EULAR (European League Against Rheumatism): 2012 Congress

BERLIN – Recent evidence strongly suggests that enthesis-related arthritis in adolescents has two distinct clinical phenotypes, according to Dr. John Ioannou of University College London.

"The traditional view of enthesis-related arthritis has been that peripheral joint involvement and entheseal disease are common at presentation and then sacroiliitis occurs after many years as a late feature. I think that’s a paradigm that has been borne out not to be true. We can confidently shred that up and throw it away," he declared at the annual European Congress of Rheumatology.

The increasing use of MRI in the evaluation of patients who meet revised International League of Associations for Rheumatology diagnostic criteria for enthesis-related arthritis (ERA) has demonstrated that sacroiliitis appears early in the course of the disease in many of them. This early-onset sacroiliitis doesn’t show up on standard radiography, he explained.

ERA is an understudied subtype of juvenile idiopathic arthritis. The true incidence and prevalence of ERA aren’t known. Dr. Ioannou and his coworkers are conducting a long-term observational study at University College London. Analysis of the first 68 patients in the ERA cohort who have undergone MRI scanning indicated that 36, or 62%, had axial disease while the remainder did not.

The axial phenotype of ERA is characterized by a strong association with HLA-B27-positivity; more than 80% of patients with axial ERA were HLA-B27 positive, as was true for only a minority of those with the peripheral ERA phenotype. Extra-articular manifestations of ERA – inflammatory bowel disease and acute anterior uveitis – occurred only in HLA-B27-positive patients with axial disease.

Patients who were unaffected by axial disease had a strong proclivity for ankle arthritis, which was present in 80% of that group, compared with one-fourth of patients with axial ERA.

Fifty-eight of the 68 patients in the ERA cohort are male. Their median age at disease onset was 11 years and 1 month. The median time from disease onset to the appearance of inflammatory spinal symptoms was 2 years and 8 months.

The London experience matches that described by Italian investigators at the University of Florence, who are following a cohort of 59 patients with ERA. Twenty-one of the 59 reported symptoms of inflammatory back pain beginning a median of 1 year and 3 months after onset of ERA. MRI revealed the presence of sacroiliitis in 17 of the 21, all of whom had negative X-rays of the sacroiliac joints. As in the London series, the Italian patients with axial involvement were far more likely to be HLA-B27-positive, while those without axial disease had a greater frequency of ankle arthritis (J. Rheumatol. 2010;37:2395-401).

Twenty-nine of the 68 patients in the London cohort are on anti–tumor necrosis factor (anti-TNF) therapy plus methotrexate or another nonbiologic disease-modifying antirheumatic drug.

"Our anecdotal experience is that anti-TNF therapy tends to work pretty well in patients with ERA, but the remission rate is low. We’ve not been able to discontinue anti-TNF therapy in our patients," Dr. Ioannou noted.

This is consistent with the experience of a Dutch group. They reported that two-thirds of 22 ERA patients treated with an anti-TNF agent had inactive arthritis and enthesis after 15 months; however, none was able to discontinue biologic therapy without flaring of their disease (J. Rheumatol. 2011;38:2258-63).

The pathogenic mechanisms driving the two clinical patterns of ERA aren’t understood yet. Defining those mechanisms will provide a rationale for deciding on the best treatments for patients with one clinical phenotype or the other. At present, treatment is largely based upon extrapolation from data gathered in treating other forms of juvenile idiopathic arthritis or adult ankylosing spondylitis, the rheumatologist said.

Dr. Ioannou reported having no financial conflicts.

BERLIN – Recent evidence strongly suggests that enthesis-related arthritis in adolescents has two distinct clinical phenotypes, according to Dr. John Ioannou of University College London.

"The traditional view of enthesis-related arthritis has been that peripheral joint involvement and entheseal disease are common at presentation and then sacroiliitis occurs after many years as a late feature. I think that’s a paradigm that has been borne out not to be true. We can confidently shred that up and throw it away," he declared at the annual European Congress of Rheumatology.

The increasing use of MRI in the evaluation of patients who meet revised International League of Associations for Rheumatology diagnostic criteria for enthesis-related arthritis (ERA) has demonstrated that sacroiliitis appears early in the course of the disease in many of them. This early-onset sacroiliitis doesn’t show up on standard radiography, he explained.

ERA is an understudied subtype of juvenile idiopathic arthritis. The true incidence and prevalence of ERA aren’t known. Dr. Ioannou and his coworkers are conducting a long-term observational study at University College London. Analysis of the first 68 patients in the ERA cohort who have undergone MRI scanning indicated that 36, or 62%, had axial disease while the remainder did not.

The axial phenotype of ERA is characterized by a strong association with HLA-B27-positivity; more than 80% of patients with axial ERA were HLA-B27 positive, as was true for only a minority of those with the peripheral ERA phenotype. Extra-articular manifestations of ERA – inflammatory bowel disease and acute anterior uveitis – occurred only in HLA-B27-positive patients with axial disease.

Patients who were unaffected by axial disease had a strong proclivity for ankle arthritis, which was present in 80% of that group, compared with one-fourth of patients with axial ERA.

Fifty-eight of the 68 patients in the ERA cohort are male. Their median age at disease onset was 11 years and 1 month. The median time from disease onset to the appearance of inflammatory spinal symptoms was 2 years and 8 months.

The London experience matches that described by Italian investigators at the University of Florence, who are following a cohort of 59 patients with ERA. Twenty-one of the 59 reported symptoms of inflammatory back pain beginning a median of 1 year and 3 months after onset of ERA. MRI revealed the presence of sacroiliitis in 17 of the 21, all of whom had negative X-rays of the sacroiliac joints. As in the London series, the Italian patients with axial involvement were far more likely to be HLA-B27-positive, while those without axial disease had a greater frequency of ankle arthritis (J. Rheumatol. 2010;37:2395-401).

Twenty-nine of the 68 patients in the London cohort are on anti–tumor necrosis factor (anti-TNF) therapy plus methotrexate or another nonbiologic disease-modifying antirheumatic drug.

"Our anecdotal experience is that anti-TNF therapy tends to work pretty well in patients with ERA, but the remission rate is low. We’ve not been able to discontinue anti-TNF therapy in our patients," Dr. Ioannou noted.

This is consistent with the experience of a Dutch group. They reported that two-thirds of 22 ERA patients treated with an anti-TNF agent had inactive arthritis and enthesis after 15 months; however, none was able to discontinue biologic therapy without flaring of their disease (J. Rheumatol. 2011;38:2258-63).

The pathogenic mechanisms driving the two clinical patterns of ERA aren’t understood yet. Defining those mechanisms will provide a rationale for deciding on the best treatments for patients with one clinical phenotype or the other. At present, treatment is largely based upon extrapolation from data gathered in treating other forms of juvenile idiopathic arthritis or adult ankylosing spondylitis, the rheumatologist said.

Dr. Ioannou reported having no financial conflicts.

BERLIN – Recent evidence strongly suggests that enthesis-related arthritis in adolescents has two distinct clinical phenotypes, according to Dr. John Ioannou of University College London.

"The traditional view of enthesis-related arthritis has been that peripheral joint involvement and entheseal disease are common at presentation and then sacroiliitis occurs after many years as a late feature. I think that’s a paradigm that has been borne out not to be true. We can confidently shred that up and throw it away," he declared at the annual European Congress of Rheumatology.

The increasing use of MRI in the evaluation of patients who meet revised International League of Associations for Rheumatology diagnostic criteria for enthesis-related arthritis (ERA) has demonstrated that sacroiliitis appears early in the course of the disease in many of them. This early-onset sacroiliitis doesn’t show up on standard radiography, he explained.

ERA is an understudied subtype of juvenile idiopathic arthritis. The true incidence and prevalence of ERA aren’t known. Dr. Ioannou and his coworkers are conducting a long-term observational study at University College London. Analysis of the first 68 patients in the ERA cohort who have undergone MRI scanning indicated that 36, or 62%, had axial disease while the remainder did not.

The axial phenotype of ERA is characterized by a strong association with HLA-B27-positivity; more than 80% of patients with axial ERA were HLA-B27 positive, as was true for only a minority of those with the peripheral ERA phenotype. Extra-articular manifestations of ERA – inflammatory bowel disease and acute anterior uveitis – occurred only in HLA-B27-positive patients with axial disease.

Patients who were unaffected by axial disease had a strong proclivity for ankle arthritis, which was present in 80% of that group, compared with one-fourth of patients with axial ERA.

Fifty-eight of the 68 patients in the ERA cohort are male. Their median age at disease onset was 11 years and 1 month. The median time from disease onset to the appearance of inflammatory spinal symptoms was 2 years and 8 months.

The London experience matches that described by Italian investigators at the University of Florence, who are following a cohort of 59 patients with ERA. Twenty-one of the 59 reported symptoms of inflammatory back pain beginning a median of 1 year and 3 months after onset of ERA. MRI revealed the presence of sacroiliitis in 17 of the 21, all of whom had negative X-rays of the sacroiliac joints. As in the London series, the Italian patients with axial involvement were far more likely to be HLA-B27-positive, while those without axial disease had a greater frequency of ankle arthritis (J. Rheumatol. 2010;37:2395-401).

Twenty-nine of the 68 patients in the London cohort are on anti–tumor necrosis factor (anti-TNF) therapy plus methotrexate or another nonbiologic disease-modifying antirheumatic drug.

"Our anecdotal experience is that anti-TNF therapy tends to work pretty well in patients with ERA, but the remission rate is low. We’ve not been able to discontinue anti-TNF therapy in our patients," Dr. Ioannou noted.

This is consistent with the experience of a Dutch group. They reported that two-thirds of 22 ERA patients treated with an anti-TNF agent had inactive arthritis and enthesis after 15 months; however, none was able to discontinue biologic therapy without flaring of their disease (J. Rheumatol. 2011;38:2258-63).

The pathogenic mechanisms driving the two clinical patterns of ERA aren’t understood yet. Defining those mechanisms will provide a rationale for deciding on the best treatments for patients with one clinical phenotype or the other. At present, treatment is largely based upon extrapolation from data gathered in treating other forms of juvenile idiopathic arthritis or adult ankylosing spondylitis, the rheumatologist said.

Dr. Ioannou reported having no financial conflicts.

BERLIN – Medical therapy might prove to be the preferred approach for treating patients with early-stage Dupuytren’s contracture, suggest the findings of a small retrospective study.

Injection of collagenase Clostridium histolyticum in patients with early-stage Dupuytren’s contracture resulted in significantly better clinical outcomes than those that were seen in patients with advanced disease. Collagenase C. histolyticum (Xiaflex) injections are generally given only after patients with Dupuytren’s contracture develop fixed-flexion contracture angles of 30 degrees or more.

The retrospective study suggests a new treatment paradigm: The early injection of palpable cords with lesser fixed-flexion contracture angles results in near normal correction, bringing improvement that’s significantly greater than that achieved with delayed therapy, according to Dr. Clayton A. Peimer, an orthopedic surgeon at Michigan State University, East Lansing.

This is off-label therapy. At present, Xiaflex is approved in the United States and Europe under more restrictive conditions (injection of only a single palpable cord at a time, with a 4-week hiatus before either a repeat injection or an injection of another affected cord).

The finding warrants confirmation in prospective longitudinal studies aimed at determining whether collagenase injections into early-stage joints slows progression of Dupuytren’s contracture and improves upon the high contracture recurrence rate that follows surgical release, he added.

In a separate Australian study presented at the annual European Congress of Rheumatology, Dr. David Gilpin of the Brisbane (Queensland) Hand and Upper Limb Clinic reported that concurrent injections of collagenase C. histolyticum into two affected palpable cords in the same hand proved safe, effective, and well tolerated.

The advantages of being able to safely treat multiple contractures at the same time include shortened recovery times, fewer office visits for patients, and more efficient use of physicians’ time, noted Dr. Gilpin.

His study included 12 patients with three or more fixed-flexion contractures of 20% or greater in the proximal interphalangeal (PIP) and/or metacarpophalangeal (MP) joints on the same hand. The participants initially received a single collagenase injection in one palpable cord, followed roughly 24 hours later by the standard finger extension procedure that breaks the now-weakened cord. After 30 days, the patients received two injections into two different palpable cords on the same hand, followed by finger extension procedures the next day.

The first injection resulted in a mean 81% reduction in the degree of fixed-flexion contracture in treated MP joints, and a 66% decrease in PIP joints. The subsequent two concurrent injections of other affected cords showed near identical effectiveness (mean reduction in fixed-flexion contractures, 80% in MP and 63% in PIP joints).

Blood samples that were obtained 24 hours after the dual injections showed no detectable systemic levels of the biologic agent.

Not surprisingly, several treatment-related adverse events were more common when patients received two injections rather than one. These included injection site pain or discomfort, skin discoloration, itching, and blood blisters.

Dr. Peimer reviewed the charts of 302 patients with Dupuytren’s contracture who were treated with collagenase injections at 10 U.S. community and academic practices. Of affected joints, 20% were treated at an early stage (defined as a fixed-flexion contracture angle of 30 degrees or less). Their mean initial fixed-flexion contracture angle was 25 degrees, improving to 3.8 degrees after treatment. In contrast, the mean baseline fixed-flexion contracture angle in patients with advanced disease was 58 degrees, with an improvement to 14 degrees following collagenase treatment. No serious treatment-related adverse events occurred.

Dupuytren’s contracture is the result of a usually painless progressive thickening and shortening of the palmar fascia. This leads to curling of the fingers and impaired hand function. The most common surgical treatment, limited fasciectomy, can result in complications including digital nerve injury, hematoma, and complex regional pain syndrome. Xiaflex was approved in the United States in 2010 as the first nonsurgical treatment for Dupuytren’s contracture. European approval followed the next year.

The studies were sponsored by Auxillium Pharmaceuticals, which markets Xiaflex. Dr. Peimer and Dr. Gilpin were paid by the company for their research, and Dr. Gilpin owns stock in Auxillium.

BERLIN – Medical therapy might prove to be the preferred approach for treating patients with early-stage Dupuytren’s contracture, suggest the findings of a small retrospective study.

Injection of collagenase Clostridium histolyticum in patients with early-stage Dupuytren’s contracture resulted in significantly better clinical outcomes than those that were seen in patients with advanced disease. Collagenase C. histolyticum (Xiaflex) injections are generally given only after patients with Dupuytren’s contracture develop fixed-flexion contracture angles of 30 degrees or more.

The retrospective study suggests a new treatment paradigm: The early injection of palpable cords with lesser fixed-flexion contracture angles results in near normal correction, bringing improvement that’s significantly greater than that achieved with delayed therapy, according to Dr. Clayton A. Peimer, an orthopedic surgeon at Michigan State University, East Lansing.

This is off-label therapy. At present, Xiaflex is approved in the United States and Europe under more restrictive conditions (injection of only a single palpable cord at a time, with a 4-week hiatus before either a repeat injection or an injection of another affected cord).

The finding warrants confirmation in prospective longitudinal studies aimed at determining whether collagenase injections into early-stage joints slows progression of Dupuytren’s contracture and improves upon the high contracture recurrence rate that follows surgical release, he added.

In a separate Australian study presented at the annual European Congress of Rheumatology, Dr. David Gilpin of the Brisbane (Queensland) Hand and Upper Limb Clinic reported that concurrent injections of collagenase C. histolyticum into two affected palpable cords in the same hand proved safe, effective, and well tolerated.

The advantages of being able to safely treat multiple contractures at the same time include shortened recovery times, fewer office visits for patients, and more efficient use of physicians’ time, noted Dr. Gilpin.

His study included 12 patients with three or more fixed-flexion contractures of 20% or greater in the proximal interphalangeal (PIP) and/or metacarpophalangeal (MP) joints on the same hand. The participants initially received a single collagenase injection in one palpable cord, followed roughly 24 hours later by the standard finger extension procedure that breaks the now-weakened cord. After 30 days, the patients received two injections into two different palpable cords on the same hand, followed by finger extension procedures the next day.

The first injection resulted in a mean 81% reduction in the degree of fixed-flexion contracture in treated MP joints, and a 66% decrease in PIP joints. The subsequent two concurrent injections of other affected cords showed near identical effectiveness (mean reduction in fixed-flexion contractures, 80% in MP and 63% in PIP joints).

Blood samples that were obtained 24 hours after the dual injections showed no detectable systemic levels of the biologic agent.

Not surprisingly, several treatment-related adverse events were more common when patients received two injections rather than one. These included injection site pain or discomfort, skin discoloration, itching, and blood blisters.

Dr. Peimer reviewed the charts of 302 patients with Dupuytren’s contracture who were treated with collagenase injections at 10 U.S. community and academic practices. Of affected joints, 20% were treated at an early stage (defined as a fixed-flexion contracture angle of 30 degrees or less). Their mean initial fixed-flexion contracture angle was 25 degrees, improving to 3.8 degrees after treatment. In contrast, the mean baseline fixed-flexion contracture angle in patients with advanced disease was 58 degrees, with an improvement to 14 degrees following collagenase treatment. No serious treatment-related adverse events occurred.

Dupuytren’s contracture is the result of a usually painless progressive thickening and shortening of the palmar fascia. This leads to curling of the fingers and impaired hand function. The most common surgical treatment, limited fasciectomy, can result in complications including digital nerve injury, hematoma, and complex regional pain syndrome. Xiaflex was approved in the United States in 2010 as the first nonsurgical treatment for Dupuytren’s contracture. European approval followed the next year.

The studies were sponsored by Auxillium Pharmaceuticals, which markets Xiaflex. Dr. Peimer and Dr. Gilpin were paid by the company for their research, and Dr. Gilpin owns stock in Auxillium.

BERLIN – Medical therapy might prove to be the preferred approach for treating patients with early-stage Dupuytren’s contracture, suggest the findings of a small retrospective study.

Injection of collagenase Clostridium histolyticum in patients with early-stage Dupuytren’s contracture resulted in significantly better clinical outcomes than those that were seen in patients with advanced disease. Collagenase C. histolyticum (Xiaflex) injections are generally given only after patients with Dupuytren’s contracture develop fixed-flexion contracture angles of 30 degrees or more.

The retrospective study suggests a new treatment paradigm: The early injection of palpable cords with lesser fixed-flexion contracture angles results in near normal correction, bringing improvement that’s significantly greater than that achieved with delayed therapy, according to Dr. Clayton A. Peimer, an orthopedic surgeon at Michigan State University, East Lansing.

This is off-label therapy. At present, Xiaflex is approved in the United States and Europe under more restrictive conditions (injection of only a single palpable cord at a time, with a 4-week hiatus before either a repeat injection or an injection of another affected cord).

The finding warrants confirmation in prospective longitudinal studies aimed at determining whether collagenase injections into early-stage joints slows progression of Dupuytren’s contracture and improves upon the high contracture recurrence rate that follows surgical release, he added.

In a separate Australian study presented at the annual European Congress of Rheumatology, Dr. David Gilpin of the Brisbane (Queensland) Hand and Upper Limb Clinic reported that concurrent injections of collagenase C. histolyticum into two affected palpable cords in the same hand proved safe, effective, and well tolerated.

The advantages of being able to safely treat multiple contractures at the same time include shortened recovery times, fewer office visits for patients, and more efficient use of physicians’ time, noted Dr. Gilpin.

His study included 12 patients with three or more fixed-flexion contractures of 20% or greater in the proximal interphalangeal (PIP) and/or metacarpophalangeal (MP) joints on the same hand. The participants initially received a single collagenase injection in one palpable cord, followed roughly 24 hours later by the standard finger extension procedure that breaks the now-weakened cord. After 30 days, the patients received two injections into two different palpable cords on the same hand, followed by finger extension procedures the next day.

The first injection resulted in a mean 81% reduction in the degree of fixed-flexion contracture in treated MP joints, and a 66% decrease in PIP joints. The subsequent two concurrent injections of other affected cords showed near identical effectiveness (mean reduction in fixed-flexion contractures, 80% in MP and 63% in PIP joints).

Blood samples that were obtained 24 hours after the dual injections showed no detectable systemic levels of the biologic agent.

Not surprisingly, several treatment-related adverse events were more common when patients received two injections rather than one. These included injection site pain or discomfort, skin discoloration, itching, and blood blisters.

Dr. Peimer reviewed the charts of 302 patients with Dupuytren’s contracture who were treated with collagenase injections at 10 U.S. community and academic practices. Of affected joints, 20% were treated at an early stage (defined as a fixed-flexion contracture angle of 30 degrees or less). Their mean initial fixed-flexion contracture angle was 25 degrees, improving to 3.8 degrees after treatment. In contrast, the mean baseline fixed-flexion contracture angle in patients with advanced disease was 58 degrees, with an improvement to 14 degrees following collagenase treatment. No serious treatment-related adverse events occurred.

Dupuytren’s contracture is the result of a usually painless progressive thickening and shortening of the palmar fascia. This leads to curling of the fingers and impaired hand function. The most common surgical treatment, limited fasciectomy, can result in complications including digital nerve injury, hematoma, and complex regional pain syndrome. Xiaflex was approved in the United States in 2010 as the first nonsurgical treatment for Dupuytren’s contracture. European approval followed the next year.

The studies were sponsored by Auxillium Pharmaceuticals, which markets Xiaflex. Dr. Peimer and Dr. Gilpin were paid by the company for their research, and Dr. Gilpin owns stock in Auxillium.

BERLIN – Rheumatoid arthritis patients who respond favorably to a first course of rituximab and later need retreatment do as well with a follow-up single 1-g intravenous infusion as with the approved dosing regimen consisting of two 1-g infusions given 2 weeks apart, according to a randomized trial presented at the annual European Congress of Rheumatology.

The study findings point the way to a simpler, less costly, and more patient friendly dosing regimen than the one now contained in the product labeling, noted Dr. Maxime Dougados, professor of rheumatology at René Descartes University, Paris.

He presented data from a 2-year, prospective, multicenter, randomized, controlled trial involving 224 patients with moderate to severe RA that was inadequately responsive to antitumor necrosis factor–alpha therapy. All the study subjects had received a first induction cycle of rituximab (Rituxan) at the approved dosage of two 1-g intravenous infusions delivered 2 weeks apart.

The good or moderate response rate at 6 months by EULAR (European League Against Rheumatism) criteria was 71%. At that point, 100 responders were randomized to either open-label retreatment with the licensed regimen of two 1-g infusions 2 weeks apart or the investigational dose consisting of a single 1-g infusion.

Participants were reassessed for disease activity every 8 weeks. Additional retreatment with the assigned regimen was carried out as warranted by return of active RA, defined as a DAS28 (disease activity score based on a 28-joint count) greater than 3.2), as long as at least 6 months had elapsed since the last course of treatment.

The primary study end point was the area under the curve for the DAS28-CRP (C-reactive protein) score at week 104. It averaged 2,761 in the single-infusion retreatment group and was similar at 2,666 in the standard retreatment group, demonstrating the noninferiority of the investigational retreatment regimen.

The median time to a second retreatment was 263 days in the single-infusion group and similar at 255 days in the two-infusion group.

The safety profiles were comparable. Serious adverse events occurred in 29% of single-infusion retreatment patients over the course of the 2-year study, compared with 37% of those who received the approved two-infusion regimen. In all, 2% of patients in the single-infusion group had an IgG level less than 6.82 g/L (the lower limit of normal) at the 2-year mark, compared with 11% in the twin-infusion arm.

The serious infection rate was 7.2 per 100 person-years in the single-infusion group and 1.5 per 100 person-years in those retreated with two 1-g infusions 2 weeks apart.

A caveat regarding this study is that the radiographic or structural effect of the two retreatment strategies wasn’t assessed, the rheumatologist observed.

This clinical trial was supported by Roche. The presenter reported having received research grant support from the sponsor to conduct the study.

BERLIN – Rheumatoid arthritis patients who respond favorably to a first course of rituximab and later need retreatment do as well with a follow-up single 1-g intravenous infusion as with the approved dosing regimen consisting of two 1-g infusions given 2 weeks apart, according to a randomized trial presented at the annual European Congress of Rheumatology.

The study findings point the way to a simpler, less costly, and more patient friendly dosing regimen than the one now contained in the product labeling, noted Dr. Maxime Dougados, professor of rheumatology at René Descartes University, Paris.

He presented data from a 2-year, prospective, multicenter, randomized, controlled trial involving 224 patients with moderate to severe RA that was inadequately responsive to antitumor necrosis factor–alpha therapy. All the study subjects had received a first induction cycle of rituximab (Rituxan) at the approved dosage of two 1-g intravenous infusions delivered 2 weeks apart.

The good or moderate response rate at 6 months by EULAR (European League Against Rheumatism) criteria was 71%. At that point, 100 responders were randomized to either open-label retreatment with the licensed regimen of two 1-g infusions 2 weeks apart or the investigational dose consisting of a single 1-g infusion.

Participants were reassessed for disease activity every 8 weeks. Additional retreatment with the assigned regimen was carried out as warranted by return of active RA, defined as a DAS28 (disease activity score based on a 28-joint count) greater than 3.2), as long as at least 6 months had elapsed since the last course of treatment.

The primary study end point was the area under the curve for the DAS28-CRP (C-reactive protein) score at week 104. It averaged 2,761 in the single-infusion retreatment group and was similar at 2,666 in the standard retreatment group, demonstrating the noninferiority of the investigational retreatment regimen.

The median time to a second retreatment was 263 days in the single-infusion group and similar at 255 days in the two-infusion group.

The safety profiles were comparable. Serious adverse events occurred in 29% of single-infusion retreatment patients over the course of the 2-year study, compared with 37% of those who received the approved two-infusion regimen. In all, 2% of patients in the single-infusion group had an IgG level less than 6.82 g/L (the lower limit of normal) at the 2-year mark, compared with 11% in the twin-infusion arm.

The serious infection rate was 7.2 per 100 person-years in the single-infusion group and 1.5 per 100 person-years in those retreated with two 1-g infusions 2 weeks apart.

A caveat regarding this study is that the radiographic or structural effect of the two retreatment strategies wasn’t assessed, the rheumatologist observed.

This clinical trial was supported by Roche. The presenter reported having received research grant support from the sponsor to conduct the study.

BERLIN – Rheumatoid arthritis patients who respond favorably to a first course of rituximab and later need retreatment do as well with a follow-up single 1-g intravenous infusion as with the approved dosing regimen consisting of two 1-g infusions given 2 weeks apart, according to a randomized trial presented at the annual European Congress of Rheumatology.

The study findings point the way to a simpler, less costly, and more patient friendly dosing regimen than the one now contained in the product labeling, noted Dr. Maxime Dougados, professor of rheumatology at René Descartes University, Paris.

He presented data from a 2-year, prospective, multicenter, randomized, controlled trial involving 224 patients with moderate to severe RA that was inadequately responsive to antitumor necrosis factor–alpha therapy. All the study subjects had received a first induction cycle of rituximab (Rituxan) at the approved dosage of two 1-g intravenous infusions delivered 2 weeks apart.

The good or moderate response rate at 6 months by EULAR (European League Against Rheumatism) criteria was 71%. At that point, 100 responders were randomized to either open-label retreatment with the licensed regimen of two 1-g infusions 2 weeks apart or the investigational dose consisting of a single 1-g infusion.

Participants were reassessed for disease activity every 8 weeks. Additional retreatment with the assigned regimen was carried out as warranted by return of active RA, defined as a DAS28 (disease activity score based on a 28-joint count) greater than 3.2), as long as at least 6 months had elapsed since the last course of treatment.

The primary study end point was the area under the curve for the DAS28-CRP (C-reactive protein) score at week 104. It averaged 2,761 in the single-infusion retreatment group and was similar at 2,666 in the standard retreatment group, demonstrating the noninferiority of the investigational retreatment regimen.

The median time to a second retreatment was 263 days in the single-infusion group and similar at 255 days in the two-infusion group.

The safety profiles were comparable. Serious adverse events occurred in 29% of single-infusion retreatment patients over the course of the 2-year study, compared with 37% of those who received the approved two-infusion regimen. In all, 2% of patients in the single-infusion group had an IgG level less than 6.82 g/L (the lower limit of normal) at the 2-year mark, compared with 11% in the twin-infusion arm.

The serious infection rate was 7.2 per 100 person-years in the single-infusion group and 1.5 per 100 person-years in those retreated with two 1-g infusions 2 weeks apart.

A caveat regarding this study is that the radiographic or structural effect of the two retreatment strategies wasn’t assessed, the rheumatologist observed.

This clinical trial was supported by Roche. The presenter reported having received research grant support from the sponsor to conduct the study.

Medical students in the United Kingdom are not interested in making rheumatology a core part of their training, and some see time spent studying in the subspecialty as a "holiday," according to the results of a survey of 256 medical students presented at the annual European Congress of Rheumatology.

The results show that only about 9% of respondents (24 students) see rheumatology as a specialty that would be useful to study during their foundation years, the 2 years of study between medical school and specialty training. The top choices were acute medicine, emergency medicine, and surgery. When asked if they would consider rheumatology as one of the rotations during the foundation years, 53% said no. And 55% said they would not want to see more rheumatology posts be made available during the foundation years.

Dr. Thalia Roussou, a rheumatologist at BHRUT (Barking, Havering, and Redbridge University Hospitals in Essex, England) who designed the survey, said the results were both disappointing and surprising.

"We work toward inspiring people to careers in rheumatology, but whatever we’re doing is not working," said Dr. Roussou, who is also a clinical senior lecturer at Queen Mary University of London.

Part of the issue is the lack of exposure to rheumatology patients during the medical school years, she said in an interview.

Most students who responded to the 2009 online survey said they had limited exposure to rheumatology so far in their training. More than 60% reported they had received only 3 weeks of exposure to the subspecialty. Another 21% reported that they had no exposure to rheumatology. Dr. Roussou said it’s likely that students are underreporting their exposure, but it’s their perception, more than the reality, that matters in this case.

Respondents who answered open-ended questions about rheumatology said they shied away from the specialty because it seemed like a small, niche specialty that wasn’t relevant to their intended practice area.

Dr. Roussou reported that she had no relevant conflicts of interest.

Medical students in the United Kingdom are not interested in making rheumatology a core part of their training, and some see time spent studying in the subspecialty as a "holiday," according to the results of a survey of 256 medical students presented at the annual European Congress of Rheumatology.

The results show that only about 9% of respondents (24 students) see rheumatology as a specialty that would be useful to study during their foundation years, the 2 years of study between medical school and specialty training. The top choices were acute medicine, emergency medicine, and surgery. When asked if they would consider rheumatology as one of the rotations during the foundation years, 53% said no. And 55% said they would not want to see more rheumatology posts be made available during the foundation years.

Dr. Thalia Roussou, a rheumatologist at BHRUT (Barking, Havering, and Redbridge University Hospitals in Essex, England) who designed the survey, said the results were both disappointing and surprising.

"We work toward inspiring people to careers in rheumatology, but whatever we’re doing is not working," said Dr. Roussou, who is also a clinical senior lecturer at Queen Mary University of London.

Part of the issue is the lack of exposure to rheumatology patients during the medical school years, she said in an interview.

Most students who responded to the 2009 online survey said they had limited exposure to rheumatology so far in their training. More than 60% reported they had received only 3 weeks of exposure to the subspecialty. Another 21% reported that they had no exposure to rheumatology. Dr. Roussou said it’s likely that students are underreporting their exposure, but it’s their perception, more than the reality, that matters in this case.

Respondents who answered open-ended questions about rheumatology said they shied away from the specialty because it seemed like a small, niche specialty that wasn’t relevant to their intended practice area.

Dr. Roussou reported that she had no relevant conflicts of interest.

Medical students in the United Kingdom are not interested in making rheumatology a core part of their training, and some see time spent studying in the subspecialty as a "holiday," according to the results of a survey of 256 medical students presented at the annual European Congress of Rheumatology.

The results show that only about 9% of respondents (24 students) see rheumatology as a specialty that would be useful to study during their foundation years, the 2 years of study between medical school and specialty training. The top choices were acute medicine, emergency medicine, and surgery. When asked if they would consider rheumatology as one of the rotations during the foundation years, 53% said no. And 55% said they would not want to see more rheumatology posts be made available during the foundation years.

Dr. Thalia Roussou, a rheumatologist at BHRUT (Barking, Havering, and Redbridge University Hospitals in Essex, England) who designed the survey, said the results were both disappointing and surprising.

"We work toward inspiring people to careers in rheumatology, but whatever we’re doing is not working," said Dr. Roussou, who is also a clinical senior lecturer at Queen Mary University of London.

Part of the issue is the lack of exposure to rheumatology patients during the medical school years, she said in an interview.

Most students who responded to the 2009 online survey said they had limited exposure to rheumatology so far in their training. More than 60% reported they had received only 3 weeks of exposure to the subspecialty. Another 21% reported that they had no exposure to rheumatology. Dr. Roussou said it’s likely that students are underreporting their exposure, but it’s their perception, more than the reality, that matters in this case.

Respondents who answered open-ended questions about rheumatology said they shied away from the specialty because it seemed like a small, niche specialty that wasn’t relevant to their intended practice area.

Dr. Roussou reported that she had no relevant conflicts of interest.

BERLIN – The prevalence of major central nervous system manifestations in patients with systemic lupus erythematosus is considerably lower than commonly reported, according to a 3-year study presented at the annual European Congress of Rheumatology.

The prevalence of major CNS involvement was found to be "very low" at 4.3% (7.8 cases/100 person-years), "whilst in most studies when the prevalence of all CNS events is recorded, this figure can be between 15-40%," said Dr. Eleni Kampylafka of the pathophysiology department at the National University of Athens.

Previous studies of CNS involvement probably yielded high estimates because they did not tease out minor from major CNS events, clouding the true picture. "There are lots of nonspecific manifestations such as headache and mild depression, and we wanted to know the true prevalence of major events, which have an impact on the patient’s status and outcome," she said.

In the study, Dr. Kampylafka and her colleagues also investigated associations between CNS involvement, disease activity, and neuromyelitis optica (NMO)-IgG antibodies, which can be predictors of disease and are highly specific for both neuromyelitis optica and myelitis in lupus, though not lupus itself.

According to Dr. Kampylafka, minor CNS manifestations included headache, mild cognitive dysfunction, depression, and anxiety. Major CNS involvements were seizures, demyelinating syndrome, acute confusional state, psychosis, aseptic meningitis, chorea, myelopathy, and cerebral vascular events (mainly stroke).

From an initial cohort of 1,093 patients with systemic lupus erythematosus (SLE), the investigators focused on 458 patients who underwent regular follow-up for the 3 years. Only patients without a prior history of SLE-related CNS involvement were included, leaving 370 in the analysis.

Of these patients, 16 (4.3%) were found to have major CNS involvement. All CNS manifestations were recorded and codified according to American College of Rheumatology criteria, but minor CNS events were excluded. Furthermore, patients’ disease activity was evaluated using the ECLAM (European Consensus Lupus Activity Measurement) score and the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) SELENA Modification. Accumulated damage associated with the disease was assessed using the SLICC/ACR (Systemic Lupus International Collaborating Clinics/ACR) Damage Index.

Patients were routinely assessed for 3 years using clinical, laboratory, neurological, serological, and immunological tests. "Whenever a new CNS event occurred, an expert neurologist conducted neurological tests with magnetic resonance imaging, electroencephalograms, and cerebrospinal fluid studies, if necessary," reported Dr. Kampylafka.

Out of a total of 23 CNS events, the most common were epileptic seizures (35%), strokes (26%), and myelopathy (22%).

"We also found that nearly half of our patients presented their CNS event at diagnosis," she noted. "This shows that CNS involvement is an early event in lupus, which is something expected."

There was a stark contrast in disease activity measures between patients with CNS involvement and those without it. Lupus patients with CNS involvement had a mean ECLAM score of 4.8, versus 1.4 in patients who lacked CNS involvement (P less than .001). The mean SLEDAI score was 18 in lupus patients with CNS involvement, in contrast to 3 in patients without CNS involvement (P less than .001).

"An important finding here is the presence of NMO-IgG antibodies, which have been shown to exist in patients with lupus and myelopathy specifically, which is a subgroup of manifestations in the disease," said Dr. Kampylafka.

Epileptic seizures correlated with a high ECLAM/SLEDAI score; myelopathy correlated with low ECLAM/SLEDAI scores and NMO-IgG antibody levels; and strokes correlated with antiphospholipid syndrome.

Dr. Kampylafka concluded that overall, the study results demonstrate that CNS involvement correlates with high disease activity at the time of its appearance. But she added a note of caution: Patients presenting with a neurological complication should always receive a complete assessment, because the event might not be related to the patient’s lupus.

Dr. Kampylafka reported having no conflicts of interest.

BERLIN – The prevalence of major central nervous system manifestations in patients with systemic lupus erythematosus is considerably lower than commonly reported, according to a 3-year study presented at the annual European Congress of Rheumatology.

The prevalence of major CNS involvement was found to be "very low" at 4.3% (7.8 cases/100 person-years), "whilst in most studies when the prevalence of all CNS events is recorded, this figure can be between 15-40%," said Dr. Eleni Kampylafka of the pathophysiology department at the National University of Athens.

Previous studies of CNS involvement probably yielded high estimates because they did not tease out minor from major CNS events, clouding the true picture. "There are lots of nonspecific manifestations such as headache and mild depression, and we wanted to know the true prevalence of major events, which have an impact on the patient’s status and outcome," she said.

In the study, Dr. Kampylafka and her colleagues also investigated associations between CNS involvement, disease activity, and neuromyelitis optica (NMO)-IgG antibodies, which can be predictors of disease and are highly specific for both neuromyelitis optica and myelitis in lupus, though not lupus itself.

According to Dr. Kampylafka, minor CNS manifestations included headache, mild cognitive dysfunction, depression, and anxiety. Major CNS involvements were seizures, demyelinating syndrome, acute confusional state, psychosis, aseptic meningitis, chorea, myelopathy, and cerebral vascular events (mainly stroke).

From an initial cohort of 1,093 patients with systemic lupus erythematosus (SLE), the investigators focused on 458 patients who underwent regular follow-up for the 3 years. Only patients without a prior history of SLE-related CNS involvement were included, leaving 370 in the analysis.

Of these patients, 16 (4.3%) were found to have major CNS involvement. All CNS manifestations were recorded and codified according to American College of Rheumatology criteria, but minor CNS events were excluded. Furthermore, patients’ disease activity was evaluated using the ECLAM (European Consensus Lupus Activity Measurement) score and the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) SELENA Modification. Accumulated damage associated with the disease was assessed using the SLICC/ACR (Systemic Lupus International Collaborating Clinics/ACR) Damage Index.

Patients were routinely assessed for 3 years using clinical, laboratory, neurological, serological, and immunological tests. "Whenever a new CNS event occurred, an expert neurologist conducted neurological tests with magnetic resonance imaging, electroencephalograms, and cerebrospinal fluid studies, if necessary," reported Dr. Kampylafka.

Out of a total of 23 CNS events, the most common were epileptic seizures (35%), strokes (26%), and myelopathy (22%).

"We also found that nearly half of our patients presented their CNS event at diagnosis," she noted. "This shows that CNS involvement is an early event in lupus, which is something expected."

There was a stark contrast in disease activity measures between patients with CNS involvement and those without it. Lupus patients with CNS involvement had a mean ECLAM score of 4.8, versus 1.4 in patients who lacked CNS involvement (P less than .001). The mean SLEDAI score was 18 in lupus patients with CNS involvement, in contrast to 3 in patients without CNS involvement (P less than .001).

"An important finding here is the presence of NMO-IgG antibodies, which have been shown to exist in patients with lupus and myelopathy specifically, which is a subgroup of manifestations in the disease," said Dr. Kampylafka.

Epileptic seizures correlated with a high ECLAM/SLEDAI score; myelopathy correlated with low ECLAM/SLEDAI scores and NMO-IgG antibody levels; and strokes correlated with antiphospholipid syndrome.

Dr. Kampylafka concluded that overall, the study results demonstrate that CNS involvement correlates with high disease activity at the time of its appearance. But she added a note of caution: Patients presenting with a neurological complication should always receive a complete assessment, because the event might not be related to the patient’s lupus.

Dr. Kampylafka reported having no conflicts of interest.

BERLIN – The prevalence of major central nervous system manifestations in patients with systemic lupus erythematosus is considerably lower than commonly reported, according to a 3-year study presented at the annual European Congress of Rheumatology.

The prevalence of major CNS involvement was found to be "very low" at 4.3% (7.8 cases/100 person-years), "whilst in most studies when the prevalence of all CNS events is recorded, this figure can be between 15-40%," said Dr. Eleni Kampylafka of the pathophysiology department at the National University of Athens.

Previous studies of CNS involvement probably yielded high estimates because they did not tease out minor from major CNS events, clouding the true picture. "There are lots of nonspecific manifestations such as headache and mild depression, and we wanted to know the true prevalence of major events, which have an impact on the patient’s status and outcome," she said.

In the study, Dr. Kampylafka and her colleagues also investigated associations between CNS involvement, disease activity, and neuromyelitis optica (NMO)-IgG antibodies, which can be predictors of disease and are highly specific for both neuromyelitis optica and myelitis in lupus, though not lupus itself.

According to Dr. Kampylafka, minor CNS manifestations included headache, mild cognitive dysfunction, depression, and anxiety. Major CNS involvements were seizures, demyelinating syndrome, acute confusional state, psychosis, aseptic meningitis, chorea, myelopathy, and cerebral vascular events (mainly stroke).

From an initial cohort of 1,093 patients with systemic lupus erythematosus (SLE), the investigators focused on 458 patients who underwent regular follow-up for the 3 years. Only patients without a prior history of SLE-related CNS involvement were included, leaving 370 in the analysis.

Of these patients, 16 (4.3%) were found to have major CNS involvement. All CNS manifestations were recorded and codified according to American College of Rheumatology criteria, but minor CNS events were excluded. Furthermore, patients’ disease activity was evaluated using the ECLAM (European Consensus Lupus Activity Measurement) score and the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) SELENA Modification. Accumulated damage associated with the disease was assessed using the SLICC/ACR (Systemic Lupus International Collaborating Clinics/ACR) Damage Index.

Patients were routinely assessed for 3 years using clinical, laboratory, neurological, serological, and immunological tests. "Whenever a new CNS event occurred, an expert neurologist conducted neurological tests with magnetic resonance imaging, electroencephalograms, and cerebrospinal fluid studies, if necessary," reported Dr. Kampylafka.

Out of a total of 23 CNS events, the most common were epileptic seizures (35%), strokes (26%), and myelopathy (22%).

"We also found that nearly half of our patients presented their CNS event at diagnosis," she noted. "This shows that CNS involvement is an early event in lupus, which is something expected."

There was a stark contrast in disease activity measures between patients with CNS involvement and those without it. Lupus patients with CNS involvement had a mean ECLAM score of 4.8, versus 1.4 in patients who lacked CNS involvement (P less than .001). The mean SLEDAI score was 18 in lupus patients with CNS involvement, in contrast to 3 in patients without CNS involvement (P less than .001).

"An important finding here is the presence of NMO-IgG antibodies, which have been shown to exist in patients with lupus and myelopathy specifically, which is a subgroup of manifestations in the disease," said Dr. Kampylafka.

Epileptic seizures correlated with a high ECLAM/SLEDAI score; myelopathy correlated with low ECLAM/SLEDAI scores and NMO-IgG antibody levels; and strokes correlated with antiphospholipid syndrome.

Dr. Kampylafka concluded that overall, the study results demonstrate that CNS involvement correlates with high disease activity at the time of its appearance. But she added a note of caution: Patients presenting with a neurological complication should always receive a complete assessment, because the event might not be related to the patient’s lupus.

Dr. Kampylafka reported having no conflicts of interest.

BERLIN – Patients with childhood primary angiitis of the central nervous system are at elevated risk for poor cognitive outcome, and the risk is highest by far in the subgroup with small-vessel disease presenting with seizures.

In the years since use of immunosuppressive therapy has become common, mortality among affected children has lessened. "Most children survive. However, in day-to-day clinical practice, it’s our observation that what matters most to parents of these children is their long-term cognitive outcome. Parents ask us, ‘Will our child attend a regular school? Will our child achieve the same levels of academic performance and social and vocational accomplishments as their siblings?’ " observed Dr. Peter Gowdie of the University of Toronto Hospital for Sick Children.

He and his coinvestigators sought answers to these questions in their single-center, retrospective, cohort study involving 63 patients with childhood primary angiitis of the CNS (cPACNS) without known premorbid cognitive deficits. Nineteen children had the small-vessel subtype, which is angiography negative and requires brain biopsy for diagnosis. Forty-four had large-vessel disease, which is identifiable on angiography and for which brain biopsy is therefore not indicated.

The median age at diagnosis was 8.1 years, with a median time to cognitive testing of 14.8 months.

Patients with large- and small-vessel cPACNS differed in several key ways in terms of clinical presentation, as previously noted in other studies.

Neurocognitive testing was carried out using the Wechsler Intelligence Scale for Children (WISC), a comprehensive battery of 10 subtests assessing a variety of domains.

Scores of 85-115 on the full scale IQ portion of the WISC are considered within average range. The majority of children with small-vessel cPACNS – 53% to be exact – scored below 85, which indicates global cognitive impairment. This was twice the rate seen in children with large-vessel disease. The mean full-scale IQ score in patients with small-vessel cPACNS was 82, compared with 97 in those with large-vessel disease.

The specific cognitive domains where patients with small-vessel disease were disadvantaged were verbal comprehension, with a mean score of 91 compared with 101 in youngsters with large-vessel disease; processing speed, where the difference in mean scores was 83 versus 96; and working memory, on which patients with small-vessel cPACNS had an average score of 81 compared with 96 in those with large-vessel disease.

"Neurocognitive testing is helpful in determining the cognitive burden of cPACNS. Characterization of the cognitive deficits may be helpful in tailoring early rehabilitation interventions," the rheumatologist said.

Patients with large-vessel cPACNS and no seizures had an average Full Scale IQ score of 99. IQ scores were slightly but not significantly lower in those with large-vessel disease who presented with seizures as well as in those with small-vessel disease and no seizures. However, the mean full-scale IQ score was 79 in patients with small-vessel cPACNS who presented with seizures.

Dr. Gowdie reported having no financial conflicts of interest.

BERLIN – Patients with childhood primary angiitis of the central nervous system are at elevated risk for poor cognitive outcome, and the risk is highest by far in the subgroup with small-vessel disease presenting with seizures.

In the years since use of immunosuppressive therapy has become common, mortality among affected children has lessened. "Most children survive. However, in day-to-day clinical practice, it’s our observation that what matters most to parents of these children is their long-term cognitive outcome. Parents ask us, ‘Will our child attend a regular school? Will our child achieve the same levels of academic performance and social and vocational accomplishments as their siblings?’ " observed Dr. Peter Gowdie of the University of Toronto Hospital for Sick Children.

He and his coinvestigators sought answers to these questions in their single-center, retrospective, cohort study involving 63 patients with childhood primary angiitis of the CNS (cPACNS) without known premorbid cognitive deficits. Nineteen children had the small-vessel subtype, which is angiography negative and requires brain biopsy for diagnosis. Forty-four had large-vessel disease, which is identifiable on angiography and for which brain biopsy is therefore not indicated.

The median age at diagnosis was 8.1 years, with a median time to cognitive testing of 14.8 months.

Patients with large- and small-vessel cPACNS differed in several key ways in terms of clinical presentation, as previously noted in other studies.

Neurocognitive testing was carried out using the Wechsler Intelligence Scale for Children (WISC), a comprehensive battery of 10 subtests assessing a variety of domains.

Scores of 85-115 on the full scale IQ portion of the WISC are considered within average range. The majority of children with small-vessel cPACNS – 53% to be exact – scored below 85, which indicates global cognitive impairment. This was twice the rate seen in children with large-vessel disease. The mean full-scale IQ score in patients with small-vessel cPACNS was 82, compared with 97 in those with large-vessel disease.

The specific cognitive domains where patients with small-vessel disease were disadvantaged were verbal comprehension, with a mean score of 91 compared with 101 in youngsters with large-vessel disease; processing speed, where the difference in mean scores was 83 versus 96; and working memory, on which patients with small-vessel cPACNS had an average score of 81 compared with 96 in those with large-vessel disease.

"Neurocognitive testing is helpful in determining the cognitive burden of cPACNS. Characterization of the cognitive deficits may be helpful in tailoring early rehabilitation interventions," the rheumatologist said.

Patients with large-vessel cPACNS and no seizures had an average Full Scale IQ score of 99. IQ scores were slightly but not significantly lower in those with large-vessel disease who presented with seizures as well as in those with small-vessel disease and no seizures. However, the mean full-scale IQ score was 79 in patients with small-vessel cPACNS who presented with seizures.

Dr. Gowdie reported having no financial conflicts of interest.

BERLIN – Patients with childhood primary angiitis of the central nervous system are at elevated risk for poor cognitive outcome, and the risk is highest by far in the subgroup with small-vessel disease presenting with seizures.

In the years since use of immunosuppressive therapy has become common, mortality among affected children has lessened. "Most children survive. However, in day-to-day clinical practice, it’s our observation that what matters most to parents of these children is their long-term cognitive outcome. Parents ask us, ‘Will our child attend a regular school? Will our child achieve the same levels of academic performance and social and vocational accomplishments as their siblings?’ " observed Dr. Peter Gowdie of the University of Toronto Hospital for Sick Children.

He and his coinvestigators sought answers to these questions in their single-center, retrospective, cohort study involving 63 patients with childhood primary angiitis of the CNS (cPACNS) without known premorbid cognitive deficits. Nineteen children had the small-vessel subtype, which is angiography negative and requires brain biopsy for diagnosis. Forty-four had large-vessel disease, which is identifiable on angiography and for which brain biopsy is therefore not indicated.

The median age at diagnosis was 8.1 years, with a median time to cognitive testing of 14.8 months.

Patients with large- and small-vessel cPACNS differed in several key ways in terms of clinical presentation, as previously noted in other studies.

Neurocognitive testing was carried out using the Wechsler Intelligence Scale for Children (WISC), a comprehensive battery of 10 subtests assessing a variety of domains.

Scores of 85-115 on the full scale IQ portion of the WISC are considered within average range. The majority of children with small-vessel cPACNS – 53% to be exact – scored below 85, which indicates global cognitive impairment. This was twice the rate seen in children with large-vessel disease. The mean full-scale IQ score in patients with small-vessel cPACNS was 82, compared with 97 in those with large-vessel disease.

The specific cognitive domains where patients with small-vessel disease were disadvantaged were verbal comprehension, with a mean score of 91 compared with 101 in youngsters with large-vessel disease; processing speed, where the difference in mean scores was 83 versus 96; and working memory, on which patients with small-vessel cPACNS had an average score of 81 compared with 96 in those with large-vessel disease.

"Neurocognitive testing is helpful in determining the cognitive burden of cPACNS. Characterization of the cognitive deficits may be helpful in tailoring early rehabilitation interventions," the rheumatologist said.

Patients with large-vessel cPACNS and no seizures had an average Full Scale IQ score of 99. IQ scores were slightly but not significantly lower in those with large-vessel disease who presented with seizures as well as in those with small-vessel disease and no seizures. However, the mean full-scale IQ score was 79 in patients with small-vessel cPACNS who presented with seizures.

Dr. Gowdie reported having no financial conflicts of interest.

BERLIN – Multiple tooth loss appears to be a marker for increased risk of subsequent rheumatoid arthritis – and the more missing teeth, the higher the arthritis disease activity and the worse the treatment response, according to studies presented at the annual European Congress of Rheumatology.

Tooth loss is considered a surrogate marker for periodontitis, a common chronic inflammatory process involving the gums and other tooth-supporting structures. Investigators are increasingly interested in exploring a possible causal relationship between this oral disease and chronic diseases elsewhere in the body having a prominent systemic inflammatory component, including coronary artery disease and rheumatoid arthritis (RA).

Dr. Gisela Westhoff reported on 540 patients with early arthritis participating in the ongoing observational CAPEA (Course and Prognosis of Early Arthritis) study. Patients averaged 56 years of age, with a mean symptom duration of 13 weeks at enrollment. A total of 59% were negative for rheumatoid factor and/or positive for anti–citrullinated protein antibody, 67% met current diagnostic criteria for RA, and 87% were on disease-modifying antirheumatic drugs.

At 6 months, 52% of the patients achieved a good response to treatment according to EULAR response criteria. Another 32% had a moderate response, and 16% had no response.

Patients had a mean of 19 teeth at enrollment. In all, 24% of subjects had 10 or fewer teeth, 15% had 11-20, and 22% had 28 or more teeth. Patients missing teeth tended to be older, heavier, and smokers. At 6 months of follow-up, those with 10 or fewer teeth had a significantly greater erythrocyte sedimentation rate, higher tender and swollen joint counts, and a higher Disease Activity Score-28 than did those with more than 10 teeth.

In a multivariate analysis adjusted for age, body mass index, and other potential confounders, patients with 10 or fewer teeth at baseline were 3.8 times as likely to have an insufficient treatment response as those with at least 28 teeth. The only other significant predictor of poor therapeutic response was smoking, which was associated with a 1.7-fold increased likelihood, noted Dr. Westhoff of the German Rheumatism Research Center in Berlin.

In a separate presentation, Dr. Axel Finckh of University Hospital, Geneva, reported that tooth loss was associated with swollen joints in a group of healthy individuals at increased risk of developing RA.

He presented data from an ongoing prospective observational study of 366 first-degree relatives of patients with RA. All were healthy at enrollment, at which time they had a mean of 28 teeth. Six percent had 20 or fewer teeth, 20% had 21-27, and 28% had a full complement of 32 teeth.

Subjects with one or more swollen joints on physical examination had an average of 26 teeth, compared with 29 teeth for those with no swollen joints. In a multivariate analysis, patients with less than 20 teeth were at 8.1-fold greater risk of having at least one swollen joint than those with 32 teeth. Individuals with 20-28 teeth were at 4.1-fold increased likelihood, while those with 28-31 teeth were at 3.6-fold increased risk.

Moreover, participants with less than 20 teeth had an adjusted 5.3-fold increased likelihood of having morning stiffness lasting more than 1 hour for at least 6 weeks than subjects with 32 teeth.

This study was sponsored by the Swiss League Against Rheumatism. Neither Dr. Finckh nor Dr. Westhoff reported having any financial conflicts.

BERLIN – Multiple tooth loss appears to be a marker for increased risk of subsequent rheumatoid arthritis – and the more missing teeth, the higher the arthritis disease activity and the worse the treatment response, according to studies presented at the annual European Congress of Rheumatology.

Tooth loss is considered a surrogate marker for periodontitis, a common chronic inflammatory process involving the gums and other tooth-supporting structures. Investigators are increasingly interested in exploring a possible causal relationship between this oral disease and chronic diseases elsewhere in the body having a prominent systemic inflammatory component, including coronary artery disease and rheumatoid arthritis (RA).

Dr. Gisela Westhoff reported on 540 patients with early arthritis participating in the ongoing observational CAPEA (Course and Prognosis of Early Arthritis) study. Patients averaged 56 years of age, with a mean symptom duration of 13 weeks at enrollment. A total of 59% were negative for rheumatoid factor and/or positive for anti–citrullinated protein antibody, 67% met current diagnostic criteria for RA, and 87% were on disease-modifying antirheumatic drugs.

At 6 months, 52% of the patients achieved a good response to treatment according to EULAR response criteria. Another 32% had a moderate response, and 16% had no response.

Patients had a mean of 19 teeth at enrollment. In all, 24% of subjects had 10 or fewer teeth, 15% had 11-20, and 22% had 28 or more teeth. Patients missing teeth tended to be older, heavier, and smokers. At 6 months of follow-up, those with 10 or fewer teeth had a significantly greater erythrocyte sedimentation rate, higher tender and swollen joint counts, and a higher Disease Activity Score-28 than did those with more than 10 teeth.

In a multivariate analysis adjusted for age, body mass index, and other potential confounders, patients with 10 or fewer teeth at baseline were 3.8 times as likely to have an insufficient treatment response as those with at least 28 teeth. The only other significant predictor of poor therapeutic response was smoking, which was associated with a 1.7-fold increased likelihood, noted Dr. Westhoff of the German Rheumatism Research Center in Berlin.

In a separate presentation, Dr. Axel Finckh of University Hospital, Geneva, reported that tooth loss was associated with swollen joints in a group of healthy individuals at increased risk of developing RA.

He presented data from an ongoing prospective observational study of 366 first-degree relatives of patients with RA. All were healthy at enrollment, at which time they had a mean of 28 teeth. Six percent had 20 or fewer teeth, 20% had 21-27, and 28% had a full complement of 32 teeth.

Subjects with one or more swollen joints on physical examination had an average of 26 teeth, compared with 29 teeth for those with no swollen joints. In a multivariate analysis, patients with less than 20 teeth were at 8.1-fold greater risk of having at least one swollen joint than those with 32 teeth. Individuals with 20-28 teeth were at 4.1-fold increased likelihood, while those with 28-31 teeth were at 3.6-fold increased risk.

Moreover, participants with less than 20 teeth had an adjusted 5.3-fold increased likelihood of having morning stiffness lasting more than 1 hour for at least 6 weeks than subjects with 32 teeth.

This study was sponsored by the Swiss League Against Rheumatism. Neither Dr. Finckh nor Dr. Westhoff reported having any financial conflicts.

BERLIN – Multiple tooth loss appears to be a marker for increased risk of subsequent rheumatoid arthritis – and the more missing teeth, the higher the arthritis disease activity and the worse the treatment response, according to studies presented at the annual European Congress of Rheumatology.

Tooth loss is considered a surrogate marker for periodontitis, a common chronic inflammatory process involving the gums and other tooth-supporting structures. Investigators are increasingly interested in exploring a possible causal relationship between this oral disease and chronic diseases elsewhere in the body having a prominent systemic inflammatory component, including coronary artery disease and rheumatoid arthritis (RA).

Dr. Gisela Westhoff reported on 540 patients with early arthritis participating in the ongoing observational CAPEA (Course and Prognosis of Early Arthritis) study. Patients averaged 56 years of age, with a mean symptom duration of 13 weeks at enrollment. A total of 59% were negative for rheumatoid factor and/or positive for anti–citrullinated protein antibody, 67% met current diagnostic criteria for RA, and 87% were on disease-modifying antirheumatic drugs.

At 6 months, 52% of the patients achieved a good response to treatment according to EULAR response criteria. Another 32% had a moderate response, and 16% had no response.

Patients had a mean of 19 teeth at enrollment. In all, 24% of subjects had 10 or fewer teeth, 15% had 11-20, and 22% had 28 or more teeth. Patients missing teeth tended to be older, heavier, and smokers. At 6 months of follow-up, those with 10 or fewer teeth had a significantly greater erythrocyte sedimentation rate, higher tender and swollen joint counts, and a higher Disease Activity Score-28 than did those with more than 10 teeth.

In a multivariate analysis adjusted for age, body mass index, and other potential confounders, patients with 10 or fewer teeth at baseline were 3.8 times as likely to have an insufficient treatment response as those with at least 28 teeth. The only other significant predictor of poor therapeutic response was smoking, which was associated with a 1.7-fold increased likelihood, noted Dr. Westhoff of the German Rheumatism Research Center in Berlin.

In a separate presentation, Dr. Axel Finckh of University Hospital, Geneva, reported that tooth loss was associated with swollen joints in a group of healthy individuals at increased risk of developing RA.

He presented data from an ongoing prospective observational study of 366 first-degree relatives of patients with RA. All were healthy at enrollment, at which time they had a mean of 28 teeth. Six percent had 20 or fewer teeth, 20% had 21-27, and 28% had a full complement of 32 teeth.

Subjects with one or more swollen joints on physical examination had an average of 26 teeth, compared with 29 teeth for those with no swollen joints. In a multivariate analysis, patients with less than 20 teeth were at 8.1-fold greater risk of having at least one swollen joint than those with 32 teeth. Individuals with 20-28 teeth were at 4.1-fold increased likelihood, while those with 28-31 teeth were at 3.6-fold increased risk.

Moreover, participants with less than 20 teeth had an adjusted 5.3-fold increased likelihood of having morning stiffness lasting more than 1 hour for at least 6 weeks than subjects with 32 teeth.

This study was sponsored by the Swiss League Against Rheumatism. Neither Dr. Finckh nor Dr. Westhoff reported having any financial conflicts.

BERLIN – Traumeel ointment and gel proved equal to diclofenac gel 1% in achieving pain reduction and improved joint function in patients with acute ankle sprain, according to a large randomized trial presented at the annual European Congress of Rheumatology.

The Traumeel Acute Ankle Sprain Study (TAASS) was a multicenter, double-blind clinical trial of 449 physically active patients aged 18-40 years with a grade 1 or 2 acute lateral ankle sprain. They were randomized to 2 g of Traumeel ointment, Traumeel gel, or diclofenac 1% gel applied three times daily for 2 weeks.

Traumeel is an over-the-counter homeopathic remedy containing a proprietary mix of 12 medicinal herbs, including arnica, calendula, hypericum, chamomile, witch hazel, belladonna, and monkshood, as well as two minerals. It is available in the United States and more than 60 other countries. Diclofenac gel 1% (Voltaren), in contrast, is a prescription medication that is approved for treating osteoarthritic joints.

Dr. Carlos G. de Vega explained that TAASS had two primary end points. One was change in self-assessed ankle pain between baseline and day 7 on a 0-100 visual analog scale. The Traumeel ointment group had a median 61% reduction from a baseline pain score of 53. Patients on Traumeel gel averaged a 71% reduction, while the diclofenac gel group had a median 69% reduction.

Total pain relief was reported on day 7 by 8.5% of the Traumeel ointment group, 5.0% of patients on Traumeel gel, and 5.9% on topical diclofenac.

The other primary end point in TAASS was change in the Activities of Daily Living 0-100 subscale of the Foot and Ankle Ability Measurement between baseline and day 7. The Traumeel ointment group improved by a median of 26.2 points from a baseline score of 51. The Traumeel gel group also improved by a median of 26.2 points, while the diclofenac gel group improved by 25 points, reported Dr. de Vega of the Medyr Clinic in Madrid.

At 6 weeks of follow-up, all participants reported total pain relief and normal functioning. The median time to normal activity was 19.1 days in the Traumeel ointment group and 19.4 days in each of the other two study arms.

All treatments were similarly well tolerated.

The clinical relevance of the TAASS findings lies in the fact that acute lateral ankle sprain is the most common ligamentous injury caused by sports and other physical activity. And a significant proportion of patients are more favorably disposed to a "natural" herbal therapy than to prescription medications, Dr. de Vega noted.

He reported receiving a research grant from Biologische Heilmittel Heel, which sponsored TAASS.

BERLIN – Traumeel ointment and gel proved equal to diclofenac gel 1% in achieving pain reduction and improved joint function in patients with acute ankle sprain, according to a large randomized trial presented at the annual European Congress of Rheumatology.

The Traumeel Acute Ankle Sprain Study (TAASS) was a multicenter, double-blind clinical trial of 449 physically active patients aged 18-40 years with a grade 1 or 2 acute lateral ankle sprain. They were randomized to 2 g of Traumeel ointment, Traumeel gel, or diclofenac 1% gel applied three times daily for 2 weeks.

Traumeel is an over-the-counter homeopathic remedy containing a proprietary mix of 12 medicinal herbs, including arnica, calendula, hypericum, chamomile, witch hazel, belladonna, and monkshood, as well as two minerals. It is available in the United States and more than 60 other countries. Diclofenac gel 1% (Voltaren), in contrast, is a prescription medication that is approved for treating osteoarthritic joints.

Dr. Carlos G. de Vega explained that TAASS had two primary end points. One was change in self-assessed ankle pain between baseline and day 7 on a 0-100 visual analog scale. The Traumeel ointment group had a median 61% reduction from a baseline pain score of 53. Patients on Traumeel gel averaged a 71% reduction, while the diclofenac gel group had a median 69% reduction.

Total pain relief was reported on day 7 by 8.5% of the Traumeel ointment group, 5.0% of patients on Traumeel gel, and 5.9% on topical diclofenac.

The other primary end point in TAASS was change in the Activities of Daily Living 0-100 subscale of the Foot and Ankle Ability Measurement between baseline and day 7. The Traumeel ointment group improved by a median of 26.2 points from a baseline score of 51. The Traumeel gel group also improved by a median of 26.2 points, while the diclofenac gel group improved by 25 points, reported Dr. de Vega of the Medyr Clinic in Madrid.

At 6 weeks of follow-up, all participants reported total pain relief and normal functioning. The median time to normal activity was 19.1 days in the Traumeel ointment group and 19.4 days in each of the other two study arms.

All treatments were similarly well tolerated.

The clinical relevance of the TAASS findings lies in the fact that acute lateral ankle sprain is the most common ligamentous injury caused by sports and other physical activity. And a significant proportion of patients are more favorably disposed to a "natural" herbal therapy than to prescription medications, Dr. de Vega noted.

He reported receiving a research grant from Biologische Heilmittel Heel, which sponsored TAASS.

BERLIN – Traumeel ointment and gel proved equal to diclofenac gel 1% in achieving pain reduction and improved joint function in patients with acute ankle sprain, according to a large randomized trial presented at the annual European Congress of Rheumatology.

The Traumeel Acute Ankle Sprain Study (TAASS) was a multicenter, double-blind clinical trial of 449 physically active patients aged 18-40 years with a grade 1 or 2 acute lateral ankle sprain. They were randomized to 2 g of Traumeel ointment, Traumeel gel, or diclofenac 1% gel applied three times daily for 2 weeks.

Traumeel is an over-the-counter homeopathic remedy containing a proprietary mix of 12 medicinal herbs, including arnica, calendula, hypericum, chamomile, witch hazel, belladonna, and monkshood, as well as two minerals. It is available in the United States and more than 60 other countries. Diclofenac gel 1% (Voltaren), in contrast, is a prescription medication that is approved for treating osteoarthritic joints.

Dr. Carlos G. de Vega explained that TAASS had two primary end points. One was change in self-assessed ankle pain between baseline and day 7 on a 0-100 visual analog scale. The Traumeel ointment group had a median 61% reduction from a baseline pain score of 53. Patients on Traumeel gel averaged a 71% reduction, while the diclofenac gel group had a median 69% reduction.

Total pain relief was reported on day 7 by 8.5% of the Traumeel ointment group, 5.0% of patients on Traumeel gel, and 5.9% on topical diclofenac.

The other primary end point in TAASS was change in the Activities of Daily Living 0-100 subscale of the Foot and Ankle Ability Measurement between baseline and day 7. The Traumeel ointment group improved by a median of 26.2 points from a baseline score of 51. The Traumeel gel group also improved by a median of 26.2 points, while the diclofenac gel group improved by 25 points, reported Dr. de Vega of the Medyr Clinic in Madrid.

At 6 weeks of follow-up, all participants reported total pain relief and normal functioning. The median time to normal activity was 19.1 days in the Traumeel ointment group and 19.4 days in each of the other two study arms.

All treatments were similarly well tolerated.

The clinical relevance of the TAASS findings lies in the fact that acute lateral ankle sprain is the most common ligamentous injury caused by sports and other physical activity. And a significant proportion of patients are more favorably disposed to a "natural" herbal therapy than to prescription medications, Dr. de Vega noted.

He reported receiving a research grant from Biologische Heilmittel Heel, which sponsored TAASS.

BERLIN – Patients with nonradiographic axial spondyloarthritis should be treated as aggressively as patients with ankylosing spondylitis, as the burden of disease is comparable based on clinical disease activity measures, pain levels, and global assessment scores.

Using data from registries and randomized controlled trials, Dr. Joachim Sieper, head of the medical clinic of rheumatology at the Benjamin Franklin University Clinic, Charité Medical University Berlin, compared disease burden in the two patient groups. "The question arises as to whether patients in the earlier phase of disease have a similar level of disease activity, pain, and stiffness as later-stage patients with ankylosing spondylitis," he said at the annual European Congress of Rheumatology.

Dr. Sieper explained that it is known that a delay exists between the onset of symptoms and the final diagnosis of ankylosing spondylitis (AS). Data from the ABILITY 1 trial showed that time to diagnosis was delayed by a mean of 7.2 years in patients with nonradiographic axial spondyloarthritis.

Even when patients have symptoms, diagnosis can take several years, suggesting that referral needs to be considered earlier in patients presenting with symptoms.

Before the onset of structural damage, a diagnosis can be made on the basis of an MRI scan that shows bone inflammation, he explained. "However, we also know that MRI can have limited sensitivity, so we might miss some patients." It is possible, however, to classify these patients on the basis of clinical findings.

According to the new ASAS (Assessment of Spondyloarthritis International Society) classification criteria for axial spondyloarthritis, patients can be divided into those who have already developed radiographic damage as seen in the sacroiliac joints on x-ray, termed AS patients, and those who do not yet have structural damage, termed nonradiographic axial spondyloarthritis (nr axSpA) patients, who require MRI or clinical parameters for diagnosis (Best Pract. Res. Clin. Rheumatol. 2012;26:135-45).

Dr. Sieper analyzed baseline disease activity data derived from spondyloarthritis registries and randomized controlled trials to determine the extent of disease burden between the two classifications of axial SpA patients.

Analysis showed that the ages of patients between the two groups were similar across the databases, at around 35-40 years, as were the levels of human leukocyte antigen-B27 (HLA-B27) positivity. The ratio of females was higher in patients with nr axSpA (around 60%) than in patients with established AS (around 25%). "This is probably because females develop structural damage later, but they still have a similar level of inflammation all the time," he pointed out.

Scores on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) hovered at 6.3-6.5 in both groups. Pain level and patient global assessment were similar in the two groups, according to the registry data and a randomized controlled trial.

The proportion of abnormal C-reactive protein levels was higher in the AS patients than in the nr axSpA patients (68% vs. 36%-38%, depending on the trial).

"The level of total pain is comparable no matter which of the groups a patient falls into," he said.

Nor were there differences between the groups in terms of patient and physician global assessment scores. The Patient’s Global Assessment of Disease Activity on a 0-10 visual analog scale was 5.0 for AS patients and 4.9 for nr axSpA patients, according to one trial.

Dr. Sieper disclosed ties with Abbott, Merck, Pfizer, and UCB.

BERLIN – Patients with nonradiographic axial spondyloarthritis should be treated as aggressively as patients with ankylosing spondylitis, as the burden of disease is comparable based on clinical disease activity measures, pain levels, and global assessment scores.

Using data from registries and randomized controlled trials, Dr. Joachim Sieper, head of the medical clinic of rheumatology at the Benjamin Franklin University Clinic, Charité Medical University Berlin, compared disease burden in the two patient groups. "The question arises as to whether patients in the earlier phase of disease have a similar level of disease activity, pain, and stiffness as later-stage patients with ankylosing spondylitis," he said at the annual European Congress of Rheumatology.

Dr. Sieper explained that it is known that a delay exists between the onset of symptoms and the final diagnosis of ankylosing spondylitis (AS). Data from the ABILITY 1 trial showed that time to diagnosis was delayed by a mean of 7.2 years in patients with nonradiographic axial spondyloarthritis.

Even when patients have symptoms, diagnosis can take several years, suggesting that referral needs to be considered earlier in patients presenting with symptoms.

Before the onset of structural damage, a diagnosis can be made on the basis of an MRI scan that shows bone inflammation, he explained. "However, we also know that MRI can have limited sensitivity, so we might miss some patients." It is possible, however, to classify these patients on the basis of clinical findings.

According to the new ASAS (Assessment of Spondyloarthritis International Society) classification criteria for axial spondyloarthritis, patients can be divided into those who have already developed radiographic damage as seen in the sacroiliac joints on x-ray, termed AS patients, and those who do not yet have structural damage, termed nonradiographic axial spondyloarthritis (nr axSpA) patients, who require MRI or clinical parameters for diagnosis (Best Pract. Res. Clin. Rheumatol. 2012;26:135-45).

Dr. Sieper analyzed baseline disease activity data derived from spondyloarthritis registries and randomized controlled trials to determine the extent of disease burden between the two classifications of axial SpA patients.

Analysis showed that the ages of patients between the two groups were similar across the databases, at around 35-40 years, as were the levels of human leukocyte antigen-B27 (HLA-B27) positivity. The ratio of females was higher in patients with nr axSpA (around 60%) than in patients with established AS (around 25%). "This is probably because females develop structural damage later, but they still have a similar level of inflammation all the time," he pointed out.

Scores on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) hovered at 6.3-6.5 in both groups. Pain level and patient global assessment were similar in the two groups, according to the registry data and a randomized controlled trial.

The proportion of abnormal C-reactive protein levels was higher in the AS patients than in the nr axSpA patients (68% vs. 36%-38%, depending on the trial).

"The level of total pain is comparable no matter which of the groups a patient falls into," he said.

Nor were there differences between the groups in terms of patient and physician global assessment scores. The Patient’s Global Assessment of Disease Activity on a 0-10 visual analog scale was 5.0 for AS patients and 4.9 for nr axSpA patients, according to one trial.

Dr. Sieper disclosed ties with Abbott, Merck, Pfizer, and UCB.

BERLIN – Patients with nonradiographic axial spondyloarthritis should be treated as aggressively as patients with ankylosing spondylitis, as the burden of disease is comparable based on clinical disease activity measures, pain levels, and global assessment scores.

Using data from registries and randomized controlled trials, Dr. Joachim Sieper, head of the medical clinic of rheumatology at the Benjamin Franklin University Clinic, Charité Medical University Berlin, compared disease burden in the two patient groups. "The question arises as to whether patients in the earlier phase of disease have a similar level of disease activity, pain, and stiffness as later-stage patients with ankylosing spondylitis," he said at the annual European Congress of Rheumatology.

Dr. Sieper explained that it is known that a delay exists between the onset of symptoms and the final diagnosis of ankylosing spondylitis (AS). Data from the ABILITY 1 trial showed that time to diagnosis was delayed by a mean of 7.2 years in patients with nonradiographic axial spondyloarthritis.

Even when patients have symptoms, diagnosis can take several years, suggesting that referral needs to be considered earlier in patients presenting with symptoms.

Before the onset of structural damage, a diagnosis can be made on the basis of an MRI scan that shows bone inflammation, he explained. "However, we also know that MRI can have limited sensitivity, so we might miss some patients." It is possible, however, to classify these patients on the basis of clinical findings.

According to the new ASAS (Assessment of Spondyloarthritis International Society) classification criteria for axial spondyloarthritis, patients can be divided into those who have already developed radiographic damage as seen in the sacroiliac joints on x-ray, termed AS patients, and those who do not yet have structural damage, termed nonradiographic axial spondyloarthritis (nr axSpA) patients, who require MRI or clinical parameters for diagnosis (Best Pract. Res. Clin. Rheumatol. 2012;26:135-45).

Dr. Sieper analyzed baseline disease activity data derived from spondyloarthritis registries and randomized controlled trials to determine the extent of disease burden between the two classifications of axial SpA patients.

Analysis showed that the ages of patients between the two groups were similar across the databases, at around 35-40 years, as were the levels of human leukocyte antigen-B27 (HLA-B27) positivity. The ratio of females was higher in patients with nr axSpA (around 60%) than in patients with established AS (around 25%). "This is probably because females develop structural damage later, but they still have a similar level of inflammation all the time," he pointed out.

Scores on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) hovered at 6.3-6.5 in both groups. Pain level and patient global assessment were similar in the two groups, according to the registry data and a randomized controlled trial.

The proportion of abnormal C-reactive protein levels was higher in the AS patients than in the nr axSpA patients (68% vs. 36%-38%, depending on the trial).

"The level of total pain is comparable no matter which of the groups a patient falls into," he said.

Nor were there differences between the groups in terms of patient and physician global assessment scores. The Patient’s Global Assessment of Disease Activity on a 0-10 visual analog scale was 5.0 for AS patients and 4.9 for nr axSpA patients, according to one trial.

Dr. Sieper disclosed ties with Abbott, Merck, Pfizer, and UCB.