Becky McCall

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 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.

BERLIN – The risk of cardiovascular events in patients with systemic lupus erythematosus is sevenfold higher than the risk predicted by the Framingham equation, a study shows.

The role of risk factors varies widely, with the presence of high triglyceride levels upping the risk nearly fourfold while use of cyclophosphamide, which may be a proxy for disease severity, raises the risk almost 17-fold, Dr. Sarah Skeoch, a clinical research fellow at the Arthritis Research UK Epidemiology Unit at the University of Manchester, England, said at the annual European Congress of Rheumatology.

The research also showed that triglyceride level was the only independent traditional risk factor, with a 3.6-fold increased risk association. Damage related to lupus, according to the Systemic Lupus International Collaborating Clinics (SLICC) damage index, increased risk 10-fold. Cyclophosphamide therapy was associated with a 16.7-fold increase in risk.

Although the patients have more of the classical risk factors, this does not seem to account for all the increased risk. Disease characteristics such as chronic inflammation or treatments may contribute, she suggested.

"We wanted to look at the association between risk and disease, for example, how active their lupus is, damage accrued over time, whether they have renal disease, and also whether their treatments are associated with CV events like heart disease and stroke," Dr. Skeoch added.

The study looked at these factors in 200 patients who were diagnosed between 2000 and 2003.

At baseline, 12 patients of the eventual 124 who were followed up had experienced a prior CV event. Also at baseline, the SLE disease activity index (SLEDAI) score was 1, indicating low disease activity, and the SLICC damage index was low.

All patients included in the study were over 18 years of age, female, and white. Their lupus was stable with therapy for at least 2 months prior to inclusion in the study. "They were a relatively well population of patients," said Dr. Skeoch.

Blood tests and clinical assessments were carried out to determine levels of traditional risk factors, lupus disease activity, and lupus-related damage, as well as measurements related to disease therapies.

After a 5-year interval, patients were invited back for assessments and the incidence of CV events, including coronary events, cerebral events, and peripheral vascular disease over the elapsed time period, was recorded.

Next, a comparison was made between the predicted CV risk at baseline according to the Framingham equation and the observed results in 112 patients with no prior CV disease.

CV Risk Higher Than Expected

Upon follow-up, patients were, on average, 56 years old and had had disease for approximately 16 years. Out of the 124 patients followed up over approximately 5 years, 12 (9.7%) had a CV event. Coronary events accounted for seven of these, cerebrovascular events were recorded in five patients, and peripheral vascular disease occurred in one patient. "One patient had both a coronary event and a cerebral event within the follow up," Dr. Skeoch said.

In those who had no prior CV event at baseline, predicted risk of a CV event according to the Framingham equation suggested that 1% of patients should have an event in the next 5 years. "In fact, we found 7% had an event – so seven times higher than predicted. This excess risk is most likely attributed to uncaptured traditional risk factors or alternatively, the disease itself, which is more likely," she commented.

The investigators looked at independent risk factors for a CV event regardless of which other risk factors a patient had and found that triglyceride levels were the only traditional risk factor, with an odds ratio (OR) of 3.61 (95% confidence interval, 1.23-10.56). Triglyceride levels often were not the primary target of lipid-lowering therapy, which was usually aimed at reducing total cholesterol or cholesterol ratio, she noted.

Other multivariable analyses of baseline characteristics associated with CV events suggested that the risk was elevated by two factors: the SLICC damage score (OR, 9.62; CI, 1.46-63.5) and cyclophosphamide therapy (OR, 16.7; CI, 1.46-123). "Factors associated with the patients’ lupus disease included having had a venous thromboembolism, damage related to SLE in the past, cyclophosphamide exposure, and a higher steroid dose at baseline which predisposed the patient to having an event," Dr. Skeoch said.

Marker for Disease Severity

"This is the first time cyclophosphamide [therapy] has been marked as an example of an independent predictor of CV risk. We don’t think it is the cyclophosphamide itself because it has been used in a number of diseases and there’s no known evidence to suggest it causes heart disease, but we think it is a measure of people with severe disease. Also, patients exposed to cyclophosphamide tend to have had more steroids," she explained.

If patients with lupus had severe disease, then they might be more likely to be at risk of CV events in the future, she concluded. "We have found that patients with SLE are at higher risk than expected of CV disease and that those with severe disease may be most at risk. We should endeavor to monitor and treat traditional risk factors and aim for good control of SLE disease activity in order to minimize this risk."

Dr. Skeoch has no relevant conflicts of interest. She is funded by the UK Medical Research Council.

BERLIN – The risk of cardiovascular events in patients with systemic lupus erythematosus is sevenfold higher than the risk predicted by the Framingham equation, a study shows.

The role of risk factors varies widely, with the presence of high triglyceride levels upping the risk nearly fourfold while use of cyclophosphamide, which may be a proxy for disease severity, raises the risk almost 17-fold, Dr. Sarah Skeoch, a clinical research fellow at the Arthritis Research UK Epidemiology Unit at the University of Manchester, England, said at the annual European Congress of Rheumatology.

The research also showed that triglyceride level was the only independent traditional risk factor, with a 3.6-fold increased risk association. Damage related to lupus, according to the Systemic Lupus International Collaborating Clinics (SLICC) damage index, increased risk 10-fold. Cyclophosphamide therapy was associated with a 16.7-fold increase in risk.

Although the patients have more of the classical risk factors, this does not seem to account for all the increased risk. Disease characteristics such as chronic inflammation or treatments may contribute, she suggested.

"We wanted to look at the association between risk and disease, for example, how active their lupus is, damage accrued over time, whether they have renal disease, and also whether their treatments are associated with CV events like heart disease and stroke," Dr. Skeoch added.

The study looked at these factors in 200 patients who were diagnosed between 2000 and 2003.

At baseline, 12 patients of the eventual 124 who were followed up had experienced a prior CV event. Also at baseline, the SLE disease activity index (SLEDAI) score was 1, indicating low disease activity, and the SLICC damage index was low.

All patients included in the study were over 18 years of age, female, and white. Their lupus was stable with therapy for at least 2 months prior to inclusion in the study. "They were a relatively well population of patients," said Dr. Skeoch.

Blood tests and clinical assessments were carried out to determine levels of traditional risk factors, lupus disease activity, and lupus-related damage, as well as measurements related to disease therapies.

After a 5-year interval, patients were invited back for assessments and the incidence of CV events, including coronary events, cerebral events, and peripheral vascular disease over the elapsed time period, was recorded.

Next, a comparison was made between the predicted CV risk at baseline according to the Framingham equation and the observed results in 112 patients with no prior CV disease.

CV Risk Higher Than Expected

Upon follow-up, patients were, on average, 56 years old and had had disease for approximately 16 years. Out of the 124 patients followed up over approximately 5 years, 12 (9.7%) had a CV event. Coronary events accounted for seven of these, cerebrovascular events were recorded in five patients, and peripheral vascular disease occurred in one patient. "One patient had both a coronary event and a cerebral event within the follow up," Dr. Skeoch said.

In those who had no prior CV event at baseline, predicted risk of a CV event according to the Framingham equation suggested that 1% of patients should have an event in the next 5 years. "In fact, we found 7% had an event – so seven times higher than predicted. This excess risk is most likely attributed to uncaptured traditional risk factors or alternatively, the disease itself, which is more likely," she commented.

The investigators looked at independent risk factors for a CV event regardless of which other risk factors a patient had and found that triglyceride levels were the only traditional risk factor, with an odds ratio (OR) of 3.61 (95% confidence interval, 1.23-10.56). Triglyceride levels often were not the primary target of lipid-lowering therapy, which was usually aimed at reducing total cholesterol or cholesterol ratio, she noted.

Other multivariable analyses of baseline characteristics associated with CV events suggested that the risk was elevated by two factors: the SLICC damage score (OR, 9.62; CI, 1.46-63.5) and cyclophosphamide therapy (OR, 16.7; CI, 1.46-123). "Factors associated with the patients’ lupus disease included having had a venous thromboembolism, damage related to SLE in the past, cyclophosphamide exposure, and a higher steroid dose at baseline which predisposed the patient to having an event," Dr. Skeoch said.

Marker for Disease Severity

"This is the first time cyclophosphamide [therapy] has been marked as an example of an independent predictor of CV risk. We don’t think it is the cyclophosphamide itself because it has been used in a number of diseases and there’s no known evidence to suggest it causes heart disease, but we think it is a measure of people with severe disease. Also, patients exposed to cyclophosphamide tend to have had more steroids," she explained.

If patients with lupus had severe disease, then they might be more likely to be at risk of CV events in the future, she concluded. "We have found that patients with SLE are at higher risk than expected of CV disease and that those with severe disease may be most at risk. We should endeavor to monitor and treat traditional risk factors and aim for good control of SLE disease activity in order to minimize this risk."

Dr. Skeoch has no relevant conflicts of interest. She is funded by the UK Medical Research Council.

BERLIN – The risk of cardiovascular events in patients with systemic lupus erythematosus is sevenfold higher than the risk predicted by the Framingham equation, a study shows.

The role of risk factors varies widely, with the presence of high triglyceride levels upping the risk nearly fourfold while use of cyclophosphamide, which may be a proxy for disease severity, raises the risk almost 17-fold, Dr. Sarah Skeoch, a clinical research fellow at the Arthritis Research UK Epidemiology Unit at the University of Manchester, England, said at the annual European Congress of Rheumatology.

The research also showed that triglyceride level was the only independent traditional risk factor, with a 3.6-fold increased risk association. Damage related to lupus, according to the Systemic Lupus International Collaborating Clinics (SLICC) damage index, increased risk 10-fold. Cyclophosphamide therapy was associated with a 16.7-fold increase in risk.

Although the patients have more of the classical risk factors, this does not seem to account for all the increased risk. Disease characteristics such as chronic inflammation or treatments may contribute, she suggested.

"We wanted to look at the association between risk and disease, for example, how active their lupus is, damage accrued over time, whether they have renal disease, and also whether their treatments are associated with CV events like heart disease and stroke," Dr. Skeoch added.

The study looked at these factors in 200 patients who were diagnosed between 2000 and 2003.

At baseline, 12 patients of the eventual 124 who were followed up had experienced a prior CV event. Also at baseline, the SLE disease activity index (SLEDAI) score was 1, indicating low disease activity, and the SLICC damage index was low.

All patients included in the study were over 18 years of age, female, and white. Their lupus was stable with therapy for at least 2 months prior to inclusion in the study. "They were a relatively well population of patients," said Dr. Skeoch.

Blood tests and clinical assessments were carried out to determine levels of traditional risk factors, lupus disease activity, and lupus-related damage, as well as measurements related to disease therapies.

After a 5-year interval, patients were invited back for assessments and the incidence of CV events, including coronary events, cerebral events, and peripheral vascular disease over the elapsed time period, was recorded.

Next, a comparison was made between the predicted CV risk at baseline according to the Framingham equation and the observed results in 112 patients with no prior CV disease.

CV Risk Higher Than Expected

Upon follow-up, patients were, on average, 56 years old and had had disease for approximately 16 years. Out of the 124 patients followed up over approximately 5 years, 12 (9.7%) had a CV event. Coronary events accounted for seven of these, cerebrovascular events were recorded in five patients, and peripheral vascular disease occurred in one patient. "One patient had both a coronary event and a cerebral event within the follow up," Dr. Skeoch said.

In those who had no prior CV event at baseline, predicted risk of a CV event according to the Framingham equation suggested that 1% of patients should have an event in the next 5 years. "In fact, we found 7% had an event – so seven times higher than predicted. This excess risk is most likely attributed to uncaptured traditional risk factors or alternatively, the disease itself, which is more likely," she commented.

The investigators looked at independent risk factors for a CV event regardless of which other risk factors a patient had and found that triglyceride levels were the only traditional risk factor, with an odds ratio (OR) of 3.61 (95% confidence interval, 1.23-10.56). Triglyceride levels often were not the primary target of lipid-lowering therapy, which was usually aimed at reducing total cholesterol or cholesterol ratio, she noted.

Other multivariable analyses of baseline characteristics associated with CV events suggested that the risk was elevated by two factors: the SLICC damage score (OR, 9.62; CI, 1.46-63.5) and cyclophosphamide therapy (OR, 16.7; CI, 1.46-123). "Factors associated with the patients’ lupus disease included having had a venous thromboembolism, damage related to SLE in the past, cyclophosphamide exposure, and a higher steroid dose at baseline which predisposed the patient to having an event," Dr. Skeoch said.

Marker for Disease Severity

"This is the first time cyclophosphamide [therapy] has been marked as an example of an independent predictor of CV risk. We don’t think it is the cyclophosphamide itself because it has been used in a number of diseases and there’s no known evidence to suggest it causes heart disease, but we think it is a measure of people with severe disease. Also, patients exposed to cyclophosphamide tend to have had more steroids," she explained.

If patients with lupus had severe disease, then they might be more likely to be at risk of CV events in the future, she concluded. "We have found that patients with SLE are at higher risk than expected of CV disease and that those with severe disease may be most at risk. We should endeavor to monitor and treat traditional risk factors and aim for good control of SLE disease activity in order to minimize this risk."

Dr. Skeoch has no relevant conflicts of interest. She is funded by the UK Medical Research Council.

BERLIN – Patients who have inflammatory rheumatic diseases and are on anti–tumor necrosis factor therapy have nearly double the risk of herpes zoster when they are compared with patients on disease-modifying antirheumatic drugs, according to the first meta-analysis in these patient populations.

Although the risk of bacterial infection is known to be increased among patients on anti-TNF therapy, less well known is whether the use of anti-TNF agents increases the risk for viral infections, especially herpes zoster, said Dr. Cedric Lukas of the department of rheumatology at Lapeyronie Hospital in Montpellier, France.

The meta-analysis of literature that was published between 2002 and 2010 involved a review of 655 articles and 134 congress abstracts, of which 22 articles and 28 abstracts eventually were included in the study. The anti-TNF therapies that were investigated included etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade), which were the agents available at the time.

National registries from the United States, United Kingdom, and other European countries were included in the meta-analysis, including BSRBR (British Society for Rheumatology Biologics Register), BIOBADASER (Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases), CORRONA (Consortium of Rheumatology Researchers of North America), the McDonald cohort of U.S. veterans (Clin. Infect. Dis. 2009;48:1364-71), and RABBIT (the German Rheumatoid Arthritis Observation of Biologic Therapy) were selected for inclusion. After selection for appropriate treatment regimens and diseases, 124, 966 patient years were included.

Upon meta-analysis, Dr. Lukas showed that there was a similar trend across the different registries, and no significant heterogeneity among data sources.

The meta-analysis showed an overall increased risk of herpes zoster infection up to 75% in patients whose inflammatory rheumatic diseases were treated with anti-TNF inhibitors. Overall, the pooled odds ratio for herpes zoster infection with anti-TNF therapy was 1.75 (95% confidence interval, 1.50-2.04). This was almost a twofold risk of developing disease with these drugs compared with DMARDs, Dr. Lukas said at the annual European Congress of Rheumatology.

Odds ratios by national registries were BIOBADASER, 2.45; BSRBR, 1.45; CORRONA, 2.34; McDonald, 1.33; and RABBIT, 1.82.

In addition to the meta-analysis, investigators used data from three registries specifically to determine whether the use of any particular anti-TNF drug was associated with a higher risk. "We found that one registry showed [that] infliximab had a somewhat higher risk, but this was only one out of three studies. The other two studies showed a similar risk across all anti-TNF agents."

In the McDonald registry, the risk was found to e higher with infliximab (OR, 1.32; 95% CI, 0.85-2.03) compared with etanercept (OR, 0.62; 95% CI, 0.40-0.95) and adalimumab (OR 0.53; 95% CI, 0.31-0.91).

"We already knew that these patients were prone to herpes zoster; we see the lesions in clinics." But there are preventive measures available that one can take, he said.

In the United States, there are vaccines to prevent herpes zoster, which are available to people who are older than age 60 years, or are at high specific risk of developing herpes zoster infection. "In these patients, we could think about vaccines before treatment is started," pointed out Dr. Lukas. "It is a live vaccine so it should be given a month before start of anti-TNF therapy. In Europe, where the vaccine is unavailable, we need to give patients prophylaxis."

Dr. Lukas reported no relevant conflicts of interest. The study was supported by an unrestricted educational grant from Abbott France.

BERLIN – Patients who have inflammatory rheumatic diseases and are on anti–tumor necrosis factor therapy have nearly double the risk of herpes zoster when they are compared with patients on disease-modifying antirheumatic drugs, according to the first meta-analysis in these patient populations.

Although the risk of bacterial infection is known to be increased among patients on anti-TNF therapy, less well known is whether the use of anti-TNF agents increases the risk for viral infections, especially herpes zoster, said Dr. Cedric Lukas of the department of rheumatology at Lapeyronie Hospital in Montpellier, France.

The meta-analysis of literature that was published between 2002 and 2010 involved a review of 655 articles and 134 congress abstracts, of which 22 articles and 28 abstracts eventually were included in the study. The anti-TNF therapies that were investigated included etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade), which were the agents available at the time.

National registries from the United States, United Kingdom, and other European countries were included in the meta-analysis, including BSRBR (British Society for Rheumatology Biologics Register), BIOBADASER (Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases), CORRONA (Consortium of Rheumatology Researchers of North America), the McDonald cohort of U.S. veterans (Clin. Infect. Dis. 2009;48:1364-71), and RABBIT (the German Rheumatoid Arthritis Observation of Biologic Therapy) were selected for inclusion. After selection for appropriate treatment regimens and diseases, 124, 966 patient years were included.

Upon meta-analysis, Dr. Lukas showed that there was a similar trend across the different registries, and no significant heterogeneity among data sources.

The meta-analysis showed an overall increased risk of herpes zoster infection up to 75% in patients whose inflammatory rheumatic diseases were treated with anti-TNF inhibitors. Overall, the pooled odds ratio for herpes zoster infection with anti-TNF therapy was 1.75 (95% confidence interval, 1.50-2.04). This was almost a twofold risk of developing disease with these drugs compared with DMARDs, Dr. Lukas said at the annual European Congress of Rheumatology.

Odds ratios by national registries were BIOBADASER, 2.45; BSRBR, 1.45; CORRONA, 2.34; McDonald, 1.33; and RABBIT, 1.82.

In addition to the meta-analysis, investigators used data from three registries specifically to determine whether the use of any particular anti-TNF drug was associated with a higher risk. "We found that one registry showed [that] infliximab had a somewhat higher risk, but this was only one out of three studies. The other two studies showed a similar risk across all anti-TNF agents."

In the McDonald registry, the risk was found to e higher with infliximab (OR, 1.32; 95% CI, 0.85-2.03) compared with etanercept (OR, 0.62; 95% CI, 0.40-0.95) and adalimumab (OR 0.53; 95% CI, 0.31-0.91).

"We already knew that these patients were prone to herpes zoster; we see the lesions in clinics." But there are preventive measures available that one can take, he said.

In the United States, there are vaccines to prevent herpes zoster, which are available to people who are older than age 60 years, or are at high specific risk of developing herpes zoster infection. "In these patients, we could think about vaccines before treatment is started," pointed out Dr. Lukas. "It is a live vaccine so it should be given a month before start of anti-TNF therapy. In Europe, where the vaccine is unavailable, we need to give patients prophylaxis."

Dr. Lukas reported no relevant conflicts of interest. The study was supported by an unrestricted educational grant from Abbott France.

BERLIN – Patients who have inflammatory rheumatic diseases and are on anti–tumor necrosis factor therapy have nearly double the risk of herpes zoster when they are compared with patients on disease-modifying antirheumatic drugs, according to the first meta-analysis in these patient populations.

Although the risk of bacterial infection is known to be increased among patients on anti-TNF therapy, less well known is whether the use of anti-TNF agents increases the risk for viral infections, especially herpes zoster, said Dr. Cedric Lukas of the department of rheumatology at Lapeyronie Hospital in Montpellier, France.

The meta-analysis of literature that was published between 2002 and 2010 involved a review of 655 articles and 134 congress abstracts, of which 22 articles and 28 abstracts eventually were included in the study. The anti-TNF therapies that were investigated included etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade), which were the agents available at the time.

National registries from the United States, United Kingdom, and other European countries were included in the meta-analysis, including BSRBR (British Society for Rheumatology Biologics Register), BIOBADASER (Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases), CORRONA (Consortium of Rheumatology Researchers of North America), the McDonald cohort of U.S. veterans (Clin. Infect. Dis. 2009;48:1364-71), and RABBIT (the German Rheumatoid Arthritis Observation of Biologic Therapy) were selected for inclusion. After selection for appropriate treatment regimens and diseases, 124, 966 patient years were included.

Upon meta-analysis, Dr. Lukas showed that there was a similar trend across the different registries, and no significant heterogeneity among data sources.

The meta-analysis showed an overall increased risk of herpes zoster infection up to 75% in patients whose inflammatory rheumatic diseases were treated with anti-TNF inhibitors. Overall, the pooled odds ratio for herpes zoster infection with anti-TNF therapy was 1.75 (95% confidence interval, 1.50-2.04). This was almost a twofold risk of developing disease with these drugs compared with DMARDs, Dr. Lukas said at the annual European Congress of Rheumatology.

Odds ratios by national registries were BIOBADASER, 2.45; BSRBR, 1.45; CORRONA, 2.34; McDonald, 1.33; and RABBIT, 1.82.

In addition to the meta-analysis, investigators used data from three registries specifically to determine whether the use of any particular anti-TNF drug was associated with a higher risk. "We found that one registry showed [that] infliximab had a somewhat higher risk, but this was only one out of three studies. The other two studies showed a similar risk across all anti-TNF agents."

In the McDonald registry, the risk was found to e higher with infliximab (OR, 1.32; 95% CI, 0.85-2.03) compared with etanercept (OR, 0.62; 95% CI, 0.40-0.95) and adalimumab (OR 0.53; 95% CI, 0.31-0.91).

"We already knew that these patients were prone to herpes zoster; we see the lesions in clinics." But there are preventive measures available that one can take, he said.

In the United States, there are vaccines to prevent herpes zoster, which are available to people who are older than age 60 years, or are at high specific risk of developing herpes zoster infection. "In these patients, we could think about vaccines before treatment is started," pointed out Dr. Lukas. "It is a live vaccine so it should be given a month before start of anti-TNF therapy. In Europe, where the vaccine is unavailable, we need to give patients prophylaxis."

Dr. Lukas reported no relevant conflicts of interest. The study was supported by an unrestricted educational grant from Abbott France.

BERLIN – Prednisolone improves pain scores in patients with moderate to severe knee osteoarthritis by nearly one-third, according to the WOMAC pain scale, compared with patients on placebo, according to a new study presented at the annual European Congress of Rheumatology.

"Given the limitations of current nonspecific symptom-relieving drugs such as NSAIDs, we need medications that control pain in the medium to long term as well as short term," said Dr. Anna Abou-Raya of the University of Alexandria (Egypt).

Dr. Abou-Raya conducted a randomized, double-blind, controlled trial to assess whether 6 weeks of daily, low-dose oral prednisolone would lessen pain, improve mobility, and ease systemic low-grade inflammation, as well as be sustained over 12 weeks in older adults with moderate to severe knee osteoarthritis (OA).

In all, 125 adults older than 65 years were recruited from among OA patients who attended her institution’s outpatient clinic. Patients met ACR (American College of Rheumatology) clinical and radiographic criteria of primary knee OA and had a mean pain score greater than 4 on a scale of 0-10 in the week prior to treatment that had occurred for at least 14 days a month for 3 months prior to randomization.

Oral prednisolone (7.5 mg/day) was given to 63 patients, and placebo was given to 62; all completers were followed up at 6 and 12 weeks. All patients received physical examination and were reviewed for their pain levels, flares, and analgesic use.

The primary outcome was pain reduction, with secondary outcomes of systemic inflammation and improvement in physical functioning score. Dr. Abou-Raya assessed knee OA using the Kellgren-Lawrence scale; clinical function on a 0-100 VAS (Visual Analogue Scale); self-reported physical function, pain, and stiffness as reported by the WOMAC (Western Ontario and McMaster Universities) osteoarthritis index; and a 6-minute walk distance test. Blood levels of interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF)–alpha, and high-sensitivity C-reactive protein (hsCRP) were also measured.

"There was a significantly greater absolute change from baseline in all three subscale scores – function, pain, and stiffness – [at both] 6 and 12 weeks in the prednisolone group," compared with the placebo group.

WOMAC pain scores showed a change of –3.4 (95% confidence interval, –5.15 to –2.99) over 12 weeks on prednisolone, compared with –0.4 (95% CI, –0.193 to –0.41) for patients on placebo (P = .001). WOMAC function scores also showed improvement in the prednisolone group, with a change from baseline of –10.9 (95% CI, –4.46 to –2.31) over 12 weeks, compared with –0.4 (95% CI, –0.196 to –0.29) in the placebo group (P = .005).

"The mean number of analgesic users decreased significantly in the intervention group" compared with the placebo group at both 6 and 12 weeks when compared with baseline, added Dr. Abou-Raya.

The researcher also found that mean levels of inflammatory markers IL-1, IL-6, TNF-alpha, and hsCRP were all reduced in the prednisolone group vs. the placebo group. For example, IL-1 levels at 6 weeks were 18.7 pg/mL vs. 25 pg/mL in the prednisolone and placebo groups, respectively (P = .005), and this was maintained at 12 weeks. The hsCRP levels were 2.3 mg/L vs. 3.6 mg/L at 6 weeks for the prednisolone and placebo groups, respectively (P = .005), and these were also maintained at 12 weeks.

"There was a significant improvement in the 6-minute walk distance test at 6 and 12 weeks," reported Dr. Abou-Raya, with an absolute change from baseline of 7.6 m in the prednisolone group compared with 0 m in the placebo arm.

Treatment-related adverse effects were similar in both groups, with no serious events recorded.

"The findings may provide evidence of efficacy and tolerability of low-dose oral prednisolone in reducing pain and subsequently improving function in older adults with knee OA; however, we need larger scale longitudinal studies to further verify this information," concluded Dr. Abou-Raya.

Dr. Abou-Raya reported that she had no relevant conflicts of interest.

BERLIN – Prednisolone improves pain scores in patients with moderate to severe knee osteoarthritis by nearly one-third, according to the WOMAC pain scale, compared with patients on placebo, according to a new study presented at the annual European Congress of Rheumatology.

"Given the limitations of current nonspecific symptom-relieving drugs such as NSAIDs, we need medications that control pain in the medium to long term as well as short term," said Dr. Anna Abou-Raya of the University of Alexandria (Egypt).

Dr. Abou-Raya conducted a randomized, double-blind, controlled trial to assess whether 6 weeks of daily, low-dose oral prednisolone would lessen pain, improve mobility, and ease systemic low-grade inflammation, as well as be sustained over 12 weeks in older adults with moderate to severe knee osteoarthritis (OA).

In all, 125 adults older than 65 years were recruited from among OA patients who attended her institution’s outpatient clinic. Patients met ACR (American College of Rheumatology) clinical and radiographic criteria of primary knee OA and had a mean pain score greater than 4 on a scale of 0-10 in the week prior to treatment that had occurred for at least 14 days a month for 3 months prior to randomization.

Oral prednisolone (7.5 mg/day) was given to 63 patients, and placebo was given to 62; all completers were followed up at 6 and 12 weeks. All patients received physical examination and were reviewed for their pain levels, flares, and analgesic use.

The primary outcome was pain reduction, with secondary outcomes of systemic inflammation and improvement in physical functioning score. Dr. Abou-Raya assessed knee OA using the Kellgren-Lawrence scale; clinical function on a 0-100 VAS (Visual Analogue Scale); self-reported physical function, pain, and stiffness as reported by the WOMAC (Western Ontario and McMaster Universities) osteoarthritis index; and a 6-minute walk distance test. Blood levels of interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF)–alpha, and high-sensitivity C-reactive protein (hsCRP) were also measured.

"There was a significantly greater absolute change from baseline in all three subscale scores – function, pain, and stiffness – [at both] 6 and 12 weeks in the prednisolone group," compared with the placebo group.

WOMAC pain scores showed a change of –3.4 (95% confidence interval, –5.15 to –2.99) over 12 weeks on prednisolone, compared with –0.4 (95% CI, –0.193 to –0.41) for patients on placebo (P = .001). WOMAC function scores also showed improvement in the prednisolone group, with a change from baseline of –10.9 (95% CI, –4.46 to –2.31) over 12 weeks, compared with –0.4 (95% CI, –0.196 to –0.29) in the placebo group (P = .005).

"The mean number of analgesic users decreased significantly in the intervention group" compared with the placebo group at both 6 and 12 weeks when compared with baseline, added Dr. Abou-Raya.

The researcher also found that mean levels of inflammatory markers IL-1, IL-6, TNF-alpha, and hsCRP were all reduced in the prednisolone group vs. the placebo group. For example, IL-1 levels at 6 weeks were 18.7 pg/mL vs. 25 pg/mL in the prednisolone and placebo groups, respectively (P = .005), and this was maintained at 12 weeks. The hsCRP levels were 2.3 mg/L vs. 3.6 mg/L at 6 weeks for the prednisolone and placebo groups, respectively (P = .005), and these were also maintained at 12 weeks.

"There was a significant improvement in the 6-minute walk distance test at 6 and 12 weeks," reported Dr. Abou-Raya, with an absolute change from baseline of 7.6 m in the prednisolone group compared with 0 m in the placebo arm.

Treatment-related adverse effects were similar in both groups, with no serious events recorded.

"The findings may provide evidence of efficacy and tolerability of low-dose oral prednisolone in reducing pain and subsequently improving function in older adults with knee OA; however, we need larger scale longitudinal studies to further verify this information," concluded Dr. Abou-Raya.

Dr. Abou-Raya reported that she had no relevant conflicts of interest.

BERLIN – Prednisolone improves pain scores in patients with moderate to severe knee osteoarthritis by nearly one-third, according to the WOMAC pain scale, compared with patients on placebo, according to a new study presented at the annual European Congress of Rheumatology.

"Given the limitations of current nonspecific symptom-relieving drugs such as NSAIDs, we need medications that control pain in the medium to long term as well as short term," said Dr. Anna Abou-Raya of the University of Alexandria (Egypt).

Dr. Abou-Raya conducted a randomized, double-blind, controlled trial to assess whether 6 weeks of daily, low-dose oral prednisolone would lessen pain, improve mobility, and ease systemic low-grade inflammation, as well as be sustained over 12 weeks in older adults with moderate to severe knee osteoarthritis (OA).

In all, 125 adults older than 65 years were recruited from among OA patients who attended her institution’s outpatient clinic. Patients met ACR (American College of Rheumatology) clinical and radiographic criteria of primary knee OA and had a mean pain score greater than 4 on a scale of 0-10 in the week prior to treatment that had occurred for at least 14 days a month for 3 months prior to randomization.

Oral prednisolone (7.5 mg/day) was given to 63 patients, and placebo was given to 62; all completers were followed up at 6 and 12 weeks. All patients received physical examination and were reviewed for their pain levels, flares, and analgesic use.

The primary outcome was pain reduction, with secondary outcomes of systemic inflammation and improvement in physical functioning score. Dr. Abou-Raya assessed knee OA using the Kellgren-Lawrence scale; clinical function on a 0-100 VAS (Visual Analogue Scale); self-reported physical function, pain, and stiffness as reported by the WOMAC (Western Ontario and McMaster Universities) osteoarthritis index; and a 6-minute walk distance test. Blood levels of interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF)–alpha, and high-sensitivity C-reactive protein (hsCRP) were also measured.

"There was a significantly greater absolute change from baseline in all three subscale scores – function, pain, and stiffness – [at both] 6 and 12 weeks in the prednisolone group," compared with the placebo group.

WOMAC pain scores showed a change of –3.4 (95% confidence interval, –5.15 to –2.99) over 12 weeks on prednisolone, compared with –0.4 (95% CI, –0.193 to –0.41) for patients on placebo (P = .001). WOMAC function scores also showed improvement in the prednisolone group, with a change from baseline of –10.9 (95% CI, –4.46 to –2.31) over 12 weeks, compared with –0.4 (95% CI, –0.196 to –0.29) in the placebo group (P = .005).

"The mean number of analgesic users decreased significantly in the intervention group" compared with the placebo group at both 6 and 12 weeks when compared with baseline, added Dr. Abou-Raya.

The researcher also found that mean levels of inflammatory markers IL-1, IL-6, TNF-alpha, and hsCRP were all reduced in the prednisolone group vs. the placebo group. For example, IL-1 levels at 6 weeks were 18.7 pg/mL vs. 25 pg/mL in the prednisolone and placebo groups, respectively (P = .005), and this was maintained at 12 weeks. The hsCRP levels were 2.3 mg/L vs. 3.6 mg/L at 6 weeks for the prednisolone and placebo groups, respectively (P = .005), and these were also maintained at 12 weeks.

"There was a significant improvement in the 6-minute walk distance test at 6 and 12 weeks," reported Dr. Abou-Raya, with an absolute change from baseline of 7.6 m in the prednisolone group compared with 0 m in the placebo arm.

Treatment-related adverse effects were similar in both groups, with no serious events recorded.

"The findings may provide evidence of efficacy and tolerability of low-dose oral prednisolone in reducing pain and subsequently improving function in older adults with knee OA; however, we need larger scale longitudinal studies to further verify this information," concluded Dr. Abou-Raya.

Dr. Abou-Raya reported that she had no relevant conflicts of interest.

BERLIN – Delaying treatment of long-standing rheumatoid arthritis with adalimumab by 1 year leads to greater joint space narrowing 10 years later.

"This analysis demonstrates the cost of delay," remarked Dr. Edward Keystone, professor of medicine at the University of Toronto and lead investigator on the study. "Allowing a patient to have active disease a year longer is taking a toll on never catching up on quality of life, never catching up on radiographic outcome, and never catching up with persistent active disease."

These findings come from the final analysis of results of the DEO19 trial, which compared patients on methotrexate plus either adalimumab or placebo for 1 year and followed up with all patients receiving active drug for a further 9 years.

"Earlier treatment is better. You are treating to prevent irreversible joint damage, so over time, you want a patient’s quality of life to remain the same," Dr. Keystone said at the annual European Congress of Rheumatology.

Trial DEO19 was a 1-year, randomized, double-blind, placebo-controlled study of adalimumab in patients inadequately controlled on methotrexate. Patients with moderate to severely active disease were randomly assigned to receiving either adalimumab at 40 mg every other week (209 patients), adalimumab 20 mg every week (212), or placebo (200). All patients continued on methotrexate.

After the initial 1-year blinded stage, all patents were eligible to receive open-label adalimumab 40 mg for the next 9 years. Of the initial entrants, 457 went through to the open-label phase, and 202 completed the 9-year extension. Average disease duration upon entry was 11 years.

"Even at 11 years’ duration of RA, when they all have active disease, you can improve patients’ signs and symptoms when they receive adalimumab," pointed out Dr. Keystone. "It is possible to maintain quality of life and actually prevent radiographic progression or stabilize it and show minimal progression after treatment."

The 10-year follow-up data showed that 63.5% of completers reached an American College of Rheumatology 50; 48.4% reached an ACR 70 and 17.7% an ACR 90. A disease activity score 28 of less than 3.2 was achieved by 73.6% of patients, and a Health Assessment Questionnaire less than 0.5 was achieved by 42.8%.

Mean swollen joint count (SJC) persisted in patients who were originally treated with placebo as opposed to adalimumab, with a SJC of just under 5 at 10 years in the group given either dose of adalimumab at year 1 versus approximately 7.5 in the year 1 placebo group.

Furthermore, 30.3% of patients who received adalimumab originally achieved comprehensive disease control – indicated by a DAS28 C-reactive protein of less than 3.2 – at year 10 vs. 11.3% of those on placebo.

"These results show that one in three people who started on adalimumab ended up in a comprehensive disease state, that is no disability, no radiographic progression, and clinical remission," reported Dr. Keystone.

"I treat patients with 10 years of active disease and I improve them to only a few swollen joints, but I treat them at 11 years and I still can’t get them down to the level I want."

"For me, that is a surprise," said Dr. Keystone. "I thought the placebo patients would eventually reach the same level as the others who started a year earlier, but that didn’t happen."

Dr. Keystone noted that joint space narrowing continued over time as seen by the change in Sharp score over 10 years. "This is accounted for not by erosions, but by the change in joint space narrowing," Dr. Keystone noted.

Radiographic damage was assessed using the modified total Sharp score. Patients who initially received adalimumab in year 1 had significantly lower mean change in modified total Sharp score at year 10, compared with patients who initially received placebo plus methotrexate [0.7 (ADA-40) and 2.6 (ADA-20) vs. 6.2 on placebo (P = .002 and 0.01, respectively).

Dr. Keystone highlighted this dramatic increase in joint space narrowing. "Patients treated on placebo initially ended up with more joint space narrowing over that period of time."

He also pointed out that joint space narrowing decreases quality of life, in addition to patients’ work productivity and ability to stay at work or not.

"Every drug has side effects. Everyone has a different answer to this. I’d like to see a study that helps us decide when it is optimal to start these types of drugs. But 10 years is a long time to follow these patients- it’s a good study. I would start patients earlier but I would also like to see data on which patients to start."

Dr. Keystone disclosed financial relationships with Abbott, Amgen, AstraZeneca, Biotest, Bristol-Myers Squibb, Centocor, Genentech, Genzyme, Merck, Novartis, Nycomed, Pfizer, Roche, and UCB.

BERLIN – Delaying treatment of long-standing rheumatoid arthritis with adalimumab by 1 year leads to greater joint space narrowing 10 years later.

"This analysis demonstrates the cost of delay," remarked Dr. Edward Keystone, professor of medicine at the University of Toronto and lead investigator on the study. "Allowing a patient to have active disease a year longer is taking a toll on never catching up on quality of life, never catching up on radiographic outcome, and never catching up with persistent active disease."

These findings come from the final analysis of results of the DEO19 trial, which compared patients on methotrexate plus either adalimumab or placebo for 1 year and followed up with all patients receiving active drug for a further 9 years.

"Earlier treatment is better. You are treating to prevent irreversible joint damage, so over time, you want a patient’s quality of life to remain the same," Dr. Keystone said at the annual European Congress of Rheumatology.

Trial DEO19 was a 1-year, randomized, double-blind, placebo-controlled study of adalimumab in patients inadequately controlled on methotrexate. Patients with moderate to severely active disease were randomly assigned to receiving either adalimumab at 40 mg every other week (209 patients), adalimumab 20 mg every week (212), or placebo (200). All patients continued on methotrexate.

After the initial 1-year blinded stage, all patents were eligible to receive open-label adalimumab 40 mg for the next 9 years. Of the initial entrants, 457 went through to the open-label phase, and 202 completed the 9-year extension. Average disease duration upon entry was 11 years.

"Even at 11 years’ duration of RA, when they all have active disease, you can improve patients’ signs and symptoms when they receive adalimumab," pointed out Dr. Keystone. "It is possible to maintain quality of life and actually prevent radiographic progression or stabilize it and show minimal progression after treatment."

The 10-year follow-up data showed that 63.5% of completers reached an American College of Rheumatology 50; 48.4% reached an ACR 70 and 17.7% an ACR 90. A disease activity score 28 of less than 3.2 was achieved by 73.6% of patients, and a Health Assessment Questionnaire less than 0.5 was achieved by 42.8%.

Mean swollen joint count (SJC) persisted in patients who were originally treated with placebo as opposed to adalimumab, with a SJC of just under 5 at 10 years in the group given either dose of adalimumab at year 1 versus approximately 7.5 in the year 1 placebo group.

Furthermore, 30.3% of patients who received adalimumab originally achieved comprehensive disease control – indicated by a DAS28 C-reactive protein of less than 3.2 – at year 10 vs. 11.3% of those on placebo.

"These results show that one in three people who started on adalimumab ended up in a comprehensive disease state, that is no disability, no radiographic progression, and clinical remission," reported Dr. Keystone.

"I treat patients with 10 years of active disease and I improve them to only a few swollen joints, but I treat them at 11 years and I still can’t get them down to the level I want."

"For me, that is a surprise," said Dr. Keystone. "I thought the placebo patients would eventually reach the same level as the others who started a year earlier, but that didn’t happen."

Dr. Keystone noted that joint space narrowing continued over time as seen by the change in Sharp score over 10 years. "This is accounted for not by erosions, but by the change in joint space narrowing," Dr. Keystone noted.

Radiographic damage was assessed using the modified total Sharp score. Patients who initially received adalimumab in year 1 had significantly lower mean change in modified total Sharp score at year 10, compared with patients who initially received placebo plus methotrexate [0.7 (ADA-40) and 2.6 (ADA-20) vs. 6.2 on placebo (P = .002 and 0.01, respectively).

Dr. Keystone highlighted this dramatic increase in joint space narrowing. "Patients treated on placebo initially ended up with more joint space narrowing over that period of time."

He also pointed out that joint space narrowing decreases quality of life, in addition to patients’ work productivity and ability to stay at work or not.

"Every drug has side effects. Everyone has a different answer to this. I’d like to see a study that helps us decide when it is optimal to start these types of drugs. But 10 years is a long time to follow these patients- it’s a good study. I would start patients earlier but I would also like to see data on which patients to start."

Dr. Keystone disclosed financial relationships with Abbott, Amgen, AstraZeneca, Biotest, Bristol-Myers Squibb, Centocor, Genentech, Genzyme, Merck, Novartis, Nycomed, Pfizer, Roche, and UCB.

BERLIN – Delaying treatment of long-standing rheumatoid arthritis with adalimumab by 1 year leads to greater joint space narrowing 10 years later.

"This analysis demonstrates the cost of delay," remarked Dr. Edward Keystone, professor of medicine at the University of Toronto and lead investigator on the study. "Allowing a patient to have active disease a year longer is taking a toll on never catching up on quality of life, never catching up on radiographic outcome, and never catching up with persistent active disease."

These findings come from the final analysis of results of the DEO19 trial, which compared patients on methotrexate plus either adalimumab or placebo for 1 year and followed up with all patients receiving active drug for a further 9 years.

"Earlier treatment is better. You are treating to prevent irreversible joint damage, so over time, you want a patient’s quality of life to remain the same," Dr. Keystone said at the annual European Congress of Rheumatology.

Trial DEO19 was a 1-year, randomized, double-blind, placebo-controlled study of adalimumab in patients inadequately controlled on methotrexate. Patients with moderate to severely active disease were randomly assigned to receiving either adalimumab at 40 mg every other week (209 patients), adalimumab 20 mg every week (212), or placebo (200). All patients continued on methotrexate.

After the initial 1-year blinded stage, all patents were eligible to receive open-label adalimumab 40 mg for the next 9 years. Of the initial entrants, 457 went through to the open-label phase, and 202 completed the 9-year extension. Average disease duration upon entry was 11 years.

"Even at 11 years’ duration of RA, when they all have active disease, you can improve patients’ signs and symptoms when they receive adalimumab," pointed out Dr. Keystone. "It is possible to maintain quality of life and actually prevent radiographic progression or stabilize it and show minimal progression after treatment."

The 10-year follow-up data showed that 63.5% of completers reached an American College of Rheumatology 50; 48.4% reached an ACR 70 and 17.7% an ACR 90. A disease activity score 28 of less than 3.2 was achieved by 73.6% of patients, and a Health Assessment Questionnaire less than 0.5 was achieved by 42.8%.

Mean swollen joint count (SJC) persisted in patients who were originally treated with placebo as opposed to adalimumab, with a SJC of just under 5 at 10 years in the group given either dose of adalimumab at year 1 versus approximately 7.5 in the year 1 placebo group.

Furthermore, 30.3% of patients who received adalimumab originally achieved comprehensive disease control – indicated by a DAS28 C-reactive protein of less than 3.2 – at year 10 vs. 11.3% of those on placebo.

"These results show that one in three people who started on adalimumab ended up in a comprehensive disease state, that is no disability, no radiographic progression, and clinical remission," reported Dr. Keystone.

"I treat patients with 10 years of active disease and I improve them to only a few swollen joints, but I treat them at 11 years and I still can’t get them down to the level I want."

"For me, that is a surprise," said Dr. Keystone. "I thought the placebo patients would eventually reach the same level as the others who started a year earlier, but that didn’t happen."

Dr. Keystone noted that joint space narrowing continued over time as seen by the change in Sharp score over 10 years. "This is accounted for not by erosions, but by the change in joint space narrowing," Dr. Keystone noted.

Radiographic damage was assessed using the modified total Sharp score. Patients who initially received adalimumab in year 1 had significantly lower mean change in modified total Sharp score at year 10, compared with patients who initially received placebo plus methotrexate [0.7 (ADA-40) and 2.6 (ADA-20) vs. 6.2 on placebo (P = .002 and 0.01, respectively).

Dr. Keystone highlighted this dramatic increase in joint space narrowing. "Patients treated on placebo initially ended up with more joint space narrowing over that period of time."

He also pointed out that joint space narrowing decreases quality of life, in addition to patients’ work productivity and ability to stay at work or not.

"Every drug has side effects. Everyone has a different answer to this. I’d like to see a study that helps us decide when it is optimal to start these types of drugs. But 10 years is a long time to follow these patients- it’s a good study. I would start patients earlier but I would also like to see data on which patients to start."

Dr. Keystone disclosed financial relationships with Abbott, Amgen, AstraZeneca, Biotest, Bristol-Myers Squibb, Centocor, Genentech, Genzyme, Merck, Novartis, Nycomed, Pfizer, Roche, and UCB.

BERLIN – A 6-month course of rosuvastatin (Crestor) significantly lessened endothelial dysfunction and lowered levels of C-reactive protein in patients with systemic sclerosis, judging from findings from a new study presented at the annual European Congress of Rheumatology.

Dr. Gabriella Szucs of the department of rheumatology, University of Debrecen, Hungary, presented results from the first study of rosuvastatin therapy in systemic sclerosis (SSc), measuring the extent of endothelial dysfunction and response to the drug in the small and large vessels of these patients.

The most significant results were seen in flow-mediated dilatation (FMD), which improved from 2.2% plus or minus 3.1% to 5.7% plus or minus 3.8% (P = .0033) over the 6 months of rosuvastatin therapy. A normal level of FMD would be 8%.

The Hungarian researcher said she and her colleagues wanted to find out whether statin therapy improved the endothelial and macrovascular function as well as arterial stiffness. "These patients had systemic sclerosis with continuous progression for which we don’t even have basic therapy or so-called disease-modifying therapy. We need to try everything to see if something works or not," said Dr. Szucs, the principal investigator.

"Endothelial dysfunction is one of the first steps in the pathogenesis of the disease. If we can improve this step, it is possible that we can slow disease progression, but if this is allowed to worsen then vascular complications lead to clinical symptoms."

All 28 patients who entered the case series study had SSc, according to American College of Rheumatology criteria. The majority (25/28) were female, and average disease duration was just over 13 years. The limited form of SSc, which is most common in females, was present in 21 patients, and 7 had the cutaneous form. Patients included had not received any statin medication for 6 months prior to the study. All patients received 20 mg of rosuvastatin daily for the 6 months of the case-series study.

Other therapies used by patients, and on which they were stable at entry to the study, included ARB/ACE inhibitors (75%), calcium channel blockers (57%), and pentoxifylline (82%).

Vascular and laboratory parameters were checked both before and after rosuvastatin therapy, including triglycerides, total and low-density lipoprotein (LDL) cholesterol, and C-reactive protein (CRP) levels.

Notably, brachial artery flow-mediated dilatation significantly improved in 23 of the total of 28 patients (82%). "For stiffness in the larger arteries [pulse-wave velocity of the aorto-femoral and carotid-femoral] we didn’t see any changes but this might vary if treatment continues for longer. We intend to follow these patients up at 12 months and thereafter."

She added that CRP levels were also shown to improve. CRP levels dropped from 5.1 plus or minus 5.2 mg/L before treatment to 3.4 plus or minus 2.7 mg/L (P = .01) after 6 months. "They are almost in the normal range, but it is better for the patient to have a lower CRP because later cardiovascular morbidity and mortality can decrease."

As expected, LDL levels decreased over the 6 months from 3.0 plus or minus 1.3 mmol/L to 2.2 plus or minus 1.0 mmol/L (P = .005), and mean triglyceride levels dropped from 1.7 plus or minus 0.97 mmol/L to 1.3 plus or minus 0.46 mmol/L (P = .0004).

No difference was seen between the limited form or the diffuse cutaneous form, reported Dr. Szucs.

"Systemic sclerosis is basically a vascular disease and rosuvastatin may improve endothelial dysfunction, correct dyslipidemia, and decrease CRP levels," said Dr. Szucs. "These results suggest that statins should be used together with more conventional vasodilator therapy throughout the disease course in order to protect from micro- and macrovascular damage and complications in scleroderma."

Dr. Szucs has declared no relevant conflicts of interest.

BERLIN – A 6-month course of rosuvastatin (Crestor) significantly lessened endothelial dysfunction and lowered levels of C-reactive protein in patients with systemic sclerosis, judging from findings from a new study presented at the annual European Congress of Rheumatology.

Dr. Gabriella Szucs of the department of rheumatology, University of Debrecen, Hungary, presented results from the first study of rosuvastatin therapy in systemic sclerosis (SSc), measuring the extent of endothelial dysfunction and response to the drug in the small and large vessels of these patients.

The most significant results were seen in flow-mediated dilatation (FMD), which improved from 2.2% plus or minus 3.1% to 5.7% plus or minus 3.8% (P = .0033) over the 6 months of rosuvastatin therapy. A normal level of FMD would be 8%.

The Hungarian researcher said she and her colleagues wanted to find out whether statin therapy improved the endothelial and macrovascular function as well as arterial stiffness. "These patients had systemic sclerosis with continuous progression for which we don’t even have basic therapy or so-called disease-modifying therapy. We need to try everything to see if something works or not," said Dr. Szucs, the principal investigator.

"Endothelial dysfunction is one of the first steps in the pathogenesis of the disease. If we can improve this step, it is possible that we can slow disease progression, but if this is allowed to worsen then vascular complications lead to clinical symptoms."

All 28 patients who entered the case series study had SSc, according to American College of Rheumatology criteria. The majority (25/28) were female, and average disease duration was just over 13 years. The limited form of SSc, which is most common in females, was present in 21 patients, and 7 had the cutaneous form. Patients included had not received any statin medication for 6 months prior to the study. All patients received 20 mg of rosuvastatin daily for the 6 months of the case-series study.

Other therapies used by patients, and on which they were stable at entry to the study, included ARB/ACE inhibitors (75%), calcium channel blockers (57%), and pentoxifylline (82%).

Vascular and laboratory parameters were checked both before and after rosuvastatin therapy, including triglycerides, total and low-density lipoprotein (LDL) cholesterol, and C-reactive protein (CRP) levels.

Notably, brachial artery flow-mediated dilatation significantly improved in 23 of the total of 28 patients (82%). "For stiffness in the larger arteries [pulse-wave velocity of the aorto-femoral and carotid-femoral] we didn’t see any changes but this might vary if treatment continues for longer. We intend to follow these patients up at 12 months and thereafter."

She added that CRP levels were also shown to improve. CRP levels dropped from 5.1 plus or minus 5.2 mg/L before treatment to 3.4 plus or minus 2.7 mg/L (P = .01) after 6 months. "They are almost in the normal range, but it is better for the patient to have a lower CRP because later cardiovascular morbidity and mortality can decrease."

As expected, LDL levels decreased over the 6 months from 3.0 plus or minus 1.3 mmol/L to 2.2 plus or minus 1.0 mmol/L (P = .005), and mean triglyceride levels dropped from 1.7 plus or minus 0.97 mmol/L to 1.3 plus or minus 0.46 mmol/L (P = .0004).

No difference was seen between the limited form or the diffuse cutaneous form, reported Dr. Szucs.

"Systemic sclerosis is basically a vascular disease and rosuvastatin may improve endothelial dysfunction, correct dyslipidemia, and decrease CRP levels," said Dr. Szucs. "These results suggest that statins should be used together with more conventional vasodilator therapy throughout the disease course in order to protect from micro- and macrovascular damage and complications in scleroderma."

Dr. Szucs has declared no relevant conflicts of interest.

BERLIN – A 6-month course of rosuvastatin (Crestor) significantly lessened endothelial dysfunction and lowered levels of C-reactive protein in patients with systemic sclerosis, judging from findings from a new study presented at the annual European Congress of Rheumatology.

Dr. Gabriella Szucs of the department of rheumatology, University of Debrecen, Hungary, presented results from the first study of rosuvastatin therapy in systemic sclerosis (SSc), measuring the extent of endothelial dysfunction and response to the drug in the small and large vessels of these patients.

The most significant results were seen in flow-mediated dilatation (FMD), which improved from 2.2% plus or minus 3.1% to 5.7% plus or minus 3.8% (P = .0033) over the 6 months of rosuvastatin therapy. A normal level of FMD would be 8%.

The Hungarian researcher said she and her colleagues wanted to find out whether statin therapy improved the endothelial and macrovascular function as well as arterial stiffness. "These patients had systemic sclerosis with continuous progression for which we don’t even have basic therapy or so-called disease-modifying therapy. We need to try everything to see if something works or not," said Dr. Szucs, the principal investigator.

"Endothelial dysfunction is one of the first steps in the pathogenesis of the disease. If we can improve this step, it is possible that we can slow disease progression, but if this is allowed to worsen then vascular complications lead to clinical symptoms."

All 28 patients who entered the case series study had SSc, according to American College of Rheumatology criteria. The majority (25/28) were female, and average disease duration was just over 13 years. The limited form of SSc, which is most common in females, was present in 21 patients, and 7 had the cutaneous form. Patients included had not received any statin medication for 6 months prior to the study. All patients received 20 mg of rosuvastatin daily for the 6 months of the case-series study.

Other therapies used by patients, and on which they were stable at entry to the study, included ARB/ACE inhibitors (75%), calcium channel blockers (57%), and pentoxifylline (82%).

Vascular and laboratory parameters were checked both before and after rosuvastatin therapy, including triglycerides, total and low-density lipoprotein (LDL) cholesterol, and C-reactive protein (CRP) levels.

Notably, brachial artery flow-mediated dilatation significantly improved in 23 of the total of 28 patients (82%). "For stiffness in the larger arteries [pulse-wave velocity of the aorto-femoral and carotid-femoral] we didn’t see any changes but this might vary if treatment continues for longer. We intend to follow these patients up at 12 months and thereafter."

She added that CRP levels were also shown to improve. CRP levels dropped from 5.1 plus or minus 5.2 mg/L before treatment to 3.4 plus or minus 2.7 mg/L (P = .01) after 6 months. "They are almost in the normal range, but it is better for the patient to have a lower CRP because later cardiovascular morbidity and mortality can decrease."

As expected, LDL levels decreased over the 6 months from 3.0 plus or minus 1.3 mmol/L to 2.2 plus or minus 1.0 mmol/L (P = .005), and mean triglyceride levels dropped from 1.7 plus or minus 0.97 mmol/L to 1.3 plus or minus 0.46 mmol/L (P = .0004).

No difference was seen between the limited form or the diffuse cutaneous form, reported Dr. Szucs.

"Systemic sclerosis is basically a vascular disease and rosuvastatin may improve endothelial dysfunction, correct dyslipidemia, and decrease CRP levels," said Dr. Szucs. "These results suggest that statins should be used together with more conventional vasodilator therapy throughout the disease course in order to protect from micro- and macrovascular damage and complications in scleroderma."

Dr. Szucs has declared no relevant conflicts of interest.

BERLIN – Obese patients with psoriatic arthritis demonstrate a worse response when starting anti–tumor necrosis factor therapy than do normal weight patients, but achievement of minimal disease activity can be improved by weight loss, based on two studies by Dr. Giovanni Di Minno, lead investigator on both.

The first study investigated the influence of obesity and the second, the influence of weight loss on response to starting anti–tumor necrosis factor (TNF) therapy.

The study on the effect of obesity on response to anti-TNF therapy in psoriatic arthritis (PsA) involved 135 psoriatic arthritis patients with a body mass index (BMI) over 30 kg/m²and 135 normal weight controls. Dr. Di Minno and his coinvestigators found that the two groups did not differ significantly in terms of disease activity and vascular risk factors including swollen and tender joint counts, levels of C-reactive protein, erythrocyte sedimentation rates, and psoriasis area severity index scores. They found that patients with a BMI over 30 had a higher prevalence of hypercholesterolemia and hypertriglyceridemia.

"Controlling weight is very important for these patients in the long term."

Dr. Di Minno and his associates in the department of clinical and experimental medicine, Federico II University, Naples, Italy, found that at 12 months’ follow-up, 98 of the 270 patients (36.3%) had achieved minimal disease activity (MDA). The prevalence of obesity was higher in those not achieving MDA than in those achieving it (64% vs. 25.5%, P less than .001).

"A BMI of over 30 was shown to be a strong predictor [of not achieving MDA] with a hazard ratio of 4.90 (95%CI: 3.04-7.87; P less than .001)," according to Cox regression analysis findings, reported Dr. Di Minno.

At 24 months, 17.3% of those who achieved MDA a year earlier relapsed, and 82.7% maintained their MDA. "A BMI greater than 30 was associated with a higher risk of disease relapse, with a hazard ratio of 2.04 [95% CI: 1.02-3.61; P = .014]," he said at the annual European Congress of Rheumatology.

Dr. Di Minno also noted that there was no difference found between the three anti-TNF blockers (infliximab, etanercept, and adalimumab) used in the study.

Session moderator Dr. Laura Coates said that the study was valuable because patients with PsA were prone to being overweight, and there was an established link between excess weight, metabolic syndrome, and psoriasis. "Until this study, there were no data to support the concept that weight loss could alter people’s outcome in terms of their arthritis response.

"This provides evidence of an immediate improvement to people’s health with weight loss, in terms of a better response to the anti-TNF therapies," said Dr. Coates of the division of rheumatic and musculoskeletal disease at Chapel Allerton Hospital in Leeds, England.

Furthermore, Dr. Coates noted that there was also a known association between psoriasis/PsA and cardiovascular morbidity related to the metabolic syndrome. "Controlling weight is very important for these patients in the long term as well," she said.

Introducing his second study, which investigated the effect of weight loss in obese patients, Dr Di Minno noted that prior studies had shown that restricting calorie intake reduced obesity-related inflammation.

The study specifically investigated the impact of changes in body weight on the achievement of MDA in PsA patients starting treatment on anti-TNF therapy.

A total of 126 obese (BMI greater than 30) patients with active PsA, who had not responded to traditional disease-modifying antirheumaic drugs were randomized to either a diet of 1,300 calories per day (n = 63), or an unrestricted diet (n = 63), with the advice to eat more vegetables, fish, and fresh fruits and no more than 2 tablespoons of olive oil per day. All patients were encouraged to exercise five times a week, and all started on anti-TNF therapy immediately.

"The intervention diet was the traditional Mediterranean diet rich in fibers, with a careful balance of sugar, proteins, and lipids, similar to the diet used by diabetics," explained Dr. Di Minno. The Mediterranean diet has been shown to lessen inflammation because it is rich in mono- and polyunsaturated fatty acids, antioxidants, dietary fiber, and phytochemicals.

At the 6-month follow-up, the researchers found a 5%-10% weight loss was achieved by 47.6% of patients on the hypocaloric diet versus 28.6% on the unrestricted diet. Only 41.3% of patients on the hypocaloric diet lost more than 10% of their body weight.

Furthermore, patients on the hypocaloric diet had more significant reductions in triglycerides and cholesterol compared with those on the unrestricted diet (29.1% vs. 10% for triglycerides. and 23.7% vs. 8.1% for cholesterol, for hypocaloric and unrestricted diets, respectively).

"To our surprise we found that the Mediterranean diet was not much better than the other diet in terms of MDA achievement [42.9% on the hypocaloric diet vs. 34.9% on the free diet; P = .465]," reported Dr. Di Minno.

MDA was achieved more frequently by patients who achieved a greater than 5% weight loss compared with those who did not [50% vs. 23.1%]. Furthermore, as weight loss increased so did the achievement of MDA, with 16.7%, 42.9%, and 59.5% MDA achievement for a weight loss of less than 5%, 5%-10%, and more than 10%, respectively.

The data strongly support the need for the control of body weight and cardiometabolic parameters in PsA subjects starting anti-TNF treatment, Dr. Di Minno said. "This may result in a better achievement of minimal disease activity in these patients."

Dr. Di Minno and Dr. Coates reported having no relevant financial conflicts.

BERLIN – Obese patients with psoriatic arthritis demonstrate a worse response when starting anti–tumor necrosis factor therapy than do normal weight patients, but achievement of minimal disease activity can be improved by weight loss, based on two studies by Dr. Giovanni Di Minno, lead investigator on both.

The first study investigated the influence of obesity and the second, the influence of weight loss on response to starting anti–tumor necrosis factor (TNF) therapy.

The study on the effect of obesity on response to anti-TNF therapy in psoriatic arthritis (PsA) involved 135 psoriatic arthritis patients with a body mass index (BMI) over 30 kg/m²and 135 normal weight controls. Dr. Di Minno and his coinvestigators found that the two groups did not differ significantly in terms of disease activity and vascular risk factors including swollen and tender joint counts, levels of C-reactive protein, erythrocyte sedimentation rates, and psoriasis area severity index scores. They found that patients with a BMI over 30 had a higher prevalence of hypercholesterolemia and hypertriglyceridemia.

"Controlling weight is very important for these patients in the long term."

Dr. Di Minno and his associates in the department of clinical and experimental medicine, Federico II University, Naples, Italy, found that at 12 months’ follow-up, 98 of the 270 patients (36.3%) had achieved minimal disease activity (MDA). The prevalence of obesity was higher in those not achieving MDA than in those achieving it (64% vs. 25.5%, P less than .001).

"A BMI of over 30 was shown to be a strong predictor [of not achieving MDA] with a hazard ratio of 4.90 (95%CI: 3.04-7.87; P less than .001)," according to Cox regression analysis findings, reported Dr. Di Minno.

At 24 months, 17.3% of those who achieved MDA a year earlier relapsed, and 82.7% maintained their MDA. "A BMI greater than 30 was associated with a higher risk of disease relapse, with a hazard ratio of 2.04 [95% CI: 1.02-3.61; P = .014]," he said at the annual European Congress of Rheumatology.

Dr. Di Minno also noted that there was no difference found between the three anti-TNF blockers (infliximab, etanercept, and adalimumab) used in the study.

Session moderator Dr. Laura Coates said that the study was valuable because patients with PsA were prone to being overweight, and there was an established link between excess weight, metabolic syndrome, and psoriasis. "Until this study, there were no data to support the concept that weight loss could alter people’s outcome in terms of their arthritis response.

"This provides evidence of an immediate improvement to people’s health with weight loss, in terms of a better response to the anti-TNF therapies," said Dr. Coates of the division of rheumatic and musculoskeletal disease at Chapel Allerton Hospital in Leeds, England.

Furthermore, Dr. Coates noted that there was also a known association between psoriasis/PsA and cardiovascular morbidity related to the metabolic syndrome. "Controlling weight is very important for these patients in the long term as well," she said.

Introducing his second study, which investigated the effect of weight loss in obese patients, Dr Di Minno noted that prior studies had shown that restricting calorie intake reduced obesity-related inflammation.

The study specifically investigated the impact of changes in body weight on the achievement of MDA in PsA patients starting treatment on anti-TNF therapy.

A total of 126 obese (BMI greater than 30) patients with active PsA, who had not responded to traditional disease-modifying antirheumaic drugs were randomized to either a diet of 1,300 calories per day (n = 63), or an unrestricted diet (n = 63), with the advice to eat more vegetables, fish, and fresh fruits and no more than 2 tablespoons of olive oil per day. All patients were encouraged to exercise five times a week, and all started on anti-TNF therapy immediately.

"The intervention diet was the traditional Mediterranean diet rich in fibers, with a careful balance of sugar, proteins, and lipids, similar to the diet used by diabetics," explained Dr. Di Minno. The Mediterranean diet has been shown to lessen inflammation because it is rich in mono- and polyunsaturated fatty acids, antioxidants, dietary fiber, and phytochemicals.

At the 6-month follow-up, the researchers found a 5%-10% weight loss was achieved by 47.6% of patients on the hypocaloric diet versus 28.6% on the unrestricted diet. Only 41.3% of patients on the hypocaloric diet lost more than 10% of their body weight.

Furthermore, patients on the hypocaloric diet had more significant reductions in triglycerides and cholesterol compared with those on the unrestricted diet (29.1% vs. 10% for triglycerides. and 23.7% vs. 8.1% for cholesterol, for hypocaloric and unrestricted diets, respectively).

"To our surprise we found that the Mediterranean diet was not much better than the other diet in terms of MDA achievement [42.9% on the hypocaloric diet vs. 34.9% on the free diet; P = .465]," reported Dr. Di Minno.

MDA was achieved more frequently by patients who achieved a greater than 5% weight loss compared with those who did not [50% vs. 23.1%]. Furthermore, as weight loss increased so did the achievement of MDA, with 16.7%, 42.9%, and 59.5% MDA achievement for a weight loss of less than 5%, 5%-10%, and more than 10%, respectively.

The data strongly support the need for the control of body weight and cardiometabolic parameters in PsA subjects starting anti-TNF treatment, Dr. Di Minno said. "This may result in a better achievement of minimal disease activity in these patients."

Dr. Di Minno and Dr. Coates reported having no relevant financial conflicts.

BERLIN – Obese patients with psoriatic arthritis demonstrate a worse response when starting anti–tumor necrosis factor therapy than do normal weight patients, but achievement of minimal disease activity can be improved by weight loss, based on two studies by Dr. Giovanni Di Minno, lead investigator on both.

The first study investigated the influence of obesity and the second, the influence of weight loss on response to starting anti–tumor necrosis factor (TNF) therapy.

The study on the effect of obesity on response to anti-TNF therapy in psoriatic arthritis (PsA) involved 135 psoriatic arthritis patients with a body mass index (BMI) over 30 kg/m²and 135 normal weight controls. Dr. Di Minno and his coinvestigators found that the two groups did not differ significantly in terms of disease activity and vascular risk factors including swollen and tender joint counts, levels of C-reactive protein, erythrocyte sedimentation rates, and psoriasis area severity index scores. They found that patients with a BMI over 30 had a higher prevalence of hypercholesterolemia and hypertriglyceridemia.

"Controlling weight is very important for these patients in the long term."

Dr. Di Minno and his associates in the department of clinical and experimental medicine, Federico II University, Naples, Italy, found that at 12 months’ follow-up, 98 of the 270 patients (36.3%) had achieved minimal disease activity (MDA). The prevalence of obesity was higher in those not achieving MDA than in those achieving it (64% vs. 25.5%, P less than .001).

"A BMI of over 30 was shown to be a strong predictor [of not achieving MDA] with a hazard ratio of 4.90 (95%CI: 3.04-7.87; P less than .001)," according to Cox regression analysis findings, reported Dr. Di Minno.

At 24 months, 17.3% of those who achieved MDA a year earlier relapsed, and 82.7% maintained their MDA. "A BMI greater than 30 was associated with a higher risk of disease relapse, with a hazard ratio of 2.04 [95% CI: 1.02-3.61; P = .014]," he said at the annual European Congress of Rheumatology.

Dr. Di Minno also noted that there was no difference found between the three anti-TNF blockers (infliximab, etanercept, and adalimumab) used in the study.

Session moderator Dr. Laura Coates said that the study was valuable because patients with PsA were prone to being overweight, and there was an established link between excess weight, metabolic syndrome, and psoriasis. "Until this study, there were no data to support the concept that weight loss could alter people’s outcome in terms of their arthritis response.

"This provides evidence of an immediate improvement to people’s health with weight loss, in terms of a better response to the anti-TNF therapies," said Dr. Coates of the division of rheumatic and musculoskeletal disease at Chapel Allerton Hospital in Leeds, England.

Furthermore, Dr. Coates noted that there was also a known association between psoriasis/PsA and cardiovascular morbidity related to the metabolic syndrome. "Controlling weight is very important for these patients in the long term as well," she said.

Introducing his second study, which investigated the effect of weight loss in obese patients, Dr Di Minno noted that prior studies had shown that restricting calorie intake reduced obesity-related inflammation.

The study specifically investigated the impact of changes in body weight on the achievement of MDA in PsA patients starting treatment on anti-TNF therapy.

A total of 126 obese (BMI greater than 30) patients with active PsA, who had not responded to traditional disease-modifying antirheumaic drugs were randomized to either a diet of 1,300 calories per day (n = 63), or an unrestricted diet (n = 63), with the advice to eat more vegetables, fish, and fresh fruits and no more than 2 tablespoons of olive oil per day. All patients were encouraged to exercise five times a week, and all started on anti-TNF therapy immediately.

"The intervention diet was the traditional Mediterranean diet rich in fibers, with a careful balance of sugar, proteins, and lipids, similar to the diet used by diabetics," explained Dr. Di Minno. The Mediterranean diet has been shown to lessen inflammation because it is rich in mono- and polyunsaturated fatty acids, antioxidants, dietary fiber, and phytochemicals.

At the 6-month follow-up, the researchers found a 5%-10% weight loss was achieved by 47.6% of patients on the hypocaloric diet versus 28.6% on the unrestricted diet. Only 41.3% of patients on the hypocaloric diet lost more than 10% of their body weight.

Furthermore, patients on the hypocaloric diet had more significant reductions in triglycerides and cholesterol compared with those on the unrestricted diet (29.1% vs. 10% for triglycerides. and 23.7% vs. 8.1% for cholesterol, for hypocaloric and unrestricted diets, respectively).

"To our surprise we found that the Mediterranean diet was not much better than the other diet in terms of MDA achievement [42.9% on the hypocaloric diet vs. 34.9% on the free diet; P = .465]," reported Dr. Di Minno.

MDA was achieved more frequently by patients who achieved a greater than 5% weight loss compared with those who did not [50% vs. 23.1%]. Furthermore, as weight loss increased so did the achievement of MDA, with 16.7%, 42.9%, and 59.5% MDA achievement for a weight loss of less than 5%, 5%-10%, and more than 10%, respectively.

The data strongly support the need for the control of body weight and cardiometabolic parameters in PsA subjects starting anti-TNF treatment, Dr. Di Minno said. "This may result in a better achievement of minimal disease activity in these patients."

Dr. Di Minno and Dr. Coates reported having no relevant financial conflicts.

BARCELONA – A cartilage transplant procedure known as osteochondral allografting for femoral condyle lesions eased pain and improved function in the majority of patients, with grafts lasting as long as 20 years in more than half the recipients studied, according to Dr. Yadin Levy of Tel Aviv Medical Center, who conducted the study while a research fellow at the Scripps Clinic in La Jolla, Calif.

For this follow-up study, Dr. Levy used data from the Scripps Clinic’s osteochondral allografting (OCA) outcomes program, which has information on 614 OCA knee transplantations in 536 patients. Of these, 122 patients (129 knees) who had undergone OCA transplantation of the femoral condyle and were at least 10 years on from their initial surgery were eligible for this analysis. Most (91%) of these patients had over 10 years of follow-up. The average patient age was 31 years, and 85% were younger than 45 years.

Patients underwent surgery for pathologies including osteochondritis dissecans (45%), traumatic cartilage injury (22.5%), degenerative chondral lesion (15.5%), avascular necrosis (14.7%), and osteochondral fracture (2.3%), he said at the World Congress on Osteoarthritis.

Clinical outcome measures included the modified D’Aubigne and 18-point Postel score, the International Knee Documentation Committee (IKDC), the Knee Society (KS) function score, and subjective patient satisfaction with the outcome of their procedure. Reoperations were recorded by frequency and type, and graft survivorship was also assessed.

A mean follow-up of 14.4 years (2.4-27.5) showed that 24% of knees failed with a mean time to failure of 7.2 +/- 5.2 years.

IKDC pain scores dropped from a mean of 7.0 preoperatively to 3.8 (P less than .001) postoperatively. Function also showed improvement over the follow-up period from a mean IKDC function score of 3.4 preoperatively to 7.2 postoperatively (P less than .001). KS function improved from 65.6 to 82.5 (P less than .001). The vast majority (72%) of patients rated their operation outcome as "extremely satisfied."

With respect to graft survival, results showed that 82% survived intact for 10 years and 66% for 20 years. Patients who were older than 30 years were 3.5 times more likely to fail than patients who were younger (P less than .05). Also, patients who had experienced over two operations were 2.8 times more likely to fail than patients who had undergone one or no previous operations (P less than .05).

"The results demonstrate that this is a good treatment modality for young patients," remarked Dr. Levy.

"Firstly, [OCA] successfully treats the condition and allows the majority of patients to return to their daily activities, and secondly, it postpones the need for arthroplasty or graft removal," he added.

Many short-term follow-up studies exist providing evidence of clinical results, but very few long-term follow-up studies were available that address graft survivorship and durability, he said.

Dr. Levy explained the principle of OCA. "We basically transfer a structured articular cartilage with viable chondrocytes on the surface and underneath the bone, which acts as a scaffold," he said at the congress, sponsored by the Osteoarthritis Research Society International.

The operation is suitable for large and small chondral and osteochondral defects and can be clinically applied for cartilage repair and in complex reconstructions. "In complex reconstruction we are trying to repair the bone underneath the cartilage as well as the cartilage," he said.

"Since there is cartilage wear, the joint surfaces are not smooth and gliding, which will lead to accelerated wear and ultimately to osteoarthritis," Dr. Levy pointed out.

Cartilage problems pose a treatment challenge because the tissue is incapable of self-repair and self-regrowth. Both artificial and biological modalities exist, but according to Dr. Levy, biological treatment modalities, such as OCA, are a viable option before artificial joint replacement especially in young patients for whom there is a high risk of revision.

"ACI [autologous chondrocyte implantation] and OCA are commonly used for large lesions, of more than 4 cm. The advantage of OCA is the ability to perform a single-stage operation for large bone defect," he said.

A major advantage of the method was that, even if the first allograft failed, patients could reconvert to another allograft in the revision surgery, which would again postpone the need for arthroplasty, Dr. Levy added.

Reoperations were conducted in 47% of knees. The number of reoperations was roughly equal for graft-related and non-graft-related reasons: 23% of patients required non-graft-related reoperations including arthroscopy, such as hardware removal, while graft-related reoperations were required by 24% of patients, the majority of which (48%) were OCA revision. "The majority of failures were because of pain and radiographic fragmentation of the allografts," reported Dr. Levy.

In addition, the researchers evaluated predictors for OCA failure using logistical regression analysis. "We found that older patients who had had several pervious surgeries tended to fail more," he said. "This raises the question of whether, in the era of MRI and advanced radiographic assessments, we should treat younger patients with single operations increasing the likelihood of success."

In conclusion, Dr. Levy said that he believed OCA was a very good treatment modality, which many young patients could benefit from. "It can reduce pain, return functional ability and can postpone the need for arthroplasty."

"Ultimately, I would be happy to see [fewer] failures in the short term; however, I believe that we do not fully understand what causes graft failure and this will need further studies," he said.

Dr. Levy has not reported any relevant financial conflicts.

BARCELONA – A cartilage transplant procedure known as osteochondral allografting for femoral condyle lesions eased pain and improved function in the majority of patients, with grafts lasting as long as 20 years in more than half the recipients studied, according to Dr. Yadin Levy of Tel Aviv Medical Center, who conducted the study while a research fellow at the Scripps Clinic in La Jolla, Calif.

For this follow-up study, Dr. Levy used data from the Scripps Clinic’s osteochondral allografting (OCA) outcomes program, which has information on 614 OCA knee transplantations in 536 patients. Of these, 122 patients (129 knees) who had undergone OCA transplantation of the femoral condyle and were at least 10 years on from their initial surgery were eligible for this analysis. Most (91%) of these patients had over 10 years of follow-up. The average patient age was 31 years, and 85% were younger than 45 years.

Patients underwent surgery for pathologies including osteochondritis dissecans (45%), traumatic cartilage injury (22.5%), degenerative chondral lesion (15.5%), avascular necrosis (14.7%), and osteochondral fracture (2.3%), he said at the World Congress on Osteoarthritis.

Clinical outcome measures included the modified D’Aubigne and 18-point Postel score, the International Knee Documentation Committee (IKDC), the Knee Society (KS) function score, and subjective patient satisfaction with the outcome of their procedure. Reoperations were recorded by frequency and type, and graft survivorship was also assessed.

A mean follow-up of 14.4 years (2.4-27.5) showed that 24% of knees failed with a mean time to failure of 7.2 +/- 5.2 years.

IKDC pain scores dropped from a mean of 7.0 preoperatively to 3.8 (P less than .001) postoperatively. Function also showed improvement over the follow-up period from a mean IKDC function score of 3.4 preoperatively to 7.2 postoperatively (P less than .001). KS function improved from 65.6 to 82.5 (P less than .001). The vast majority (72%) of patients rated their operation outcome as "extremely satisfied."

With respect to graft survival, results showed that 82% survived intact for 10 years and 66% for 20 years. Patients who were older than 30 years were 3.5 times more likely to fail than patients who were younger (P less than .05). Also, patients who had experienced over two operations were 2.8 times more likely to fail than patients who had undergone one or no previous operations (P less than .05).

"The results demonstrate that this is a good treatment modality for young patients," remarked Dr. Levy.

"Firstly, [OCA] successfully treats the condition and allows the majority of patients to return to their daily activities, and secondly, it postpones the need for arthroplasty or graft removal," he added.

Many short-term follow-up studies exist providing evidence of clinical results, but very few long-term follow-up studies were available that address graft survivorship and durability, he said.

Dr. Levy explained the principle of OCA. "We basically transfer a structured articular cartilage with viable chondrocytes on the surface and underneath the bone, which acts as a scaffold," he said at the congress, sponsored by the Osteoarthritis Research Society International.

The operation is suitable for large and small chondral and osteochondral defects and can be clinically applied for cartilage repair and in complex reconstructions. "In complex reconstruction we are trying to repair the bone underneath the cartilage as well as the cartilage," he said.

"Since there is cartilage wear, the joint surfaces are not smooth and gliding, which will lead to accelerated wear and ultimately to osteoarthritis," Dr. Levy pointed out.

Cartilage problems pose a treatment challenge because the tissue is incapable of self-repair and self-regrowth. Both artificial and biological modalities exist, but according to Dr. Levy, biological treatment modalities, such as OCA, are a viable option before artificial joint replacement especially in young patients for whom there is a high risk of revision.

"ACI [autologous chondrocyte implantation] and OCA are commonly used for large lesions, of more than 4 cm. The advantage of OCA is the ability to perform a single-stage operation for large bone defect," he said.

A major advantage of the method was that, even if the first allograft failed, patients could reconvert to another allograft in the revision surgery, which would again postpone the need for arthroplasty, Dr. Levy added.

Reoperations were conducted in 47% of knees. The number of reoperations was roughly equal for graft-related and non-graft-related reasons: 23% of patients required non-graft-related reoperations including arthroscopy, such as hardware removal, while graft-related reoperations were required by 24% of patients, the majority of which (48%) were OCA revision. "The majority of failures were because of pain and radiographic fragmentation of the allografts," reported Dr. Levy.

In addition, the researchers evaluated predictors for OCA failure using logistical regression analysis. "We found that older patients who had had several pervious surgeries tended to fail more," he said. "This raises the question of whether, in the era of MRI and advanced radiographic assessments, we should treat younger patients with single operations increasing the likelihood of success."

In conclusion, Dr. Levy said that he believed OCA was a very good treatment modality, which many young patients could benefit from. "It can reduce pain, return functional ability and can postpone the need for arthroplasty."

"Ultimately, I would be happy to see [fewer] failures in the short term; however, I believe that we do not fully understand what causes graft failure and this will need further studies," he said.

Dr. Levy has not reported any relevant financial conflicts.

BARCELONA – A cartilage transplant procedure known as osteochondral allografting for femoral condyle lesions eased pain and improved function in the majority of patients, with grafts lasting as long as 20 years in more than half the recipients studied, according to Dr. Yadin Levy of Tel Aviv Medical Center, who conducted the study while a research fellow at the Scripps Clinic in La Jolla, Calif.

For this follow-up study, Dr. Levy used data from the Scripps Clinic’s osteochondral allografting (OCA) outcomes program, which has information on 614 OCA knee transplantations in 536 patients. Of these, 122 patients (129 knees) who had undergone OCA transplantation of the femoral condyle and were at least 10 years on from their initial surgery were eligible for this analysis. Most (91%) of these patients had over 10 years of follow-up. The average patient age was 31 years, and 85% were younger than 45 years.

Patients underwent surgery for pathologies including osteochondritis dissecans (45%), traumatic cartilage injury (22.5%), degenerative chondral lesion (15.5%), avascular necrosis (14.7%), and osteochondral fracture (2.3%), he said at the World Congress on Osteoarthritis.

Clinical outcome measures included the modified D’Aubigne and 18-point Postel score, the International Knee Documentation Committee (IKDC), the Knee Society (KS) function score, and subjective patient satisfaction with the outcome of their procedure. Reoperations were recorded by frequency and type, and graft survivorship was also assessed.

A mean follow-up of 14.4 years (2.4-27.5) showed that 24% of knees failed with a mean time to failure of 7.2 +/- 5.2 years.

IKDC pain scores dropped from a mean of 7.0 preoperatively to 3.8 (P less than .001) postoperatively. Function also showed improvement over the follow-up period from a mean IKDC function score of 3.4 preoperatively to 7.2 postoperatively (P less than .001). KS function improved from 65.6 to 82.5 (P less than .001). The vast majority (72%) of patients rated their operation outcome as "extremely satisfied."

With respect to graft survival, results showed that 82% survived intact for 10 years and 66% for 20 years. Patients who were older than 30 years were 3.5 times more likely to fail than patients who were younger (P less than .05). Also, patients who had experienced over two operations were 2.8 times more likely to fail than patients who had undergone one or no previous operations (P less than .05).

"The results demonstrate that this is a good treatment modality for young patients," remarked Dr. Levy.

"Firstly, [OCA] successfully treats the condition and allows the majority of patients to return to their daily activities, and secondly, it postpones the need for arthroplasty or graft removal," he added.

Many short-term follow-up studies exist providing evidence of clinical results, but very few long-term follow-up studies were available that address graft survivorship and durability, he said.

Dr. Levy explained the principle of OCA. "We basically transfer a structured articular cartilage with viable chondrocytes on the surface and underneath the bone, which acts as a scaffold," he said at the congress, sponsored by the Osteoarthritis Research Society International.

The operation is suitable for large and small chondral and osteochondral defects and can be clinically applied for cartilage repair and in complex reconstructions. "In complex reconstruction we are trying to repair the bone underneath the cartilage as well as the cartilage," he said.

"Since there is cartilage wear, the joint surfaces are not smooth and gliding, which will lead to accelerated wear and ultimately to osteoarthritis," Dr. Levy pointed out.

Cartilage problems pose a treatment challenge because the tissue is incapable of self-repair and self-regrowth. Both artificial and biological modalities exist, but according to Dr. Levy, biological treatment modalities, such as OCA, are a viable option before artificial joint replacement especially in young patients for whom there is a high risk of revision.

"ACI [autologous chondrocyte implantation] and OCA are commonly used for large lesions, of more than 4 cm. The advantage of OCA is the ability to perform a single-stage operation for large bone defect," he said.

A major advantage of the method was that, even if the first allograft failed, patients could reconvert to another allograft in the revision surgery, which would again postpone the need for arthroplasty, Dr. Levy added.

Reoperations were conducted in 47% of knees. The number of reoperations was roughly equal for graft-related and non-graft-related reasons: 23% of patients required non-graft-related reoperations including arthroscopy, such as hardware removal, while graft-related reoperations were required by 24% of patients, the majority of which (48%) were OCA revision. "The majority of failures were because of pain and radiographic fragmentation of the allografts," reported Dr. Levy.

In addition, the researchers evaluated predictors for OCA failure using logistical regression analysis. "We found that older patients who had had several pervious surgeries tended to fail more," he said. "This raises the question of whether, in the era of MRI and advanced radiographic assessments, we should treat younger patients with single operations increasing the likelihood of success."

In conclusion, Dr. Levy said that he believed OCA was a very good treatment modality, which many young patients could benefit from. "It can reduce pain, return functional ability and can postpone the need for arthroplasty."

"Ultimately, I would be happy to see [fewer] failures in the short term; however, I believe that we do not fully understand what causes graft failure and this will need further studies," he said.

Dr. Levy has not reported any relevant financial conflicts.