhood Arthritis Response to Medication Study), which used a cohort of previously untreated children with juvenile idiopathic arthritis (JIA) (n = 109) to assess predictors of success with methotrexate. The findings represent a step toward the "ambitious goal of personalized medicine for JIA," said Halima Moncrieffe, Ph.D., of University College London (Pediatr. Rheum. 2011;9[Suppl. 1]:O10), who presented the data on MRP8/14. Using a blood sample, clinicians might be able to know "whether or not, when a child walks in, is methotrexate going to be appropriate," she noted.

Dr. Moncrieffe noted that serum MRP8/14 is "relatively easy to measure" and that samples do not require cold storage, making laboratory transport and processing easier. High levels of MRP8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an ACR score of 50 or higher at 6 months on methotrexate, the researchers found, with likelihood of achieving ACR 50 or better seen increasing with every 500 ng/ml serum increase.

Of patients with MRP8/14 levels above 3,000 ng/ml at baseline, 96% went on to achieve an ACR 50 or higher response to methotrexate. High serum levels were predictive of methotrexate success regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.

Investigator Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam presented data on clinical indicators of treatment success or failure with etanercept in a cohort of JIA patients (Pediatr. Rheum. 2011;9[Suppl 1]:O28). Ongoing research is examining the usefulness of baseline MRP levels as response predictors, she noted.

Dr. Otten and colleagues enrolled 262 patients who had never been prescribed a biological agent to control their disease before starting etanercept. The patients had been enrolled as the Dutch Arthritis and Biologicals in Children register, which has since 1999 kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.

They then collected baseline clinical data using the physician’s global assessment of disease activity and children’s health assessment questionnaire scores. The investigators’ goal was to identify clinical predictors of poor response to etanercept and which clinical characteristics might be predictive of adverse events during treatment. However, the study failed to show any significant associations for adverse effects.

"It has been proven that etanercept is highly effective in juvenile idiopathic arthritis, and under current treatment strategies inactive disease seems to be a realistic treatment goal," Dr. Otten said at the conference. "However, a still-substantial proportion of patients do not reach the goal of inactive disease."

About a third of the patients in Dr. Otten and colleagues’ study (32%, n = 85) reached clinically inactive disease after 15 months on etanercept. Another third had an ACR 50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR 50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.

Children who began treatment with etanercept before trying disease-modifying anti-rheumatic drugs (DMARDs) saw more improvement than those who had been on them previously, the investigators learned. The finding that children who had taken fewer DMARDS did better was "really important," as it indicated "the earlier and more aggressively we treat, the better the patients get," she said.

Girls and children with systemic-onset JIA were more likely to fare poorly on etanercept, Dr. Otten and her colleagues found. However, about a quarter of children with systemic onset were able to achieve inactive disease after 15 months of treatment.

Dr. Moncrieffe’s study was sponsored by Sparks-UK, the Big Lottery Fund, Arthritis Research U.K., and the Great Ormond Street Hospital Children’s Charity. University College London has filed a patent relating to methods for predicting effectiveness of drug treatment for arthritis. Dr Moncrieffe is an inventor on this patent application.

Some funding for the study came from Abbott and Pfizer, Dr. Otten disclosed.

BRUGES, BELGIUM – Canakinumab, an investigational interleukin-1b antibody also known as ACZ885, has been shown to lessen symptoms of systemic juvenile idiopathic arthritis more than placebo.

The medication, which has yet to be licensed in any country, is administered once a month by subcutaneous injection, instead of intravenous infusion.

The endpoint of the study was a reduction in disease activity by 30% according to American College of Rheumatology Pediatric criteria (ACR Pedi 30), which were modified for the study to include absence of fever, according to Dr. Nicolino Ruperto of the Pediatric Rheumatology International Trials Organization (PRINTO) and Istituto G Gaslini in Genoa, Italy.

Results from a phase III, manufacturer-sponsored, randomized controlled trial (n = 84) of canakinumab showed that a single injection of 4 mg/kg lessened symptoms by 30% or more in 83.7% of patients in the treatment arm (n = 43), compared with 9.8% in the placebo arm (n = 41), at 15 days (Pediatr. Rheum. 2011;9[Suppl 1]:O21).

Patients enrolled in the study were between 2 and 19 years old, with active disease but no macrophage activation syndrome. For the study group as a whole, the mean disease duration was 3.4 years; mean CRP 200.6 mg/L, mean number of active joints was 14.1; and mean prednisone equivalent therapy was 0.3 mg/kg per day.

Dr. Ruperto told the conference that the study participants had spiking intermittent fever at enrollment lasting at least 3 days, and they were allowed to continue on methotrexate or corticosteroids during the trial, but no biological agents besides the study medication.

A majority of patients in the treatment arm (67.4%) achieved ACR Pedi 50 improvement, compared with 4.9% for placebo, and about a third (32.6%) in the study arm saw improvement of ACR Pedi 100, compared with none for placebo. Both ACR Pedi 30 and ACR Pedi 50 responses with canakinumab remained significantly higher than with placebo at day 29.

Adverse events occurred in 55.8% of canakinumab and 39% of placebo patients. Dr. Ruperto said that the most frequently reported adverse events in the study group were upper respiratory problems and gastrointestinal complaints. No patients discontinued the trial because of side effects; however, 6 patients in the treatment arm and 37 in the placebo arm discontinued because for lack of therapeutic effect.

Two deaths occurred in the study group after the completion of the trial, during the long-term follow-up period, Dr. Ruperto told the congress. Both deaths were due to macrophage activation syndrome; one complicated with sepsis and the other with pulmonary hypertension.

The study was funded by Novartis. Dr. Ruperto reported having no financial conflicts of interest. Two of his coinvestigators are Novartis shareholders and one is a Novartis employee.

BRUGES, BELGIUM – Canakinumab, an investigational interleukin-1b antibody also known as ACZ885, has been shown to lessen symptoms of systemic juvenile idiopathic arthritis more than placebo.

The medication, which has yet to be licensed in any country, is administered once a month by subcutaneous injection, instead of intravenous infusion.

The endpoint of the study was a reduction in disease activity by 30% according to American College of Rheumatology Pediatric criteria (ACR Pedi 30), which were modified for the study to include absence of fever, according to Dr. Nicolino Ruperto of the Pediatric Rheumatology International Trials Organization (PRINTO) and Istituto G Gaslini in Genoa, Italy.

Results from a phase III, manufacturer-sponsored, randomized controlled trial (n = 84) of canakinumab showed that a single injection of 4 mg/kg lessened symptoms by 30% or more in 83.7% of patients in the treatment arm (n = 43), compared with 9.8% in the placebo arm (n = 41), at 15 days (Pediatr. Rheum. 2011;9[Suppl 1]:O21).

Patients enrolled in the study were between 2 and 19 years old, with active disease but no macrophage activation syndrome. For the study group as a whole, the mean disease duration was 3.4 years; mean CRP 200.6 mg/L, mean number of active joints was 14.1; and mean prednisone equivalent therapy was 0.3 mg/kg per day.

Dr. Ruperto told the conference that the study participants had spiking intermittent fever at enrollment lasting at least 3 days, and they were allowed to continue on methotrexate or corticosteroids during the trial, but no biological agents besides the study medication.

A majority of patients in the treatment arm (67.4%) achieved ACR Pedi 50 improvement, compared with 4.9% for placebo, and about a third (32.6%) in the study arm saw improvement of ACR Pedi 100, compared with none for placebo. Both ACR Pedi 30 and ACR Pedi 50 responses with canakinumab remained significantly higher than with placebo at day 29.

Adverse events occurred in 55.8% of canakinumab and 39% of placebo patients. Dr. Ruperto said that the most frequently reported adverse events in the study group were upper respiratory problems and gastrointestinal complaints. No patients discontinued the trial because of side effects; however, 6 patients in the treatment arm and 37 in the placebo arm discontinued because for lack of therapeutic effect.

Two deaths occurred in the study group after the completion of the trial, during the long-term follow-up period, Dr. Ruperto told the congress. Both deaths were due to macrophage activation syndrome; one complicated with sepsis and the other with pulmonary hypertension.

The study was funded by Novartis. Dr. Ruperto reported having no financial conflicts of interest. Two of his coinvestigators are Novartis shareholders and one is a Novartis employee.

BRUGES, BELGIUM – Canakinumab, an investigational interleukin-1b antibody also known as ACZ885, has been shown to lessen symptoms of systemic juvenile idiopathic arthritis more than placebo.

The medication, which has yet to be licensed in any country, is administered once a month by subcutaneous injection, instead of intravenous infusion.

The endpoint of the study was a reduction in disease activity by 30% according to American College of Rheumatology Pediatric criteria (ACR Pedi 30), which were modified for the study to include absence of fever, according to Dr. Nicolino Ruperto of the Pediatric Rheumatology International Trials Organization (PRINTO) and Istituto G Gaslini in Genoa, Italy.

Results from a phase III, manufacturer-sponsored, randomized controlled trial (n = 84) of canakinumab showed that a single injection of 4 mg/kg lessened symptoms by 30% or more in 83.7% of patients in the treatment arm (n = 43), compared with 9.8% in the placebo arm (n = 41), at 15 days (Pediatr. Rheum. 2011;9[Suppl 1]:O21).

Patients enrolled in the study were between 2 and 19 years old, with active disease but no macrophage activation syndrome. For the study group as a whole, the mean disease duration was 3.4 years; mean CRP 200.6 mg/L, mean number of active joints was 14.1; and mean prednisone equivalent therapy was 0.3 mg/kg per day.

Dr. Ruperto told the conference that the study participants had spiking intermittent fever at enrollment lasting at least 3 days, and they were allowed to continue on methotrexate or corticosteroids during the trial, but no biological agents besides the study medication.

A majority of patients in the treatment arm (67.4%) achieved ACR Pedi 50 improvement, compared with 4.9% for placebo, and about a third (32.6%) in the study arm saw improvement of ACR Pedi 100, compared with none for placebo. Both ACR Pedi 30 and ACR Pedi 50 responses with canakinumab remained significantly higher than with placebo at day 29.

Adverse events occurred in 55.8% of canakinumab and 39% of placebo patients. Dr. Ruperto said that the most frequently reported adverse events in the study group were upper respiratory problems and gastrointestinal complaints. No patients discontinued the trial because of side effects; however, 6 patients in the treatment arm and 37 in the placebo arm discontinued because for lack of therapeutic effect.

Two deaths occurred in the study group after the completion of the trial, during the long-term follow-up period, Dr. Ruperto told the congress. Both deaths were due to macrophage activation syndrome; one complicated with sepsis and the other with pulmonary hypertension.

The study was funded by Novartis. Dr. Ruperto reported having no financial conflicts of interest. Two of his coinvestigators are Novartis shareholders and one is a Novartis employee.

BRUGES, BELGIUM – A vaccine to prevent human papilloma virus infection, thereby limiting the risk for cervical cancer, has been found to be safe and effective in girls with juvenile idiopathic arthritis.

No changes in disease activity or differences in the girls’ ability to mount healthy antibody titers compared with healthy controls occurred, according to investigator Dr. Marloes Heijstek.

However, while the vaccine was also shown not to influence disease activity in girls with systemic lupus erythematosus (SLE) and juvenile dermatomyositis (JDM), these groups did not mount antibody titers comparable to those seen in girls with juvenile idiopathic arthritis (JIA) and healthy controls, suggesting that the vaccine may offer girls with SLE or JDM less protection against acquiring cancer-causing types of human papilloma virus (HPV).

Even in JIA, the duration of protection remains to be determined and may be shorter than in healthy controls, investigators cautioned.

These findings come from a Dutch study of 58 patients with rheumatic disease and 51 healthy controls (Pediatr. Rheumatol. 2011;9[suppl. 1]:O41 ). Dr. Heijstek of the University Medical Center Utrecht (the Netherlands) collaborated on the ongoing study with principal investigator Dr. Nico M. Wulffraat, also of UMC Utrecht. Dr. Heijstek and Dr. Wulffraat also collaborated on an earlier safety study of measles, mumps, and rubella vaccine in JIA patients (Ann. Rheum. Dis. 2007;66:1384-7).

Dr. Heijstek’s HPV vaccine study enrolled girls with rheumatic disease who had been immunized with the bivalent HPV 16/18 vaccine Cervarix as part of a national program in the Netherlands that aims to vaccinate starting at age 12, before the girls are likely to be sexually active, in three doses at 0, 1, and 6 months, and followed up a year after vaccination. Study subjects and controls were between the ages of 12 and 18. Patients enrolled had JIA (n = 45), JDM (n = 5), or SLE (n = 8). Some of the subjects were taking medication to manage their disease at the time of vaccination. Specifically, 42% of JIA patients and 40% of JDM patients were taking methotrexate; 24% of JIA patients were taking anti-TNF medications.

The percentage of patients able to mount an immunological response to vaccination was shown to be the same in patients and controls, but geometric mean antibody titers for HPV16 were found to be lower in JIA (5,119 LU/mL), SLE (1,461 LU/mL), and JDM patients (3,233 LU/mL) compared with controls.

Geometric mean antibody titers for HPV18 were seen as similar in JIA patients and controls (2,764 LU/mL vs. 2,522 LU/mL). However, SLE and JDM patients showed markedly lower geometric mean antibody titers. Methotrexate use did not lower vaccine responses. One JDM patient did not seroconvert, Dr. Heijstek said. That patient was on both methotrexate and anti-TNF for disease control.

The group as a whole had fairly low, stable disease activity, Dr. Heijstek explained. However, this was not part of the enrollment criteria. When patients have high disease activity, they or their parents often fear a flare of disease due to vaccination or they have the general feeling that it is better to postpone the vaccination until the disease is stable, she told attendees at the congress.

The median juvenile arthritis disease activity score (JADAS)-27 did change considerably between visits (1.9-2.5), but JADAS-27 was significantly elevated at 7 months (P = .001) due to one outlier. SLE and JDM disease activity remained similar.

Days before Dr. Heijstek’s presentation, Dr. Wulffraat provided a background discussion on vaccinations in children with rheumatic diseases. Dr. Wulffraat and Dr. Heijstek’s investigation of MMR vaccine in JIA patients had shown the vaccine not to cause rheumatic disease flare ups or viral disease, and methotrexate use did not appear to affect antibody response.

What is remains unknown is how durable any vaccine protection is in children with rheumatic disease, according to Dr. Wulffraat. Longer study will be required to determine how long the titers persist, and whether they are protective in children on biological therapies such as anti-TNF inhibitors.

Neither Dr. Wulffraat nor Dr. Heijstek disclosed conflicts of interest related to their findings.

BRUGES, BELGIUM – A vaccine to prevent human papilloma virus infection, thereby limiting the risk for cervical cancer, has been found to be safe and effective in girls with juvenile idiopathic arthritis.

No changes in disease activity or differences in the girls’ ability to mount healthy antibody titers compared with healthy controls occurred, according to investigator Dr. Marloes Heijstek.

However, while the vaccine was also shown not to influence disease activity in girls with systemic lupus erythematosus (SLE) and juvenile dermatomyositis (JDM), these groups did not mount antibody titers comparable to those seen in girls with juvenile idiopathic arthritis (JIA) and healthy controls, suggesting that the vaccine may offer girls with SLE or JDM less protection against acquiring cancer-causing types of human papilloma virus (HPV).

Even in JIA, the duration of protection remains to be determined and may be shorter than in healthy controls, investigators cautioned.

These findings come from a Dutch study of 58 patients with rheumatic disease and 51 healthy controls (Pediatr. Rheumatol. 2011;9[suppl. 1]:O41 ). Dr. Heijstek of the University Medical Center Utrecht (the Netherlands) collaborated on the ongoing study with principal investigator Dr. Nico M. Wulffraat, also of UMC Utrecht. Dr. Heijstek and Dr. Wulffraat also collaborated on an earlier safety study of measles, mumps, and rubella vaccine in JIA patients (Ann. Rheum. Dis. 2007;66:1384-7).

Dr. Heijstek’s HPV vaccine study enrolled girls with rheumatic disease who had been immunized with the bivalent HPV 16/18 vaccine Cervarix as part of a national program in the Netherlands that aims to vaccinate starting at age 12, before the girls are likely to be sexually active, in three doses at 0, 1, and 6 months, and followed up a year after vaccination. Study subjects and controls were between the ages of 12 and 18. Patients enrolled had JIA (n = 45), JDM (n = 5), or SLE (n = 8). Some of the subjects were taking medication to manage their disease at the time of vaccination. Specifically, 42% of JIA patients and 40% of JDM patients were taking methotrexate; 24% of JIA patients were taking anti-TNF medications.

The percentage of patients able to mount an immunological response to vaccination was shown to be the same in patients and controls, but geometric mean antibody titers for HPV16 were found to be lower in JIA (5,119 LU/mL), SLE (1,461 LU/mL), and JDM patients (3,233 LU/mL) compared with controls.

Geometric mean antibody titers for HPV18 were seen as similar in JIA patients and controls (2,764 LU/mL vs. 2,522 LU/mL). However, SLE and JDM patients showed markedly lower geometric mean antibody titers. Methotrexate use did not lower vaccine responses. One JDM patient did not seroconvert, Dr. Heijstek said. That patient was on both methotrexate and anti-TNF for disease control.

The group as a whole had fairly low, stable disease activity, Dr. Heijstek explained. However, this was not part of the enrollment criteria. When patients have high disease activity, they or their parents often fear a flare of disease due to vaccination or they have the general feeling that it is better to postpone the vaccination until the disease is stable, she told attendees at the congress.

The median juvenile arthritis disease activity score (JADAS)-27 did change considerably between visits (1.9-2.5), but JADAS-27 was significantly elevated at 7 months (P = .001) due to one outlier. SLE and JDM disease activity remained similar.

Days before Dr. Heijstek’s presentation, Dr. Wulffraat provided a background discussion on vaccinations in children with rheumatic diseases. Dr. Wulffraat and Dr. Heijstek’s investigation of MMR vaccine in JIA patients had shown the vaccine not to cause rheumatic disease flare ups or viral disease, and methotrexate use did not appear to affect antibody response.

What is remains unknown is how durable any vaccine protection is in children with rheumatic disease, according to Dr. Wulffraat. Longer study will be required to determine how long the titers persist, and whether they are protective in children on biological therapies such as anti-TNF inhibitors.

Neither Dr. Wulffraat nor Dr. Heijstek disclosed conflicts of interest related to their findings.

BRUGES, BELGIUM – A vaccine to prevent human papilloma virus infection, thereby limiting the risk for cervical cancer, has been found to be safe and effective in girls with juvenile idiopathic arthritis.

No changes in disease activity or differences in the girls’ ability to mount healthy antibody titers compared with healthy controls occurred, according to investigator Dr. Marloes Heijstek.

However, while the vaccine was also shown not to influence disease activity in girls with systemic lupus erythematosus (SLE) and juvenile dermatomyositis (JDM), these groups did not mount antibody titers comparable to those seen in girls with juvenile idiopathic arthritis (JIA) and healthy controls, suggesting that the vaccine may offer girls with SLE or JDM less protection against acquiring cancer-causing types of human papilloma virus (HPV).

Even in JIA, the duration of protection remains to be determined and may be shorter than in healthy controls, investigators cautioned.

These findings come from a Dutch study of 58 patients with rheumatic disease and 51 healthy controls (Pediatr. Rheumatol. 2011;9[suppl. 1]:O41 ). Dr. Heijstek of the University Medical Center Utrecht (the Netherlands) collaborated on the ongoing study with principal investigator Dr. Nico M. Wulffraat, also of UMC Utrecht. Dr. Heijstek and Dr. Wulffraat also collaborated on an earlier safety study of measles, mumps, and rubella vaccine in JIA patients (Ann. Rheum. Dis. 2007;66:1384-7).

Dr. Heijstek’s HPV vaccine study enrolled girls with rheumatic disease who had been immunized with the bivalent HPV 16/18 vaccine Cervarix as part of a national program in the Netherlands that aims to vaccinate starting at age 12, before the girls are likely to be sexually active, in three doses at 0, 1, and 6 months, and followed up a year after vaccination. Study subjects and controls were between the ages of 12 and 18. Patients enrolled had JIA (n = 45), JDM (n = 5), or SLE (n = 8). Some of the subjects were taking medication to manage their disease at the time of vaccination. Specifically, 42% of JIA patients and 40% of JDM patients were taking methotrexate; 24% of JIA patients were taking anti-TNF medications.

The percentage of patients able to mount an immunological response to vaccination was shown to be the same in patients and controls, but geometric mean antibody titers for HPV16 were found to be lower in JIA (5,119 LU/mL), SLE (1,461 LU/mL), and JDM patients (3,233 LU/mL) compared with controls.

Geometric mean antibody titers for HPV18 were seen as similar in JIA patients and controls (2,764 LU/mL vs. 2,522 LU/mL). However, SLE and JDM patients showed markedly lower geometric mean antibody titers. Methotrexate use did not lower vaccine responses. One JDM patient did not seroconvert, Dr. Heijstek said. That patient was on both methotrexate and anti-TNF for disease control.

The group as a whole had fairly low, stable disease activity, Dr. Heijstek explained. However, this was not part of the enrollment criteria. When patients have high disease activity, they or their parents often fear a flare of disease due to vaccination or they have the general feeling that it is better to postpone the vaccination until the disease is stable, she told attendees at the congress.

The median juvenile arthritis disease activity score (JADAS)-27 did change considerably between visits (1.9-2.5), but JADAS-27 was significantly elevated at 7 months (P = .001) due to one outlier. SLE and JDM disease activity remained similar.

Days before Dr. Heijstek’s presentation, Dr. Wulffraat provided a background discussion on vaccinations in children with rheumatic diseases. Dr. Wulffraat and Dr. Heijstek’s investigation of MMR vaccine in JIA patients had shown the vaccine not to cause rheumatic disease flare ups or viral disease, and methotrexate use did not appear to affect antibody response.

What is remains unknown is how durable any vaccine protection is in children with rheumatic disease, according to Dr. Wulffraat. Longer study will be required to determine how long the titers persist, and whether they are protective in children on biological therapies such as anti-TNF inhibitors.

Neither Dr. Wulffraat nor Dr. Heijstek disclosed conflicts of interest related to their findings.

BRUGES, BELGIUM – A normal physical examination may be all that it takes to confirm inactive disease in a child with juvenile-onset systemic lupus erythematosus, according to new criteria.

Dr. Rina Mina of Cincinnati Children’s Medical Center said that she and her associated developed the criteria to determine clinical remission and clinically inactive disease in juvenile-onset systemic lupus erythematosus (JSLE), a complex disease. They used Delphi surveys of 210 pediatric rheumatologists. The senior author on the paper (Pediatr. Rheum. 2011;9[suppl. 1]:O17) was Dr. Hermine I. Brunner, also of Cincinnati Children’s.

The surveys achieved consensus on four descriptors: clinically inactive disease – which is defined without regard to medications used – and clinical remission on medication (including steroids and immunosuppressants), clinical remission on preventive medication, and clinical remission off medication. Consensus was lowest – only 86% – on what defined clinical remission off medication, while consensus for the other categories was between 94% and 96%.

According to the criteria, a JSLE patient with either inactive disease or clinical remission "should have no signs of disease activity on physical examination," Dr. Mina explained, adding that physical examination may ultimately prove to be enough to define inactivity. A patient with inactive disease or remission can have at most two nonlimiting symptoms such as headaches or fatigue.

Some select laboratory abnormalities can persist under either definition, she said, including a persistently positive antinuclear antibody test result, proteinuria from lupus-related kidney damage, or low levels of C4, for example. Members of the conference challenged Dr. Mina on the proteinuria, suggesting that it was dangerous to accept a patient with proteinuria as in remission; however, Dr. Mina argued that proteinuria was defined as a stable proteinuria as the result of damage, not a changing condition.

Use of preventive medication other than a steroid or immunosuppressant was defined as any medication to thwart disease progression or the development of disease-related damage. This category includes angiotensin-converting enzyme inhibitors, vitamin D, omega-3 acids, statins, and/or bisphosphonates. There was no consensus among the surveyed pediatric rheumatologists on whether nonsteroidal anti-inflammatory agents used daily could be considered preventive, Dr. Mina said at the meeting. Also lacking was any consensus on whether antimalarial drugs were to be considered preventive.

One of the key areas of consensus achieved by the surveys was that "inactive disease and clinical remission are distinct and should be differentiated from cure as well as from minimal disease activity," Dr. Mina said. What was "crucial" in differentiating between inactive disease and clinical remission was the time frame. Clinical remission on medication or with preventive medication is defined as requiring 6 continuous months. The criteria, she noted, are similar to current American College of Rheumatology/European League Against Rheumatism criteria for defining clinically inactive disease and remission in juvenile idiopathic arthritis.

Remission off medication was defined as disease inactivity for at least 12 continuous months. Patients could be considered "off medication" if they were not being treated with steroids, immunosuppressants, or preventive medications; however a patient could be treated with insulin to treat steroid-induced diabetes, for example, and still be included in this definition.

Dr. Mina reported that her group had validated the consensus definitions with a cohort of JSLE patients and had found the accuracy to be "outstanding" compared with scores from widely used disease indexes for JSLE. The new criteria surpassed both the SLE Disease Activity Index and the British Isles Lupus Assessment Group score in establishing inactive disease and remission. "All core parameters support the content validity of the consensus process," she said.

Dr. Mina said she had no relevant financial disclosures.

BRUGES, BELGIUM – A normal physical examination may be all that it takes to confirm inactive disease in a child with juvenile-onset systemic lupus erythematosus, according to new criteria.

Dr. Rina Mina of Cincinnati Children’s Medical Center said that she and her associated developed the criteria to determine clinical remission and clinically inactive disease in juvenile-onset systemic lupus erythematosus (JSLE), a complex disease. They used Delphi surveys of 210 pediatric rheumatologists. The senior author on the paper (Pediatr. Rheum. 2011;9[suppl. 1]:O17) was Dr. Hermine I. Brunner, also of Cincinnati Children’s.

The surveys achieved consensus on four descriptors: clinically inactive disease – which is defined without regard to medications used – and clinical remission on medication (including steroids and immunosuppressants), clinical remission on preventive medication, and clinical remission off medication. Consensus was lowest – only 86% – on what defined clinical remission off medication, while consensus for the other categories was between 94% and 96%.

According to the criteria, a JSLE patient with either inactive disease or clinical remission "should have no signs of disease activity on physical examination," Dr. Mina explained, adding that physical examination may ultimately prove to be enough to define inactivity. A patient with inactive disease or remission can have at most two nonlimiting symptoms such as headaches or fatigue.

Some select laboratory abnormalities can persist under either definition, she said, including a persistently positive antinuclear antibody test result, proteinuria from lupus-related kidney damage, or low levels of C4, for example. Members of the conference challenged Dr. Mina on the proteinuria, suggesting that it was dangerous to accept a patient with proteinuria as in remission; however, Dr. Mina argued that proteinuria was defined as a stable proteinuria as the result of damage, not a changing condition.

Use of preventive medication other than a steroid or immunosuppressant was defined as any medication to thwart disease progression or the development of disease-related damage. This category includes angiotensin-converting enzyme inhibitors, vitamin D, omega-3 acids, statins, and/or bisphosphonates. There was no consensus among the surveyed pediatric rheumatologists on whether nonsteroidal anti-inflammatory agents used daily could be considered preventive, Dr. Mina said at the meeting. Also lacking was any consensus on whether antimalarial drugs were to be considered preventive.

One of the key areas of consensus achieved by the surveys was that "inactive disease and clinical remission are distinct and should be differentiated from cure as well as from minimal disease activity," Dr. Mina said. What was "crucial" in differentiating between inactive disease and clinical remission was the time frame. Clinical remission on medication or with preventive medication is defined as requiring 6 continuous months. The criteria, she noted, are similar to current American College of Rheumatology/European League Against Rheumatism criteria for defining clinically inactive disease and remission in juvenile idiopathic arthritis.

Remission off medication was defined as disease inactivity for at least 12 continuous months. Patients could be considered "off medication" if they were not being treated with steroids, immunosuppressants, or preventive medications; however a patient could be treated with insulin to treat steroid-induced diabetes, for example, and still be included in this definition.

Dr. Mina reported that her group had validated the consensus definitions with a cohort of JSLE patients and had found the accuracy to be "outstanding" compared with scores from widely used disease indexes for JSLE. The new criteria surpassed both the SLE Disease Activity Index and the British Isles Lupus Assessment Group score in establishing inactive disease and remission. "All core parameters support the content validity of the consensus process," she said.

Dr. Mina said she had no relevant financial disclosures.

BRUGES, BELGIUM – A normal physical examination may be all that it takes to confirm inactive disease in a child with juvenile-onset systemic lupus erythematosus, according to new criteria.

Dr. Rina Mina of Cincinnati Children’s Medical Center said that she and her associated developed the criteria to determine clinical remission and clinically inactive disease in juvenile-onset systemic lupus erythematosus (JSLE), a complex disease. They used Delphi surveys of 210 pediatric rheumatologists. The senior author on the paper (Pediatr. Rheum. 2011;9[suppl. 1]:O17) was Dr. Hermine I. Brunner, also of Cincinnati Children’s.

The surveys achieved consensus on four descriptors: clinically inactive disease – which is defined without regard to medications used – and clinical remission on medication (including steroids and immunosuppressants), clinical remission on preventive medication, and clinical remission off medication. Consensus was lowest – only 86% – on what defined clinical remission off medication, while consensus for the other categories was between 94% and 96%.

According to the criteria, a JSLE patient with either inactive disease or clinical remission "should have no signs of disease activity on physical examination," Dr. Mina explained, adding that physical examination may ultimately prove to be enough to define inactivity. A patient with inactive disease or remission can have at most two nonlimiting symptoms such as headaches or fatigue.

Some select laboratory abnormalities can persist under either definition, she said, including a persistently positive antinuclear antibody test result, proteinuria from lupus-related kidney damage, or low levels of C4, for example. Members of the conference challenged Dr. Mina on the proteinuria, suggesting that it was dangerous to accept a patient with proteinuria as in remission; however, Dr. Mina argued that proteinuria was defined as a stable proteinuria as the result of damage, not a changing condition.

Use of preventive medication other than a steroid or immunosuppressant was defined as any medication to thwart disease progression or the development of disease-related damage. This category includes angiotensin-converting enzyme inhibitors, vitamin D, omega-3 acids, statins, and/or bisphosphonates. There was no consensus among the surveyed pediatric rheumatologists on whether nonsteroidal anti-inflammatory agents used daily could be considered preventive, Dr. Mina said at the meeting. Also lacking was any consensus on whether antimalarial drugs were to be considered preventive.

One of the key areas of consensus achieved by the surveys was that "inactive disease and clinical remission are distinct and should be differentiated from cure as well as from minimal disease activity," Dr. Mina said. What was "crucial" in differentiating between inactive disease and clinical remission was the time frame. Clinical remission on medication or with preventive medication is defined as requiring 6 continuous months. The criteria, she noted, are similar to current American College of Rheumatology/European League Against Rheumatism criteria for defining clinically inactive disease and remission in juvenile idiopathic arthritis.

Remission off medication was defined as disease inactivity for at least 12 continuous months. Patients could be considered "off medication" if they were not being treated with steroids, immunosuppressants, or preventive medications; however a patient could be treated with insulin to treat steroid-induced diabetes, for example, and still be included in this definition.

Dr. Mina reported that her group had validated the consensus definitions with a cohort of JSLE patients and had found the accuracy to be "outstanding" compared with scores from widely used disease indexes for JSLE. The new criteria surpassed both the SLE Disease Activity Index and the British Isles Lupus Assessment Group score in establishing inactive disease and remission. "All core parameters support the content validity of the consensus process," she said.

Dr. Mina said she had no relevant financial disclosures.