BSR Annual Conference 2016

GLASGOW – People with giant cell arteritis may be more likely to go blind if they have underlying vascular disease, according to an analysis of the Diagnostic and Classification Criteria in Vasculitis Study.

The results of the analysis showed that 7.9% of patients with this common type of vasculitis go blind in at least one eye within 6 months of a diagnosis, and that those with a history of peripheral vascular disease (PVD) could be up to 10 times more at risk than those without additional vascular comorbidity.

“This is the first multinational study for patients with [giant cell arteritis], and it shows that blindness is a significant problem,” said Dr. Max Yates of the University of East Anglia in Norwich, England, who presented the findings at the British Society for Rheumatology annual conference. Blindness was defined as complete visual loss rather than by a full ophthalmology assessment, so the findings probably underplay the problem in patients with some form of visual loss, he observed. Visual disturbance had been noted in 42.9% of the patients who were studied at the first clinic review.

©Nephron/Wikimedia Commons

“It is interesting that there is the association with vascular disease,” Dr. Yates said. “Perhaps we need greater vigilance in those people who already have a diagnosis of vascular disease [and] to really watch and monitor those people carefully for sight loss.”

The Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) is an ongoing project designed to develop and then validate new classification and diagnostic criteria for systemic vasculitis that can be used routinely in clinical practice and in clinical trials. So far, more than 3,500 participants over age 18 have been recruited from secondary care clinics, and of those, 2,000 have a new or established diagnosis of vasculitis. The others have a similar presentation but an alternative diagnosis.

A total of 433 patients participating in the DCVAS were identified as having GCA with more than 75% diagnostic certainty, of which 93% fulfilled the 1990 American College of Rheumatology (ACR) criteria for GCA and just over half (54%) had a positive temporal artery biopsy. Visual loss was recorded by completion of the Vasculitis Damage Index (VDI) 6 months after diagnosis.

Two-thirds of patients studied were female, the median age at diagnosis was 73 years, 40% had jaw claudication, 34% had lost weight, and 16% presented with a fever. In addition, 9.2% had diabetes, 3.2% a prior stroke, and 2.5% had PVD.

Looking for predictive factors, baseline laboratory findings such as the presence of anemia, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, or platelet counts were not associated with sight loss. Dr. Yates noted in discussion that the baseline ESR range was 35-120 mm/h and the CRP ranged from 12 to over 100 mg/dL in the patients studied.

However, prior vascular disease was found to be predictive of later blindness. The odds ratio (OR) for being blind in at least one eye 6 months after a GCA diagnosis was 10.44 for PVD, with the 95% confidence interval (CI) ranging from 2.94 to 37.03. A prior diagnosis of cerebral vascular accident (OR, 4.47; 95% CI, 1.30-15.41), and diabetes (OR, 2.48; 95% CI, 0.98-6.25) also upped the risk for complete sight loss at 6 months.

Dr. Yates noted that patients were selected from multiple clinics across secondary care, so there should be better generalizability than in prior, single-center studies. However, there could be some residual referral bias.

During discussion, it was pointed out that it would be helpful to know the rate of blindness in patients taking steroids, as this was one of the major reasons for emergency rheumatology calls at one clinic, a delegate observed.

“Giant cell arteritis is really the major rheumatology emergency for practicing clinicians. We recently set up a rheumatology day service and get usually 8-10 calls about it per day,” the delegate said. “It’s often said that once a patient is on any dose of steroids, there is not risk of them going blind.” There is a lot of angst about whether it is safe to use higher doses (60 mg vs. 40 mg) and “it’s important for us as clinicians to be able to reassure people.”

Dr. Yates noted that a prospective trial would be needed to answer the question and that trials were planned. “We don’t have any data on treatment,” he said. “So we’re unable to say whether steroids were started instantly or whether there was any improvement in the visual function of these people.” Long-term complications also would be something to look at, particularly in older people who have an increased risk for eye problems such as cataracts, and could be at higher risk for visual problems if treated with steroids or other agents.

The DCVAS study is supported by the ACR and is funded by the European League Against Rheumatism and the Vasculitis Foundation. Dr. Yates reported that he had no relevant disclosures.

GLASGOW – People with giant cell arteritis may be more likely to go blind if they have underlying vascular disease, according to an analysis of the Diagnostic and Classification Criteria in Vasculitis Study.

The results of the analysis showed that 7.9% of patients with this common type of vasculitis go blind in at least one eye within 6 months of a diagnosis, and that those with a history of peripheral vascular disease (PVD) could be up to 10 times more at risk than those without additional vascular comorbidity.

“This is the first multinational study for patients with [giant cell arteritis], and it shows that blindness is a significant problem,” said Dr. Max Yates of the University of East Anglia in Norwich, England, who presented the findings at the British Society for Rheumatology annual conference. Blindness was defined as complete visual loss rather than by a full ophthalmology assessment, so the findings probably underplay the problem in patients with some form of visual loss, he observed. Visual disturbance had been noted in 42.9% of the patients who were studied at the first clinic review.

©Nephron/Wikimedia Commons

“It is interesting that there is the association with vascular disease,” Dr. Yates said. “Perhaps we need greater vigilance in those people who already have a diagnosis of vascular disease [and] to really watch and monitor those people carefully for sight loss.”

The Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) is an ongoing project designed to develop and then validate new classification and diagnostic criteria for systemic vasculitis that can be used routinely in clinical practice and in clinical trials. So far, more than 3,500 participants over age 18 have been recruited from secondary care clinics, and of those, 2,000 have a new or established diagnosis of vasculitis. The others have a similar presentation but an alternative diagnosis.

A total of 433 patients participating in the DCVAS were identified as having GCA with more than 75% diagnostic certainty, of which 93% fulfilled the 1990 American College of Rheumatology (ACR) criteria for GCA and just over half (54%) had a positive temporal artery biopsy. Visual loss was recorded by completion of the Vasculitis Damage Index (VDI) 6 months after diagnosis.

Two-thirds of patients studied were female, the median age at diagnosis was 73 years, 40% had jaw claudication, 34% had lost weight, and 16% presented with a fever. In addition, 9.2% had diabetes, 3.2% a prior stroke, and 2.5% had PVD.

Looking for predictive factors, baseline laboratory findings such as the presence of anemia, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, or platelet counts were not associated with sight loss. Dr. Yates noted in discussion that the baseline ESR range was 35-120 mm/h and the CRP ranged from 12 to over 100 mg/dL in the patients studied.

However, prior vascular disease was found to be predictive of later blindness. The odds ratio (OR) for being blind in at least one eye 6 months after a GCA diagnosis was 10.44 for PVD, with the 95% confidence interval (CI) ranging from 2.94 to 37.03. A prior diagnosis of cerebral vascular accident (OR, 4.47; 95% CI, 1.30-15.41), and diabetes (OR, 2.48; 95% CI, 0.98-6.25) also upped the risk for complete sight loss at 6 months.

Dr. Yates noted that patients were selected from multiple clinics across secondary care, so there should be better generalizability than in prior, single-center studies. However, there could be some residual referral bias.

During discussion, it was pointed out that it would be helpful to know the rate of blindness in patients taking steroids, as this was one of the major reasons for emergency rheumatology calls at one clinic, a delegate observed.

“Giant cell arteritis is really the major rheumatology emergency for practicing clinicians. We recently set up a rheumatology day service and get usually 8-10 calls about it per day,” the delegate said. “It’s often said that once a patient is on any dose of steroids, there is not risk of them going blind.” There is a lot of angst about whether it is safe to use higher doses (60 mg vs. 40 mg) and “it’s important for us as clinicians to be able to reassure people.”

Dr. Yates noted that a prospective trial would be needed to answer the question and that trials were planned. “We don’t have any data on treatment,” he said. “So we’re unable to say whether steroids were started instantly or whether there was any improvement in the visual function of these people.” Long-term complications also would be something to look at, particularly in older people who have an increased risk for eye problems such as cataracts, and could be at higher risk for visual problems if treated with steroids or other agents.

The DCVAS study is supported by the ACR and is funded by the European League Against Rheumatism and the Vasculitis Foundation. Dr. Yates reported that he had no relevant disclosures.

GLASGOW – People with giant cell arteritis may be more likely to go blind if they have underlying vascular disease, according to an analysis of the Diagnostic and Classification Criteria in Vasculitis Study.

The results of the analysis showed that 7.9% of patients with this common type of vasculitis go blind in at least one eye within 6 months of a diagnosis, and that those with a history of peripheral vascular disease (PVD) could be up to 10 times more at risk than those without additional vascular comorbidity.

“This is the first multinational study for patients with [giant cell arteritis], and it shows that blindness is a significant problem,” said Dr. Max Yates of the University of East Anglia in Norwich, England, who presented the findings at the British Society for Rheumatology annual conference. Blindness was defined as complete visual loss rather than by a full ophthalmology assessment, so the findings probably underplay the problem in patients with some form of visual loss, he observed. Visual disturbance had been noted in 42.9% of the patients who were studied at the first clinic review.

©Nephron/Wikimedia Commons

“It is interesting that there is the association with vascular disease,” Dr. Yates said. “Perhaps we need greater vigilance in those people who already have a diagnosis of vascular disease [and] to really watch and monitor those people carefully for sight loss.”

The Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) is an ongoing project designed to develop and then validate new classification and diagnostic criteria for systemic vasculitis that can be used routinely in clinical practice and in clinical trials. So far, more than 3,500 participants over age 18 have been recruited from secondary care clinics, and of those, 2,000 have a new or established diagnosis of vasculitis. The others have a similar presentation but an alternative diagnosis.

A total of 433 patients participating in the DCVAS were identified as having GCA with more than 75% diagnostic certainty, of which 93% fulfilled the 1990 American College of Rheumatology (ACR) criteria for GCA and just over half (54%) had a positive temporal artery biopsy. Visual loss was recorded by completion of the Vasculitis Damage Index (VDI) 6 months after diagnosis.

Two-thirds of patients studied were female, the median age at diagnosis was 73 years, 40% had jaw claudication, 34% had lost weight, and 16% presented with a fever. In addition, 9.2% had diabetes, 3.2% a prior stroke, and 2.5% had PVD.

Looking for predictive factors, baseline laboratory findings such as the presence of anemia, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, or platelet counts were not associated with sight loss. Dr. Yates noted in discussion that the baseline ESR range was 35-120 mm/h and the CRP ranged from 12 to over 100 mg/dL in the patients studied.

However, prior vascular disease was found to be predictive of later blindness. The odds ratio (OR) for being blind in at least one eye 6 months after a GCA diagnosis was 10.44 for PVD, with the 95% confidence interval (CI) ranging from 2.94 to 37.03. A prior diagnosis of cerebral vascular accident (OR, 4.47; 95% CI, 1.30-15.41), and diabetes (OR, 2.48; 95% CI, 0.98-6.25) also upped the risk for complete sight loss at 6 months.

Dr. Yates noted that patients were selected from multiple clinics across secondary care, so there should be better generalizability than in prior, single-center studies. However, there could be some residual referral bias.

During discussion, it was pointed out that it would be helpful to know the rate of blindness in patients taking steroids, as this was one of the major reasons for emergency rheumatology calls at one clinic, a delegate observed.

“Giant cell arteritis is really the major rheumatology emergency for practicing clinicians. We recently set up a rheumatology day service and get usually 8-10 calls about it per day,” the delegate said. “It’s often said that once a patient is on any dose of steroids, there is not risk of them going blind.” There is a lot of angst about whether it is safe to use higher doses (60 mg vs. 40 mg) and “it’s important for us as clinicians to be able to reassure people.”

Dr. Yates noted that a prospective trial would be needed to answer the question and that trials were planned. “We don’t have any data on treatment,” he said. “So we’re unable to say whether steroids were started instantly or whether there was any improvement in the visual function of these people.” Long-term complications also would be something to look at, particularly in older people who have an increased risk for eye problems such as cataracts, and could be at higher risk for visual problems if treated with steroids or other agents.

The DCVAS study is supported by the ACR and is funded by the European League Against Rheumatism and the Vasculitis Foundation. Dr. Yates reported that he had no relevant disclosures.

GLASGOW – Rituximab is unlikely to work as a treatment for Sjögren’s syndrome, according to a sneak peak of results from a multicenter study.

The study, the Trial of Anti–B Cell Therapy in Patients With Primary Sjögren’s Syndrome (TRACTISS), showed that there were no significant differences between the active and placebo arms in terms of alleviating oral dryness or fatigue, Dr. Simon J. Bowman, a principal investigator for the trial, observed at the British Society for Rheumatology annual conference. In addition, no difference was found in the EULAR Sjögren’s syndrome disease activity index (ESSDAI).

In TRACTISS, 110 patients with primary Sjögren’s syndrome received two courses of rituximab (Rituxan) or placebo in addition to standard therapy, and they were followed up for up to 48 weeks (BMC Musculoskelet Disord. 2014;15:21).

Dr. Bowman, a consultant rheumatologist and honorary professor of rheumatology at the Queen Elizabeth Hospital, Birmingham, England, noted that there was some indication of an effect of rituximab on fatigue and oral dryness in another large, randomized, controlled trial – the Tolerance and Efficacy of Rituximab in Sjögren’s syndrome (TEARS) study – a couple of years ago (Ann Rheum Dis. 2013;72[6]:1026-31), but these were not the primary endpoints of the study, so those results were essentially negative.

Calling the TRACTISS findings something of disappointment, Dr. Bowman said: “I think we’ll have to wait and see, but having had two big formal trials, I have to say that it doesn’t look like rituximab on its own is going to be any [great] success.”

Hopes were high for rituximab 5 years ago, when recruitment into the TRACTISS trial started, principally because drugs like rituximab already were available for use, Dr. Bowman said at the time. The focus was on anti–B cell therapies, because not only were they available but several features of Sjögren’s syndrome potentially are linked to B-cell activity, such as fatigue in about two-thirds of patients, the presence of anti-Ro and anti-La antibodies in about 40% of patients, and lymphoma in about 5% of patients. Also, several small studies had suggested rituximab might prove beneficial.

Other B-cell therapeutic options

Clearly, other B-cell targets might offer alternative therapeutic approaches. One of those under investigation is using belimumab (Benlysta) to target B cell–activating factor (BAFF) or B-cell lymphocyte stimulator (BLyS). Results of the BELISS study, a small, open-label, phase II trial in 30 patients with Sjögren’s syndrome (Ann Rheum Dis. 2015;74[3]:526-31) showed there were some improvements in the ESSDAI and the EULAR Sjögren’s Syndrome Patient-Reported Index (ESSPRI). The improvements were great enough to justify proceeding to a larger clinical trial.

Perhaps the real hope for biologic therapy lies in targeting the T cells for which there is a very good rationale, said Wan-Fai Ng, Ph.D., professor of rheumatology at Newcastle University, Newcastle upon Tyne, England. Various approaches are available, and in addition, there have been some “encouraging” data from early-phase clinical trials.

Abatacept (Orencia), for example, has been looked at in a few trials, with positive drops in ESSDAI and other endpoints, and currently, there is an ongoing phase III trial in 88 patients with primary Sjögren’s syndrome. There are a couple of ongoing phase II trials, one with the anti-CD40 molecule CFZ533 and another with the anti-B7RP1 molecule AMG 557.

Dr. Ng noted that a trial of efalizumab (Raptiva) had terminated because of an increased risk for progressive multifocal leukoencephalopathy. In addition, a couple of other molecules, rhIL-2 and alefacept (Amevive), are under investigation, he said.

Four additional therapeutic targets

Other novel approaches to developing biologic therapy for Sjögren’s were summarized by Dr. Francesca Barone, a senior lecturer at the Queen Elizabeth Hospital in Birmingham, England. She described four strategies, the first of which was targeting the cross talk between antigen-presenting dendritic cells and T cells using a novel molecule RO5459072 that targets a protein called cathepsin S. Cathepsin S is involved in the assembly of the major histocompatibility complex II protein, and by interfering with this process, the theory is that the effector T-helper cell response will be muted and T-cell interaction with B cells will be decreased. A phase II “proof-of-concept” trial is underway with RO5459072 and will recruit 70 patients, she said.

A second strategy is targeting intracellular B cell signaling by targeting P13 kinase delta with UCB 5857. P13 kinase delta catalyzes B cell activation and “is really at the core of the biology of the B cell,” Dr. Barone observed. A phase II trial with UCB 5857 is planned in 52 patients.

A third approach is to target lymphoneogenesis more generally by interfering with the production of the chemokines CXCL13 and CXCL12. This might be achieved via interleukin (IL)–17 and IL-22 blockade. A trial with the novel agent baminercept, a lymphotoxin beta receptor fusion protein. However, that trial was stopped in 2014 for technical reasons.

A fourth strategy is to use combination “sandwich” treatment, consisting of belimumab, rituximab, and then belimumab again. “This is what is going to come next, putting two drugs together,” Dr. Barone said. A randomized, double-blind, controlled trial now open to recruitment aims to investigate whether there is value in this approach.

“We’ve bombarded you with a lot of targets,” Dr. Barone observed. “What do we believe is going to be the best one is very, very unclear.”

TRACTISS was funded by Arthritis Research UK with rituximab provided by Roche. Dr. Bowman did not provide any disclosures but previously has been a consultant for Roche, UCB Pharma, and Merck-Serono. Dr. Ng reported no conflicts of interest, and Dr. Barone disclosed consultancy or collaboration with UCB Pharma, GlaxoSmithKline, Celgene, Eli Lilly, and Roche.

GLASGOW – Rituximab is unlikely to work as a treatment for Sjögren’s syndrome, according to a sneak peak of results from a multicenter study.

The study, the Trial of Anti–B Cell Therapy in Patients With Primary Sjögren’s Syndrome (TRACTISS), showed that there were no significant differences between the active and placebo arms in terms of alleviating oral dryness or fatigue, Dr. Simon J. Bowman, a principal investigator for the trial, observed at the British Society for Rheumatology annual conference. In addition, no difference was found in the EULAR Sjögren’s syndrome disease activity index (ESSDAI).

In TRACTISS, 110 patients with primary Sjögren’s syndrome received two courses of rituximab (Rituxan) or placebo in addition to standard therapy, and they were followed up for up to 48 weeks (BMC Musculoskelet Disord. 2014;15:21).

Dr. Bowman, a consultant rheumatologist and honorary professor of rheumatology at the Queen Elizabeth Hospital, Birmingham, England, noted that there was some indication of an effect of rituximab on fatigue and oral dryness in another large, randomized, controlled trial – the Tolerance and Efficacy of Rituximab in Sjögren’s syndrome (TEARS) study – a couple of years ago (Ann Rheum Dis. 2013;72[6]:1026-31), but these were not the primary endpoints of the study, so those results were essentially negative.

Calling the TRACTISS findings something of disappointment, Dr. Bowman said: “I think we’ll have to wait and see, but having had two big formal trials, I have to say that it doesn’t look like rituximab on its own is going to be any [great] success.”

Hopes were high for rituximab 5 years ago, when recruitment into the TRACTISS trial started, principally because drugs like rituximab already were available for use, Dr. Bowman said at the time. The focus was on anti–B cell therapies, because not only were they available but several features of Sjögren’s syndrome potentially are linked to B-cell activity, such as fatigue in about two-thirds of patients, the presence of anti-Ro and anti-La antibodies in about 40% of patients, and lymphoma in about 5% of patients. Also, several small studies had suggested rituximab might prove beneficial.

Other B-cell therapeutic options

Clearly, other B-cell targets might offer alternative therapeutic approaches. One of those under investigation is using belimumab (Benlysta) to target B cell–activating factor (BAFF) or B-cell lymphocyte stimulator (BLyS). Results of the BELISS study, a small, open-label, phase II trial in 30 patients with Sjögren’s syndrome (Ann Rheum Dis. 2015;74[3]:526-31) showed there were some improvements in the ESSDAI and the EULAR Sjögren’s Syndrome Patient-Reported Index (ESSPRI). The improvements were great enough to justify proceeding to a larger clinical trial.

Perhaps the real hope for biologic therapy lies in targeting the T cells for which there is a very good rationale, said Wan-Fai Ng, Ph.D., professor of rheumatology at Newcastle University, Newcastle upon Tyne, England. Various approaches are available, and in addition, there have been some “encouraging” data from early-phase clinical trials.

Abatacept (Orencia), for example, has been looked at in a few trials, with positive drops in ESSDAI and other endpoints, and currently, there is an ongoing phase III trial in 88 patients with primary Sjögren’s syndrome. There are a couple of ongoing phase II trials, one with the anti-CD40 molecule CFZ533 and another with the anti-B7RP1 molecule AMG 557.

Dr. Ng noted that a trial of efalizumab (Raptiva) had terminated because of an increased risk for progressive multifocal leukoencephalopathy. In addition, a couple of other molecules, rhIL-2 and alefacept (Amevive), are under investigation, he said.

Four additional therapeutic targets

Other novel approaches to developing biologic therapy for Sjögren’s were summarized by Dr. Francesca Barone, a senior lecturer at the Queen Elizabeth Hospital in Birmingham, England. She described four strategies, the first of which was targeting the cross talk between antigen-presenting dendritic cells and T cells using a novel molecule RO5459072 that targets a protein called cathepsin S. Cathepsin S is involved in the assembly of the major histocompatibility complex II protein, and by interfering with this process, the theory is that the effector T-helper cell response will be muted and T-cell interaction with B cells will be decreased. A phase II “proof-of-concept” trial is underway with RO5459072 and will recruit 70 patients, she said.

A second strategy is targeting intracellular B cell signaling by targeting P13 kinase delta with UCB 5857. P13 kinase delta catalyzes B cell activation and “is really at the core of the biology of the B cell,” Dr. Barone observed. A phase II trial with UCB 5857 is planned in 52 patients.

A third approach is to target lymphoneogenesis more generally by interfering with the production of the chemokines CXCL13 and CXCL12. This might be achieved via interleukin (IL)–17 and IL-22 blockade. A trial with the novel agent baminercept, a lymphotoxin beta receptor fusion protein. However, that trial was stopped in 2014 for technical reasons.

A fourth strategy is to use combination “sandwich” treatment, consisting of belimumab, rituximab, and then belimumab again. “This is what is going to come next, putting two drugs together,” Dr. Barone said. A randomized, double-blind, controlled trial now open to recruitment aims to investigate whether there is value in this approach.

“We’ve bombarded you with a lot of targets,” Dr. Barone observed. “What do we believe is going to be the best one is very, very unclear.”

TRACTISS was funded by Arthritis Research UK with rituximab provided by Roche. Dr. Bowman did not provide any disclosures but previously has been a consultant for Roche, UCB Pharma, and Merck-Serono. Dr. Ng reported no conflicts of interest, and Dr. Barone disclosed consultancy or collaboration with UCB Pharma, GlaxoSmithKline, Celgene, Eli Lilly, and Roche.

GLASGOW – Rituximab is unlikely to work as a treatment for Sjögren’s syndrome, according to a sneak peak of results from a multicenter study.

The study, the Trial of Anti–B Cell Therapy in Patients With Primary Sjögren’s Syndrome (TRACTISS), showed that there were no significant differences between the active and placebo arms in terms of alleviating oral dryness or fatigue, Dr. Simon J. Bowman, a principal investigator for the trial, observed at the British Society for Rheumatology annual conference. In addition, no difference was found in the EULAR Sjögren’s syndrome disease activity index (ESSDAI).

In TRACTISS, 110 patients with primary Sjögren’s syndrome received two courses of rituximab (Rituxan) or placebo in addition to standard therapy, and they were followed up for up to 48 weeks (BMC Musculoskelet Disord. 2014;15:21).

Dr. Bowman, a consultant rheumatologist and honorary professor of rheumatology at the Queen Elizabeth Hospital, Birmingham, England, noted that there was some indication of an effect of rituximab on fatigue and oral dryness in another large, randomized, controlled trial – the Tolerance and Efficacy of Rituximab in Sjögren’s syndrome (TEARS) study – a couple of years ago (Ann Rheum Dis. 2013;72[6]:1026-31), but these were not the primary endpoints of the study, so those results were essentially negative.

Calling the TRACTISS findings something of disappointment, Dr. Bowman said: “I think we’ll have to wait and see, but having had two big formal trials, I have to say that it doesn’t look like rituximab on its own is going to be any [great] success.”

Hopes were high for rituximab 5 years ago, when recruitment into the TRACTISS trial started, principally because drugs like rituximab already were available for use, Dr. Bowman said at the time. The focus was on anti–B cell therapies, because not only were they available but several features of Sjögren’s syndrome potentially are linked to B-cell activity, such as fatigue in about two-thirds of patients, the presence of anti-Ro and anti-La antibodies in about 40% of patients, and lymphoma in about 5% of patients. Also, several small studies had suggested rituximab might prove beneficial.

Other B-cell therapeutic options

Clearly, other B-cell targets might offer alternative therapeutic approaches. One of those under investigation is using belimumab (Benlysta) to target B cell–activating factor (BAFF) or B-cell lymphocyte stimulator (BLyS). Results of the BELISS study, a small, open-label, phase II trial in 30 patients with Sjögren’s syndrome (Ann Rheum Dis. 2015;74[3]:526-31) showed there were some improvements in the ESSDAI and the EULAR Sjögren’s Syndrome Patient-Reported Index (ESSPRI). The improvements were great enough to justify proceeding to a larger clinical trial.

Perhaps the real hope for biologic therapy lies in targeting the T cells for which there is a very good rationale, said Wan-Fai Ng, Ph.D., professor of rheumatology at Newcastle University, Newcastle upon Tyne, England. Various approaches are available, and in addition, there have been some “encouraging” data from early-phase clinical trials.

Abatacept (Orencia), for example, has been looked at in a few trials, with positive drops in ESSDAI and other endpoints, and currently, there is an ongoing phase III trial in 88 patients with primary Sjögren’s syndrome. There are a couple of ongoing phase II trials, one with the anti-CD40 molecule CFZ533 and another with the anti-B7RP1 molecule AMG 557.

Dr. Ng noted that a trial of efalizumab (Raptiva) had terminated because of an increased risk for progressive multifocal leukoencephalopathy. In addition, a couple of other molecules, rhIL-2 and alefacept (Amevive), are under investigation, he said.

Four additional therapeutic targets

Other novel approaches to developing biologic therapy for Sjögren’s were summarized by Dr. Francesca Barone, a senior lecturer at the Queen Elizabeth Hospital in Birmingham, England. She described four strategies, the first of which was targeting the cross talk between antigen-presenting dendritic cells and T cells using a novel molecule RO5459072 that targets a protein called cathepsin S. Cathepsin S is involved in the assembly of the major histocompatibility complex II protein, and by interfering with this process, the theory is that the effector T-helper cell response will be muted and T-cell interaction with B cells will be decreased. A phase II “proof-of-concept” trial is underway with RO5459072 and will recruit 70 patients, she said.

A second strategy is targeting intracellular B cell signaling by targeting P13 kinase delta with UCB 5857. P13 kinase delta catalyzes B cell activation and “is really at the core of the biology of the B cell,” Dr. Barone observed. A phase II trial with UCB 5857 is planned in 52 patients.

A third approach is to target lymphoneogenesis more generally by interfering with the production of the chemokines CXCL13 and CXCL12. This might be achieved via interleukin (IL)–17 and IL-22 blockade. A trial with the novel agent baminercept, a lymphotoxin beta receptor fusion protein. However, that trial was stopped in 2014 for technical reasons.

A fourth strategy is to use combination “sandwich” treatment, consisting of belimumab, rituximab, and then belimumab again. “This is what is going to come next, putting two drugs together,” Dr. Barone said. A randomized, double-blind, controlled trial now open to recruitment aims to investigate whether there is value in this approach.

“We’ve bombarded you with a lot of targets,” Dr. Barone observed. “What do we believe is going to be the best one is very, very unclear.”

TRACTISS was funded by Arthritis Research UK with rituximab provided by Roche. Dr. Bowman did not provide any disclosures but previously has been a consultant for Roche, UCB Pharma, and Merck-Serono. Dr. Ng reported no conflicts of interest, and Dr. Barone disclosed consultancy or collaboration with UCB Pharma, GlaxoSmithKline, Celgene, Eli Lilly, and Roche.

GLASGOW – Two novel clinical signs can be used to determine whether people who have had a fracture are likely to develop complex regional pain syndrome, a condition for which there is currently no specific diagnostic test.

The way in which patients perceived which of their fingers was being touched when their eyes were closed (finger perception) and the position of different parts of their body in relation to one another generally (body scheme) were found to be reliable ways of identifying those who would experience prolonged pain in the future. The positive and negative predictive values of using those tests together were a respective 84.1% and 76.9%.

“Digit misperception and body scheme combined can be useful in predicting chronic pain,” Dr. Nicholas Shenker of Addenbrooke’s Hospital in Cambridge, England, said in an interview at the British Society for Rheumatology annual conference.

“This may allow a reduction in chronic pain by identifying a cohort requiring more intensive intervention with physiotherapy and intervention,” he added. It also may help to reduce the incidence of complex regional pain syndrome (CRPS) after sustaining a fracture.

CPRS is characterized by prolonged, intractable pain that often follows injury to a limb, such as a fracture or another traumatic event. “It’s a nervy type pain, burning, and shooting, and it’s a horrible condition,” Dr. Shenker explained. “If you ask patients to rate the amount of pain they get from their condition, whether it is rheumatoid arthritis, fibromyalgia, or osteoarthritis, this is the condition that commonly comes top.”

With differential diagnoses spanning many rheumatologic and neurologic conditions, it is perhaps no surprise that patients with CRPS often go undiagnosed for many months. In fact, according to CRPS Registry UK findings, it can take up to 6 months after symptoms start before patients are diagnosed with the pain syndrome (Br J Pain. 2015;9[2]:122-8).

While pain symptoms may resolve by themselves in about one-third of patients by 3 months and three-quarters of patients by 12 months, there are a significant number of patients whose symptoms do not resolve, and their window of opportunity for treatment may have closed. Although treatment may be largely reassurance based for many, some patients may benefit from early physical therapy or pain medication.

“Once you have any chronic pain condition for more than 12 months, the chances of it getting better are pretty slim. So we want to identify these people early, but that is not easy,” Dr. Shenker observed.

Since there is currently no diagnostic test, Dr. Shenker and his associates identified four novel clinical signs – abnormal finger perception, hand laterality identification, body scheme report, and astereognosis – from a cohort of patients with CRPS and developed tests for them.

Finger perception was assessed by asking the subjects to place their hands on their laps, close their eyes and say which finger or thumb was being touched within a 20-second time limit. A positive test was a score of 8 or less out of 10.

Hand laterality was tested using a computer program showing the subjects a series of images of left and right hands and asking them to click whether the image was of a person’s right or left hand. A positive test was a score of fewer than 50 out of 56 or if the subject took longer than 3 minutes to complete the exercise.

Astereognosis, the inability to identify an object by the touch of the hands only, was assessed by asking the subjects to close their eyes and present their hand palms upward, then placing three different objects into it and asking them what they were touching. A test was considered positive if only two out of three objects were recognized, or if the subjects took longer than 6 seconds to identify the objects.

Finally, body scheme is about assessing how patients generally sense the parts of their bodies with their eyes closed, or how one side of the body compares in terms of size, weight, and length to the other. For this test, the body is divided into 17 areas, and over the course of 2 minutes, patients are asked to describe, without moving, how their left side compares to their right side. A test is considered positive if patients’ responses differ by more than 10% in two contiguous areas, such as the arm and elbow.

Only finger perception and body scheme were found to have good positive and negative predictive values individually.

The aim of the prospective observational cohort study Dr. Shenkar presented at the meeting on behalf of colleague Dr. Anoop Kuttikat was to look at those signs to see how common those scenarios were and to determine if these could be used as simple bedside tests to identify those likely to develop CRPS.

Dr. Shenkar reported data on 47 patients aged a mean of 53 years who needed a plaster cast for an upper (wrist) or lower (ankle/tibia) limb fracture who were assessed fewer than 2 weeks after their injury and followed up for 6 months. Their medical records were reviewed 3 years later to see whether chronic pain was present.

One patient developed CRPS. This patient had both a positive finger perception and body scheme test at the baseline assessment. Three patients had persistent pain, and two of those had positive finger perception and body scheme tests. The remaining 43 patients did not have persistent pain, and four of these patients had positive finger perception and body scheme tests. This means that 7 out of the 47 patients would be flagged very early on for further assessment and possible treatment, Dr. Shenker observed.

Future plans are to refine a quicker test for body scheme assessment and to perform a larger prospective multicenter study.

Dr. Shenker has received grant or research support from the British Medical Association, the U.K. National Institute for Health Research’s Clinical Research Network, and the Cambridge Arthritis Research Endeavour.

GLASGOW – Two novel clinical signs can be used to determine whether people who have had a fracture are likely to develop complex regional pain syndrome, a condition for which there is currently no specific diagnostic test.

The way in which patients perceived which of their fingers was being touched when their eyes were closed (finger perception) and the position of different parts of their body in relation to one another generally (body scheme) were found to be reliable ways of identifying those who would experience prolonged pain in the future. The positive and negative predictive values of using those tests together were a respective 84.1% and 76.9%.

“Digit misperception and body scheme combined can be useful in predicting chronic pain,” Dr. Nicholas Shenker of Addenbrooke’s Hospital in Cambridge, England, said in an interview at the British Society for Rheumatology annual conference.

“This may allow a reduction in chronic pain by identifying a cohort requiring more intensive intervention with physiotherapy and intervention,” he added. It also may help to reduce the incidence of complex regional pain syndrome (CRPS) after sustaining a fracture.

CPRS is characterized by prolonged, intractable pain that often follows injury to a limb, such as a fracture or another traumatic event. “It’s a nervy type pain, burning, and shooting, and it’s a horrible condition,” Dr. Shenker explained. “If you ask patients to rate the amount of pain they get from their condition, whether it is rheumatoid arthritis, fibromyalgia, or osteoarthritis, this is the condition that commonly comes top.”

With differential diagnoses spanning many rheumatologic and neurologic conditions, it is perhaps no surprise that patients with CRPS often go undiagnosed for many months. In fact, according to CRPS Registry UK findings, it can take up to 6 months after symptoms start before patients are diagnosed with the pain syndrome (Br J Pain. 2015;9[2]:122-8).

While pain symptoms may resolve by themselves in about one-third of patients by 3 months and three-quarters of patients by 12 months, there are a significant number of patients whose symptoms do not resolve, and their window of opportunity for treatment may have closed. Although treatment may be largely reassurance based for many, some patients may benefit from early physical therapy or pain medication.

“Once you have any chronic pain condition for more than 12 months, the chances of it getting better are pretty slim. So we want to identify these people early, but that is not easy,” Dr. Shenker observed.

Since there is currently no diagnostic test, Dr. Shenker and his associates identified four novel clinical signs – abnormal finger perception, hand laterality identification, body scheme report, and astereognosis – from a cohort of patients with CRPS and developed tests for them.

Finger perception was assessed by asking the subjects to place their hands on their laps, close their eyes and say which finger or thumb was being touched within a 20-second time limit. A positive test was a score of 8 or less out of 10.

Hand laterality was tested using a computer program showing the subjects a series of images of left and right hands and asking them to click whether the image was of a person’s right or left hand. A positive test was a score of fewer than 50 out of 56 or if the subject took longer than 3 minutes to complete the exercise.

Astereognosis, the inability to identify an object by the touch of the hands only, was assessed by asking the subjects to close their eyes and present their hand palms upward, then placing three different objects into it and asking them what they were touching. A test was considered positive if only two out of three objects were recognized, or if the subjects took longer than 6 seconds to identify the objects.

Finally, body scheme is about assessing how patients generally sense the parts of their bodies with their eyes closed, or how one side of the body compares in terms of size, weight, and length to the other. For this test, the body is divided into 17 areas, and over the course of 2 minutes, patients are asked to describe, without moving, how their left side compares to their right side. A test is considered positive if patients’ responses differ by more than 10% in two contiguous areas, such as the arm and elbow.

Only finger perception and body scheme were found to have good positive and negative predictive values individually.

The aim of the prospective observational cohort study Dr. Shenkar presented at the meeting on behalf of colleague Dr. Anoop Kuttikat was to look at those signs to see how common those scenarios were and to determine if these could be used as simple bedside tests to identify those likely to develop CRPS.

Dr. Shenkar reported data on 47 patients aged a mean of 53 years who needed a plaster cast for an upper (wrist) or lower (ankle/tibia) limb fracture who were assessed fewer than 2 weeks after their injury and followed up for 6 months. Their medical records were reviewed 3 years later to see whether chronic pain was present.

One patient developed CRPS. This patient had both a positive finger perception and body scheme test at the baseline assessment. Three patients had persistent pain, and two of those had positive finger perception and body scheme tests. The remaining 43 patients did not have persistent pain, and four of these patients had positive finger perception and body scheme tests. This means that 7 out of the 47 patients would be flagged very early on for further assessment and possible treatment, Dr. Shenker observed.

Future plans are to refine a quicker test for body scheme assessment and to perform a larger prospective multicenter study.

Dr. Shenker has received grant or research support from the British Medical Association, the U.K. National Institute for Health Research’s Clinical Research Network, and the Cambridge Arthritis Research Endeavour.

GLASGOW – Two novel clinical signs can be used to determine whether people who have had a fracture are likely to develop complex regional pain syndrome, a condition for which there is currently no specific diagnostic test.

The way in which patients perceived which of their fingers was being touched when their eyes were closed (finger perception) and the position of different parts of their body in relation to one another generally (body scheme) were found to be reliable ways of identifying those who would experience prolonged pain in the future. The positive and negative predictive values of using those tests together were a respective 84.1% and 76.9%.

“Digit misperception and body scheme combined can be useful in predicting chronic pain,” Dr. Nicholas Shenker of Addenbrooke’s Hospital in Cambridge, England, said in an interview at the British Society for Rheumatology annual conference.

“This may allow a reduction in chronic pain by identifying a cohort requiring more intensive intervention with physiotherapy and intervention,” he added. It also may help to reduce the incidence of complex regional pain syndrome (CRPS) after sustaining a fracture.

CPRS is characterized by prolonged, intractable pain that often follows injury to a limb, such as a fracture or another traumatic event. “It’s a nervy type pain, burning, and shooting, and it’s a horrible condition,” Dr. Shenker explained. “If you ask patients to rate the amount of pain they get from their condition, whether it is rheumatoid arthritis, fibromyalgia, or osteoarthritis, this is the condition that commonly comes top.”

With differential diagnoses spanning many rheumatologic and neurologic conditions, it is perhaps no surprise that patients with CRPS often go undiagnosed for many months. In fact, according to CRPS Registry UK findings, it can take up to 6 months after symptoms start before patients are diagnosed with the pain syndrome (Br J Pain. 2015;9[2]:122-8).

While pain symptoms may resolve by themselves in about one-third of patients by 3 months and three-quarters of patients by 12 months, there are a significant number of patients whose symptoms do not resolve, and their window of opportunity for treatment may have closed. Although treatment may be largely reassurance based for many, some patients may benefit from early physical therapy or pain medication.

“Once you have any chronic pain condition for more than 12 months, the chances of it getting better are pretty slim. So we want to identify these people early, but that is not easy,” Dr. Shenker observed.

Since there is currently no diagnostic test, Dr. Shenker and his associates identified four novel clinical signs – abnormal finger perception, hand laterality identification, body scheme report, and astereognosis – from a cohort of patients with CRPS and developed tests for them.

Finger perception was assessed by asking the subjects to place their hands on their laps, close their eyes and say which finger or thumb was being touched within a 20-second time limit. A positive test was a score of 8 or less out of 10.

Hand laterality was tested using a computer program showing the subjects a series of images of left and right hands and asking them to click whether the image was of a person’s right or left hand. A positive test was a score of fewer than 50 out of 56 or if the subject took longer than 3 minutes to complete the exercise.

Astereognosis, the inability to identify an object by the touch of the hands only, was assessed by asking the subjects to close their eyes and present their hand palms upward, then placing three different objects into it and asking them what they were touching. A test was considered positive if only two out of three objects were recognized, or if the subjects took longer than 6 seconds to identify the objects.

Finally, body scheme is about assessing how patients generally sense the parts of their bodies with their eyes closed, or how one side of the body compares in terms of size, weight, and length to the other. For this test, the body is divided into 17 areas, and over the course of 2 minutes, patients are asked to describe, without moving, how their left side compares to their right side. A test is considered positive if patients’ responses differ by more than 10% in two contiguous areas, such as the arm and elbow.

Only finger perception and body scheme were found to have good positive and negative predictive values individually.

The aim of the prospective observational cohort study Dr. Shenkar presented at the meeting on behalf of colleague Dr. Anoop Kuttikat was to look at those signs to see how common those scenarios were and to determine if these could be used as simple bedside tests to identify those likely to develop CRPS.

Dr. Shenkar reported data on 47 patients aged a mean of 53 years who needed a plaster cast for an upper (wrist) or lower (ankle/tibia) limb fracture who were assessed fewer than 2 weeks after their injury and followed up for 6 months. Their medical records were reviewed 3 years later to see whether chronic pain was present.

One patient developed CRPS. This patient had both a positive finger perception and body scheme test at the baseline assessment. Three patients had persistent pain, and two of those had positive finger perception and body scheme tests. The remaining 43 patients did not have persistent pain, and four of these patients had positive finger perception and body scheme tests. This means that 7 out of the 47 patients would be flagged very early on for further assessment and possible treatment, Dr. Shenker observed.

Future plans are to refine a quicker test for body scheme assessment and to perform a larger prospective multicenter study.

Dr. Shenker has received grant or research support from the British Medical Association, the U.K. National Institute for Health Research’s Clinical Research Network, and the Cambridge Arthritis Research Endeavour.

GLASGOW – Two novel clinical signs can be used to determine whether people who have had a fracture are likely to develop complex regional pain syndrome, a condition for which there is currently no specific diagnostic test.

The way in which patients perceived which of their fingers was being touched when their eyes were closed (finger perception) and the position of different parts of their body in relation to one another generally (body scheme) were found to be reliable ways of identifying those who would experience prolonged pain in the future. The positive and negative predictive values of using those tests together were a respective 84.1% and 76.9%.

“Digit misperception and body scheme combined can be useful in predicting chronic pain,” Dr. Nicholas Shenker of Addenbrooke’s Hospital in Cambridge, England, said in an interview at the British Society for Rheumatology annual conference.

“This may allow a reduction in chronic pain by identifying a cohort requiring more intensive intervention with physiotherapy and intervention,” he added. It also may help to reduce the incidence of complex regional pain syndrome (CRPS) after sustaining a fracture.

CPRS is characterized by prolonged, intractable pain that often follows injury to a limb, such as a fracture or another traumatic event. “It’s a nervy type pain, burning, and shooting, and it’s a horrible condition,” Dr. Shenker explained. “If you ask patients to rate the amount of pain they get from their condition, whether it is rheumatoid arthritis, fibromyalgia, or osteoarthritis, this is the condition that commonly comes top.”

With differential diagnoses spanning many rheumatologic and neurologic conditions, it is perhaps no surprise that patients with CRPS often go undiagnosed for many months. In fact, according to CRPS Registry UK findings, it can take up to 6 months after symptoms start before patients are diagnosed with the pain syndrome (Br J Pain. 2015;9[2]:122-8).

While pain symptoms may resolve by themselves in about one-third of patients by 3 months and three-quarters of patients by 12 months, there are a significant number of patients whose symptoms do not resolve, and their window of opportunity for treatment may have closed. Although treatment may be largely reassurance based for many, some patients may benefit from early physical therapy or pain medication.

“Once you have any chronic pain condition for more than 12 months, the chances of it getting better are pretty slim. So we want to identify these people early, but that is not easy,” Dr. Shenker observed.

Since there is currently no diagnostic test, Dr. Shenker and his associates identified four novel clinical signs – abnormal finger perception, hand laterality identification, body scheme report, and astereognosis – from a cohort of patients with CRPS and developed tests for them.

Finger perception was assessed by asking the subjects to place their hands on their laps, close their eyes and say which finger or thumb was being touched within a 20-second time limit. A positive test was a score of 8 or less out of 10.

Hand laterality was tested using a computer program showing the subjects a series of images of left and right hands and asking them to click whether the image was of a person’s right or left hand. A positive test was a score of fewer than 50 out of 56 or if the subject took longer than 3 minutes to complete the exercise.

Astereognosis, the inability to identify an object by the touch of the hands only, was assessed by asking the subjects to close their eyes and present their hand palms upward, then placing three different objects into it and asking them what they were touching. A test was considered positive if only two out of three objects were recognized, or if the subjects took longer than 6 seconds to identify the objects.

Finally, body scheme is about assessing how patients generally sense the parts of their bodies with their eyes closed, or how one side of the body compares in terms of size, weight, and length to the other. For this test, the body is divided into 17 areas, and over the course of 2 minutes, patients are asked to describe, without moving, how their left side compares to their right side. A test is considered positive if patients’ responses differ by more than 10% in two contiguous areas, such as the arm and elbow.

Only finger perception and body scheme were found to have good positive and negative predictive values individually.

The aim of the prospective observational cohort study Dr. Shenkar presented at the meeting on behalf of colleague Dr. Anoop Kuttikat was to look at those signs to see how common those scenarios were and to determine if these could be used as simple bedside tests to identify those likely to develop CRPS.

Dr. Shenkar reported data on 47 patients aged a mean of 53 years who needed a plaster cast for an upper (wrist) or lower (ankle/tibia) limb fracture who were assessed fewer than 2 weeks after their injury and followed up for 6 months. Their medical records were reviewed 3 years later to see whether chronic pain was present.

One patient developed CRPS. This patient had both a positive finger perception and body scheme test at the baseline assessment. Three patients had persistent pain, and two of those had positive finger perception and body scheme tests. The remaining 43 patients did not have persistent pain, and four of these patients had positive finger perception and body scheme tests. This means that 7 out of the 47 patients would be flagged very early on for further assessment and possible treatment, Dr. Shenker observed.

Future plans are to refine a quicker test for body scheme assessment and to perform a larger prospective multicenter study.

Dr. Shenker has received grant or research support from the British Medical Association, the U.K. National Institute for Health Research’s Clinical Research Network, and the Cambridge Arthritis Research Endeavour.

GLASGOW – Two novel clinical signs can be used to determine whether people who have had a fracture are likely to develop complex regional pain syndrome, a condition for which there is currently no specific diagnostic test.

The way in which patients perceived which of their fingers was being touched when their eyes were closed (finger perception) and the position of different parts of their body in relation to one another generally (body scheme) were found to be reliable ways of identifying those who would experience prolonged pain in the future. The positive and negative predictive values of using those tests together were a respective 84.1% and 76.9%.

“Digit misperception and body scheme combined can be useful in predicting chronic pain,” Dr. Nicholas Shenker of Addenbrooke’s Hospital in Cambridge, England, said in an interview at the British Society for Rheumatology annual conference.

“This may allow a reduction in chronic pain by identifying a cohort requiring more intensive intervention with physiotherapy and intervention,” he added. It also may help to reduce the incidence of complex regional pain syndrome (CRPS) after sustaining a fracture.

CPRS is characterized by prolonged, intractable pain that often follows injury to a limb, such as a fracture or another traumatic event. “It’s a nervy type pain, burning, and shooting, and it’s a horrible condition,” Dr. Shenker explained. “If you ask patients to rate the amount of pain they get from their condition, whether it is rheumatoid arthritis, fibromyalgia, or osteoarthritis, this is the condition that commonly comes top.”

With differential diagnoses spanning many rheumatologic and neurologic conditions, it is perhaps no surprise that patients with CRPS often go undiagnosed for many months. In fact, according to CRPS Registry UK findings, it can take up to 6 months after symptoms start before patients are diagnosed with the pain syndrome (Br J Pain. 2015;9[2]:122-8).

While pain symptoms may resolve by themselves in about one-third of patients by 3 months and three-quarters of patients by 12 months, there are a significant number of patients whose symptoms do not resolve, and their window of opportunity for treatment may have closed. Although treatment may be largely reassurance based for many, some patients may benefit from early physical therapy or pain medication.

“Once you have any chronic pain condition for more than 12 months, the chances of it getting better are pretty slim. So we want to identify these people early, but that is not easy,” Dr. Shenker observed.

Since there is currently no diagnostic test, Dr. Shenker and his associates identified four novel clinical signs – abnormal finger perception, hand laterality identification, body scheme report, and astereognosis – from a cohort of patients with CRPS and developed tests for them.

Finger perception was assessed by asking the subjects to place their hands on their laps, close their eyes and say which finger or thumb was being touched within a 20-second time limit. A positive test was a score of 8 or less out of 10.

Hand laterality was tested using a computer program showing the subjects a series of images of left and right hands and asking them to click whether the image was of a person’s right or left hand. A positive test was a score of fewer than 50 out of 56 or if the subject took longer than 3 minutes to complete the exercise.

Astereognosis, the inability to identify an object by the touch of the hands only, was assessed by asking the subjects to close their eyes and present their hand palms upward, then placing three different objects into it and asking them what they were touching. A test was considered positive if only two out of three objects were recognized, or if the subjects took longer than 6 seconds to identify the objects.

Finally, body scheme is about assessing how patients generally sense the parts of their bodies with their eyes closed, or how one side of the body compares in terms of size, weight, and length to the other. For this test, the body is divided into 17 areas, and over the course of 2 minutes, patients are asked to describe, without moving, how their left side compares to their right side. A test is considered positive if patients’ responses differ by more than 10% in two contiguous areas, such as the arm and elbow.

Only finger perception and body scheme were found to have good positive and negative predictive values individually.

The aim of the prospective observational cohort study Dr. Shenkar presented at the meeting on behalf of colleague Dr. Anoop Kuttikat was to look at those signs to see how common those scenarios were and to determine if these could be used as simple bedside tests to identify those likely to develop CRPS.

Dr. Shenkar reported data on 47 patients aged a mean of 53 years who needed a plaster cast for an upper (wrist) or lower (ankle/tibia) limb fracture who were assessed fewer than 2 weeks after their injury and followed up for 6 months. Their medical records were reviewed 3 years later to see whether chronic pain was present.

One patient developed CRPS. This patient had both a positive finger perception and body scheme test at the baseline assessment. Three patients had persistent pain, and two of those had positive finger perception and body scheme tests. The remaining 43 patients did not have persistent pain, and four of these patients had positive finger perception and body scheme tests. This means that 7 out of the 47 patients would be flagged very early on for further assessment and possible treatment, Dr. Shenker observed.

Future plans are to refine a quicker test for body scheme assessment and to perform a larger prospective multicenter study.

Dr. Shenker has received grant or research support from the British Medical Association, the U.K. National Institute for Health Research’s Clinical Research Network, and the Cambridge Arthritis Research Endeavour.

GLASGOW – Two novel clinical signs can be used to determine whether people who have had a fracture are likely to develop complex regional pain syndrome, a condition for which there is currently no specific diagnostic test.

The way in which patients perceived which of their fingers was being touched when their eyes were closed (finger perception) and the position of different parts of their body in relation to one another generally (body scheme) were found to be reliable ways of identifying those who would experience prolonged pain in the future. The positive and negative predictive values of using those tests together were a respective 84.1% and 76.9%.

“Digit misperception and body scheme combined can be useful in predicting chronic pain,” Dr. Nicholas Shenker of Addenbrooke’s Hospital in Cambridge, England, said in an interview at the British Society for Rheumatology annual conference.

“This may allow a reduction in chronic pain by identifying a cohort requiring more intensive intervention with physiotherapy and intervention,” he added. It also may help to reduce the incidence of complex regional pain syndrome (CRPS) after sustaining a fracture.

CPRS is characterized by prolonged, intractable pain that often follows injury to a limb, such as a fracture or another traumatic event. “It’s a nervy type pain, burning, and shooting, and it’s a horrible condition,” Dr. Shenker explained. “If you ask patients to rate the amount of pain they get from their condition, whether it is rheumatoid arthritis, fibromyalgia, or osteoarthritis, this is the condition that commonly comes top.”

With differential diagnoses spanning many rheumatologic and neurologic conditions, it is perhaps no surprise that patients with CRPS often go undiagnosed for many months. In fact, according to CRPS Registry UK findings, it can take up to 6 months after symptoms start before patients are diagnosed with the pain syndrome (Br J Pain. 2015;9[2]:122-8).

While pain symptoms may resolve by themselves in about one-third of patients by 3 months and three-quarters of patients by 12 months, there are a significant number of patients whose symptoms do not resolve, and their window of opportunity for treatment may have closed. Although treatment may be largely reassurance based for many, some patients may benefit from early physical therapy or pain medication.

“Once you have any chronic pain condition for more than 12 months, the chances of it getting better are pretty slim. So we want to identify these people early, but that is not easy,” Dr. Shenker observed.

Since there is currently no diagnostic test, Dr. Shenker and his associates identified four novel clinical signs – abnormal finger perception, hand laterality identification, body scheme report, and astereognosis – from a cohort of patients with CRPS and developed tests for them.

Finger perception was assessed by asking the subjects to place their hands on their laps, close their eyes and say which finger or thumb was being touched within a 20-second time limit. A positive test was a score of 8 or less out of 10.

Hand laterality was tested using a computer program showing the subjects a series of images of left and right hands and asking them to click whether the image was of a person’s right or left hand. A positive test was a score of fewer than 50 out of 56 or if the subject took longer than 3 minutes to complete the exercise.

Astereognosis, the inability to identify an object by the touch of the hands only, was assessed by asking the subjects to close their eyes and present their hand palms upward, then placing three different objects into it and asking them what they were touching. A test was considered positive if only two out of three objects were recognized, or if the subjects took longer than 6 seconds to identify the objects.

Finally, body scheme is about assessing how patients generally sense the parts of their bodies with their eyes closed, or how one side of the body compares in terms of size, weight, and length to the other. For this test, the body is divided into 17 areas, and over the course of 2 minutes, patients are asked to describe, without moving, how their left side compares to their right side. A test is considered positive if patients’ responses differ by more than 10% in two contiguous areas, such as the arm and elbow.

Only finger perception and body scheme were found to have good positive and negative predictive values individually.

The aim of the prospective observational cohort study Dr. Shenkar presented at the meeting on behalf of colleague Dr. Anoop Kuttikat was to look at those signs to see how common those scenarios were and to determine if these could be used as simple bedside tests to identify those likely to develop CRPS.

Dr. Shenkar reported data on 47 patients aged a mean of 53 years who needed a plaster cast for an upper (wrist) or lower (ankle/tibia) limb fracture who were assessed fewer than 2 weeks after their injury and followed up for 6 months. Their medical records were reviewed 3 years later to see whether chronic pain was present.

One patient developed CRPS. This patient had both a positive finger perception and body scheme test at the baseline assessment. Three patients had persistent pain, and two of those had positive finger perception and body scheme tests. The remaining 43 patients did not have persistent pain, and four of these patients had positive finger perception and body scheme tests. This means that 7 out of the 47 patients would be flagged very early on for further assessment and possible treatment, Dr. Shenker observed.

Future plans are to refine a quicker test for body scheme assessment and to perform a larger prospective multicenter study.

Dr. Shenker has received grant or research support from the British Medical Association, the U.K. National Institute for Health Research’s Clinical Research Network, and the Cambridge Arthritis Research Endeavour.

GLASGOW – Advising patients with rheumatoid arthritis who are being treated with methotrexate to moderate their alcohol intake remains sound advice, the results of a large clinical database study showed.

Increasing alcohol intake was found to be associated with an increased risk for developing abnormal results on serum liver function tests (LFTs). However, the clinical importance of this was thought to be small if the number of alcoholic units per week remained below 14 – which is general advice for men and women in the United Kingdom.

“We advise our patients to restrict their alcohol consumption, because we know that alcohol is hepatotoxic …, methotrexate is hepatotoxic, and there is a presumed interaction there,” the presenting study author, Dr. Jenny H. Humphreys, said in an interview at the British Society for Rheumatology annual conference. “But actually, the data to support that advice [are] fairly limited and may not reflect our current patient population,” added Dr. Humphreys of the Arthritis Research U.K. Centre for Epidemiology at the University of Manchester (England).

In a poster presentation, Dr. Humphreys aimed to quantify the association between alcohol intake and serum alanine or aspartate aminotransferase (ALT/AST) levels using routinely collected clinical data from the Clinical Practice Research Datalink (CPRD). Data on more than 8,000 patients starting methotrexate (MTX) for treating rheumatoid arthritis (RA) between 1987 and 2011 were obtained and analyzed.

Patients were included in the analysis if they had information on their alcohol consumption recorded and if serum LFTs had been assessed routinely by their primary care physician at least six times per year. They were then grouped based on their weekly reported alcohol consumption from none (0 units) to excessive (more than 28 units). In the United Kingdom, a unit of alcohol is defined as 10 mL (8 g) of pure alcohol, and the typical alcoholic beverage may contain 1-3 units of alcohol. The mean age of participants in the study was 58 years, and 71% were female.

When 38,000 person-years of follow-up were evaluated, 241 abnormal LFT events, defined as ALT/AST levels more than three times the upper limit of normal, were identified.

Crude incidence rates of abnormal LFTs per 1,000 person-years were 5.58 in nondrinkers, 5.57 in those who drank 1-7 units of alcohol per week, 5.99 in those who drank 8-14 units, 7.58 in those who drank 15-21 units, 8.61 in those who drank 22-28 units, and 9.05 in those who drank more than 28 units. Although the hazard ratios adjusted for age and sex also increased with increasing alcohol intake, from 1.02 in the lightest drinkers to 1.92 in the heaviest drinkers, no statistical significance was found overall between the drinkers and nondrinkers.

“When treated as a continuous variable, there was a statistically significant increase of 1% abnormal LFTs for every unit of alcohol consumed, but you wonder how clinically relevant is a 1% increase,” Dr. Humphreys said.

To look at the data another way, a clinically relevant increase was set for abnormal LFTs; then the data for increasing alcohol consumption were used to see how many patients had crossed that boundary. The investigators found an increase with higher alcohol consumption levels, but that power was limited to patients who drank 14 units a week or fewer. “So essentially, increasing alcohol consumption does increase your risk of abnormal LFTs. But when you are drinking less than about 14 units a week, there is little clinical significance of that, “ Dr. Humphreys said. So for patients who do want to continue drinking while on MTX, it should be reasonably safe to advise them that they can do so as long as they moderate their intake.

Separate research presented in a poster by Dr. Ravi Narang of Frimley Health NHS Foundation Trust in Surrey, England, and associates looked at the use of hepatic elastography (FibroScan) in MTX-treated patients and found 91% of 44 patients had normal ALT levels before their liver was scanned. Of 23 patients who were scanned, 11 (48%) had abnormal findings, and 9 (39%) showed signs of fatty liver. Seven (16%) patients underwent a liver biopsy based on the liver scan findings, and five stopped treatment with MTX based on the findings. Methotrexate also was stopped in nine other patients who did not undergo biopsy but had raised liver stiffness, which is a sign of fibrosis. Meanwhile, three patients continued at a reduced dose.

The patients in their retrospective case note study included those who had undergone FibroScan between 2011 and 2015 while on MTX. Most (56%) patients were taking MTX for RA; 27%, for psoriatic arthritis; 9%, for psoriasis; and the remainder, for other rheumatologic or dermatologic conditions. The median age at the time of the scan was 64 years. Eight patients had comorbid diabetes mellitus, and 11% consumed more than 14 units of alcohol per week.

“FibroScan led to a change in management in many of our patients confirming its value as a noninvasive adjunct for assessing hepatic fibrosis,” said Dr. Narang. He and his associates noted that the imaging technique was “guiding practice” and confirmed the “relative insensitivity of current methotrexate liver monitoring.”

Dr. Humphreys, Dr. Narang, and their associates had no relevant financial disclosures.

GLASGOW – Advising patients with rheumatoid arthritis who are being treated with methotrexate to moderate their alcohol intake remains sound advice, the results of a large clinical database study showed.

Increasing alcohol intake was found to be associated with an increased risk for developing abnormal results on serum liver function tests (LFTs). However, the clinical importance of this was thought to be small if the number of alcoholic units per week remained below 14 – which is general advice for men and women in the United Kingdom.

“We advise our patients to restrict their alcohol consumption, because we know that alcohol is hepatotoxic …, methotrexate is hepatotoxic, and there is a presumed interaction there,” the presenting study author, Dr. Jenny H. Humphreys, said in an interview at the British Society for Rheumatology annual conference. “But actually, the data to support that advice [are] fairly limited and may not reflect our current patient population,” added Dr. Humphreys of the Arthritis Research U.K. Centre for Epidemiology at the University of Manchester (England).

In a poster presentation, Dr. Humphreys aimed to quantify the association between alcohol intake and serum alanine or aspartate aminotransferase (ALT/AST) levels using routinely collected clinical data from the Clinical Practice Research Datalink (CPRD). Data on more than 8,000 patients starting methotrexate (MTX) for treating rheumatoid arthritis (RA) between 1987 and 2011 were obtained and analyzed.

Patients were included in the analysis if they had information on their alcohol consumption recorded and if serum LFTs had been assessed routinely by their primary care physician at least six times per year. They were then grouped based on their weekly reported alcohol consumption from none (0 units) to excessive (more than 28 units). In the United Kingdom, a unit of alcohol is defined as 10 mL (8 g) of pure alcohol, and the typical alcoholic beverage may contain 1-3 units of alcohol. The mean age of participants in the study was 58 years, and 71% were female.

When 38,000 person-years of follow-up were evaluated, 241 abnormal LFT events, defined as ALT/AST levels more than three times the upper limit of normal, were identified.

Crude incidence rates of abnormal LFTs per 1,000 person-years were 5.58 in nondrinkers, 5.57 in those who drank 1-7 units of alcohol per week, 5.99 in those who drank 8-14 units, 7.58 in those who drank 15-21 units, 8.61 in those who drank 22-28 units, and 9.05 in those who drank more than 28 units. Although the hazard ratios adjusted for age and sex also increased with increasing alcohol intake, from 1.02 in the lightest drinkers to 1.92 in the heaviest drinkers, no statistical significance was found overall between the drinkers and nondrinkers.

“When treated as a continuous variable, there was a statistically significant increase of 1% abnormal LFTs for every unit of alcohol consumed, but you wonder how clinically relevant is a 1% increase,” Dr. Humphreys said.

To look at the data another way, a clinically relevant increase was set for abnormal LFTs; then the data for increasing alcohol consumption were used to see how many patients had crossed that boundary. The investigators found an increase with higher alcohol consumption levels, but that power was limited to patients who drank 14 units a week or fewer. “So essentially, increasing alcohol consumption does increase your risk of abnormal LFTs. But when you are drinking less than about 14 units a week, there is little clinical significance of that, “ Dr. Humphreys said. So for patients who do want to continue drinking while on MTX, it should be reasonably safe to advise them that they can do so as long as they moderate their intake.

Separate research presented in a poster by Dr. Ravi Narang of Frimley Health NHS Foundation Trust in Surrey, England, and associates looked at the use of hepatic elastography (FibroScan) in MTX-treated patients and found 91% of 44 patients had normal ALT levels before their liver was scanned. Of 23 patients who were scanned, 11 (48%) had abnormal findings, and 9 (39%) showed signs of fatty liver. Seven (16%) patients underwent a liver biopsy based on the liver scan findings, and five stopped treatment with MTX based on the findings. Methotrexate also was stopped in nine other patients who did not undergo biopsy but had raised liver stiffness, which is a sign of fibrosis. Meanwhile, three patients continued at a reduced dose.

The patients in their retrospective case note study included those who had undergone FibroScan between 2011 and 2015 while on MTX. Most (56%) patients were taking MTX for RA; 27%, for psoriatic arthritis; 9%, for psoriasis; and the remainder, for other rheumatologic or dermatologic conditions. The median age at the time of the scan was 64 years. Eight patients had comorbid diabetes mellitus, and 11% consumed more than 14 units of alcohol per week.

“FibroScan led to a change in management in many of our patients confirming its value as a noninvasive adjunct for assessing hepatic fibrosis,” said Dr. Narang. He and his associates noted that the imaging technique was “guiding practice” and confirmed the “relative insensitivity of current methotrexate liver monitoring.”

Dr. Humphreys, Dr. Narang, and their associates had no relevant financial disclosures.

GLASGOW – Advising patients with rheumatoid arthritis who are being treated with methotrexate to moderate their alcohol intake remains sound advice, the results of a large clinical database study showed.

Increasing alcohol intake was found to be associated with an increased risk for developing abnormal results on serum liver function tests (LFTs). However, the clinical importance of this was thought to be small if the number of alcoholic units per week remained below 14 – which is general advice for men and women in the United Kingdom.

“We advise our patients to restrict their alcohol consumption, because we know that alcohol is hepatotoxic …, methotrexate is hepatotoxic, and there is a presumed interaction there,” the presenting study author, Dr. Jenny H. Humphreys, said in an interview at the British Society for Rheumatology annual conference. “But actually, the data to support that advice [are] fairly limited and may not reflect our current patient population,” added Dr. Humphreys of the Arthritis Research U.K. Centre for Epidemiology at the University of Manchester (England).

In a poster presentation, Dr. Humphreys aimed to quantify the association between alcohol intake and serum alanine or aspartate aminotransferase (ALT/AST) levels using routinely collected clinical data from the Clinical Practice Research Datalink (CPRD). Data on more than 8,000 patients starting methotrexate (MTX) for treating rheumatoid arthritis (RA) between 1987 and 2011 were obtained and analyzed.

Patients were included in the analysis if they had information on their alcohol consumption recorded and if serum LFTs had been assessed routinely by their primary care physician at least six times per year. They were then grouped based on their weekly reported alcohol consumption from none (0 units) to excessive (more than 28 units). In the United Kingdom, a unit of alcohol is defined as 10 mL (8 g) of pure alcohol, and the typical alcoholic beverage may contain 1-3 units of alcohol. The mean age of participants in the study was 58 years, and 71% were female.

When 38,000 person-years of follow-up were evaluated, 241 abnormal LFT events, defined as ALT/AST levels more than three times the upper limit of normal, were identified.

Crude incidence rates of abnormal LFTs per 1,000 person-years were 5.58 in nondrinkers, 5.57 in those who drank 1-7 units of alcohol per week, 5.99 in those who drank 8-14 units, 7.58 in those who drank 15-21 units, 8.61 in those who drank 22-28 units, and 9.05 in those who drank more than 28 units. Although the hazard ratios adjusted for age and sex also increased with increasing alcohol intake, from 1.02 in the lightest drinkers to 1.92 in the heaviest drinkers, no statistical significance was found overall between the drinkers and nondrinkers.

“When treated as a continuous variable, there was a statistically significant increase of 1% abnormal LFTs for every unit of alcohol consumed, but you wonder how clinically relevant is a 1% increase,” Dr. Humphreys said.

To look at the data another way, a clinically relevant increase was set for abnormal LFTs; then the data for increasing alcohol consumption were used to see how many patients had crossed that boundary. The investigators found an increase with higher alcohol consumption levels, but that power was limited to patients who drank 14 units a week or fewer. “So essentially, increasing alcohol consumption does increase your risk of abnormal LFTs. But when you are drinking less than about 14 units a week, there is little clinical significance of that, “ Dr. Humphreys said. So for patients who do want to continue drinking while on MTX, it should be reasonably safe to advise them that they can do so as long as they moderate their intake.

Separate research presented in a poster by Dr. Ravi Narang of Frimley Health NHS Foundation Trust in Surrey, England, and associates looked at the use of hepatic elastography (FibroScan) in MTX-treated patients and found 91% of 44 patients had normal ALT levels before their liver was scanned. Of 23 patients who were scanned, 11 (48%) had abnormal findings, and 9 (39%) showed signs of fatty liver. Seven (16%) patients underwent a liver biopsy based on the liver scan findings, and five stopped treatment with MTX based on the findings. Methotrexate also was stopped in nine other patients who did not undergo biopsy but had raised liver stiffness, which is a sign of fibrosis. Meanwhile, three patients continued at a reduced dose.

The patients in their retrospective case note study included those who had undergone FibroScan between 2011 and 2015 while on MTX. Most (56%) patients were taking MTX for RA; 27%, for psoriatic arthritis; 9%, for psoriasis; and the remainder, for other rheumatologic or dermatologic conditions. The median age at the time of the scan was 64 years. Eight patients had comorbid diabetes mellitus, and 11% consumed more than 14 units of alcohol per week.

“FibroScan led to a change in management in many of our patients confirming its value as a noninvasive adjunct for assessing hepatic fibrosis,” said Dr. Narang. He and his associates noted that the imaging technique was “guiding practice” and confirmed the “relative insensitivity of current methotrexate liver monitoring.”

Dr. Humphreys, Dr. Narang, and their associates had no relevant financial disclosures.

GLASGOW, SCOTLAND – Adverse events ranging from major trauma to osteoporosis to death from any cause occurred at significantly higher rates among people who were prescribed opioids long term for musculoskeletal pain in comparison to those who used a single prescription, in a large retrospective matched cohort study.

The analysis of almost 200,000 patient records from 190 primary care practices held within the U.K. Clinical Practice Research Datalink found that use of opioids to control pain for more than 3 months was associated with an increased risk for major trauma and almost doubled the risk of overdose of nonopioid drugs, compared with short-term use.

©Thomas Northcut/ Thinkstockphotos.com

The absolute risk for major trauma, which included bone fracture, joint dislocation, ligament or tendon rupture, or head trauma, was 387.4 per 10,000 person-years with long-term opioid use and 269.7 per 10,000 person-years for short-term opioid use, with a hazard ratio (HR) of 1.26 and a 95% confident interval (CI) of 1.20 to 1.33. The absolute risk for overdose with drugs other than opioids was 37.7 and 12.9 per 10,000 person-years, respectively (HR 2.03; 95% CI 1.63-2.53).

Long-term use of opioids led to a significant increase in the risk of accidental poisoning (HR 4.12; 95% CI 1.66-10.19) and becoming newly addicted (HR 2.76; 95% CI 1.76-4.35) in comparison with short-term opioid use. The risk of addiction significantly rose with long-term users of nonopioid drugs (HR 2.16; 95% CI 1.78-2.62), compared with short-term users.

Other risks included an increase in falls (HR 1.20; 95% CI 1.14-1.25) and new cases of osteoporosis (HR 1.65; 95% CI 1.52-1.79), incident depression (HR 1.45; 95% CI 1.37-1.53), new gastric (HR 1.38; 95% CI 1.20-1.60) and nongastric (1.33; 95% CI 1.21-1.45) gastrointestinal bleeding, incident iron deficiency anemia (HR 1.22; 95% CI 1.12-1.33), and death from any cause (HR 1.20; 95% CI 1.12-1.29).

There was no increase in the risk for attempted suicide or self-harm, however, nor in a couple of control outcomes (new cases of eczema or psoriasis) that were tested.

“Long-term users [of opioids] appear to be a very vulnerable group at high risk of experiencing quite a lot of adverse events,” said Dr. John Bedson of Keele (England) University who presented the findings at the British Society for Rheumatology annual conference. “So GPs [general practitioners], naturally, need to be actively managing these patients and ... as this is in the very early stages of prescribing, they need to be assessing the benefit and whether there is a need to carry on taking these medications and stop them if appropriate.”

The use of opioids in patients with musculoskeletal conditions has been increasing in the past 10 years, particularly the use of more potent and long-acting opioids, Dr. Bedson observed. He noted that of all the adults who newly present with musculoskeletal conditions in the United Kingdom – estimated to be 20% of all primary care consulters annually – one in seven will be prescribed an opioid analgesic. In fact, as it was noted during the discussion, U.K. clinicians are now often opting to use opioids over nonsteroidal anti-inflammatory drugs (NSAIDs) to avoid gastrointestinal bleeding.

While there has been some evidence obtained on the risks associated with long-term opioid use in the United States, there has not been data on the risks in a U.K. population. With differing health systems, guidelines, and practices between the two countries, the aim of the retrospective matched cohort study was to compare the adverse event profiles of long- and short-term opioids users over a period of 12 months in a U.K. primary care practice population.

Between 2002 and 2013 there were 98,140 patients with musculoskeletal conditions who had been prescribed opioids and had received two or more further opioid prescriptions within a 90-day period. These were the long-term opioid users; they were matched according to age, gender, and practice to 98,140 short-term opioid users who were patients with musculoskeletal conditions who did not fulfill the criteria for the long-term definition. The median age of patients was 61 years and 41% were male.

Numerous covariates were taken into account, including previous adverse events in the 15 months prior to the start of follow-up, smoking status, alcohol consumption, body mass index, where patients lived and their socioeconomic status, the presence of any comorbidities, and the coprescription of NSAIDs.

Further research into how and why patients on long-term opioids experience more adverse effects needs to be conducted, Dr. Bedson noted, adding that causality had not been found in this study. The next step would be to look at the morphine equivalent doses of the opioids used to see if that had an effect.

But how does the risk compare to long-term use of NSAIDs? Has the preference for opioids been mistaken as being safer?

“The problem is that we have started using these drugs and we don’t know if they work,” Dr. Bedson said. “So we are now at the point of identifying more and more risks, but do they do any good? So I think the jury is still out, and I think GPs have very little else to use at the moment because of the worries over anti-inflammatories, but from an anecdotal point of view I think people are beginning to swing back to using them again.”

Dr. Bedson had no conflicts of interest to disclose.

GLASGOW, SCOTLAND – Adverse events ranging from major trauma to osteoporosis to death from any cause occurred at significantly higher rates among people who were prescribed opioids long term for musculoskeletal pain in comparison to those who used a single prescription, in a large retrospective matched cohort study.

The analysis of almost 200,000 patient records from 190 primary care practices held within the U.K. Clinical Practice Research Datalink found that use of opioids to control pain for more than 3 months was associated with an increased risk for major trauma and almost doubled the risk of overdose of nonopioid drugs, compared with short-term use.

©Thomas Northcut/ Thinkstockphotos.com

The absolute risk for major trauma, which included bone fracture, joint dislocation, ligament or tendon rupture, or head trauma, was 387.4 per 10,000 person-years with long-term opioid use and 269.7 per 10,000 person-years for short-term opioid use, with a hazard ratio (HR) of 1.26 and a 95% confident interval (CI) of 1.20 to 1.33. The absolute risk for overdose with drugs other than opioids was 37.7 and 12.9 per 10,000 person-years, respectively (HR 2.03; 95% CI 1.63-2.53).

Long-term use of opioids led to a significant increase in the risk of accidental poisoning (HR 4.12; 95% CI 1.66-10.19) and becoming newly addicted (HR 2.76; 95% CI 1.76-4.35) in comparison with short-term opioid use. The risk of addiction significantly rose with long-term users of nonopioid drugs (HR 2.16; 95% CI 1.78-2.62), compared with short-term users.

Other risks included an increase in falls (HR 1.20; 95% CI 1.14-1.25) and new cases of osteoporosis (HR 1.65; 95% CI 1.52-1.79), incident depression (HR 1.45; 95% CI 1.37-1.53), new gastric (HR 1.38; 95% CI 1.20-1.60) and nongastric (1.33; 95% CI 1.21-1.45) gastrointestinal bleeding, incident iron deficiency anemia (HR 1.22; 95% CI 1.12-1.33), and death from any cause (HR 1.20; 95% CI 1.12-1.29).

There was no increase in the risk for attempted suicide or self-harm, however, nor in a couple of control outcomes (new cases of eczema or psoriasis) that were tested.

“Long-term users [of opioids] appear to be a very vulnerable group at high risk of experiencing quite a lot of adverse events,” said Dr. John Bedson of Keele (England) University who presented the findings at the British Society for Rheumatology annual conference. “So GPs [general practitioners], naturally, need to be actively managing these patients and ... as this is in the very early stages of prescribing, they need to be assessing the benefit and whether there is a need to carry on taking these medications and stop them if appropriate.”

The use of opioids in patients with musculoskeletal conditions has been increasing in the past 10 years, particularly the use of more potent and long-acting opioids, Dr. Bedson observed. He noted that of all the adults who newly present with musculoskeletal conditions in the United Kingdom – estimated to be 20% of all primary care consulters annually – one in seven will be prescribed an opioid analgesic. In fact, as it was noted during the discussion, U.K. clinicians are now often opting to use opioids over nonsteroidal anti-inflammatory drugs (NSAIDs) to avoid gastrointestinal bleeding.

While there has been some evidence obtained on the risks associated with long-term opioid use in the United States, there has not been data on the risks in a U.K. population. With differing health systems, guidelines, and practices between the two countries, the aim of the retrospective matched cohort study was to compare the adverse event profiles of long- and short-term opioids users over a period of 12 months in a U.K. primary care practice population.

Between 2002 and 2013 there were 98,140 patients with musculoskeletal conditions who had been prescribed opioids and had received two or more further opioid prescriptions within a 90-day period. These were the long-term opioid users; they were matched according to age, gender, and practice to 98,140 short-term opioid users who were patients with musculoskeletal conditions who did not fulfill the criteria for the long-term definition. The median age of patients was 61 years and 41% were male.

Numerous covariates were taken into account, including previous adverse events in the 15 months prior to the start of follow-up, smoking status, alcohol consumption, body mass index, where patients lived and their socioeconomic status, the presence of any comorbidities, and the coprescription of NSAIDs.

Further research into how and why patients on long-term opioids experience more adverse effects needs to be conducted, Dr. Bedson noted, adding that causality had not been found in this study. The next step would be to look at the morphine equivalent doses of the opioids used to see if that had an effect.

But how does the risk compare to long-term use of NSAIDs? Has the preference for opioids been mistaken as being safer?

“The problem is that we have started using these drugs and we don’t know if they work,” Dr. Bedson said. “So we are now at the point of identifying more and more risks, but do they do any good? So I think the jury is still out, and I think GPs have very little else to use at the moment because of the worries over anti-inflammatories, but from an anecdotal point of view I think people are beginning to swing back to using them again.”

Dr. Bedson had no conflicts of interest to disclose.

GLASGOW, SCOTLAND – Adverse events ranging from major trauma to osteoporosis to death from any cause occurred at significantly higher rates among people who were prescribed opioids long term for musculoskeletal pain in comparison to those who used a single prescription, in a large retrospective matched cohort study.

The analysis of almost 200,000 patient records from 190 primary care practices held within the U.K. Clinical Practice Research Datalink found that use of opioids to control pain for more than 3 months was associated with an increased risk for major trauma and almost doubled the risk of overdose of nonopioid drugs, compared with short-term use.

©Thomas Northcut/ Thinkstockphotos.com

The absolute risk for major trauma, which included bone fracture, joint dislocation, ligament or tendon rupture, or head trauma, was 387.4 per 10,000 person-years with long-term opioid use and 269.7 per 10,000 person-years for short-term opioid use, with a hazard ratio (HR) of 1.26 and a 95% confident interval (CI) of 1.20 to 1.33. The absolute risk for overdose with drugs other than opioids was 37.7 and 12.9 per 10,000 person-years, respectively (HR 2.03; 95% CI 1.63-2.53).

Long-term use of opioids led to a significant increase in the risk of accidental poisoning (HR 4.12; 95% CI 1.66-10.19) and becoming newly addicted (HR 2.76; 95% CI 1.76-4.35) in comparison with short-term opioid use. The risk of addiction significantly rose with long-term users of nonopioid drugs (HR 2.16; 95% CI 1.78-2.62), compared with short-term users.

Other risks included an increase in falls (HR 1.20; 95% CI 1.14-1.25) and new cases of osteoporosis (HR 1.65; 95% CI 1.52-1.79), incident depression (HR 1.45; 95% CI 1.37-1.53), new gastric (HR 1.38; 95% CI 1.20-1.60) and nongastric (1.33; 95% CI 1.21-1.45) gastrointestinal bleeding, incident iron deficiency anemia (HR 1.22; 95% CI 1.12-1.33), and death from any cause (HR 1.20; 95% CI 1.12-1.29).

There was no increase in the risk for attempted suicide or self-harm, however, nor in a couple of control outcomes (new cases of eczema or psoriasis) that were tested.

“Long-term users [of opioids] appear to be a very vulnerable group at high risk of experiencing quite a lot of adverse events,” said Dr. John Bedson of Keele (England) University who presented the findings at the British Society for Rheumatology annual conference. “So GPs [general practitioners], naturally, need to be actively managing these patients and ... as this is in the very early stages of prescribing, they need to be assessing the benefit and whether there is a need to carry on taking these medications and stop them if appropriate.”

The use of opioids in patients with musculoskeletal conditions has been increasing in the past 10 years, particularly the use of more potent and long-acting opioids, Dr. Bedson observed. He noted that of all the adults who newly present with musculoskeletal conditions in the United Kingdom – estimated to be 20% of all primary care consulters annually – one in seven will be prescribed an opioid analgesic. In fact, as it was noted during the discussion, U.K. clinicians are now often opting to use opioids over nonsteroidal anti-inflammatory drugs (NSAIDs) to avoid gastrointestinal bleeding.

While there has been some evidence obtained on the risks associated with long-term opioid use in the United States, there has not been data on the risks in a U.K. population. With differing health systems, guidelines, and practices between the two countries, the aim of the retrospective matched cohort study was to compare the adverse event profiles of long- and short-term opioids users over a period of 12 months in a U.K. primary care practice population.

Between 2002 and 2013 there were 98,140 patients with musculoskeletal conditions who had been prescribed opioids and had received two or more further opioid prescriptions within a 90-day period. These were the long-term opioid users; they were matched according to age, gender, and practice to 98,140 short-term opioid users who were patients with musculoskeletal conditions who did not fulfill the criteria for the long-term definition. The median age of patients was 61 years and 41% were male.

Numerous covariates were taken into account, including previous adverse events in the 15 months prior to the start of follow-up, smoking status, alcohol consumption, body mass index, where patients lived and their socioeconomic status, the presence of any comorbidities, and the coprescription of NSAIDs.

Further research into how and why patients on long-term opioids experience more adverse effects needs to be conducted, Dr. Bedson noted, adding that causality had not been found in this study. The next step would be to look at the morphine equivalent doses of the opioids used to see if that had an effect.

But how does the risk compare to long-term use of NSAIDs? Has the preference for opioids been mistaken as being safer?

“The problem is that we have started using these drugs and we don’t know if they work,” Dr. Bedson said. “So we are now at the point of identifying more and more risks, but do they do any good? So I think the jury is still out, and I think GPs have very little else to use at the moment because of the worries over anti-inflammatories, but from an anecdotal point of view I think people are beginning to swing back to using them again.”

Dr. Bedson had no conflicts of interest to disclose.