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Long-term TNFi tapering possible for some with ankylosing spondylitis
BIRMINGHAM, ENGLAND – A proportion of patients with ankylosing spondylitis (AS) were able to remain on a reduced-dose regimen of a tumor necrosis factor inhibitor (TNFi) for almost 4 years, according to data from a small study presented at the British Society for Rheumatology annual conference.
In an extension of the ANSWERS (Ankylosing Spondylitis with Etanercept Regimens) trial, 4 of 12 patients receiving a once-weekly 25-mg dose of etanercept (Enbrel) had a sustained response as did 14 of 21 patients who remained on the usual once-weekly dose of 50 mg.
“Although a minority of patients maintained response to the lower dose of etanercept over the longer term, the costs savings are substantial,” said Lauren Steel and coauthors from the Norfolk and Norwich Hospitals NHS Foundation Trust in a poster presentation. Almost 18,000 pounds sterling ($23,000) could be saved per each patient who is able to stay on the lower dose for 50 months.
Further, patients who did not maintain a response on the lower dose were usually able to regain their responses when the higher dose therapy was reinstituted. On average, disease control was reestablished in three out of four patients within 14 months of reverting to standard therapy.
ANSWERS was an open-label, multicenter, randomized, pilot study that sought to determine if tapering the dose of etanercept from the recommended 50 mg to 25 mg was feasible in 47 patients with AS (J Rheumatol. 2015;42:1177–85). The premise was that dose tapering in patients who achieved a response would perhaps reduce the risk for side effects in the long term, as well as provide considerable cost savings.
About half of the patients studied achieved a response to full-dose etanercept and were able to reduce their dose. At 6 months, a clinical response was maintained by 52% of the patients taking 25 mg and 92% of the patients taking 50 mg (P = .003).
The current prospective extension of the study looked at the longer-term outcomes of the patients who successfully maintained a response to the lower dose of etanercept.
Maintenance of response was defined as no change in the primary outcome of a reduction of 50% or more or a fall of at least 2 units in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and at least a 2-unit reduction in spinal pain measured using a 10-point scale.
In all, 12 patients, 9 of them male, with a mean age of 52 years entered the extension study. The comparator group consisted of 21 patients who had continued taking the 50-mg dose, 20 of them male, with a mean age of 60 years.
Of the 12 patients in the 25-mg group, 1 discontinued treatment because of side effects and did not restart any further biologic treatment; 7 patients experienced a disease flare after a median of 16 months and were retreated with the 50-mg dose. Five of the seven patients who reverted to the higher dose of etanercept regained a good response; the other two patients were switched to adalimumab (Humira) because of a loss of efficacy.
Pfizer funded the original study. One author disclosed he had received research funding and acted as an adviser to Pfizer and other pharmaceutical companies.
BIRMINGHAM, ENGLAND – A proportion of patients with ankylosing spondylitis (AS) were able to remain on a reduced-dose regimen of a tumor necrosis factor inhibitor (TNFi) for almost 4 years, according to data from a small study presented at the British Society for Rheumatology annual conference.
In an extension of the ANSWERS (Ankylosing Spondylitis with Etanercept Regimens) trial, 4 of 12 patients receiving a once-weekly 25-mg dose of etanercept (Enbrel) had a sustained response as did 14 of 21 patients who remained on the usual once-weekly dose of 50 mg.
“Although a minority of patients maintained response to the lower dose of etanercept over the longer term, the costs savings are substantial,” said Lauren Steel and coauthors from the Norfolk and Norwich Hospitals NHS Foundation Trust in a poster presentation. Almost 18,000 pounds sterling ($23,000) could be saved per each patient who is able to stay on the lower dose for 50 months.
Further, patients who did not maintain a response on the lower dose were usually able to regain their responses when the higher dose therapy was reinstituted. On average, disease control was reestablished in three out of four patients within 14 months of reverting to standard therapy.
ANSWERS was an open-label, multicenter, randomized, pilot study that sought to determine if tapering the dose of etanercept from the recommended 50 mg to 25 mg was feasible in 47 patients with AS (J Rheumatol. 2015;42:1177–85). The premise was that dose tapering in patients who achieved a response would perhaps reduce the risk for side effects in the long term, as well as provide considerable cost savings.
About half of the patients studied achieved a response to full-dose etanercept and were able to reduce their dose. At 6 months, a clinical response was maintained by 52% of the patients taking 25 mg and 92% of the patients taking 50 mg (P = .003).
The current prospective extension of the study looked at the longer-term outcomes of the patients who successfully maintained a response to the lower dose of etanercept.
Maintenance of response was defined as no change in the primary outcome of a reduction of 50% or more or a fall of at least 2 units in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and at least a 2-unit reduction in spinal pain measured using a 10-point scale.
In all, 12 patients, 9 of them male, with a mean age of 52 years entered the extension study. The comparator group consisted of 21 patients who had continued taking the 50-mg dose, 20 of them male, with a mean age of 60 years.
Of the 12 patients in the 25-mg group, 1 discontinued treatment because of side effects and did not restart any further biologic treatment; 7 patients experienced a disease flare after a median of 16 months and were retreated with the 50-mg dose. Five of the seven patients who reverted to the higher dose of etanercept regained a good response; the other two patients were switched to adalimumab (Humira) because of a loss of efficacy.
Pfizer funded the original study. One author disclosed he had received research funding and acted as an adviser to Pfizer and other pharmaceutical companies.
BIRMINGHAM, ENGLAND – A proportion of patients with ankylosing spondylitis (AS) were able to remain on a reduced-dose regimen of a tumor necrosis factor inhibitor (TNFi) for almost 4 years, according to data from a small study presented at the British Society for Rheumatology annual conference.
In an extension of the ANSWERS (Ankylosing Spondylitis with Etanercept Regimens) trial, 4 of 12 patients receiving a once-weekly 25-mg dose of etanercept (Enbrel) had a sustained response as did 14 of 21 patients who remained on the usual once-weekly dose of 50 mg.
“Although a minority of patients maintained response to the lower dose of etanercept over the longer term, the costs savings are substantial,” said Lauren Steel and coauthors from the Norfolk and Norwich Hospitals NHS Foundation Trust in a poster presentation. Almost 18,000 pounds sterling ($23,000) could be saved per each patient who is able to stay on the lower dose for 50 months.
Further, patients who did not maintain a response on the lower dose were usually able to regain their responses when the higher dose therapy was reinstituted. On average, disease control was reestablished in three out of four patients within 14 months of reverting to standard therapy.
ANSWERS was an open-label, multicenter, randomized, pilot study that sought to determine if tapering the dose of etanercept from the recommended 50 mg to 25 mg was feasible in 47 patients with AS (J Rheumatol. 2015;42:1177–85). The premise was that dose tapering in patients who achieved a response would perhaps reduce the risk for side effects in the long term, as well as provide considerable cost savings.
About half of the patients studied achieved a response to full-dose etanercept and were able to reduce their dose. At 6 months, a clinical response was maintained by 52% of the patients taking 25 mg and 92% of the patients taking 50 mg (P = .003).
The current prospective extension of the study looked at the longer-term outcomes of the patients who successfully maintained a response to the lower dose of etanercept.
Maintenance of response was defined as no change in the primary outcome of a reduction of 50% or more or a fall of at least 2 units in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and at least a 2-unit reduction in spinal pain measured using a 10-point scale.
In all, 12 patients, 9 of them male, with a mean age of 52 years entered the extension study. The comparator group consisted of 21 patients who had continued taking the 50-mg dose, 20 of them male, with a mean age of 60 years.
Of the 12 patients in the 25-mg group, 1 discontinued treatment because of side effects and did not restart any further biologic treatment; 7 patients experienced a disease flare after a median of 16 months and were retreated with the 50-mg dose. Five of the seven patients who reverted to the higher dose of etanercept regained a good response; the other two patients were switched to adalimumab (Humira) because of a loss of efficacy.
Pfizer funded the original study. One author disclosed he had received research funding and acted as an adviser to Pfizer and other pharmaceutical companies.
AT RHEUMATOLOGY 2017
Key clinical point:
Major finding: Four of 12 patients treated with etanercept 25 mg once weekly maintained a response at 50 months.
Data source: An extension study of 33 patients in the open-label, multicenter, randomized Ankylosing Spondylitis with Etanercept Regimens (ANSWERS) trial.
Disclosures: Pfizer funded the original study. One author disclosed he had received research funding and acted as an adviser to Pfizer and other pharmaceutical companies.
Targeted treatment does not address RA patients’ mental health
BIRMINGHAM, ENGLAND – Improvements in physical health with response to treatment of rheumatoid arthritis (RA) don’t necessarily translate into improvements in patients’ mental health, based on results of a systematic review presented at the British Society for Rheumatology annual conference.
Reducing levels of joint pain and inflammation did not appreciably improve mental well-being, said Faith Matcham, PhD, of the Institute of Psychiatry, Psychology, and Neuroscience, King’s College London. The standardized mean difference between biologics and disease-modifying antirheumatic drugs (DMARDs) in improving the physical and mental components of the 36-item Short Form survey were a respective 0.47 and 0.25.
A pairwise meta-analysis was performed on 58 and 48 randomized controlled trials, respectively. More than 34,000 patients had been treated in these trials with 28 current or investigational RA therapies, and treatment outcomes were compared with an active, placebo, or usual-care arm. Studies were included if they had assessed any type of mood outcome.
Mental health had been measured in more than half of the RA treatment trials found on the original search, but just 40% of those trials reported mental health outcomes with enough information to be used in the meta-analyses.
Although studies that had compared biologics with placebo accounted for only four studies, none of those showed significant change in mental health outcomes with active therapy.
“Providing effective pharmacotherapy alone is going to be insufficient to produce meaningful improvement in mental health outcomes for the majority,” Dr. Matcham observed. She added that, even after treatment, mental health measures in RA patients remained lower than those in the general population. “It is essential to optimize both mental and physical health care outcomes,” she concluded, and an integrated approach needs to be taken.
Dr. Matcham reported having no financial disclosures.
BIRMINGHAM, ENGLAND – Improvements in physical health with response to treatment of rheumatoid arthritis (RA) don’t necessarily translate into improvements in patients’ mental health, based on results of a systematic review presented at the British Society for Rheumatology annual conference.
Reducing levels of joint pain and inflammation did not appreciably improve mental well-being, said Faith Matcham, PhD, of the Institute of Psychiatry, Psychology, and Neuroscience, King’s College London. The standardized mean difference between biologics and disease-modifying antirheumatic drugs (DMARDs) in improving the physical and mental components of the 36-item Short Form survey were a respective 0.47 and 0.25.
A pairwise meta-analysis was performed on 58 and 48 randomized controlled trials, respectively. More than 34,000 patients had been treated in these trials with 28 current or investigational RA therapies, and treatment outcomes were compared with an active, placebo, or usual-care arm. Studies were included if they had assessed any type of mood outcome.
Mental health had been measured in more than half of the RA treatment trials found on the original search, but just 40% of those trials reported mental health outcomes with enough information to be used in the meta-analyses.
Although studies that had compared biologics with placebo accounted for only four studies, none of those showed significant change in mental health outcomes with active therapy.
“Providing effective pharmacotherapy alone is going to be insufficient to produce meaningful improvement in mental health outcomes for the majority,” Dr. Matcham observed. She added that, even after treatment, mental health measures in RA patients remained lower than those in the general population. “It is essential to optimize both mental and physical health care outcomes,” she concluded, and an integrated approach needs to be taken.
Dr. Matcham reported having no financial disclosures.
BIRMINGHAM, ENGLAND – Improvements in physical health with response to treatment of rheumatoid arthritis (RA) don’t necessarily translate into improvements in patients’ mental health, based on results of a systematic review presented at the British Society for Rheumatology annual conference.
Reducing levels of joint pain and inflammation did not appreciably improve mental well-being, said Faith Matcham, PhD, of the Institute of Psychiatry, Psychology, and Neuroscience, King’s College London. The standardized mean difference between biologics and disease-modifying antirheumatic drugs (DMARDs) in improving the physical and mental components of the 36-item Short Form survey were a respective 0.47 and 0.25.
A pairwise meta-analysis was performed on 58 and 48 randomized controlled trials, respectively. More than 34,000 patients had been treated in these trials with 28 current or investigational RA therapies, and treatment outcomes were compared with an active, placebo, or usual-care arm. Studies were included if they had assessed any type of mood outcome.
Mental health had been measured in more than half of the RA treatment trials found on the original search, but just 40% of those trials reported mental health outcomes with enough information to be used in the meta-analyses.
Although studies that had compared biologics with placebo accounted for only four studies, none of those showed significant change in mental health outcomes with active therapy.
“Providing effective pharmacotherapy alone is going to be insufficient to produce meaningful improvement in mental health outcomes for the majority,” Dr. Matcham observed. She added that, even after treatment, mental health measures in RA patients remained lower than those in the general population. “It is essential to optimize both mental and physical health care outcomes,” she concluded, and an integrated approach needs to be taken.
Dr. Matcham reported having no financial disclosures.
AT RHEUMATOLOGY 2017
Key clinical point: A response to pharmacotherapy per se is not directly related to improved mental health outcomes in patients with rheumatoid arthritis.
Major finding: The standardized mean difference between biologics and DMARDs in improving the physical and mental components of the 36-item Short Form survey were 0.47 and 0.25, respectively.
Data source: A systematic review and meta-analysis of RA treatment trials involving 34,087 patients.
Disclosures: Dr. Matcham reported having no relevant financial disclosures.
Smartphone apps may aid home rheumatoid arthritis monitoring
BIRMINGHAM, ENGLAND – Researchers in the United Kingdom are looking at how smartphone technology can help to improve how patients with rheumatoid arthritis (RA) monitor their disease at home and between clinic visits.
As part of the Remote Monitoring of Rheumatoid Arthritis (REMORA) study, a team led by Will Dixon, MD, at the University of Manchester (England), has developed an app that links directly into electronic patient records to help collect information from patients between their regular clinic visits for both self-monitoring and research purposes.
“REMORA is motivated by the need to learn about what happens to patients in between clinic visits, and that’s both for clinical care and for research but also to have the opportunity to support self-management, so we’ve designed the study to meet those three needs,” Dr. Dixon, professor and chair of digital epidemiology in Manchester University’s division of musculoskeletal and dermatological sciences, said in an interview at the British Society for Rheumatology annual conference.
Dr. Dixon explained that when patients are seen every few months they might forget or underplay events that could have significance for their clinical care. Use of the beta version of the app between clinic consultations in the study proved there was recall error.
“In the consultation, we’d ask people how they’d been doing before looking at the graphs in the app, and even people who had said they’d been absolutely fine since they’d last been seen, even in the previous month of beta-testing, have signs that they could have been [having] pain flares,” Dr. Dixon said. This sort of prospective data collection by the app could enable discussion of any irregularities even if more stoic patients reported having no problems.
The responses showed that there were some similarities in the information that clinicians and researchers and patients want to record, but also some key differences.
All groups wanted the app to be able to collect information about possible changes in disease activity (indicated by levels of pain, joint swelling, or disease flares) and the impact that these had on physical and emotional well-being.
Patients were open to regular monitoring, if not too burdensome, but would prefer to note things down “when something happened.” On the other hand, clinicians and researchers wanted regularity and consistency in the monitoring, although they saw the benefit of a more “ad hoc” approach.
Clinicians and researchers felt no need to “reinvent the wheel” and indicated that existing validated tools could be used to collect the information. Conversely, patients preferred a more pictorial or free-text approach, although were aware of some standardized tools in common use.
Daily, weekly, and monthly question sets were developed, with a diary that uses emojis to indicate how people using the app are feeling and a free-text area to allow them to note down any significant health events or thoughts.
Pilot testing of the app has been done in one hospital so far, but it was so well received that patients did not want to have to stop using it at the end of the study, Dr. Austin said in an interview.
Linking into the patient records is a unique approach, and if it proves successful in RA, it could be rolled out across the country’s National Health Service (NHS) and perhaps even into other chronic conditions where self-monitoring is needed.
“We all know we have a limited time in our consultations, so we need to develop a system whereby a clinician, in the 15 minutes they have got for a follow-up appointment, can set somebody up with an ‘app prescription,’ ” Dr. Dixon said. “We’re looking to really develop a blueprint for how apps can successfully connect into the NHS,” Dr. Dixon said. At present, however, the next step is to try to scale up the app for use in several hospitals within an area rather than roll it out nationally, he said.
Using built-in accelerometer for research
Another approach to harnessing smartphone technology is being taken by researchers at the University of Southampton (England), where engineering postgraduate student Jimmy Caroupapoulle and his collaborators are working on an app that continually uses the built-in sensors in a phone to detect movements, and thus how physically active someone is.
“What we are trying to achieve is to develop an application that can just run in the background so people do not have to do too much,” Mr. Caroupapoulle explained in an interview around his poster presentation.
Using the app, called RApp, patients will be able to answer daily questions based on existing tools (RAPID3 and MDHAQ) to record their levels of pain, joint inflammation, and physical activity. The latter would be recorded via the phone’s onboard accelerometer to give a more objective view of whether the patient is moving around, as well as the patient’s speed in getting up from a seated position. The app collects data using the 28-joint Disease Activity Score so an indication of the severity of joint pain or inflammation can be assessed.
The aim is to give the patients the power to monitor themselves but also to facilitate discussion with their physicians. Data from the app will be integrated into an online portal so that patients and their doctors can see the information provided.
So far, 5 patients with RA have tested the application and the next stage is to release the application to a wider group, perhaps 20 patients, Mr. Caroupapoulle said.
“There are lots of apps out there, but this is something that looks at the quality of movement.” consultant rheumatologist Christopher Edwards, MD, a member of the team behind the RApp, said in an interview.
As opposed to pedometers or other devices that monitor physical activity to varying degrees of accuracy, RApp looks at how people accelerate as they stand up or move, which can be important for those with arthritis, and how that relates to their disease activity, said Dr. Edwards, professor of rheumatology at the University of Southampton.
“You can’t guarantee that someone always had their phone in their hand or in their bag,” Dr. Edwards said, “so what you want to do is get a sample from time during the day that gives you an overall representation, even if that is a very short period, just once during the day, then we’ll see if that makes a difference over time and whether that correlates with someone’s disease activity.”
The REMORA study is sponsored by Arthritis Research UK and the National Institute of Health Research Collaboration for Leadership in Applied Health Research and Care Greater Manchester. RApp is being developed without commercial funding. Dr. Austin, Dr. Dixon, Mr. Caroupapoulle, and Dr. Edwards stated they had no conflicts of interest.
BIRMINGHAM, ENGLAND – Researchers in the United Kingdom are looking at how smartphone technology can help to improve how patients with rheumatoid arthritis (RA) monitor their disease at home and between clinic visits.
As part of the Remote Monitoring of Rheumatoid Arthritis (REMORA) study, a team led by Will Dixon, MD, at the University of Manchester (England), has developed an app that links directly into electronic patient records to help collect information from patients between their regular clinic visits for both self-monitoring and research purposes.
“REMORA is motivated by the need to learn about what happens to patients in between clinic visits, and that’s both for clinical care and for research but also to have the opportunity to support self-management, so we’ve designed the study to meet those three needs,” Dr. Dixon, professor and chair of digital epidemiology in Manchester University’s division of musculoskeletal and dermatological sciences, said in an interview at the British Society for Rheumatology annual conference.
Dr. Dixon explained that when patients are seen every few months they might forget or underplay events that could have significance for their clinical care. Use of the beta version of the app between clinic consultations in the study proved there was recall error.
“In the consultation, we’d ask people how they’d been doing before looking at the graphs in the app, and even people who had said they’d been absolutely fine since they’d last been seen, even in the previous month of beta-testing, have signs that they could have been [having] pain flares,” Dr. Dixon said. This sort of prospective data collection by the app could enable discussion of any irregularities even if more stoic patients reported having no problems.
The responses showed that there were some similarities in the information that clinicians and researchers and patients want to record, but also some key differences.
All groups wanted the app to be able to collect information about possible changes in disease activity (indicated by levels of pain, joint swelling, or disease flares) and the impact that these had on physical and emotional well-being.
Patients were open to regular monitoring, if not too burdensome, but would prefer to note things down “when something happened.” On the other hand, clinicians and researchers wanted regularity and consistency in the monitoring, although they saw the benefit of a more “ad hoc” approach.
Clinicians and researchers felt no need to “reinvent the wheel” and indicated that existing validated tools could be used to collect the information. Conversely, patients preferred a more pictorial or free-text approach, although were aware of some standardized tools in common use.
Daily, weekly, and monthly question sets were developed, with a diary that uses emojis to indicate how people using the app are feeling and a free-text area to allow them to note down any significant health events or thoughts.
Pilot testing of the app has been done in one hospital so far, but it was so well received that patients did not want to have to stop using it at the end of the study, Dr. Austin said in an interview.
Linking into the patient records is a unique approach, and if it proves successful in RA, it could be rolled out across the country’s National Health Service (NHS) and perhaps even into other chronic conditions where self-monitoring is needed.
“We all know we have a limited time in our consultations, so we need to develop a system whereby a clinician, in the 15 minutes they have got for a follow-up appointment, can set somebody up with an ‘app prescription,’ ” Dr. Dixon said. “We’re looking to really develop a blueprint for how apps can successfully connect into the NHS,” Dr. Dixon said. At present, however, the next step is to try to scale up the app for use in several hospitals within an area rather than roll it out nationally, he said.
Using built-in accelerometer for research
Another approach to harnessing smartphone technology is being taken by researchers at the University of Southampton (England), where engineering postgraduate student Jimmy Caroupapoulle and his collaborators are working on an app that continually uses the built-in sensors in a phone to detect movements, and thus how physically active someone is.
“What we are trying to achieve is to develop an application that can just run in the background so people do not have to do too much,” Mr. Caroupapoulle explained in an interview around his poster presentation.
Using the app, called RApp, patients will be able to answer daily questions based on existing tools (RAPID3 and MDHAQ) to record their levels of pain, joint inflammation, and physical activity. The latter would be recorded via the phone’s onboard accelerometer to give a more objective view of whether the patient is moving around, as well as the patient’s speed in getting up from a seated position. The app collects data using the 28-joint Disease Activity Score so an indication of the severity of joint pain or inflammation can be assessed.
The aim is to give the patients the power to monitor themselves but also to facilitate discussion with their physicians. Data from the app will be integrated into an online portal so that patients and their doctors can see the information provided.
So far, 5 patients with RA have tested the application and the next stage is to release the application to a wider group, perhaps 20 patients, Mr. Caroupapoulle said.
“There are lots of apps out there, but this is something that looks at the quality of movement.” consultant rheumatologist Christopher Edwards, MD, a member of the team behind the RApp, said in an interview.
As opposed to pedometers or other devices that monitor physical activity to varying degrees of accuracy, RApp looks at how people accelerate as they stand up or move, which can be important for those with arthritis, and how that relates to their disease activity, said Dr. Edwards, professor of rheumatology at the University of Southampton.
“You can’t guarantee that someone always had their phone in their hand or in their bag,” Dr. Edwards said, “so what you want to do is get a sample from time during the day that gives you an overall representation, even if that is a very short period, just once during the day, then we’ll see if that makes a difference over time and whether that correlates with someone’s disease activity.”
The REMORA study is sponsored by Arthritis Research UK and the National Institute of Health Research Collaboration for Leadership in Applied Health Research and Care Greater Manchester. RApp is being developed without commercial funding. Dr. Austin, Dr. Dixon, Mr. Caroupapoulle, and Dr. Edwards stated they had no conflicts of interest.
BIRMINGHAM, ENGLAND – Researchers in the United Kingdom are looking at how smartphone technology can help to improve how patients with rheumatoid arthritis (RA) monitor their disease at home and between clinic visits.
As part of the Remote Monitoring of Rheumatoid Arthritis (REMORA) study, a team led by Will Dixon, MD, at the University of Manchester (England), has developed an app that links directly into electronic patient records to help collect information from patients between their regular clinic visits for both self-monitoring and research purposes.
“REMORA is motivated by the need to learn about what happens to patients in between clinic visits, and that’s both for clinical care and for research but also to have the opportunity to support self-management, so we’ve designed the study to meet those three needs,” Dr. Dixon, professor and chair of digital epidemiology in Manchester University’s division of musculoskeletal and dermatological sciences, said in an interview at the British Society for Rheumatology annual conference.
Dr. Dixon explained that when patients are seen every few months they might forget or underplay events that could have significance for their clinical care. Use of the beta version of the app between clinic consultations in the study proved there was recall error.
“In the consultation, we’d ask people how they’d been doing before looking at the graphs in the app, and even people who had said they’d been absolutely fine since they’d last been seen, even in the previous month of beta-testing, have signs that they could have been [having] pain flares,” Dr. Dixon said. This sort of prospective data collection by the app could enable discussion of any irregularities even if more stoic patients reported having no problems.
The responses showed that there were some similarities in the information that clinicians and researchers and patients want to record, but also some key differences.
All groups wanted the app to be able to collect information about possible changes in disease activity (indicated by levels of pain, joint swelling, or disease flares) and the impact that these had on physical and emotional well-being.
Patients were open to regular monitoring, if not too burdensome, but would prefer to note things down “when something happened.” On the other hand, clinicians and researchers wanted regularity and consistency in the monitoring, although they saw the benefit of a more “ad hoc” approach.
Clinicians and researchers felt no need to “reinvent the wheel” and indicated that existing validated tools could be used to collect the information. Conversely, patients preferred a more pictorial or free-text approach, although were aware of some standardized tools in common use.
Daily, weekly, and monthly question sets were developed, with a diary that uses emojis to indicate how people using the app are feeling and a free-text area to allow them to note down any significant health events or thoughts.
Pilot testing of the app has been done in one hospital so far, but it was so well received that patients did not want to have to stop using it at the end of the study, Dr. Austin said in an interview.
Linking into the patient records is a unique approach, and if it proves successful in RA, it could be rolled out across the country’s National Health Service (NHS) and perhaps even into other chronic conditions where self-monitoring is needed.
“We all know we have a limited time in our consultations, so we need to develop a system whereby a clinician, in the 15 minutes they have got for a follow-up appointment, can set somebody up with an ‘app prescription,’ ” Dr. Dixon said. “We’re looking to really develop a blueprint for how apps can successfully connect into the NHS,” Dr. Dixon said. At present, however, the next step is to try to scale up the app for use in several hospitals within an area rather than roll it out nationally, he said.
Using built-in accelerometer for research
Another approach to harnessing smartphone technology is being taken by researchers at the University of Southampton (England), where engineering postgraduate student Jimmy Caroupapoulle and his collaborators are working on an app that continually uses the built-in sensors in a phone to detect movements, and thus how physically active someone is.
“What we are trying to achieve is to develop an application that can just run in the background so people do not have to do too much,” Mr. Caroupapoulle explained in an interview around his poster presentation.
Using the app, called RApp, patients will be able to answer daily questions based on existing tools (RAPID3 and MDHAQ) to record their levels of pain, joint inflammation, and physical activity. The latter would be recorded via the phone’s onboard accelerometer to give a more objective view of whether the patient is moving around, as well as the patient’s speed in getting up from a seated position. The app collects data using the 28-joint Disease Activity Score so an indication of the severity of joint pain or inflammation can be assessed.
The aim is to give the patients the power to monitor themselves but also to facilitate discussion with their physicians. Data from the app will be integrated into an online portal so that patients and their doctors can see the information provided.
So far, 5 patients with RA have tested the application and the next stage is to release the application to a wider group, perhaps 20 patients, Mr. Caroupapoulle said.
“There are lots of apps out there, but this is something that looks at the quality of movement.” consultant rheumatologist Christopher Edwards, MD, a member of the team behind the RApp, said in an interview.
As opposed to pedometers or other devices that monitor physical activity to varying degrees of accuracy, RApp looks at how people accelerate as they stand up or move, which can be important for those with arthritis, and how that relates to their disease activity, said Dr. Edwards, professor of rheumatology at the University of Southampton.
“You can’t guarantee that someone always had their phone in their hand or in their bag,” Dr. Edwards said, “so what you want to do is get a sample from time during the day that gives you an overall representation, even if that is a very short period, just once during the day, then we’ll see if that makes a difference over time and whether that correlates with someone’s disease activity.”
The REMORA study is sponsored by Arthritis Research UK and the National Institute of Health Research Collaboration for Leadership in Applied Health Research and Care Greater Manchester. RApp is being developed without commercial funding. Dr. Austin, Dr. Dixon, Mr. Caroupapoulle, and Dr. Edwards stated they had no conflicts of interest.
Ankylosing spondylitis disease severity worsened by smoking
BIRMINGHAM, ENGLAND – Patients with axial spondyloarthritis who currently smoke have been found to have worse disease activity than those who do not in an early analysis of data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS).
Smoking was associated with worse disease not only when comparing ever smokers with never smokers, but also when current smokers were compared to ex-smokers, and there was some evidence that the amount of smoking was important with heavier smokers having worse disease activity than light smokers.
Dr. Zhao, of Aintree University Hospital in Liverpool, England, added that, as in previous studies, these data show that “smoking is associated with worse disease activity at baseline and this needs to be accounted for in the next stage of longitudinal analysis.”
An association between smoking and worse disease activity in patients with axSpA has been reported previously, Dr. Zhao acknowledged, but this is not as clear cut as in rheumatoid arthritis where smoking is known to have a pathogenic effect. The small number of earlier studies looking at the possible effect of smoking in AS have been limited by their size and varying methodology, he added, and the studies’ researchers were not able to see if there was any potential dose effect of smoking.
The BSRBR-AS, which started recruiting patients with an Assessment of SpondyloArthritis international Society (ASAS) classification of axSpA in 2012, offers a unique opportunity to explore the association between smoking and axSpA further, he said. More than 2,500 patients are included in the register at present, none of whom should have not been treated with biologic agents at the time of recruitment.
The aim of the present analysis that looked at data on 932 patients was to quantify the effect of smoking status and quantity on several disease outcomes as measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Bath Ankylosing Spondylitis Metrology Index (BASMI). Spinal pain was also assessed, by way of a visual analog scale (VAS), and quality of life was determined via the disease-specific Ankylosing Spondylitis Quality of Life Instruments (ASQoL).
Most of the patients recruited were male (71%), and the mean age was 50 years. HLA-B27 data were available for 64% of the cohort, and 84% were positive.
Self-reported smoking status was recorded, with 19% saying they were current smokers, 37% saying they were ex-smokers, and 44% saying they had never smoked. If patients reported being ever smokers, the frequency with which they smoked (daily, weekly, monthly, once or twice, or never) was recorded, and if patients smoked daily, then the number of cigarettes smoked per day was obtained. Heavy smoking was defined as smoking 10 or more cigarettes per day and light smoking as fewer than 10 cigarettes per day. By this definition, around 37% of daily smokers were classed as heavy smokers.
In a comparison of ever smokers with never smokers, the mean BASDAI, BASFI, BASMI, spinal VAS, and ASQoL were significantly higher if patients had smoked at some point. All comparisons were adjusted for age, gender, body mass index, and HLA-B27 status.
The mean BASDAI score, for example, was more than 1 unit higher in a comparison of ever smokers with never smokers, with an adjusted regression coefficient of 1.04 and a 95% confidence interval (CI) of 0.72-1.36.
The adjusted regression coefficients for the other measures assessed were 1.34 (95% CI, 0.98-1.69) for BASFI, 0.61 (95% CI 0.36-0.87) for BASMI, 1.11 (95% CI, 0.74-1.49) for spinal VAS, and 2.71 (95% CI, 2.01–3.41) for ASQoL.
Similar findings were seen in the analysis comparing current with ex-smokers across all measures studied, and there was a trend for disease activity to be worse in heavier than in lighter smokers. The latter may not have reached significance because of the smaller number of patients (n = 172) involved in that part of the analysis. Nevertheless, these preliminary findings suggest that even being a light smoker can affect disease outcomes and so cutting down (i.e., to fewer than 10 cigarettes per day) may not be sufficient to reduce the effect that smoking has on disease activity.
“We should be actively encouraging our patients [with axSpA] to stop smoking,” Dr. Zhao concluded.
The BSRBR-AS is managed by a team of investigators based at the University of Aberdeen in collaboration with 83 centers throughout the United Kingdom. It is funded by the BSR, which in turn receives funding from the manufacturers of the biologic therapies included in this study (currently AbbVie, Pfizer, and UCB). Dr. Zhao and coauthors had no conflicts of interest to disclose.
BIRMINGHAM, ENGLAND – Patients with axial spondyloarthritis who currently smoke have been found to have worse disease activity than those who do not in an early analysis of data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS).
Smoking was associated with worse disease not only when comparing ever smokers with never smokers, but also when current smokers were compared to ex-smokers, and there was some evidence that the amount of smoking was important with heavier smokers having worse disease activity than light smokers.
Dr. Zhao, of Aintree University Hospital in Liverpool, England, added that, as in previous studies, these data show that “smoking is associated with worse disease activity at baseline and this needs to be accounted for in the next stage of longitudinal analysis.”
An association between smoking and worse disease activity in patients with axSpA has been reported previously, Dr. Zhao acknowledged, but this is not as clear cut as in rheumatoid arthritis where smoking is known to have a pathogenic effect. The small number of earlier studies looking at the possible effect of smoking in AS have been limited by their size and varying methodology, he added, and the studies’ researchers were not able to see if there was any potential dose effect of smoking.
The BSRBR-AS, which started recruiting patients with an Assessment of SpondyloArthritis international Society (ASAS) classification of axSpA in 2012, offers a unique opportunity to explore the association between smoking and axSpA further, he said. More than 2,500 patients are included in the register at present, none of whom should have not been treated with biologic agents at the time of recruitment.
The aim of the present analysis that looked at data on 932 patients was to quantify the effect of smoking status and quantity on several disease outcomes as measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Bath Ankylosing Spondylitis Metrology Index (BASMI). Spinal pain was also assessed, by way of a visual analog scale (VAS), and quality of life was determined via the disease-specific Ankylosing Spondylitis Quality of Life Instruments (ASQoL).
Most of the patients recruited were male (71%), and the mean age was 50 years. HLA-B27 data were available for 64% of the cohort, and 84% were positive.
Self-reported smoking status was recorded, with 19% saying they were current smokers, 37% saying they were ex-smokers, and 44% saying they had never smoked. If patients reported being ever smokers, the frequency with which they smoked (daily, weekly, monthly, once or twice, or never) was recorded, and if patients smoked daily, then the number of cigarettes smoked per day was obtained. Heavy smoking was defined as smoking 10 or more cigarettes per day and light smoking as fewer than 10 cigarettes per day. By this definition, around 37% of daily smokers were classed as heavy smokers.
In a comparison of ever smokers with never smokers, the mean BASDAI, BASFI, BASMI, spinal VAS, and ASQoL were significantly higher if patients had smoked at some point. All comparisons were adjusted for age, gender, body mass index, and HLA-B27 status.
The mean BASDAI score, for example, was more than 1 unit higher in a comparison of ever smokers with never smokers, with an adjusted regression coefficient of 1.04 and a 95% confidence interval (CI) of 0.72-1.36.
The adjusted regression coefficients for the other measures assessed were 1.34 (95% CI, 0.98-1.69) for BASFI, 0.61 (95% CI 0.36-0.87) for BASMI, 1.11 (95% CI, 0.74-1.49) for spinal VAS, and 2.71 (95% CI, 2.01–3.41) for ASQoL.
Similar findings were seen in the analysis comparing current with ex-smokers across all measures studied, and there was a trend for disease activity to be worse in heavier than in lighter smokers. The latter may not have reached significance because of the smaller number of patients (n = 172) involved in that part of the analysis. Nevertheless, these preliminary findings suggest that even being a light smoker can affect disease outcomes and so cutting down (i.e., to fewer than 10 cigarettes per day) may not be sufficient to reduce the effect that smoking has on disease activity.
“We should be actively encouraging our patients [with axSpA] to stop smoking,” Dr. Zhao concluded.
The BSRBR-AS is managed by a team of investigators based at the University of Aberdeen in collaboration with 83 centers throughout the United Kingdom. It is funded by the BSR, which in turn receives funding from the manufacturers of the biologic therapies included in this study (currently AbbVie, Pfizer, and UCB). Dr. Zhao and coauthors had no conflicts of interest to disclose.
BIRMINGHAM, ENGLAND – Patients with axial spondyloarthritis who currently smoke have been found to have worse disease activity than those who do not in an early analysis of data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS).
Smoking was associated with worse disease not only when comparing ever smokers with never smokers, but also when current smokers were compared to ex-smokers, and there was some evidence that the amount of smoking was important with heavier smokers having worse disease activity than light smokers.
Dr. Zhao, of Aintree University Hospital in Liverpool, England, added that, as in previous studies, these data show that “smoking is associated with worse disease activity at baseline and this needs to be accounted for in the next stage of longitudinal analysis.”
An association between smoking and worse disease activity in patients with axSpA has been reported previously, Dr. Zhao acknowledged, but this is not as clear cut as in rheumatoid arthritis where smoking is known to have a pathogenic effect. The small number of earlier studies looking at the possible effect of smoking in AS have been limited by their size and varying methodology, he added, and the studies’ researchers were not able to see if there was any potential dose effect of smoking.
The BSRBR-AS, which started recruiting patients with an Assessment of SpondyloArthritis international Society (ASAS) classification of axSpA in 2012, offers a unique opportunity to explore the association between smoking and axSpA further, he said. More than 2,500 patients are included in the register at present, none of whom should have not been treated with biologic agents at the time of recruitment.
The aim of the present analysis that looked at data on 932 patients was to quantify the effect of smoking status and quantity on several disease outcomes as measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Bath Ankylosing Spondylitis Metrology Index (BASMI). Spinal pain was also assessed, by way of a visual analog scale (VAS), and quality of life was determined via the disease-specific Ankylosing Spondylitis Quality of Life Instruments (ASQoL).
Most of the patients recruited were male (71%), and the mean age was 50 years. HLA-B27 data were available for 64% of the cohort, and 84% were positive.
Self-reported smoking status was recorded, with 19% saying they were current smokers, 37% saying they were ex-smokers, and 44% saying they had never smoked. If patients reported being ever smokers, the frequency with which they smoked (daily, weekly, monthly, once or twice, or never) was recorded, and if patients smoked daily, then the number of cigarettes smoked per day was obtained. Heavy smoking was defined as smoking 10 or more cigarettes per day and light smoking as fewer than 10 cigarettes per day. By this definition, around 37% of daily smokers were classed as heavy smokers.
In a comparison of ever smokers with never smokers, the mean BASDAI, BASFI, BASMI, spinal VAS, and ASQoL were significantly higher if patients had smoked at some point. All comparisons were adjusted for age, gender, body mass index, and HLA-B27 status.
The mean BASDAI score, for example, was more than 1 unit higher in a comparison of ever smokers with never smokers, with an adjusted regression coefficient of 1.04 and a 95% confidence interval (CI) of 0.72-1.36.
The adjusted regression coefficients for the other measures assessed were 1.34 (95% CI, 0.98-1.69) for BASFI, 0.61 (95% CI 0.36-0.87) for BASMI, 1.11 (95% CI, 0.74-1.49) for spinal VAS, and 2.71 (95% CI, 2.01–3.41) for ASQoL.
Similar findings were seen in the analysis comparing current with ex-smokers across all measures studied, and there was a trend for disease activity to be worse in heavier than in lighter smokers. The latter may not have reached significance because of the smaller number of patients (n = 172) involved in that part of the analysis. Nevertheless, these preliminary findings suggest that even being a light smoker can affect disease outcomes and so cutting down (i.e., to fewer than 10 cigarettes per day) may not be sufficient to reduce the effect that smoking has on disease activity.
“We should be actively encouraging our patients [with axSpA] to stop smoking,” Dr. Zhao concluded.
The BSRBR-AS is managed by a team of investigators based at the University of Aberdeen in collaboration with 83 centers throughout the United Kingdom. It is funded by the BSR, which in turn receives funding from the manufacturers of the biologic therapies included in this study (currently AbbVie, Pfizer, and UCB). Dr. Zhao and coauthors had no conflicts of interest to disclose.
AT RHEUMATOLOGY 2017
Key clinical point:
Major finding: Mean BASDAI, BASFI, BASMI, spinal VAS, and ASQoL were all significantly higher in ever vs. never smokers.
Data source: The British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS).
Disclosures: The BSRBR-AS is managed by a team of investigators based at the University of Aberdeen in collaboration with 83 centers throughout the United Kingdom. It is funded by the BSR, which in turn receives funding from the manufacturers of the biologic therapies included in this study (currently AbbVie, Pfizer, and UCB). Dr. Zhao and coauthors had no conflicts of interest to disclose.
New ACR-EULAR diagnostic criteria proposed for ANCA-associated vasculitides
BIRMINGHAM, ENGLAND – New criteria for classifying granulomatosis with polyangiitis (GPA) have been proposed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) .
GPA, a type of antineutrophil cytoplasmic antibody (ANCA)–associated systemic vasculitis, was formerly known as Wegener’s granulomatosis. When a small or medium vessel vasculitis has been diagnosed, the new criteria – which are provisional at present – are invoked to confirm the GPA diagnosis. Patients are assessed for five clinical and four laboratory variables.
The new criteria were developed as part of the Diagnostic and Classification of the Systemic Vasculitides (DCVAS) study. An international project set up to update the classification criteria for all types of systemic vasculitis, DCVAS involves more than 6,000 patients from 133 sites in 32 countries.
To develop the criteria for GPA, a team of 49 vasculitis experts was asked to review over 1, 400 clinical vignettes of newly diagnosed vasculitis based on cases submitted to the DCVAS. The expert panel was not told the suspected diagnosis. When the panel did not reach consensus on a case, it was further reviewed by seven members of the DCVAS study steering committee.
Using this approach, 85% of 578 cases submitted as GPA were confirmed. Compared with other vasculitides, GPA occurred in younger patients (53 vs. 58 years), was more likely to be proteinase 3–ANCA (81% vs. 3.4%) and c-ANCA (72% vs. 5.5%) positive, and was less likely to be p-ANCA (10.3% vs. 47.3%) and myeloperoxidase-antibody (8% vs. 59.3%) positive.
The next stage was to identify data-driven items that might be used to distinguish GPA from other vasculitides and obtain a clinical consensus on those that were the most important for a diagnosis. Of 1000 possible items that included clinical, laboratory, imaging, and biopsy findings, 91 were retained after regression analysis and 22 appeared independently predictive for GPA.
The top five data-driven items had both c-ANCA and PR3-ANCA antibodies, bloody nasal discharge, nasal ulcers, crusting, or sinonasal congestion or blockage; a high (greater than 1 x 109/L) eosinophil count; and the presence of nasal polyps. There were also some clinical and data-driven items that were considered and used in a final nine-item model, Dr. Robson explained.
A point-based risk score was subsequently developed, with a total score of 5 or more suggesting GPA.
The presence of c-ANCA and PR3-ANCA antibodies, an almost certain indicator of GPA with an odds ratio of 134.8 (95% confidence interval, 62.4–291.1; P less than .001), was given the highest score of 5.
Having bloody or nasal discharge or other nasal symptoms or seeing a granuloma on biopsy were both given a score of 3. A score of 2 was awarded if there were nodules, a mass or cavity on chest imaging, or if there was cartilaginous involvement. A score of 1 was given if there was a loss or reduction in hearing or if the patient had red or painful eyes. Two items – the presence of a high eosinophil count and nasal polyps – were given negative scores (-3 and -4, respectively).
Dr. Robson reported that the nine-item model had an area under the curve of 0.98 and high sensitivity (90.7%) and specificity (93.5%).
Dr. Robson reported having no conflicts of interest.
BIRMINGHAM, ENGLAND – New criteria for classifying granulomatosis with polyangiitis (GPA) have been proposed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) .
GPA, a type of antineutrophil cytoplasmic antibody (ANCA)–associated systemic vasculitis, was formerly known as Wegener’s granulomatosis. When a small or medium vessel vasculitis has been diagnosed, the new criteria – which are provisional at present – are invoked to confirm the GPA diagnosis. Patients are assessed for five clinical and four laboratory variables.
The new criteria were developed as part of the Diagnostic and Classification of the Systemic Vasculitides (DCVAS) study. An international project set up to update the classification criteria for all types of systemic vasculitis, DCVAS involves more than 6,000 patients from 133 sites in 32 countries.
To develop the criteria for GPA, a team of 49 vasculitis experts was asked to review over 1, 400 clinical vignettes of newly diagnosed vasculitis based on cases submitted to the DCVAS. The expert panel was not told the suspected diagnosis. When the panel did not reach consensus on a case, it was further reviewed by seven members of the DCVAS study steering committee.
Using this approach, 85% of 578 cases submitted as GPA were confirmed. Compared with other vasculitides, GPA occurred in younger patients (53 vs. 58 years), was more likely to be proteinase 3–ANCA (81% vs. 3.4%) and c-ANCA (72% vs. 5.5%) positive, and was less likely to be p-ANCA (10.3% vs. 47.3%) and myeloperoxidase-antibody (8% vs. 59.3%) positive.
The next stage was to identify data-driven items that might be used to distinguish GPA from other vasculitides and obtain a clinical consensus on those that were the most important for a diagnosis. Of 1000 possible items that included clinical, laboratory, imaging, and biopsy findings, 91 were retained after regression analysis and 22 appeared independently predictive for GPA.
The top five data-driven items had both c-ANCA and PR3-ANCA antibodies, bloody nasal discharge, nasal ulcers, crusting, or sinonasal congestion or blockage; a high (greater than 1 x 109/L) eosinophil count; and the presence of nasal polyps. There were also some clinical and data-driven items that were considered and used in a final nine-item model, Dr. Robson explained.
A point-based risk score was subsequently developed, with a total score of 5 or more suggesting GPA.
The presence of c-ANCA and PR3-ANCA antibodies, an almost certain indicator of GPA with an odds ratio of 134.8 (95% confidence interval, 62.4–291.1; P less than .001), was given the highest score of 5.
Having bloody or nasal discharge or other nasal symptoms or seeing a granuloma on biopsy were both given a score of 3. A score of 2 was awarded if there were nodules, a mass or cavity on chest imaging, or if there was cartilaginous involvement. A score of 1 was given if there was a loss or reduction in hearing or if the patient had red or painful eyes. Two items – the presence of a high eosinophil count and nasal polyps – were given negative scores (-3 and -4, respectively).
Dr. Robson reported that the nine-item model had an area under the curve of 0.98 and high sensitivity (90.7%) and specificity (93.5%).
Dr. Robson reported having no conflicts of interest.
BIRMINGHAM, ENGLAND – New criteria for classifying granulomatosis with polyangiitis (GPA) have been proposed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) .
GPA, a type of antineutrophil cytoplasmic antibody (ANCA)–associated systemic vasculitis, was formerly known as Wegener’s granulomatosis. When a small or medium vessel vasculitis has been diagnosed, the new criteria – which are provisional at present – are invoked to confirm the GPA diagnosis. Patients are assessed for five clinical and four laboratory variables.
The new criteria were developed as part of the Diagnostic and Classification of the Systemic Vasculitides (DCVAS) study. An international project set up to update the classification criteria for all types of systemic vasculitis, DCVAS involves more than 6,000 patients from 133 sites in 32 countries.
To develop the criteria for GPA, a team of 49 vasculitis experts was asked to review over 1, 400 clinical vignettes of newly diagnosed vasculitis based on cases submitted to the DCVAS. The expert panel was not told the suspected diagnosis. When the panel did not reach consensus on a case, it was further reviewed by seven members of the DCVAS study steering committee.
Using this approach, 85% of 578 cases submitted as GPA were confirmed. Compared with other vasculitides, GPA occurred in younger patients (53 vs. 58 years), was more likely to be proteinase 3–ANCA (81% vs. 3.4%) and c-ANCA (72% vs. 5.5%) positive, and was less likely to be p-ANCA (10.3% vs. 47.3%) and myeloperoxidase-antibody (8% vs. 59.3%) positive.
The next stage was to identify data-driven items that might be used to distinguish GPA from other vasculitides and obtain a clinical consensus on those that were the most important for a diagnosis. Of 1000 possible items that included clinical, laboratory, imaging, and biopsy findings, 91 were retained after regression analysis and 22 appeared independently predictive for GPA.
The top five data-driven items had both c-ANCA and PR3-ANCA antibodies, bloody nasal discharge, nasal ulcers, crusting, or sinonasal congestion or blockage; a high (greater than 1 x 109/L) eosinophil count; and the presence of nasal polyps. There were also some clinical and data-driven items that were considered and used in a final nine-item model, Dr. Robson explained.
A point-based risk score was subsequently developed, with a total score of 5 or more suggesting GPA.
The presence of c-ANCA and PR3-ANCA antibodies, an almost certain indicator of GPA with an odds ratio of 134.8 (95% confidence interval, 62.4–291.1; P less than .001), was given the highest score of 5.
Having bloody or nasal discharge or other nasal symptoms or seeing a granuloma on biopsy were both given a score of 3. A score of 2 was awarded if there were nodules, a mass or cavity on chest imaging, or if there was cartilaginous involvement. A score of 1 was given if there was a loss or reduction in hearing or if the patient had red or painful eyes. Two items – the presence of a high eosinophil count and nasal polyps – were given negative scores (-3 and -4, respectively).
Dr. Robson reported that the nine-item model had an area under the curve of 0.98 and high sensitivity (90.7%) and specificity (93.5%).
Dr. Robson reported having no conflicts of interest.
AT RHEUMATOLOGY 2017
Key clinical point: Provisional classification criteria have been developed to identify patients with granulomatosis with polyangiitis.
Major finding: The nine-item classification criteria model has an area under the curve of 0.98, with high sensitivity (90.7%) and specificity (93.5%).
Data source: More than 1,400 vasculitis cases submitted to the Diagnostic and Classification of the Systemic Vasculitides (DCVAS) study.
Disclosures: Dr. Robson reported having no conflicts of interest.
Opportunistic infection rates are low with biologics
BIRMINGHAM, ENGLAND – Patients being treated with biologics for rheumatoid arthritis have a low risk for developing opportunistic infections, based on a new analysis of data from one of the largest and longest running biologics registers.
Data on 19,162 patients included in the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) showed that the incidence rate of opportunistic infections was 1.33 cases per 1,000 patient years when using any biologic drug, including anti–tumor necrosis factor (anti-TNF) drugs, rituximab (Rituxan/MabThera), or the interleukin-6 receptor inhibitor tocilizumab (Actemra).
Incidence rates for opportunistic infections appeared to be lowest with tocilizumab at 0.88 per 1,000 patient years, although the duration of follow-up with this drug was the shortest. Rates for anti-TNF drugs as a whole and rituximab were a respective 1.30 and 1.58 per 1,000 patient years.
“Opportunistic infections remain very rare events,” said Dr. Andrew Rutherford, a rheumatology clinical fellow at King’s College London, England.
The potential for serious infections to develop with biologic treatment is well known, and several analyses have already been performed on the BSRBR-RA data, Dr. Rutherford acknowledged at the British Society for Rheumatology annual conference. However, these prior analyses have become somewhat outdated and don’t reflect current practice or the current cohort of patients starting biologic therapy, he said.
“Using the old comparator arm of continuing patients on DMARD [disease-modifying anti-rheumatic drug] therapy isn’t really relevant for us in clinical practice any more,” he said. “I think for the majority of us, when we’re faced with a patient who’s got high disease activity, we are going to start them on a biologic, and the question is ‘Which biologic is safest or most effective?’ as opposed to ‘Should they just remain on DMARDs?’ ”
Patients currently starting biologic treatments who are included in the Register are also less likely to have been treated with steroids and more likely to have been diagnosed with RA for less than 5 years. Then, there are the newer biologics, such as tocilizumab and even more recently the Janus kinase (JAK) inhibitors.
“So, I think, clearly, there is a need to do updated analyses using the BSRBR,” Dr. Rutherford reasoned.
In the current analysis, which covers more than 99,000 patient years of follow-up overall, the primary aim was to estimate the incidence of opportunistic infections other than tuberculosis (TB) by biologic drug class.
Of 106 cases of opportunistic infections seen in patients treated with anti-TNF drugs, most (48%) resulted from herpes zoster, Pneumocystis pneumonia (PCP; 11.3%), or Aspergillus (11.3%).
There were 24 opportunistic infections in patients treated with rituximab, of which PCP (33.3%) or herpes zoster (29%) were the most common causes.
There were just three opportunistic infections in patients treated with tocilizumab, which were all different organisms, Dr. Rutherford reported.
Using anti-TNF therapy as the control, the unadjusted and adjusted hazard ratios for an opportunistic infection were a respective 1.21 and 0.92 for rituximab and 0.60 and 0.28 for tocilizumab. The confidence intervals were wide, however, crossing 1.0 in all comparisons, Dr. Rutherford emphasized.
PCP is rare with all biologics, but the incidence was almost four-times higher (HR, 3.91) with rituximab versus anti-TNF therapy, but the 95% CIs were wide (1.60–9.92) and probably not enough to influence practice.
A secondary analysis also looked at the incidence of TB by biologic drug class, although this was originally excluded from the study design. Not only has it been previously reported on from BSRBR, “guidelines have come into place that have probably changed the rates of TB dramatically over the years,” Dr. Rutherford said, so comparing older and new cohorts of biologic-treated patients might be “a little bit unfair.”
The incidence of TB per 100,000 patient years was 67.8 for all anti-TNF therapies, with a lower rate seen with rituximab (13.2 per 100,000 patient years) than any individual anti-TNF drug (48.9 for etanercept, 75.5 for infliximab, 84.6 for adalimumab, and 99.0 for certolizumab per 100,000 patient years).
These rates might potentially influence the choice of drug for a patient with a high-risk for reactivation of TB, Dr. Rutherford suggested.
Overall, rates of TB have fallen year over year in the Register. However, that likely reflects better screening and treatment of the infection, he added.
The BSRBR-RA is funded by the BSR through restricted grants from UK pharmaceutical companies. Past and present participating companies include Abbvie, Celltrion, Hospira, Pfizer, UCB, Roche, Merck and Samsung. Dr. Rutherford had no conflicts of interest.
BIRMINGHAM, ENGLAND – Patients being treated with biologics for rheumatoid arthritis have a low risk for developing opportunistic infections, based on a new analysis of data from one of the largest and longest running biologics registers.
Data on 19,162 patients included in the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) showed that the incidence rate of opportunistic infections was 1.33 cases per 1,000 patient years when using any biologic drug, including anti–tumor necrosis factor (anti-TNF) drugs, rituximab (Rituxan/MabThera), or the interleukin-6 receptor inhibitor tocilizumab (Actemra).
Incidence rates for opportunistic infections appeared to be lowest with tocilizumab at 0.88 per 1,000 patient years, although the duration of follow-up with this drug was the shortest. Rates for anti-TNF drugs as a whole and rituximab were a respective 1.30 and 1.58 per 1,000 patient years.
“Opportunistic infections remain very rare events,” said Dr. Andrew Rutherford, a rheumatology clinical fellow at King’s College London, England.
The potential for serious infections to develop with biologic treatment is well known, and several analyses have already been performed on the BSRBR-RA data, Dr. Rutherford acknowledged at the British Society for Rheumatology annual conference. However, these prior analyses have become somewhat outdated and don’t reflect current practice or the current cohort of patients starting biologic therapy, he said.
“Using the old comparator arm of continuing patients on DMARD [disease-modifying anti-rheumatic drug] therapy isn’t really relevant for us in clinical practice any more,” he said. “I think for the majority of us, when we’re faced with a patient who’s got high disease activity, we are going to start them on a biologic, and the question is ‘Which biologic is safest or most effective?’ as opposed to ‘Should they just remain on DMARDs?’ ”
Patients currently starting biologic treatments who are included in the Register are also less likely to have been treated with steroids and more likely to have been diagnosed with RA for less than 5 years. Then, there are the newer biologics, such as tocilizumab and even more recently the Janus kinase (JAK) inhibitors.
“So, I think, clearly, there is a need to do updated analyses using the BSRBR,” Dr. Rutherford reasoned.
In the current analysis, which covers more than 99,000 patient years of follow-up overall, the primary aim was to estimate the incidence of opportunistic infections other than tuberculosis (TB) by biologic drug class.
Of 106 cases of opportunistic infections seen in patients treated with anti-TNF drugs, most (48%) resulted from herpes zoster, Pneumocystis pneumonia (PCP; 11.3%), or Aspergillus (11.3%).
There were 24 opportunistic infections in patients treated with rituximab, of which PCP (33.3%) or herpes zoster (29%) were the most common causes.
There were just three opportunistic infections in patients treated with tocilizumab, which were all different organisms, Dr. Rutherford reported.
Using anti-TNF therapy as the control, the unadjusted and adjusted hazard ratios for an opportunistic infection were a respective 1.21 and 0.92 for rituximab and 0.60 and 0.28 for tocilizumab. The confidence intervals were wide, however, crossing 1.0 in all comparisons, Dr. Rutherford emphasized.
PCP is rare with all biologics, but the incidence was almost four-times higher (HR, 3.91) with rituximab versus anti-TNF therapy, but the 95% CIs were wide (1.60–9.92) and probably not enough to influence practice.
A secondary analysis also looked at the incidence of TB by biologic drug class, although this was originally excluded from the study design. Not only has it been previously reported on from BSRBR, “guidelines have come into place that have probably changed the rates of TB dramatically over the years,” Dr. Rutherford said, so comparing older and new cohorts of biologic-treated patients might be “a little bit unfair.”
The incidence of TB per 100,000 patient years was 67.8 for all anti-TNF therapies, with a lower rate seen with rituximab (13.2 per 100,000 patient years) than any individual anti-TNF drug (48.9 for etanercept, 75.5 for infliximab, 84.6 for adalimumab, and 99.0 for certolizumab per 100,000 patient years).
These rates might potentially influence the choice of drug for a patient with a high-risk for reactivation of TB, Dr. Rutherford suggested.
Overall, rates of TB have fallen year over year in the Register. However, that likely reflects better screening and treatment of the infection, he added.
The BSRBR-RA is funded by the BSR through restricted grants from UK pharmaceutical companies. Past and present participating companies include Abbvie, Celltrion, Hospira, Pfizer, UCB, Roche, Merck and Samsung. Dr. Rutherford had no conflicts of interest.
BIRMINGHAM, ENGLAND – Patients being treated with biologics for rheumatoid arthritis have a low risk for developing opportunistic infections, based on a new analysis of data from one of the largest and longest running biologics registers.
Data on 19,162 patients included in the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) showed that the incidence rate of opportunistic infections was 1.33 cases per 1,000 patient years when using any biologic drug, including anti–tumor necrosis factor (anti-TNF) drugs, rituximab (Rituxan/MabThera), or the interleukin-6 receptor inhibitor tocilizumab (Actemra).
Incidence rates for opportunistic infections appeared to be lowest with tocilizumab at 0.88 per 1,000 patient years, although the duration of follow-up with this drug was the shortest. Rates for anti-TNF drugs as a whole and rituximab were a respective 1.30 and 1.58 per 1,000 patient years.
“Opportunistic infections remain very rare events,” said Dr. Andrew Rutherford, a rheumatology clinical fellow at King’s College London, England.
The potential for serious infections to develop with biologic treatment is well known, and several analyses have already been performed on the BSRBR-RA data, Dr. Rutherford acknowledged at the British Society for Rheumatology annual conference. However, these prior analyses have become somewhat outdated and don’t reflect current practice or the current cohort of patients starting biologic therapy, he said.
“Using the old comparator arm of continuing patients on DMARD [disease-modifying anti-rheumatic drug] therapy isn’t really relevant for us in clinical practice any more,” he said. “I think for the majority of us, when we’re faced with a patient who’s got high disease activity, we are going to start them on a biologic, and the question is ‘Which biologic is safest or most effective?’ as opposed to ‘Should they just remain on DMARDs?’ ”
Patients currently starting biologic treatments who are included in the Register are also less likely to have been treated with steroids and more likely to have been diagnosed with RA for less than 5 years. Then, there are the newer biologics, such as tocilizumab and even more recently the Janus kinase (JAK) inhibitors.
“So, I think, clearly, there is a need to do updated analyses using the BSRBR,” Dr. Rutherford reasoned.
In the current analysis, which covers more than 99,000 patient years of follow-up overall, the primary aim was to estimate the incidence of opportunistic infections other than tuberculosis (TB) by biologic drug class.
Of 106 cases of opportunistic infections seen in patients treated with anti-TNF drugs, most (48%) resulted from herpes zoster, Pneumocystis pneumonia (PCP; 11.3%), or Aspergillus (11.3%).
There were 24 opportunistic infections in patients treated with rituximab, of which PCP (33.3%) or herpes zoster (29%) were the most common causes.
There were just three opportunistic infections in patients treated with tocilizumab, which were all different organisms, Dr. Rutherford reported.
Using anti-TNF therapy as the control, the unadjusted and adjusted hazard ratios for an opportunistic infection were a respective 1.21 and 0.92 for rituximab and 0.60 and 0.28 for tocilizumab. The confidence intervals were wide, however, crossing 1.0 in all comparisons, Dr. Rutherford emphasized.
PCP is rare with all biologics, but the incidence was almost four-times higher (HR, 3.91) with rituximab versus anti-TNF therapy, but the 95% CIs were wide (1.60–9.92) and probably not enough to influence practice.
A secondary analysis also looked at the incidence of TB by biologic drug class, although this was originally excluded from the study design. Not only has it been previously reported on from BSRBR, “guidelines have come into place that have probably changed the rates of TB dramatically over the years,” Dr. Rutherford said, so comparing older and new cohorts of biologic-treated patients might be “a little bit unfair.”
The incidence of TB per 100,000 patient years was 67.8 for all anti-TNF therapies, with a lower rate seen with rituximab (13.2 per 100,000 patient years) than any individual anti-TNF drug (48.9 for etanercept, 75.5 for infliximab, 84.6 for adalimumab, and 99.0 for certolizumab per 100,000 patient years).
These rates might potentially influence the choice of drug for a patient with a high-risk for reactivation of TB, Dr. Rutherford suggested.
Overall, rates of TB have fallen year over year in the Register. However, that likely reflects better screening and treatment of the infection, he added.
The BSRBR-RA is funded by the BSR through restricted grants from UK pharmaceutical companies. Past and present participating companies include Abbvie, Celltrion, Hospira, Pfizer, UCB, Roche, Merck and Samsung. Dr. Rutherford had no conflicts of interest.
AT RHEUMATOLOGY 2017
Key clinical point: Opportunistic infections rarely occur in patients being treated with biologic drugs for rheumatoid arthritis.
Major finding: The unadjusted rate for opportunistic infections was 1.33 per 1000 patient years for all biologics.
Data source: 19,162 patient records held within the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA).
Disclosures: The BSRBR-RA is funded by the BSR through restricted grants from UK pharmaceutical companies. Past and present participating companies include Abbvie, Celltrion, Hospira, Pfizer, UCB, Roche, Merck and Samsung. Dr. Rutherford did not provide disclosures.
Fibromyalgia may affect one in five with ankylosing spondylitis
BIRMINGHAM, ENGLAND – One in five people with ankylosing spondylitis could have comorbid fibromyalgia, according to data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS).
The analysis, which included more than 880 patients with axial spondyloarthritis (SpA), found that 20.7% met 2011 research criteria for the chronic pain condition.
The prevalence of fibromyalgia was similar when the modified New York (mNY) criteria were used to diagnose SpA, at 19.7%, but slightly higher at 25.2% when SpA patients met the Assessment of SpondyloArthritis international Society (ASAS) imaging criteria but not mNY criteria, and substantially lower at 9.5% when SpA patients met ASAS clinical criteria only.
Dr. Macfarlane, chief investigator of the BSRBR-AS and professor and chair of clinical epidemiology at the University of Aberdeen (Scotland), added that having comorbid fibromyalgia might “distort the responses of some of the key patient-reported measures and that may lead to some patients having inappropriate therapy.”
So the aim of the present analysis was to provide data on the frequency of SpA and fibromyalgia co-occurrence, characterize which patients might be more likely to have both conditions, and also provide information that would inform future studies looking at the optimal management of such patients.
“The patients most likely to meet fibromyalgia criteria were female, either HLA-B27 negative or untested, and there was a particularly strong association with higher levels of [social] deprivation,” Dr. Macfarlane reported.
Patients who had both SpA and fibromyalgia also were found to be more likely to have been treated with a biologic than those who had SpA alone (51% vs. 32%), and there also was an associated with the time missed (15.1% vs. 2.5%) or impaired (50.8% vs. 22.8%) at work.
In a comparison of the characteristics of patients with SpA who met the fibromyalgia research criteria with those who did not, Dr. Macfarlane observed that they had worse disease activity, function, metrology, and global scores as measured using Bath Ankylosing Spondylitis disease indices:
• Disease activity scores were a respective 6.7 and 3.6, giving a difference of 3.1 (95% confidence interval, 2.9-3.3).
• Function scores were a respective 6.6 and 3.7, with a difference of 2.9 (95% CI, 2.6-3.3).
• Metrology scores were a respective 4.2 and 3.6, with a difference of 0.6 (95% CI, 0.3-0.9).
• Global scores were a respective 6.9 and 3.7, with a different of 3.2 (95% CI, 2.9-3.6).
Dr. Macfarlane reported that there were “extremely large differences” on the patient-reported measures of quality of life, depression, and anxiety. Other common problems in the group meeting the fibromyalgia criteria were sleeping difficulties and high levels of fatigue, he said.
Patients with both SpA and fibromyalgia fared worse on quality of life scores measured using the disease-specific Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire where they scored a mean of 7.1 points (95% CI, 6.4-7.7) higher than did those with SpA alone.
The mean differences in depression and anxiety, both measured using the Hospital Anxiety and Depression Scale (HADS), was 4.8 (95% CI, 4.3-5.2) and 4.7 (95% CI, 4.1-5.2).
The mean difference in the sleep disturbance scale was 5.3 (95% CI, 4.5-6.0), and the mean difference in Chalder Fatigue Scale scores was 4.0 (95% CI, 3.5-4.4).
In contrast, there was no difference in the proportion of patients who had levels of C-reactive protein above 1 mg/dL or in the number of proportion of patients who had extraspinal manifestations of SpA, with the exception of tender or swollen joint counts.
Dr. Macfarlane noted that the fibromyalgia research criteria had not been validated for use in patients with axial SpA but that a grant had been awarded by Arthritis Research UK to look at this and also to look into optimizing options for managing patients with both conditions.
The BSRBR-AS is currently the newest of the biologics registries and began recruiting patients with axial SpA as of December 2012 from 82 centers across the United Kingdom. The register enrolls patients who have not previously been treated with a tumor necrosis factor inhibitor drug and are then followed-up for a 5-year period. The 2011 fibromyalgia research criteria have been used as part of the baseline assessment since September 2015, and clinicians also are asked to report whether they think that patients have fibromyalgia.
The BSRBR-AS is funded by the British Society for Rheumatology, which receives funds from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not report having any conflicts of interest.
BIRMINGHAM, ENGLAND – One in five people with ankylosing spondylitis could have comorbid fibromyalgia, according to data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS).
The analysis, which included more than 880 patients with axial spondyloarthritis (SpA), found that 20.7% met 2011 research criteria for the chronic pain condition.
The prevalence of fibromyalgia was similar when the modified New York (mNY) criteria were used to diagnose SpA, at 19.7%, but slightly higher at 25.2% when SpA patients met the Assessment of SpondyloArthritis international Society (ASAS) imaging criteria but not mNY criteria, and substantially lower at 9.5% when SpA patients met ASAS clinical criteria only.
Dr. Macfarlane, chief investigator of the BSRBR-AS and professor and chair of clinical epidemiology at the University of Aberdeen (Scotland), added that having comorbid fibromyalgia might “distort the responses of some of the key patient-reported measures and that may lead to some patients having inappropriate therapy.”
So the aim of the present analysis was to provide data on the frequency of SpA and fibromyalgia co-occurrence, characterize which patients might be more likely to have both conditions, and also provide information that would inform future studies looking at the optimal management of such patients.
“The patients most likely to meet fibromyalgia criteria were female, either HLA-B27 negative or untested, and there was a particularly strong association with higher levels of [social] deprivation,” Dr. Macfarlane reported.
Patients who had both SpA and fibromyalgia also were found to be more likely to have been treated with a biologic than those who had SpA alone (51% vs. 32%), and there also was an associated with the time missed (15.1% vs. 2.5%) or impaired (50.8% vs. 22.8%) at work.
In a comparison of the characteristics of patients with SpA who met the fibromyalgia research criteria with those who did not, Dr. Macfarlane observed that they had worse disease activity, function, metrology, and global scores as measured using Bath Ankylosing Spondylitis disease indices:
• Disease activity scores were a respective 6.7 and 3.6, giving a difference of 3.1 (95% confidence interval, 2.9-3.3).
• Function scores were a respective 6.6 and 3.7, with a difference of 2.9 (95% CI, 2.6-3.3).
• Metrology scores were a respective 4.2 and 3.6, with a difference of 0.6 (95% CI, 0.3-0.9).
• Global scores were a respective 6.9 and 3.7, with a different of 3.2 (95% CI, 2.9-3.6).
Dr. Macfarlane reported that there were “extremely large differences” on the patient-reported measures of quality of life, depression, and anxiety. Other common problems in the group meeting the fibromyalgia criteria were sleeping difficulties and high levels of fatigue, he said.
Patients with both SpA and fibromyalgia fared worse on quality of life scores measured using the disease-specific Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire where they scored a mean of 7.1 points (95% CI, 6.4-7.7) higher than did those with SpA alone.
The mean differences in depression and anxiety, both measured using the Hospital Anxiety and Depression Scale (HADS), was 4.8 (95% CI, 4.3-5.2) and 4.7 (95% CI, 4.1-5.2).
The mean difference in the sleep disturbance scale was 5.3 (95% CI, 4.5-6.0), and the mean difference in Chalder Fatigue Scale scores was 4.0 (95% CI, 3.5-4.4).
In contrast, there was no difference in the proportion of patients who had levels of C-reactive protein above 1 mg/dL or in the number of proportion of patients who had extraspinal manifestations of SpA, with the exception of tender or swollen joint counts.
Dr. Macfarlane noted that the fibromyalgia research criteria had not been validated for use in patients with axial SpA but that a grant had been awarded by Arthritis Research UK to look at this and also to look into optimizing options for managing patients with both conditions.
The BSRBR-AS is currently the newest of the biologics registries and began recruiting patients with axial SpA as of December 2012 from 82 centers across the United Kingdom. The register enrolls patients who have not previously been treated with a tumor necrosis factor inhibitor drug and are then followed-up for a 5-year period. The 2011 fibromyalgia research criteria have been used as part of the baseline assessment since September 2015, and clinicians also are asked to report whether they think that patients have fibromyalgia.
The BSRBR-AS is funded by the British Society for Rheumatology, which receives funds from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not report having any conflicts of interest.
BIRMINGHAM, ENGLAND – One in five people with ankylosing spondylitis could have comorbid fibromyalgia, according to data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS).
The analysis, which included more than 880 patients with axial spondyloarthritis (SpA), found that 20.7% met 2011 research criteria for the chronic pain condition.
The prevalence of fibromyalgia was similar when the modified New York (mNY) criteria were used to diagnose SpA, at 19.7%, but slightly higher at 25.2% when SpA patients met the Assessment of SpondyloArthritis international Society (ASAS) imaging criteria but not mNY criteria, and substantially lower at 9.5% when SpA patients met ASAS clinical criteria only.
Dr. Macfarlane, chief investigator of the BSRBR-AS and professor and chair of clinical epidemiology at the University of Aberdeen (Scotland), added that having comorbid fibromyalgia might “distort the responses of some of the key patient-reported measures and that may lead to some patients having inappropriate therapy.”
So the aim of the present analysis was to provide data on the frequency of SpA and fibromyalgia co-occurrence, characterize which patients might be more likely to have both conditions, and also provide information that would inform future studies looking at the optimal management of such patients.
“The patients most likely to meet fibromyalgia criteria were female, either HLA-B27 negative or untested, and there was a particularly strong association with higher levels of [social] deprivation,” Dr. Macfarlane reported.
Patients who had both SpA and fibromyalgia also were found to be more likely to have been treated with a biologic than those who had SpA alone (51% vs. 32%), and there also was an associated with the time missed (15.1% vs. 2.5%) or impaired (50.8% vs. 22.8%) at work.
In a comparison of the characteristics of patients with SpA who met the fibromyalgia research criteria with those who did not, Dr. Macfarlane observed that they had worse disease activity, function, metrology, and global scores as measured using Bath Ankylosing Spondylitis disease indices:
• Disease activity scores were a respective 6.7 and 3.6, giving a difference of 3.1 (95% confidence interval, 2.9-3.3).
• Function scores were a respective 6.6 and 3.7, with a difference of 2.9 (95% CI, 2.6-3.3).
• Metrology scores were a respective 4.2 and 3.6, with a difference of 0.6 (95% CI, 0.3-0.9).
• Global scores were a respective 6.9 and 3.7, with a different of 3.2 (95% CI, 2.9-3.6).
Dr. Macfarlane reported that there were “extremely large differences” on the patient-reported measures of quality of life, depression, and anxiety. Other common problems in the group meeting the fibromyalgia criteria were sleeping difficulties and high levels of fatigue, he said.
Patients with both SpA and fibromyalgia fared worse on quality of life scores measured using the disease-specific Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire where they scored a mean of 7.1 points (95% CI, 6.4-7.7) higher than did those with SpA alone.
The mean differences in depression and anxiety, both measured using the Hospital Anxiety and Depression Scale (HADS), was 4.8 (95% CI, 4.3-5.2) and 4.7 (95% CI, 4.1-5.2).
The mean difference in the sleep disturbance scale was 5.3 (95% CI, 4.5-6.0), and the mean difference in Chalder Fatigue Scale scores was 4.0 (95% CI, 3.5-4.4).
In contrast, there was no difference in the proportion of patients who had levels of C-reactive protein above 1 mg/dL or in the number of proportion of patients who had extraspinal manifestations of SpA, with the exception of tender or swollen joint counts.
Dr. Macfarlane noted that the fibromyalgia research criteria had not been validated for use in patients with axial SpA but that a grant had been awarded by Arthritis Research UK to look at this and also to look into optimizing options for managing patients with both conditions.
The BSRBR-AS is currently the newest of the biologics registries and began recruiting patients with axial SpA as of December 2012 from 82 centers across the United Kingdom. The register enrolls patients who have not previously been treated with a tumor necrosis factor inhibitor drug and are then followed-up for a 5-year period. The 2011 fibromyalgia research criteria have been used as part of the baseline assessment since September 2015, and clinicians also are asked to report whether they think that patients have fibromyalgia.
The BSRBR-AS is funded by the British Society for Rheumatology, which receives funds from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not report having any conflicts of interest.
AT RHEUMATOLOGY 2017
Key clinical point:
Major finding: Of more than 880 patients with axial SpA, 20.7% met 2011 research criteria for the chronic pain condition.
Data source: British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS).
Disclosures: The BSRBR-AS is funded by the British Society for Rheumatology, which receives funds from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not report having any conflicts of interest.
Sarilumab showed sustained effect on RA progression at 3 years
BIRMINGHAM, ENGLAND – A “durable clinical response and stabilization of structural damage” was observed at 3 years of follow-up in the Long Term Evaluation of Sarilumab in Rheumatoid Arthritis Patients (SARIL-RA-EXTEND) study.
Désirée van der Heijde, MD, PhD, who reported the findings of the EXTEND study at the British Society for Rheumatology annual conference, noted that the benefit was seen regardless of the initial treatment that had been given at baseline.
The aim of the EXTEND trial was to examine the continuity of response to sarilumab seen in the MOBILITY trial, said Dr. van der Heijde, professor of rheumatology at Leiden (The Netherlands) University Medical Center.
Sarilumab is a fully human (IgG1) monoclonal antibody that binds to interleukin (IL)-6 receptors, both soluble and membrane-bound, and thus inhibits IL-6-mediated signaling through the soluble IL-6R alpha and membrane-bound IL-6R alpha receptors. It is undergoing regulatory approval in the United States, European Union, and Japan, but was recently approved in Canada for treatment of adult patients with moderate to severe rheumatoid arthritis (RA) who have had an inadequate response to one or more biologic or nonbiologic disease-modifying antirheumatic drugs (DMARDs) (Drugs. 2017;77:705-12).
In the MOBILITY trial, 1,197 patients who were being treated with methotrexate but who had an inadequate response were randomized to receive placebo (n = 398) or sarilumab given subcutaneously every 2 weeks at one of two doses: 150 mg (n = 400) or 200 mg (n = 399).
EXTEND allowed patients completing this trial who still had active disease to continue or start (if they had been given placebo) treatment with sarilumab at a dose of 200 mg given every 2 weeks, with dose reduction to 150 mg every 2 weeks if needed, in addition to methotrexate. A total of 901 patients participated in the extension study.
“In the MOBILITY trial, all three groups were very balanced, and if you then take the patients who entered the EXTEND trial, they are very similar to the patients who also were randomized into MOBILITY,” Dr. van der Heijde said.
This was a fairly typical RA population, she observed: About 80% were female, the mean age was 50 years, and the mean duration of RA was 9 years. About 20%-25% had prior treatment with a DMARD, more than 80% were rheumatoid factor or anti-CCP antibody positive. There were similar mean C-reactive protein (CRP) levels between the groups, and the 28-joint disease activity score (DAS28) with CRP was around 6, and Clinical Disease Activity Index (CDAI) score around 40.
Radiographs that were taken at baseline, at the end of year 2, and at the end of year 3 were reread by two independent readers and scored together in one session. Data had to be extrapolated for 29 patients who did not have a radiographs taken at year 3 but who had been seen during the third year of treatment.
The significant radiographic inhibition seen at the end of the MOBILITY trial in both the 150-mg and 200-mg active treatment groups was sustained in the EXTEND study.
“There is a small progression between year 2 and 3, and this progression is quite similar in all the three treatment arms,” Dr. van der Heijde reported, nothing that all patients were taking 200 mg of sarilumab at this point.
The mean change in the modified total Sharp score (mTSS) from year 2 to 3 was 0.35 in the patients who had originally been randomized to the placebo arm, 0.64 in patients originally randomized to 150 mg sarilumab every 2 weeks, and 0.44 in those originally taking 200 mg sarilumab every 2 weeks.
From baseline to year 3, the mean change in mTSS were a respective 3.3, 1.9, and 0.8.
“If you present the data in a different way, like the percentage of patients showing no progression, you see the differentiation between the patients who started on placebo versus those who were started on sarilumab 150 mg or 200 mg,” said Dr. van der Heijde.
At year 2, 67%, 59%, and 48% of patients treated with sarilumab 200 mg, sarilumab 150 mg, or placebo, respectively had no progression in mTSS (signified by a change from baseline of 0.5 points or more).
At year 3, corresponding rates were a respective 75%, 55%, and 49%.
DAS-28-CRP response at year 3 was similar across the initial treatment groups, Dr. van der Heijde observed. Reductions seen in the MOBILITY trial were clearly continued, she said. The percentage of patients achieving DAS-28-CRP of less than 2.6 was 22%, 34%, and 36% of placebo, sarilumab 150-mg, and sarilumab 200-mg treated patients at the end of the MOBILITY study. At the end of year 2, the corresponding numbers were 60%, 62%, and 62%, and by year 3, not much had changed in the percentage of patients achieving DAS-28-CRP of less than 2.6: 58% for placebo, 62% for sarilumab 150 mg, and 68% for sarilumab 200 mg.
Similar results were seen for patients achieving a CDAI of 2.8 or lower at years 2 and 3 in the extension study.
Treatment-emergent adverse events (TEAEs) occurred in 89.7% of patients over 3 years. One in five (20%) patients experienced serious adverse events, with 23% of patients discontinuing treatment because of TEAEs. There were 9 (0.8%) deaths during the trial.
TEAEs that occurred at rates of 5% or higher in any treatment group were neutropenia in 19.4%, increased alanine aminotransferase in 13.0%, and upper respiratory tract infections in 12.7%.
There were some changes in laboratory values, Dr. van der Heijde said, but “most of the changes were very small” and in line with the effects expected with IL-6 inhibition.
The study was sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals. Dr. van der Heijde and coauthors disclosed receiving consulting fees, research grants, or both from multiple pharmaceutical companies, including the sponsors of the study. Dr. van der Heijde is director of Imaging Rheumatology.
BIRMINGHAM, ENGLAND – A “durable clinical response and stabilization of structural damage” was observed at 3 years of follow-up in the Long Term Evaluation of Sarilumab in Rheumatoid Arthritis Patients (SARIL-RA-EXTEND) study.
Désirée van der Heijde, MD, PhD, who reported the findings of the EXTEND study at the British Society for Rheumatology annual conference, noted that the benefit was seen regardless of the initial treatment that had been given at baseline.
The aim of the EXTEND trial was to examine the continuity of response to sarilumab seen in the MOBILITY trial, said Dr. van der Heijde, professor of rheumatology at Leiden (The Netherlands) University Medical Center.
Sarilumab is a fully human (IgG1) monoclonal antibody that binds to interleukin (IL)-6 receptors, both soluble and membrane-bound, and thus inhibits IL-6-mediated signaling through the soluble IL-6R alpha and membrane-bound IL-6R alpha receptors. It is undergoing regulatory approval in the United States, European Union, and Japan, but was recently approved in Canada for treatment of adult patients with moderate to severe rheumatoid arthritis (RA) who have had an inadequate response to one or more biologic or nonbiologic disease-modifying antirheumatic drugs (DMARDs) (Drugs. 2017;77:705-12).
In the MOBILITY trial, 1,197 patients who were being treated with methotrexate but who had an inadequate response were randomized to receive placebo (n = 398) or sarilumab given subcutaneously every 2 weeks at one of two doses: 150 mg (n = 400) or 200 mg (n = 399).
EXTEND allowed patients completing this trial who still had active disease to continue or start (if they had been given placebo) treatment with sarilumab at a dose of 200 mg given every 2 weeks, with dose reduction to 150 mg every 2 weeks if needed, in addition to methotrexate. A total of 901 patients participated in the extension study.
“In the MOBILITY trial, all three groups were very balanced, and if you then take the patients who entered the EXTEND trial, they are very similar to the patients who also were randomized into MOBILITY,” Dr. van der Heijde said.
This was a fairly typical RA population, she observed: About 80% were female, the mean age was 50 years, and the mean duration of RA was 9 years. About 20%-25% had prior treatment with a DMARD, more than 80% were rheumatoid factor or anti-CCP antibody positive. There were similar mean C-reactive protein (CRP) levels between the groups, and the 28-joint disease activity score (DAS28) with CRP was around 6, and Clinical Disease Activity Index (CDAI) score around 40.
Radiographs that were taken at baseline, at the end of year 2, and at the end of year 3 were reread by two independent readers and scored together in one session. Data had to be extrapolated for 29 patients who did not have a radiographs taken at year 3 but who had been seen during the third year of treatment.
The significant radiographic inhibition seen at the end of the MOBILITY trial in both the 150-mg and 200-mg active treatment groups was sustained in the EXTEND study.
“There is a small progression between year 2 and 3, and this progression is quite similar in all the three treatment arms,” Dr. van der Heijde reported, nothing that all patients were taking 200 mg of sarilumab at this point.
The mean change in the modified total Sharp score (mTSS) from year 2 to 3 was 0.35 in the patients who had originally been randomized to the placebo arm, 0.64 in patients originally randomized to 150 mg sarilumab every 2 weeks, and 0.44 in those originally taking 200 mg sarilumab every 2 weeks.
From baseline to year 3, the mean change in mTSS were a respective 3.3, 1.9, and 0.8.
“If you present the data in a different way, like the percentage of patients showing no progression, you see the differentiation between the patients who started on placebo versus those who were started on sarilumab 150 mg or 200 mg,” said Dr. van der Heijde.
At year 2, 67%, 59%, and 48% of patients treated with sarilumab 200 mg, sarilumab 150 mg, or placebo, respectively had no progression in mTSS (signified by a change from baseline of 0.5 points or more).
At year 3, corresponding rates were a respective 75%, 55%, and 49%.
DAS-28-CRP response at year 3 was similar across the initial treatment groups, Dr. van der Heijde observed. Reductions seen in the MOBILITY trial were clearly continued, she said. The percentage of patients achieving DAS-28-CRP of less than 2.6 was 22%, 34%, and 36% of placebo, sarilumab 150-mg, and sarilumab 200-mg treated patients at the end of the MOBILITY study. At the end of year 2, the corresponding numbers were 60%, 62%, and 62%, and by year 3, not much had changed in the percentage of patients achieving DAS-28-CRP of less than 2.6: 58% for placebo, 62% for sarilumab 150 mg, and 68% for sarilumab 200 mg.
Similar results were seen for patients achieving a CDAI of 2.8 or lower at years 2 and 3 in the extension study.
Treatment-emergent adverse events (TEAEs) occurred in 89.7% of patients over 3 years. One in five (20%) patients experienced serious adverse events, with 23% of patients discontinuing treatment because of TEAEs. There were 9 (0.8%) deaths during the trial.
TEAEs that occurred at rates of 5% or higher in any treatment group were neutropenia in 19.4%, increased alanine aminotransferase in 13.0%, and upper respiratory tract infections in 12.7%.
There were some changes in laboratory values, Dr. van der Heijde said, but “most of the changes were very small” and in line with the effects expected with IL-6 inhibition.
The study was sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals. Dr. van der Heijde and coauthors disclosed receiving consulting fees, research grants, or both from multiple pharmaceutical companies, including the sponsors of the study. Dr. van der Heijde is director of Imaging Rheumatology.
BIRMINGHAM, ENGLAND – A “durable clinical response and stabilization of structural damage” was observed at 3 years of follow-up in the Long Term Evaluation of Sarilumab in Rheumatoid Arthritis Patients (SARIL-RA-EXTEND) study.
Désirée van der Heijde, MD, PhD, who reported the findings of the EXTEND study at the British Society for Rheumatology annual conference, noted that the benefit was seen regardless of the initial treatment that had been given at baseline.
The aim of the EXTEND trial was to examine the continuity of response to sarilumab seen in the MOBILITY trial, said Dr. van der Heijde, professor of rheumatology at Leiden (The Netherlands) University Medical Center.
Sarilumab is a fully human (IgG1) monoclonal antibody that binds to interleukin (IL)-6 receptors, both soluble and membrane-bound, and thus inhibits IL-6-mediated signaling through the soluble IL-6R alpha and membrane-bound IL-6R alpha receptors. It is undergoing regulatory approval in the United States, European Union, and Japan, but was recently approved in Canada for treatment of adult patients with moderate to severe rheumatoid arthritis (RA) who have had an inadequate response to one or more biologic or nonbiologic disease-modifying antirheumatic drugs (DMARDs) (Drugs. 2017;77:705-12).
In the MOBILITY trial, 1,197 patients who were being treated with methotrexate but who had an inadequate response were randomized to receive placebo (n = 398) or sarilumab given subcutaneously every 2 weeks at one of two doses: 150 mg (n = 400) or 200 mg (n = 399).
EXTEND allowed patients completing this trial who still had active disease to continue or start (if they had been given placebo) treatment with sarilumab at a dose of 200 mg given every 2 weeks, with dose reduction to 150 mg every 2 weeks if needed, in addition to methotrexate. A total of 901 patients participated in the extension study.
“In the MOBILITY trial, all three groups were very balanced, and if you then take the patients who entered the EXTEND trial, they are very similar to the patients who also were randomized into MOBILITY,” Dr. van der Heijde said.
This was a fairly typical RA population, she observed: About 80% were female, the mean age was 50 years, and the mean duration of RA was 9 years. About 20%-25% had prior treatment with a DMARD, more than 80% were rheumatoid factor or anti-CCP antibody positive. There were similar mean C-reactive protein (CRP) levels between the groups, and the 28-joint disease activity score (DAS28) with CRP was around 6, and Clinical Disease Activity Index (CDAI) score around 40.
Radiographs that were taken at baseline, at the end of year 2, and at the end of year 3 were reread by two independent readers and scored together in one session. Data had to be extrapolated for 29 patients who did not have a radiographs taken at year 3 but who had been seen during the third year of treatment.
The significant radiographic inhibition seen at the end of the MOBILITY trial in both the 150-mg and 200-mg active treatment groups was sustained in the EXTEND study.
“There is a small progression between year 2 and 3, and this progression is quite similar in all the three treatment arms,” Dr. van der Heijde reported, nothing that all patients were taking 200 mg of sarilumab at this point.
The mean change in the modified total Sharp score (mTSS) from year 2 to 3 was 0.35 in the patients who had originally been randomized to the placebo arm, 0.64 in patients originally randomized to 150 mg sarilumab every 2 weeks, and 0.44 in those originally taking 200 mg sarilumab every 2 weeks.
From baseline to year 3, the mean change in mTSS were a respective 3.3, 1.9, and 0.8.
“If you present the data in a different way, like the percentage of patients showing no progression, you see the differentiation between the patients who started on placebo versus those who were started on sarilumab 150 mg or 200 mg,” said Dr. van der Heijde.
At year 2, 67%, 59%, and 48% of patients treated with sarilumab 200 mg, sarilumab 150 mg, or placebo, respectively had no progression in mTSS (signified by a change from baseline of 0.5 points or more).
At year 3, corresponding rates were a respective 75%, 55%, and 49%.
DAS-28-CRP response at year 3 was similar across the initial treatment groups, Dr. van der Heijde observed. Reductions seen in the MOBILITY trial were clearly continued, she said. The percentage of patients achieving DAS-28-CRP of less than 2.6 was 22%, 34%, and 36% of placebo, sarilumab 150-mg, and sarilumab 200-mg treated patients at the end of the MOBILITY study. At the end of year 2, the corresponding numbers were 60%, 62%, and 62%, and by year 3, not much had changed in the percentage of patients achieving DAS-28-CRP of less than 2.6: 58% for placebo, 62% for sarilumab 150 mg, and 68% for sarilumab 200 mg.
Similar results were seen for patients achieving a CDAI of 2.8 or lower at years 2 and 3 in the extension study.
Treatment-emergent adverse events (TEAEs) occurred in 89.7% of patients over 3 years. One in five (20%) patients experienced serious adverse events, with 23% of patients discontinuing treatment because of TEAEs. There were 9 (0.8%) deaths during the trial.
TEAEs that occurred at rates of 5% or higher in any treatment group were neutropenia in 19.4%, increased alanine aminotransferase in 13.0%, and upper respiratory tract infections in 12.7%.
There were some changes in laboratory values, Dr. van der Heijde said, but “most of the changes were very small” and in line with the effects expected with IL-6 inhibition.
The study was sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals. Dr. van der Heijde and coauthors disclosed receiving consulting fees, research grants, or both from multiple pharmaceutical companies, including the sponsors of the study. Dr. van der Heijde is director of Imaging Rheumatology.
AT RHEUMATOLOGY 2017
Key clinical point:
Major finding: The mean change in the modified total Sharp score (mTSS) from year 2 to 3 was 0.35 in the patients who had originally been randomized to the placebo arm, 0.64 in patients originally randomized to 150 mg sarilumab every 2 weeks, and 0.44 in those originally taking 200 mg sarilumab every 2 weeks.
Data source: SARIL-RA-EXTEND: a multicenter, uncontrolled extension study involving 1,197 patients who had participated in the phase III SARIL-RA-MOBILITY trial.
Disclosures: The study was sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals. Dr. van der Heijde and her coauthors disclosed receiving consulting fees, research grants, or both from multiple pharmaceutical companies, including the sponsors of the study. Dr. van der Heijde is director of Imaging Rheumatology.
Trial supports naproxen over low-dose colchicine for acute gout
BIRMINGHAM, ENGLAND – Naproxen may be considered the first-choice treatment for patients with acute gout in primary care, based on the results of the CONTACT (Colchicine or Naproxen Treatment for Acute Gout) trial.
“Our findings suggest that both naproxen and low-dose colchicine are effective treatments for acute gout,” Edward Roddy, MD, said at the British Society for Rheumatology annual conference.
The trial results showed, however, that there might be “a small, early treatment difference” favoring naproxen, and that the nonsteroidal anti-inflammatory drug “appeared to be associated with fewer side effects and less use of rescue analgesia for gout than low-dose colchicine,” said Dr. Roddy, a rheumatologist at Keele University, Staffordshire, England.
CONTACT was a multicenter, randomized, open-label trial involving 399 patients recruited at 100 primary care practices. Participants were mostly men (87%) and had a mean age of 59 years.
“The eligibility criteria were designed to reflect the pragmatic nature of the trial, but also to enable us to recruit the sorts of patients in whom either treatment option would be appropriate in routine practice,” Dr. Roddy explained.
Patients were eligible for inclusion if they had consulted a general practitioner for gout in the preceding 2 years and had a recent attack of acute gout that had been clinically assessed. Patients with medical or other contraindications to using either drug were excluded.
After giving their informed consent and completing a baseline questionnaire, patients were randomized to receive either naproxen as a single 750-mg dose, then as 250 mg three times a day for a maximum of 7 days, which is the licensed dose for gout in the United Kingdom, or 500 mcg of colchicine three times a day for 4 days. Patients completed a daily diary for 1 week, noting any pain, side effects, and analgesic drug use and then completed a follow-up questionnaire 4 weeks later.
The primary outcome was the worst pain intensity experienced in the preceding 24 hours, assessed on days 1-7 with a 10-point numeric rating scale (where 10 was the worst pain experienced).
The results showed that pain was reduced to a similar extent in both groups, with a mean difference in pain score between the treatments of 0.20 (95% confidence interval, –0.60 to 0.20) at 7 days and 0.08 (95% CI, –0.54 to 0.39) at 4 weeks’ follow-up, after adjustment for patients’ age, sex, and individual pain scores at baseline.
Greater mean improvement in pain intensity was seen with naproxen than colchicine on the second day of treatment, with a mean difference in pain scores between the groups of 0.48 (95% CI, –0.86 to –0.09) but not on any other day.
During the first 7 days of the study, diarrhea was the most commonly reported side effect occurring in the low-dose colchicine arm, reported by 43.2% of patients vs. 18.0% of those treated with naproxen (adjusted odds ratio, 3.04; 95% CI, 1.75-5.27). Conversely, constipation was a less frequently reported side effect occurring in 4.8% and 18.7% of patients, respectively (OR, 0.20; 95% CI, 0.08-0.49).
Patients treated with low-dose colchicine were also more likely than those treated with naproxen to report headache during the first 7 days (20.5% vs. 10.7%; OR, 1.90; 95% CI, 1.01-3.58).
There were no deaths in the study, and the three serious adverse events that occurred were thought to be unrelated to the study treatment. One NSAID-treated patient developed hospital-acquired pneumonia after elective heart valve surgery, and another NSAID-treated patient had noncardiac chest pain needing hospital treatment. One patient in the colchicine arm developed osteomyelitis that required hospitalization, but it was later thought that the patient might not have had gout to start with.
Between days 1 and 7 of the study, patients treated with low-dose colchicine were more likely to use other analgesic medications than were those treated with naproxen. This included the use of acetaminophen (23.6% vs. 13.4%; adjusted OR, 2.04; 95% CI, 1.10-3.78) and codeine (14.6% vs. 4.7%; aOR, 3.38; 95% CI, 1.45-7.91).
Patients in the low-dose colchicine group were also more likely to use an NSAID other than naproxen at week 4 than were those in the naproxen arm (24.0% vs. 13.4%; aOR, 1.93; 95% CI, 1.05-3.55).
Other secondary endpoints assessed showed no significant difference between the treatments, including changes in global assessment of response, acute gout recurrence, number of health care consultations, and ability to work.
The study was funded by the National Institute for Health Research School for Primary Care Research. Dr. Roddy had no conflicts of interest.
It’s not surprising that a relatively high dose of an NSAID like naproxen worked well for acute gout in the CONTACT study. That has been shown for multiple NSAIDs, although the quality of that evidence has been questioned (Cochrane Database Syst Rev. 2014 Sep 16;[9]:CD010120). What’s surprising is that colchicine did so well. It would have been informative to include the percentage of patients that responded to each treatment based on a predefined criterion, such as a 50% or greater reduction in pain scores at a given time point. The total colchicine dose used is on the high end of the “low dose” protocols, at 6.0 mg over 4 days, identical to the maximum low-dose over 4 days using current U.S. guidelines (Arthritis Care Res. 2012;64:1447-61). The higher dose may account for its efficacy, but also undoubtedly contributed to the high diarrhea rate of 43% (Arthritis Rheum. 2010;62:1060-8).
Christopher M. Burns, MD, is a rheumatologist at Dartmouth-Hitchcock Medical Center, Lebanon, N.H. He has no relevant disclosures.
It’s not surprising that a relatively high dose of an NSAID like naproxen worked well for acute gout in the CONTACT study. That has been shown for multiple NSAIDs, although the quality of that evidence has been questioned (Cochrane Database Syst Rev. 2014 Sep 16;[9]:CD010120). What’s surprising is that colchicine did so well. It would have been informative to include the percentage of patients that responded to each treatment based on a predefined criterion, such as a 50% or greater reduction in pain scores at a given time point. The total colchicine dose used is on the high end of the “low dose” protocols, at 6.0 mg over 4 days, identical to the maximum low-dose over 4 days using current U.S. guidelines (Arthritis Care Res. 2012;64:1447-61). The higher dose may account for its efficacy, but also undoubtedly contributed to the high diarrhea rate of 43% (Arthritis Rheum. 2010;62:1060-8).
Christopher M. Burns, MD, is a rheumatologist at Dartmouth-Hitchcock Medical Center, Lebanon, N.H. He has no relevant disclosures.
It’s not surprising that a relatively high dose of an NSAID like naproxen worked well for acute gout in the CONTACT study. That has been shown for multiple NSAIDs, although the quality of that evidence has been questioned (Cochrane Database Syst Rev. 2014 Sep 16;[9]:CD010120). What’s surprising is that colchicine did so well. It would have been informative to include the percentage of patients that responded to each treatment based on a predefined criterion, such as a 50% or greater reduction in pain scores at a given time point. The total colchicine dose used is on the high end of the “low dose” protocols, at 6.0 mg over 4 days, identical to the maximum low-dose over 4 days using current U.S. guidelines (Arthritis Care Res. 2012;64:1447-61). The higher dose may account for its efficacy, but also undoubtedly contributed to the high diarrhea rate of 43% (Arthritis Rheum. 2010;62:1060-8).
Christopher M. Burns, MD, is a rheumatologist at Dartmouth-Hitchcock Medical Center, Lebanon, N.H. He has no relevant disclosures.
BIRMINGHAM, ENGLAND – Naproxen may be considered the first-choice treatment for patients with acute gout in primary care, based on the results of the CONTACT (Colchicine or Naproxen Treatment for Acute Gout) trial.
“Our findings suggest that both naproxen and low-dose colchicine are effective treatments for acute gout,” Edward Roddy, MD, said at the British Society for Rheumatology annual conference.
The trial results showed, however, that there might be “a small, early treatment difference” favoring naproxen, and that the nonsteroidal anti-inflammatory drug “appeared to be associated with fewer side effects and less use of rescue analgesia for gout than low-dose colchicine,” said Dr. Roddy, a rheumatologist at Keele University, Staffordshire, England.
CONTACT was a multicenter, randomized, open-label trial involving 399 patients recruited at 100 primary care practices. Participants were mostly men (87%) and had a mean age of 59 years.
“The eligibility criteria were designed to reflect the pragmatic nature of the trial, but also to enable us to recruit the sorts of patients in whom either treatment option would be appropriate in routine practice,” Dr. Roddy explained.
Patients were eligible for inclusion if they had consulted a general practitioner for gout in the preceding 2 years and had a recent attack of acute gout that had been clinically assessed. Patients with medical or other contraindications to using either drug were excluded.
After giving their informed consent and completing a baseline questionnaire, patients were randomized to receive either naproxen as a single 750-mg dose, then as 250 mg three times a day for a maximum of 7 days, which is the licensed dose for gout in the United Kingdom, or 500 mcg of colchicine three times a day for 4 days. Patients completed a daily diary for 1 week, noting any pain, side effects, and analgesic drug use and then completed a follow-up questionnaire 4 weeks later.
The primary outcome was the worst pain intensity experienced in the preceding 24 hours, assessed on days 1-7 with a 10-point numeric rating scale (where 10 was the worst pain experienced).
The results showed that pain was reduced to a similar extent in both groups, with a mean difference in pain score between the treatments of 0.20 (95% confidence interval, –0.60 to 0.20) at 7 days and 0.08 (95% CI, –0.54 to 0.39) at 4 weeks’ follow-up, after adjustment for patients’ age, sex, and individual pain scores at baseline.
Greater mean improvement in pain intensity was seen with naproxen than colchicine on the second day of treatment, with a mean difference in pain scores between the groups of 0.48 (95% CI, –0.86 to –0.09) but not on any other day.
During the first 7 days of the study, diarrhea was the most commonly reported side effect occurring in the low-dose colchicine arm, reported by 43.2% of patients vs. 18.0% of those treated with naproxen (adjusted odds ratio, 3.04; 95% CI, 1.75-5.27). Conversely, constipation was a less frequently reported side effect occurring in 4.8% and 18.7% of patients, respectively (OR, 0.20; 95% CI, 0.08-0.49).
Patients treated with low-dose colchicine were also more likely than those treated with naproxen to report headache during the first 7 days (20.5% vs. 10.7%; OR, 1.90; 95% CI, 1.01-3.58).
There were no deaths in the study, and the three serious adverse events that occurred were thought to be unrelated to the study treatment. One NSAID-treated patient developed hospital-acquired pneumonia after elective heart valve surgery, and another NSAID-treated patient had noncardiac chest pain needing hospital treatment. One patient in the colchicine arm developed osteomyelitis that required hospitalization, but it was later thought that the patient might not have had gout to start with.
Between days 1 and 7 of the study, patients treated with low-dose colchicine were more likely to use other analgesic medications than were those treated with naproxen. This included the use of acetaminophen (23.6% vs. 13.4%; adjusted OR, 2.04; 95% CI, 1.10-3.78) and codeine (14.6% vs. 4.7%; aOR, 3.38; 95% CI, 1.45-7.91).
Patients in the low-dose colchicine group were also more likely to use an NSAID other than naproxen at week 4 than were those in the naproxen arm (24.0% vs. 13.4%; aOR, 1.93; 95% CI, 1.05-3.55).
Other secondary endpoints assessed showed no significant difference between the treatments, including changes in global assessment of response, acute gout recurrence, number of health care consultations, and ability to work.
The study was funded by the National Institute for Health Research School for Primary Care Research. Dr. Roddy had no conflicts of interest.
BIRMINGHAM, ENGLAND – Naproxen may be considered the first-choice treatment for patients with acute gout in primary care, based on the results of the CONTACT (Colchicine or Naproxen Treatment for Acute Gout) trial.
“Our findings suggest that both naproxen and low-dose colchicine are effective treatments for acute gout,” Edward Roddy, MD, said at the British Society for Rheumatology annual conference.
The trial results showed, however, that there might be “a small, early treatment difference” favoring naproxen, and that the nonsteroidal anti-inflammatory drug “appeared to be associated with fewer side effects and less use of rescue analgesia for gout than low-dose colchicine,” said Dr. Roddy, a rheumatologist at Keele University, Staffordshire, England.
CONTACT was a multicenter, randomized, open-label trial involving 399 patients recruited at 100 primary care practices. Participants were mostly men (87%) and had a mean age of 59 years.
“The eligibility criteria were designed to reflect the pragmatic nature of the trial, but also to enable us to recruit the sorts of patients in whom either treatment option would be appropriate in routine practice,” Dr. Roddy explained.
Patients were eligible for inclusion if they had consulted a general practitioner for gout in the preceding 2 years and had a recent attack of acute gout that had been clinically assessed. Patients with medical or other contraindications to using either drug were excluded.
After giving their informed consent and completing a baseline questionnaire, patients were randomized to receive either naproxen as a single 750-mg dose, then as 250 mg three times a day for a maximum of 7 days, which is the licensed dose for gout in the United Kingdom, or 500 mcg of colchicine three times a day for 4 days. Patients completed a daily diary for 1 week, noting any pain, side effects, and analgesic drug use and then completed a follow-up questionnaire 4 weeks later.
The primary outcome was the worst pain intensity experienced in the preceding 24 hours, assessed on days 1-7 with a 10-point numeric rating scale (where 10 was the worst pain experienced).
The results showed that pain was reduced to a similar extent in both groups, with a mean difference in pain score between the treatments of 0.20 (95% confidence interval, –0.60 to 0.20) at 7 days and 0.08 (95% CI, –0.54 to 0.39) at 4 weeks’ follow-up, after adjustment for patients’ age, sex, and individual pain scores at baseline.
Greater mean improvement in pain intensity was seen with naproxen than colchicine on the second day of treatment, with a mean difference in pain scores between the groups of 0.48 (95% CI, –0.86 to –0.09) but not on any other day.
During the first 7 days of the study, diarrhea was the most commonly reported side effect occurring in the low-dose colchicine arm, reported by 43.2% of patients vs. 18.0% of those treated with naproxen (adjusted odds ratio, 3.04; 95% CI, 1.75-5.27). Conversely, constipation was a less frequently reported side effect occurring in 4.8% and 18.7% of patients, respectively (OR, 0.20; 95% CI, 0.08-0.49).
Patients treated with low-dose colchicine were also more likely than those treated with naproxen to report headache during the first 7 days (20.5% vs. 10.7%; OR, 1.90; 95% CI, 1.01-3.58).
There were no deaths in the study, and the three serious adverse events that occurred were thought to be unrelated to the study treatment. One NSAID-treated patient developed hospital-acquired pneumonia after elective heart valve surgery, and another NSAID-treated patient had noncardiac chest pain needing hospital treatment. One patient in the colchicine arm developed osteomyelitis that required hospitalization, but it was later thought that the patient might not have had gout to start with.
Between days 1 and 7 of the study, patients treated with low-dose colchicine were more likely to use other analgesic medications than were those treated with naproxen. This included the use of acetaminophen (23.6% vs. 13.4%; adjusted OR, 2.04; 95% CI, 1.10-3.78) and codeine (14.6% vs. 4.7%; aOR, 3.38; 95% CI, 1.45-7.91).
Patients in the low-dose colchicine group were also more likely to use an NSAID other than naproxen at week 4 than were those in the naproxen arm (24.0% vs. 13.4%; aOR, 1.93; 95% CI, 1.05-3.55).
Other secondary endpoints assessed showed no significant difference between the treatments, including changes in global assessment of response, acute gout recurrence, number of health care consultations, and ability to work.
The study was funded by the National Institute for Health Research School for Primary Care Research. Dr. Roddy had no conflicts of interest.
Key clinical point:
Major finding: The mean difference in pain score between the treatments was 0.20 (95% CI, –0.60 to 0.20) at 7 days, but there was greater mean improvement in pain intensity on day 2 with naproxen.
Data source: The Colchicine or Naproxen Treatment for Acute Gout trial, a randomized, multicenter, open-label trial involving 399 patients with acute gout.
Disclosures: The study was funded by the National Institute for Health Research School for Primary Care Research. Dr. Roddy had no conflicts of interest.