User login
Limited Bone Loss With Low-dose Glucocorticoids
Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the posttest.
PARIS – Bone loss at 1 year is limited at the low doses of glucocorticoids typically used to treat adults with chronic inflammatory disorders like rheumatoid arthritis, based on a meta-analysis of prospective studies of 1,565 patients with chronic inflammatory diseases (44 studies) and 635 transplant patients (16 studies).
Glucocorticoid treatment at the high doses used in transplantation patients leads to considerable bone loss, especially in the lumbar spine. In contrast, bone loss is limited during glucocorticoid treatment at the lower doses used in chronic inflammatory disease, Dr. Maarten Boers, professor of clinical epidemiology at VU University Medical Center, Amsterdam, reported at the annual European Congress of Rheumatology.
All patients in the meta-analysis had at least two bone mineral density (BMD) measurements over at least 8 months. None received bisphosphonates or antiresorptive therapies, only vitamin D3 and calcium were allowed.
Glucocorticoid doses ranged from 1 to 16 mg/day (mean 9 mg/day) in the patients with chronic inflammatory diseases and from 6 to 53 mg/day (mean 20 mg/day) in the transplant patients. In those with chronic inflammatory diseases, bone loss at the lumbar spine at 1 year averaged –1.7%. For the patients who had measures of femoral neck bone loss, the average loss was –1.3%. In the transplantation group, average bone loss was much higher at –3.6% in the lumbar spine and –3.1% in the femoral neck.
Among the 44 studies that reported BMD in patients with chronic inflammatory diseases, BMD declined from baseline in the lumbar spine by as much as 6% in 1 study and increased by as much as 2% in another. The 39 studies that also reported changes in femoral neck BMD described a decline as high as 7% and an increase as great as 4%.
"We sought to quantify the ‘pure’ effect of GC [glucocorticoid(s)], because so little high-quality information is available," Dr. Boers explained.
The data analysis in these studies was limited to 1 year, but about two-thirds of the patients with chronic inflammatory disease were on chronic glucocorticoid therapy and almost all of the transplant patients were just starting glucocorticoids, Dr. Boers said.
"On average, the yearly loss in a wide range of doses is limited, but starters have more bone loss. The heterogeneity of studies suggests that factors other than GC dose are the main drivers in determining bone loss. Although the data were not available to study these factors, it appears likely that disease activity is very important and acts as a confounder. In other words, disease activity leads to bone loss, and high GC doses lead to bone loss. Effective treatment of high disease activity requires high GC doses, but the interaction of these factors may lead to bone loss comparable to low disease activity being treated with low doses," he explained in an interview.
Many rheumatoid arthritis patients are initially treated with "bridge" glucocorticoid therapy for a few months, until the effect of methotrexate is established, he said. "We prefer ‘COBRA [combination therapy for rheumatoid arthritis] light,’ where patients are initially treated with a higher dose of 30 mg, rapidly tapered to 7.5 mg/day, and maintained for at least 6 months. Several groups are advising to treat for longer periods, and observational data suggest many patients are kept on chronic therapy for periods longer than 1 year," he said.
Local guidelines differ, but all guidelines agree on the necessity of prophylaxis in high-risk situations and on screening for intermediate-risk patients. Unfortunately, many patients requiring antiresorptive treatment according to the guidelines are still not receiving it, with surveys showing about 70% uptake in patients treated by rheumatologists and only about 30% in patients receiving care from other specialists, he said.
"Given the effects of starting GC therapy in our review, we strongly suggest all patients requiring GC therapy for longer than 3 months at any dose should at least be assessed by DXA scan; postmenopausal women, males age 70 or older, and patients with other risk factors should be treated with antiresorptive agents from the start," Dr. Boers advised.
Dr. Boers his coinvestigators reported having no financial conflicts.
To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.
Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the posttest.
PARIS – Bone loss at 1 year is limited at the low doses of glucocorticoids typically used to treat adults with chronic inflammatory disorders like rheumatoid arthritis, based on a meta-analysis of prospective studies of 1,565 patients with chronic inflammatory diseases (44 studies) and 635 transplant patients (16 studies).
Glucocorticoid treatment at the high doses used in transplantation patients leads to considerable bone loss, especially in the lumbar spine. In contrast, bone loss is limited during glucocorticoid treatment at the lower doses used in chronic inflammatory disease, Dr. Maarten Boers, professor of clinical epidemiology at VU University Medical Center, Amsterdam, reported at the annual European Congress of Rheumatology.
All patients in the meta-analysis had at least two bone mineral density (BMD) measurements over at least 8 months. None received bisphosphonates or antiresorptive therapies, only vitamin D3 and calcium were allowed.
Glucocorticoid doses ranged from 1 to 16 mg/day (mean 9 mg/day) in the patients with chronic inflammatory diseases and from 6 to 53 mg/day (mean 20 mg/day) in the transplant patients. In those with chronic inflammatory diseases, bone loss at the lumbar spine at 1 year averaged –1.7%. For the patients who had measures of femoral neck bone loss, the average loss was –1.3%. In the transplantation group, average bone loss was much higher at –3.6% in the lumbar spine and –3.1% in the femoral neck.
Among the 44 studies that reported BMD in patients with chronic inflammatory diseases, BMD declined from baseline in the lumbar spine by as much as 6% in 1 study and increased by as much as 2% in another. The 39 studies that also reported changes in femoral neck BMD described a decline as high as 7% and an increase as great as 4%.
"We sought to quantify the ‘pure’ effect of GC [glucocorticoid(s)], because so little high-quality information is available," Dr. Boers explained.
The data analysis in these studies was limited to 1 year, but about two-thirds of the patients with chronic inflammatory disease were on chronic glucocorticoid therapy and almost all of the transplant patients were just starting glucocorticoids, Dr. Boers said.
"On average, the yearly loss in a wide range of doses is limited, but starters have more bone loss. The heterogeneity of studies suggests that factors other than GC dose are the main drivers in determining bone loss. Although the data were not available to study these factors, it appears likely that disease activity is very important and acts as a confounder. In other words, disease activity leads to bone loss, and high GC doses lead to bone loss. Effective treatment of high disease activity requires high GC doses, but the interaction of these factors may lead to bone loss comparable to low disease activity being treated with low doses," he explained in an interview.
Many rheumatoid arthritis patients are initially treated with "bridge" glucocorticoid therapy for a few months, until the effect of methotrexate is established, he said. "We prefer ‘COBRA [combination therapy for rheumatoid arthritis] light,’ where patients are initially treated with a higher dose of 30 mg, rapidly tapered to 7.5 mg/day, and maintained for at least 6 months. Several groups are advising to treat for longer periods, and observational data suggest many patients are kept on chronic therapy for periods longer than 1 year," he said.
Local guidelines differ, but all guidelines agree on the necessity of prophylaxis in high-risk situations and on screening for intermediate-risk patients. Unfortunately, many patients requiring antiresorptive treatment according to the guidelines are still not receiving it, with surveys showing about 70% uptake in patients treated by rheumatologists and only about 30% in patients receiving care from other specialists, he said.
"Given the effects of starting GC therapy in our review, we strongly suggest all patients requiring GC therapy for longer than 3 months at any dose should at least be assessed by DXA scan; postmenopausal women, males age 70 or older, and patients with other risk factors should be treated with antiresorptive agents from the start," Dr. Boers advised.
Dr. Boers his coinvestigators reported having no financial conflicts.
To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.
Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the posttest.
PARIS – Bone loss at 1 year is limited at the low doses of glucocorticoids typically used to treat adults with chronic inflammatory disorders like rheumatoid arthritis, based on a meta-analysis of prospective studies of 1,565 patients with chronic inflammatory diseases (44 studies) and 635 transplant patients (16 studies).
Glucocorticoid treatment at the high doses used in transplantation patients leads to considerable bone loss, especially in the lumbar spine. In contrast, bone loss is limited during glucocorticoid treatment at the lower doses used in chronic inflammatory disease, Dr. Maarten Boers, professor of clinical epidemiology at VU University Medical Center, Amsterdam, reported at the annual European Congress of Rheumatology.
All patients in the meta-analysis had at least two bone mineral density (BMD) measurements over at least 8 months. None received bisphosphonates or antiresorptive therapies, only vitamin D3 and calcium were allowed.
Glucocorticoid doses ranged from 1 to 16 mg/day (mean 9 mg/day) in the patients with chronic inflammatory diseases and from 6 to 53 mg/day (mean 20 mg/day) in the transplant patients. In those with chronic inflammatory diseases, bone loss at the lumbar spine at 1 year averaged –1.7%. For the patients who had measures of femoral neck bone loss, the average loss was –1.3%. In the transplantation group, average bone loss was much higher at –3.6% in the lumbar spine and –3.1% in the femoral neck.
Among the 44 studies that reported BMD in patients with chronic inflammatory diseases, BMD declined from baseline in the lumbar spine by as much as 6% in 1 study and increased by as much as 2% in another. The 39 studies that also reported changes in femoral neck BMD described a decline as high as 7% and an increase as great as 4%.
"We sought to quantify the ‘pure’ effect of GC [glucocorticoid(s)], because so little high-quality information is available," Dr. Boers explained.
The data analysis in these studies was limited to 1 year, but about two-thirds of the patients with chronic inflammatory disease were on chronic glucocorticoid therapy and almost all of the transplant patients were just starting glucocorticoids, Dr. Boers said.
"On average, the yearly loss in a wide range of doses is limited, but starters have more bone loss. The heterogeneity of studies suggests that factors other than GC dose are the main drivers in determining bone loss. Although the data were not available to study these factors, it appears likely that disease activity is very important and acts as a confounder. In other words, disease activity leads to bone loss, and high GC doses lead to bone loss. Effective treatment of high disease activity requires high GC doses, but the interaction of these factors may lead to bone loss comparable to low disease activity being treated with low doses," he explained in an interview.
Many rheumatoid arthritis patients are initially treated with "bridge" glucocorticoid therapy for a few months, until the effect of methotrexate is established, he said. "We prefer ‘COBRA [combination therapy for rheumatoid arthritis] light,’ where patients are initially treated with a higher dose of 30 mg, rapidly tapered to 7.5 mg/day, and maintained for at least 6 months. Several groups are advising to treat for longer periods, and observational data suggest many patients are kept on chronic therapy for periods longer than 1 year," he said.
Local guidelines differ, but all guidelines agree on the necessity of prophylaxis in high-risk situations and on screening for intermediate-risk patients. Unfortunately, many patients requiring antiresorptive treatment according to the guidelines are still not receiving it, with surveys showing about 70% uptake in patients treated by rheumatologists and only about 30% in patients receiving care from other specialists, he said.
"Given the effects of starting GC therapy in our review, we strongly suggest all patients requiring GC therapy for longer than 3 months at any dose should at least be assessed by DXA scan; postmenopausal women, males age 70 or older, and patients with other risk factors should be treated with antiresorptive agents from the start," Dr. Boers advised.
Dr. Boers his coinvestigators reported having no financial conflicts.
To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.
AT THE EULAR CONGRESS 2014
High aortic aneurysm dissection risk in giant-cell arteritis patients
PARIS – The usual rule that the larger an aortic aneurysm grows the greater the risk it will undergo dissection or rupture doesn’t work in patients with giant-cell arteritis. Their aortic aneurysms appear liable to dissect or rupture at any size after the diagnosis of giant-cell arteritis occurs, based on a retrospective study of 195 patients followed at a single U.S. center.
"Aortic size at diagnosis or last follow-up did not predict aortic dissection or rupture," Dr. Ashima Makol reported at the annual European Congress of Rheumatology, nor were linear, serial measurements of aortic size able to reliably predict risk for these complications in patients with GCA. Without a reliable way to identify patients with GCA at risk for dissection or rupture, the only management advice remaining is to follow GCA patients annually with imaging, said Dr. Makol, a rheumatologist at the Mayo Clinic in Rochester, Minn.
Positron emission tomography, CT angiography, or MR angiography seem to be the best ways to follow these patients, but if those are too costly to do annually, then transesophageal echocardiography or a chest x-ray are other options, Dr. Makol said in an interview.
Although 30% of patients with GCA have a vasculitis that involves the aorta and its branches and an increased risk for developing aortic aneurysms, the way these aneurysms change over time and the relationship between aneurysm size and the risk for dissection or rupture in GCA patients were not previously reported. To address this, Dr. Makol and her associates reviewed 195 patients with GCA and an aortic aneurysm seen at the Mayo Clinic during 2000-2012.
The aneurysms occurred in the ascending thoracic aorta in 161 patients (83%), the descending thoracic aorta in 21 (11%), and the abdominal aorta in the remaining 13 patients (7%). (Percentages total 101% because of rounding.) The patients averaged 74 years old, 62% were women, and 49% had a history of smoking.
During follow-up, 14 patients (7%) had an aneurysm dissection, and 1 patient (1%) had an aneurysm rupture, the investigators reported. All of the dissections and the rupture occurred in thoracic aorta aneurysms.
At the time of GCA diagnosis, the average aneurysm size in the 15 patients who developed an aneurysm complication was 51 mm, which was very similar to the average size of 49 mm in the 180 patients who did not have an aneurysm dissection or rupture during follow-up.
Patients also showed no clear link between aneurysm size at the time of dissection or rupture and the aneurysm size during follow-up of patients without these complications. The average maximum aneurysm diameter among the 15 patients with a complication at the time of their event was 54 mm, while the average aneurysm size at last follow-up among those without a dissection or rupture during follow-up was 50 mm, a difference that was not statistically significant, Dr. Makol said.
The average rate of aneurysm growth during 3 years of follow-up for all the GCA patients in the analysis was 1.59 mm/year, a rate "somewhat higher" than the average annual growth rate of 1 mm/year reported for aortic aneurysms in patients without inflammatory disease. The 54-mm average aneurysm diameter at the time of dissection or rupture in the CGA patients was "somewhat lower" than the 65-mm average aneurysm diameter seen at the time of dissection or rupture in patients without inflammatory disease, she noted.
The study is the first reported to look at the pattern of aneurysm growth and complications in GCA patients, although it is limited to the retrospective experience at one tertiary referral center and so may reflect a referral bias, Dr. Makol said. But the inability of the analysis to identify aneurysm characteristics in GCA patients that can telegraph an increased risk for complications means that all GCA patients with an aortic aneurysm need careful surveillance by annual imaging, she advised.
Dr. Makol said that she had no disclosures.
The take home message from this article can be summed up in this manner: Aneurysms in patients with, or that are the result of, giant-cell arteritis (GCA) may be at increased risk for a catastrophic event at an earlier, or at least more unpredictable point, than aneurysms that are not associated with GCA. As the article states, "the usual rule that the larger an aortic aneurysm grows the greater the risk" may not hold in this small subset of patients with GCA. Further interpretation of this article leads me to conclude, however, that the discussion centers (nearly) exclusively on pathology involving the ascending aorta. Only a very small percentage of the cohort that was studied had aneurysms distal to the subclavian artery and none of the fifteen catastrophic events that were noted occurred below the diaphragm. While not clear from the article, it is quite likely all of the catastrophic events, rupture or dissection, occurred in association with disease involving the ascending aorta. As such, the article’s content may be more appropriate for those who routinely treat patients with ascending aortic pathology and not so much for vascular surgeons who traditionally treat aortic pathology from the transverse arch down. In addition, there seems to be the inference in the article that this data can be directly translated to disease affecting the infra-renal aorta which is a conclusion that I would hold, is premature, at best. I, for one, must admit that while I have seen a number of patients with GCA, I have never had the occasion to treat an aneurysm in one of them. While this may be true for many of us, the point of the article does have merit and the information should be stored somewhere in our memory banks. Who knows, perhaps someday we may see it pop up on some board question.
Dr. Mark D. Morasch is a vascular surgeon at St Vincent Healthcare Heart and Vascular, Billings, Montana, and an associate medical editor for Vascular Specialist.
The take home message from this article can be summed up in this manner: Aneurysms in patients with, or that are the result of, giant-cell arteritis (GCA) may be at increased risk for a catastrophic event at an earlier, or at least more unpredictable point, than aneurysms that are not associated with GCA. As the article states, "the usual rule that the larger an aortic aneurysm grows the greater the risk" may not hold in this small subset of patients with GCA. Further interpretation of this article leads me to conclude, however, that the discussion centers (nearly) exclusively on pathology involving the ascending aorta. Only a very small percentage of the cohort that was studied had aneurysms distal to the subclavian artery and none of the fifteen catastrophic events that were noted occurred below the diaphragm. While not clear from the article, it is quite likely all of the catastrophic events, rupture or dissection, occurred in association with disease involving the ascending aorta. As such, the article’s content may be more appropriate for those who routinely treat patients with ascending aortic pathology and not so much for vascular surgeons who traditionally treat aortic pathology from the transverse arch down. In addition, there seems to be the inference in the article that this data can be directly translated to disease affecting the infra-renal aorta which is a conclusion that I would hold, is premature, at best. I, for one, must admit that while I have seen a number of patients with GCA, I have never had the occasion to treat an aneurysm in one of them. While this may be true for many of us, the point of the article does have merit and the information should be stored somewhere in our memory banks. Who knows, perhaps someday we may see it pop up on some board question.
Dr. Mark D. Morasch is a vascular surgeon at St Vincent Healthcare Heart and Vascular, Billings, Montana, and an associate medical editor for Vascular Specialist.
The take home message from this article can be summed up in this manner: Aneurysms in patients with, or that are the result of, giant-cell arteritis (GCA) may be at increased risk for a catastrophic event at an earlier, or at least more unpredictable point, than aneurysms that are not associated with GCA. As the article states, "the usual rule that the larger an aortic aneurysm grows the greater the risk" may not hold in this small subset of patients with GCA. Further interpretation of this article leads me to conclude, however, that the discussion centers (nearly) exclusively on pathology involving the ascending aorta. Only a very small percentage of the cohort that was studied had aneurysms distal to the subclavian artery and none of the fifteen catastrophic events that were noted occurred below the diaphragm. While not clear from the article, it is quite likely all of the catastrophic events, rupture or dissection, occurred in association with disease involving the ascending aorta. As such, the article’s content may be more appropriate for those who routinely treat patients with ascending aortic pathology and not so much for vascular surgeons who traditionally treat aortic pathology from the transverse arch down. In addition, there seems to be the inference in the article that this data can be directly translated to disease affecting the infra-renal aorta which is a conclusion that I would hold, is premature, at best. I, for one, must admit that while I have seen a number of patients with GCA, I have never had the occasion to treat an aneurysm in one of them. While this may be true for many of us, the point of the article does have merit and the information should be stored somewhere in our memory banks. Who knows, perhaps someday we may see it pop up on some board question.
Dr. Mark D. Morasch is a vascular surgeon at St Vincent Healthcare Heart and Vascular, Billings, Montana, and an associate medical editor for Vascular Specialist.
PARIS – The usual rule that the larger an aortic aneurysm grows the greater the risk it will undergo dissection or rupture doesn’t work in patients with giant-cell arteritis. Their aortic aneurysms appear liable to dissect or rupture at any size after the diagnosis of giant-cell arteritis occurs, based on a retrospective study of 195 patients followed at a single U.S. center.
"Aortic size at diagnosis or last follow-up did not predict aortic dissection or rupture," Dr. Ashima Makol reported at the annual European Congress of Rheumatology, nor were linear, serial measurements of aortic size able to reliably predict risk for these complications in patients with GCA. Without a reliable way to identify patients with GCA at risk for dissection or rupture, the only management advice remaining is to follow GCA patients annually with imaging, said Dr. Makol, a rheumatologist at the Mayo Clinic in Rochester, Minn.
Positron emission tomography, CT angiography, or MR angiography seem to be the best ways to follow these patients, but if those are too costly to do annually, then transesophageal echocardiography or a chest x-ray are other options, Dr. Makol said in an interview.
Although 30% of patients with GCA have a vasculitis that involves the aorta and its branches and an increased risk for developing aortic aneurysms, the way these aneurysms change over time and the relationship between aneurysm size and the risk for dissection or rupture in GCA patients were not previously reported. To address this, Dr. Makol and her associates reviewed 195 patients with GCA and an aortic aneurysm seen at the Mayo Clinic during 2000-2012.
The aneurysms occurred in the ascending thoracic aorta in 161 patients (83%), the descending thoracic aorta in 21 (11%), and the abdominal aorta in the remaining 13 patients (7%). (Percentages total 101% because of rounding.) The patients averaged 74 years old, 62% were women, and 49% had a history of smoking.
During follow-up, 14 patients (7%) had an aneurysm dissection, and 1 patient (1%) had an aneurysm rupture, the investigators reported. All of the dissections and the rupture occurred in thoracic aorta aneurysms.
At the time of GCA diagnosis, the average aneurysm size in the 15 patients who developed an aneurysm complication was 51 mm, which was very similar to the average size of 49 mm in the 180 patients who did not have an aneurysm dissection or rupture during follow-up.
Patients also showed no clear link between aneurysm size at the time of dissection or rupture and the aneurysm size during follow-up of patients without these complications. The average maximum aneurysm diameter among the 15 patients with a complication at the time of their event was 54 mm, while the average aneurysm size at last follow-up among those without a dissection or rupture during follow-up was 50 mm, a difference that was not statistically significant, Dr. Makol said.
The average rate of aneurysm growth during 3 years of follow-up for all the GCA patients in the analysis was 1.59 mm/year, a rate "somewhat higher" than the average annual growth rate of 1 mm/year reported for aortic aneurysms in patients without inflammatory disease. The 54-mm average aneurysm diameter at the time of dissection or rupture in the CGA patients was "somewhat lower" than the 65-mm average aneurysm diameter seen at the time of dissection or rupture in patients without inflammatory disease, she noted.
The study is the first reported to look at the pattern of aneurysm growth and complications in GCA patients, although it is limited to the retrospective experience at one tertiary referral center and so may reflect a referral bias, Dr. Makol said. But the inability of the analysis to identify aneurysm characteristics in GCA patients that can telegraph an increased risk for complications means that all GCA patients with an aortic aneurysm need careful surveillance by annual imaging, she advised.
Dr. Makol said that she had no disclosures.
PARIS – The usual rule that the larger an aortic aneurysm grows the greater the risk it will undergo dissection or rupture doesn’t work in patients with giant-cell arteritis. Their aortic aneurysms appear liable to dissect or rupture at any size after the diagnosis of giant-cell arteritis occurs, based on a retrospective study of 195 patients followed at a single U.S. center.
"Aortic size at diagnosis or last follow-up did not predict aortic dissection or rupture," Dr. Ashima Makol reported at the annual European Congress of Rheumatology, nor were linear, serial measurements of aortic size able to reliably predict risk for these complications in patients with GCA. Without a reliable way to identify patients with GCA at risk for dissection or rupture, the only management advice remaining is to follow GCA patients annually with imaging, said Dr. Makol, a rheumatologist at the Mayo Clinic in Rochester, Minn.
Positron emission tomography, CT angiography, or MR angiography seem to be the best ways to follow these patients, but if those are too costly to do annually, then transesophageal echocardiography or a chest x-ray are other options, Dr. Makol said in an interview.
Although 30% of patients with GCA have a vasculitis that involves the aorta and its branches and an increased risk for developing aortic aneurysms, the way these aneurysms change over time and the relationship between aneurysm size and the risk for dissection or rupture in GCA patients were not previously reported. To address this, Dr. Makol and her associates reviewed 195 patients with GCA and an aortic aneurysm seen at the Mayo Clinic during 2000-2012.
The aneurysms occurred in the ascending thoracic aorta in 161 patients (83%), the descending thoracic aorta in 21 (11%), and the abdominal aorta in the remaining 13 patients (7%). (Percentages total 101% because of rounding.) The patients averaged 74 years old, 62% were women, and 49% had a history of smoking.
During follow-up, 14 patients (7%) had an aneurysm dissection, and 1 patient (1%) had an aneurysm rupture, the investigators reported. All of the dissections and the rupture occurred in thoracic aorta aneurysms.
At the time of GCA diagnosis, the average aneurysm size in the 15 patients who developed an aneurysm complication was 51 mm, which was very similar to the average size of 49 mm in the 180 patients who did not have an aneurysm dissection or rupture during follow-up.
Patients also showed no clear link between aneurysm size at the time of dissection or rupture and the aneurysm size during follow-up of patients without these complications. The average maximum aneurysm diameter among the 15 patients with a complication at the time of their event was 54 mm, while the average aneurysm size at last follow-up among those without a dissection or rupture during follow-up was 50 mm, a difference that was not statistically significant, Dr. Makol said.
The average rate of aneurysm growth during 3 years of follow-up for all the GCA patients in the analysis was 1.59 mm/year, a rate "somewhat higher" than the average annual growth rate of 1 mm/year reported for aortic aneurysms in patients without inflammatory disease. The 54-mm average aneurysm diameter at the time of dissection or rupture in the CGA patients was "somewhat lower" than the 65-mm average aneurysm diameter seen at the time of dissection or rupture in patients without inflammatory disease, she noted.
The study is the first reported to look at the pattern of aneurysm growth and complications in GCA patients, although it is limited to the retrospective experience at one tertiary referral center and so may reflect a referral bias, Dr. Makol said. But the inability of the analysis to identify aneurysm characteristics in GCA patients that can telegraph an increased risk for complications means that all GCA patients with an aortic aneurysm need careful surveillance by annual imaging, she advised.
Dr. Makol said that she had no disclosures.
AT THE EULAR CONGRESS 2014
Key clinical point: Risk for aortic aneurysm dissection in patients with giant-cell arteritis showed no link to aneurysm size.
Major finding: GCA patients with dissection or rupture of an aortic aneurysm had aneurysms that were similar in size to those of GCA patients without these complications.
Data source: Retrospective study of 195 patients with GCA at one U.S. center.
Disclosures: Dr. Makol said that she had no disclosures.
VIDEO: JIA response predicted after start of therapy
PARIS – Thanks to microarray analysis of gene expression in patients with juvenile idiopathic arthritis, response to treatment at 12 months can be predicted after just 4 months of therapy, based on a longitudinal analysis of whole blood samples from children participating in the TREAT study.
The prediction of active versus inactive disease could be made even more strongly when stratifying patients based on the presence of rheumatoid factor (RF), which is an "exciting" finding, study investigator Dr. James Jarvis said in a video interview at the annual European Congress of Rheumatology. "We’ve known for a long time that children with rheumatoid factor–positive disease are just harder to treat."
The National Institutes of Health–funded TREAT (Trial of Early Aggressive Drug Therapy in Juvenile Idiopathic Arthritis) study compared treatment with methotrexate alone against methotrexate plus etanercept for children with newly diagnosed juvenile idiopathic arthritis. The current analysis found that treatment in RF-positive patients led to changes in fewer genes than in RF-negative patients, and also changed the expression of different genes than in those with RF-negative disease. Dr. Jarvis is chief of allergy/immunology and rheumatology in the pediatrics department at the University at Buffalo, The State University of New York.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
PARIS – Thanks to microarray analysis of gene expression in patients with juvenile idiopathic arthritis, response to treatment at 12 months can be predicted after just 4 months of therapy, based on a longitudinal analysis of whole blood samples from children participating in the TREAT study.
The prediction of active versus inactive disease could be made even more strongly when stratifying patients based on the presence of rheumatoid factor (RF), which is an "exciting" finding, study investigator Dr. James Jarvis said in a video interview at the annual European Congress of Rheumatology. "We’ve known for a long time that children with rheumatoid factor–positive disease are just harder to treat."
The National Institutes of Health–funded TREAT (Trial of Early Aggressive Drug Therapy in Juvenile Idiopathic Arthritis) study compared treatment with methotrexate alone against methotrexate plus etanercept for children with newly diagnosed juvenile idiopathic arthritis. The current analysis found that treatment in RF-positive patients led to changes in fewer genes than in RF-negative patients, and also changed the expression of different genes than in those with RF-negative disease. Dr. Jarvis is chief of allergy/immunology and rheumatology in the pediatrics department at the University at Buffalo, The State University of New York.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
PARIS – Thanks to microarray analysis of gene expression in patients with juvenile idiopathic arthritis, response to treatment at 12 months can be predicted after just 4 months of therapy, based on a longitudinal analysis of whole blood samples from children participating in the TREAT study.
The prediction of active versus inactive disease could be made even more strongly when stratifying patients based on the presence of rheumatoid factor (RF), which is an "exciting" finding, study investigator Dr. James Jarvis said in a video interview at the annual European Congress of Rheumatology. "We’ve known for a long time that children with rheumatoid factor–positive disease are just harder to treat."
The National Institutes of Health–funded TREAT (Trial of Early Aggressive Drug Therapy in Juvenile Idiopathic Arthritis) study compared treatment with methotrexate alone against methotrexate plus etanercept for children with newly diagnosed juvenile idiopathic arthritis. The current analysis found that treatment in RF-positive patients led to changes in fewer genes than in RF-negative patients, and also changed the expression of different genes than in those with RF-negative disease. Dr. Jarvis is chief of allergy/immunology and rheumatology in the pediatrics department at the University at Buffalo, The State University of New York.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE EULAR CONGRESS 2014
Meta-analysis finds limited bone loss with low-dose glucocorticoids
PARIS – Bone loss at 1 year is limited at the low doses of glucocorticoids typically used to treat adults with chronic inflammatory disorders like rheumatoid arthritis, based on a meta-analysis of prospective studies of 1,565 patients with chronic inflammatory diseases (44 studies) and 635 transplant patients (16 studies).
Glucocorticoid treatment at the high doses used in transplantation patients leads to considerable bone loss, especially in the lumbar spine. In contrast, bone loss is limited during glucocorticoid treatment at the lower doses used in chronic inflammatory disease, Dr. Maarten Boers, professor of clinical epidemiology at VU University Medical Center, Amsterdam, reported at the annual European Congress of Rheumatology.
All patients in the meta-analysis had at least two bone mineral density (BMD) measurements over at least 8 months. None received bisphosphonates or antiresorptive therapies, only vitamin D3 and calcium were allowed.
Glucocorticoid doses ranged from 1 to 16 mg/day (mean 9 mg/day) in the patients with chronic inflammatory diseases and from 6 to 53 mg/day (mean 20 mg/day) in the transplant patients. In those with chronic inflammatory diseases, bone loss at the lumbar spine at 1 year averaged –1.7%. For the patients who had measures of femoral neck bone loss, the average loss was –1.3%. In the transplantation group, average bone loss was much higher at –3.6% in the lumbar spine and –3.1% in the femoral neck.
Among the 44 studies that reported BMD in patients with chronic inflammatory diseases, BMD declined from baseline in the lumbar spine by as much as 6% in 1 study and increased by as much as 2% in another. The 39 studies that also reported changes in femoral neck BMD described a decline as high as 7% and an increase as great as 4%.
"We sought to quantify the ‘pure’ effect of GC [glucocorticoid(s)], because so little high-quality information is available," Dr. Boers explained.
The data analysis in these studies was limited to 1 year, but about two-thirds of the patients with chronic inflammatory disease were on chronic glucocorticoid therapy and almost all of the transplant patients were just starting glucocorticoids, Dr. Boers said.
"On average, the yearly loss in a wide range of doses is limited, but starters have more bone loss. The heterogeneity of studies suggests that factors other than GC dose are the main drivers in determining bone loss. Although the data were not available to study these factors, it appears likely that disease activity is very important and acts as a confounder. In other words, disease activity leads to bone loss, and high GC doses lead to bone loss. Effective treatment of high disease activity requires high GC doses, but the interaction of these factors may lead to bone loss comparable to low disease activity being treated with low doses," he explained in an interview.
Many rheumatoid arthritis patients are initially treated with "bridge" glucocorticoid therapy for a few months, until the effect of methotrexate is established, he said. "We prefer ‘COBRA [combination therapy for rheumatoid arthritis] light,’ where patients are initially treated with a higher dose of 30 mg, rapidly tapered to 7.5 mg/day, and maintained for at least 6 months. Several groups are advising to treat for longer periods, and observational data suggest many patients are kept on chronic therapy for periods longer than 1 year," he said.
Local guidelines differ, but all guidelines agree on the necessity of prophylaxis in high-risk situations and on screening for intermediate-risk patients. Unfortunately, many patients requiring antiresorptive treatment according to the guidelines are still not receiving it, with surveys showing about 70% uptake in patients treated by rheumatologists and only about 30% in patients receiving care from other specialists, he said.
"Given the effects of starting GC therapy in our review, we strongly suggest all patients requiring GC therapy for longer than 3 months at any dose should at least be assessed by DXA scan; postmenopausal women, males age 70 or older, and patients with other risk factors should be treated with antiresorptive agents from the start," Dr. Boers advised.
Dr. Boers his coinvestigators reported having no financial conflicts.
PARIS – Bone loss at 1 year is limited at the low doses of glucocorticoids typically used to treat adults with chronic inflammatory disorders like rheumatoid arthritis, based on a meta-analysis of prospective studies of 1,565 patients with chronic inflammatory diseases (44 studies) and 635 transplant patients (16 studies).
Glucocorticoid treatment at the high doses used in transplantation patients leads to considerable bone loss, especially in the lumbar spine. In contrast, bone loss is limited during glucocorticoid treatment at the lower doses used in chronic inflammatory disease, Dr. Maarten Boers, professor of clinical epidemiology at VU University Medical Center, Amsterdam, reported at the annual European Congress of Rheumatology.
All patients in the meta-analysis had at least two bone mineral density (BMD) measurements over at least 8 months. None received bisphosphonates or antiresorptive therapies, only vitamin D3 and calcium were allowed.
Glucocorticoid doses ranged from 1 to 16 mg/day (mean 9 mg/day) in the patients with chronic inflammatory diseases and from 6 to 53 mg/day (mean 20 mg/day) in the transplant patients. In those with chronic inflammatory diseases, bone loss at the lumbar spine at 1 year averaged –1.7%. For the patients who had measures of femoral neck bone loss, the average loss was –1.3%. In the transplantation group, average bone loss was much higher at –3.6% in the lumbar spine and –3.1% in the femoral neck.
Among the 44 studies that reported BMD in patients with chronic inflammatory diseases, BMD declined from baseline in the lumbar spine by as much as 6% in 1 study and increased by as much as 2% in another. The 39 studies that also reported changes in femoral neck BMD described a decline as high as 7% and an increase as great as 4%.
"We sought to quantify the ‘pure’ effect of GC [glucocorticoid(s)], because so little high-quality information is available," Dr. Boers explained.
The data analysis in these studies was limited to 1 year, but about two-thirds of the patients with chronic inflammatory disease were on chronic glucocorticoid therapy and almost all of the transplant patients were just starting glucocorticoids, Dr. Boers said.
"On average, the yearly loss in a wide range of doses is limited, but starters have more bone loss. The heterogeneity of studies suggests that factors other than GC dose are the main drivers in determining bone loss. Although the data were not available to study these factors, it appears likely that disease activity is very important and acts as a confounder. In other words, disease activity leads to bone loss, and high GC doses lead to bone loss. Effective treatment of high disease activity requires high GC doses, but the interaction of these factors may lead to bone loss comparable to low disease activity being treated with low doses," he explained in an interview.
Many rheumatoid arthritis patients are initially treated with "bridge" glucocorticoid therapy for a few months, until the effect of methotrexate is established, he said. "We prefer ‘COBRA [combination therapy for rheumatoid arthritis] light,’ where patients are initially treated with a higher dose of 30 mg, rapidly tapered to 7.5 mg/day, and maintained for at least 6 months. Several groups are advising to treat for longer periods, and observational data suggest many patients are kept on chronic therapy for periods longer than 1 year," he said.
Local guidelines differ, but all guidelines agree on the necessity of prophylaxis in high-risk situations and on screening for intermediate-risk patients. Unfortunately, many patients requiring antiresorptive treatment according to the guidelines are still not receiving it, with surveys showing about 70% uptake in patients treated by rheumatologists and only about 30% in patients receiving care from other specialists, he said.
"Given the effects of starting GC therapy in our review, we strongly suggest all patients requiring GC therapy for longer than 3 months at any dose should at least be assessed by DXA scan; postmenopausal women, males age 70 or older, and patients with other risk factors should be treated with antiresorptive agents from the start," Dr. Boers advised.
Dr. Boers his coinvestigators reported having no financial conflicts.
PARIS – Bone loss at 1 year is limited at the low doses of glucocorticoids typically used to treat adults with chronic inflammatory disorders like rheumatoid arthritis, based on a meta-analysis of prospective studies of 1,565 patients with chronic inflammatory diseases (44 studies) and 635 transplant patients (16 studies).
Glucocorticoid treatment at the high doses used in transplantation patients leads to considerable bone loss, especially in the lumbar spine. In contrast, bone loss is limited during glucocorticoid treatment at the lower doses used in chronic inflammatory disease, Dr. Maarten Boers, professor of clinical epidemiology at VU University Medical Center, Amsterdam, reported at the annual European Congress of Rheumatology.
All patients in the meta-analysis had at least two bone mineral density (BMD) measurements over at least 8 months. None received bisphosphonates or antiresorptive therapies, only vitamin D3 and calcium were allowed.
Glucocorticoid doses ranged from 1 to 16 mg/day (mean 9 mg/day) in the patients with chronic inflammatory diseases and from 6 to 53 mg/day (mean 20 mg/day) in the transplant patients. In those with chronic inflammatory diseases, bone loss at the lumbar spine at 1 year averaged –1.7%. For the patients who had measures of femoral neck bone loss, the average loss was –1.3%. In the transplantation group, average bone loss was much higher at –3.6% in the lumbar spine and –3.1% in the femoral neck.
Among the 44 studies that reported BMD in patients with chronic inflammatory diseases, BMD declined from baseline in the lumbar spine by as much as 6% in 1 study and increased by as much as 2% in another. The 39 studies that also reported changes in femoral neck BMD described a decline as high as 7% and an increase as great as 4%.
"We sought to quantify the ‘pure’ effect of GC [glucocorticoid(s)], because so little high-quality information is available," Dr. Boers explained.
The data analysis in these studies was limited to 1 year, but about two-thirds of the patients with chronic inflammatory disease were on chronic glucocorticoid therapy and almost all of the transplant patients were just starting glucocorticoids, Dr. Boers said.
"On average, the yearly loss in a wide range of doses is limited, but starters have more bone loss. The heterogeneity of studies suggests that factors other than GC dose are the main drivers in determining bone loss. Although the data were not available to study these factors, it appears likely that disease activity is very important and acts as a confounder. In other words, disease activity leads to bone loss, and high GC doses lead to bone loss. Effective treatment of high disease activity requires high GC doses, but the interaction of these factors may lead to bone loss comparable to low disease activity being treated with low doses," he explained in an interview.
Many rheumatoid arthritis patients are initially treated with "bridge" glucocorticoid therapy for a few months, until the effect of methotrexate is established, he said. "We prefer ‘COBRA [combination therapy for rheumatoid arthritis] light,’ where patients are initially treated with a higher dose of 30 mg, rapidly tapered to 7.5 mg/day, and maintained for at least 6 months. Several groups are advising to treat for longer periods, and observational data suggest many patients are kept on chronic therapy for periods longer than 1 year," he said.
Local guidelines differ, but all guidelines agree on the necessity of prophylaxis in high-risk situations and on screening for intermediate-risk patients. Unfortunately, many patients requiring antiresorptive treatment according to the guidelines are still not receiving it, with surveys showing about 70% uptake in patients treated by rheumatologists and only about 30% in patients receiving care from other specialists, he said.
"Given the effects of starting GC therapy in our review, we strongly suggest all patients requiring GC therapy for longer than 3 months at any dose should at least be assessed by DXA scan; postmenopausal women, males age 70 or older, and patients with other risk factors should be treated with antiresorptive agents from the start," Dr. Boers advised.
Dr. Boers his coinvestigators reported having no financial conflicts.
AT THE EULAR CONGRESS 2014
Key clinical point: One-year bone loss is limited during glucocorticoid treatment at the lower doses used in chronic inflammatory disease.
Major finding: In those with chronic inflammatory diseases, bone loss at the lumbar spine at 1 year averaged –1.7%. For the patients who had measures of femoral neck bone loss, the average loss was –1.3%.
Data source: A meta-analysis of prospective studies of 1,565 patients with chronic inflammatory diseases (44 studies) and 635 transplant patients (16 studies).
Disclosures: Dr. Boers his coinvestigators reported having no financial conflicts.
Rituximab yielded long-term benefit in lupus nephritis
PARIS – Treatment with rituximab in patients with refractory lupus nephritis was associated with significant long-term improvement in symptoms, histology, and laboratory markers in a prospective study.
Over a median follow-up period of 18 months (interquartile range, 12-36 months), the drug normalized proteinuria and was associated with a median reduction in glucocorticoid use of 28 mg/day, according to Dr. Maria Tsanyan of the Nasonova Research Institute of Rheumatology, Moscow.
She and her colleagues followed 60 patients with refractory lupus nephritis who had a median age of 26 years and median disease duration of 37.5 months. At baseline, the patients’ median glomerular filtration rate was 46 mL/min, and their median amount of proteinuria was 1.83 g/day. A total of 14 patients (23%) had nephrotic syndrome.
All patients had failed prior therapy. These treatments included high-dose glucocorticoids (45%), pulsed high-dose glucocorticoid and cyclophosphamide (90%), mycophenolate mofetil (17%), azathioprine (7%), hydroxychloroquine (17%), and cyclosporine A (8%).
Treatment with rituximab varied according to clinical status and response. The initial doses were 1,000 mg in 25 patients and 2,000 mg in 30 patients. Five patients did not receive a full initial course of rituximab because of the development of end-stage renal disease, including four who received only 500 mg and one who received 1,500 mg.
Most (37) required more than one course: 21 needed two courses, 11 needed three, 4 needed four courses, and 1 received five courses of the drug.
In response to an audience member’s question about the basis on which the investigators decided to re-treat patients with rituximab, Dr. Tsanyan said that they tried to achieve complete responses in patients with disease exacerbation or partial response at 6 months or 12 months after the initial dose.
Based on the Systemic Lupus Erythematosus International Collaborating Clinics renal activity/response exercise criteria, 58% had a complete response, 22% had a partial response, 12% were nonresponders, and 8% died of acute renal failure. Overall, 28% of patients had an exacerbation of disease during treatment.
There was no difference in response between patients who received 1,000 mg and 2,000 mg rituximab, she said at the annual European Congress of Rheumatology.
By 6 months of treatment, the median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score had decreased from 20 to 4. This improvement held at 12 months. By 42 months, the median score had dropped to 2. By SLEDAI-2K index, 50% were considered to be complete responders, 30% partial responders, and 12% nonresponders.
Antibodies to double-stranded DNA fell from a mean of 67.7 U/mL at baseline to 34.5 U/mL at 42 months. Daily glucocorticoid use dropped from 35 mg to 7.5 mg.
C3 and C4 complement components also improved. C3 rose from 0.7 to 0.98 g/L, and C4 from 0.1 g/L to 0.24 g/L. Daily proteinuria fell from 1.6 g/day to 0.01 g/day and serum total protein rose from 59 g/L to 72 g/L.
Sixteen patients had renal biopsies both at baseline and at the end of their follow-up period. Of 14 patients who had World Health Organization class IV nephritis at baseline, 5 were unchanged, 3 moved to class III, 5 to class II, and 1 to class I. Two class III patients improved to class I.
There were 13 adverse events, all of which occurred during the first 3 months of rituximab therapy. These included pneumonia (4), aspergillosis (1), bronchitis (1), cystitis (2), shingles (3), furunculosis (1) and pityriasis versicolor (1).
Dr. Tsanyan did not have any financial disclosures.
PARIS – Treatment with rituximab in patients with refractory lupus nephritis was associated with significant long-term improvement in symptoms, histology, and laboratory markers in a prospective study.
Over a median follow-up period of 18 months (interquartile range, 12-36 months), the drug normalized proteinuria and was associated with a median reduction in glucocorticoid use of 28 mg/day, according to Dr. Maria Tsanyan of the Nasonova Research Institute of Rheumatology, Moscow.
She and her colleagues followed 60 patients with refractory lupus nephritis who had a median age of 26 years and median disease duration of 37.5 months. At baseline, the patients’ median glomerular filtration rate was 46 mL/min, and their median amount of proteinuria was 1.83 g/day. A total of 14 patients (23%) had nephrotic syndrome.
All patients had failed prior therapy. These treatments included high-dose glucocorticoids (45%), pulsed high-dose glucocorticoid and cyclophosphamide (90%), mycophenolate mofetil (17%), azathioprine (7%), hydroxychloroquine (17%), and cyclosporine A (8%).
Treatment with rituximab varied according to clinical status and response. The initial doses were 1,000 mg in 25 patients and 2,000 mg in 30 patients. Five patients did not receive a full initial course of rituximab because of the development of end-stage renal disease, including four who received only 500 mg and one who received 1,500 mg.
Most (37) required more than one course: 21 needed two courses, 11 needed three, 4 needed four courses, and 1 received five courses of the drug.
In response to an audience member’s question about the basis on which the investigators decided to re-treat patients with rituximab, Dr. Tsanyan said that they tried to achieve complete responses in patients with disease exacerbation or partial response at 6 months or 12 months after the initial dose.
Based on the Systemic Lupus Erythematosus International Collaborating Clinics renal activity/response exercise criteria, 58% had a complete response, 22% had a partial response, 12% were nonresponders, and 8% died of acute renal failure. Overall, 28% of patients had an exacerbation of disease during treatment.
There was no difference in response between patients who received 1,000 mg and 2,000 mg rituximab, she said at the annual European Congress of Rheumatology.
By 6 months of treatment, the median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score had decreased from 20 to 4. This improvement held at 12 months. By 42 months, the median score had dropped to 2. By SLEDAI-2K index, 50% were considered to be complete responders, 30% partial responders, and 12% nonresponders.
Antibodies to double-stranded DNA fell from a mean of 67.7 U/mL at baseline to 34.5 U/mL at 42 months. Daily glucocorticoid use dropped from 35 mg to 7.5 mg.
C3 and C4 complement components also improved. C3 rose from 0.7 to 0.98 g/L, and C4 from 0.1 g/L to 0.24 g/L. Daily proteinuria fell from 1.6 g/day to 0.01 g/day and serum total protein rose from 59 g/L to 72 g/L.
Sixteen patients had renal biopsies both at baseline and at the end of their follow-up period. Of 14 patients who had World Health Organization class IV nephritis at baseline, 5 were unchanged, 3 moved to class III, 5 to class II, and 1 to class I. Two class III patients improved to class I.
There were 13 adverse events, all of which occurred during the first 3 months of rituximab therapy. These included pneumonia (4), aspergillosis (1), bronchitis (1), cystitis (2), shingles (3), furunculosis (1) and pityriasis versicolor (1).
Dr. Tsanyan did not have any financial disclosures.
PARIS – Treatment with rituximab in patients with refractory lupus nephritis was associated with significant long-term improvement in symptoms, histology, and laboratory markers in a prospective study.
Over a median follow-up period of 18 months (interquartile range, 12-36 months), the drug normalized proteinuria and was associated with a median reduction in glucocorticoid use of 28 mg/day, according to Dr. Maria Tsanyan of the Nasonova Research Institute of Rheumatology, Moscow.
She and her colleagues followed 60 patients with refractory lupus nephritis who had a median age of 26 years and median disease duration of 37.5 months. At baseline, the patients’ median glomerular filtration rate was 46 mL/min, and their median amount of proteinuria was 1.83 g/day. A total of 14 patients (23%) had nephrotic syndrome.
All patients had failed prior therapy. These treatments included high-dose glucocorticoids (45%), pulsed high-dose glucocorticoid and cyclophosphamide (90%), mycophenolate mofetil (17%), azathioprine (7%), hydroxychloroquine (17%), and cyclosporine A (8%).
Treatment with rituximab varied according to clinical status and response. The initial doses were 1,000 mg in 25 patients and 2,000 mg in 30 patients. Five patients did not receive a full initial course of rituximab because of the development of end-stage renal disease, including four who received only 500 mg and one who received 1,500 mg.
Most (37) required more than one course: 21 needed two courses, 11 needed three, 4 needed four courses, and 1 received five courses of the drug.
In response to an audience member’s question about the basis on which the investigators decided to re-treat patients with rituximab, Dr. Tsanyan said that they tried to achieve complete responses in patients with disease exacerbation or partial response at 6 months or 12 months after the initial dose.
Based on the Systemic Lupus Erythematosus International Collaborating Clinics renal activity/response exercise criteria, 58% had a complete response, 22% had a partial response, 12% were nonresponders, and 8% died of acute renal failure. Overall, 28% of patients had an exacerbation of disease during treatment.
There was no difference in response between patients who received 1,000 mg and 2,000 mg rituximab, she said at the annual European Congress of Rheumatology.
By 6 months of treatment, the median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score had decreased from 20 to 4. This improvement held at 12 months. By 42 months, the median score had dropped to 2. By SLEDAI-2K index, 50% were considered to be complete responders, 30% partial responders, and 12% nonresponders.
Antibodies to double-stranded DNA fell from a mean of 67.7 U/mL at baseline to 34.5 U/mL at 42 months. Daily glucocorticoid use dropped from 35 mg to 7.5 mg.
C3 and C4 complement components also improved. C3 rose from 0.7 to 0.98 g/L, and C4 from 0.1 g/L to 0.24 g/L. Daily proteinuria fell from 1.6 g/day to 0.01 g/day and serum total protein rose from 59 g/L to 72 g/L.
Sixteen patients had renal biopsies both at baseline and at the end of their follow-up period. Of 14 patients who had World Health Organization class IV nephritis at baseline, 5 were unchanged, 3 moved to class III, 5 to class II, and 1 to class I. Two class III patients improved to class I.
There were 13 adverse events, all of which occurred during the first 3 months of rituximab therapy. These included pneumonia (4), aspergillosis (1), bronchitis (1), cystitis (2), shingles (3), furunculosis (1) and pityriasis versicolor (1).
Dr. Tsanyan did not have any financial disclosures.
AT THE EULAR CONGRESS 2014
Key clinical point: Rituximab delivered long-term results for patients with refractory lupus nephritis.
Major finding: During a median follow-up period of 18 months, the drug normalized proteinuria, improved glomerular filtration rate, and was associated with a median steroid reduction of 28 mg/day.
Data source: An open-label, prospective study of 60 patients with refractory lupus nephritis.
Disclosures: Dr. Maria Tsanyan had no financial disclosures.
Deaths mar atacicept trial for lupus, but research continues
PARIS – A randomized trial of two doses of atacicept for systemic lupus erythematosus was interrupted after two deaths occurred in patients taking 150 mg of the drug.
However, since a post hoc analysis concluded that the 150-mg dose was more effective at reducing flares than was the 75-mg dose, research on it continues, Dr. Caroline Gordon said at the annual European Congress of Rheumatology.
Additionally, said Dr. Gordon, professor of rheumatology at the University of Birmingham, England, the 150-mg dose was significantly more effective than was the 75-mg dose or placebo at reducing mucocutaneous and musculoskeletal flares (9% vs. 18%).
"This finding, and the suggestion that atacicept may have a steroid-sparing effect, allows for assessing its safety and efficacy further," she said.
EMD Serono, a subsidiary of Merck, is now recruiting for a 24-week trial comparing the 75- and 150-mg doses in patients with systemic lupus erythematosus (SLE).
Atacicept is an investigational, fully human recombinant fusion protein that inhibits B-lymphocyte stimulator (BLyS) and the A proliferation-inducing ligand (APRIL). Both proteins stimulate B-cell production and are elevated in patients with lupus.
At the congress, Dr. Gordon reported the results of the APRIL-SLE study, which randomized 461 patients to atacicept at either dose or placebo. Its primary endpoint was the rate of new flares in patients with lupus. Secondary endpoints included changes in disease activity scores, overall safety, biomarkers, and pharmacodynamics. The full results of the study were published after the congress (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-205067]).
Patients had to achieve stable condition before being randomized. After screening, they were assigned to a 10-week corticosteroid taper. If they had improved to a score of C or D on the British Isles Assessment Group (BILAG) scale, they were randomized. After the 52-week treatment period, there was a 24-week safety observation period.
Most patients in the placebo and 75-mg groups completed the study (70%). In the 150-mg arm, 43% completed the trial. After the two deaths, 38% patients in the 150 mg-arm stopped treatment. Both patients died of pneumonia complicated by pulmonary hemorrhage.
One of these was a 22-year-old man from the Philippines on week 42 of treatment, who had complicating comorbidities of systemic sclerosis and may have had leptospirosis as well, Dr. Gordon said. "There may have also been some delays in getting him treated, although we are not sure of that."
The other was a 30-year-old woman on treatment week 22. She developed a pneumococcal pneumonia "and deteriorated rapidly," Dr. Gordon said.
There were no withdrawals because of infection or any other adverse events in any of the treatment groups.
The patients had a mean age of 39 years, and most were women (93%). The mean disease severity by BILAG score was A (severe) in 31% and B (moderate) in the remainder.
In the primary intent-to-treat analysis, there was no significant difference between placebo and 75 mg in flare rate. The 150-mg dose was associated with significantly fewer flares than was placebo (40% vs. 55%), but the difference between it and the lower dose was not statistically significant. Both doses prolonged the time to first flare significantly more than placebo.
The investigators also conducted a post hoc, potential completer analysis to examine the effect in all patients who had completed the entire 52 weeks of treatment. Atacicept 75 mg was not significantly better than placebo, but the 150-mg dose was, reducing the odds of a flare by 51% (flare rate 43% vs. 60%) – a finding similar to the intent-to-treat analysis.
The largest portion of flares (about 23%) was in the mucocutaneous and musculoskeletal systems. The 150-mg dose halved the occurrence of these flares relative to placebo.
The study was not powered to detect flare severity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). However, another post hoc analysis concluded that, compared with placebo, the 150-mg dose reduced the chance of a severe flare by 55% on SLEDAI scoring.
The study was sponsored by EMD Serono, a subsidiary of Merck. Dr. Gordon disclosed that she received personal remuneration from Merck Serono during the study. The three coauthors were Merck employees.
On Twitter @alz_gal
PARIS – A randomized trial of two doses of atacicept for systemic lupus erythematosus was interrupted after two deaths occurred in patients taking 150 mg of the drug.
However, since a post hoc analysis concluded that the 150-mg dose was more effective at reducing flares than was the 75-mg dose, research on it continues, Dr. Caroline Gordon said at the annual European Congress of Rheumatology.
Additionally, said Dr. Gordon, professor of rheumatology at the University of Birmingham, England, the 150-mg dose was significantly more effective than was the 75-mg dose or placebo at reducing mucocutaneous and musculoskeletal flares (9% vs. 18%).
"This finding, and the suggestion that atacicept may have a steroid-sparing effect, allows for assessing its safety and efficacy further," she said.
EMD Serono, a subsidiary of Merck, is now recruiting for a 24-week trial comparing the 75- and 150-mg doses in patients with systemic lupus erythematosus (SLE).
Atacicept is an investigational, fully human recombinant fusion protein that inhibits B-lymphocyte stimulator (BLyS) and the A proliferation-inducing ligand (APRIL). Both proteins stimulate B-cell production and are elevated in patients with lupus.
At the congress, Dr. Gordon reported the results of the APRIL-SLE study, which randomized 461 patients to atacicept at either dose or placebo. Its primary endpoint was the rate of new flares in patients with lupus. Secondary endpoints included changes in disease activity scores, overall safety, biomarkers, and pharmacodynamics. The full results of the study were published after the congress (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-205067]).
Patients had to achieve stable condition before being randomized. After screening, they were assigned to a 10-week corticosteroid taper. If they had improved to a score of C or D on the British Isles Assessment Group (BILAG) scale, they were randomized. After the 52-week treatment period, there was a 24-week safety observation period.
Most patients in the placebo and 75-mg groups completed the study (70%). In the 150-mg arm, 43% completed the trial. After the two deaths, 38% patients in the 150 mg-arm stopped treatment. Both patients died of pneumonia complicated by pulmonary hemorrhage.
One of these was a 22-year-old man from the Philippines on week 42 of treatment, who had complicating comorbidities of systemic sclerosis and may have had leptospirosis as well, Dr. Gordon said. "There may have also been some delays in getting him treated, although we are not sure of that."
The other was a 30-year-old woman on treatment week 22. She developed a pneumococcal pneumonia "and deteriorated rapidly," Dr. Gordon said.
There were no withdrawals because of infection or any other adverse events in any of the treatment groups.
The patients had a mean age of 39 years, and most were women (93%). The mean disease severity by BILAG score was A (severe) in 31% and B (moderate) in the remainder.
In the primary intent-to-treat analysis, there was no significant difference between placebo and 75 mg in flare rate. The 150-mg dose was associated with significantly fewer flares than was placebo (40% vs. 55%), but the difference between it and the lower dose was not statistically significant. Both doses prolonged the time to first flare significantly more than placebo.
The investigators also conducted a post hoc, potential completer analysis to examine the effect in all patients who had completed the entire 52 weeks of treatment. Atacicept 75 mg was not significantly better than placebo, but the 150-mg dose was, reducing the odds of a flare by 51% (flare rate 43% vs. 60%) – a finding similar to the intent-to-treat analysis.
The largest portion of flares (about 23%) was in the mucocutaneous and musculoskeletal systems. The 150-mg dose halved the occurrence of these flares relative to placebo.
The study was not powered to detect flare severity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). However, another post hoc analysis concluded that, compared with placebo, the 150-mg dose reduced the chance of a severe flare by 55% on SLEDAI scoring.
The study was sponsored by EMD Serono, a subsidiary of Merck. Dr. Gordon disclosed that she received personal remuneration from Merck Serono during the study. The three coauthors were Merck employees.
On Twitter @alz_gal
PARIS – A randomized trial of two doses of atacicept for systemic lupus erythematosus was interrupted after two deaths occurred in patients taking 150 mg of the drug.
However, since a post hoc analysis concluded that the 150-mg dose was more effective at reducing flares than was the 75-mg dose, research on it continues, Dr. Caroline Gordon said at the annual European Congress of Rheumatology.
Additionally, said Dr. Gordon, professor of rheumatology at the University of Birmingham, England, the 150-mg dose was significantly more effective than was the 75-mg dose or placebo at reducing mucocutaneous and musculoskeletal flares (9% vs. 18%).
"This finding, and the suggestion that atacicept may have a steroid-sparing effect, allows for assessing its safety and efficacy further," she said.
EMD Serono, a subsidiary of Merck, is now recruiting for a 24-week trial comparing the 75- and 150-mg doses in patients with systemic lupus erythematosus (SLE).
Atacicept is an investigational, fully human recombinant fusion protein that inhibits B-lymphocyte stimulator (BLyS) and the A proliferation-inducing ligand (APRIL). Both proteins stimulate B-cell production and are elevated in patients with lupus.
At the congress, Dr. Gordon reported the results of the APRIL-SLE study, which randomized 461 patients to atacicept at either dose or placebo. Its primary endpoint was the rate of new flares in patients with lupus. Secondary endpoints included changes in disease activity scores, overall safety, biomarkers, and pharmacodynamics. The full results of the study were published after the congress (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-205067]).
Patients had to achieve stable condition before being randomized. After screening, they were assigned to a 10-week corticosteroid taper. If they had improved to a score of C or D on the British Isles Assessment Group (BILAG) scale, they were randomized. After the 52-week treatment period, there was a 24-week safety observation period.
Most patients in the placebo and 75-mg groups completed the study (70%). In the 150-mg arm, 43% completed the trial. After the two deaths, 38% patients in the 150 mg-arm stopped treatment. Both patients died of pneumonia complicated by pulmonary hemorrhage.
One of these was a 22-year-old man from the Philippines on week 42 of treatment, who had complicating comorbidities of systemic sclerosis and may have had leptospirosis as well, Dr. Gordon said. "There may have also been some delays in getting him treated, although we are not sure of that."
The other was a 30-year-old woman on treatment week 22. She developed a pneumococcal pneumonia "and deteriorated rapidly," Dr. Gordon said.
There were no withdrawals because of infection or any other adverse events in any of the treatment groups.
The patients had a mean age of 39 years, and most were women (93%). The mean disease severity by BILAG score was A (severe) in 31% and B (moderate) in the remainder.
In the primary intent-to-treat analysis, there was no significant difference between placebo and 75 mg in flare rate. The 150-mg dose was associated with significantly fewer flares than was placebo (40% vs. 55%), but the difference between it and the lower dose was not statistically significant. Both doses prolonged the time to first flare significantly more than placebo.
The investigators also conducted a post hoc, potential completer analysis to examine the effect in all patients who had completed the entire 52 weeks of treatment. Atacicept 75 mg was not significantly better than placebo, but the 150-mg dose was, reducing the odds of a flare by 51% (flare rate 43% vs. 60%) – a finding similar to the intent-to-treat analysis.
The largest portion of flares (about 23%) was in the mucocutaneous and musculoskeletal systems. The 150-mg dose halved the occurrence of these flares relative to placebo.
The study was not powered to detect flare severity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). However, another post hoc analysis concluded that, compared with placebo, the 150-mg dose reduced the chance of a severe flare by 55% on SLEDAI scoring.
The study was sponsored by EMD Serono, a subsidiary of Merck. Dr. Gordon disclosed that she received personal remuneration from Merck Serono during the study. The three coauthors were Merck employees.
On Twitter @alz_gal
AT THE EULAR CONGRESS 2014
Key clinical point: Research continues on atacicept for lupus, despite the deaths of two patients taking 150 mg of the drug.
Major finding: In a post hoc analysis, 150 mg atacicept reduced the odds of a flare by 51%.
Data source: The three-way trial randomized 461 patients to atacicept at 75 mg or 150 mg or placebo.
Disclosures: The study was sponsored by EMD Serono, a subsidiary of Merck. Dr. Gordon disclosed that she received personal remuneration from Merck Serono during the study. The three coauthors were Merck employees.
Trial of sirukumab for lupus nephritis falls flat
PARIS – The investigational interleukin-6 blocker sirukumab provided no benefit to patients with lupus nephritis but put them at a very high risk of developing a serious infection in a small, randomized, placebo-controlled trial.
Based on the study results, the study sponsor, Janssen, has shut down its program for the lupus nephritis indication, Dr. Ronald van Vollenhoven said at the annual European Congress of Rheumatology.
"While a few patients did experience a reduction in proteinuria, we had an unacceptably high rate of adverse events," said Dr. van Vollenhoven, chief of the Unit for Clinical Therapy Research, Inflammatory Diseases, at the Karolinska Institute, Stockholm. "Based on these findings, we will not be advancing any further investigation of sirukumab for patients with active lupus nephritis."
The company continues to develop the drug for rheumatoid arthritis.
In the trial, 21 patients received intravenous sirukumab 10 mg/kg once every 4 weeks for 24 weeks, and 4 received placebo. During the trial and a 16-week safety observation follow-up period, 48% of those who took the investigational IL-6 blocker developed a serious adverse event, including infections serious enough to require hospital admission.
While not specifying the infections, which occurred in 10 patients, Dr. van Vollenhoven noted that five patients taking the drug discontinued it because of adverse events, which included Haemophilus influenzae pneumonia, elevated liver enzymes, anaphylactic reaction after the first dose, worsening nephritis, and severe neutropenia.
Overall, 19 patients completed the study. In addition to the five who quit because of adverse events, one additional patient withdrew voluntarily. All had active lupus nephritis of about 50 months’ duration, with a mean daily proteinuria of more than 2 g; about a third of the group had nephrotic proteinuria. The mean Systemic Lupus Erythematosus Disease Activity Index 2000 was about 16. All were taking concomitant mycophenolate mofetil or azathioprine.
At the end of the treatment period, there was no significant between-group difference in proteinuria, Dr. van Vollenhoven said. Four of those in the active group experienced at least a 50% reduction in proteinuria over baseline, while none of those in the placebo group experienced this change. However, this difference was not statistically significant. There were no significant changes in the patient or physical global assessment for either group.
Serious adverse events occurred in 48% of those taking the drug, including serious infections (30%) as well as renal/urinary (19%), blood (9.5%), and gastrointestinal (9.5%) events. None occurred in the placebo group.
Among patients in the sirukumab group, there was one grade 4 lymphocytopenia, one grade 4 neutropenia, and two grade 3 neutropenias. One patient had a grade 2 liver enzyme elevation.
Dr. van Vollenhoven was on the study steering committee and is a consultant and speaker for Janssen, as well as other drug manufacturers. Four coauthors are employees of Janssen.
PARIS – The investigational interleukin-6 blocker sirukumab provided no benefit to patients with lupus nephritis but put them at a very high risk of developing a serious infection in a small, randomized, placebo-controlled trial.
Based on the study results, the study sponsor, Janssen, has shut down its program for the lupus nephritis indication, Dr. Ronald van Vollenhoven said at the annual European Congress of Rheumatology.
"While a few patients did experience a reduction in proteinuria, we had an unacceptably high rate of adverse events," said Dr. van Vollenhoven, chief of the Unit for Clinical Therapy Research, Inflammatory Diseases, at the Karolinska Institute, Stockholm. "Based on these findings, we will not be advancing any further investigation of sirukumab for patients with active lupus nephritis."
The company continues to develop the drug for rheumatoid arthritis.
In the trial, 21 patients received intravenous sirukumab 10 mg/kg once every 4 weeks for 24 weeks, and 4 received placebo. During the trial and a 16-week safety observation follow-up period, 48% of those who took the investigational IL-6 blocker developed a serious adverse event, including infections serious enough to require hospital admission.
While not specifying the infections, which occurred in 10 patients, Dr. van Vollenhoven noted that five patients taking the drug discontinued it because of adverse events, which included Haemophilus influenzae pneumonia, elevated liver enzymes, anaphylactic reaction after the first dose, worsening nephritis, and severe neutropenia.
Overall, 19 patients completed the study. In addition to the five who quit because of adverse events, one additional patient withdrew voluntarily. All had active lupus nephritis of about 50 months’ duration, with a mean daily proteinuria of more than 2 g; about a third of the group had nephrotic proteinuria. The mean Systemic Lupus Erythematosus Disease Activity Index 2000 was about 16. All were taking concomitant mycophenolate mofetil or azathioprine.
At the end of the treatment period, there was no significant between-group difference in proteinuria, Dr. van Vollenhoven said. Four of those in the active group experienced at least a 50% reduction in proteinuria over baseline, while none of those in the placebo group experienced this change. However, this difference was not statistically significant. There were no significant changes in the patient or physical global assessment for either group.
Serious adverse events occurred in 48% of those taking the drug, including serious infections (30%) as well as renal/urinary (19%), blood (9.5%), and gastrointestinal (9.5%) events. None occurred in the placebo group.
Among patients in the sirukumab group, there was one grade 4 lymphocytopenia, one grade 4 neutropenia, and two grade 3 neutropenias. One patient had a grade 2 liver enzyme elevation.
Dr. van Vollenhoven was on the study steering committee and is a consultant and speaker for Janssen, as well as other drug manufacturers. Four coauthors are employees of Janssen.
PARIS – The investigational interleukin-6 blocker sirukumab provided no benefit to patients with lupus nephritis but put them at a very high risk of developing a serious infection in a small, randomized, placebo-controlled trial.
Based on the study results, the study sponsor, Janssen, has shut down its program for the lupus nephritis indication, Dr. Ronald van Vollenhoven said at the annual European Congress of Rheumatology.
"While a few patients did experience a reduction in proteinuria, we had an unacceptably high rate of adverse events," said Dr. van Vollenhoven, chief of the Unit for Clinical Therapy Research, Inflammatory Diseases, at the Karolinska Institute, Stockholm. "Based on these findings, we will not be advancing any further investigation of sirukumab for patients with active lupus nephritis."
The company continues to develop the drug for rheumatoid arthritis.
In the trial, 21 patients received intravenous sirukumab 10 mg/kg once every 4 weeks for 24 weeks, and 4 received placebo. During the trial and a 16-week safety observation follow-up period, 48% of those who took the investigational IL-6 blocker developed a serious adverse event, including infections serious enough to require hospital admission.
While not specifying the infections, which occurred in 10 patients, Dr. van Vollenhoven noted that five patients taking the drug discontinued it because of adverse events, which included Haemophilus influenzae pneumonia, elevated liver enzymes, anaphylactic reaction after the first dose, worsening nephritis, and severe neutropenia.
Overall, 19 patients completed the study. In addition to the five who quit because of adverse events, one additional patient withdrew voluntarily. All had active lupus nephritis of about 50 months’ duration, with a mean daily proteinuria of more than 2 g; about a third of the group had nephrotic proteinuria. The mean Systemic Lupus Erythematosus Disease Activity Index 2000 was about 16. All were taking concomitant mycophenolate mofetil or azathioprine.
At the end of the treatment period, there was no significant between-group difference in proteinuria, Dr. van Vollenhoven said. Four of those in the active group experienced at least a 50% reduction in proteinuria over baseline, while none of those in the placebo group experienced this change. However, this difference was not statistically significant. There were no significant changes in the patient or physical global assessment for either group.
Serious adverse events occurred in 48% of those taking the drug, including serious infections (30%) as well as renal/urinary (19%), blood (9.5%), and gastrointestinal (9.5%) events. None occurred in the placebo group.
Among patients in the sirukumab group, there was one grade 4 lymphocytopenia, one grade 4 neutropenia, and two grade 3 neutropenias. One patient had a grade 2 liver enzyme elevation.
Dr. van Vollenhoven was on the study steering committee and is a consultant and speaker for Janssen, as well as other drug manufacturers. Four coauthors are employees of Janssen.
AT THE EULAR CONGRESS 2014
Key clinical point: Janssen has discontinued its investigation of sirukumab for lupus nephritis.
Major finding: Almost half of those who took sirukumab developed a serious adverse event, including infections requiring hospitalization.
Data source: A randomized, placebo-controlled trial of 21 patients.
Disclosures: The study was sponsored by Janssen. Dr. van Vollenhoven was on the study steering committee and is a consultant and speaker for the company, as well as other drug manufacturers. Four coauthors are employees of Janssen.
VIDEO: Does obesity’s effect on RA support different treatment goals?
PARIS – Treat-to-target goals for obese patients with rheumatoid arthritis should take into account new research indicating that they already have a higher level of systemic inflammation and higher Disease Activity Scores than do normal-weight patients, according to Dr. Christopher Sparks of the University of Liverpool, England.
In an international sample of 3,534 patients with rheumatoid arthritis (RA), Dr. Sparks and his colleagues found that those with a body mass index of 30-34.9 kg/m2 (obese) or 35 kg/m2 or greater (obese II) had higher 28-joint Disease Activity Scores (DAS28) than did normal-weight patients, a difference that was largely driven by higher erythrocyte sedimentation rates and higher Visual Analog Scale scores, rather than higher tender and swollen joint counts. The data were reported at the annual European Congress of Rheumatology.
It cannot be known whether obese patients with higher DAS28 scores have clinically more severe disease, so it leads one to wonder, "Is it just an inflated DAS28 score that’s really driving this? And so potentially it brings up the question, Is obesity a confounding factor when looking at DAS28 scores in the RA population?" Dr. Sparks said in a video interview with Dr. Christian Beyer of the University of Erlangen-Nuremberg, Germany.
"If there is an artificial rise in the DAS28 in all of our obese patients out there, should the treatment goals in terms of remission or response be potentially slightly different for obese patients, compared to normal-weight patients, because they have a baseline higher DAS28?"
PARIS – Treat-to-target goals for obese patients with rheumatoid arthritis should take into account new research indicating that they already have a higher level of systemic inflammation and higher Disease Activity Scores than do normal-weight patients, according to Dr. Christopher Sparks of the University of Liverpool, England.
In an international sample of 3,534 patients with rheumatoid arthritis (RA), Dr. Sparks and his colleagues found that those with a body mass index of 30-34.9 kg/m2 (obese) or 35 kg/m2 or greater (obese II) had higher 28-joint Disease Activity Scores (DAS28) than did normal-weight patients, a difference that was largely driven by higher erythrocyte sedimentation rates and higher Visual Analog Scale scores, rather than higher tender and swollen joint counts. The data were reported at the annual European Congress of Rheumatology.
It cannot be known whether obese patients with higher DAS28 scores have clinically more severe disease, so it leads one to wonder, "Is it just an inflated DAS28 score that’s really driving this? And so potentially it brings up the question, Is obesity a confounding factor when looking at DAS28 scores in the RA population?" Dr. Sparks said in a video interview with Dr. Christian Beyer of the University of Erlangen-Nuremberg, Germany.
"If there is an artificial rise in the DAS28 in all of our obese patients out there, should the treatment goals in terms of remission or response be potentially slightly different for obese patients, compared to normal-weight patients, because they have a baseline higher DAS28?"
PARIS – Treat-to-target goals for obese patients with rheumatoid arthritis should take into account new research indicating that they already have a higher level of systemic inflammation and higher Disease Activity Scores than do normal-weight patients, according to Dr. Christopher Sparks of the University of Liverpool, England.
In an international sample of 3,534 patients with rheumatoid arthritis (RA), Dr. Sparks and his colleagues found that those with a body mass index of 30-34.9 kg/m2 (obese) or 35 kg/m2 or greater (obese II) had higher 28-joint Disease Activity Scores (DAS28) than did normal-weight patients, a difference that was largely driven by higher erythrocyte sedimentation rates and higher Visual Analog Scale scores, rather than higher tender and swollen joint counts. The data were reported at the annual European Congress of Rheumatology.
It cannot be known whether obese patients with higher DAS28 scores have clinically more severe disease, so it leads one to wonder, "Is it just an inflated DAS28 score that’s really driving this? And so potentially it brings up the question, Is obesity a confounding factor when looking at DAS28 scores in the RA population?" Dr. Sparks said in a video interview with Dr. Christian Beyer of the University of Erlangen-Nuremberg, Germany.
"If there is an artificial rise in the DAS28 in all of our obese patients out there, should the treatment goals in terms of remission or response be potentially slightly different for obese patients, compared to normal-weight patients, because they have a baseline higher DAS28?"
AT THE EULAR CONGRESS 2014
Real-world use supports belimumab clinical trial data
PARIS – Belimumab produced significant clinical improvement in 74% of patients with systemic lupus erythematosus who took it over a 6-month period, reducing disease symptoms and steroid use and significantly improving quality of life.
Results from the multicenter German OBSErve study paralleled – and even exceeded – those of the BLISS randomized trials, Dr. Andreas Schwarting said at the annual European Congress of Rheumatology.
"OBSErve data suggest even greater improvements and lower discontinuation rates in real-world practice," said Dr. Schwarting of the Johannes Gutenberg University of Mainz (Germany). "We also saw a lower discontinuation rate than in the BLISS trials, and our study shows that you can identify responders well within 6 months."
Dr. Schwarting was the lead author of the retrospective, observational study , which included 102 patients with active lupus who were treated with open-label belimumab (Benlysta) over a 6-month period. Most (85%) had moderate or severe disease, and 80% had been on four to five different lupus medications before starting belimumab. The most common reasons for starting belimumab were ineffective prior treatment (88%), worsening disease (61%), and the need to decrease steroid use (40%).
At baseline, the mean steroid dose was 13.7 mg/day; 62% were taking a high dose, with a mean of 17.5 mg/day.
The primary endpoint was overall clinical response after 6 months of treatment. Most (75) had a disease activity improvement of at least 20%, including 35 who had an improvement of up to 49%, 31 with at least a 50% improvement, and 9 with at least an 80% improvement.
Five patients showed no improvement. Two became worse on the medication, and 14 had less than a 20% improvement. Six patients discontinued the drug: three because of disease progression, one because of an allergic reaction, one as a result of a lack of compliance, and one because of heart failure after hospitalization. The patient with heart failure died, but Dr. Schwarting said there was no apparent causal relationship with belimumab.
The improvement occurred in all lupus manifestations, including arthritis (71% response rate), a high level of anti–double-stranded DNA antibodies (50%), low complement levels (34%), fatigue (65%), and rash (62%).
The Systemic Lupus Erythematosus Disease Activity Index scores decreased from a mean of 10.6 to 5.6.
Belimumab exerted a steroid-sparing effect, Dr. Schwarting noted. The mean daily steroid dose decreased from 13.7 mg to 7.6 mg. Among those using more than 17.5 mg/day, the dosage decreased to 8.6 mg/day.
GlaxoSmithKline sponsored the study. Dr. Schwarting said he has received honoraria, consulting, and speakers fees from the company.
On Twitter @alz_gal
PARIS – Belimumab produced significant clinical improvement in 74% of patients with systemic lupus erythematosus who took it over a 6-month period, reducing disease symptoms and steroid use and significantly improving quality of life.
Results from the multicenter German OBSErve study paralleled – and even exceeded – those of the BLISS randomized trials, Dr. Andreas Schwarting said at the annual European Congress of Rheumatology.
"OBSErve data suggest even greater improvements and lower discontinuation rates in real-world practice," said Dr. Schwarting of the Johannes Gutenberg University of Mainz (Germany). "We also saw a lower discontinuation rate than in the BLISS trials, and our study shows that you can identify responders well within 6 months."
Dr. Schwarting was the lead author of the retrospective, observational study , which included 102 patients with active lupus who were treated with open-label belimumab (Benlysta) over a 6-month period. Most (85%) had moderate or severe disease, and 80% had been on four to five different lupus medications before starting belimumab. The most common reasons for starting belimumab were ineffective prior treatment (88%), worsening disease (61%), and the need to decrease steroid use (40%).
At baseline, the mean steroid dose was 13.7 mg/day; 62% were taking a high dose, with a mean of 17.5 mg/day.
The primary endpoint was overall clinical response after 6 months of treatment. Most (75) had a disease activity improvement of at least 20%, including 35 who had an improvement of up to 49%, 31 with at least a 50% improvement, and 9 with at least an 80% improvement.
Five patients showed no improvement. Two became worse on the medication, and 14 had less than a 20% improvement. Six patients discontinued the drug: three because of disease progression, one because of an allergic reaction, one as a result of a lack of compliance, and one because of heart failure after hospitalization. The patient with heart failure died, but Dr. Schwarting said there was no apparent causal relationship with belimumab.
The improvement occurred in all lupus manifestations, including arthritis (71% response rate), a high level of anti–double-stranded DNA antibodies (50%), low complement levels (34%), fatigue (65%), and rash (62%).
The Systemic Lupus Erythematosus Disease Activity Index scores decreased from a mean of 10.6 to 5.6.
Belimumab exerted a steroid-sparing effect, Dr. Schwarting noted. The mean daily steroid dose decreased from 13.7 mg to 7.6 mg. Among those using more than 17.5 mg/day, the dosage decreased to 8.6 mg/day.
GlaxoSmithKline sponsored the study. Dr. Schwarting said he has received honoraria, consulting, and speakers fees from the company.
On Twitter @alz_gal
PARIS – Belimumab produced significant clinical improvement in 74% of patients with systemic lupus erythematosus who took it over a 6-month period, reducing disease symptoms and steroid use and significantly improving quality of life.
Results from the multicenter German OBSErve study paralleled – and even exceeded – those of the BLISS randomized trials, Dr. Andreas Schwarting said at the annual European Congress of Rheumatology.
"OBSErve data suggest even greater improvements and lower discontinuation rates in real-world practice," said Dr. Schwarting of the Johannes Gutenberg University of Mainz (Germany). "We also saw a lower discontinuation rate than in the BLISS trials, and our study shows that you can identify responders well within 6 months."
Dr. Schwarting was the lead author of the retrospective, observational study , which included 102 patients with active lupus who were treated with open-label belimumab (Benlysta) over a 6-month period. Most (85%) had moderate or severe disease, and 80% had been on four to five different lupus medications before starting belimumab. The most common reasons for starting belimumab were ineffective prior treatment (88%), worsening disease (61%), and the need to decrease steroid use (40%).
At baseline, the mean steroid dose was 13.7 mg/day; 62% were taking a high dose, with a mean of 17.5 mg/day.
The primary endpoint was overall clinical response after 6 months of treatment. Most (75) had a disease activity improvement of at least 20%, including 35 who had an improvement of up to 49%, 31 with at least a 50% improvement, and 9 with at least an 80% improvement.
Five patients showed no improvement. Two became worse on the medication, and 14 had less than a 20% improvement. Six patients discontinued the drug: three because of disease progression, one because of an allergic reaction, one as a result of a lack of compliance, and one because of heart failure after hospitalization. The patient with heart failure died, but Dr. Schwarting said there was no apparent causal relationship with belimumab.
The improvement occurred in all lupus manifestations, including arthritis (71% response rate), a high level of anti–double-stranded DNA antibodies (50%), low complement levels (34%), fatigue (65%), and rash (62%).
The Systemic Lupus Erythematosus Disease Activity Index scores decreased from a mean of 10.6 to 5.6.
Belimumab exerted a steroid-sparing effect, Dr. Schwarting noted. The mean daily steroid dose decreased from 13.7 mg to 7.6 mg. Among those using more than 17.5 mg/day, the dosage decreased to 8.6 mg/day.
GlaxoSmithKline sponsored the study. Dr. Schwarting said he has received honoraria, consulting, and speakers fees from the company.
On Twitter @alz_gal
AT THE EULAR CONGRESS 2014
Key clinical point: Belimumab reduced disease activity, improved quality of life, and reduced steroid usage for patients with systemic lupus erythematosus.
Major finding: The improvement occurred in all lupus manifestations, including arthritis (71% response rate), a high level of anti–double-stranded DNA antibodies (50%), low complement levels (34%), fatigue (65%), and rash (62%).
Data source: A 6-month, retrospective, observational study of 102 patients.
Disclosures GlaxoSmithKline sponsored the study. Dr. Schwarting said he has received honoraria, consulting, and speakers fees from the company.
Obesity may drive symptom severity in rheumatoid arthritis
PARIS – The higher disease activity scores seen in obese patients with rheumatoid arthritis may be driven by the proinflammatory state that is associated with obesity, Dr. Christopher Sparks reported in a press conference at the annual European Congress of Rheumatology.
Although obese RA patients tend to have less radiographic joint damage than do normal-weight RA patients, they have comparable DAS (disease activity score) 28. With the clinical focus on treat-to-target, an approach guided by DAS scores, obese RA patients may be getting more aggressive treatment. The finding may explain why obese patients with RA have better outcomes than normal-weight and thin RA patients, said Dr. Sparks, a clinical research fellow at the University of Liverpool, England.
Dr. Sparks and his colleagues used an international RA database to examine two patient subgroups: those diagnosed with RA in the previous year and those with longstanding RA. The 3,534 patients were stratified by their body mass index into five groups: underweight (less than 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obese (30-34.9 kg/m2), and obese II (35 kg/m2 or more). In the 1,981 patients with longstanding disease, median disease duration was about 7 years; the other 1,553 patients had disease duration of 1 year or less.
About 73% of the each cohort was female, and the distribution of BMI measures was similar for the two cohorts.
The groups were compared by BMI and RA disease measures that included DAS28, erythrocyte sedimentation rate, tender joint count; swollen joint count; and visual analog scale disease activity.
After adjusting for RA risk factors, obesity (BMI of 28 kg/m2 or greater) was significantly associated with a DAS28 exceeding 5.1, an elevated erythrocyte sedimentation rate, high tender joint count, and high visual analog scale score. For instance, compared with normal weight and overweight patients, underweight and both groups of obese patients were 1.5-2.2 times as likely to have a DAS28 exceeding 5.1, Dr. Sparks reported.
He had no financial disclosures.
PARIS – The higher disease activity scores seen in obese patients with rheumatoid arthritis may be driven by the proinflammatory state that is associated with obesity, Dr. Christopher Sparks reported in a press conference at the annual European Congress of Rheumatology.
Although obese RA patients tend to have less radiographic joint damage than do normal-weight RA patients, they have comparable DAS (disease activity score) 28. With the clinical focus on treat-to-target, an approach guided by DAS scores, obese RA patients may be getting more aggressive treatment. The finding may explain why obese patients with RA have better outcomes than normal-weight and thin RA patients, said Dr. Sparks, a clinical research fellow at the University of Liverpool, England.
Dr. Sparks and his colleagues used an international RA database to examine two patient subgroups: those diagnosed with RA in the previous year and those with longstanding RA. The 3,534 patients were stratified by their body mass index into five groups: underweight (less than 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obese (30-34.9 kg/m2), and obese II (35 kg/m2 or more). In the 1,981 patients with longstanding disease, median disease duration was about 7 years; the other 1,553 patients had disease duration of 1 year or less.
About 73% of the each cohort was female, and the distribution of BMI measures was similar for the two cohorts.
The groups were compared by BMI and RA disease measures that included DAS28, erythrocyte sedimentation rate, tender joint count; swollen joint count; and visual analog scale disease activity.
After adjusting for RA risk factors, obesity (BMI of 28 kg/m2 or greater) was significantly associated with a DAS28 exceeding 5.1, an elevated erythrocyte sedimentation rate, high tender joint count, and high visual analog scale score. For instance, compared with normal weight and overweight patients, underweight and both groups of obese patients were 1.5-2.2 times as likely to have a DAS28 exceeding 5.1, Dr. Sparks reported.
He had no financial disclosures.
PARIS – The higher disease activity scores seen in obese patients with rheumatoid arthritis may be driven by the proinflammatory state that is associated with obesity, Dr. Christopher Sparks reported in a press conference at the annual European Congress of Rheumatology.
Although obese RA patients tend to have less radiographic joint damage than do normal-weight RA patients, they have comparable DAS (disease activity score) 28. With the clinical focus on treat-to-target, an approach guided by DAS scores, obese RA patients may be getting more aggressive treatment. The finding may explain why obese patients with RA have better outcomes than normal-weight and thin RA patients, said Dr. Sparks, a clinical research fellow at the University of Liverpool, England.
Dr. Sparks and his colleagues used an international RA database to examine two patient subgroups: those diagnosed with RA in the previous year and those with longstanding RA. The 3,534 patients were stratified by their body mass index into five groups: underweight (less than 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obese (30-34.9 kg/m2), and obese II (35 kg/m2 or more). In the 1,981 patients with longstanding disease, median disease duration was about 7 years; the other 1,553 patients had disease duration of 1 year or less.
About 73% of the each cohort was female, and the distribution of BMI measures was similar for the two cohorts.
The groups were compared by BMI and RA disease measures that included DAS28, erythrocyte sedimentation rate, tender joint count; swollen joint count; and visual analog scale disease activity.
After adjusting for RA risk factors, obesity (BMI of 28 kg/m2 or greater) was significantly associated with a DAS28 exceeding 5.1, an elevated erythrocyte sedimentation rate, high tender joint count, and high visual analog scale score. For instance, compared with normal weight and overweight patients, underweight and both groups of obese patients were 1.5-2.2 times as likely to have a DAS28 exceeding 5.1, Dr. Sparks reported.
He had no financial disclosures.
AT THE EULAR CONGRESS 2014
Key clinical point: Obesity and underweight status are associated with worse symptoms of RA.
Major finding: Compared with normal weight and overweight patients, underweight and both groups of obese patients were 1.5-2.2 times as likely to have a DAS28 exceeding 5.1.
Data source: An international RA database sample of 3,534 patients.
Disclosures: Dr. Sparks had no financial disclosures.
