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Biosimilar switch accepted by most rheumatic disease patients
LIVERPOOL, ENGLAND – , although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.
Of 35 patients who expressed concerns about the switch, most (n = 27) were concerned about the efficacy of the biosimilar, with others were mainly concerned about safety (n = 5), side effects (n = 3), or other factors (n = 5).
“This is the population of patients we were worried about, because we had got them on a drug that had finally worked for them,” poster presenter Joanne Kitchen, MBChB, said in an interview.
“It’s hard enough to get on the biologic, and we were concerned about whether they would lose response. ... There wasn’t a lot of evidence about if they didn’t respond and we switched back, would it still work for them,” explained Dr. Kitchen, a consultant rheumatologist who works at the Royal Berkshire Hospital in Reading, England.
Biosimilar etanercept became available in the United Kingdom in April 2016, and many rheumatology centers had to make the switch to its use at the behest of their health trusts in a cost-saving effort. The switch at the Royal Berkshire occurred in August 2016, and Dr. Kitchen explained that prior to the switch, letters were sent out to inform patients, who were then seen in the clinic. There also was an understanding between the medical team and the patients that, if things did not work out, patients could switch back to the originator etanercept.
Between August 2016 and February 2017, 113 patients had switched to biosimilar etanercept for their rheumatoid arthritis (RA), spondyloarthritis, or psoriatic arthritis.
Although worsening joint pain or stiffness (n = 12) or increased fatigue (n = 4) were reported by some patients, the fact that 88% of those who responded to the survey in October 2017 were still taking the drug 6-12 months after initiation suggests that these side effects were minor or manageable. Adherence to medication was not checked, however, which might have been a factor in any flare ups.
Medication changes occurred for four patients who switched back to originator etanercept, three to an alternative biologic, and four who discontinued biologics.
Other adverse effects reported by patients were more painful injections (n = 5), infections (n = 2), and others incidents such as individual cases of rash and headache in the remainder.
“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.
“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”
In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.
They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.
Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”
However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).
Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.
The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.
There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.
Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”
Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).
Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.
“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”
However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.
“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”
All authors had nothing to disclose.
SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
LIVERPOOL, ENGLAND – , although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.
Of 35 patients who expressed concerns about the switch, most (n = 27) were concerned about the efficacy of the biosimilar, with others were mainly concerned about safety (n = 5), side effects (n = 3), or other factors (n = 5).
“This is the population of patients we were worried about, because we had got them on a drug that had finally worked for them,” poster presenter Joanne Kitchen, MBChB, said in an interview.
“It’s hard enough to get on the biologic, and we were concerned about whether they would lose response. ... There wasn’t a lot of evidence about if they didn’t respond and we switched back, would it still work for them,” explained Dr. Kitchen, a consultant rheumatologist who works at the Royal Berkshire Hospital in Reading, England.
Biosimilar etanercept became available in the United Kingdom in April 2016, and many rheumatology centers had to make the switch to its use at the behest of their health trusts in a cost-saving effort. The switch at the Royal Berkshire occurred in August 2016, and Dr. Kitchen explained that prior to the switch, letters were sent out to inform patients, who were then seen in the clinic. There also was an understanding between the medical team and the patients that, if things did not work out, patients could switch back to the originator etanercept.
Between August 2016 and February 2017, 113 patients had switched to biosimilar etanercept for their rheumatoid arthritis (RA), spondyloarthritis, or psoriatic arthritis.
Although worsening joint pain or stiffness (n = 12) or increased fatigue (n = 4) were reported by some patients, the fact that 88% of those who responded to the survey in October 2017 were still taking the drug 6-12 months after initiation suggests that these side effects were minor or manageable. Adherence to medication was not checked, however, which might have been a factor in any flare ups.
Medication changes occurred for four patients who switched back to originator etanercept, three to an alternative biologic, and four who discontinued biologics.
Other adverse effects reported by patients were more painful injections (n = 5), infections (n = 2), and others incidents such as individual cases of rash and headache in the remainder.
“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.
“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”
In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.
They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.
Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”
However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).
Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.
The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.
There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.
Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”
Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).
Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.
“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”
However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.
“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”
All authors had nothing to disclose.
SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
LIVERPOOL, ENGLAND – , although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.
Of 35 patients who expressed concerns about the switch, most (n = 27) were concerned about the efficacy of the biosimilar, with others were mainly concerned about safety (n = 5), side effects (n = 3), or other factors (n = 5).
“This is the population of patients we were worried about, because we had got them on a drug that had finally worked for them,” poster presenter Joanne Kitchen, MBChB, said in an interview.
“It’s hard enough to get on the biologic, and we were concerned about whether they would lose response. ... There wasn’t a lot of evidence about if they didn’t respond and we switched back, would it still work for them,” explained Dr. Kitchen, a consultant rheumatologist who works at the Royal Berkshire Hospital in Reading, England.
Biosimilar etanercept became available in the United Kingdom in April 2016, and many rheumatology centers had to make the switch to its use at the behest of their health trusts in a cost-saving effort. The switch at the Royal Berkshire occurred in August 2016, and Dr. Kitchen explained that prior to the switch, letters were sent out to inform patients, who were then seen in the clinic. There also was an understanding between the medical team and the patients that, if things did not work out, patients could switch back to the originator etanercept.
Between August 2016 and February 2017, 113 patients had switched to biosimilar etanercept for their rheumatoid arthritis (RA), spondyloarthritis, or psoriatic arthritis.
Although worsening joint pain or stiffness (n = 12) or increased fatigue (n = 4) were reported by some patients, the fact that 88% of those who responded to the survey in October 2017 were still taking the drug 6-12 months after initiation suggests that these side effects were minor or manageable. Adherence to medication was not checked, however, which might have been a factor in any flare ups.
Medication changes occurred for four patients who switched back to originator etanercept, three to an alternative biologic, and four who discontinued biologics.
Other adverse effects reported by patients were more painful injections (n = 5), infections (n = 2), and others incidents such as individual cases of rash and headache in the remainder.
“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.
“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”
In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.
They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.
Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”
However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).
Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.
The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.
There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.
Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”
Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).
Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.
“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”
However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.
“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”
All authors had nothing to disclose.
SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
REPORTING FROM BSR 2018
Serum troponin predicts cardiovascular death in early arthritis
LIVERPOOL, ENGLAND – Serum levels of the cardiac biomarker troponin might prove useful for assessing the risk of death from cardiovascular causes in patients with inflammatory arthritis, according to study findings presented at the British Society for Rheumatology annual conference.
“In this analysis we have shown that baseline troponin levels predict cardiovascular death in inflammatory arthritis, and this association is independent of the traditional risk factors, inflammation, and disease characteristics at baseline,” said study author Sarah Skeoch, MBChB, who works at the Arthritis Research UK Centre for Epidemiology in the division of musculoskeletal and dermatological sciences at the University of Manchester (England).
Furthermore, the association remained in patients who had rheumatoid arthritis classified according to the 2010 American College of Rheumatology and European League Against Rheumatism criteria (overall adjusted HR, 2.25) and in those without prior cardiovascular disease at baseline (HR, 1.63).
Individuals with inflammatory arthritis are known to have an increased risk of developing cardiovascular problems versus the general population, but current prediction models using traditional risk factors do not fully account for the increased risk seen in patients with inflammatory arthritis, Dr. Skeoch explained.
“There has been some work looking at troponin in inflammatory arthritis already,” she said, with “higher levels observed versus age- and sex-matched controls, and associations have been shown with traditional risk factors.” There has also been a link to C-reactive protein levels and disease activity, and there has also been an association with coronary stenosis on CT scans. The aim of the current study was to see if there was any link to cardiovascular events and death.
A total of 1,023 patients who had been recruited into NOAR between 2000 and 2009 were studied. NOAR is an inception cohort study that includes patients with a history of two or more swollen joints for 4 weeks or more and has been running for almost 30 years. At baseline serum samples are taken and a variety of assessments made, including cardiovascular risk factors.
The study population was mostly female (66%), aged a median of 56 years, and had symptoms for a median of 10.6 months. Around half were seropositive for rheumatoid factor, anti–citrullinated protein antibodies, or both. The median baseline disease activity score in 28 joints (DAS28) was 3.73, and 61% met ACR/EULAR 2010 criteria for RA.
Baseline serum samples were analyzed using a chemiluminescent assay to determine hs-TnI levels, with the median being 6.3 pg/mL. All patients had detectable hs-TnI levels, and 2.6% had levels exceeding 26.1 pg/mL, which is the level associated with having had an acute myocardial infarction. Almost 4% had a previous cardiovascular event, and 7% had diabetes. One in five were current smokers, and roughly 18% had hypertension. The investigators adjusted for all of these factors in the multivariate analyses.
The median follow up was 11.2 years, totaling 11,237 person-years, and during that time 158 deaths occurred, of which 27 were due to ischemic events. The median time from inclusion in NOAR to death was 7.4 years.
When levels of hs-TnI were separated into tertiles, a 12.5-fold increased risk was observed when comparing patients in the highest (more than 7.7 pg/mL) to lowest tertiles (less than 5.2 pg/mL).
“The magnitude of risk between the highest and the lowest tertile was much greater than observed in the general population,” Dr. Skeoch said, and although not directly comparable, she said the hazard ratios were 12.5 and 1.67, “which again suggests that troponin may be an effective tool or addition to the risk prediction models in inflammatory arthritis.”
Unlike some biomarkers, assays to assess troponin are already available in the clinic, Dr. Skeoch commented, “so if further work by us and other groups do suggest a role for troponin, this could be translated fairly rapidly into clinical practice.”
Further research needs to look at why troponin is raised and what is its relationship to other risk factors. “There is a strong association with traditional risk factors such as lipids, so it would stand to reason that managing those risk factors, as well as lifestyle factors, would have a positive impact,” Dr. Skeoch suggested.
The NOAR register is funded by Arthritis Research UK and the U.K. National Institute for Health Research. Dr. Skeoch and her coauthors had no relevant financial conflicts of interest.
SOURCE: Skeoch S et al. BSR 2018. Rheumatology. 2018;57[Suppl. 3]:key075.192.
LIVERPOOL, ENGLAND – Serum levels of the cardiac biomarker troponin might prove useful for assessing the risk of death from cardiovascular causes in patients with inflammatory arthritis, according to study findings presented at the British Society for Rheumatology annual conference.
“In this analysis we have shown that baseline troponin levels predict cardiovascular death in inflammatory arthritis, and this association is independent of the traditional risk factors, inflammation, and disease characteristics at baseline,” said study author Sarah Skeoch, MBChB, who works at the Arthritis Research UK Centre for Epidemiology in the division of musculoskeletal and dermatological sciences at the University of Manchester (England).
Furthermore, the association remained in patients who had rheumatoid arthritis classified according to the 2010 American College of Rheumatology and European League Against Rheumatism criteria (overall adjusted HR, 2.25) and in those without prior cardiovascular disease at baseline (HR, 1.63).
Individuals with inflammatory arthritis are known to have an increased risk of developing cardiovascular problems versus the general population, but current prediction models using traditional risk factors do not fully account for the increased risk seen in patients with inflammatory arthritis, Dr. Skeoch explained.
“There has been some work looking at troponin in inflammatory arthritis already,” she said, with “higher levels observed versus age- and sex-matched controls, and associations have been shown with traditional risk factors.” There has also been a link to C-reactive protein levels and disease activity, and there has also been an association with coronary stenosis on CT scans. The aim of the current study was to see if there was any link to cardiovascular events and death.
A total of 1,023 patients who had been recruited into NOAR between 2000 and 2009 were studied. NOAR is an inception cohort study that includes patients with a history of two or more swollen joints for 4 weeks or more and has been running for almost 30 years. At baseline serum samples are taken and a variety of assessments made, including cardiovascular risk factors.
The study population was mostly female (66%), aged a median of 56 years, and had symptoms for a median of 10.6 months. Around half were seropositive for rheumatoid factor, anti–citrullinated protein antibodies, or both. The median baseline disease activity score in 28 joints (DAS28) was 3.73, and 61% met ACR/EULAR 2010 criteria for RA.
Baseline serum samples were analyzed using a chemiluminescent assay to determine hs-TnI levels, with the median being 6.3 pg/mL. All patients had detectable hs-TnI levels, and 2.6% had levels exceeding 26.1 pg/mL, which is the level associated with having had an acute myocardial infarction. Almost 4% had a previous cardiovascular event, and 7% had diabetes. One in five were current smokers, and roughly 18% had hypertension. The investigators adjusted for all of these factors in the multivariate analyses.
The median follow up was 11.2 years, totaling 11,237 person-years, and during that time 158 deaths occurred, of which 27 were due to ischemic events. The median time from inclusion in NOAR to death was 7.4 years.
When levels of hs-TnI were separated into tertiles, a 12.5-fold increased risk was observed when comparing patients in the highest (more than 7.7 pg/mL) to lowest tertiles (less than 5.2 pg/mL).
“The magnitude of risk between the highest and the lowest tertile was much greater than observed in the general population,” Dr. Skeoch said, and although not directly comparable, she said the hazard ratios were 12.5 and 1.67, “which again suggests that troponin may be an effective tool or addition to the risk prediction models in inflammatory arthritis.”
Unlike some biomarkers, assays to assess troponin are already available in the clinic, Dr. Skeoch commented, “so if further work by us and other groups do suggest a role for troponin, this could be translated fairly rapidly into clinical practice.”
Further research needs to look at why troponin is raised and what is its relationship to other risk factors. “There is a strong association with traditional risk factors such as lipids, so it would stand to reason that managing those risk factors, as well as lifestyle factors, would have a positive impact,” Dr. Skeoch suggested.
The NOAR register is funded by Arthritis Research UK and the U.K. National Institute for Health Research. Dr. Skeoch and her coauthors had no relevant financial conflicts of interest.
SOURCE: Skeoch S et al. BSR 2018. Rheumatology. 2018;57[Suppl. 3]:key075.192.
LIVERPOOL, ENGLAND – Serum levels of the cardiac biomarker troponin might prove useful for assessing the risk of death from cardiovascular causes in patients with inflammatory arthritis, according to study findings presented at the British Society for Rheumatology annual conference.
“In this analysis we have shown that baseline troponin levels predict cardiovascular death in inflammatory arthritis, and this association is independent of the traditional risk factors, inflammation, and disease characteristics at baseline,” said study author Sarah Skeoch, MBChB, who works at the Arthritis Research UK Centre for Epidemiology in the division of musculoskeletal and dermatological sciences at the University of Manchester (England).
Furthermore, the association remained in patients who had rheumatoid arthritis classified according to the 2010 American College of Rheumatology and European League Against Rheumatism criteria (overall adjusted HR, 2.25) and in those without prior cardiovascular disease at baseline (HR, 1.63).
Individuals with inflammatory arthritis are known to have an increased risk of developing cardiovascular problems versus the general population, but current prediction models using traditional risk factors do not fully account for the increased risk seen in patients with inflammatory arthritis, Dr. Skeoch explained.
“There has been some work looking at troponin in inflammatory arthritis already,” she said, with “higher levels observed versus age- and sex-matched controls, and associations have been shown with traditional risk factors.” There has also been a link to C-reactive protein levels and disease activity, and there has also been an association with coronary stenosis on CT scans. The aim of the current study was to see if there was any link to cardiovascular events and death.
A total of 1,023 patients who had been recruited into NOAR between 2000 and 2009 were studied. NOAR is an inception cohort study that includes patients with a history of two or more swollen joints for 4 weeks or more and has been running for almost 30 years. At baseline serum samples are taken and a variety of assessments made, including cardiovascular risk factors.
The study population was mostly female (66%), aged a median of 56 years, and had symptoms for a median of 10.6 months. Around half were seropositive for rheumatoid factor, anti–citrullinated protein antibodies, or both. The median baseline disease activity score in 28 joints (DAS28) was 3.73, and 61% met ACR/EULAR 2010 criteria for RA.
Baseline serum samples were analyzed using a chemiluminescent assay to determine hs-TnI levels, with the median being 6.3 pg/mL. All patients had detectable hs-TnI levels, and 2.6% had levels exceeding 26.1 pg/mL, which is the level associated with having had an acute myocardial infarction. Almost 4% had a previous cardiovascular event, and 7% had diabetes. One in five were current smokers, and roughly 18% had hypertension. The investigators adjusted for all of these factors in the multivariate analyses.
The median follow up was 11.2 years, totaling 11,237 person-years, and during that time 158 deaths occurred, of which 27 were due to ischemic events. The median time from inclusion in NOAR to death was 7.4 years.
When levels of hs-TnI were separated into tertiles, a 12.5-fold increased risk was observed when comparing patients in the highest (more than 7.7 pg/mL) to lowest tertiles (less than 5.2 pg/mL).
“The magnitude of risk between the highest and the lowest tertile was much greater than observed in the general population,” Dr. Skeoch said, and although not directly comparable, she said the hazard ratios were 12.5 and 1.67, “which again suggests that troponin may be an effective tool or addition to the risk prediction models in inflammatory arthritis.”
Unlike some biomarkers, assays to assess troponin are already available in the clinic, Dr. Skeoch commented, “so if further work by us and other groups do suggest a role for troponin, this could be translated fairly rapidly into clinical practice.”
Further research needs to look at why troponin is raised and what is its relationship to other risk factors. “There is a strong association with traditional risk factors such as lipids, so it would stand to reason that managing those risk factors, as well as lifestyle factors, would have a positive impact,” Dr. Skeoch suggested.
The NOAR register is funded by Arthritis Research UK and the U.K. National Institute for Health Research. Dr. Skeoch and her coauthors had no relevant financial conflicts of interest.
SOURCE: Skeoch S et al. BSR 2018. Rheumatology. 2018;57[Suppl. 3]:key075.192.
REPORTING FROM BSR 2018
Key clinical point: Cardiovascular mortality was predicted by baseline levels of high-sensitivity troponin I.
Major finding: For every log unit increase in hs-TnI at baseline, there was an increase in cardiovascular mortality (HR, 2.16).
Study details: Analysis of data on 1,023 patients with inflammatory arthritis listed in the Norfolk Arthritis Register.
Disclosures: Dr. Skeoch and coauthors had no relevant financial conflicts of interest.
Source: Skeoch S et al. BSR 2018. Rheumatology. 2018;57[Suppl. 3]:key075.192.
Biologics improve axial spondyloarthritis patients’ work performance
LIVERPOOL, ENGLAND – Biologic therapy for axial spondyloarthritis can improve individuals’ work productivity and decrease the extent that the disease impairs overall work and overall activity, new data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis have shown.
A variety of work outcomes on the Work Productivity and Impairment Specific Health Problem (WPAI-SHP) questionnaire improved to a significantly greater extent with biologics use than without. Presenteeism, or working while sick, improved by a mean of –9.4%. Overall work impairment reduced by 13.9%, and overall activity impairment decreased by 19.2%. There was no great effect on absenteeism, however, with a mean difference in improvement of –1.5% between the groups.
“Research into this chronic condition has shown that it has detrimental impact on one’s ability to work,” she added. People may take sick leave and be less productive at work, which can have a psychological effect and cause worry about job loss.
While there is “strong evidence” to show that biologic therapy can improve disease activity in those with axSpA, there is equivocal evidence on whether it has any effect on work outcomes, explained Dr. Shim, a physiotherapist and a postdoctoral research fellow in the Epidemiology Group at the University of Aberdeen (Scotland).
The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) started recruiting patients with axSpA from 84 centers across the United Kingdom in 2012 and there are now more than 2,500 participants included in the register. Similar to other biologics registers run under the auspices of the British Society for Rheumatology, the BSRBR-AS consists of two cohorts of patients, one who are about to start biologic therapy (with Enbrel [etanercept], Humira [adalimumab], or Cimzia [certolizumab pegol]) and one not receiving biologics.
The current analysis of 577 participants included 161 who had been treated with biologics and 416 who had not. Dr. Shim pointed out that people treated with biologics were younger (42 vs. 47 years), had shorter disease duration (7.7 vs. 12.3 years), and were more likely to be smokers (21% vs. 11%) than were those who had not taken biologics. Biologics-treated patients also had higher mean baseline disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (5.8 vs. 3.3), poorer function as measured by the Bath Ankylosing Spondylitis Functional Index (5.4 vs. 2.7), and worse overall Bath Ankylosing Spondylitis Global status scores (6.7 vs. 3.2).
“That’s the reason why they are given biologic therapy in the first place,” Dr. Shim said. To even out these differences, the investigators used propensity score matching before assessing work outcomes with the WPAI-SHP questionnaire. This consists of four components that are assessed in the last 7 days: absenteeism, presenteeism, overall work impairments (a combination of absenteeism and presenteeism), and overall activity impairment.
At recruitment, the investigators found that patients who later received biologics had greater impairment in work outcomes than did patients who later did not receive biologics. Patients who went on to receive biologics reported more absenteeism (13.0% vs. 3.0%), presenteeism (41.5% vs. 19.9%), overall work impairment (43.3% vs. 20.6%), and overall activity impairment (59.9% vs. 32.5%).
“Despite the improvements that we observed, there is still substantial unmet need, in the sense that people in the biologic therapy group are still experiencing significantly higher work impairments, compared to people in the nonbiologic therapy group,” Dr. Shim said. She added that, ideally, there should be no work impairment at all.
Dr. Shim and her associates combined the new BSRBR-AS findings with data from four prior randomized, controlled studies that met criteria for a meta-analysis. The results showed a mean difference between biologic and nonbiologic treatment of –5.35 on presenteeism, –11.20 on overall work impairment, and –12.13 on overall activity impairment. Again, there was little overall effect on absenteeism, with a mean difference of 0.84 between the groups.
The apparent lack of effect of biologic treatment on absenteeism could be from several reasons, one being that absenteeism was reportedly low in the BSRBR-AS and in other studies. Also, there is some evidence that presenteeism precedes absenteeism. The type of work done or number of allowed sick days may also play a role, Dr. Shim suggested.
“Work is a very important economic and social outcome,” Dr. Shim said. “We propose that future work should look into the assessment of work outcomes as standard measures,” in order to generate a greater evidence base around pharmacologic and nonpharmacologic approaches to improve work outcomes.
The BSRBR-AS is funded by the British Society for Rheumatology, which in turn has received function from AbbVie, Pfizer, and UCB. Dr. Shim reported that she had no conflicts of interest in relation to her presentation.
SOURCE: Shim J et al. Rheumatology. 2018;57[Suppl. 3]:key075.181.
LIVERPOOL, ENGLAND – Biologic therapy for axial spondyloarthritis can improve individuals’ work productivity and decrease the extent that the disease impairs overall work and overall activity, new data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis have shown.
A variety of work outcomes on the Work Productivity and Impairment Specific Health Problem (WPAI-SHP) questionnaire improved to a significantly greater extent with biologics use than without. Presenteeism, or working while sick, improved by a mean of –9.4%. Overall work impairment reduced by 13.9%, and overall activity impairment decreased by 19.2%. There was no great effect on absenteeism, however, with a mean difference in improvement of –1.5% between the groups.
“Research into this chronic condition has shown that it has detrimental impact on one’s ability to work,” she added. People may take sick leave and be less productive at work, which can have a psychological effect and cause worry about job loss.
While there is “strong evidence” to show that biologic therapy can improve disease activity in those with axSpA, there is equivocal evidence on whether it has any effect on work outcomes, explained Dr. Shim, a physiotherapist and a postdoctoral research fellow in the Epidemiology Group at the University of Aberdeen (Scotland).
The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) started recruiting patients with axSpA from 84 centers across the United Kingdom in 2012 and there are now more than 2,500 participants included in the register. Similar to other biologics registers run under the auspices of the British Society for Rheumatology, the BSRBR-AS consists of two cohorts of patients, one who are about to start biologic therapy (with Enbrel [etanercept], Humira [adalimumab], or Cimzia [certolizumab pegol]) and one not receiving biologics.
The current analysis of 577 participants included 161 who had been treated with biologics and 416 who had not. Dr. Shim pointed out that people treated with biologics were younger (42 vs. 47 years), had shorter disease duration (7.7 vs. 12.3 years), and were more likely to be smokers (21% vs. 11%) than were those who had not taken biologics. Biologics-treated patients also had higher mean baseline disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (5.8 vs. 3.3), poorer function as measured by the Bath Ankylosing Spondylitis Functional Index (5.4 vs. 2.7), and worse overall Bath Ankylosing Spondylitis Global status scores (6.7 vs. 3.2).
“That’s the reason why they are given biologic therapy in the first place,” Dr. Shim said. To even out these differences, the investigators used propensity score matching before assessing work outcomes with the WPAI-SHP questionnaire. This consists of four components that are assessed in the last 7 days: absenteeism, presenteeism, overall work impairments (a combination of absenteeism and presenteeism), and overall activity impairment.
At recruitment, the investigators found that patients who later received biologics had greater impairment in work outcomes than did patients who later did not receive biologics. Patients who went on to receive biologics reported more absenteeism (13.0% vs. 3.0%), presenteeism (41.5% vs. 19.9%), overall work impairment (43.3% vs. 20.6%), and overall activity impairment (59.9% vs. 32.5%).
“Despite the improvements that we observed, there is still substantial unmet need, in the sense that people in the biologic therapy group are still experiencing significantly higher work impairments, compared to people in the nonbiologic therapy group,” Dr. Shim said. She added that, ideally, there should be no work impairment at all.
Dr. Shim and her associates combined the new BSRBR-AS findings with data from four prior randomized, controlled studies that met criteria for a meta-analysis. The results showed a mean difference between biologic and nonbiologic treatment of –5.35 on presenteeism, –11.20 on overall work impairment, and –12.13 on overall activity impairment. Again, there was little overall effect on absenteeism, with a mean difference of 0.84 between the groups.
The apparent lack of effect of biologic treatment on absenteeism could be from several reasons, one being that absenteeism was reportedly low in the BSRBR-AS and in other studies. Also, there is some evidence that presenteeism precedes absenteeism. The type of work done or number of allowed sick days may also play a role, Dr. Shim suggested.
“Work is a very important economic and social outcome,” Dr. Shim said. “We propose that future work should look into the assessment of work outcomes as standard measures,” in order to generate a greater evidence base around pharmacologic and nonpharmacologic approaches to improve work outcomes.
The BSRBR-AS is funded by the British Society for Rheumatology, which in turn has received function from AbbVie, Pfizer, and UCB. Dr. Shim reported that she had no conflicts of interest in relation to her presentation.
SOURCE: Shim J et al. Rheumatology. 2018;57[Suppl. 3]:key075.181.
LIVERPOOL, ENGLAND – Biologic therapy for axial spondyloarthritis can improve individuals’ work productivity and decrease the extent that the disease impairs overall work and overall activity, new data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis have shown.
A variety of work outcomes on the Work Productivity and Impairment Specific Health Problem (WPAI-SHP) questionnaire improved to a significantly greater extent with biologics use than without. Presenteeism, or working while sick, improved by a mean of –9.4%. Overall work impairment reduced by 13.9%, and overall activity impairment decreased by 19.2%. There was no great effect on absenteeism, however, with a mean difference in improvement of –1.5% between the groups.
“Research into this chronic condition has shown that it has detrimental impact on one’s ability to work,” she added. People may take sick leave and be less productive at work, which can have a psychological effect and cause worry about job loss.
While there is “strong evidence” to show that biologic therapy can improve disease activity in those with axSpA, there is equivocal evidence on whether it has any effect on work outcomes, explained Dr. Shim, a physiotherapist and a postdoctoral research fellow in the Epidemiology Group at the University of Aberdeen (Scotland).
The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) started recruiting patients with axSpA from 84 centers across the United Kingdom in 2012 and there are now more than 2,500 participants included in the register. Similar to other biologics registers run under the auspices of the British Society for Rheumatology, the BSRBR-AS consists of two cohorts of patients, one who are about to start biologic therapy (with Enbrel [etanercept], Humira [adalimumab], or Cimzia [certolizumab pegol]) and one not receiving biologics.
The current analysis of 577 participants included 161 who had been treated with biologics and 416 who had not. Dr. Shim pointed out that people treated with biologics were younger (42 vs. 47 years), had shorter disease duration (7.7 vs. 12.3 years), and were more likely to be smokers (21% vs. 11%) than were those who had not taken biologics. Biologics-treated patients also had higher mean baseline disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (5.8 vs. 3.3), poorer function as measured by the Bath Ankylosing Spondylitis Functional Index (5.4 vs. 2.7), and worse overall Bath Ankylosing Spondylitis Global status scores (6.7 vs. 3.2).
“That’s the reason why they are given biologic therapy in the first place,” Dr. Shim said. To even out these differences, the investigators used propensity score matching before assessing work outcomes with the WPAI-SHP questionnaire. This consists of four components that are assessed in the last 7 days: absenteeism, presenteeism, overall work impairments (a combination of absenteeism and presenteeism), and overall activity impairment.
At recruitment, the investigators found that patients who later received biologics had greater impairment in work outcomes than did patients who later did not receive biologics. Patients who went on to receive biologics reported more absenteeism (13.0% vs. 3.0%), presenteeism (41.5% vs. 19.9%), overall work impairment (43.3% vs. 20.6%), and overall activity impairment (59.9% vs. 32.5%).
“Despite the improvements that we observed, there is still substantial unmet need, in the sense that people in the biologic therapy group are still experiencing significantly higher work impairments, compared to people in the nonbiologic therapy group,” Dr. Shim said. She added that, ideally, there should be no work impairment at all.
Dr. Shim and her associates combined the new BSRBR-AS findings with data from four prior randomized, controlled studies that met criteria for a meta-analysis. The results showed a mean difference between biologic and nonbiologic treatment of –5.35 on presenteeism, –11.20 on overall work impairment, and –12.13 on overall activity impairment. Again, there was little overall effect on absenteeism, with a mean difference of 0.84 between the groups.
The apparent lack of effect of biologic treatment on absenteeism could be from several reasons, one being that absenteeism was reportedly low in the BSRBR-AS and in other studies. Also, there is some evidence that presenteeism precedes absenteeism. The type of work done or number of allowed sick days may also play a role, Dr. Shim suggested.
“Work is a very important economic and social outcome,” Dr. Shim said. “We propose that future work should look into the assessment of work outcomes as standard measures,” in order to generate a greater evidence base around pharmacologic and nonpharmacologic approaches to improve work outcomes.
The BSRBR-AS is funded by the British Society for Rheumatology, which in turn has received function from AbbVie, Pfizer, and UCB. Dr. Shim reported that she had no conflicts of interest in relation to her presentation.
SOURCE: Shim J et al. Rheumatology. 2018;57[Suppl. 3]:key075.181.
REPORTING FROM RHEUMATOLOGY 2018
Key clinical point: Treatment with biologic therapy led to improved work outcomes to a greater extent over time than in patients who did not take biologics.
Major finding: Presenteeism improved by a mean of –9.4%, overall work impairment reduced by 13.9%, and overall activity impairment decreased by 19.2%.
Study details: 577 patients registered in BSRBR-AS (the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis).
Disclosures: The BSRBR-AS is funded by the British Society for Rheumatology, which in turn has received function from AbbVie, Pfizer, and UCB. Dr. Shim reported that she has no conflicts of interest in relation to her presentation.
Source: Shim J et al. Rheumatology. 2018;57(Suppl. 3):key075.181.
New JAK-1 inhibitor had high, early efficacy in rheumatoid arthritis trial
LIVERPOOL, ENGLAND – Treatment with the investigational drug upadacitinib resulted in higher percentages of patients with active rheumatoid arthritis achieving good disease control within 12 weeks than did treatment with placebo in a phase 3 trial.
Two-thirds of patients met American College of Rheumatology 20% (ACR 20) response criteria, and almost half (48%) achieved a Disease Activity Score in 28 Joints–C-reactive protein (DAS28-CRP) of 3.2 or less versus 17% of placebo-treated patients (P less than .001).
All patients had been given upadacitinib on top of their existing conventional synthetic disease-modifying antirheumatic drug therapy because they had not been fully responding to csDMARDs alone.
“Onset of action was rapid: By week 1 significantly more patients achieved ACR 20 on upadacitinib at both doses versus placebo,” the study’s investigators noted in a poster presentation given at the British Society for Rheumatology annual conference. Significant improvements in DAS28-CRP and Clinical Disease Activity Index (CDAI) were also seen as early as week 1.
Gerd R. Burmester, MD, of Charité-Universitätsmedizin, Berlin, and associates reported the results of the SELECT-NEXT study, one of six global phase 3 studies testing the efficacy and safety of upadacitinib targeting “a range of different patient populations” with RA; together the trials include more than 4,500 patients.
Upadacitinib (ABT-494) is a selective Janus kinase (JAK)-1 inhibitor and is also in phase 3 trials for the treatment of psoriatic arthritis and Crohn’s disease, as well as being tested as a potential treatment for axial spondyloarthritis, giant cell arteritis, ulcerative colitis, and atopic dermatitis.
SELECT-NEXT consists of two phases, the first of which has been completed and was reported at the meeting. Phase 1 consisted of randomized, double-blind treatment with upadacitinib 15 mg or 30 mg once daily or matching placebo. After the coprimary endpoint assessment of ACR 20 and DAS28-CRP was undertaken at 12 weeks, the trial entered its second phase: This is a blinded-extension phase that will last up to 5 years and during which patients randomized to upadacitinib will continue their treatment, and the patients randomized to placebo will split into two groups and be treated with one or the other dose of upadacitinib.
The study included 661 patients who had been treated with csDMARDs for at least 3 months but still had swollen and tender joint counts of six or higher and high-sensitivity CRP levels of 3 mg/L or higher. At entry, patients were allowed to continue on up to two csDMARDs; stable-dose steroids (less than 10 mg/week), nonsteroidal anti-inflammatory drugs, and acetaminophen were also allowed.
“Significant changes from baseline in several patient-reported outcomes were observed,” with the active treatment versus placebo, the investigators observed. Indeed, by week 12, morning stiffness was reduced by an average of 85 minutes in patients taking upadacitinib versus a decrease of 34 minutes in the placebo group. Significant (P less than .01) improvements were also seen in Short-Form 36–Mental Component scores, they reported.
Furthermore, more patients taking the active treatment than placebo achieved clinical remission by 12 weeks.
“The safety and tolerability profile was consistent with observations in the phase 2 studies,” Dr. Burmester and associates observed. The most frequently reported adverse events in more than 3% of patients were nasopharyngitis, upper respiratory infection, headache, urinary tract infection, cough, nausea, and diarrhea.
Serious adverse events and those leading to discontinuation were both higher in the two upadacitinib groups versus placebo, at 2.7% and 5.9% for the 30-mg dose, 4.1% and 3.2% for the 15-mg dose, and 2.3% and 3.2% for placebo. Of note, infections occurred in a 31.5% of patients on 30 mg, 29.0% on 15 mg, and 21.3% on placebo, and hepatic disorders occurred in 2.7% of patients on 30 mg, 1.8% on 15 mg, and 2.3% on placebo. One (0.5%) patient taking the 30-mg dose had a major cardiovascular event and two (0.9%) patients in the 15-mg group had other adjudicated cardiovascular events.
The study was sponsored and run by Abbvie. The study authors acknowledged receiving research support or consulting fees from Abbvie or being employees of the company.
SOURCE: Burmester GR et al.; BSR 2018 Rheumatology. 2018;57[Suppl. 3]:key075.466.
LIVERPOOL, ENGLAND – Treatment with the investigational drug upadacitinib resulted in higher percentages of patients with active rheumatoid arthritis achieving good disease control within 12 weeks than did treatment with placebo in a phase 3 trial.
Two-thirds of patients met American College of Rheumatology 20% (ACR 20) response criteria, and almost half (48%) achieved a Disease Activity Score in 28 Joints–C-reactive protein (DAS28-CRP) of 3.2 or less versus 17% of placebo-treated patients (P less than .001).
All patients had been given upadacitinib on top of their existing conventional synthetic disease-modifying antirheumatic drug therapy because they had not been fully responding to csDMARDs alone.
“Onset of action was rapid: By week 1 significantly more patients achieved ACR 20 on upadacitinib at both doses versus placebo,” the study’s investigators noted in a poster presentation given at the British Society for Rheumatology annual conference. Significant improvements in DAS28-CRP and Clinical Disease Activity Index (CDAI) were also seen as early as week 1.
Gerd R. Burmester, MD, of Charité-Universitätsmedizin, Berlin, and associates reported the results of the SELECT-NEXT study, one of six global phase 3 studies testing the efficacy and safety of upadacitinib targeting “a range of different patient populations” with RA; together the trials include more than 4,500 patients.
Upadacitinib (ABT-494) is a selective Janus kinase (JAK)-1 inhibitor and is also in phase 3 trials for the treatment of psoriatic arthritis and Crohn’s disease, as well as being tested as a potential treatment for axial spondyloarthritis, giant cell arteritis, ulcerative colitis, and atopic dermatitis.
SELECT-NEXT consists of two phases, the first of which has been completed and was reported at the meeting. Phase 1 consisted of randomized, double-blind treatment with upadacitinib 15 mg or 30 mg once daily or matching placebo. After the coprimary endpoint assessment of ACR 20 and DAS28-CRP was undertaken at 12 weeks, the trial entered its second phase: This is a blinded-extension phase that will last up to 5 years and during which patients randomized to upadacitinib will continue their treatment, and the patients randomized to placebo will split into two groups and be treated with one or the other dose of upadacitinib.
The study included 661 patients who had been treated with csDMARDs for at least 3 months but still had swollen and tender joint counts of six or higher and high-sensitivity CRP levels of 3 mg/L or higher. At entry, patients were allowed to continue on up to two csDMARDs; stable-dose steroids (less than 10 mg/week), nonsteroidal anti-inflammatory drugs, and acetaminophen were also allowed.
“Significant changes from baseline in several patient-reported outcomes were observed,” with the active treatment versus placebo, the investigators observed. Indeed, by week 12, morning stiffness was reduced by an average of 85 minutes in patients taking upadacitinib versus a decrease of 34 minutes in the placebo group. Significant (P less than .01) improvements were also seen in Short-Form 36–Mental Component scores, they reported.
Furthermore, more patients taking the active treatment than placebo achieved clinical remission by 12 weeks.
“The safety and tolerability profile was consistent with observations in the phase 2 studies,” Dr. Burmester and associates observed. The most frequently reported adverse events in more than 3% of patients were nasopharyngitis, upper respiratory infection, headache, urinary tract infection, cough, nausea, and diarrhea.
Serious adverse events and those leading to discontinuation were both higher in the two upadacitinib groups versus placebo, at 2.7% and 5.9% for the 30-mg dose, 4.1% and 3.2% for the 15-mg dose, and 2.3% and 3.2% for placebo. Of note, infections occurred in a 31.5% of patients on 30 mg, 29.0% on 15 mg, and 21.3% on placebo, and hepatic disorders occurred in 2.7% of patients on 30 mg, 1.8% on 15 mg, and 2.3% on placebo. One (0.5%) patient taking the 30-mg dose had a major cardiovascular event and two (0.9%) patients in the 15-mg group had other adjudicated cardiovascular events.
The study was sponsored and run by Abbvie. The study authors acknowledged receiving research support or consulting fees from Abbvie or being employees of the company.
SOURCE: Burmester GR et al.; BSR 2018 Rheumatology. 2018;57[Suppl. 3]:key075.466.
LIVERPOOL, ENGLAND – Treatment with the investigational drug upadacitinib resulted in higher percentages of patients with active rheumatoid arthritis achieving good disease control within 12 weeks than did treatment with placebo in a phase 3 trial.
Two-thirds of patients met American College of Rheumatology 20% (ACR 20) response criteria, and almost half (48%) achieved a Disease Activity Score in 28 Joints–C-reactive protein (DAS28-CRP) of 3.2 or less versus 17% of placebo-treated patients (P less than .001).
All patients had been given upadacitinib on top of their existing conventional synthetic disease-modifying antirheumatic drug therapy because they had not been fully responding to csDMARDs alone.
“Onset of action was rapid: By week 1 significantly more patients achieved ACR 20 on upadacitinib at both doses versus placebo,” the study’s investigators noted in a poster presentation given at the British Society for Rheumatology annual conference. Significant improvements in DAS28-CRP and Clinical Disease Activity Index (CDAI) were also seen as early as week 1.
Gerd R. Burmester, MD, of Charité-Universitätsmedizin, Berlin, and associates reported the results of the SELECT-NEXT study, one of six global phase 3 studies testing the efficacy and safety of upadacitinib targeting “a range of different patient populations” with RA; together the trials include more than 4,500 patients.
Upadacitinib (ABT-494) is a selective Janus kinase (JAK)-1 inhibitor and is also in phase 3 trials for the treatment of psoriatic arthritis and Crohn’s disease, as well as being tested as a potential treatment for axial spondyloarthritis, giant cell arteritis, ulcerative colitis, and atopic dermatitis.
SELECT-NEXT consists of two phases, the first of which has been completed and was reported at the meeting. Phase 1 consisted of randomized, double-blind treatment with upadacitinib 15 mg or 30 mg once daily or matching placebo. After the coprimary endpoint assessment of ACR 20 and DAS28-CRP was undertaken at 12 weeks, the trial entered its second phase: This is a blinded-extension phase that will last up to 5 years and during which patients randomized to upadacitinib will continue their treatment, and the patients randomized to placebo will split into two groups and be treated with one or the other dose of upadacitinib.
The study included 661 patients who had been treated with csDMARDs for at least 3 months but still had swollen and tender joint counts of six or higher and high-sensitivity CRP levels of 3 mg/L or higher. At entry, patients were allowed to continue on up to two csDMARDs; stable-dose steroids (less than 10 mg/week), nonsteroidal anti-inflammatory drugs, and acetaminophen were also allowed.
“Significant changes from baseline in several patient-reported outcomes were observed,” with the active treatment versus placebo, the investigators observed. Indeed, by week 12, morning stiffness was reduced by an average of 85 minutes in patients taking upadacitinib versus a decrease of 34 minutes in the placebo group. Significant (P less than .01) improvements were also seen in Short-Form 36–Mental Component scores, they reported.
Furthermore, more patients taking the active treatment than placebo achieved clinical remission by 12 weeks.
“The safety and tolerability profile was consistent with observations in the phase 2 studies,” Dr. Burmester and associates observed. The most frequently reported adverse events in more than 3% of patients were nasopharyngitis, upper respiratory infection, headache, urinary tract infection, cough, nausea, and diarrhea.
Serious adverse events and those leading to discontinuation were both higher in the two upadacitinib groups versus placebo, at 2.7% and 5.9% for the 30-mg dose, 4.1% and 3.2% for the 15-mg dose, and 2.3% and 3.2% for placebo. Of note, infections occurred in a 31.5% of patients on 30 mg, 29.0% on 15 mg, and 21.3% on placebo, and hepatic disorders occurred in 2.7% of patients on 30 mg, 1.8% on 15 mg, and 2.3% on placebo. One (0.5%) patient taking the 30-mg dose had a major cardiovascular event and two (0.9%) patients in the 15-mg group had other adjudicated cardiovascular events.
The study was sponsored and run by Abbvie. The study authors acknowledged receiving research support or consulting fees from Abbvie or being employees of the company.
SOURCE: Burmester GR et al.; BSR 2018 Rheumatology. 2018;57[Suppl. 3]:key075.466.
REPORTING FROM Rheumatology 2018
Key clinical point: Upadacitinib met both of the coprimary endpoints in the trial – ACR 20 response and low disease activity at 12 weeks.
Major finding: ACR 20 was achieved by 64%/66%/36% of patients taking upadacitinib 15 mg once daily, patients taking upadacitinib 30 mg once daily, and placebo-treated patients, respectively. Low disease activity was achieved by 48%/48%/17% of patients taking upadacitinib 15 mg once daily, patients taking upadacitinib 30 mg once daily, and placebo-treated patients, respectively (P less than .001).
Study details: SELECT-NEXT, a phase 3, randomized, double-blind, placebo-controlled trial of two doses of upadacitinib in 661 patients with rheumatoid arthritis who were not responding to conventional disease-modifying drug treatment.
Disclosures: The study was sponsored by Abbvie. The study authors acknowledged receiving research support or consulting fees from Abbvie or being employees of the company.
Source: Burmester GR et al. BSR 2018; Rheumatology. 2018;57[Suppl. 3]:key075.466.
Long-term follow-up most important for hydroxychloroquine retinal screening
LIVERPOOL, ENGLAND – , but long-term follow-up is much more important, according to data presented at the British Society for Rheumatology annual conference.
In just one specialist rheumatology center in England, which treats more than 8,000 patients annually, the cost of the first year’s optical coherence tomography (OCT) assessment would be more than $60,000. Additional costs would be incurred to screen those who had been on the drug for more than 5 years ,who were known to be at greater risk of hydroxychloroquine-induced retinopathy. This is within the National Health Service in England where the cost of a single OCT scan is around $70; in the private health sector, the cost of one test can be as high as $400.
Indeed, of 887 hydroxychloroquine users identified, 44% had at least one risk factor for hydroxychloroquine-induced retinopathy. These included being older than 60 years of age (30% of all users), having renal (10%) or hepatic (2%) impairment, retinal disease at baseline (8%), or using high (more than 6.5 mg/kg) doses of the drug based on their actual (9%) or ideal (4%) body weight.
“The retinal toxicity of hydroxychloroquine is a bit of a hot topic at the moment,” Dr. Yates said at the conference. While the drug has been around for years and used successfully to treat many patients with rheumatoid arthritis and systemic lupus erythematosus (SLE), a known side effect is retinal toxicity.
Traditionally, retinopathy has been quoted as being a relatively rare side effect, affecting around 0.5%-2% of the treated population. Recent data (JAMA Ophthalmol. 2014;132[12]:1453-60) suggest, however, that is probably a vast underestimate, with 7.5% of patients taking hydroxychloroquine for more than 5 years likely to be affected, as are up to 20% of those taking the drug for up to 20 years of treatment.
Dr. Yates and associates wanted to assess the burden of hydroxychloroquine use at their center and look at the risk factors and impact of the recent screening guidelines issued by the British Society for Rheumatology (Rheumatology [Oxford]. 2017;56[6]:865-8) in 2017 and by the Royal College of Ophthalmologists in 2018. These state that patients should have a formal baseline ophthalmic examination, ideally including OCT, within 6-12 months of starting therapy and an annual eye assessment with repeat OCT thereafter for the following 5 years; the ophthalmology guidelines recommending annual screening for the duration of therapy.
One criticism of increased screening for retinal toxicity in routine practice is consultants saying that they see only a handful of cases during their career, Dr. Yates observed. However, if you consider that in an average rheumatology department there are five consultants and 900 patients on hydroxychloroquine, 500 patients take the drug for 5 years or longer, 2% are picked up with non-OCT screening, that amounts to around two cases per year over a 5- to 10-year period. “So that fits with the narrative of only having seen a handful of cases pre-OCT,” Dr. Yates reasoned.
“I believe that this is a real problem, but I’m afraid this is the tip of the iceberg,” commented Caroline Gordon, MD, after her presentation. “We’ve been screening our patients in Birmingham now for about 5 years and we are definitely finding a significant number of patients with hydroxychloroquine toxicity who can be picked up with OCT and visual fields screening.”
Dr. Gordon, professor of rheumatology at the University of Birmingham (England) and a consultant rheumatologist for the University Hospitals NHS Foundation Trust and the Sandwell & West Birmingham Hospitals NHS Trust, helps look after one of the largest cohorts of patients with SLE in the United Kingdom.
A baseline eye examination has always been recommended, Dr. Gordon said, but she suggested that this could remain in the realm of the opticians with further assessment and referral as needed.
“I’m not convinced, from the work we’ve done, that there is any value in the baseline OCT,” Dr. Gordon said, “because we never find anything on the baseline OCT that we didn’t already expect from the opticians’ assessment.”
It is the long-term (longer than10 years) follow-up that needs to be the focus, rather than the initial period, she stressed, as the highest risk appears to be in patients who have been taking the drug for 15 years or longer. Prior to this, different types of retinopathy can occur that are actually attributable to the underlying disease and are not related hydroxychloroquine. Of course, patients on higher doses of hydroxychloroquine may need closer monitoring early on, “as they are at risk,” she acknowledged.
Dr. Gordon suggested that the guidelines as they currently stand may not be that useful for real-life practice. Following them could result in a large amount of money being spent on early tests that are perhaps not necessary.
“What we do need to do is focus on the patients who’ve been on treatment long term,” she said.
SOURCE: Yates M et al. Rheumatology. 2018;57(Suppl. 3):key075.188.
LIVERPOOL, ENGLAND – , but long-term follow-up is much more important, according to data presented at the British Society for Rheumatology annual conference.
In just one specialist rheumatology center in England, which treats more than 8,000 patients annually, the cost of the first year’s optical coherence tomography (OCT) assessment would be more than $60,000. Additional costs would be incurred to screen those who had been on the drug for more than 5 years ,who were known to be at greater risk of hydroxychloroquine-induced retinopathy. This is within the National Health Service in England where the cost of a single OCT scan is around $70; in the private health sector, the cost of one test can be as high as $400.
Indeed, of 887 hydroxychloroquine users identified, 44% had at least one risk factor for hydroxychloroquine-induced retinopathy. These included being older than 60 years of age (30% of all users), having renal (10%) or hepatic (2%) impairment, retinal disease at baseline (8%), or using high (more than 6.5 mg/kg) doses of the drug based on their actual (9%) or ideal (4%) body weight.
“The retinal toxicity of hydroxychloroquine is a bit of a hot topic at the moment,” Dr. Yates said at the conference. While the drug has been around for years and used successfully to treat many patients with rheumatoid arthritis and systemic lupus erythematosus (SLE), a known side effect is retinal toxicity.
Traditionally, retinopathy has been quoted as being a relatively rare side effect, affecting around 0.5%-2% of the treated population. Recent data (JAMA Ophthalmol. 2014;132[12]:1453-60) suggest, however, that is probably a vast underestimate, with 7.5% of patients taking hydroxychloroquine for more than 5 years likely to be affected, as are up to 20% of those taking the drug for up to 20 years of treatment.
Dr. Yates and associates wanted to assess the burden of hydroxychloroquine use at their center and look at the risk factors and impact of the recent screening guidelines issued by the British Society for Rheumatology (Rheumatology [Oxford]. 2017;56[6]:865-8) in 2017 and by the Royal College of Ophthalmologists in 2018. These state that patients should have a formal baseline ophthalmic examination, ideally including OCT, within 6-12 months of starting therapy and an annual eye assessment with repeat OCT thereafter for the following 5 years; the ophthalmology guidelines recommending annual screening for the duration of therapy.
One criticism of increased screening for retinal toxicity in routine practice is consultants saying that they see only a handful of cases during their career, Dr. Yates observed. However, if you consider that in an average rheumatology department there are five consultants and 900 patients on hydroxychloroquine, 500 patients take the drug for 5 years or longer, 2% are picked up with non-OCT screening, that amounts to around two cases per year over a 5- to 10-year period. “So that fits with the narrative of only having seen a handful of cases pre-OCT,” Dr. Yates reasoned.
“I believe that this is a real problem, but I’m afraid this is the tip of the iceberg,” commented Caroline Gordon, MD, after her presentation. “We’ve been screening our patients in Birmingham now for about 5 years and we are definitely finding a significant number of patients with hydroxychloroquine toxicity who can be picked up with OCT and visual fields screening.”
Dr. Gordon, professor of rheumatology at the University of Birmingham (England) and a consultant rheumatologist for the University Hospitals NHS Foundation Trust and the Sandwell & West Birmingham Hospitals NHS Trust, helps look after one of the largest cohorts of patients with SLE in the United Kingdom.
A baseline eye examination has always been recommended, Dr. Gordon said, but she suggested that this could remain in the realm of the opticians with further assessment and referral as needed.
“I’m not convinced, from the work we’ve done, that there is any value in the baseline OCT,” Dr. Gordon said, “because we never find anything on the baseline OCT that we didn’t already expect from the opticians’ assessment.”
It is the long-term (longer than10 years) follow-up that needs to be the focus, rather than the initial period, she stressed, as the highest risk appears to be in patients who have been taking the drug for 15 years or longer. Prior to this, different types of retinopathy can occur that are actually attributable to the underlying disease and are not related hydroxychloroquine. Of course, patients on higher doses of hydroxychloroquine may need closer monitoring early on, “as they are at risk,” she acknowledged.
Dr. Gordon suggested that the guidelines as they currently stand may not be that useful for real-life practice. Following them could result in a large amount of money being spent on early tests that are perhaps not necessary.
“What we do need to do is focus on the patients who’ve been on treatment long term,” she said.
SOURCE: Yates M et al. Rheumatology. 2018;57(Suppl. 3):key075.188.
LIVERPOOL, ENGLAND – , but long-term follow-up is much more important, according to data presented at the British Society for Rheumatology annual conference.
In just one specialist rheumatology center in England, which treats more than 8,000 patients annually, the cost of the first year’s optical coherence tomography (OCT) assessment would be more than $60,000. Additional costs would be incurred to screen those who had been on the drug for more than 5 years ,who were known to be at greater risk of hydroxychloroquine-induced retinopathy. This is within the National Health Service in England where the cost of a single OCT scan is around $70; in the private health sector, the cost of one test can be as high as $400.
Indeed, of 887 hydroxychloroquine users identified, 44% had at least one risk factor for hydroxychloroquine-induced retinopathy. These included being older than 60 years of age (30% of all users), having renal (10%) or hepatic (2%) impairment, retinal disease at baseline (8%), or using high (more than 6.5 mg/kg) doses of the drug based on their actual (9%) or ideal (4%) body weight.
“The retinal toxicity of hydroxychloroquine is a bit of a hot topic at the moment,” Dr. Yates said at the conference. While the drug has been around for years and used successfully to treat many patients with rheumatoid arthritis and systemic lupus erythematosus (SLE), a known side effect is retinal toxicity.
Traditionally, retinopathy has been quoted as being a relatively rare side effect, affecting around 0.5%-2% of the treated population. Recent data (JAMA Ophthalmol. 2014;132[12]:1453-60) suggest, however, that is probably a vast underestimate, with 7.5% of patients taking hydroxychloroquine for more than 5 years likely to be affected, as are up to 20% of those taking the drug for up to 20 years of treatment.
Dr. Yates and associates wanted to assess the burden of hydroxychloroquine use at their center and look at the risk factors and impact of the recent screening guidelines issued by the British Society for Rheumatology (Rheumatology [Oxford]. 2017;56[6]:865-8) in 2017 and by the Royal College of Ophthalmologists in 2018. These state that patients should have a formal baseline ophthalmic examination, ideally including OCT, within 6-12 months of starting therapy and an annual eye assessment with repeat OCT thereafter for the following 5 years; the ophthalmology guidelines recommending annual screening for the duration of therapy.
One criticism of increased screening for retinal toxicity in routine practice is consultants saying that they see only a handful of cases during their career, Dr. Yates observed. However, if you consider that in an average rheumatology department there are five consultants and 900 patients on hydroxychloroquine, 500 patients take the drug for 5 years or longer, 2% are picked up with non-OCT screening, that amounts to around two cases per year over a 5- to 10-year period. “So that fits with the narrative of only having seen a handful of cases pre-OCT,” Dr. Yates reasoned.
“I believe that this is a real problem, but I’m afraid this is the tip of the iceberg,” commented Caroline Gordon, MD, after her presentation. “We’ve been screening our patients in Birmingham now for about 5 years and we are definitely finding a significant number of patients with hydroxychloroquine toxicity who can be picked up with OCT and visual fields screening.”
Dr. Gordon, professor of rheumatology at the University of Birmingham (England) and a consultant rheumatologist for the University Hospitals NHS Foundation Trust and the Sandwell & West Birmingham Hospitals NHS Trust, helps look after one of the largest cohorts of patients with SLE in the United Kingdom.
A baseline eye examination has always been recommended, Dr. Gordon said, but she suggested that this could remain in the realm of the opticians with further assessment and referral as needed.
“I’m not convinced, from the work we’ve done, that there is any value in the baseline OCT,” Dr. Gordon said, “because we never find anything on the baseline OCT that we didn’t already expect from the opticians’ assessment.”
It is the long-term (longer than10 years) follow-up that needs to be the focus, rather than the initial period, she stressed, as the highest risk appears to be in patients who have been taking the drug for 15 years or longer. Prior to this, different types of retinopathy can occur that are actually attributable to the underlying disease and are not related hydroxychloroquine. Of course, patients on higher doses of hydroxychloroquine may need closer monitoring early on, “as they are at risk,” she acknowledged.
Dr. Gordon suggested that the guidelines as they currently stand may not be that useful for real-life practice. Following them could result in a large amount of money being spent on early tests that are perhaps not necessary.
“What we do need to do is focus on the patients who’ve been on treatment long term,” she said.
SOURCE: Yates M et al. Rheumatology. 2018;57(Suppl. 3):key075.188.
REPORTING FROM BSR 2018
Key clinical point: Long-term follow up is important for assessing hydroxychloroquine toxicity.
Major finding: 44% of patients had at least one risk factor for hydroxychloroquine-induced retinopathy after more than 5 years of treatment.
Study details: Electronic record review of 887 patients treated with hydroxychloroquine for about 5 years in a large tertiary rheumatology service.
Disclosures: Dr. Yates had nothing to disclose.
Source: Yates M et al. Rheumatology. 2018;57(Suppl. 3):key075.312.
Raised LDL cholesterol, hsCRP tied to polymyalgia rheumatica, GCA
LIVERPOOL, ENGLAND – The presence of traditional cardiovascular risk factors may precede the development of polymyalgia rheumatica and giant cell arteritis.
Data from the EPIC-Norfolk study, reported at the British Society for Rheumatology annual conference, showed that raised LDL cholesterol was associated with the onset of polymyalgia rheumatica (PMR) and that high sensitivity C-reactive protein (hsCRP) was associated with giant cell arteritis (GCA).
“There’s been an association between vascular disease and PMR and GCA reported, but the way cardiovascular disease has been defined has been based on rather late endpoints, such as angina, myocardial infarction, peripheral vascular disease, and ischemia,” said Max Yates, MBBS, MRCP, in an interview.
“So, what we wanted to do was look at underlying risk factors for those diseases and see how they play in, in terms of the timing of the diagnosis of PMR and GCA,” he explained. Dr. Yates, who is a National Institute for Health Research clinical lecturer in rheumatology at the University of East Anglia, Norwich, England, noted that this was probably the first prospective study to look at clinical and laboratory parameters for vascular disease prior to the onset of these diseases.
Previously, French researchers suggested that there might be a link between hypertension and subsequent PMR, but that was a descriptive study published over 30 years ago, Dr. Yates said. “There was another case-control study from the Mayo Clinic where they said that smoking was associated with incidence GCA,” he added. “So most of the work has been retrospective, case-control studies.”
The EPIC (European Prospective Investigation of Cancer)-Norfolk study is a large, prospective, community-based cohort study that, as its name might suggest, was originally set up to look at risk factors for cancer. Since then it has broadened to enable the study of risk factors for a whole host of other conditions.
More than 30,000 people aged 40-70 years were recruited into the study during 1993-1997, and 25,600 people (440,237 at-risk person-years) who had the necessary baseline and follow-up data were included in the current analysis performed by Dr. Yates and associates.
A total of 395 cases of PMR and 118 cases of GCA were identified using current classification criteria. Those with PMR were diagnosed at a mean age of 73.6 years and those with GCA at a mean age of 74.1 years. For both conditions, about three-quarters of patients were women.
The investigators then looked back at the patients’ original recruitment data in terms of their cardiovascular risk factors, which included their blood pressure readings; body mass index; smoking status; presence of diabetes; hsCRP; and LDL cholesterol, triglycerides, and HDL cholesterol levels.
“Ultimately, these traditional cardiovascular risk factors are present early on, prior to PMR and GCA,” Dr. Yates said.
What this means is that perhaps clinicians need to be more aware of managing these risk factors aggressively, he suggested, but therein lies a problem. “It’s obviously very difficult, early on, before anyone’s developed any disease, to target these risk factors, and you have to balance the risk and benefit for individuals.”
GCA is a “pretty rare” disease whereas PMR is “quite common,” Dr. Yates said, “but we probably need to target these risk factors as soon as people are diagnosed with these conditions, to try to prevent the cardiovascular morbidity that is seen.”
These data might also help explain the underlying etiology and why there is an increased risk of vascular disease seen in populations of patients with inflammatory arthritides.
Dr. Yates had no conflicts of interest to disclose.
SOURCE: Yates M et al. Rheumatology. 2018 Apr;57[Suppl. 3]:key075.312.
LIVERPOOL, ENGLAND – The presence of traditional cardiovascular risk factors may precede the development of polymyalgia rheumatica and giant cell arteritis.
Data from the EPIC-Norfolk study, reported at the British Society for Rheumatology annual conference, showed that raised LDL cholesterol was associated with the onset of polymyalgia rheumatica (PMR) and that high sensitivity C-reactive protein (hsCRP) was associated with giant cell arteritis (GCA).
“There’s been an association between vascular disease and PMR and GCA reported, but the way cardiovascular disease has been defined has been based on rather late endpoints, such as angina, myocardial infarction, peripheral vascular disease, and ischemia,” said Max Yates, MBBS, MRCP, in an interview.
“So, what we wanted to do was look at underlying risk factors for those diseases and see how they play in, in terms of the timing of the diagnosis of PMR and GCA,” he explained. Dr. Yates, who is a National Institute for Health Research clinical lecturer in rheumatology at the University of East Anglia, Norwich, England, noted that this was probably the first prospective study to look at clinical and laboratory parameters for vascular disease prior to the onset of these diseases.
Previously, French researchers suggested that there might be a link between hypertension and subsequent PMR, but that was a descriptive study published over 30 years ago, Dr. Yates said. “There was another case-control study from the Mayo Clinic where they said that smoking was associated with incidence GCA,” he added. “So most of the work has been retrospective, case-control studies.”
The EPIC (European Prospective Investigation of Cancer)-Norfolk study is a large, prospective, community-based cohort study that, as its name might suggest, was originally set up to look at risk factors for cancer. Since then it has broadened to enable the study of risk factors for a whole host of other conditions.
More than 30,000 people aged 40-70 years were recruited into the study during 1993-1997, and 25,600 people (440,237 at-risk person-years) who had the necessary baseline and follow-up data were included in the current analysis performed by Dr. Yates and associates.
A total of 395 cases of PMR and 118 cases of GCA were identified using current classification criteria. Those with PMR were diagnosed at a mean age of 73.6 years and those with GCA at a mean age of 74.1 years. For both conditions, about three-quarters of patients were women.
The investigators then looked back at the patients’ original recruitment data in terms of their cardiovascular risk factors, which included their blood pressure readings; body mass index; smoking status; presence of diabetes; hsCRP; and LDL cholesterol, triglycerides, and HDL cholesterol levels.
“Ultimately, these traditional cardiovascular risk factors are present early on, prior to PMR and GCA,” Dr. Yates said.
What this means is that perhaps clinicians need to be more aware of managing these risk factors aggressively, he suggested, but therein lies a problem. “It’s obviously very difficult, early on, before anyone’s developed any disease, to target these risk factors, and you have to balance the risk and benefit for individuals.”
GCA is a “pretty rare” disease whereas PMR is “quite common,” Dr. Yates said, “but we probably need to target these risk factors as soon as people are diagnosed with these conditions, to try to prevent the cardiovascular morbidity that is seen.”
These data might also help explain the underlying etiology and why there is an increased risk of vascular disease seen in populations of patients with inflammatory arthritides.
Dr. Yates had no conflicts of interest to disclose.
SOURCE: Yates M et al. Rheumatology. 2018 Apr;57[Suppl. 3]:key075.312.
LIVERPOOL, ENGLAND – The presence of traditional cardiovascular risk factors may precede the development of polymyalgia rheumatica and giant cell arteritis.
Data from the EPIC-Norfolk study, reported at the British Society for Rheumatology annual conference, showed that raised LDL cholesterol was associated with the onset of polymyalgia rheumatica (PMR) and that high sensitivity C-reactive protein (hsCRP) was associated with giant cell arteritis (GCA).
“There’s been an association between vascular disease and PMR and GCA reported, but the way cardiovascular disease has been defined has been based on rather late endpoints, such as angina, myocardial infarction, peripheral vascular disease, and ischemia,” said Max Yates, MBBS, MRCP, in an interview.
“So, what we wanted to do was look at underlying risk factors for those diseases and see how they play in, in terms of the timing of the diagnosis of PMR and GCA,” he explained. Dr. Yates, who is a National Institute for Health Research clinical lecturer in rheumatology at the University of East Anglia, Norwich, England, noted that this was probably the first prospective study to look at clinical and laboratory parameters for vascular disease prior to the onset of these diseases.
Previously, French researchers suggested that there might be a link between hypertension and subsequent PMR, but that was a descriptive study published over 30 years ago, Dr. Yates said. “There was another case-control study from the Mayo Clinic where they said that smoking was associated with incidence GCA,” he added. “So most of the work has been retrospective, case-control studies.”
The EPIC (European Prospective Investigation of Cancer)-Norfolk study is a large, prospective, community-based cohort study that, as its name might suggest, was originally set up to look at risk factors for cancer. Since then it has broadened to enable the study of risk factors for a whole host of other conditions.
More than 30,000 people aged 40-70 years were recruited into the study during 1993-1997, and 25,600 people (440,237 at-risk person-years) who had the necessary baseline and follow-up data were included in the current analysis performed by Dr. Yates and associates.
A total of 395 cases of PMR and 118 cases of GCA were identified using current classification criteria. Those with PMR were diagnosed at a mean age of 73.6 years and those with GCA at a mean age of 74.1 years. For both conditions, about three-quarters of patients were women.
The investigators then looked back at the patients’ original recruitment data in terms of their cardiovascular risk factors, which included their blood pressure readings; body mass index; smoking status; presence of diabetes; hsCRP; and LDL cholesterol, triglycerides, and HDL cholesterol levels.
“Ultimately, these traditional cardiovascular risk factors are present early on, prior to PMR and GCA,” Dr. Yates said.
What this means is that perhaps clinicians need to be more aware of managing these risk factors aggressively, he suggested, but therein lies a problem. “It’s obviously very difficult, early on, before anyone’s developed any disease, to target these risk factors, and you have to balance the risk and benefit for individuals.”
GCA is a “pretty rare” disease whereas PMR is “quite common,” Dr. Yates said, “but we probably need to target these risk factors as soon as people are diagnosed with these conditions, to try to prevent the cardiovascular morbidity that is seen.”
These data might also help explain the underlying etiology and why there is an increased risk of vascular disease seen in populations of patients with inflammatory arthritides.
Dr. Yates had no conflicts of interest to disclose.
SOURCE: Yates M et al. Rheumatology. 2018 Apr;57[Suppl. 3]:key075.312.
REPORTING FROM BSR 2018
Key clinical point: The presence of traditional cardiovascular risk factors may precede the development of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA).
Major finding: Raised LDL cholesterol was linked with the onset of PMR (subhazard ratio, 1.29) and raised hsCRP was associated with GCA (SHR, 1.85).
Study details: Data from the EPIC-Norfolk study: 385 cases of PMR and 118 cases of GCA identified from a population of more than 25,000 subjects.
Disclosures: Dr. Yates had no conflicts of interest to disclose.
Source: Yates M et al. Rheumatology. 2018 Apr;57[Suppl. 3]:key075.312.
Idiopathic pulmonary fibrosis a ‘robust diagnosis’
LIVERPOOL, ENGLAND – Very few patients with idiopathic pulmonary fibrosis have connective tissue disease antibodies, suggesting that IPF is a “robust diagnosis” when made on the basis of standard diagnostic tests, it was reported at the British Society for Rheumatology annual conference.
“The results were perhaps not what we’d expected,” said Caroline V. Cotton, PhD, of the Institute of Ageing and Chronic Disease at the University of Liverpool, England.
This means that chest physicians are getting the diagnosis right in the majority of cases, based on currently available methods, such as patients’ clinical history and examination, the results of high resolution–computed tomography, and widely available serology. “Which is good news,” Dr. Cotton observed.
Interstitial lung disease (ILD) comprises a huge spectrum of disorders. The main groups of ILDs are idiopathic, granulomatous, connective tissue disease–associated environmental, or medication exposure–associated; and the rare causes of ILD, each of which contain multiple subgroups of which IPF is one.
Sometimes it is obvious to respiratory physicians what the cause is, such as environmental exposure to asbestos or sarcoidosis for the granulomatous ILD, Dr. Cotton noted. Identifying connective tissue disease (CTD)–associated ILD can be more diagnostically challenging, however, and there are a large number of rheumatic conditions associated with CTD-associated ILD, including rheumatoid arthritis, systemic sclerosis, and Sjögren’s syndrome, to name a few.
One of the problems is that signs and symptoms of CTD may be absent at the time ILD starts to manifest and, even if signs are present, they may too subtle to be picked up in a general chest clinic. There also is a large number of antibodies for CTDs, but not all are widely available.
Dr. Cotton and her associates, therefore, wondered if there was a chance that patients being diagnosed with IPF actually could have covert CTD-associated ILD; this is an important distinction to make because the treatment differs for the two conditions. While ILD associated with CTD has a strong inflammatory component and is treated with corticosteroids and immunosuppressants, steroids can be harmful and increase mortality in IPF-ILD. The latter is treated with antifibrotic medications, such as pirfenidone and nintedanib.
For the study, serum samples from 250 patients with a definite diagnosis of IPF who were participating in the UK-BILD study were obtained and screened for known CTD antibodies using immunoprecipitation. Antibodies could be detected in just five (2%) patients – these included one patient each with anti-KS and anti-OJ antibodies, which are antisynthetase antibodies that are associated with myositis. Anti-Ku, another myositis-associated antibody, was identified in another patient, and one patient had an anti-RNA polymerase II antibody, which is associated with systemic sclerosis. Antimitochondrial autoantibodies were observed in one patient, and these are linked to primary biliary cirrhosis, which the patient was known to have.
There was nothing remarkable between the patients who did and did not have CTD antibodies in terms of their demographics, 76% and 80% were male, the mean ages were 73 and 70 years, respectively, and all were white.
However, 40% of patients did have unknown strong bands on immunoprecipitation, Dr. Cotton reported. This could suggest that there is an underlying immunological component to IPF, she added, but they had no recognized antibodies.
“A very small number of patients with IPF actually have the presence of autoantibodies strongly associated with CTDs. This suggests IPF is a very robust diagnosis; chest physicians are diagnosing it correctly most of the time, and they are really good at good at weeding out those who have got IPF and those who have potentially got connective tissue disease.” Dr. Cotton concluded.
Dr. Cotton had no conflicts of interest.
SOURCE: Cotton CV et al. Rheumatology. 2018;57[Suppl. 3]:key075.206.
LIVERPOOL, ENGLAND – Very few patients with idiopathic pulmonary fibrosis have connective tissue disease antibodies, suggesting that IPF is a “robust diagnosis” when made on the basis of standard diagnostic tests, it was reported at the British Society for Rheumatology annual conference.
“The results were perhaps not what we’d expected,” said Caroline V. Cotton, PhD, of the Institute of Ageing and Chronic Disease at the University of Liverpool, England.
This means that chest physicians are getting the diagnosis right in the majority of cases, based on currently available methods, such as patients’ clinical history and examination, the results of high resolution–computed tomography, and widely available serology. “Which is good news,” Dr. Cotton observed.
Interstitial lung disease (ILD) comprises a huge spectrum of disorders. The main groups of ILDs are idiopathic, granulomatous, connective tissue disease–associated environmental, or medication exposure–associated; and the rare causes of ILD, each of which contain multiple subgroups of which IPF is one.
Sometimes it is obvious to respiratory physicians what the cause is, such as environmental exposure to asbestos or sarcoidosis for the granulomatous ILD, Dr. Cotton noted. Identifying connective tissue disease (CTD)–associated ILD can be more diagnostically challenging, however, and there are a large number of rheumatic conditions associated with CTD-associated ILD, including rheumatoid arthritis, systemic sclerosis, and Sjögren’s syndrome, to name a few.
One of the problems is that signs and symptoms of CTD may be absent at the time ILD starts to manifest and, even if signs are present, they may too subtle to be picked up in a general chest clinic. There also is a large number of antibodies for CTDs, but not all are widely available.
Dr. Cotton and her associates, therefore, wondered if there was a chance that patients being diagnosed with IPF actually could have covert CTD-associated ILD; this is an important distinction to make because the treatment differs for the two conditions. While ILD associated with CTD has a strong inflammatory component and is treated with corticosteroids and immunosuppressants, steroids can be harmful and increase mortality in IPF-ILD. The latter is treated with antifibrotic medications, such as pirfenidone and nintedanib.
For the study, serum samples from 250 patients with a definite diagnosis of IPF who were participating in the UK-BILD study were obtained and screened for known CTD antibodies using immunoprecipitation. Antibodies could be detected in just five (2%) patients – these included one patient each with anti-KS and anti-OJ antibodies, which are antisynthetase antibodies that are associated with myositis. Anti-Ku, another myositis-associated antibody, was identified in another patient, and one patient had an anti-RNA polymerase II antibody, which is associated with systemic sclerosis. Antimitochondrial autoantibodies were observed in one patient, and these are linked to primary biliary cirrhosis, which the patient was known to have.
There was nothing remarkable between the patients who did and did not have CTD antibodies in terms of their demographics, 76% and 80% were male, the mean ages were 73 and 70 years, respectively, and all were white.
However, 40% of patients did have unknown strong bands on immunoprecipitation, Dr. Cotton reported. This could suggest that there is an underlying immunological component to IPF, she added, but they had no recognized antibodies.
“A very small number of patients with IPF actually have the presence of autoantibodies strongly associated with CTDs. This suggests IPF is a very robust diagnosis; chest physicians are diagnosing it correctly most of the time, and they are really good at good at weeding out those who have got IPF and those who have potentially got connective tissue disease.” Dr. Cotton concluded.
Dr. Cotton had no conflicts of interest.
SOURCE: Cotton CV et al. Rheumatology. 2018;57[Suppl. 3]:key075.206.
LIVERPOOL, ENGLAND – Very few patients with idiopathic pulmonary fibrosis have connective tissue disease antibodies, suggesting that IPF is a “robust diagnosis” when made on the basis of standard diagnostic tests, it was reported at the British Society for Rheumatology annual conference.
“The results were perhaps not what we’d expected,” said Caroline V. Cotton, PhD, of the Institute of Ageing and Chronic Disease at the University of Liverpool, England.
This means that chest physicians are getting the diagnosis right in the majority of cases, based on currently available methods, such as patients’ clinical history and examination, the results of high resolution–computed tomography, and widely available serology. “Which is good news,” Dr. Cotton observed.
Interstitial lung disease (ILD) comprises a huge spectrum of disorders. The main groups of ILDs are idiopathic, granulomatous, connective tissue disease–associated environmental, or medication exposure–associated; and the rare causes of ILD, each of which contain multiple subgroups of which IPF is one.
Sometimes it is obvious to respiratory physicians what the cause is, such as environmental exposure to asbestos or sarcoidosis for the granulomatous ILD, Dr. Cotton noted. Identifying connective tissue disease (CTD)–associated ILD can be more diagnostically challenging, however, and there are a large number of rheumatic conditions associated with CTD-associated ILD, including rheumatoid arthritis, systemic sclerosis, and Sjögren’s syndrome, to name a few.
One of the problems is that signs and symptoms of CTD may be absent at the time ILD starts to manifest and, even if signs are present, they may too subtle to be picked up in a general chest clinic. There also is a large number of antibodies for CTDs, but not all are widely available.
Dr. Cotton and her associates, therefore, wondered if there was a chance that patients being diagnosed with IPF actually could have covert CTD-associated ILD; this is an important distinction to make because the treatment differs for the two conditions. While ILD associated with CTD has a strong inflammatory component and is treated with corticosteroids and immunosuppressants, steroids can be harmful and increase mortality in IPF-ILD. The latter is treated with antifibrotic medications, such as pirfenidone and nintedanib.
For the study, serum samples from 250 patients with a definite diagnosis of IPF who were participating in the UK-BILD study were obtained and screened for known CTD antibodies using immunoprecipitation. Antibodies could be detected in just five (2%) patients – these included one patient each with anti-KS and anti-OJ antibodies, which are antisynthetase antibodies that are associated with myositis. Anti-Ku, another myositis-associated antibody, was identified in another patient, and one patient had an anti-RNA polymerase II antibody, which is associated with systemic sclerosis. Antimitochondrial autoantibodies were observed in one patient, and these are linked to primary biliary cirrhosis, which the patient was known to have.
There was nothing remarkable between the patients who did and did not have CTD antibodies in terms of their demographics, 76% and 80% were male, the mean ages were 73 and 70 years, respectively, and all were white.
However, 40% of patients did have unknown strong bands on immunoprecipitation, Dr. Cotton reported. This could suggest that there is an underlying immunological component to IPF, she added, but they had no recognized antibodies.
“A very small number of patients with IPF actually have the presence of autoantibodies strongly associated with CTDs. This suggests IPF is a very robust diagnosis; chest physicians are diagnosing it correctly most of the time, and they are really good at good at weeding out those who have got IPF and those who have potentially got connective tissue disease.” Dr. Cotton concluded.
Dr. Cotton had no conflicts of interest.
SOURCE: Cotton CV et al. Rheumatology. 2018;57[Suppl. 3]:key075.206.
REPORTING FROM RHEUMATOLOGY 2018
Key clinical point: Few patients diagnosed as having idiopathic pulmonary fibrosis (IPF) are likely to have connective tissue disorders (CTD).
Major finding: Only 2% of patients had a recognized CTD antibody present.
Study details: 250 patients with IPF participating in the UK-BILD multicenter study.
Disclosures: Dr. Cotton stated she had no conflicts of interest.
Source: Cotton CV et al. Rheumatology. 2018;57(Suppl. 3):key075.206.
Emergency gout admission increase is ‘call to arms’
LIVERPOOL, ENGLAND – The rate of emergency hospital admissions for gout in England has seen a 59% increase over the past decade, while that of rheumatoid arthritis has halved, it was reported at the British Society for Rheumatology annual conference.
Over an approximate 10-year period (2006-2017), the incidence rate of unplanned gout admissions increased from 7.9 to 12.5 admissions per 100,000 of the population. This represented an increase from 0.023% to 0.032% of all hospital admissions during the period.
To put that into perspective, unplanned admissions for rheumatoid arthritis (RA), decreased from 8.6 to 4.3 admissions per 100,000 of the population, said Mark D. Russell, MD, a rheumatology registrar at Guy’s and St Thomas’ Hospital in London.
Furthermore, primary care prescriptions for common gout medications have seen a dramatic increase over the same time period in England; allopurinol prescriptions are up 72%, there’s been a 166% increase in colchicine prescriptions, and a 20-fold increase in febuxostat (Uloric) prescriptions since data became available for its in 2010.
“Gout’s very much a treatable condition,” Dr. Russell said, but with 82% of all gout admissions being unplanned, “there’s clearly more to do; this should be a call to arms for rheumatologists to help reduce the in-patient burden of this condition.”
The mean length of hospital stay was estimated at 6.6 days, with the median being 3.2 days. Gout accounted for just under 350,000 hospital bed days from 2006 to 2017, and with the cost of a single gout admission being anything from £850 up to £5,600, it constitutes a significant burden for the country’s National Health Service.
But what can be done? Would a “door-to-needle time campaign” help? So that when patients attend the emergency department they are assessed rapidly and treated accordingly? Dr. Russell queried.
Education could be the key, was the consensus during the discussion following his presentation. Education, and not just of those affected by the condition, but also of the family physicians who seem to have a “knee-jerk reaction” to prescribe medications, and not always appropriately. Even hospital staff may need help in differentiating gout from other emergency presentations, with some admitting patients suspecting infection or wrongly discharging them.
Pharmacist-led gout clinics
Another approach to try to avoid emergency hospital visits could be better management and perhaps setting up specialist gout clinics. Such clinics have already been piloted, and rheumatology pharmacist Jane Whiteman shared her experience of setting up a monthly, pharmacist-led gout clinic in a separate presentation.
Dr. Whiteman, who works at Royal Victoria Hospital, part of the Belfast Health and Social Care Trust in Ireland, presented data on 52 patients who were seen at the clinic between June 2015 and May 2017. The total number of patient visits was 87, with an average of 1.7 visits per patient.
Of 38 patients who were discharged from the clinic, 29 (76%) had met target levels of serum uric acid, which guidelines from the British Society for Rheumatology set at less than 0.3 mmol/L (5 mg/dL) and those from the European League of Rheumatism set at less than 0.36 mmol/L (6 mg/dL).
It is important to reduce serum uric acid levels, Dr. Whiteman explained. “Gout occurs when serum uric acid rises and urate crystals reach their saturation point in the serum and start to crystallize out into the joints and into the tissues,” she said. “It’s a progressive disease that usually starts in one joint, but if the serum uric acid isn’t controlled then it can go on to affect a number of joints,” and cause chronic arthritis, among other potentially serious conditions, and is an independent risk factor for cardiovascular and renal disease.
“Studies across the world have shown that gout is not well looked after; patient adherence to treatment is very poor,” Dr. Whiteman said. “Among all the chronic diseases it has the lowest adherence to treatment,” she added, noting that one study showed just one-fifth of patients remained on gout medication at 1 year.
Patient education is an important part of the clinic’s services, as when people are asymptomatic and between bouts of gout, they perhaps do not realize that they still need to take their medication. Education thus needs to include talking about their diet and lifestyle, providing information on medication, and why it is important to keep their serum uric acid levels in check.
After patients’ initial referral to the clinic, they are followed up by the clinic every month until their serum urate levels are below the 0.3 mmol/L target. They can then be discharged and monitored by their family physician.
Postdischarge, Dr. Whiteman and her colleagues found that 22 (76%) of the 29 patients who had met their target levels of serum uric acid later had serum uric acid tested at least once, showing an average level of 0.29 mmol/L at follow-up. This reassuring result occurred perhaps because of a majority of patients (79%) who were still being prescribed, and presumably taking, urate-lowering therapy. Seven patients did not undergo follow-up serum uric acid testing because they had died (one), were in the hospital (one), were not taking medication because they had made diet or lifestyle changes (three), or had their treatment on hold (two).
“I think the gout clinic has been a success; it has addressed barriers to optimal management through education of the patient,” Dr. Whiteman said.
Both presenters had nothing to disclose.
SOURCE: Russel M et al. Rheumatology. 2018;57[Suppl. 3]:key075.186; Whiteman J, et al. Rheumatology. 2018;57[Suppl. 3]:key075.215.
LIVERPOOL, ENGLAND – The rate of emergency hospital admissions for gout in England has seen a 59% increase over the past decade, while that of rheumatoid arthritis has halved, it was reported at the British Society for Rheumatology annual conference.
Over an approximate 10-year period (2006-2017), the incidence rate of unplanned gout admissions increased from 7.9 to 12.5 admissions per 100,000 of the population. This represented an increase from 0.023% to 0.032% of all hospital admissions during the period.
To put that into perspective, unplanned admissions for rheumatoid arthritis (RA), decreased from 8.6 to 4.3 admissions per 100,000 of the population, said Mark D. Russell, MD, a rheumatology registrar at Guy’s and St Thomas’ Hospital in London.
Furthermore, primary care prescriptions for common gout medications have seen a dramatic increase over the same time period in England; allopurinol prescriptions are up 72%, there’s been a 166% increase in colchicine prescriptions, and a 20-fold increase in febuxostat (Uloric) prescriptions since data became available for its in 2010.
“Gout’s very much a treatable condition,” Dr. Russell said, but with 82% of all gout admissions being unplanned, “there’s clearly more to do; this should be a call to arms for rheumatologists to help reduce the in-patient burden of this condition.”
The mean length of hospital stay was estimated at 6.6 days, with the median being 3.2 days. Gout accounted for just under 350,000 hospital bed days from 2006 to 2017, and with the cost of a single gout admission being anything from £850 up to £5,600, it constitutes a significant burden for the country’s National Health Service.
But what can be done? Would a “door-to-needle time campaign” help? So that when patients attend the emergency department they are assessed rapidly and treated accordingly? Dr. Russell queried.
Education could be the key, was the consensus during the discussion following his presentation. Education, and not just of those affected by the condition, but also of the family physicians who seem to have a “knee-jerk reaction” to prescribe medications, and not always appropriately. Even hospital staff may need help in differentiating gout from other emergency presentations, with some admitting patients suspecting infection or wrongly discharging them.
Pharmacist-led gout clinics
Another approach to try to avoid emergency hospital visits could be better management and perhaps setting up specialist gout clinics. Such clinics have already been piloted, and rheumatology pharmacist Jane Whiteman shared her experience of setting up a monthly, pharmacist-led gout clinic in a separate presentation.
Dr. Whiteman, who works at Royal Victoria Hospital, part of the Belfast Health and Social Care Trust in Ireland, presented data on 52 patients who were seen at the clinic between June 2015 and May 2017. The total number of patient visits was 87, with an average of 1.7 visits per patient.
Of 38 patients who were discharged from the clinic, 29 (76%) had met target levels of serum uric acid, which guidelines from the British Society for Rheumatology set at less than 0.3 mmol/L (5 mg/dL) and those from the European League of Rheumatism set at less than 0.36 mmol/L (6 mg/dL).
It is important to reduce serum uric acid levels, Dr. Whiteman explained. “Gout occurs when serum uric acid rises and urate crystals reach their saturation point in the serum and start to crystallize out into the joints and into the tissues,” she said. “It’s a progressive disease that usually starts in one joint, but if the serum uric acid isn’t controlled then it can go on to affect a number of joints,” and cause chronic arthritis, among other potentially serious conditions, and is an independent risk factor for cardiovascular and renal disease.
“Studies across the world have shown that gout is not well looked after; patient adherence to treatment is very poor,” Dr. Whiteman said. “Among all the chronic diseases it has the lowest adherence to treatment,” she added, noting that one study showed just one-fifth of patients remained on gout medication at 1 year.
Patient education is an important part of the clinic’s services, as when people are asymptomatic and between bouts of gout, they perhaps do not realize that they still need to take their medication. Education thus needs to include talking about their diet and lifestyle, providing information on medication, and why it is important to keep their serum uric acid levels in check.
After patients’ initial referral to the clinic, they are followed up by the clinic every month until their serum urate levels are below the 0.3 mmol/L target. They can then be discharged and monitored by their family physician.
Postdischarge, Dr. Whiteman and her colleagues found that 22 (76%) of the 29 patients who had met their target levels of serum uric acid later had serum uric acid tested at least once, showing an average level of 0.29 mmol/L at follow-up. This reassuring result occurred perhaps because of a majority of patients (79%) who were still being prescribed, and presumably taking, urate-lowering therapy. Seven patients did not undergo follow-up serum uric acid testing because they had died (one), were in the hospital (one), were not taking medication because they had made diet or lifestyle changes (three), or had their treatment on hold (two).
“I think the gout clinic has been a success; it has addressed barriers to optimal management through education of the patient,” Dr. Whiteman said.
Both presenters had nothing to disclose.
SOURCE: Russel M et al. Rheumatology. 2018;57[Suppl. 3]:key075.186; Whiteman J, et al. Rheumatology. 2018;57[Suppl. 3]:key075.215.
LIVERPOOL, ENGLAND – The rate of emergency hospital admissions for gout in England has seen a 59% increase over the past decade, while that of rheumatoid arthritis has halved, it was reported at the British Society for Rheumatology annual conference.
Over an approximate 10-year period (2006-2017), the incidence rate of unplanned gout admissions increased from 7.9 to 12.5 admissions per 100,000 of the population. This represented an increase from 0.023% to 0.032% of all hospital admissions during the period.
To put that into perspective, unplanned admissions for rheumatoid arthritis (RA), decreased from 8.6 to 4.3 admissions per 100,000 of the population, said Mark D. Russell, MD, a rheumatology registrar at Guy’s and St Thomas’ Hospital in London.
Furthermore, primary care prescriptions for common gout medications have seen a dramatic increase over the same time period in England; allopurinol prescriptions are up 72%, there’s been a 166% increase in colchicine prescriptions, and a 20-fold increase in febuxostat (Uloric) prescriptions since data became available for its in 2010.
“Gout’s very much a treatable condition,” Dr. Russell said, but with 82% of all gout admissions being unplanned, “there’s clearly more to do; this should be a call to arms for rheumatologists to help reduce the in-patient burden of this condition.”
The mean length of hospital stay was estimated at 6.6 days, with the median being 3.2 days. Gout accounted for just under 350,000 hospital bed days from 2006 to 2017, and with the cost of a single gout admission being anything from £850 up to £5,600, it constitutes a significant burden for the country’s National Health Service.
But what can be done? Would a “door-to-needle time campaign” help? So that when patients attend the emergency department they are assessed rapidly and treated accordingly? Dr. Russell queried.
Education could be the key, was the consensus during the discussion following his presentation. Education, and not just of those affected by the condition, but also of the family physicians who seem to have a “knee-jerk reaction” to prescribe medications, and not always appropriately. Even hospital staff may need help in differentiating gout from other emergency presentations, with some admitting patients suspecting infection or wrongly discharging them.
Pharmacist-led gout clinics
Another approach to try to avoid emergency hospital visits could be better management and perhaps setting up specialist gout clinics. Such clinics have already been piloted, and rheumatology pharmacist Jane Whiteman shared her experience of setting up a monthly, pharmacist-led gout clinic in a separate presentation.
Dr. Whiteman, who works at Royal Victoria Hospital, part of the Belfast Health and Social Care Trust in Ireland, presented data on 52 patients who were seen at the clinic between June 2015 and May 2017. The total number of patient visits was 87, with an average of 1.7 visits per patient.
Of 38 patients who were discharged from the clinic, 29 (76%) had met target levels of serum uric acid, which guidelines from the British Society for Rheumatology set at less than 0.3 mmol/L (5 mg/dL) and those from the European League of Rheumatism set at less than 0.36 mmol/L (6 mg/dL).
It is important to reduce serum uric acid levels, Dr. Whiteman explained. “Gout occurs when serum uric acid rises and urate crystals reach their saturation point in the serum and start to crystallize out into the joints and into the tissues,” she said. “It’s a progressive disease that usually starts in one joint, but if the serum uric acid isn’t controlled then it can go on to affect a number of joints,” and cause chronic arthritis, among other potentially serious conditions, and is an independent risk factor for cardiovascular and renal disease.
“Studies across the world have shown that gout is not well looked after; patient adherence to treatment is very poor,” Dr. Whiteman said. “Among all the chronic diseases it has the lowest adherence to treatment,” she added, noting that one study showed just one-fifth of patients remained on gout medication at 1 year.
Patient education is an important part of the clinic’s services, as when people are asymptomatic and between bouts of gout, they perhaps do not realize that they still need to take their medication. Education thus needs to include talking about their diet and lifestyle, providing information on medication, and why it is important to keep their serum uric acid levels in check.
After patients’ initial referral to the clinic, they are followed up by the clinic every month until their serum urate levels are below the 0.3 mmol/L target. They can then be discharged and monitored by their family physician.
Postdischarge, Dr. Whiteman and her colleagues found that 22 (76%) of the 29 patients who had met their target levels of serum uric acid later had serum uric acid tested at least once, showing an average level of 0.29 mmol/L at follow-up. This reassuring result occurred perhaps because of a majority of patients (79%) who were still being prescribed, and presumably taking, urate-lowering therapy. Seven patients did not undergo follow-up serum uric acid testing because they had died (one), were in the hospital (one), were not taking medication because they had made diet or lifestyle changes (three), or had their treatment on hold (two).
“I think the gout clinic has been a success; it has addressed barriers to optimal management through education of the patient,” Dr. Whiteman said.
Both presenters had nothing to disclose.
SOURCE: Russel M et al. Rheumatology. 2018;57[Suppl. 3]:key075.186; Whiteman J, et al. Rheumatology. 2018;57[Suppl. 3]:key075.215.
AT RHEUMATOLOGY 2018
Key clinical point:
Major finding: The rate of emergency hospital admissions for gout in England increased by 59%, from 7.9 to 12.5 admissions per 100,000 of the population; 76% of patients attending a pharmacist-led gout clinic achieved target serum uric acid levels.
Study details: An analysis of National Health Service data from April 2006 to March 2017 on hospital admissions for gout and primary care prescription data and a separate study of 52 patients attending a pharmacist-led gout clinic.
Disclosures: Both presenters had nothing to disclose.
Sources: Russell M et al. Rheumatology. 2018;57[Suppl. 3]:key075.186; Whiteman J et al. Rheumatology. 2018;57[Suppl. 3]:key075.215.
Ixekizumab improves psoriatic arthritis patient-reported outcomes
LIVERPOOL, ENGLAND – In biologic-experienced patients with psoriatic arthritis, the interleukin-17 inhibitor ixekizumab not only met the primary efficacy endpoint of a pivotal phase 3 trial, but also improved multiple patient-reported outcomes in doing so.
Newly-released results from the Study of Ixekizumab in Participants With Active Psoriatic Arthritis (SPIRIT-P2) showed that patients who received active treatment exhibited significantly better changes in physical function, quality of life, itch score, and work productivity compared with those given placebo.
Patients treated with ixekizumab 80 mg every 2 or 4 weeks more often achieved the MCID by week 24, reaching 40% for 80 mg every 2 weeks and 43% for every 4 weeks, compared with 17% for placebo.
A total of 363 patients who met CASPAR (Classification Criteria for Psoriatic Arthritis) criteria were randomized into the SPIRIT-P2 trial. Patients could be included only if they had at least three tender and three swollen joints, active skin lesions, or a documented history of skin psoriasis, and had received prior treatment with a tumor necrosis factor inhibitor (TNFi).
“The population of patients studied is representative of the patients we see in our clinics,” said Dr. Marzo-Ortega, a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust, England. The mean age was 52 years, a similar percentage of men and women were seen, and the majority (53%-58%) were inadequate responders to one TNFi. One-third had not responded to two TNFis, and 8%-10% had an intolerance.
The primary endpoint results, which have been previously presented and published (Lancet. 2017;389[10086]:2317-27), showed that a significantly (P less than .0001) higher percentage of patients treated with either of the two regimens of ixekizumab achieved a 20% response level on American College of Rheumatology criteria (ACR20) at 24 weeks. Indeed, 48% of 123 patients given 80 mg of ixekizumab every 2 weeks and 53% of 122 given 80 mg every 4 weeks achieved an ACR20 versus 20% of 118 placebo-treated patients. Also, on two key secondary endpoints at 24 weeks, an ACR50 response was achieved by a respective 33%, 35%, and 5% of patients, and an ACR70 by 12%, 22%, and 0%, she said.
Dr. Marzo-Ortega noted that the study had only been powered to show a difference between the active treatment and placebo, and not between the two doses, and that, looking at the speed of response, a difference from placebo was already being seen by week 2 “and certainly by week 4,” indicating an early effect. Data from the trial at 52 weeks are being analyzed and should be available soon, she said.
Another efficacy measure used was the percentage of patients achieving minimum disease activity at week 24. “These are stringent criteria to achieve: Five of seven criteria need to be met,” Dr. Marzo-Ortega said. “This was achieved by almost 30% of patients on the 4-weekly dose,” and by 24% on the 2-weekly dose, but by just 3% of those given placebo.
“One of the remarkable things is that nearly a third [of patients] achieved PASI [Psoriasis Area Severity Index] 100 by week 24, which is complete resolution of skin psoriasis,” she said. This is one of the first times this type of skin response has been seen in a psoriasis trial, she noted.
However, there was little difference between the active treatment and placebo arms in terms of the percentage of patients seeing a response on enthesitis, and only the dose taken every 4 weeks had a significant benefit over placebo in terms of improving dactylitis.
It is not clear why these modest results were seen in the joints, perhaps there were too few patients. While this is surprising, Dr. Marzo-Ortega noted that she “wouldn’t put too much weight on” the lack of an enthesis response; these are “fantastic drugs for the skin,” she said. “There is no doubt about it.”
Other findings from the trial included a significant improvement in itch with both ixekizumab regimens versus placebo, as shown by a greater reduction in numerical rating scale scores from baseline to week 24 (–3.4 and –3.5 vs. –1.2; P less than .001).
Significant improvements with ixekizumab versus placebo in patients’ mental and physical health were also seen when data from the Short Form–36 and EQ-5D instruments were analyzed.
There was also evidence that treatment with ixekizumab significantly improved patients’ presenteeism, work productivity, and activity impairment at work when compared against placebo. There was no difference in absenteeism, as measured by changes in Work Productivity and Activity Impairment Questionnaire–Specific Health Problem scores from baseline to week 24.
SPIRIT-P2 is one of two pivotal trials conducted with ixekizumab in patients with psoriatic arthritis; the other is SPIRIT-P1, which was conducted in biologic-naive patients (Ann Rheum Dis. 2017;76[1]:79-87). Investigators recently reported 1-year data from it (J Rheumatol. 2018;45[3]:367-77.).
Eli Lilly, which markets ixekizumab as Taltz, sponsored the study. Dr. Marzo-Ortega disclosed receiving honoraria from AbbVie, Celgene, Eli Lilly, Novartis, and UCB, and honoraria and research funding from Janssen and Pfizer. Several other authors reported disclosures with many manufacturers of biologics for psoriatic arthritis, including Eli Lilly.
SOURCE: Marzo-Ortega H et al. Rheumatology. 2018;57[Suppl. 3]:key075.185.
LIVERPOOL, ENGLAND – In biologic-experienced patients with psoriatic arthritis, the interleukin-17 inhibitor ixekizumab not only met the primary efficacy endpoint of a pivotal phase 3 trial, but also improved multiple patient-reported outcomes in doing so.
Newly-released results from the Study of Ixekizumab in Participants With Active Psoriatic Arthritis (SPIRIT-P2) showed that patients who received active treatment exhibited significantly better changes in physical function, quality of life, itch score, and work productivity compared with those given placebo.
Patients treated with ixekizumab 80 mg every 2 or 4 weeks more often achieved the MCID by week 24, reaching 40% for 80 mg every 2 weeks and 43% for every 4 weeks, compared with 17% for placebo.
A total of 363 patients who met CASPAR (Classification Criteria for Psoriatic Arthritis) criteria were randomized into the SPIRIT-P2 trial. Patients could be included only if they had at least three tender and three swollen joints, active skin lesions, or a documented history of skin psoriasis, and had received prior treatment with a tumor necrosis factor inhibitor (TNFi).
“The population of patients studied is representative of the patients we see in our clinics,” said Dr. Marzo-Ortega, a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust, England. The mean age was 52 years, a similar percentage of men and women were seen, and the majority (53%-58%) were inadequate responders to one TNFi. One-third had not responded to two TNFis, and 8%-10% had an intolerance.
The primary endpoint results, which have been previously presented and published (Lancet. 2017;389[10086]:2317-27), showed that a significantly (P less than .0001) higher percentage of patients treated with either of the two regimens of ixekizumab achieved a 20% response level on American College of Rheumatology criteria (ACR20) at 24 weeks. Indeed, 48% of 123 patients given 80 mg of ixekizumab every 2 weeks and 53% of 122 given 80 mg every 4 weeks achieved an ACR20 versus 20% of 118 placebo-treated patients. Also, on two key secondary endpoints at 24 weeks, an ACR50 response was achieved by a respective 33%, 35%, and 5% of patients, and an ACR70 by 12%, 22%, and 0%, she said.
Dr. Marzo-Ortega noted that the study had only been powered to show a difference between the active treatment and placebo, and not between the two doses, and that, looking at the speed of response, a difference from placebo was already being seen by week 2 “and certainly by week 4,” indicating an early effect. Data from the trial at 52 weeks are being analyzed and should be available soon, she said.
Another efficacy measure used was the percentage of patients achieving minimum disease activity at week 24. “These are stringent criteria to achieve: Five of seven criteria need to be met,” Dr. Marzo-Ortega said. “This was achieved by almost 30% of patients on the 4-weekly dose,” and by 24% on the 2-weekly dose, but by just 3% of those given placebo.
“One of the remarkable things is that nearly a third [of patients] achieved PASI [Psoriasis Area Severity Index] 100 by week 24, which is complete resolution of skin psoriasis,” she said. This is one of the first times this type of skin response has been seen in a psoriasis trial, she noted.
However, there was little difference between the active treatment and placebo arms in terms of the percentage of patients seeing a response on enthesitis, and only the dose taken every 4 weeks had a significant benefit over placebo in terms of improving dactylitis.
It is not clear why these modest results were seen in the joints, perhaps there were too few patients. While this is surprising, Dr. Marzo-Ortega noted that she “wouldn’t put too much weight on” the lack of an enthesis response; these are “fantastic drugs for the skin,” she said. “There is no doubt about it.”
Other findings from the trial included a significant improvement in itch with both ixekizumab regimens versus placebo, as shown by a greater reduction in numerical rating scale scores from baseline to week 24 (–3.4 and –3.5 vs. –1.2; P less than .001).
Significant improvements with ixekizumab versus placebo in patients’ mental and physical health were also seen when data from the Short Form–36 and EQ-5D instruments were analyzed.
There was also evidence that treatment with ixekizumab significantly improved patients’ presenteeism, work productivity, and activity impairment at work when compared against placebo. There was no difference in absenteeism, as measured by changes in Work Productivity and Activity Impairment Questionnaire–Specific Health Problem scores from baseline to week 24.
SPIRIT-P2 is one of two pivotal trials conducted with ixekizumab in patients with psoriatic arthritis; the other is SPIRIT-P1, which was conducted in biologic-naive patients (Ann Rheum Dis. 2017;76[1]:79-87). Investigators recently reported 1-year data from it (J Rheumatol. 2018;45[3]:367-77.).
Eli Lilly, which markets ixekizumab as Taltz, sponsored the study. Dr. Marzo-Ortega disclosed receiving honoraria from AbbVie, Celgene, Eli Lilly, Novartis, and UCB, and honoraria and research funding from Janssen and Pfizer. Several other authors reported disclosures with many manufacturers of biologics for psoriatic arthritis, including Eli Lilly.
SOURCE: Marzo-Ortega H et al. Rheumatology. 2018;57[Suppl. 3]:key075.185.
LIVERPOOL, ENGLAND – In biologic-experienced patients with psoriatic arthritis, the interleukin-17 inhibitor ixekizumab not only met the primary efficacy endpoint of a pivotal phase 3 trial, but also improved multiple patient-reported outcomes in doing so.
Newly-released results from the Study of Ixekizumab in Participants With Active Psoriatic Arthritis (SPIRIT-P2) showed that patients who received active treatment exhibited significantly better changes in physical function, quality of life, itch score, and work productivity compared with those given placebo.
Patients treated with ixekizumab 80 mg every 2 or 4 weeks more often achieved the MCID by week 24, reaching 40% for 80 mg every 2 weeks and 43% for every 4 weeks, compared with 17% for placebo.
A total of 363 patients who met CASPAR (Classification Criteria for Psoriatic Arthritis) criteria were randomized into the SPIRIT-P2 trial. Patients could be included only if they had at least three tender and three swollen joints, active skin lesions, or a documented history of skin psoriasis, and had received prior treatment with a tumor necrosis factor inhibitor (TNFi).
“The population of patients studied is representative of the patients we see in our clinics,” said Dr. Marzo-Ortega, a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust, England. The mean age was 52 years, a similar percentage of men and women were seen, and the majority (53%-58%) were inadequate responders to one TNFi. One-third had not responded to two TNFis, and 8%-10% had an intolerance.
The primary endpoint results, which have been previously presented and published (Lancet. 2017;389[10086]:2317-27), showed that a significantly (P less than .0001) higher percentage of patients treated with either of the two regimens of ixekizumab achieved a 20% response level on American College of Rheumatology criteria (ACR20) at 24 weeks. Indeed, 48% of 123 patients given 80 mg of ixekizumab every 2 weeks and 53% of 122 given 80 mg every 4 weeks achieved an ACR20 versus 20% of 118 placebo-treated patients. Also, on two key secondary endpoints at 24 weeks, an ACR50 response was achieved by a respective 33%, 35%, and 5% of patients, and an ACR70 by 12%, 22%, and 0%, she said.
Dr. Marzo-Ortega noted that the study had only been powered to show a difference between the active treatment and placebo, and not between the two doses, and that, looking at the speed of response, a difference from placebo was already being seen by week 2 “and certainly by week 4,” indicating an early effect. Data from the trial at 52 weeks are being analyzed and should be available soon, she said.
Another efficacy measure used was the percentage of patients achieving minimum disease activity at week 24. “These are stringent criteria to achieve: Five of seven criteria need to be met,” Dr. Marzo-Ortega said. “This was achieved by almost 30% of patients on the 4-weekly dose,” and by 24% on the 2-weekly dose, but by just 3% of those given placebo.
“One of the remarkable things is that nearly a third [of patients] achieved PASI [Psoriasis Area Severity Index] 100 by week 24, which is complete resolution of skin psoriasis,” she said. This is one of the first times this type of skin response has been seen in a psoriasis trial, she noted.
However, there was little difference between the active treatment and placebo arms in terms of the percentage of patients seeing a response on enthesitis, and only the dose taken every 4 weeks had a significant benefit over placebo in terms of improving dactylitis.
It is not clear why these modest results were seen in the joints, perhaps there were too few patients. While this is surprising, Dr. Marzo-Ortega noted that she “wouldn’t put too much weight on” the lack of an enthesis response; these are “fantastic drugs for the skin,” she said. “There is no doubt about it.”
Other findings from the trial included a significant improvement in itch with both ixekizumab regimens versus placebo, as shown by a greater reduction in numerical rating scale scores from baseline to week 24 (–3.4 and –3.5 vs. –1.2; P less than .001).
Significant improvements with ixekizumab versus placebo in patients’ mental and physical health were also seen when data from the Short Form–36 and EQ-5D instruments were analyzed.
There was also evidence that treatment with ixekizumab significantly improved patients’ presenteeism, work productivity, and activity impairment at work when compared against placebo. There was no difference in absenteeism, as measured by changes in Work Productivity and Activity Impairment Questionnaire–Specific Health Problem scores from baseline to week 24.
SPIRIT-P2 is one of two pivotal trials conducted with ixekizumab in patients with psoriatic arthritis; the other is SPIRIT-P1, which was conducted in biologic-naive patients (Ann Rheum Dis. 2017;76[1]:79-87). Investigators recently reported 1-year data from it (J Rheumatol. 2018;45[3]:367-77.).
Eli Lilly, which markets ixekizumab as Taltz, sponsored the study. Dr. Marzo-Ortega disclosed receiving honoraria from AbbVie, Celgene, Eli Lilly, Novartis, and UCB, and honoraria and research funding from Janssen and Pfizer. Several other authors reported disclosures with many manufacturers of biologics for psoriatic arthritis, including Eli Lilly.
SOURCE: Marzo-Ortega H et al. Rheumatology. 2018;57[Suppl. 3]:key075.185.
REPORTING FROM RHEUMATOLOGY 2018
Key clinical point: Ixekizumab has multiple beneficial effects in patients with psoriatic arthritis previously treated with biologics.
Major finding: Mean HAQ-DI score changes (baseline to week 24) were –0.4 and –0.6 with ixekizumab (80 mg every 2 or 4 weeks) and –0.2 for placebo (P less than or equal to .001).
Study details: SPIRIT-P2: A randomized, double-blind, placebo-controlled phase 3 trial of ixekizumab in 363 biologic-experienced patients.
Disclosures: Eli Lilly, which markets ixekizumab as Taltz, sponsored the study. Dr. Marzo-Ortega disclosed receiving honoraria from AbbVie, Celgene, Eli Lilly, Novartis, and UCB, and honoraria and research funding from Janssen and Pfizer. Several other authors reported disclosures with many manufacturers of biologics for psoriatic arthritis, including Eli Lilly.
Source: Marzo-Ortega H et al. Rheumatology. 2018;57[Suppl. 3]:key075.185.
Comorbid spondyloarthritis and fibromyalgia lower response to TNF inhibitors
LIVERPOOL, ENGLAND – Individuals with axial spondyloarthritis (axSpA) who have comorbid fibromyalgia do respond to biologic therapy but at a seemingly lower rate if they have a high symptom score during early assessments.
Data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) showed that participants with axSpA who were starting biologic therapy with a tumor necrosis factor inhibitor (TNFi) for the first time also had worse disease activity at baseline if they met fibromyalgia research criteria than if they did not.
“The issue of fibromyalgia as a comorbidity in axial SpA has been the subject of current considerable interest,” said Dr. Macfarlane, who is Clinical Chair in Epidemiology at the University of Aberdeen (Scotland), where the BSRBR-AS is run. This is for several reasons: “One is the challenge of identifying patients with axial SpA who have comorbid fibromyalgia.
“The second is the concern that comorbid fibromyalgia may have an effect on disease indices such as BASDAI [Bath Ankylosing Spondylitis Disease Activity Index],” Dr. Macfarlane observed.
This leads to the third issue: “Are patients with comorbid fibromyalgia inappropriately receiving biological therapy, and how do they respond if they do receive it?”
Previous data from the BSRBR-AS have shown that approximately one in five patients with axSpA meet research criteria for fibromyalgia (Arthritis Rheumatol. 2017;69:2144-50) and that the prevalence of the comorbidity was higher in those who met Assessment of SpondyloArthritis International Society imaging criteria and lower in those who only met clinical criteria (25% vs. 10%).
The current aims of the study presented by Dr. Macfarlane were to first quantify the extent to which meeting fibromyalgia criteria was associated with higher measures of disease activity and impact, and then to see if meeting these criteria was associated with a poorer response to first use of a TNFi.
In order to find out, Dr. Macfarlane and his associates examined data from the prospective BSRBR-AS, which has been running since 2012. The BSRBR-AS recruits patients with ASAS-confirmed axSpA who are newly starting biologics from 83 U.K. centers.
At recruitment and at 3 months, patients starting biologic treatment undergo several assessments, which since 2015 has included research criteria for fibromyalgia (J Rheumatol. 2011;38:1113–22). The latter incorporate a Widespread Pain Index rated 0-19 and a Symptom Severity Scale rated 0-12 and cover items such as fatigue and waking up unrefreshed, and the presence of lower abdominal pain or headaches.
To date, around 1,750 participants in the BSRBR-AS have completed the fibromyalgia criteria, Dr. Macfarlane said.
Across the board, baseline measures of disease activity were lower in patients who met the fibromyalgia criteria versus those who did not. This included the BASDAI and the Bath Ankylosing Spondylitis Functional Index, where scores were approximately 6.5 and 4.5 for each measure.
“Quality of life was significantly lower in those who were fibromyalgia positive,” Dr. Macfarlane said. Indeed, whatever the measure used, from the disease-specific Ankylosing Spondylitis Quality of Life (ASQoL) Scale to the general EuroQoL Quality of Life Scale, there were significant differences between those who did and did not meet fibromyalgia criteria. There were also higher scores for depression, anxiety, poorer-quality sleep, and higher levels of fatigue.
Patients treated with TNFi therapy showed improvement in both BASDAI and ASQoL scores regardless of whether they met fibromyalgia criteria, but crucially, the responses were still lower and significantly different from those without fibromyalgia.
An ASAS20 response to TNFi therapy was met by “slightly fewer” patients who met the fibromyalgia criteria than by those who did not at all follow-up points: at 3 months (about 35% vs. 45%), 6 months (about 58% vs. 61%), and 12 months (about 60% vs. 62%).
A high score on the Symptom Severity Scale but not the Widespread Pain Index of the fibromyalgia criteria was associated with a lower response to TNFi therapy at 3 months. “Such patients may benefit from the use of TNFi and nonpharmacological therapy,” Dr. Macfarlane said.
The BSRBR-AS is funded by the British Society for Rheumatology, which in turn receives funding from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not provide any disclosures but has previously acknowledged receiving an honorarium from Pfizer and research funding from AbbVie and Pfizer for the Scotland Registry for Ankylosing Spondylitis study.
SOURCE: Macfarlane GJ et al. Rheumatology. 2018;57(Suppl. 3):key075.183.
LIVERPOOL, ENGLAND – Individuals with axial spondyloarthritis (axSpA) who have comorbid fibromyalgia do respond to biologic therapy but at a seemingly lower rate if they have a high symptom score during early assessments.
Data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) showed that participants with axSpA who were starting biologic therapy with a tumor necrosis factor inhibitor (TNFi) for the first time also had worse disease activity at baseline if they met fibromyalgia research criteria than if they did not.
“The issue of fibromyalgia as a comorbidity in axial SpA has been the subject of current considerable interest,” said Dr. Macfarlane, who is Clinical Chair in Epidemiology at the University of Aberdeen (Scotland), where the BSRBR-AS is run. This is for several reasons: “One is the challenge of identifying patients with axial SpA who have comorbid fibromyalgia.
“The second is the concern that comorbid fibromyalgia may have an effect on disease indices such as BASDAI [Bath Ankylosing Spondylitis Disease Activity Index],” Dr. Macfarlane observed.
This leads to the third issue: “Are patients with comorbid fibromyalgia inappropriately receiving biological therapy, and how do they respond if they do receive it?”
Previous data from the BSRBR-AS have shown that approximately one in five patients with axSpA meet research criteria for fibromyalgia (Arthritis Rheumatol. 2017;69:2144-50) and that the prevalence of the comorbidity was higher in those who met Assessment of SpondyloArthritis International Society imaging criteria and lower in those who only met clinical criteria (25% vs. 10%).
The current aims of the study presented by Dr. Macfarlane were to first quantify the extent to which meeting fibromyalgia criteria was associated with higher measures of disease activity and impact, and then to see if meeting these criteria was associated with a poorer response to first use of a TNFi.
In order to find out, Dr. Macfarlane and his associates examined data from the prospective BSRBR-AS, which has been running since 2012. The BSRBR-AS recruits patients with ASAS-confirmed axSpA who are newly starting biologics from 83 U.K. centers.
At recruitment and at 3 months, patients starting biologic treatment undergo several assessments, which since 2015 has included research criteria for fibromyalgia (J Rheumatol. 2011;38:1113–22). The latter incorporate a Widespread Pain Index rated 0-19 and a Symptom Severity Scale rated 0-12 and cover items such as fatigue and waking up unrefreshed, and the presence of lower abdominal pain or headaches.
To date, around 1,750 participants in the BSRBR-AS have completed the fibromyalgia criteria, Dr. Macfarlane said.
Across the board, baseline measures of disease activity were lower in patients who met the fibromyalgia criteria versus those who did not. This included the BASDAI and the Bath Ankylosing Spondylitis Functional Index, where scores were approximately 6.5 and 4.5 for each measure.
“Quality of life was significantly lower in those who were fibromyalgia positive,” Dr. Macfarlane said. Indeed, whatever the measure used, from the disease-specific Ankylosing Spondylitis Quality of Life (ASQoL) Scale to the general EuroQoL Quality of Life Scale, there were significant differences between those who did and did not meet fibromyalgia criteria. There were also higher scores for depression, anxiety, poorer-quality sleep, and higher levels of fatigue.
Patients treated with TNFi therapy showed improvement in both BASDAI and ASQoL scores regardless of whether they met fibromyalgia criteria, but crucially, the responses were still lower and significantly different from those without fibromyalgia.
An ASAS20 response to TNFi therapy was met by “slightly fewer” patients who met the fibromyalgia criteria than by those who did not at all follow-up points: at 3 months (about 35% vs. 45%), 6 months (about 58% vs. 61%), and 12 months (about 60% vs. 62%).
A high score on the Symptom Severity Scale but not the Widespread Pain Index of the fibromyalgia criteria was associated with a lower response to TNFi therapy at 3 months. “Such patients may benefit from the use of TNFi and nonpharmacological therapy,” Dr. Macfarlane said.
The BSRBR-AS is funded by the British Society for Rheumatology, which in turn receives funding from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not provide any disclosures but has previously acknowledged receiving an honorarium from Pfizer and research funding from AbbVie and Pfizer for the Scotland Registry for Ankylosing Spondylitis study.
SOURCE: Macfarlane GJ et al. Rheumatology. 2018;57(Suppl. 3):key075.183.
LIVERPOOL, ENGLAND – Individuals with axial spondyloarthritis (axSpA) who have comorbid fibromyalgia do respond to biologic therapy but at a seemingly lower rate if they have a high symptom score during early assessments.
Data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) showed that participants with axSpA who were starting biologic therapy with a tumor necrosis factor inhibitor (TNFi) for the first time also had worse disease activity at baseline if they met fibromyalgia research criteria than if they did not.
“The issue of fibromyalgia as a comorbidity in axial SpA has been the subject of current considerable interest,” said Dr. Macfarlane, who is Clinical Chair in Epidemiology at the University of Aberdeen (Scotland), where the BSRBR-AS is run. This is for several reasons: “One is the challenge of identifying patients with axial SpA who have comorbid fibromyalgia.
“The second is the concern that comorbid fibromyalgia may have an effect on disease indices such as BASDAI [Bath Ankylosing Spondylitis Disease Activity Index],” Dr. Macfarlane observed.
This leads to the third issue: “Are patients with comorbid fibromyalgia inappropriately receiving biological therapy, and how do they respond if they do receive it?”
Previous data from the BSRBR-AS have shown that approximately one in five patients with axSpA meet research criteria for fibromyalgia (Arthritis Rheumatol. 2017;69:2144-50) and that the prevalence of the comorbidity was higher in those who met Assessment of SpondyloArthritis International Society imaging criteria and lower in those who only met clinical criteria (25% vs. 10%).
The current aims of the study presented by Dr. Macfarlane were to first quantify the extent to which meeting fibromyalgia criteria was associated with higher measures of disease activity and impact, and then to see if meeting these criteria was associated with a poorer response to first use of a TNFi.
In order to find out, Dr. Macfarlane and his associates examined data from the prospective BSRBR-AS, which has been running since 2012. The BSRBR-AS recruits patients with ASAS-confirmed axSpA who are newly starting biologics from 83 U.K. centers.
At recruitment and at 3 months, patients starting biologic treatment undergo several assessments, which since 2015 has included research criteria for fibromyalgia (J Rheumatol. 2011;38:1113–22). The latter incorporate a Widespread Pain Index rated 0-19 and a Symptom Severity Scale rated 0-12 and cover items such as fatigue and waking up unrefreshed, and the presence of lower abdominal pain or headaches.
To date, around 1,750 participants in the BSRBR-AS have completed the fibromyalgia criteria, Dr. Macfarlane said.
Across the board, baseline measures of disease activity were lower in patients who met the fibromyalgia criteria versus those who did not. This included the BASDAI and the Bath Ankylosing Spondylitis Functional Index, where scores were approximately 6.5 and 4.5 for each measure.
“Quality of life was significantly lower in those who were fibromyalgia positive,” Dr. Macfarlane said. Indeed, whatever the measure used, from the disease-specific Ankylosing Spondylitis Quality of Life (ASQoL) Scale to the general EuroQoL Quality of Life Scale, there were significant differences between those who did and did not meet fibromyalgia criteria. There were also higher scores for depression, anxiety, poorer-quality sleep, and higher levels of fatigue.
Patients treated with TNFi therapy showed improvement in both BASDAI and ASQoL scores regardless of whether they met fibromyalgia criteria, but crucially, the responses were still lower and significantly different from those without fibromyalgia.
An ASAS20 response to TNFi therapy was met by “slightly fewer” patients who met the fibromyalgia criteria than by those who did not at all follow-up points: at 3 months (about 35% vs. 45%), 6 months (about 58% vs. 61%), and 12 months (about 60% vs. 62%).
A high score on the Symptom Severity Scale but not the Widespread Pain Index of the fibromyalgia criteria was associated with a lower response to TNFi therapy at 3 months. “Such patients may benefit from the use of TNFi and nonpharmacological therapy,” Dr. Macfarlane said.
The BSRBR-AS is funded by the British Society for Rheumatology, which in turn receives funding from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not provide any disclosures but has previously acknowledged receiving an honorarium from Pfizer and research funding from AbbVie and Pfizer for the Scotland Registry for Ankylosing Spondylitis study.
SOURCE: Macfarlane GJ et al. Rheumatology. 2018;57(Suppl. 3):key075.183.
REPORTING FROM RHEUMATOLOGY 2018
Key clinical point: Comorbid axial spondyloarthritis and fibromyalgia are associated with a lower response to biologic therapy.
Major finding: About 35% vs. 45% of patients who did and did not meet research criteria for fibromyalgia had an ASAS20 response at 3 months.
Study details: Data on 1,750 participants of the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS).
Disclosures: The BSRBR-AS is funded by the British Society for Rheumatology, which in turn receives funding from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not provide any disclosures but has previously acknowledged receiving an honorarium from Pfizer and research funding from AbbVie and Pfizer for the Scotland Registry for Ankylosing Spondylitis study.
Source: Macfarlane GJ et al. Rheumatology. 2018;57(Suppl. 3):key075.183.