Amy Rothman Schonfeld

NEW YORK – When magnetic resonance imaging is used instead of plain x-rays in patients with early inflammatory back pain, the diagnostic accuracy for spondyloarthritis jumps from 25% to 70%, according to Dr. Maxime Dougados, who spoke at a rheumatology meeting sponsored by New York University.

"Seventy-five percent of the time, you cannot make the diagnosis with plain x-rays," said Dr. Dougados, professor of rheumatology at Paris-Descartes University/Cochin Hospital in Paris and the president-elect of EULAR. He presented the Ira Goldstein Memorial Lecture at the meeting, focusing on spondyloarthritis (SpA).

Dr. Dougados presented the as yet unpublished results from the DESIR cohort, a large French national multicenter database of long-term follow-up of 708 patients presenting with early inflammatory back pain that was initiated by the French Society of Rheumatology. Patients were recruited between December 2007 and April 2010 if they had inflammatory back pain lasting more than 3 months and less than 3 years. The group will be followed for 10 years in the ongoing study. At baseline, the mean age was 35 years, 54% were female and 57% were HLA-B27 positive (Joint Bone Spine 2011 March 30 [doi: 10.1016/j.jbspin.2011.01.013]).

Looking at radiological sacroiliac changes, the diagnosis was "obvious" for 25.6% of the cohort, "doubtful" for 21.3%, and "normal" for 53.1%. "These results indicate that at the first clinical visit, the interview is very important to pick up other clinical symptoms," said Dr. Dougados. In fact, about 80% were found to have non-axial clinical manifestations, including articular peripheral involvement, enthesopathy, dactylitis, anterior chest wall pain, uveitis, or psoriasis.

Using MRI, 70% of the cohort were determined to have "obvious" sacroiliitis, about 20% had a "doubtful" diagnosis and about 10% were thought to be "normal."

"These results indicate that you can detect early abnormalities of the sacroiliac joint on MRI even if x-rays are normal," he said.

According to Dr. Dougados, these imaging findings fit well with recent results from the DECLIC study, in which 163 rheumatologists were asked to diagnose 472 patients with early inflammatory back pain, including 161 patients with spondyloarthritis, according to four different sets of criteria. The specificity of the modified New York criteria, which relies on radiographic signs of sacroiliitis (unilateral grade III or bilateral grade II), fell well below that of the modified Amor criteria, the modified ESSG (European Spondyloarthropathy Study Group) criteria, and the ASAS (Assessment of Spondyloarthritis International Society) criteria. The latter three criteria include the option of diagnosing sacroiliitis with MRI.

In the new classification criteria from the ASAS, separate criteria are listed for patients with axial SpA with and without peripheral manifestations and patients with peripheral manifestations only. For axial SpA, one diagnostic pathway requires sacroiliitis on imaging plus one or more SpA feature. Sacroiliitis on MRI is given as much weight as is sacroiliitis on radiographs (Best Pract. Res. Clin. Rheumatol. 2010;24:589-604). The other pathway requires HLA-B27 positivity plus two or more SpA features. In patients with peripheral manifestations only, the requirements include peripheral arthritis, enthesitis or dactylitis plus one or more SpA features, including sacroiliitis on imaging.

Dr. Dougados also spoke about recent findings showing that patients with SpA were more likely to have distinct noninflammatory spinal MRI lesions (known as Fatty Romanus lesions) than were patients with degenerative arthritis or spinal malignancy (Ann. Rheum. Dis. 2010; 69:891-94).

"As MRI is becoming more important, rheumatologists should be trained to interpret MRIs," he said. "You don’t need to be a specialist in radiology."

Dr. Dougados has received grants for research projects and/or honorarium fees for participation at advisory boards/symposiums from Abbott, Bristol-Myers Squibb, Merck, Pfizer, Sanofi, and UCB.

NEW YORK – When magnetic resonance imaging is used instead of plain x-rays in patients with early inflammatory back pain, the diagnostic accuracy for spondyloarthritis jumps from 25% to 70%, according to Dr. Maxime Dougados, who spoke at a rheumatology meeting sponsored by New York University.

"Seventy-five percent of the time, you cannot make the diagnosis with plain x-rays," said Dr. Dougados, professor of rheumatology at Paris-Descartes University/Cochin Hospital in Paris and the president-elect of EULAR. He presented the Ira Goldstein Memorial Lecture at the meeting, focusing on spondyloarthritis (SpA).

Dr. Dougados presented the as yet unpublished results from the DESIR cohort, a large French national multicenter database of long-term follow-up of 708 patients presenting with early inflammatory back pain that was initiated by the French Society of Rheumatology. Patients were recruited between December 2007 and April 2010 if they had inflammatory back pain lasting more than 3 months and less than 3 years. The group will be followed for 10 years in the ongoing study. At baseline, the mean age was 35 years, 54% were female and 57% were HLA-B27 positive (Joint Bone Spine 2011 March 30 [doi: 10.1016/j.jbspin.2011.01.013]).

Looking at radiological sacroiliac changes, the diagnosis was "obvious" for 25.6% of the cohort, "doubtful" for 21.3%, and "normal" for 53.1%. "These results indicate that at the first clinical visit, the interview is very important to pick up other clinical symptoms," said Dr. Dougados. In fact, about 80% were found to have non-axial clinical manifestations, including articular peripheral involvement, enthesopathy, dactylitis, anterior chest wall pain, uveitis, or psoriasis.

Using MRI, 70% of the cohort were determined to have "obvious" sacroiliitis, about 20% had a "doubtful" diagnosis and about 10% were thought to be "normal."

"These results indicate that you can detect early abnormalities of the sacroiliac joint on MRI even if x-rays are normal," he said.

According to Dr. Dougados, these imaging findings fit well with recent results from the DECLIC study, in which 163 rheumatologists were asked to diagnose 472 patients with early inflammatory back pain, including 161 patients with spondyloarthritis, according to four different sets of criteria. The specificity of the modified New York criteria, which relies on radiographic signs of sacroiliitis (unilateral grade III or bilateral grade II), fell well below that of the modified Amor criteria, the modified ESSG (European Spondyloarthropathy Study Group) criteria, and the ASAS (Assessment of Spondyloarthritis International Society) criteria. The latter three criteria include the option of diagnosing sacroiliitis with MRI.

In the new classification criteria from the ASAS, separate criteria are listed for patients with axial SpA with and without peripheral manifestations and patients with peripheral manifestations only. For axial SpA, one diagnostic pathway requires sacroiliitis on imaging plus one or more SpA feature. Sacroiliitis on MRI is given as much weight as is sacroiliitis on radiographs (Best Pract. Res. Clin. Rheumatol. 2010;24:589-604). The other pathway requires HLA-B27 positivity plus two or more SpA features. In patients with peripheral manifestations only, the requirements include peripheral arthritis, enthesitis or dactylitis plus one or more SpA features, including sacroiliitis on imaging.

Dr. Dougados also spoke about recent findings showing that patients with SpA were more likely to have distinct noninflammatory spinal MRI lesions (known as Fatty Romanus lesions) than were patients with degenerative arthritis or spinal malignancy (Ann. Rheum. Dis. 2010; 69:891-94).

"As MRI is becoming more important, rheumatologists should be trained to interpret MRIs," he said. "You don’t need to be a specialist in radiology."

Dr. Dougados has received grants for research projects and/or honorarium fees for participation at advisory boards/symposiums from Abbott, Bristol-Myers Squibb, Merck, Pfizer, Sanofi, and UCB.

NEW YORK – When magnetic resonance imaging is used instead of plain x-rays in patients with early inflammatory back pain, the diagnostic accuracy for spondyloarthritis jumps from 25% to 70%, according to Dr. Maxime Dougados, who spoke at a rheumatology meeting sponsored by New York University.

"Seventy-five percent of the time, you cannot make the diagnosis with plain x-rays," said Dr. Dougados, professor of rheumatology at Paris-Descartes University/Cochin Hospital in Paris and the president-elect of EULAR. He presented the Ira Goldstein Memorial Lecture at the meeting, focusing on spondyloarthritis (SpA).

Dr. Dougados presented the as yet unpublished results from the DESIR cohort, a large French national multicenter database of long-term follow-up of 708 patients presenting with early inflammatory back pain that was initiated by the French Society of Rheumatology. Patients were recruited between December 2007 and April 2010 if they had inflammatory back pain lasting more than 3 months and less than 3 years. The group will be followed for 10 years in the ongoing study. At baseline, the mean age was 35 years, 54% were female and 57% were HLA-B27 positive (Joint Bone Spine 2011 March 30 [doi: 10.1016/j.jbspin.2011.01.013]).

Looking at radiological sacroiliac changes, the diagnosis was "obvious" for 25.6% of the cohort, "doubtful" for 21.3%, and "normal" for 53.1%. "These results indicate that at the first clinical visit, the interview is very important to pick up other clinical symptoms," said Dr. Dougados. In fact, about 80% were found to have non-axial clinical manifestations, including articular peripheral involvement, enthesopathy, dactylitis, anterior chest wall pain, uveitis, or psoriasis.

Using MRI, 70% of the cohort were determined to have "obvious" sacroiliitis, about 20% had a "doubtful" diagnosis and about 10% were thought to be "normal."

"These results indicate that you can detect early abnormalities of the sacroiliac joint on MRI even if x-rays are normal," he said.

According to Dr. Dougados, these imaging findings fit well with recent results from the DECLIC study, in which 163 rheumatologists were asked to diagnose 472 patients with early inflammatory back pain, including 161 patients with spondyloarthritis, according to four different sets of criteria. The specificity of the modified New York criteria, which relies on radiographic signs of sacroiliitis (unilateral grade III or bilateral grade II), fell well below that of the modified Amor criteria, the modified ESSG (European Spondyloarthropathy Study Group) criteria, and the ASAS (Assessment of Spondyloarthritis International Society) criteria. The latter three criteria include the option of diagnosing sacroiliitis with MRI.

In the new classification criteria from the ASAS, separate criteria are listed for patients with axial SpA with and without peripheral manifestations and patients with peripheral manifestations only. For axial SpA, one diagnostic pathway requires sacroiliitis on imaging plus one or more SpA feature. Sacroiliitis on MRI is given as much weight as is sacroiliitis on radiographs (Best Pract. Res. Clin. Rheumatol. 2010;24:589-604). The other pathway requires HLA-B27 positivity plus two or more SpA features. In patients with peripheral manifestations only, the requirements include peripheral arthritis, enthesitis or dactylitis plus one or more SpA features, including sacroiliitis on imaging.

Dr. Dougados also spoke about recent findings showing that patients with SpA were more likely to have distinct noninflammatory spinal MRI lesions (known as Fatty Romanus lesions) than were patients with degenerative arthritis or spinal malignancy (Ann. Rheum. Dis. 2010; 69:891-94).

"As MRI is becoming more important, rheumatologists should be trained to interpret MRIs," he said. "You don’t need to be a specialist in radiology."

Dr. Dougados has received grants for research projects and/or honorarium fees for participation at advisory boards/symposiums from Abbott, Bristol-Myers Squibb, Merck, Pfizer, Sanofi, and UCB.

NEW YORK – The good news in the management of childhood-onset systemic lupus erythematosus is that children who are diagnosed with the disease have a better prognosis and are living longer. The bad news is that over the course of a lifetime, affected children develop more morbidities and experience more medication-induced toxicities, which create additional management challenges, according to Dr. Phillip Kahn, who spoke at a meeting sponsored by New York University.

About 15%-20% of lupus cases present in childhood. Children younger than age 5 years rarely have the disease, but up to 40% of patients with childhood-onset SLE (cSLE) present prior to puberty, said Dr. Kahn of New York University. The incidence of cSLE is estimated to be 10-20 cases per 100,000 individuals, but the incidence is higher in blacks, at 200 cases per 100,000 individuals (Lupus 2007;16:546-9; 2005;14:83-8).

Often the diagnosis is delayed in children, as their clinical features do not fall within those defined by the 1997 American College of Rheumatology’s SLE criteria, which have not been validated in children. For example, Dr. Kahn described the case of a 13-year-old girl who presented with "constitutional symptoms" such as diffuse lymphadenopathy, malaise, weight loss, and fever – none of which are included in the 1997 criteria.

Mucocutaneous lesions are common in children, with up to 70% presenting with malar rash, 30% with alopecia, 66% with oral ulcers, and 10% with nasal ulcers. "Although nasal ulcers are less common in children than adults, they still may result in perforation of the septum," he said. Other common manifestations include painful polyarthritis, hepatosplenomegaly, headache, photosensitivity, and Raynaud’s phenomenon. Up to 40% of cSLE patients have neuropsychiatric symptoms, significantly more than do adults (Lupus 2008;17:314-22).

An important diagnostic tool for cSLE is a positive ANA (antinuclear antibody) finding, which is present in essentially all children with cSLE. In contrast, up to 10% of adults with SLE do not have a positive ANA, said Dr. Kahn.

Childhood-onset lupus may predict mortality in adults (Arthritis Care Res. [Hoboken] 2010;62:1152-9) and thus physicians must be vigilant about detecting, preventing, and aggressively treating some of its more dangerous manifestations. To prevent recurrent infection, Dr. Kahn recommends keeping a child up to date with immunizations, treating infections promptly when they occur, and considering PCP (pneumocystis carinii pneumonia) prophylaxis in the appropriate patient. Children with cSLE are also at increased risk for premature atherosclerosis, with dyslipidemia seen in 60%-85% of affected children (Nat. Clin. Pract. Rheumatol. 2008;4:258-65). Statin therapy may be appropriate in these children, especially to prevent long-term adverse events such as early MI. For example, adults – especially women – who had c SLE have increased incidence of MI when they reach their 30s (Arthritis Rheum. 2009;61:13-20). The ongoing APPLE (Atherosclerosis Prevention in Pediatric Lupus Erythematosus) trial is investigating, in greater detail, cardiovascular risk and the use of statins in cSLE (Lupus 2010;19:1315-25).

Because nephropathy is the main cause of mortality and morbidity in cSLE, it is important to monitor urinary markers of renal function. Nephropathy may take a greater toll on a pediatric patient, compared with adults; data show that children are more likely to have renal involvement, need hemodialysis and kidney transplantation, and require hospitalization and emergency department visits (Lupus 2008;17:314-22; Arthritis Rheum. 2009;61:13-20). To avoid end-stage renal disease, Dr. Kahn urges tight blood pressure control, as well as antihypertensive medication as necessary. "We know that 90% of the patients who ultimately develop renal disease will do so within the first 2 years of disease, so if you follow a patient for [more than 2] years and they do not develop the disease, the good news is they are much less likely to develop nephropathy," said Dr. Kahn.

In the 1950s, the 5-year survival rate for SLE in adults and children ranged from 18% to 70%; 30 years later, 5-year survival rose to 60%-93%, in large part because of the introduction of prednisone. Currently, prednisone is almost universally given to those with cSLE, and the proportion of children who are treated with prednisone is significantly higher than the proportion of adults with SLE (97% vs. 70%; P less than .0001) (Arthritis Rheum. 2008;58:556-62). The result is greater risk of osteoporosis, diabetes, and growth failure. In fact, up to 40% of cSLE patients have growth failure or short stature, in part because of chronic steroids.

That is why Dr. Kahn posed the question, "Can we move beyond steroids?" Until recently, the only Food and Drug Administration–approved medications for SLE were prednisone, hydroxychloroquine, and aspirin. Steroid-sparing immunomodulatory therapy is sometimes used off label when major organ (such as brain or kidney) involvement develops, but most evidence regarding the efficacy of these medications pertains to renal proliferative disease in adults.

Cyclophosphamide is often used for induction of nephritis, but 30% of patients may still develop end-stage renal disease despite treatment, said Dr. Kahn. Mycophenolate mofetil has been shown to have equal efficacy to cyclophosphamide in induction of remission of nephritis, but sufficient pediatric data are lacking. Azathioprine is effective for maintenance therapy of nephritis after the induction phase.

Other options that are sometimes used include intravenous immunoglobulin, methotrexate, calcineurin inhibitors (such as tacrolimus), plasmapheresis, and autologous stem cell transplantation/immunoablative therapy.

More recently, the focus has been on target-specific therapy for SLE with potentially fewer side effects. Rituximab, which targets B cells that have the CD20 surface antigen, is sometimes used to treat resistant patients, but there is no strong clinical evidence to demonstrate its effectiveness in cSLE (Arthritis Rheum. 2009;61:482-7; Clin. J. Am. Soc. Nephrol. 2009;4:579-87).

Abatacept, which targets T cells by binding to B7 peripheral membrane protein, has shown some clinical benefit in a phase IIB randomized clinical trial, and is undergoing clinical testing as an add-on induction therapy with cyclophosphamide (Arthritis Rheum. 2010;62:3077-87). Belimumab, a monoclonal antibody that targets BLyS (B-lymphocyte stimulator)/BAFF (B-cell activating factor), is the first FDA-approved medication for SLE in more than 50 years, based on recent clinical trials that demonstrate increased efficacy and fewer flares of disease, compared with placebo (Arthritis Rheum 2009;61:1168-78; Lancet 2011;377:721-31).

Although recent data regarding belimumab provide some hope, it "may be naive to think that a target-specific therapy exists in this complex, polygenic, heterogeneous disease," commented Dr. Kahn.

In concluding his talk, Dr. Kahn spoke about some barriers to the effective treatment of cSLE. These include physicians’ failure to detect the subtle changes of early disease, a lack of awareness regarding the neuropsychiatric manifestations of the disease, and physicians’ fear of being overly aggressive with treatment. He also warned about overt or covert adolescent noncompliance, and the danger of adolescents’ dropping out of the health care system once they need to transition to adult care.

NEW YORK – The good news in the management of childhood-onset systemic lupus erythematosus is that children who are diagnosed with the disease have a better prognosis and are living longer. The bad news is that over the course of a lifetime, affected children develop more morbidities and experience more medication-induced toxicities, which create additional management challenges, according to Dr. Phillip Kahn, who spoke at a meeting sponsored by New York University.

About 15%-20% of lupus cases present in childhood. Children younger than age 5 years rarely have the disease, but up to 40% of patients with childhood-onset SLE (cSLE) present prior to puberty, said Dr. Kahn of New York University. The incidence of cSLE is estimated to be 10-20 cases per 100,000 individuals, but the incidence is higher in blacks, at 200 cases per 100,000 individuals (Lupus 2007;16:546-9; 2005;14:83-8).

Often the diagnosis is delayed in children, as their clinical features do not fall within those defined by the 1997 American College of Rheumatology’s SLE criteria, which have not been validated in children. For example, Dr. Kahn described the case of a 13-year-old girl who presented with "constitutional symptoms" such as diffuse lymphadenopathy, malaise, weight loss, and fever – none of which are included in the 1997 criteria.

Mucocutaneous lesions are common in children, with up to 70% presenting with malar rash, 30% with alopecia, 66% with oral ulcers, and 10% with nasal ulcers. "Although nasal ulcers are less common in children than adults, they still may result in perforation of the septum," he said. Other common manifestations include painful polyarthritis, hepatosplenomegaly, headache, photosensitivity, and Raynaud’s phenomenon. Up to 40% of cSLE patients have neuropsychiatric symptoms, significantly more than do adults (Lupus 2008;17:314-22).

An important diagnostic tool for cSLE is a positive ANA (antinuclear antibody) finding, which is present in essentially all children with cSLE. In contrast, up to 10% of adults with SLE do not have a positive ANA, said Dr. Kahn.

Childhood-onset lupus may predict mortality in adults (Arthritis Care Res. [Hoboken] 2010;62:1152-9) and thus physicians must be vigilant about detecting, preventing, and aggressively treating some of its more dangerous manifestations. To prevent recurrent infection, Dr. Kahn recommends keeping a child up to date with immunizations, treating infections promptly when they occur, and considering PCP (pneumocystis carinii pneumonia) prophylaxis in the appropriate patient. Children with cSLE are also at increased risk for premature atherosclerosis, with dyslipidemia seen in 60%-85% of affected children (Nat. Clin. Pract. Rheumatol. 2008;4:258-65). Statin therapy may be appropriate in these children, especially to prevent long-term adverse events such as early MI. For example, adults – especially women – who had c SLE have increased incidence of MI when they reach their 30s (Arthritis Rheum. 2009;61:13-20). The ongoing APPLE (Atherosclerosis Prevention in Pediatric Lupus Erythematosus) trial is investigating, in greater detail, cardiovascular risk and the use of statins in cSLE (Lupus 2010;19:1315-25).

Because nephropathy is the main cause of mortality and morbidity in cSLE, it is important to monitor urinary markers of renal function. Nephropathy may take a greater toll on a pediatric patient, compared with adults; data show that children are more likely to have renal involvement, need hemodialysis and kidney transplantation, and require hospitalization and emergency department visits (Lupus 2008;17:314-22; Arthritis Rheum. 2009;61:13-20). To avoid end-stage renal disease, Dr. Kahn urges tight blood pressure control, as well as antihypertensive medication as necessary. "We know that 90% of the patients who ultimately develop renal disease will do so within the first 2 years of disease, so if you follow a patient for [more than 2] years and they do not develop the disease, the good news is they are much less likely to develop nephropathy," said Dr. Kahn.

In the 1950s, the 5-year survival rate for SLE in adults and children ranged from 18% to 70%; 30 years later, 5-year survival rose to 60%-93%, in large part because of the introduction of prednisone. Currently, prednisone is almost universally given to those with cSLE, and the proportion of children who are treated with prednisone is significantly higher than the proportion of adults with SLE (97% vs. 70%; P less than .0001) (Arthritis Rheum. 2008;58:556-62). The result is greater risk of osteoporosis, diabetes, and growth failure. In fact, up to 40% of cSLE patients have growth failure or short stature, in part because of chronic steroids.

That is why Dr. Kahn posed the question, "Can we move beyond steroids?" Until recently, the only Food and Drug Administration–approved medications for SLE were prednisone, hydroxychloroquine, and aspirin. Steroid-sparing immunomodulatory therapy is sometimes used off label when major organ (such as brain or kidney) involvement develops, but most evidence regarding the efficacy of these medications pertains to renal proliferative disease in adults.

Cyclophosphamide is often used for induction of nephritis, but 30% of patients may still develop end-stage renal disease despite treatment, said Dr. Kahn. Mycophenolate mofetil has been shown to have equal efficacy to cyclophosphamide in induction of remission of nephritis, but sufficient pediatric data are lacking. Azathioprine is effective for maintenance therapy of nephritis after the induction phase.

Other options that are sometimes used include intravenous immunoglobulin, methotrexate, calcineurin inhibitors (such as tacrolimus), plasmapheresis, and autologous stem cell transplantation/immunoablative therapy.

More recently, the focus has been on target-specific therapy for SLE with potentially fewer side effects. Rituximab, which targets B cells that have the CD20 surface antigen, is sometimes used to treat resistant patients, but there is no strong clinical evidence to demonstrate its effectiveness in cSLE (Arthritis Rheum. 2009;61:482-7; Clin. J. Am. Soc. Nephrol. 2009;4:579-87).

Abatacept, which targets T cells by binding to B7 peripheral membrane protein, has shown some clinical benefit in a phase IIB randomized clinical trial, and is undergoing clinical testing as an add-on induction therapy with cyclophosphamide (Arthritis Rheum. 2010;62:3077-87). Belimumab, a monoclonal antibody that targets BLyS (B-lymphocyte stimulator)/BAFF (B-cell activating factor), is the first FDA-approved medication for SLE in more than 50 years, based on recent clinical trials that demonstrate increased efficacy and fewer flares of disease, compared with placebo (Arthritis Rheum 2009;61:1168-78; Lancet 2011;377:721-31).

Although recent data regarding belimumab provide some hope, it "may be naive to think that a target-specific therapy exists in this complex, polygenic, heterogeneous disease," commented Dr. Kahn.

In concluding his talk, Dr. Kahn spoke about some barriers to the effective treatment of cSLE. These include physicians’ failure to detect the subtle changes of early disease, a lack of awareness regarding the neuropsychiatric manifestations of the disease, and physicians’ fear of being overly aggressive with treatment. He also warned about overt or covert adolescent noncompliance, and the danger of adolescents’ dropping out of the health care system once they need to transition to adult care.

NEW YORK – The good news in the management of childhood-onset systemic lupus erythematosus is that children who are diagnosed with the disease have a better prognosis and are living longer. The bad news is that over the course of a lifetime, affected children develop more morbidities and experience more medication-induced toxicities, which create additional management challenges, according to Dr. Phillip Kahn, who spoke at a meeting sponsored by New York University.

About 15%-20% of lupus cases present in childhood. Children younger than age 5 years rarely have the disease, but up to 40% of patients with childhood-onset SLE (cSLE) present prior to puberty, said Dr. Kahn of New York University. The incidence of cSLE is estimated to be 10-20 cases per 100,000 individuals, but the incidence is higher in blacks, at 200 cases per 100,000 individuals (Lupus 2007;16:546-9; 2005;14:83-8).

Often the diagnosis is delayed in children, as their clinical features do not fall within those defined by the 1997 American College of Rheumatology’s SLE criteria, which have not been validated in children. For example, Dr. Kahn described the case of a 13-year-old girl who presented with "constitutional symptoms" such as diffuse lymphadenopathy, malaise, weight loss, and fever – none of which are included in the 1997 criteria.

Mucocutaneous lesions are common in children, with up to 70% presenting with malar rash, 30% with alopecia, 66% with oral ulcers, and 10% with nasal ulcers. "Although nasal ulcers are less common in children than adults, they still may result in perforation of the septum," he said. Other common manifestations include painful polyarthritis, hepatosplenomegaly, headache, photosensitivity, and Raynaud’s phenomenon. Up to 40% of cSLE patients have neuropsychiatric symptoms, significantly more than do adults (Lupus 2008;17:314-22).

An important diagnostic tool for cSLE is a positive ANA (antinuclear antibody) finding, which is present in essentially all children with cSLE. In contrast, up to 10% of adults with SLE do not have a positive ANA, said Dr. Kahn.

Childhood-onset lupus may predict mortality in adults (Arthritis Care Res. [Hoboken] 2010;62:1152-9) and thus physicians must be vigilant about detecting, preventing, and aggressively treating some of its more dangerous manifestations. To prevent recurrent infection, Dr. Kahn recommends keeping a child up to date with immunizations, treating infections promptly when they occur, and considering PCP (pneumocystis carinii pneumonia) prophylaxis in the appropriate patient. Children with cSLE are also at increased risk for premature atherosclerosis, with dyslipidemia seen in 60%-85% of affected children (Nat. Clin. Pract. Rheumatol. 2008;4:258-65). Statin therapy may be appropriate in these children, especially to prevent long-term adverse events such as early MI. For example, adults – especially women – who had c SLE have increased incidence of MI when they reach their 30s (Arthritis Rheum. 2009;61:13-20). The ongoing APPLE (Atherosclerosis Prevention in Pediatric Lupus Erythematosus) trial is investigating, in greater detail, cardiovascular risk and the use of statins in cSLE (Lupus 2010;19:1315-25).

Because nephropathy is the main cause of mortality and morbidity in cSLE, it is important to monitor urinary markers of renal function. Nephropathy may take a greater toll on a pediatric patient, compared with adults; data show that children are more likely to have renal involvement, need hemodialysis and kidney transplantation, and require hospitalization and emergency department visits (Lupus 2008;17:314-22; Arthritis Rheum. 2009;61:13-20). To avoid end-stage renal disease, Dr. Kahn urges tight blood pressure control, as well as antihypertensive medication as necessary. "We know that 90% of the patients who ultimately develop renal disease will do so within the first 2 years of disease, so if you follow a patient for [more than 2] years and they do not develop the disease, the good news is they are much less likely to develop nephropathy," said Dr. Kahn.

In the 1950s, the 5-year survival rate for SLE in adults and children ranged from 18% to 70%; 30 years later, 5-year survival rose to 60%-93%, in large part because of the introduction of prednisone. Currently, prednisone is almost universally given to those with cSLE, and the proportion of children who are treated with prednisone is significantly higher than the proportion of adults with SLE (97% vs. 70%; P less than .0001) (Arthritis Rheum. 2008;58:556-62). The result is greater risk of osteoporosis, diabetes, and growth failure. In fact, up to 40% of cSLE patients have growth failure or short stature, in part because of chronic steroids.

That is why Dr. Kahn posed the question, "Can we move beyond steroids?" Until recently, the only Food and Drug Administration–approved medications for SLE were prednisone, hydroxychloroquine, and aspirin. Steroid-sparing immunomodulatory therapy is sometimes used off label when major organ (such as brain or kidney) involvement develops, but most evidence regarding the efficacy of these medications pertains to renal proliferative disease in adults.

Cyclophosphamide is often used for induction of nephritis, but 30% of patients may still develop end-stage renal disease despite treatment, said Dr. Kahn. Mycophenolate mofetil has been shown to have equal efficacy to cyclophosphamide in induction of remission of nephritis, but sufficient pediatric data are lacking. Azathioprine is effective for maintenance therapy of nephritis after the induction phase.

Other options that are sometimes used include intravenous immunoglobulin, methotrexate, calcineurin inhibitors (such as tacrolimus), plasmapheresis, and autologous stem cell transplantation/immunoablative therapy.

More recently, the focus has been on target-specific therapy for SLE with potentially fewer side effects. Rituximab, which targets B cells that have the CD20 surface antigen, is sometimes used to treat resistant patients, but there is no strong clinical evidence to demonstrate its effectiveness in cSLE (Arthritis Rheum. 2009;61:482-7; Clin. J. Am. Soc. Nephrol. 2009;4:579-87).

Abatacept, which targets T cells by binding to B7 peripheral membrane protein, has shown some clinical benefit in a phase IIB randomized clinical trial, and is undergoing clinical testing as an add-on induction therapy with cyclophosphamide (Arthritis Rheum. 2010;62:3077-87). Belimumab, a monoclonal antibody that targets BLyS (B-lymphocyte stimulator)/BAFF (B-cell activating factor), is the first FDA-approved medication for SLE in more than 50 years, based on recent clinical trials that demonstrate increased efficacy and fewer flares of disease, compared with placebo (Arthritis Rheum 2009;61:1168-78; Lancet 2011;377:721-31).

Although recent data regarding belimumab provide some hope, it "may be naive to think that a target-specific therapy exists in this complex, polygenic, heterogeneous disease," commented Dr. Kahn.

In concluding his talk, Dr. Kahn spoke about some barriers to the effective treatment of cSLE. These include physicians’ failure to detect the subtle changes of early disease, a lack of awareness regarding the neuropsychiatric manifestations of the disease, and physicians’ fear of being overly aggressive with treatment. He also warned about overt or covert adolescent noncompliance, and the danger of adolescents’ dropping out of the health care system once they need to transition to adult care.

NEW YORK – Imaging seems to be the sine qua non of determining cardiovascular disease risk in patients with rheumatoid arthritis.

Dr. Jeffrey D. Greenberg noted that, over the last 10-15 years, epidemiologic studies have shown patients with rheumatoid arthritis (RA) have a twofold increase in the risk of myocardial infarction and stroke and an increase in cardiovascular-related deaths. "An important issue we face is how can we risk stratify our patients to predict who will develop cardiovascular disease? Imaging is a promising area that may help us develop biomarkers of risk or better understand pathophysiological mechanisms of RA."

The need for precise tools with which to predict risk has become more urgent with the recently published findings that carotid ultrasound measurement of carotid intima-media thickness has been found to predict coronary events in patients with RA, independent of traditional cardiovascular risk factors and manifestations of RA.

The study, conducted by Dr. Matthew R. Evans and his associates at Brooke Army Medical Center, Fort Sam Houston, Tex., found that there appears to be a dose-dependent relationship between plaque and risk, with a 2.5-fold increase with unilateral plaque and 4.3-fold increase with bilateral carotid plaque, suggesting that atherosclerosis plays a significant role in acute coronary events in patients with RA (Arthritis Rheum. 2011 [doi:10.1002/art.30265]).

In discussing Dr. Evans’s research at his presentation at a rheumatology meeting sponsored by New York University, Dr. Greenberg said that this is the first study to demonstrate the predictive value of measuring carotid intima-media thickness and plaque for cardiovascular events in RA patients.

In the Evans study, carotid ultrasounds were performed on 636 RA patients as part of the prospective ORALE (Outcome of Rheumatoid Arthritis Longitudinal Evaluation) study. These patients were followed for 3,402 person-years and, during that time, 84 patients experienced 121 new or recurrent acute coronary syndrome (ACS) events, such as myocardial infarction, unstable angina, cardiac arrest, or death from ischemic heart disease. The rate of ACS events was 3.5/100 patient-years for this group. If only those without a prior history of ACS were analyzed, this group had 66 ACS events, with an incidence of 2.1 ACS/100 person-years.

Multivariate analysis of baseline factors associated with incident or recurrent acute coronary syndromes revealed that two markers of atherosclerosis were independent predictors of a subsequent coronary event. Having a past cardiovascular event raised the risk almost threefold (hazard ratio, 2.87 [1.75, 4.73]; P = .001) and carotid intima-media thickness also raised the risk significantly (HR, 1.61 [1.24, 2.08]; P = .001). After substituting carotid plaque for intima-media thickness, the investigators found a 2.5-fold increase in risk for unilateral plaque and almost a sixfold increase in risk for bilateral plaque.

The findings confirmed that traditional demographic and cardiovascular risk factors also predict coronary events as would be expected. These include male gender (HR, 1.94 [1.11, 3.39]; P =.05), diabetes (HR, 2.24 [1.44, 3.50]; P = .001), and hypertension (HR=1.56 [1.00, 2.44]; P =.05). Measures of RA severity, such as swollen joint counts (HR, 1.03 [1.01, 1.06]; P = .01) and cumulative prednisone dose of 20 g (HR, 2.12, [1.32, 3.42]; P = .01), also had predictive value.

Dr. Greenberg, who is director of the Arthritis Translational Registry and Biorepository at NYU Hospital for Joint Diseases, is involved in ongoing studies using advanced MRI and PET techniques to visualize and quantify some of key histologic features of plaque that are most likely to rupture, which he calls "vulnerable plaque." These histologic features include macrophage content, plaque neovascularization, a lipid-rich necrotic core, and a thin fibrous cap.

Dr. Greenberg receives consulting fees from Genentech Inc.

NEW YORK – Imaging seems to be the sine qua non of determining cardiovascular disease risk in patients with rheumatoid arthritis.

Dr. Jeffrey D. Greenberg noted that, over the last 10-15 years, epidemiologic studies have shown patients with rheumatoid arthritis (RA) have a twofold increase in the risk of myocardial infarction and stroke and an increase in cardiovascular-related deaths. "An important issue we face is how can we risk stratify our patients to predict who will develop cardiovascular disease? Imaging is a promising area that may help us develop biomarkers of risk or better understand pathophysiological mechanisms of RA."

The need for precise tools with which to predict risk has become more urgent with the recently published findings that carotid ultrasound measurement of carotid intima-media thickness has been found to predict coronary events in patients with RA, independent of traditional cardiovascular risk factors and manifestations of RA.

The study, conducted by Dr. Matthew R. Evans and his associates at Brooke Army Medical Center, Fort Sam Houston, Tex., found that there appears to be a dose-dependent relationship between plaque and risk, with a 2.5-fold increase with unilateral plaque and 4.3-fold increase with bilateral carotid plaque, suggesting that atherosclerosis plays a significant role in acute coronary events in patients with RA (Arthritis Rheum. 2011 [doi:10.1002/art.30265]).

In discussing Dr. Evans’s research at his presentation at a rheumatology meeting sponsored by New York University, Dr. Greenberg said that this is the first study to demonstrate the predictive value of measuring carotid intima-media thickness and plaque for cardiovascular events in RA patients.

In the Evans study, carotid ultrasounds were performed on 636 RA patients as part of the prospective ORALE (Outcome of Rheumatoid Arthritis Longitudinal Evaluation) study. These patients were followed for 3,402 person-years and, during that time, 84 patients experienced 121 new or recurrent acute coronary syndrome (ACS) events, such as myocardial infarction, unstable angina, cardiac arrest, or death from ischemic heart disease. The rate of ACS events was 3.5/100 patient-years for this group. If only those without a prior history of ACS were analyzed, this group had 66 ACS events, with an incidence of 2.1 ACS/100 person-years.

Multivariate analysis of baseline factors associated with incident or recurrent acute coronary syndromes revealed that two markers of atherosclerosis were independent predictors of a subsequent coronary event. Having a past cardiovascular event raised the risk almost threefold (hazard ratio, 2.87 [1.75, 4.73]; P = .001) and carotid intima-media thickness also raised the risk significantly (HR, 1.61 [1.24, 2.08]; P = .001). After substituting carotid plaque for intima-media thickness, the investigators found a 2.5-fold increase in risk for unilateral plaque and almost a sixfold increase in risk for bilateral plaque.

The findings confirmed that traditional demographic and cardiovascular risk factors also predict coronary events as would be expected. These include male gender (HR, 1.94 [1.11, 3.39]; P =.05), diabetes (HR, 2.24 [1.44, 3.50]; P = .001), and hypertension (HR=1.56 [1.00, 2.44]; P =.05). Measures of RA severity, such as swollen joint counts (HR, 1.03 [1.01, 1.06]; P = .01) and cumulative prednisone dose of 20 g (HR, 2.12, [1.32, 3.42]; P = .01), also had predictive value.

Dr. Greenberg, who is director of the Arthritis Translational Registry and Biorepository at NYU Hospital for Joint Diseases, is involved in ongoing studies using advanced MRI and PET techniques to visualize and quantify some of key histologic features of plaque that are most likely to rupture, which he calls "vulnerable plaque." These histologic features include macrophage content, plaque neovascularization, a lipid-rich necrotic core, and a thin fibrous cap.

Dr. Greenberg receives consulting fees from Genentech Inc.

NEW YORK – Imaging seems to be the sine qua non of determining cardiovascular disease risk in patients with rheumatoid arthritis.

Dr. Jeffrey D. Greenberg noted that, over the last 10-15 years, epidemiologic studies have shown patients with rheumatoid arthritis (RA) have a twofold increase in the risk of myocardial infarction and stroke and an increase in cardiovascular-related deaths. "An important issue we face is how can we risk stratify our patients to predict who will develop cardiovascular disease? Imaging is a promising area that may help us develop biomarkers of risk or better understand pathophysiological mechanisms of RA."

The need for precise tools with which to predict risk has become more urgent with the recently published findings that carotid ultrasound measurement of carotid intima-media thickness has been found to predict coronary events in patients with RA, independent of traditional cardiovascular risk factors and manifestations of RA.

The study, conducted by Dr. Matthew R. Evans and his associates at Brooke Army Medical Center, Fort Sam Houston, Tex., found that there appears to be a dose-dependent relationship between plaque and risk, with a 2.5-fold increase with unilateral plaque and 4.3-fold increase with bilateral carotid plaque, suggesting that atherosclerosis plays a significant role in acute coronary events in patients with RA (Arthritis Rheum. 2011 [doi:10.1002/art.30265]).

In discussing Dr. Evans’s research at his presentation at a rheumatology meeting sponsored by New York University, Dr. Greenberg said that this is the first study to demonstrate the predictive value of measuring carotid intima-media thickness and plaque for cardiovascular events in RA patients.

In the Evans study, carotid ultrasounds were performed on 636 RA patients as part of the prospective ORALE (Outcome of Rheumatoid Arthritis Longitudinal Evaluation) study. These patients were followed for 3,402 person-years and, during that time, 84 patients experienced 121 new or recurrent acute coronary syndrome (ACS) events, such as myocardial infarction, unstable angina, cardiac arrest, or death from ischemic heart disease. The rate of ACS events was 3.5/100 patient-years for this group. If only those without a prior history of ACS were analyzed, this group had 66 ACS events, with an incidence of 2.1 ACS/100 person-years.

Multivariate analysis of baseline factors associated with incident or recurrent acute coronary syndromes revealed that two markers of atherosclerosis were independent predictors of a subsequent coronary event. Having a past cardiovascular event raised the risk almost threefold (hazard ratio, 2.87 [1.75, 4.73]; P = .001) and carotid intima-media thickness also raised the risk significantly (HR, 1.61 [1.24, 2.08]; P = .001). After substituting carotid plaque for intima-media thickness, the investigators found a 2.5-fold increase in risk for unilateral plaque and almost a sixfold increase in risk for bilateral plaque.

The findings confirmed that traditional demographic and cardiovascular risk factors also predict coronary events as would be expected. These include male gender (HR, 1.94 [1.11, 3.39]; P =.05), diabetes (HR, 2.24 [1.44, 3.50]; P = .001), and hypertension (HR=1.56 [1.00, 2.44]; P =.05). Measures of RA severity, such as swollen joint counts (HR, 1.03 [1.01, 1.06]; P = .01) and cumulative prednisone dose of 20 g (HR, 2.12, [1.32, 3.42]; P = .01), also had predictive value.

Dr. Greenberg, who is director of the Arthritis Translational Registry and Biorepository at NYU Hospital for Joint Diseases, is involved in ongoing studies using advanced MRI and PET techniques to visualize and quantify some of key histologic features of plaque that are most likely to rupture, which he calls "vulnerable plaque." These histologic features include macrophage content, plaque neovascularization, a lipid-rich necrotic core, and a thin fibrous cap.

Dr. Greenberg receives consulting fees from Genentech Inc.

NEW YORK – Imaging seems to be the sine qua non of determining cardiovascular disease risk in patients with rheumatoid arthritis.

Dr. Jeffrey D. Greenberg noted that, over the last 10-15 years, epidemiologic studies have shown patients with rheumatoid arthritis (RA) have a twofold increase in the risk of myocardial infarction and stroke and an increase in cardiovascular-related deaths. "An important issue we face is how can we risk stratify our patients to predict who will develop cardiovascular disease? Imaging is a promising area that may help us develop biomarkers of risk or better understand pathophysiological mechanisms of RA."

The need for precise tools with which to predict risk has become more urgent with the recently published findings that carotid ultrasound measurement of carotid intima-media thickness has been found to predict coronary events in patients with RA, independent of traditional cardiovascular risk factors and manifestations of RA.

The study, conducted by Dr. Matthew R. Evans and his associates at Brooke Army Medical Center, Fort Sam Houston, Tex., found that there appears to be a dose-dependent relationship between plaque and risk, with a 2.5-fold increase with unilateral plaque and 4.3-fold increase with bilateral carotid plaque, suggesting that atherosclerosis plays a significant role in acute coronary events in patients with RA (Arthritis Rheum. 2011 [doi:10.1002/art.30265]).

In discussing Dr. Evans’s research at his presentation at a rheumatology meeting sponsored by New York University, Dr. Greenberg said that this is the first study to demonstrate the predictive value of measuring carotid intima-media thickness and plaque for cardiovascular events in RA patients.

In the Evans study, carotid ultrasounds were performed on 636 RA patients as part of the prospective ORALE (Outcome of Rheumatoid Arthritis Longitudinal Evaluation) study. These patients were followed for 3,402 person-years and, during that time, 84 patients experienced 121 new or recurrent acute coronary syndrome (ACS) events, such as myocardial infarction, unstable angina, cardiac arrest, or death from ischemic heart disease. The rate of ACS events was 3.5/100 patient-years for this group. If only those without a prior history of ACS were analyzed, this group had 66 ACS events, with an incidence of 2.1 ACS/100 person-years.

Multivariate analysis of baseline factors associated with incident or recurrent acute coronary syndromes revealed that two markers of atherosclerosis were independent predictors of a subsequent coronary event. Having a past cardiovascular event raised the risk almost threefold (hazard ratio, 2.87 [1.75, 4.73]; P = .001) and carotid intima-media thickness also raised the risk significantly (HR, 1.61 [1.24, 2.08]; P = .001). After substituting carotid plaque for intima-media thickness, the investigators found a 2.5-fold increase in risk for unilateral plaque and almost a sixfold increase in risk for bilateral plaque.

The findings confirmed that traditional demographic and cardiovascular risk factors also predict coronary events as would be expected. These include male gender (HR, 1.94 [1.11, 3.39]; P =.05), diabetes (HR, 2.24 [1.44, 3.50]; P = .001), and hypertension (HR=1.56 [1.00, 2.44]; P =.05). Measures of RA severity, such as swollen joint counts (HR, 1.03 [1.01, 1.06]; P = .01) and cumulative prednisone dose of 20 g (HR, 2.12, [1.32, 3.42]; P = .01), also had predictive value.

Dr. Greenberg, who is director of the Arthritis Translational Registry and Biorepository at NYU Hospital for Joint Diseases, is involved in ongoing studies using advanced MRI and PET techniques to visualize and quantify some of key histologic features of plaque that are most likely to rupture, which he calls "vulnerable plaque." These histologic features include macrophage content, plaque neovascularization, a lipid-rich necrotic core, and a thin fibrous cap.

Dr. Greenberg receives consulting fees from Genentech Inc.

NEW YORK – Imaging seems to be the sine qua non of determining cardiovascular disease risk in patients with rheumatoid arthritis.

Dr. Jeffrey D. Greenberg noted that, over the last 10-15 years, epidemiologic studies have shown patients with rheumatoid arthritis (RA) have a twofold increase in the risk of myocardial infarction and stroke and an increase in cardiovascular-related deaths. "An important issue we face is how can we risk stratify our patients to predict who will develop cardiovascular disease? Imaging is a promising area that may help us develop biomarkers of risk or better understand pathophysiological mechanisms of RA."

The need for precise tools with which to predict risk has become more urgent with the recently published findings that carotid ultrasound measurement of carotid intima-media thickness has been found to predict coronary events in patients with RA, independent of traditional cardiovascular risk factors and manifestations of RA.

The study, conducted by Dr. Matthew R. Evans and his associates at Brooke Army Medical Center, Fort Sam Houston, Tex., found that there appears to be a dose-dependent relationship between plaque and risk, with a 2.5-fold increase with unilateral plaque and 4.3-fold increase with bilateral carotid plaque, suggesting that atherosclerosis plays a significant role in acute coronary events in patients with RA (Arthritis Rheum. 2011 [doi:10.1002/art.30265]).

In discussing Dr. Evans’s research at his presentation at a rheumatology meeting sponsored by New York University, Dr. Greenberg said that this is the first study to demonstrate the predictive value of measuring carotid intima-media thickness and plaque for cardiovascular events in RA patients.

In the Evans study, carotid ultrasounds were performed on 636 RA patients as part of the prospective ORALE (Outcome of Rheumatoid Arthritis Longitudinal Evaluation) study. These patients were followed for 3,402 person-years and, during that time, 84 patients experienced 121 new or recurrent acute coronary syndrome (ACS) events, such as myocardial infarction, unstable angina, cardiac arrest, or death from ischemic heart disease. The rate of ACS events was 3.5/100 patient-years for this group. If only those without a prior history of ACS were analyzed, this group had 66 ACS events, with an incidence of 2.1 ACS/100 person-years.

Multivariate analysis of baseline factors associated with incident or recurrent acute coronary syndromes revealed that two markers of atherosclerosis were independent predictors of a subsequent coronary event. Having a past cardiovascular event raised the risk almost threefold (hazard ratio, 2.87 [1.75, 4.73]; P = .001) and carotid intima-media thickness also raised the risk significantly (HR, 1.61 [1.24, 2.08]; P = .001). After substituting carotid plaque for intima-media thickness, the investigators found a 2.5-fold increase in risk for unilateral plaque and almost a sixfold increase in risk for bilateral plaque.

The findings confirmed that traditional demographic and cardiovascular risk factors also predict coronary events as would be expected. These include male gender (HR, 1.94 [1.11, 3.39]; P =.05), diabetes (HR, 2.24 [1.44, 3.50]; P = .001), and hypertension (HR=1.56 [1.00, 2.44]; P =.05). Measures of RA severity, such as swollen joint counts (HR, 1.03 [1.01, 1.06]; P = .01) and cumulative prednisone dose of 20 g (HR, 2.12, [1.32, 3.42]; P = .01), also had predictive value.

Dr. Greenberg, who is director of the Arthritis Translational Registry and Biorepository at NYU Hospital for Joint Diseases, is involved in ongoing studies using advanced MRI and PET techniques to visualize and quantify some of key histologic features of plaque that are most likely to rupture, which he calls "vulnerable plaque." These histologic features include macrophage content, plaque neovascularization, a lipid-rich necrotic core, and a thin fibrous cap.

Dr. Greenberg receives consulting fees from Genentech Inc.

NEW YORK – Imaging seems to be the sine qua non of determining cardiovascular disease risk in patients with rheumatoid arthritis.

Dr. Jeffrey D. Greenberg noted that, over the last 10-15 years, epidemiologic studies have shown patients with rheumatoid arthritis (RA) have a twofold increase in the risk of myocardial infarction and stroke and an increase in cardiovascular-related deaths. "An important issue we face is how can we risk stratify our patients to predict who will develop cardiovascular disease? Imaging is a promising area that may help us develop biomarkers of risk or better understand pathophysiological mechanisms of RA."

The need for precise tools with which to predict risk has become more urgent with the recently published findings that carotid ultrasound measurement of carotid intima-media thickness has been found to predict coronary events in patients with RA, independent of traditional cardiovascular risk factors and manifestations of RA.

The study, conducted by Dr. Matthew R. Evans and his associates at Brooke Army Medical Center, Fort Sam Houston, Tex., found that there appears to be a dose-dependent relationship between plaque and risk, with a 2.5-fold increase with unilateral plaque and 4.3-fold increase with bilateral carotid plaque, suggesting that atherosclerosis plays a significant role in acute coronary events in patients with RA (Arthritis Rheum. 2011 [doi:10.1002/art.30265]).

In discussing Dr. Evans’s research at his presentation at a rheumatology meeting sponsored by New York University, Dr. Greenberg said that this is the first study to demonstrate the predictive value of measuring carotid intima-media thickness and plaque for cardiovascular events in RA patients.

In the Evans study, carotid ultrasounds were performed on 636 RA patients as part of the prospective ORALE (Outcome of Rheumatoid Arthritis Longitudinal Evaluation) study. These patients were followed for 3,402 person-years and, during that time, 84 patients experienced 121 new or recurrent acute coronary syndrome (ACS) events, such as myocardial infarction, unstable angina, cardiac arrest, or death from ischemic heart disease. The rate of ACS events was 3.5/100 patient-years for this group. If only those without a prior history of ACS were analyzed, this group had 66 ACS events, with an incidence of 2.1 ACS/100 person-years.

Multivariate analysis of baseline factors associated with incident or recurrent acute coronary syndromes revealed that two markers of atherosclerosis were independent predictors of a subsequent coronary event. Having a past cardiovascular event raised the risk almost threefold (hazard ratio, 2.87 [1.75, 4.73]; P = .001) and carotid intima-media thickness also raised the risk significantly (HR, 1.61 [1.24, 2.08]; P = .001). After substituting carotid plaque for intima-media thickness, the investigators found a 2.5-fold increase in risk for unilateral plaque and almost a sixfold increase in risk for bilateral plaque.

The findings confirmed that traditional demographic and cardiovascular risk factors also predict coronary events as would be expected. These include male gender (HR, 1.94 [1.11, 3.39]; P =.05), diabetes (HR, 2.24 [1.44, 3.50]; P = .001), and hypertension (HR=1.56 [1.00, 2.44]; P =.05). Measures of RA severity, such as swollen joint counts (HR, 1.03 [1.01, 1.06]; P = .01) and cumulative prednisone dose of 20 g (HR, 2.12, [1.32, 3.42]; P = .01), also had predictive value.

Dr. Greenberg, who is director of the Arthritis Translational Registry and Biorepository at NYU Hospital for Joint Diseases, is involved in ongoing studies using advanced MRI and PET techniques to visualize and quantify some of key histologic features of plaque that are most likely to rupture, which he calls "vulnerable plaque." These histologic features include macrophage content, plaque neovascularization, a lipid-rich necrotic core, and a thin fibrous cap.

Dr. Greenberg receives consulting fees from Genentech Inc.

NEW YORK - Early and aggressive therapy is warranted in the management of systemic juvenile idiopathic arthritis, which accounts for 10% of arthritis cases in children and which can be devastating, according to Dr. Randy Q. Cron, who spoke about the condition at a meeting sponsored by New York University.

Dr. Cron, director of pediatric rheumatology at the University of Alabama at Birmingham, is a coauthor of the first ever 2011 ACR Recommendations for the Treatment of Juvenile Idiopathic Arthritis (JIA) that were published on April 1 (Arthritis Care Res. 2011;63:465-82) and which include guidelines for the treatment of systemic JIA. According to the publication, "the JIA category of systemic arthritis proved to be especially challenging to evaluate. Attempts to exhaustively depict the myriad possible clinical presentations of systemic arthritis were impractical." The result was that systemic JIA guidelines include two treatment algorithms, one for the active systemic features (for example, fever) and one for the active arthritis. Patients who have both concurrent active systemic features and active arthritis can be treated according to suggestions from both algorithms.

For treating the systemic features of systemic JIA, three first-line options are available: nonsteroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, and anakinra (Kineret). It should be noted that interleukin-6 inhibitors and interleukin-1 inhibitors other than anakinra were not considered when developing the recommendations, since they were not widely available commercially at the time. TNF-alpha inhibitors were not considered because of their relatively poor effectiveness for the systemic manifestations.

While NSAID monotherapy might also help some children, the recommendations say that its use is inappropriate for patients with active fever and physician global assessment of overall disease activity (MD global) score equal to 7 of 10. It should also not be used for more than 1 month in patients with active fever.

Systemic glucocorticoids were recommended as initial therapy for patients with active fever and an MD global score of 7. Systemic glucocorticoids may also be added after 2 weeks of NSAID monotherapy in patients with active fever.

Anakinra was recommended for all patients with active fever who had poor prognostic features, no matter what they were currently taking. Anakinra was also recommended for patients who have or develop fever while on systemic glucocorticoids. Anakinra is a human recombinant interleukin-1 (IL-1) inhibitor that was approved to treat adults with moderate to severe arthritis who have not had an adequate response to conservative disease-modifying anti-rheumatic drug therapy. It is not currently approved for children with JIA.

Medications such as calcineurin inhibitors, intravenous immunoglobulin, methotrexate, and thalidomide were not formally recommended but might have roles in the treatment of systemic JIA.

For the treatment of the arthritic features of systemic JIA, initiation of NSAID monotherapy (with or without glucocorticoid joint injections) was recommended for all patients, regardless of the level of disease activity or presence of poor prognostic features. It was assumed that most patients with newly diagnosed systemic arthritis would have been started with NSAIDs. The next step would be methotrexate for all patients with active arthritis who were taking NSAID monotherapy for less than 1 month. If escalation of therapy was needed, the next choices would be either addition of a TNF-alpha inhibitor or anakinra. The recommendations indicate that initiation of anakinra should take place early rather than later in the disease course. For patients with moderate or high disease activity, regardless of features of poor prognosis, it was suggested that patients be switched from anakinra to a TNF-alpha inhibitor.

The last option is abatacept, a costimulatory blocker, for those who fail to be controlled by methotrexate or 4 months of a TNF-alpha inhibitor, and who have moderate to high disease activity.

During his presentation, Dr. Cron provided his perspective on the new systemic JIA recommendations. Most pediatric rheumatologists would probably begin with systemic corticosteroids at the onset of treatment, because that is what they are most familiar with and they are effective, he said.

He was pleased with the inclusion of anakinra in the guidelines. "With these guidelines, physicians can treat children with JIA from the start with anakinra." Inclusion of anakinra in the guidelines as a first option should help tremendously in helping patients receive reimbursement from insurance companies, he noted.

Dr. Cron cited evidence showing the effectiveness of anakinra as a first-line disease-modifying therapy in 46 patients with JIA, preventing refractory arthritis in almost 90% of patients (Arthritis Rheum. 2011;63:545-55). In this series of case studies, use of anakinra reduced elevated sedimentation rates and ferritin levels, decreased the number of active joint counts, and significantly lowered the dose of concomitant steroid therapy. "Kids can get remarkably better within days or months with anakinra. It can be a wonder drug for very sick children with systemic JIA," he said.

Although it was not discussed in the Recommendations, in his talk Dr. Cron said that anakinra is "revolutionizing" the treatment of macrophage activation syndrome (MAS) in systemic JIA (Rheumatology 2011;50:417-9) Dr. Cron reported that he has used anakinra as initial therapy to treat two children with MAS, and he found dramatic reductions in ferritin levels and liver enzymes within 2 days of initiation.

Systemic JIA is a relatively rare disease, with a prevalence of about 1 in 10,000. It has multiple systemic manifestations, including a high fever (which follows a unique pattern: typically once-daily, late-afternoon spikes in 30% of patients at presentation), rash, hepatosplenomegaly, lymphadenopathy, pericarditis, pleural effusion, pulmonary vasculitis, and even CNS stroke or seizure. Stroke or seizure might be related to MAS, a widespread coagulopathy that occurs in about 50% of patients and can be fatal.

Another common finding is asymmetry of the jaw. According to Dr. Cron, up to 80% of children with all forms of arthritis, including systemic JIA, can have arthritis of the temporomandibular joint (TMJ). This is often a subtle finding that can be overlooked until significant erosion has occurred. However, early TMJ arthritis can be detected with magnetic resonance screening.

Dr. Cron is a consultant for Genentech.

NEW YORK - Early and aggressive therapy is warranted in the management of systemic juvenile idiopathic arthritis, which accounts for 10% of arthritis cases in children and which can be devastating, according to Dr. Randy Q. Cron, who spoke about the condition at a meeting sponsored by New York University.

Dr. Cron, director of pediatric rheumatology at the University of Alabama at Birmingham, is a coauthor of the first ever 2011 ACR Recommendations for the Treatment of Juvenile Idiopathic Arthritis (JIA) that were published on April 1 (Arthritis Care Res. 2011;63:465-82) and which include guidelines for the treatment of systemic JIA. According to the publication, "the JIA category of systemic arthritis proved to be especially challenging to evaluate. Attempts to exhaustively depict the myriad possible clinical presentations of systemic arthritis were impractical." The result was that systemic JIA guidelines include two treatment algorithms, one for the active systemic features (for example, fever) and one for the active arthritis. Patients who have both concurrent active systemic features and active arthritis can be treated according to suggestions from both algorithms.

For treating the systemic features of systemic JIA, three first-line options are available: nonsteroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, and anakinra (Kineret). It should be noted that interleukin-6 inhibitors and interleukin-1 inhibitors other than anakinra were not considered when developing the recommendations, since they were not widely available commercially at the time. TNF-alpha inhibitors were not considered because of their relatively poor effectiveness for the systemic manifestations.

While NSAID monotherapy might also help some children, the recommendations say that its use is inappropriate for patients with active fever and physician global assessment of overall disease activity (MD global) score equal to 7 of 10. It should also not be used for more than 1 month in patients with active fever.

Systemic glucocorticoids were recommended as initial therapy for patients with active fever and an MD global score of 7. Systemic glucocorticoids may also be added after 2 weeks of NSAID monotherapy in patients with active fever.

Anakinra was recommended for all patients with active fever who had poor prognostic features, no matter what they were currently taking. Anakinra was also recommended for patients who have or develop fever while on systemic glucocorticoids. Anakinra is a human recombinant interleukin-1 (IL-1) inhibitor that was approved to treat adults with moderate to severe arthritis who have not had an adequate response to conservative disease-modifying anti-rheumatic drug therapy. It is not currently approved for children with JIA.

Medications such as calcineurin inhibitors, intravenous immunoglobulin, methotrexate, and thalidomide were not formally recommended but might have roles in the treatment of systemic JIA.

For the treatment of the arthritic features of systemic JIA, initiation of NSAID monotherapy (with or without glucocorticoid joint injections) was recommended for all patients, regardless of the level of disease activity or presence of poor prognostic features. It was assumed that most patients with newly diagnosed systemic arthritis would have been started with NSAIDs. The next step would be methotrexate for all patients with active arthritis who were taking NSAID monotherapy for less than 1 month. If escalation of therapy was needed, the next choices would be either addition of a TNF-alpha inhibitor or anakinra. The recommendations indicate that initiation of anakinra should take place early rather than later in the disease course. For patients with moderate or high disease activity, regardless of features of poor prognosis, it was suggested that patients be switched from anakinra to a TNF-alpha inhibitor.

The last option is abatacept, a costimulatory blocker, for those who fail to be controlled by methotrexate or 4 months of a TNF-alpha inhibitor, and who have moderate to high disease activity.

During his presentation, Dr. Cron provided his perspective on the new systemic JIA recommendations. Most pediatric rheumatologists would probably begin with systemic corticosteroids at the onset of treatment, because that is what they are most familiar with and they are effective, he said.

He was pleased with the inclusion of anakinra in the guidelines. "With these guidelines, physicians can treat children with JIA from the start with anakinra." Inclusion of anakinra in the guidelines as a first option should help tremendously in helping patients receive reimbursement from insurance companies, he noted.

Dr. Cron cited evidence showing the effectiveness of anakinra as a first-line disease-modifying therapy in 46 patients with JIA, preventing refractory arthritis in almost 90% of patients (Arthritis Rheum. 2011;63:545-55). In this series of case studies, use of anakinra reduced elevated sedimentation rates and ferritin levels, decreased the number of active joint counts, and significantly lowered the dose of concomitant steroid therapy. "Kids can get remarkably better within days or months with anakinra. It can be a wonder drug for very sick children with systemic JIA," he said.

Although it was not discussed in the Recommendations, in his talk Dr. Cron said that anakinra is "revolutionizing" the treatment of macrophage activation syndrome (MAS) in systemic JIA (Rheumatology 2011;50:417-9) Dr. Cron reported that he has used anakinra as initial therapy to treat two children with MAS, and he found dramatic reductions in ferritin levels and liver enzymes within 2 days of initiation.

Systemic JIA is a relatively rare disease, with a prevalence of about 1 in 10,000. It has multiple systemic manifestations, including a high fever (which follows a unique pattern: typically once-daily, late-afternoon spikes in 30% of patients at presentation), rash, hepatosplenomegaly, lymphadenopathy, pericarditis, pleural effusion, pulmonary vasculitis, and even CNS stroke or seizure. Stroke or seizure might be related to MAS, a widespread coagulopathy that occurs in about 50% of patients and can be fatal.

Another common finding is asymmetry of the jaw. According to Dr. Cron, up to 80% of children with all forms of arthritis, including systemic JIA, can have arthritis of the temporomandibular joint (TMJ). This is often a subtle finding that can be overlooked until significant erosion has occurred. However, early TMJ arthritis can be detected with magnetic resonance screening.

Dr. Cron is a consultant for Genentech.

NEW YORK - Early and aggressive therapy is warranted in the management of systemic juvenile idiopathic arthritis, which accounts for 10% of arthritis cases in children and which can be devastating, according to Dr. Randy Q. Cron, who spoke about the condition at a meeting sponsored by New York University.

Dr. Cron, director of pediatric rheumatology at the University of Alabama at Birmingham, is a coauthor of the first ever 2011 ACR Recommendations for the Treatment of Juvenile Idiopathic Arthritis (JIA) that were published on April 1 (Arthritis Care Res. 2011;63:465-82) and which include guidelines for the treatment of systemic JIA. According to the publication, "the JIA category of systemic arthritis proved to be especially challenging to evaluate. Attempts to exhaustively depict the myriad possible clinical presentations of systemic arthritis were impractical." The result was that systemic JIA guidelines include two treatment algorithms, one for the active systemic features (for example, fever) and one for the active arthritis. Patients who have both concurrent active systemic features and active arthritis can be treated according to suggestions from both algorithms.

For treating the systemic features of systemic JIA, three first-line options are available: nonsteroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, and anakinra (Kineret). It should be noted that interleukin-6 inhibitors and interleukin-1 inhibitors other than anakinra were not considered when developing the recommendations, since they were not widely available commercially at the time. TNF-alpha inhibitors were not considered because of their relatively poor effectiveness for the systemic manifestations.

While NSAID monotherapy might also help some children, the recommendations say that its use is inappropriate for patients with active fever and physician global assessment of overall disease activity (MD global) score equal to 7 of 10. It should also not be used for more than 1 month in patients with active fever.

Systemic glucocorticoids were recommended as initial therapy for patients with active fever and an MD global score of 7. Systemic glucocorticoids may also be added after 2 weeks of NSAID monotherapy in patients with active fever.

Anakinra was recommended for all patients with active fever who had poor prognostic features, no matter what they were currently taking. Anakinra was also recommended for patients who have or develop fever while on systemic glucocorticoids. Anakinra is a human recombinant interleukin-1 (IL-1) inhibitor that was approved to treat adults with moderate to severe arthritis who have not had an adequate response to conservative disease-modifying anti-rheumatic drug therapy. It is not currently approved for children with JIA.

Medications such as calcineurin inhibitors, intravenous immunoglobulin, methotrexate, and thalidomide were not formally recommended but might have roles in the treatment of systemic JIA.

For the treatment of the arthritic features of systemic JIA, initiation of NSAID monotherapy (with or without glucocorticoid joint injections) was recommended for all patients, regardless of the level of disease activity or presence of poor prognostic features. It was assumed that most patients with newly diagnosed systemic arthritis would have been started with NSAIDs. The next step would be methotrexate for all patients with active arthritis who were taking NSAID monotherapy for less than 1 month. If escalation of therapy was needed, the next choices would be either addition of a TNF-alpha inhibitor or anakinra. The recommendations indicate that initiation of anakinra should take place early rather than later in the disease course. For patients with moderate or high disease activity, regardless of features of poor prognosis, it was suggested that patients be switched from anakinra to a TNF-alpha inhibitor.

The last option is abatacept, a costimulatory blocker, for those who fail to be controlled by methotrexate or 4 months of a TNF-alpha inhibitor, and who have moderate to high disease activity.

During his presentation, Dr. Cron provided his perspective on the new systemic JIA recommendations. Most pediatric rheumatologists would probably begin with systemic corticosteroids at the onset of treatment, because that is what they are most familiar with and they are effective, he said.

He was pleased with the inclusion of anakinra in the guidelines. "With these guidelines, physicians can treat children with JIA from the start with anakinra." Inclusion of anakinra in the guidelines as a first option should help tremendously in helping patients receive reimbursement from insurance companies, he noted.

Dr. Cron cited evidence showing the effectiveness of anakinra as a first-line disease-modifying therapy in 46 patients with JIA, preventing refractory arthritis in almost 90% of patients (Arthritis Rheum. 2011;63:545-55). In this series of case studies, use of anakinra reduced elevated sedimentation rates and ferritin levels, decreased the number of active joint counts, and significantly lowered the dose of concomitant steroid therapy. "Kids can get remarkably better within days or months with anakinra. It can be a wonder drug for very sick children with systemic JIA," he said.

Although it was not discussed in the Recommendations, in his talk Dr. Cron said that anakinra is "revolutionizing" the treatment of macrophage activation syndrome (MAS) in systemic JIA (Rheumatology 2011;50:417-9) Dr. Cron reported that he has used anakinra as initial therapy to treat two children with MAS, and he found dramatic reductions in ferritin levels and liver enzymes within 2 days of initiation.

Systemic JIA is a relatively rare disease, with a prevalence of about 1 in 10,000. It has multiple systemic manifestations, including a high fever (which follows a unique pattern: typically once-daily, late-afternoon spikes in 30% of patients at presentation), rash, hepatosplenomegaly, lymphadenopathy, pericarditis, pleural effusion, pulmonary vasculitis, and even CNS stroke or seizure. Stroke or seizure might be related to MAS, a widespread coagulopathy that occurs in about 50% of patients and can be fatal.

Another common finding is asymmetry of the jaw. According to Dr. Cron, up to 80% of children with all forms of arthritis, including systemic JIA, can have arthritis of the temporomandibular joint (TMJ). This is often a subtle finding that can be overlooked until significant erosion has occurred. However, early TMJ arthritis can be detected with magnetic resonance screening.

Dr. Cron is a consultant for Genentech.

NEW YORK - Early and aggressive therapy is warranted in the management of systemic juvenile idiopathic arthritis, which accounts for 10% of arthritis cases in children and which can be devastating, according to Dr. Randy Q. Cron, who spoke about the condition at a meeting sponsored by New York University.

Dr. Cron, director of pediatric rheumatology at the University of Alabama at Birmingham, is a coauthor of the first ever 2011 ACR Recommendations for the Treatment of Juvenile Idiopathic Arthritis (JIA) that were published on April 1 (Arthritis Care Res. 2011;63:465-82) and which include guidelines for the treatment of systemic JIA. According to the publication, "the JIA category of systemic arthritis proved to be especially challenging to evaluate. Attempts to exhaustively depict the myriad possible clinical presentations of systemic arthritis were impractical." The result was that systemic JIA guidelines include two treatment algorithms, one for the active systemic features (for example, fever) and one for the active arthritis. Patients who have both concurrent active systemic features and active arthritis can be treated according to suggestions from both algorithms.

For treating the systemic features of systemic JIA, three first-line options are available: nonsteroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, and anakinra (Kineret). It should be noted that interleukin-6 inhibitors and interleukin-1 inhibitors other than anakinra were not considered when developing the recommendations, since they were not widely available commercially at the time. TNF-alpha inhibitors were not considered because of their relatively poor effectiveness for the systemic manifestations.

While NSAID monotherapy might also help some children, the recommendations say that its use is inappropriate for patients with active fever and physician global assessment of overall disease activity (MD global) score equal to 7 of 10. It should also not be used for more than 1 month in patients with active fever.

Systemic glucocorticoids were recommended as initial therapy for patients with active fever and an MD global score of 7. Systemic glucocorticoids may also be added after 2 weeks of NSAID monotherapy in patients with active fever.

Anakinra was recommended for all patients with active fever who had poor prognostic features, no matter what they were currently taking. Anakinra was also recommended for patients who have or develop fever while on systemic glucocorticoids. Anakinra is a human recombinant interleukin-1 (IL-1) inhibitor that was approved to treat adults with moderate to severe arthritis who have not had an adequate response to conservative disease-modifying anti-rheumatic drug therapy. It is not currently approved for children with JIA.

Medications such as calcineurin inhibitors, intravenous immunoglobulin, methotrexate, and thalidomide were not formally recommended but might have roles in the treatment of systemic JIA.

For the treatment of the arthritic features of systemic JIA, initiation of NSAID monotherapy (with or without glucocorticoid joint injections) was recommended for all patients, regardless of the level of disease activity or presence of poor prognostic features. It was assumed that most patients with newly diagnosed systemic arthritis would have been started with NSAIDs. The next step would be methotrexate for all patients with active arthritis who were taking NSAID monotherapy for less than 1 month. If escalation of therapy was needed, the next choices would be either addition of a TNF-alpha inhibitor or anakinra. The recommendations indicate that initiation of anakinra should take place early rather than later in the disease course. For patients with moderate or high disease activity, regardless of features of poor prognosis, it was suggested that patients be switched from anakinra to a TNF-alpha inhibitor.

The last option is abatacept, a costimulatory blocker, for those who fail to be controlled by methotrexate or 4 months of a TNF-alpha inhibitor, and who have moderate to high disease activity.

During his presentation, Dr. Cron provided his perspective on the new systemic JIA recommendations. Most pediatric rheumatologists would probably begin with systemic corticosteroids at the onset of treatment, because that is what they are most familiar with and they are effective, he said.

He was pleased with the inclusion of anakinra in the guidelines. "With these guidelines, physicians can treat children with JIA from the start with anakinra." Inclusion of anakinra in the guidelines as a first option should help tremendously in helping patients receive reimbursement from insurance companies, he noted.

Dr. Cron cited evidence showing the effectiveness of anakinra as a first-line disease-modifying therapy in 46 patients with JIA, preventing refractory arthritis in almost 90% of patients (Arthritis Rheum. 2011;63:545-55). In this series of case studies, use of anakinra reduced elevated sedimentation rates and ferritin levels, decreased the number of active joint counts, and significantly lowered the dose of concomitant steroid therapy. "Kids can get remarkably better within days or months with anakinra. It can be a wonder drug for very sick children with systemic JIA," he said.

Although it was not discussed in the Recommendations, in his talk Dr. Cron said that anakinra is "revolutionizing" the treatment of macrophage activation syndrome (MAS) in systemic JIA (Rheumatology 2011;50:417-9) Dr. Cron reported that he has used anakinra as initial therapy to treat two children with MAS, and he found dramatic reductions in ferritin levels and liver enzymes within 2 days of initiation.

Systemic JIA is a relatively rare disease, with a prevalence of about 1 in 10,000. It has multiple systemic manifestations, including a high fever (which follows a unique pattern: typically once-daily, late-afternoon spikes in 30% of patients at presentation), rash, hepatosplenomegaly, lymphadenopathy, pericarditis, pleural effusion, pulmonary vasculitis, and even CNS stroke or seizure. Stroke or seizure might be related to MAS, a widespread coagulopathy that occurs in about 50% of patients and can be fatal.

Another common finding is asymmetry of the jaw. According to Dr. Cron, up to 80% of children with all forms of arthritis, including systemic JIA, can have arthritis of the temporomandibular joint (TMJ). This is often a subtle finding that can be overlooked until significant erosion has occurred. However, early TMJ arthritis can be detected with magnetic resonance screening.

Dr. Cron is a consultant for Genentech.

NEW YORK - Early and aggressive therapy is warranted in the management of systemic juvenile idiopathic arthritis, which accounts for 10% of arthritis cases in children and which can be devastating, according to Dr. Randy Q. Cron, who spoke about the condition at a meeting sponsored by New York University.

Dr. Cron, director of pediatric rheumatology at the University of Alabama at Birmingham, is a coauthor of the first ever 2011 ACR Recommendations for the Treatment of Juvenile Idiopathic Arthritis (JIA) that were published on April 1 (Arthritis Care Res. 2011;63:465-82) and which include guidelines for the treatment of systemic JIA. According to the publication, "the JIA category of systemic arthritis proved to be especially challenging to evaluate. Attempts to exhaustively depict the myriad possible clinical presentations of systemic arthritis were impractical." The result was that systemic JIA guidelines include two treatment algorithms, one for the active systemic features (for example, fever) and one for the active arthritis. Patients who have both concurrent active systemic features and active arthritis can be treated according to suggestions from both algorithms.

For treating the systemic features of systemic JIA, three first-line options are available: nonsteroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, and anakinra (Kineret). It should be noted that interleukin-6 inhibitors and interleukin-1 inhibitors other than anakinra were not considered when developing the recommendations, since they were not widely available commercially at the time. TNF-alpha inhibitors were not considered because of their relatively poor effectiveness for the systemic manifestations.

While NSAID monotherapy might also help some children, the recommendations say that its use is inappropriate for patients with active fever and physician global assessment of overall disease activity (MD global) score equal to 7 of 10. It should also not be used for more than 1 month in patients with active fever.

Systemic glucocorticoids were recommended as initial therapy for patients with active fever and an MD global score of 7. Systemic glucocorticoids may also be added after 2 weeks of NSAID monotherapy in patients with active fever.

Anakinra was recommended for all patients with active fever who had poor prognostic features, no matter what they were currently taking. Anakinra was also recommended for patients who have or develop fever while on systemic glucocorticoids. Anakinra is a human recombinant interleukin-1 (IL-1) inhibitor that was approved to treat adults with moderate to severe arthritis who have not had an adequate response to conservative disease-modifying anti-rheumatic drug therapy. It is not currently approved for children with JIA.

Medications such as calcineurin inhibitors, intravenous immunoglobulin, methotrexate, and thalidomide were not formally recommended but might have roles in the treatment of systemic JIA.

For the treatment of the arthritic features of systemic JIA, initiation of NSAID monotherapy (with or without glucocorticoid joint injections) was recommended for all patients, regardless of the level of disease activity or presence of poor prognostic features. It was assumed that most patients with newly diagnosed systemic arthritis would have been started with NSAIDs. The next step would be methotrexate for all patients with active arthritis who were taking NSAID monotherapy for less than 1 month. If escalation of therapy was needed, the next choices would be either addition of a TNF-alpha inhibitor or anakinra. The recommendations indicate that initiation of anakinra should take place early rather than later in the disease course. For patients with moderate or high disease activity, regardless of features of poor prognosis, it was suggested that patients be switched from anakinra to a TNF-alpha inhibitor.

The last option is abatacept, a costimulatory blocker, for those who fail to be controlled by methotrexate or 4 months of a TNF-alpha inhibitor, and who have moderate to high disease activity.

During his presentation, Dr. Cron provided his perspective on the new systemic JIA recommendations. Most pediatric rheumatologists would probably begin with systemic corticosteroids at the onset of treatment, because that is what they are most familiar with and they are effective, he said.

He was pleased with the inclusion of anakinra in the guidelines. "With these guidelines, physicians can treat children with JIA from the start with anakinra." Inclusion of anakinra in the guidelines as a first option should help tremendously in helping patients receive reimbursement from insurance companies, he noted.

Dr. Cron cited evidence showing the effectiveness of anakinra as a first-line disease-modifying therapy in 46 patients with JIA, preventing refractory arthritis in almost 90% of patients (Arthritis Rheum. 2011;63:545-55). In this series of case studies, use of anakinra reduced elevated sedimentation rates and ferritin levels, decreased the number of active joint counts, and significantly lowered the dose of concomitant steroid therapy. "Kids can get remarkably better within days or months with anakinra. It can be a wonder drug for very sick children with systemic JIA," he said.

Although it was not discussed in the Recommendations, in his talk Dr. Cron said that anakinra is "revolutionizing" the treatment of macrophage activation syndrome (MAS) in systemic JIA (Rheumatology 2011;50:417-9) Dr. Cron reported that he has used anakinra as initial therapy to treat two children with MAS, and he found dramatic reductions in ferritin levels and liver enzymes within 2 days of initiation.

Systemic JIA is a relatively rare disease, with a prevalence of about 1 in 10,000. It has multiple systemic manifestations, including a high fever (which follows a unique pattern: typically once-daily, late-afternoon spikes in 30% of patients at presentation), rash, hepatosplenomegaly, lymphadenopathy, pericarditis, pleural effusion, pulmonary vasculitis, and even CNS stroke or seizure. Stroke or seizure might be related to MAS, a widespread coagulopathy that occurs in about 50% of patients and can be fatal.

Another common finding is asymmetry of the jaw. According to Dr. Cron, up to 80% of children with all forms of arthritis, including systemic JIA, can have arthritis of the temporomandibular joint (TMJ). This is often a subtle finding that can be overlooked until significant erosion has occurred. However, early TMJ arthritis can be detected with magnetic resonance screening.

Dr. Cron is a consultant for Genentech.

NEW YORK - Early and aggressive therapy is warranted in the management of systemic juvenile idiopathic arthritis, which accounts for 10% of arthritis cases in children and which can be devastating, according to Dr. Randy Q. Cron, who spoke about the condition at a meeting sponsored by New York University.

Dr. Cron, director of pediatric rheumatology at the University of Alabama at Birmingham, is a coauthor of the first ever 2011 ACR Recommendations for the Treatment of Juvenile Idiopathic Arthritis (JIA) that were published on April 1 (Arthritis Care Res. 2011;63:465-82) and which include guidelines for the treatment of systemic JIA. According to the publication, "the JIA category of systemic arthritis proved to be especially challenging to evaluate. Attempts to exhaustively depict the myriad possible clinical presentations of systemic arthritis were impractical." The result was that systemic JIA guidelines include two treatment algorithms, one for the active systemic features (for example, fever) and one for the active arthritis. Patients who have both concurrent active systemic features and active arthritis can be treated according to suggestions from both algorithms.

For treating the systemic features of systemic JIA, three first-line options are available: nonsteroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, and anakinra (Kineret). It should be noted that interleukin-6 inhibitors and interleukin-1 inhibitors other than anakinra were not considered when developing the recommendations, since they were not widely available commercially at the time. TNF-alpha inhibitors were not considered because of their relatively poor effectiveness for the systemic manifestations.

While NSAID monotherapy might also help some children, the recommendations say that its use is inappropriate for patients with active fever and physician global assessment of overall disease activity (MD global) score equal to 7 of 10. It should also not be used for more than 1 month in patients with active fever.

Systemic glucocorticoids were recommended as initial therapy for patients with active fever and an MD global score of 7. Systemic glucocorticoids may also be added after 2 weeks of NSAID monotherapy in patients with active fever.

Anakinra was recommended for all patients with active fever who had poor prognostic features, no matter what they were currently taking. Anakinra was also recommended for patients who have or develop fever while on systemic glucocorticoids. Anakinra is a human recombinant interleukin-1 (IL-1) inhibitor that was approved to treat adults with moderate to severe arthritis who have not had an adequate response to conservative disease-modifying anti-rheumatic drug therapy. It is not currently approved for children with JIA.

Medications such as calcineurin inhibitors, intravenous immunoglobulin, methotrexate, and thalidomide were not formally recommended but might have roles in the treatment of systemic JIA.

For the treatment of the arthritic features of systemic JIA, initiation of NSAID monotherapy (with or without glucocorticoid joint injections) was recommended for all patients, regardless of the level of disease activity or presence of poor prognostic features. It was assumed that most patients with newly diagnosed systemic arthritis would have been started with NSAIDs. The next step would be methotrexate for all patients with active arthritis who were taking NSAID monotherapy for less than 1 month. If escalation of therapy was needed, the next choices would be either addition of a TNF-alpha inhibitor or anakinra. The recommendations indicate that initiation of anakinra should take place early rather than later in the disease course. For patients with moderate or high disease activity, regardless of features of poor prognosis, it was suggested that patients be switched from anakinra to a TNF-alpha inhibitor.

The last option is abatacept, a costimulatory blocker, for those who fail to be controlled by methotrexate or 4 months of a TNF-alpha inhibitor, and who have moderate to high disease activity.

During his presentation, Dr. Cron provided his perspective on the new systemic JIA recommendations. Most pediatric rheumatologists would probably begin with systemic corticosteroids at the onset of treatment, because that is what they are most familiar with and they are effective, he said.

He was pleased with the inclusion of anakinra in the guidelines. "With these guidelines, physicians can treat children with JIA from the start with anakinra." Inclusion of anakinra in the guidelines as a first option should help tremendously in helping patients receive reimbursement from insurance companies, he noted.

Dr. Cron cited evidence showing the effectiveness of anakinra as a first-line disease-modifying therapy in 46 patients with JIA, preventing refractory arthritis in almost 90% of patients (Arthritis Rheum. 2011;63:545-55). In this series of case studies, use of anakinra reduced elevated sedimentation rates and ferritin levels, decreased the number of active joint counts, and significantly lowered the dose of concomitant steroid therapy. "Kids can get remarkably better within days or months with anakinra. It can be a wonder drug for very sick children with systemic JIA," he said.

Although it was not discussed in the Recommendations, in his talk Dr. Cron said that anakinra is "revolutionizing" the treatment of macrophage activation syndrome (MAS) in systemic JIA (Rheumatology 2011;50:417-9) Dr. Cron reported that he has used anakinra as initial therapy to treat two children with MAS, and he found dramatic reductions in ferritin levels and liver enzymes within 2 days of initiation.

Systemic JIA is a relatively rare disease, with a prevalence of about 1 in 10,000. It has multiple systemic manifestations, including a high fever (which follows a unique pattern: typically once-daily, late-afternoon spikes in 30% of patients at presentation), rash, hepatosplenomegaly, lymphadenopathy, pericarditis, pleural effusion, pulmonary vasculitis, and even CNS stroke or seizure. Stroke or seizure might be related to MAS, a widespread coagulopathy that occurs in about 50% of patients and can be fatal.

Another common finding is asymmetry of the jaw. According to Dr. Cron, up to 80% of children with all forms of arthritis, including systemic JIA, can have arthritis of the temporomandibular joint (TMJ). This is often a subtle finding that can be overlooked until significant erosion has occurred. However, early TMJ arthritis can be detected with magnetic resonance screening.

Dr. Cron is a consultant for Genentech.

The American College of Rheumatology issued its first guidelines for the treatment of juvenile idiopathic arthritis on March 30.

"Our goal was to provide evidence and consensus-based guidance that reflects the current state of the field and is useful to clinicians of all levels of experience with the treatment of JIA. The recommendations are important because the treatment of JIA has undergone major changes over the last decade with the introduction of biologic therapeutic agents," Dr. Timothy G. Beukelman, lead author of the paper, said in an interview. The ACR says that the recommendations are not meant to dictate care, and it considers adherence to be voluntary.

The guidelines are published in Arthritis Care and Research (2011;63:465-82).

Up until now, there have been no validated guidelines for the treatment of JIA. Recognizing this, in 2008, the ACR issued a formal request for proposals to develop recommendations. The recommendations were written by a core expert panel of international pediatric rheumatology experts. A separate task force panel that included internationally recognized pediatric rheumatology clinicians, a pediatric rheumatology nurse, a general pediatrician, and a patient representative also provided input.

Dr. Thomas J.A. Lehman, professor of clinical pediatrics at Cornell University, New York, noted in an interview that: "While these new guidelines are useful in emphasizing the importance of promptly initiating appropriate disease-modifying therapy for children with active juvenile idiopathic arthritis, they are flawed in their failure to recognize the many variations in the severity of the variations of the disease.

The recommendations are "as evidenced based as possible," and also include expert opinion. They were developed after a systematic literature review that identified 244 pharmacotherapeutic studies, both controlled and uncontrolled. These studies were reviewed by the core expert panel which then prepared a summary report of the scientific evidence. The core expert panel also prepared more than 1,500 clinical scenarios for each medication of interest, categorizing hypothetical patients using all possible combinations of key clinical parameters. By a formal group assessment process, the TFP then made their recommendations, based on the published literature as well as ratings of the appropriateness of each medical intervention.

While the ILAR classification divides JIA into six distinct categories, these recommendations describe five JIA treatment groups: history of arthritis of four or fewer joints; history of arthritis of five or more joints; active sacroiliac arthritis; systemic arthritis with active systemic features and without active arthritis; and systemic arthritis with active arthritis and without active systemic features. Specific features for poor prognosis are described for each category, as well as disease activity levels. For instance, the features of poor prognosis for children with a history of arthritis in five or more joints are satisfaction of at least one of the following: arthritis of the hip or cervical spine, positive rheumatoid factor or anticyclic citrullinated peptide antibodies, or radiographic damage. "Risk stratification is crucial for guiding optimal treatment," according to Dr. Beukelman.

The recommendations focus on the initiation and safety monitoring of therapeutic agents used in the treatment of JIA, specifically NSAIDs, intra-articular glucocorticoid injections, nonbiologic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and systemic glucocorticoids. Medications used "off label" as part of common and widely accepted practice were considered.

Treatment algorithms are provided for those with a history of arthritis in four or fewer joints, history of arthritis in five or more joints, and systemic arthritis with active systemic features or active arthritis. Decision-making guidance regarding severity of disease or the presence of prognostic factors is included. For instance, for patients with a history of arthritis of five or more joints, a patient on methotrexate (with or without an adjunctive NSAID or joint injections) should move on to a tumor necrosis factor (TNF) -alpha inhibitor after 3 months if disease activity is moderate or high or after 6 months if disease activity is low, regardless of the presence of poor prognostic features.

Dr. Lehman, who is also chief of the division of pediatric rheumatology at the Hospital for Special Surgery in New York, noted that, "It is very appropriate to argue for the increased use of IL1 [interleukin-1] inhibitors in children with systemic onset disease. However, there are several different diseases included in the other forms of juvenile idiopathic arthritis for many of which it is not appropriate to start with methotrexate. Indeed, in this era, one must wonder if it wouldn\'t be more appropriate to begin children with an anti-TNF, which has a more rapid onset of action and is more effective in suppressing disease activity and preventing damage."

According to the International League of Associations for Rheumatology, JIA is defined as an arthritis of unknown etiology that begins before the 16th birthday and persists for at least 6 weeks with other known conditions excluded. About 1 in 1,000 children have JIA, and the condition can persist into adulthood, resulting in significant long-term morbidity.

Dr. Beukelman and Dr. Lehman had no relevant financial disclosures.

The American College of Rheumatology issued its first guidelines for the treatment of juvenile idiopathic arthritis on March 30.

"Our goal was to provide evidence and consensus-based guidance that reflects the current state of the field and is useful to clinicians of all levels of experience with the treatment of JIA. The recommendations are important because the treatment of JIA has undergone major changes over the last decade with the introduction of biologic therapeutic agents," Dr. Timothy G. Beukelman, lead author of the paper, said in an interview. The ACR says that the recommendations are not meant to dictate care, and it considers adherence to be voluntary.

The guidelines are published in Arthritis Care and Research (2011;63:465-82).

Up until now, there have been no validated guidelines for the treatment of JIA. Recognizing this, in 2008, the ACR issued a formal request for proposals to develop recommendations. The recommendations were written by a core expert panel of international pediatric rheumatology experts. A separate task force panel that included internationally recognized pediatric rheumatology clinicians, a pediatric rheumatology nurse, a general pediatrician, and a patient representative also provided input.

Dr. Thomas J.A. Lehman, professor of clinical pediatrics at Cornell University, New York, noted in an interview that: "While these new guidelines are useful in emphasizing the importance of promptly initiating appropriate disease-modifying therapy for children with active juvenile idiopathic arthritis, they are flawed in their failure to recognize the many variations in the severity of the variations of the disease.

The recommendations are "as evidenced based as possible," and also include expert opinion. They were developed after a systematic literature review that identified 244 pharmacotherapeutic studies, both controlled and uncontrolled. These studies were reviewed by the core expert panel which then prepared a summary report of the scientific evidence. The core expert panel also prepared more than 1,500 clinical scenarios for each medication of interest, categorizing hypothetical patients using all possible combinations of key clinical parameters. By a formal group assessment process, the TFP then made their recommendations, based on the published literature as well as ratings of the appropriateness of each medical intervention.

While the ILAR classification divides JIA into six distinct categories, these recommendations describe five JIA treatment groups: history of arthritis of four or fewer joints; history of arthritis of five or more joints; active sacroiliac arthritis; systemic arthritis with active systemic features and without active arthritis; and systemic arthritis with active arthritis and without active systemic features. Specific features for poor prognosis are described for each category, as well as disease activity levels. For instance, the features of poor prognosis for children with a history of arthritis in five or more joints are satisfaction of at least one of the following: arthritis of the hip or cervical spine, positive rheumatoid factor or anticyclic citrullinated peptide antibodies, or radiographic damage. "Risk stratification is crucial for guiding optimal treatment," according to Dr. Beukelman.

The recommendations focus on the initiation and safety monitoring of therapeutic agents used in the treatment of JIA, specifically NSAIDs, intra-articular glucocorticoid injections, nonbiologic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and systemic glucocorticoids. Medications used "off label" as part of common and widely accepted practice were considered.

Treatment algorithms are provided for those with a history of arthritis in four or fewer joints, history of arthritis in five or more joints, and systemic arthritis with active systemic features or active arthritis. Decision-making guidance regarding severity of disease or the presence of prognostic factors is included. For instance, for patients with a history of arthritis of five or more joints, a patient on methotrexate (with or without an adjunctive NSAID or joint injections) should move on to a tumor necrosis factor (TNF) -alpha inhibitor after 3 months if disease activity is moderate or high or after 6 months if disease activity is low, regardless of the presence of poor prognostic features.

Dr. Lehman, who is also chief of the division of pediatric rheumatology at the Hospital for Special Surgery in New York, noted that, "It is very appropriate to argue for the increased use of IL1 [interleukin-1] inhibitors in children with systemic onset disease. However, there are several different diseases included in the other forms of juvenile idiopathic arthritis for many of which it is not appropriate to start with methotrexate. Indeed, in this era, one must wonder if it wouldn\'t be more appropriate to begin children with an anti-TNF, which has a more rapid onset of action and is more effective in suppressing disease activity and preventing damage."

According to the International League of Associations for Rheumatology, JIA is defined as an arthritis of unknown etiology that begins before the 16th birthday and persists for at least 6 weeks with other known conditions excluded. About 1 in 1,000 children have JIA, and the condition can persist into adulthood, resulting in significant long-term morbidity.

Dr. Beukelman and Dr. Lehman had no relevant financial disclosures.

The American College of Rheumatology issued its first guidelines for the treatment of juvenile idiopathic arthritis on March 30.

"Our goal was to provide evidence and consensus-based guidance that reflects the current state of the field and is useful to clinicians of all levels of experience with the treatment of JIA. The recommendations are important because the treatment of JIA has undergone major changes over the last decade with the introduction of biologic therapeutic agents," Dr. Timothy G. Beukelman, lead author of the paper, said in an interview. The ACR says that the recommendations are not meant to dictate care, and it considers adherence to be voluntary.

The guidelines are published in Arthritis Care and Research (2011;63:465-82).

Up until now, there have been no validated guidelines for the treatment of JIA. Recognizing this, in 2008, the ACR issued a formal request for proposals to develop recommendations. The recommendations were written by a core expert panel of international pediatric rheumatology experts. A separate task force panel that included internationally recognized pediatric rheumatology clinicians, a pediatric rheumatology nurse, a general pediatrician, and a patient representative also provided input.

Dr. Thomas J.A. Lehman, professor of clinical pediatrics at Cornell University, New York, noted in an interview that: "While these new guidelines are useful in emphasizing the importance of promptly initiating appropriate disease-modifying therapy for children with active juvenile idiopathic arthritis, they are flawed in their failure to recognize the many variations in the severity of the variations of the disease.

The recommendations are "as evidenced based as possible," and also include expert opinion. They were developed after a systematic literature review that identified 244 pharmacotherapeutic studies, both controlled and uncontrolled. These studies were reviewed by the core expert panel which then prepared a summary report of the scientific evidence. The core expert panel also prepared more than 1,500 clinical scenarios for each medication of interest, categorizing hypothetical patients using all possible combinations of key clinical parameters. By a formal group assessment process, the TFP then made their recommendations, based on the published literature as well as ratings of the appropriateness of each medical intervention.

While the ILAR classification divides JIA into six distinct categories, these recommendations describe five JIA treatment groups: history of arthritis of four or fewer joints; history of arthritis of five or more joints; active sacroiliac arthritis; systemic arthritis with active systemic features and without active arthritis; and systemic arthritis with active arthritis and without active systemic features. Specific features for poor prognosis are described for each category, as well as disease activity levels. For instance, the features of poor prognosis for children with a history of arthritis in five or more joints are satisfaction of at least one of the following: arthritis of the hip or cervical spine, positive rheumatoid factor or anticyclic citrullinated peptide antibodies, or radiographic damage. "Risk stratification is crucial for guiding optimal treatment," according to Dr. Beukelman.

The recommendations focus on the initiation and safety monitoring of therapeutic agents used in the treatment of JIA, specifically NSAIDs, intra-articular glucocorticoid injections, nonbiologic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and systemic glucocorticoids. Medications used "off label" as part of common and widely accepted practice were considered.

Treatment algorithms are provided for those with a history of arthritis in four or fewer joints, history of arthritis in five or more joints, and systemic arthritis with active systemic features or active arthritis. Decision-making guidance regarding severity of disease or the presence of prognostic factors is included. For instance, for patients with a history of arthritis of five or more joints, a patient on methotrexate (with or without an adjunctive NSAID or joint injections) should move on to a tumor necrosis factor (TNF) -alpha inhibitor after 3 months if disease activity is moderate or high or after 6 months if disease activity is low, regardless of the presence of poor prognostic features.

Dr. Lehman, who is also chief of the division of pediatric rheumatology at the Hospital for Special Surgery in New York, noted that, "It is very appropriate to argue for the increased use of IL1 [interleukin-1] inhibitors in children with systemic onset disease. However, there are several different diseases included in the other forms of juvenile idiopathic arthritis for many of which it is not appropriate to start with methotrexate. Indeed, in this era, one must wonder if it wouldn\'t be more appropriate to begin children with an anti-TNF, which has a more rapid onset of action and is more effective in suppressing disease activity and preventing damage."

According to the International League of Associations for Rheumatology, JIA is defined as an arthritis of unknown etiology that begins before the 16th birthday and persists for at least 6 weeks with other known conditions excluded. About 1 in 1,000 children have JIA, and the condition can persist into adulthood, resulting in significant long-term morbidity.

Dr. Beukelman and Dr. Lehman had no relevant financial disclosures.

The American College of Rheumatology issued its first guidelines for the treatment of juvenile idiopathic arthritis on March 30.

"Our goal was to provide evidence and consensus-based guidance that reflects the current state of the field and is useful to clinicians of all levels of experience with the treatment of JIA. The recommendations are important because the treatment of JIA has undergone major changes over the last decade with the introduction of biologic therapeutic agents," Dr. Timothy G. Beukelman, lead author of the paper, said in an interview. The ACR says that the recommendations are not meant to dictate care, and it considers adherence to be voluntary.

The guidelines are published in Arthritis Care and Research (2011;63:465-82).

Up until now, there have been no validated guidelines for the treatment of JIA. Recognizing this, in 2008, the ACR issued a formal request for proposals to develop recommendations. The recommendations were written by a core expert panel of international pediatric rheumatology experts. A separate task force panel that included internationally recognized pediatric rheumatology clinicians, a pediatric rheumatology nurse, a general pediatrician, and a patient representative also provided input.

Dr. Thomas J.A. Lehman, professor of clinical pediatrics at Cornell University, New York, noted in an interview that: "While these new guidelines are useful in emphasizing the importance of promptly initiating appropriate disease-modifying therapy for children with active juvenile idiopathic arthritis, they are flawed in their failure to recognize the many variations in the severity of the variations of the disease.

The recommendations are "as evidenced based as possible," and also include expert opinion. They were developed after a systematic literature review that identified 244 pharmacotherapeutic studies, both controlled and uncontrolled. These studies were reviewed by the core expert panel which then prepared a summary report of the scientific evidence. The core expert panel also prepared more than 1,500 clinical scenarios for each medication of interest, categorizing hypothetical patients using all possible combinations of key clinical parameters. By a formal group assessment process, the TFP then made their recommendations, based on the published literature as well as ratings of the appropriateness of each medical intervention.

While the ILAR classification divides JIA into six distinct categories, these recommendations describe five JIA treatment groups: history of arthritis of four or fewer joints; history of arthritis of five or more joints; active sacroiliac arthritis; systemic arthritis with active systemic features and without active arthritis; and systemic arthritis with active arthritis and without active systemic features. Specific features for poor prognosis are described for each category, as well as disease activity levels. For instance, the features of poor prognosis for children with a history of arthritis in five or more joints are satisfaction of at least one of the following: arthritis of the hip or cervical spine, positive rheumatoid factor or anticyclic citrullinated peptide antibodies, or radiographic damage. "Risk stratification is crucial for guiding optimal treatment," according to Dr. Beukelman.

The recommendations focus on the initiation and safety monitoring of therapeutic agents used in the treatment of JIA, specifically NSAIDs, intra-articular glucocorticoid injections, nonbiologic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and systemic glucocorticoids. Medications used "off label" as part of common and widely accepted practice were considered.

Treatment algorithms are provided for those with a history of arthritis in four or fewer joints, history of arthritis in five or more joints, and systemic arthritis with active systemic features or active arthritis. Decision-making guidance regarding severity of disease or the presence of prognostic factors is included. For instance, for patients with a history of arthritis of five or more joints, a patient on methotrexate (with or without an adjunctive NSAID or joint injections) should move on to a tumor necrosis factor (TNF) -alpha inhibitor after 3 months if disease activity is moderate or high or after 6 months if disease activity is low, regardless of the presence of poor prognostic features.

Dr. Lehman, who is also chief of the division of pediatric rheumatology at the Hospital for Special Surgery in New York, noted that, "It is very appropriate to argue for the increased use of IL1 [interleukin-1] inhibitors in children with systemic onset disease. However, there are several different diseases included in the other forms of juvenile idiopathic arthritis for many of which it is not appropriate to start with methotrexate. Indeed, in this era, one must wonder if it wouldn\'t be more appropriate to begin children with an anti-TNF, which has a more rapid onset of action and is more effective in suppressing disease activity and preventing damage."

According to the International League of Associations for Rheumatology, JIA is defined as an arthritis of unknown etiology that begins before the 16th birthday and persists for at least 6 weeks with other known conditions excluded. About 1 in 1,000 children have JIA, and the condition can persist into adulthood, resulting in significant long-term morbidity.

Dr. Beukelman and Dr. Lehman had no relevant financial disclosures.

The American College of Rheumatology issued its first guidelines for the treatment of juvenile idiopathic arthritis on March 30.

"Our goal was to provide evidence and consensus-based guidance that reflects the current state of the field and is useful to clinicians of all levels of experience with the treatment of JIA. The recommendations are important because the treatment of JIA has undergone major changes over the last decade with the introduction of biologic therapeutic agents," Dr. Timothy G. Beukelman, lead author of the paper, said in an interview. The ACR says that the recommendations are not meant to dictate care, and it considers adherence to be voluntary.

The guidelines are published in Arthritis Care and Research (2011;63:465-82).

Up until now, there have been no validated guidelines for the treatment of JIA. Recognizing this, in 2008, the ACR issued a formal request for proposals to develop recommendations. The recommendations were written by a core expert panel of international pediatric rheumatology experts. A separate task force panel that included internationally recognized pediatric rheumatology clinicians, a pediatric rheumatology nurse, a general pediatrician, and a patient representative also provided input.

Dr. Thomas J.A. Lehman, professor of clinical pediatrics at Cornell University, New York, noted in an interview that: "While these new guidelines are useful in emphasizing the importance of promptly initiating appropriate disease-modifying therapy for children with active juvenile idiopathic arthritis, they are flawed in their failure to recognize the many variations in the severity of the variations of the disease.

The recommendations are "as evidenced based as possible," and also include expert opinion. They were developed after a systematic literature review that identified 244 pharmacotherapeutic studies, both controlled and uncontrolled. These studies were reviewed by the core expert panel which then prepared a summary report of the scientific evidence. The core expert panel also prepared more than 1,500 clinical scenarios for each medication of interest, categorizing hypothetical patients using all possible combinations of key clinical parameters. By a formal group assessment process, the TFP then made their recommendations, based on the published literature as well as ratings of the appropriateness of each medical intervention.

While the ILAR classification divides JIA into six distinct categories, these recommendations describe five JIA treatment groups: history of arthritis of four or fewer joints; history of arthritis of five or more joints; active sacroiliac arthritis; systemic arthritis with active systemic features and without active arthritis; and systemic arthritis with active arthritis and without active systemic features. Specific features for poor prognosis are described for each category, as well as disease activity levels. For instance, the features of poor prognosis for children with a history of arthritis in five or more joints are satisfaction of at least one of the following: arthritis of the hip or cervical spine, positive rheumatoid factor or anticyclic citrullinated peptide antibodies, or radiographic damage. "Risk stratification is crucial for guiding optimal treatment," according to Dr. Beukelman.

The recommendations focus on the initiation and safety monitoring of therapeutic agents used in the treatment of JIA, specifically NSAIDs, intra-articular glucocorticoid injections, nonbiologic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and systemic glucocorticoids. Medications used "off label" as part of common and widely accepted practice were considered.

Treatment algorithms are provided for those with a history of arthritis in four or fewer joints, history of arthritis in five or more joints, and systemic arthritis with active systemic features or active arthritis. Decision-making guidance regarding severity of disease or the presence of prognostic factors is included. For instance, for patients with a history of arthritis of five or more joints, a patient on methotrexate (with or without an adjunctive NSAID or joint injections) should move on to a tumor necrosis factor (TNF) -alpha inhibitor after 3 months if disease activity is moderate or high or after 6 months if disease activity is low, regardless of the presence of poor prognostic features.

Dr. Lehman, who is also chief of the division of pediatric rheumatology at the Hospital for Special Surgery in New York, noted that, "It is very appropriate to argue for the increased use of IL1 [interleukin-1] inhibitors in children with systemic onset disease. However, there are several different diseases included in the other forms of juvenile idiopathic arthritis for many of which it is not appropriate to start with methotrexate. Indeed, in this era, one must wonder if it wouldn\'t be more appropriate to begin children with an anti-TNF, which has a more rapid onset of action and is more effective in suppressing disease activity and preventing damage."

According to the International League of Associations for Rheumatology, JIA is defined as an arthritis of unknown etiology that begins before the 16th birthday and persists for at least 6 weeks with other known conditions excluded. About 1 in 1,000 children have JIA, and the condition can persist into adulthood, resulting in significant long-term morbidity.

Dr. Beukelman and Dr. Lehman had no relevant financial disclosures.

The American College of Rheumatology issued its first guidelines for the treatment of juvenile idiopathic arthritis on March 30.

"Our goal was to provide evidence and consensus-based guidance that reflects the current state of the field and is useful to clinicians of all levels of experience with the treatment of JIA. The recommendations are important because the treatment of JIA has undergone major changes over the last decade with the introduction of biologic therapeutic agents," Dr. Timothy G. Beukelman, lead author of the paper, said in an interview. The ACR says that the recommendations are not meant to dictate care, and it considers adherence to be voluntary.

The guidelines are published in Arthritis Care and Research (2011;63:465-82).

Up until now, there have been no validated guidelines for the treatment of JIA. Recognizing this, in 2008, the ACR issued a formal request for proposals to develop recommendations. The recommendations were written by a core expert panel of international pediatric rheumatology experts. A separate task force panel that included internationally recognized pediatric rheumatology clinicians, a pediatric rheumatology nurse, a general pediatrician, and a patient representative also provided input.

Dr. Thomas J.A. Lehman, professor of clinical pediatrics at Cornell University, New York, noted in an interview that: "While these new guidelines are useful in emphasizing the importance of promptly initiating appropriate disease-modifying therapy for children with active juvenile idiopathic arthritis, they are flawed in their failure to recognize the many variations in the severity of the variations of the disease.

The recommendations are "as evidenced based as possible," and also include expert opinion. They were developed after a systematic literature review that identified 244 pharmacotherapeutic studies, both controlled and uncontrolled. These studies were reviewed by the core expert panel which then prepared a summary report of the scientific evidence. The core expert panel also prepared more than 1,500 clinical scenarios for each medication of interest, categorizing hypothetical patients using all possible combinations of key clinical parameters. By a formal group assessment process, the TFP then made their recommendations, based on the published literature as well as ratings of the appropriateness of each medical intervention.

While the ILAR classification divides JIA into six distinct categories, these recommendations describe five JIA treatment groups: history of arthritis of four or fewer joints; history of arthritis of five or more joints; active sacroiliac arthritis; systemic arthritis with active systemic features and without active arthritis; and systemic arthritis with active arthritis and without active systemic features. Specific features for poor prognosis are described for each category, as well as disease activity levels. For instance, the features of poor prognosis for children with a history of arthritis in five or more joints are satisfaction of at least one of the following: arthritis of the hip or cervical spine, positive rheumatoid factor or anticyclic citrullinated peptide antibodies, or radiographic damage. "Risk stratification is crucial for guiding optimal treatment," according to Dr. Beukelman.

The recommendations focus on the initiation and safety monitoring of therapeutic agents used in the treatment of JIA, specifically NSAIDs, intra-articular glucocorticoid injections, nonbiologic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and systemic glucocorticoids. Medications used "off label" as part of common and widely accepted practice were considered.

Treatment algorithms are provided for those with a history of arthritis in four or fewer joints, history of arthritis in five or more joints, and systemic arthritis with active systemic features or active arthritis. Decision-making guidance regarding severity of disease or the presence of prognostic factors is included. For instance, for patients with a history of arthritis of five or more joints, a patient on methotrexate (with or without an adjunctive NSAID or joint injections) should move on to a tumor necrosis factor (TNF) -alpha inhibitor after 3 months if disease activity is moderate or high or after 6 months if disease activity is low, regardless of the presence of poor prognostic features.

Dr. Lehman, who is also chief of the division of pediatric rheumatology at the Hospital for Special Surgery in New York, noted that, "It is very appropriate to argue for the increased use of IL1 [interleukin-1] inhibitors in children with systemic onset disease. However, there are several different diseases included in the other forms of juvenile idiopathic arthritis for many of which it is not appropriate to start with methotrexate. Indeed, in this era, one must wonder if it wouldn\'t be more appropriate to begin children with an anti-TNF, which has a more rapid onset of action and is more effective in suppressing disease activity and preventing damage."

According to the International League of Associations for Rheumatology, JIA is defined as an arthritis of unknown etiology that begins before the 16th birthday and persists for at least 6 weeks with other known conditions excluded. About 1 in 1,000 children have JIA, and the condition can persist into adulthood, resulting in significant long-term morbidity.

Dr. Beukelman and Dr. Lehman had no relevant financial disclosures.

NEW YORK – Prescribing errors, such as premature withdrawal of a biologic agent once remission is achieved and hasty switching of agents, can undermine optimum results with biologics in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici.

For instance, results from the BEST (Behandel Strategieen) trial (Ann. Rheum. Dis. 2009;68 [suppl. 3]:544) found that if a group of patients who achieved remission with biologic therapy stops that therapy, within 2 years 54% (62/115) stayed in drug-free remission, says Dr. Yazici, a rheumatologist who is director of the Seligman Center for Advanced Therapeutics and Behcet’s Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases. The remaining patients saw their disease flare, but while about three quarters of those (39/53 or 34% of the original group) were able to be brought back into remission within 6 months, about one-quarter (14/53 or 12% of the original group of 115) were unable to achieve remission again. "That number is too large," says Dr. Yazici.

"Just as we would not consider stopping treatment for diabetes or hypertension, this chronic disease treatment approach should also be considered in patients with RA," says Dr. Yazici. He advises against tapering or stopping the combination of medications that was required to achieve remission unless there is a safety concern.

Another problem that Dr. Yazici has noticed is failure to allow enough time for one tumor necrosis factor–inhibiting (TNFi) biologic to take effect before switching to another biologic. Common reasons for switching cited are inefficacy or adverse events.

In a retrospective analysis of an insurance claims database of 9,075 patients with RA who started a TNFi agent during the period 2000-2005, Dr. Yazici saw more frequent changes among different TNFi agents and shorter duration of treatment before change, as time progressed. The use of a first-prescribed biologic medication dropped by about 45% after the first year, 70% after the second year, and by 3 years only a small percentage remained on the same therapy. In this study, infliximab had the highest duration of continuation, about 50% at 2 years. After adalimumab was introduced into the market, a dramatic drop in time to switch was observed, from an average of 454 days to 237 days among TNFi agents (J. Rheumatol. 2009;36:907-13). "The more biologics we have, the faster we switch, it seems," commented Dr. Yazici.

Dr. Yazici also cited data from the DANBIO registry, a nationwide Danish registry of patients with RA, in which 2,326 patients were observed after initiation of biologic therapy. After 4 years, 56% were still taking etanercept, 52% were still on adalimumab, and 41% remained on infliximab. Drug withdrawal was primarily attributed to adverse effects and secondarily to lack of efficacy (Arthritis Rheum. 2010;62:22-32).

Published data on etanercept, adalimumab, infliximab, and abatacept suggest no real differences in efficacy in the majority of patients who use them, says Dr. Yazici. Data from registries tend to show no preference for one over another. He suggests that physicians allow at least a 3-6 month trial period before switching biologic agents.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene, Genentech, Roche, and UCB.

NEW YORK – Prescribing errors, such as premature withdrawal of a biologic agent once remission is achieved and hasty switching of agents, can undermine optimum results with biologics in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici.

For instance, results from the BEST (Behandel Strategieen) trial (Ann. Rheum. Dis. 2009;68 [suppl. 3]:544) found that if a group of patients who achieved remission with biologic therapy stops that therapy, within 2 years 54% (62/115) stayed in drug-free remission, says Dr. Yazici, a rheumatologist who is director of the Seligman Center for Advanced Therapeutics and Behcet’s Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases. The remaining patients saw their disease flare, but while about three quarters of those (39/53 or 34% of the original group) were able to be brought back into remission within 6 months, about one-quarter (14/53 or 12% of the original group of 115) were unable to achieve remission again. "That number is too large," says Dr. Yazici.

"Just as we would not consider stopping treatment for diabetes or hypertension, this chronic disease treatment approach should also be considered in patients with RA," says Dr. Yazici. He advises against tapering or stopping the combination of medications that was required to achieve remission unless there is a safety concern.

Another problem that Dr. Yazici has noticed is failure to allow enough time for one tumor necrosis factor–inhibiting (TNFi) biologic to take effect before switching to another biologic. Common reasons for switching cited are inefficacy or adverse events.

In a retrospective analysis of an insurance claims database of 9,075 patients with RA who started a TNFi agent during the period 2000-2005, Dr. Yazici saw more frequent changes among different TNFi agents and shorter duration of treatment before change, as time progressed. The use of a first-prescribed biologic medication dropped by about 45% after the first year, 70% after the second year, and by 3 years only a small percentage remained on the same therapy. In this study, infliximab had the highest duration of continuation, about 50% at 2 years. After adalimumab was introduced into the market, a dramatic drop in time to switch was observed, from an average of 454 days to 237 days among TNFi agents (J. Rheumatol. 2009;36:907-13). "The more biologics we have, the faster we switch, it seems," commented Dr. Yazici.

Dr. Yazici also cited data from the DANBIO registry, a nationwide Danish registry of patients with RA, in which 2,326 patients were observed after initiation of biologic therapy. After 4 years, 56% were still taking etanercept, 52% were still on adalimumab, and 41% remained on infliximab. Drug withdrawal was primarily attributed to adverse effects and secondarily to lack of efficacy (Arthritis Rheum. 2010;62:22-32).

Published data on etanercept, adalimumab, infliximab, and abatacept suggest no real differences in efficacy in the majority of patients who use them, says Dr. Yazici. Data from registries tend to show no preference for one over another. He suggests that physicians allow at least a 3-6 month trial period before switching biologic agents.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene, Genentech, Roche, and UCB.

NEW YORK – Prescribing errors, such as premature withdrawal of a biologic agent once remission is achieved and hasty switching of agents, can undermine optimum results with biologics in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici.

For instance, results from the BEST (Behandel Strategieen) trial (Ann. Rheum. Dis. 2009;68 [suppl. 3]:544) found that if a group of patients who achieved remission with biologic therapy stops that therapy, within 2 years 54% (62/115) stayed in drug-free remission, says Dr. Yazici, a rheumatologist who is director of the Seligman Center for Advanced Therapeutics and Behcet’s Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases. The remaining patients saw their disease flare, but while about three quarters of those (39/53 or 34% of the original group) were able to be brought back into remission within 6 months, about one-quarter (14/53 or 12% of the original group of 115) were unable to achieve remission again. "That number is too large," says Dr. Yazici.

"Just as we would not consider stopping treatment for diabetes or hypertension, this chronic disease treatment approach should also be considered in patients with RA," says Dr. Yazici. He advises against tapering or stopping the combination of medications that was required to achieve remission unless there is a safety concern.

Another problem that Dr. Yazici has noticed is failure to allow enough time for one tumor necrosis factor–inhibiting (TNFi) biologic to take effect before switching to another biologic. Common reasons for switching cited are inefficacy or adverse events.

In a retrospective analysis of an insurance claims database of 9,075 patients with RA who started a TNFi agent during the period 2000-2005, Dr. Yazici saw more frequent changes among different TNFi agents and shorter duration of treatment before change, as time progressed. The use of a first-prescribed biologic medication dropped by about 45% after the first year, 70% after the second year, and by 3 years only a small percentage remained on the same therapy. In this study, infliximab had the highest duration of continuation, about 50% at 2 years. After adalimumab was introduced into the market, a dramatic drop in time to switch was observed, from an average of 454 days to 237 days among TNFi agents (J. Rheumatol. 2009;36:907-13). "The more biologics we have, the faster we switch, it seems," commented Dr. Yazici.

Dr. Yazici also cited data from the DANBIO registry, a nationwide Danish registry of patients with RA, in which 2,326 patients were observed after initiation of biologic therapy. After 4 years, 56% were still taking etanercept, 52% were still on adalimumab, and 41% remained on infliximab. Drug withdrawal was primarily attributed to adverse effects and secondarily to lack of efficacy (Arthritis Rheum. 2010;62:22-32).

Published data on etanercept, adalimumab, infliximab, and abatacept suggest no real differences in efficacy in the majority of patients who use them, says Dr. Yazici. Data from registries tend to show no preference for one over another. He suggests that physicians allow at least a 3-6 month trial period before switching biologic agents.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene, Genentech, Roche, and UCB.

NEW YORK — Encouraging results from a phase III study of the oral Janus kinase 3 inhibitor tasocitinib used as monotherapy for rheumatoid arthritis have rheumatologists anticipating the possibility of a new oral disease-modifying antirheumatic drug, according to Dr. Yusuf Yazici

Tasocitinib (CP-690550) is a small-molecule, oral JAK inhibitor that blocks cytokine signaling, cytokine-induced gene expression, and activation of cells involved in the immune and inflammatory responses.

Findings from the studies “look promising,” remarked Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment, and Research Center at New York University Hospital for Joint Diseases.

In this 6-month randomized, double-blind, placebo-controlled study, 243 RA patients who had failed at least one prior disease-modifying antirheumatic drug (DMARD) trial were treated for 3 months with 5 mg of tasocitinib b.i.d., 245 patients were given 10 mg of tasocitinib b.i.d., and 122 were given placebo. After 3 months, half of the placebo-treated patients were switched to 5 mg of tasocitinib and half were switched to 10 mg of tasocitinib.

At 3 months, the American College of Rheumatology (ACR) 20 response rates for 5 mg and 10 mg of tasocitinib were 60% and 66%, respectively, which were significantly higher than the 27% rate seen with placebo (P less than .0001). Just over 20% of patients on the 10-mg dose and 15% of those on the 5-mg pill achieved ACR 70, compared with 5% of those receiving placebo.

Significant differences for each tasocitinib dose compared with placebo were also found for another primary end point, the least squares mean change in the Health Assessment Questionnaire Disability Index (−0.31 and −0.38, respectively; P less than .0001).

The percentage of patients in disease remission (defined as a disease activity score [DAS] less than 2.6) was the third primary efficacy end point. No significant differences between treatment and placebo were found (6% for the 5-mg tasocitinib group vs. 4% for placebo, P = .505), although there was a trend toward significance for the 10-mg group (10%, P = .056). Significant differences were found on DAS improvement between each of the tasocitinib doses and placebo at 3 months (P less than .0001).

Meaningful differences were found as early as the second week on the ACR 20 for both tasocitinib doses, on the ACR 50 with the 10-mg dose, and on the ACR 70 for both doses.

In the first 3 months, 330 patients had 701 treatment-emergent adverse events (AEs), with a similar frequency in each of the tasocitinib and placebo groups. Thirteen patients discontinued treatment because of treatment-emergent AEs – there were no between-group differences. No deaths were reported. A total of 25 patients developed serious AEs (6 in the 5-mg tasocitinib group, 12 in the 10-mg tasocitinib group, 5 in the group that switched from placebo to 5-mg tasocitinib, and 2 in the group that switched from placebo to 10-mg tasocitinib).

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene Corporation, Genentech, Roche, and UCB.

NEW YORK — Encouraging results from a phase III study of the oral Janus kinase 3 inhibitor tasocitinib used as monotherapy for rheumatoid arthritis have rheumatologists anticipating the possibility of a new oral disease-modifying antirheumatic drug, according to Dr. Yusuf Yazici

Tasocitinib (CP-690550) is a small-molecule, oral JAK inhibitor that blocks cytokine signaling, cytokine-induced gene expression, and activation of cells involved in the immune and inflammatory responses.

Findings from the studies “look promising,” remarked Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment, and Research Center at New York University Hospital for Joint Diseases.

In this 6-month randomized, double-blind, placebo-controlled study, 243 RA patients who had failed at least one prior disease-modifying antirheumatic drug (DMARD) trial were treated for 3 months with 5 mg of tasocitinib b.i.d., 245 patients were given 10 mg of tasocitinib b.i.d., and 122 were given placebo. After 3 months, half of the placebo-treated patients were switched to 5 mg of tasocitinib and half were switched to 10 mg of tasocitinib.

At 3 months, the American College of Rheumatology (ACR) 20 response rates for 5 mg and 10 mg of tasocitinib were 60% and 66%, respectively, which were significantly higher than the 27% rate seen with placebo (P less than .0001). Just over 20% of patients on the 10-mg dose and 15% of those on the 5-mg pill achieved ACR 70, compared with 5% of those receiving placebo.

Significant differences for each tasocitinib dose compared with placebo were also found for another primary end point, the least squares mean change in the Health Assessment Questionnaire Disability Index (−0.31 and −0.38, respectively; P less than .0001).

The percentage of patients in disease remission (defined as a disease activity score [DAS] less than 2.6) was the third primary efficacy end point. No significant differences between treatment and placebo were found (6% for the 5-mg tasocitinib group vs. 4% for placebo, P = .505), although there was a trend toward significance for the 10-mg group (10%, P = .056). Significant differences were found on DAS improvement between each of the tasocitinib doses and placebo at 3 months (P less than .0001).

Meaningful differences were found as early as the second week on the ACR 20 for both tasocitinib doses, on the ACR 50 with the 10-mg dose, and on the ACR 70 for both doses.

In the first 3 months, 330 patients had 701 treatment-emergent adverse events (AEs), with a similar frequency in each of the tasocitinib and placebo groups. Thirteen patients discontinued treatment because of treatment-emergent AEs – there were no between-group differences. No deaths were reported. A total of 25 patients developed serious AEs (6 in the 5-mg tasocitinib group, 12 in the 10-mg tasocitinib group, 5 in the group that switched from placebo to 5-mg tasocitinib, and 2 in the group that switched from placebo to 10-mg tasocitinib).

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene Corporation, Genentech, Roche, and UCB.

NEW YORK — Encouraging results from a phase III study of the oral Janus kinase 3 inhibitor tasocitinib used as monotherapy for rheumatoid arthritis have rheumatologists anticipating the possibility of a new oral disease-modifying antirheumatic drug, according to Dr. Yusuf Yazici

Tasocitinib (CP-690550) is a small-molecule, oral JAK inhibitor that blocks cytokine signaling, cytokine-induced gene expression, and activation of cells involved in the immune and inflammatory responses.

Findings from the studies “look promising,” remarked Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment, and Research Center at New York University Hospital for Joint Diseases.

In this 6-month randomized, double-blind, placebo-controlled study, 243 RA patients who had failed at least one prior disease-modifying antirheumatic drug (DMARD) trial were treated for 3 months with 5 mg of tasocitinib b.i.d., 245 patients were given 10 mg of tasocitinib b.i.d., and 122 were given placebo. After 3 months, half of the placebo-treated patients were switched to 5 mg of tasocitinib and half were switched to 10 mg of tasocitinib.

At 3 months, the American College of Rheumatology (ACR) 20 response rates for 5 mg and 10 mg of tasocitinib were 60% and 66%, respectively, which were significantly higher than the 27% rate seen with placebo (P less than .0001). Just over 20% of patients on the 10-mg dose and 15% of those on the 5-mg pill achieved ACR 70, compared with 5% of those receiving placebo.

Significant differences for each tasocitinib dose compared with placebo were also found for another primary end point, the least squares mean change in the Health Assessment Questionnaire Disability Index (−0.31 and −0.38, respectively; P less than .0001).

The percentage of patients in disease remission (defined as a disease activity score [DAS] less than 2.6) was the third primary efficacy end point. No significant differences between treatment and placebo were found (6% for the 5-mg tasocitinib group vs. 4% for placebo, P = .505), although there was a trend toward significance for the 10-mg group (10%, P = .056). Significant differences were found on DAS improvement between each of the tasocitinib doses and placebo at 3 months (P less than .0001).

Meaningful differences were found as early as the second week on the ACR 20 for both tasocitinib doses, on the ACR 50 with the 10-mg dose, and on the ACR 70 for both doses.

In the first 3 months, 330 patients had 701 treatment-emergent adverse events (AEs), with a similar frequency in each of the tasocitinib and placebo groups. Thirteen patients discontinued treatment because of treatment-emergent AEs – there were no between-group differences. No deaths were reported. A total of 25 patients developed serious AEs (6 in the 5-mg tasocitinib group, 12 in the 10-mg tasocitinib group, 5 in the group that switched from placebo to 5-mg tasocitinib, and 2 in the group that switched from placebo to 10-mg tasocitinib).

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene Corporation, Genentech, Roche, and UCB.