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RA bone destruction linked to natural killer T cells
Targeting natural killer T cells might help prevent bone destruction in rheumatoid arthritis, the results of a preclinical study suggest.
Natural killer T (NKT) cells stimulated by the glycolipid alpha-galactosylceramide (alphaGalCer) were found to have a regulatory effect on the development of osteoclasts, a type of bone cell that resorbs bone and is integral to bone repair and maintenance. These cells could have a protective effect on inflammatory bone destruction, the research team suggested after also finding that the cells’ effects were diminished in patients with RA versus healthy controls.
Hye-Mi Jin of the department of rheumatology at Chonnam National University Medical School and Hospital in Gwangju, South Korea, and associates isolated and cultured NKT cells from 25 subjects with and 15 without RA and performed in vitro experiments to investigate the role played by NKT cells in osteoclastogenesis. They also looked at the in vivo effects of the alphaGalCer-stimulated cells in a mouse model of collagen-induced arthritis (Arthritis Rheumatol. 2015 June 19 [doi:10.1002/art.39244]).
The in vitro studies showed that alphaGalCer significantly inhibited osteoclastogenesis in healthy individuals but not in patients with RA and that the effect was mediated by NKT cells. Mice treated with the glycolipid showed less severe arthritis and reduced bone destruction.
“Further studies are needed to investigate ways of repairing NKT cell dysfunction in RA,” the investigators proposed.
Targeting natural killer T cells might help prevent bone destruction in rheumatoid arthritis, the results of a preclinical study suggest.
Natural killer T (NKT) cells stimulated by the glycolipid alpha-galactosylceramide (alphaGalCer) were found to have a regulatory effect on the development of osteoclasts, a type of bone cell that resorbs bone and is integral to bone repair and maintenance. These cells could have a protective effect on inflammatory bone destruction, the research team suggested after also finding that the cells’ effects were diminished in patients with RA versus healthy controls.
Hye-Mi Jin of the department of rheumatology at Chonnam National University Medical School and Hospital in Gwangju, South Korea, and associates isolated and cultured NKT cells from 25 subjects with and 15 without RA and performed in vitro experiments to investigate the role played by NKT cells in osteoclastogenesis. They also looked at the in vivo effects of the alphaGalCer-stimulated cells in a mouse model of collagen-induced arthritis (Arthritis Rheumatol. 2015 June 19 [doi:10.1002/art.39244]).
The in vitro studies showed that alphaGalCer significantly inhibited osteoclastogenesis in healthy individuals but not in patients with RA and that the effect was mediated by NKT cells. Mice treated with the glycolipid showed less severe arthritis and reduced bone destruction.
“Further studies are needed to investigate ways of repairing NKT cell dysfunction in RA,” the investigators proposed.
Targeting natural killer T cells might help prevent bone destruction in rheumatoid arthritis, the results of a preclinical study suggest.
Natural killer T (NKT) cells stimulated by the glycolipid alpha-galactosylceramide (alphaGalCer) were found to have a regulatory effect on the development of osteoclasts, a type of bone cell that resorbs bone and is integral to bone repair and maintenance. These cells could have a protective effect on inflammatory bone destruction, the research team suggested after also finding that the cells’ effects were diminished in patients with RA versus healthy controls.
Hye-Mi Jin of the department of rheumatology at Chonnam National University Medical School and Hospital in Gwangju, South Korea, and associates isolated and cultured NKT cells from 25 subjects with and 15 without RA and performed in vitro experiments to investigate the role played by NKT cells in osteoclastogenesis. They also looked at the in vivo effects of the alphaGalCer-stimulated cells in a mouse model of collagen-induced arthritis (Arthritis Rheumatol. 2015 June 19 [doi:10.1002/art.39244]).
The in vitro studies showed that alphaGalCer significantly inhibited osteoclastogenesis in healthy individuals but not in patients with RA and that the effect was mediated by NKT cells. Mice treated with the glycolipid showed less severe arthritis and reduced bone destruction.
“Further studies are needed to investigate ways of repairing NKT cell dysfunction in RA,” the investigators proposed.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Targeting natural killer T cell dysregulation could perhaps lead to a new therapeutic strategy for preventing bone destruction in rheumatoid arthritis.
Major finding: NKT cells have a regulatory effect on osteoclastogenesis, which is dysregulated in patients with RA.
Data source: Preclinical study of peripheral blood mononuclear cells taken from 25 patients with RA and 15 healthy controls.
Disclosures: The authors had no potential conflicts to disclose.
EULAR: Panel previews updated CVD recommendations
ROME – The interval for assessing cardiovascular disease risk in patients with at least one inflamed joint can be as long as 5 years, depending on the patient, according to revised recommendations issued by a European League Against Rheumatism expert panel. The first edition of the recommendations called for annual assessment.
“We leave the assessment interval up to each clinician. Annually is very hard to incorporate into clinical practice,” said Dr. Michael T. Nurmohamed, convenor of both the initial recommendation panel as well as the group that produced the new revision. He previewed the updated recommendations during a talk at the European Congress of Rheumatology. The final form of the revised recommendations, which apply to patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, will soon be posted online and published, he said.
The context for cardiovascular disease risk assessment of patients with these rheumatoid diseases who are in primary-prevention mode has changed since the initial version was released in 2009 (Ann. Rheum. Dis. 2010;69:325-31). That changed context led to a rethinking of the appropriate interval for risk-factor assessment, said Dr. Nurmohamed, professor and head of rheumatology research at VU University Medical Center in Amsterdam. “In 2009, tight control of rheumatoid diseases generally did not exist,” he said in an interview.
In patients with well-controlled rheumatoid disease, “you can assess their cardiovascular disease [CVD] risk, and if the risk is very low” you can defer the next follow-up assessment for 5 years or longer. But if a patient’s CVD risk is high, assess the patient more often, Dr. Nurmohamed suggested. The recommendations also call for an updated CVD risk assessment following a “major change” in antirheumatoid therapy.
The updated recommendations include two other notable changes. First, there is now a much deeper evidence base behind the need for CVD risk assessment and management in patients with psoriatic arthritis or ankylosing spondylitis. “We mentioned them before, but the data weren’t all that hard. We now have more evidence,” he said in an interview.
Second, the revised recommendations say that ultrasound examination of atherosclerotic plaque number and volume in a patient’s carotid artery “may be considered.” Dr. Nurmohamed acknowledged that carotid examination by ultrasound is very discretionary; it can provide useful risk information, but “not every rheumatologist will do it.”
Most other aspects of the revised recommendations remain similar to the 2009 edition. They emphasize controlling inflammation to lower CVD risk, multiplying a patient’s CVD risk score by a factor of 1.5 to better estimate their increased risk level due to their rheumatic disease, cautious use of nonsteroidal anti-inflammatory drugs, and minimized use of glucocorticoids. Multiplying a patient’s CVD risk score results in a “rough” risk estimate, he cautioned. “The problem is we use 1.5 for all patients, regardless of their rheumatoid-disease duration,” he said.
Recommended interventions to reduce a patient’s CVD risk include lifestyle steps of healthy diet, regular exercise, and smoking cessation, and the standard drug interventions for reducing CVD risk: antihypertensive medications and lipid-lowering drugs, especially statins. Target levels for treating hypertension and hyperlipidemia remain the same as for primary prevention in the general population, he said. CVD risk assessment and management steps for patients with one of the covered rheumatoid diseases and established CVD are the same as for standard secondary-prevention measures in the general population.
A notable gap in the revision is the continued absence of recommendations for patients with gout. “Gout is on our research agenda, but represents an enormous task,” Dr. Nurmohamed said. He anticipates that his panel will eventually develop recommendations for managing CVD risk in gout patients.
On Twitter @mitchelzoler
ROME – The interval for assessing cardiovascular disease risk in patients with at least one inflamed joint can be as long as 5 years, depending on the patient, according to revised recommendations issued by a European League Against Rheumatism expert panel. The first edition of the recommendations called for annual assessment.
“We leave the assessment interval up to each clinician. Annually is very hard to incorporate into clinical practice,” said Dr. Michael T. Nurmohamed, convenor of both the initial recommendation panel as well as the group that produced the new revision. He previewed the updated recommendations during a talk at the European Congress of Rheumatology. The final form of the revised recommendations, which apply to patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, will soon be posted online and published, he said.
The context for cardiovascular disease risk assessment of patients with these rheumatoid diseases who are in primary-prevention mode has changed since the initial version was released in 2009 (Ann. Rheum. Dis. 2010;69:325-31). That changed context led to a rethinking of the appropriate interval for risk-factor assessment, said Dr. Nurmohamed, professor and head of rheumatology research at VU University Medical Center in Amsterdam. “In 2009, tight control of rheumatoid diseases generally did not exist,” he said in an interview.
In patients with well-controlled rheumatoid disease, “you can assess their cardiovascular disease [CVD] risk, and if the risk is very low” you can defer the next follow-up assessment for 5 years or longer. But if a patient’s CVD risk is high, assess the patient more often, Dr. Nurmohamed suggested. The recommendations also call for an updated CVD risk assessment following a “major change” in antirheumatoid therapy.
The updated recommendations include two other notable changes. First, there is now a much deeper evidence base behind the need for CVD risk assessment and management in patients with psoriatic arthritis or ankylosing spondylitis. “We mentioned them before, but the data weren’t all that hard. We now have more evidence,” he said in an interview.
Second, the revised recommendations say that ultrasound examination of atherosclerotic plaque number and volume in a patient’s carotid artery “may be considered.” Dr. Nurmohamed acknowledged that carotid examination by ultrasound is very discretionary; it can provide useful risk information, but “not every rheumatologist will do it.”
Most other aspects of the revised recommendations remain similar to the 2009 edition. They emphasize controlling inflammation to lower CVD risk, multiplying a patient’s CVD risk score by a factor of 1.5 to better estimate their increased risk level due to their rheumatic disease, cautious use of nonsteroidal anti-inflammatory drugs, and minimized use of glucocorticoids. Multiplying a patient’s CVD risk score results in a “rough” risk estimate, he cautioned. “The problem is we use 1.5 for all patients, regardless of their rheumatoid-disease duration,” he said.
Recommended interventions to reduce a patient’s CVD risk include lifestyle steps of healthy diet, regular exercise, and smoking cessation, and the standard drug interventions for reducing CVD risk: antihypertensive medications and lipid-lowering drugs, especially statins. Target levels for treating hypertension and hyperlipidemia remain the same as for primary prevention in the general population, he said. CVD risk assessment and management steps for patients with one of the covered rheumatoid diseases and established CVD are the same as for standard secondary-prevention measures in the general population.
A notable gap in the revision is the continued absence of recommendations for patients with gout. “Gout is on our research agenda, but represents an enormous task,” Dr. Nurmohamed said. He anticipates that his panel will eventually develop recommendations for managing CVD risk in gout patients.
On Twitter @mitchelzoler
ROME – The interval for assessing cardiovascular disease risk in patients with at least one inflamed joint can be as long as 5 years, depending on the patient, according to revised recommendations issued by a European League Against Rheumatism expert panel. The first edition of the recommendations called for annual assessment.
“We leave the assessment interval up to each clinician. Annually is very hard to incorporate into clinical practice,” said Dr. Michael T. Nurmohamed, convenor of both the initial recommendation panel as well as the group that produced the new revision. He previewed the updated recommendations during a talk at the European Congress of Rheumatology. The final form of the revised recommendations, which apply to patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, will soon be posted online and published, he said.
The context for cardiovascular disease risk assessment of patients with these rheumatoid diseases who are in primary-prevention mode has changed since the initial version was released in 2009 (Ann. Rheum. Dis. 2010;69:325-31). That changed context led to a rethinking of the appropriate interval for risk-factor assessment, said Dr. Nurmohamed, professor and head of rheumatology research at VU University Medical Center in Amsterdam. “In 2009, tight control of rheumatoid diseases generally did not exist,” he said in an interview.
In patients with well-controlled rheumatoid disease, “you can assess their cardiovascular disease [CVD] risk, and if the risk is very low” you can defer the next follow-up assessment for 5 years or longer. But if a patient’s CVD risk is high, assess the patient more often, Dr. Nurmohamed suggested. The recommendations also call for an updated CVD risk assessment following a “major change” in antirheumatoid therapy.
The updated recommendations include two other notable changes. First, there is now a much deeper evidence base behind the need for CVD risk assessment and management in patients with psoriatic arthritis or ankylosing spondylitis. “We mentioned them before, but the data weren’t all that hard. We now have more evidence,” he said in an interview.
Second, the revised recommendations say that ultrasound examination of atherosclerotic plaque number and volume in a patient’s carotid artery “may be considered.” Dr. Nurmohamed acknowledged that carotid examination by ultrasound is very discretionary; it can provide useful risk information, but “not every rheumatologist will do it.”
Most other aspects of the revised recommendations remain similar to the 2009 edition. They emphasize controlling inflammation to lower CVD risk, multiplying a patient’s CVD risk score by a factor of 1.5 to better estimate their increased risk level due to their rheumatic disease, cautious use of nonsteroidal anti-inflammatory drugs, and minimized use of glucocorticoids. Multiplying a patient’s CVD risk score results in a “rough” risk estimate, he cautioned. “The problem is we use 1.5 for all patients, regardless of their rheumatoid-disease duration,” he said.
Recommended interventions to reduce a patient’s CVD risk include lifestyle steps of healthy diet, regular exercise, and smoking cessation, and the standard drug interventions for reducing CVD risk: antihypertensive medications and lipid-lowering drugs, especially statins. Target levels for treating hypertension and hyperlipidemia remain the same as for primary prevention in the general population, he said. CVD risk assessment and management steps for patients with one of the covered rheumatoid diseases and established CVD are the same as for standard secondary-prevention measures in the general population.
A notable gap in the revision is the continued absence of recommendations for patients with gout. “Gout is on our research agenda, but represents an enormous task,” Dr. Nurmohamed said. He anticipates that his panel will eventually develop recommendations for managing CVD risk in gout patients.
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE EULAR 2015 Congress
EULAR: Women with RA have increased cervical neoplasia rates
ROME – Women with rheumatoid arthritis who have never been treated with a biologic drug had a modest but statistically significant increased rate of cervical intraepithelial neoplasia in a case-control study with more than 335,000 women.
The analysis showed an adjusted excess hazard for developing cervical intraepithelial neoplasia (CIN) I of 53%, compared with the general population, and an excess 39% rate of CIN II or III, both statistically significant differences, Dr. Hjalmar Wadstrom reported in a poster at the European Congress of Rheumatology.
The analysis also showed a small increase in the relative rate of invasive cervical cancers among the women with rheumatoid arthritis (RA) on treatment with conventional disease-modifying drugs, such as methotrexate, who never received a biologic disease-modifying drug. The 9% relative increase in the rate of invasive cancer, compared with the general population, did not achieve statistical significance, reported Dr. Wadstrom, a clinical epidemiology researcher at the Karolinska Institute in Stockholm.
The “moderately but not dramatically” increased rate of CIN “is not a reason for big concern or alarm,” but highlights that women with RA should comply with local cervical cancer–screening recommendations and programs, said Dr. Johan Askling, professor of rheumatology and clinical epidemiology at Karolinska and senior author of the study.
“It would be a shame if these RA patients with a small increased risk did not attend the [cervical screening] programs we have set up. Clinicians should make sure that women with RA attend to screening because nonattendance is their major risk factor,” he said in an interview. “Our findings don’t call for a change in screening recommendations, they just highlight the importance of attending to screening” in women with RA, Dr. Askling said.
The researchers ran a linkage analysis of Swedish registries and identified 34,984 adult women with RA and matched them with 300,331 women drawn from the general Swedish population. Age of the RA patients ranged from 18 to 97 years with a median age of 62 years, and they selected general-population controls who matched this group. In the regression analyses they ran to calculate hazard ratios they adjusted for age, education, prior cervical screening, comorbidities, marital status, and time hospitalized during prior 5 years. The analysis included CIN and invasive cancer cases during 14 years of follow-up, 1999-2012.
Both Dr. Wadstrom and Dr. Askling cited two potential factors behind the increased rates of CIN I, II, and III in women with RA: the inflammatory state of RA and treatment with immunosuppressive nonbiologic agents, such as methotrexate.
The increased CIN rates found in this analysis were also “seen in other patients treated with potent immunosuppressive drugs,” like organ transplant patients, Dr. Askling noted.
The current study serves as prelude to an analysis he and his associates are now running to assess cervical neoplasia and cancer rates among women with RA treated with biologic disease-modifying drugs.
On Twitter @mitchelzoler
ROME – Women with rheumatoid arthritis who have never been treated with a biologic drug had a modest but statistically significant increased rate of cervical intraepithelial neoplasia in a case-control study with more than 335,000 women.
The analysis showed an adjusted excess hazard for developing cervical intraepithelial neoplasia (CIN) I of 53%, compared with the general population, and an excess 39% rate of CIN II or III, both statistically significant differences, Dr. Hjalmar Wadstrom reported in a poster at the European Congress of Rheumatology.
The analysis also showed a small increase in the relative rate of invasive cervical cancers among the women with rheumatoid arthritis (RA) on treatment with conventional disease-modifying drugs, such as methotrexate, who never received a biologic disease-modifying drug. The 9% relative increase in the rate of invasive cancer, compared with the general population, did not achieve statistical significance, reported Dr. Wadstrom, a clinical epidemiology researcher at the Karolinska Institute in Stockholm.
The “moderately but not dramatically” increased rate of CIN “is not a reason for big concern or alarm,” but highlights that women with RA should comply with local cervical cancer–screening recommendations and programs, said Dr. Johan Askling, professor of rheumatology and clinical epidemiology at Karolinska and senior author of the study.
“It would be a shame if these RA patients with a small increased risk did not attend the [cervical screening] programs we have set up. Clinicians should make sure that women with RA attend to screening because nonattendance is their major risk factor,” he said in an interview. “Our findings don’t call for a change in screening recommendations, they just highlight the importance of attending to screening” in women with RA, Dr. Askling said.
The researchers ran a linkage analysis of Swedish registries and identified 34,984 adult women with RA and matched them with 300,331 women drawn from the general Swedish population. Age of the RA patients ranged from 18 to 97 years with a median age of 62 years, and they selected general-population controls who matched this group. In the regression analyses they ran to calculate hazard ratios they adjusted for age, education, prior cervical screening, comorbidities, marital status, and time hospitalized during prior 5 years. The analysis included CIN and invasive cancer cases during 14 years of follow-up, 1999-2012.
Both Dr. Wadstrom and Dr. Askling cited two potential factors behind the increased rates of CIN I, II, and III in women with RA: the inflammatory state of RA and treatment with immunosuppressive nonbiologic agents, such as methotrexate.
The increased CIN rates found in this analysis were also “seen in other patients treated with potent immunosuppressive drugs,” like organ transplant patients, Dr. Askling noted.
The current study serves as prelude to an analysis he and his associates are now running to assess cervical neoplasia and cancer rates among women with RA treated with biologic disease-modifying drugs.
On Twitter @mitchelzoler
ROME – Women with rheumatoid arthritis who have never been treated with a biologic drug had a modest but statistically significant increased rate of cervical intraepithelial neoplasia in a case-control study with more than 335,000 women.
The analysis showed an adjusted excess hazard for developing cervical intraepithelial neoplasia (CIN) I of 53%, compared with the general population, and an excess 39% rate of CIN II or III, both statistically significant differences, Dr. Hjalmar Wadstrom reported in a poster at the European Congress of Rheumatology.
The analysis also showed a small increase in the relative rate of invasive cervical cancers among the women with rheumatoid arthritis (RA) on treatment with conventional disease-modifying drugs, such as methotrexate, who never received a biologic disease-modifying drug. The 9% relative increase in the rate of invasive cancer, compared with the general population, did not achieve statistical significance, reported Dr. Wadstrom, a clinical epidemiology researcher at the Karolinska Institute in Stockholm.
The “moderately but not dramatically” increased rate of CIN “is not a reason for big concern or alarm,” but highlights that women with RA should comply with local cervical cancer–screening recommendations and programs, said Dr. Johan Askling, professor of rheumatology and clinical epidemiology at Karolinska and senior author of the study.
“It would be a shame if these RA patients with a small increased risk did not attend the [cervical screening] programs we have set up. Clinicians should make sure that women with RA attend to screening because nonattendance is their major risk factor,” he said in an interview. “Our findings don’t call for a change in screening recommendations, they just highlight the importance of attending to screening” in women with RA, Dr. Askling said.
The researchers ran a linkage analysis of Swedish registries and identified 34,984 adult women with RA and matched them with 300,331 women drawn from the general Swedish population. Age of the RA patients ranged from 18 to 97 years with a median age of 62 years, and they selected general-population controls who matched this group. In the regression analyses they ran to calculate hazard ratios they adjusted for age, education, prior cervical screening, comorbidities, marital status, and time hospitalized during prior 5 years. The analysis included CIN and invasive cancer cases during 14 years of follow-up, 1999-2012.
Both Dr. Wadstrom and Dr. Askling cited two potential factors behind the increased rates of CIN I, II, and III in women with RA: the inflammatory state of RA and treatment with immunosuppressive nonbiologic agents, such as methotrexate.
The increased CIN rates found in this analysis were also “seen in other patients treated with potent immunosuppressive drugs,” like organ transplant patients, Dr. Askling noted.
The current study serves as prelude to an analysis he and his associates are now running to assess cervical neoplasia and cancer rates among women with RA treated with biologic disease-modifying drugs.
On Twitter @mitchelzoler
AT THE EULAR 2015 CONGRESS
Key clinical point: Women with rheumatoid arthritis had significantly increased rates of CIN I, II, and III.
Major finding: Women with RA had a 53% increased rate of CIN I and a 39% increased rate of CIN II or III.
Data source: Case-control study of women drawn from Swedish national registries with 34,984 RA patients and 300,331 women from the general population.
Disclosures: Dr. Wadstrom had no disclosures. Dr. Askling has received research support from eight drug companies.
TNF tapering can be successful for patients with RA
ROME – Many patients with rheumatoid arthritis can reduce – or even discontinue – their
maintenance therapy with tumor necrosis factor inhibitors after they achieve clinical stability.
Half who reduced their medication did not have a disease flare over 12 months, Dr. James Galloway reported at the annual meeting of the European League Against Rheumatism. And those who did flare quickly became stable again after their medications were restarted.
The implications are not only clinical, but economic, said Dr. Galloway of Kings College, London.
“First of all, why would we want our patients to take more medicine than they need to control symptoms?” he said in an interview. “And cost is another consideration. Maintenance with tumor necrosis factor inhibitors is expensive. By tapering the dose we can try to achieve a balance between symptoms control and cost.”
Dr. Galloway reported results of the OPTTIRA study a 12-month randomized trial that investigated whether tapering TNF inhibitors would cause patients to lose their response.
The trial recruited 103 patients who were taking etanercept or adalimumab plus a disease-modifying antirheumatic drug. Patients had to be stable with a Disease Activity Score (DAS28) of less than 3.2 for at least 3 months. They were excluded if they had serious concomitant illness or were taking high-dose steroids.
For the first 6 months, there were three treatment arms: controls, who received constant TNF inhibition; a 33% taper group; and a 66% taper group. If patients who tapered experienced a flare (a DAS28 increase of at least 0.6 plus one or more swollen joints), their baseline dosage was restarted.
From 6-12 months, both the tapering groups stopped their TNF inhibitors altogether, and the control group tapered in the two schedules. Outcomes were flare rates and DAS28 scores after 6 months of constant or tapered TNF inhibition.
Flares occurred in 14% of the control group and 13% of the 1/3 tapering group. Both of these rates were significantly less than the 37% flare rate in the 2/3 dose tapering group. Decreasing TNF inhibition by 66% quadrupled the risk of a flare compared to the other treatment arms (OR 4.1).
However, Dr. Galloway said, all of the flares subsided quickly when patients resumed their baseline dose.
Of the patients who tapered and then stopped TNF inhibitors altogether, 45% had not flared by the end of the study; their final DAS28 score was 2.2. There were no adverse events related to medication tapering. At the end of the study, there were no significant differences in the Health Assessment Questionnaire with either tapering strategy.
Although describing the outcome as positive, Dr. Galloway admitted that TNF tapering could be a tough sell to patients who have struggled to get control of their disease and abhor the thought of losing it.
“In fact,” he said, “about 40% of those we initially screened declined to go through with the study because they feared a relapse,” he said. “But I think many patients would consider this if we explain both the potential clinical and economic benefits, and reassure them that if they do flare, they can regain control rapidly on the same regimen that has been working for them.”
Dr. Galloway had no financial disclosures.
On Twitter @Alz_Gal
ROME – Many patients with rheumatoid arthritis can reduce – or even discontinue – their
maintenance therapy with tumor necrosis factor inhibitors after they achieve clinical stability.
Half who reduced their medication did not have a disease flare over 12 months, Dr. James Galloway reported at the annual meeting of the European League Against Rheumatism. And those who did flare quickly became stable again after their medications were restarted.
The implications are not only clinical, but economic, said Dr. Galloway of Kings College, London.
“First of all, why would we want our patients to take more medicine than they need to control symptoms?” he said in an interview. “And cost is another consideration. Maintenance with tumor necrosis factor inhibitors is expensive. By tapering the dose we can try to achieve a balance between symptoms control and cost.”
Dr. Galloway reported results of the OPTTIRA study a 12-month randomized trial that investigated whether tapering TNF inhibitors would cause patients to lose their response.
The trial recruited 103 patients who were taking etanercept or adalimumab plus a disease-modifying antirheumatic drug. Patients had to be stable with a Disease Activity Score (DAS28) of less than 3.2 for at least 3 months. They were excluded if they had serious concomitant illness or were taking high-dose steroids.
For the first 6 months, there were three treatment arms: controls, who received constant TNF inhibition; a 33% taper group; and a 66% taper group. If patients who tapered experienced a flare (a DAS28 increase of at least 0.6 plus one or more swollen joints), their baseline dosage was restarted.
From 6-12 months, both the tapering groups stopped their TNF inhibitors altogether, and the control group tapered in the two schedules. Outcomes were flare rates and DAS28 scores after 6 months of constant or tapered TNF inhibition.
Flares occurred in 14% of the control group and 13% of the 1/3 tapering group. Both of these rates were significantly less than the 37% flare rate in the 2/3 dose tapering group. Decreasing TNF inhibition by 66% quadrupled the risk of a flare compared to the other treatment arms (OR 4.1).
However, Dr. Galloway said, all of the flares subsided quickly when patients resumed their baseline dose.
Of the patients who tapered and then stopped TNF inhibitors altogether, 45% had not flared by the end of the study; their final DAS28 score was 2.2. There were no adverse events related to medication tapering. At the end of the study, there were no significant differences in the Health Assessment Questionnaire with either tapering strategy.
Although describing the outcome as positive, Dr. Galloway admitted that TNF tapering could be a tough sell to patients who have struggled to get control of their disease and abhor the thought of losing it.
“In fact,” he said, “about 40% of those we initially screened declined to go through with the study because they feared a relapse,” he said. “But I think many patients would consider this if we explain both the potential clinical and economic benefits, and reassure them that if they do flare, they can regain control rapidly on the same regimen that has been working for them.”
Dr. Galloway had no financial disclosures.
On Twitter @Alz_Gal
ROME – Many patients with rheumatoid arthritis can reduce – or even discontinue – their
maintenance therapy with tumor necrosis factor inhibitors after they achieve clinical stability.
Half who reduced their medication did not have a disease flare over 12 months, Dr. James Galloway reported at the annual meeting of the European League Against Rheumatism. And those who did flare quickly became stable again after their medications were restarted.
The implications are not only clinical, but economic, said Dr. Galloway of Kings College, London.
“First of all, why would we want our patients to take more medicine than they need to control symptoms?” he said in an interview. “And cost is another consideration. Maintenance with tumor necrosis factor inhibitors is expensive. By tapering the dose we can try to achieve a balance between symptoms control and cost.”
Dr. Galloway reported results of the OPTTIRA study a 12-month randomized trial that investigated whether tapering TNF inhibitors would cause patients to lose their response.
The trial recruited 103 patients who were taking etanercept or adalimumab plus a disease-modifying antirheumatic drug. Patients had to be stable with a Disease Activity Score (DAS28) of less than 3.2 for at least 3 months. They were excluded if they had serious concomitant illness or were taking high-dose steroids.
For the first 6 months, there were three treatment arms: controls, who received constant TNF inhibition; a 33% taper group; and a 66% taper group. If patients who tapered experienced a flare (a DAS28 increase of at least 0.6 plus one or more swollen joints), their baseline dosage was restarted.
From 6-12 months, both the tapering groups stopped their TNF inhibitors altogether, and the control group tapered in the two schedules. Outcomes were flare rates and DAS28 scores after 6 months of constant or tapered TNF inhibition.
Flares occurred in 14% of the control group and 13% of the 1/3 tapering group. Both of these rates were significantly less than the 37% flare rate in the 2/3 dose tapering group. Decreasing TNF inhibition by 66% quadrupled the risk of a flare compared to the other treatment arms (OR 4.1).
However, Dr. Galloway said, all of the flares subsided quickly when patients resumed their baseline dose.
Of the patients who tapered and then stopped TNF inhibitors altogether, 45% had not flared by the end of the study; their final DAS28 score was 2.2. There were no adverse events related to medication tapering. At the end of the study, there were no significant differences in the Health Assessment Questionnaire with either tapering strategy.
Although describing the outcome as positive, Dr. Galloway admitted that TNF tapering could be a tough sell to patients who have struggled to get control of their disease and abhor the thought of losing it.
“In fact,” he said, “about 40% of those we initially screened declined to go through with the study because they feared a relapse,” he said. “But I think many patients would consider this if we explain both the potential clinical and economic benefits, and reassure them that if they do flare, they can regain control rapidly on the same regimen that has been working for them.”
Dr. Galloway had no financial disclosures.
On Twitter @Alz_Gal
AT EULAR 2015
Key clinical point: Many patients can reduce or even stop taking TNF inhibitors without losing control of their rheumatoid arthritis symptoms.
Major finding: Although up to 37% of those who tapered had a relapse, almost half were ale to stop the medication completely.Data source: The randomized OPTTIRA study comprised 103 patients.
Disclosures: Dr. Galloway had no financial disclosures.
EULAR: Imaging suggests early cardiomyopathy accompanies early RA
Patients with newly diagnosed rheumatoid arthritis already show increased aortic stiffness as well as lower left and right ventricular, end-systolic, and end-diastolic volumes, Dr. Maya Buch reported at the European Congress of Rheumatology.
The imaging findings lend support to a growing view that inflammation may underlie cardiovascular as well as rheumatic disease, Dr. Buch said in an interview.
“Rheumatoid arthritis is associated with increased cardiovascular disease and death. This is thought to be due to the inflammatory drive as well as traditional risk factors,” said Dr. Buch of the University of Leeds (England). “There is also a significant literature base suggesting atherosclerosis is inflammation driven, thus, shared mechanisms are likely.”
Dr. Buch and her colleagues conducted cardiac magnetic resonance imaging studies on 66 patients with early rheumatoid arthritis; all were treatment naive and had symptoms of less than 1 year in duration. They were matched for age, gender, and blood pressure with 30 healthy controls.
Patients had a mean age of about 48 years; mean systolic blood pressures were similar – 122 mm Hg for patients and 126 mm Hg for controls.
In the patients, the median erythrocyte sedimentation rate was 39.5 mm/hr; C-reactive protein was 18.9 mg/L. The mean Disease Activity Score 28 was 5.65. Most (82%) were positive for anticitrullinated protein antibodies; 73% were positive for rheumatoid factors.
Patients showed significantly reduced aortic distensibility, compared with controls. Aortic compliance and aortic strain were also significantly lower in patients, while aortic stiffness was significantly higher.
Evidence of early cardiac remodeling was present. Left ventricular and right ventricular end-systolic and end-diastolic volumes were all lower in the patients. A trend for lower left ventricular mass index seemed to be associated with seropositivity, Dr. Buch noted. Four patients showed evidence of overt inflammation or fibrosis with focal nonischemic patterns of late gadolinium enhancement.
These changes suggest an early cardiomyopathy, Dr. Buch said, and could imply a higher risk for cardiovascular morbidity and mortality at time of diagnosis. She added that the next steps in learning about this association will be to clarify its natural history, clinical implications, and the potential to modify outcomes with effective therapy. Although these new data are striking, they aren’t enough to recommend that newly diagnosed patients get routine cardiac imaging, Dr. Buch said.
“The study clearly implies that subclinical cardiovascular pathology exists at the early stage. Screening wouldn’t be appropriate at this stage – the clinical outcome and relevance of subclinical disease is not yet clear. However further evaluation will clarify whether additional benefits of RA disease control – for example, improving the cardiovascular risk and abnormalities seen here – are possible. This could influence future management approach.”
Patients with newly diagnosed rheumatoid arthritis already show increased aortic stiffness as well as lower left and right ventricular, end-systolic, and end-diastolic volumes, Dr. Maya Buch reported at the European Congress of Rheumatology.
The imaging findings lend support to a growing view that inflammation may underlie cardiovascular as well as rheumatic disease, Dr. Buch said in an interview.
“Rheumatoid arthritis is associated with increased cardiovascular disease and death. This is thought to be due to the inflammatory drive as well as traditional risk factors,” said Dr. Buch of the University of Leeds (England). “There is also a significant literature base suggesting atherosclerosis is inflammation driven, thus, shared mechanisms are likely.”
Dr. Buch and her colleagues conducted cardiac magnetic resonance imaging studies on 66 patients with early rheumatoid arthritis; all were treatment naive and had symptoms of less than 1 year in duration. They were matched for age, gender, and blood pressure with 30 healthy controls.
Patients had a mean age of about 48 years; mean systolic blood pressures were similar – 122 mm Hg for patients and 126 mm Hg for controls.
In the patients, the median erythrocyte sedimentation rate was 39.5 mm/hr; C-reactive protein was 18.9 mg/L. The mean Disease Activity Score 28 was 5.65. Most (82%) were positive for anticitrullinated protein antibodies; 73% were positive for rheumatoid factors.
Patients showed significantly reduced aortic distensibility, compared with controls. Aortic compliance and aortic strain were also significantly lower in patients, while aortic stiffness was significantly higher.
Evidence of early cardiac remodeling was present. Left ventricular and right ventricular end-systolic and end-diastolic volumes were all lower in the patients. A trend for lower left ventricular mass index seemed to be associated with seropositivity, Dr. Buch noted. Four patients showed evidence of overt inflammation or fibrosis with focal nonischemic patterns of late gadolinium enhancement.
These changes suggest an early cardiomyopathy, Dr. Buch said, and could imply a higher risk for cardiovascular morbidity and mortality at time of diagnosis. She added that the next steps in learning about this association will be to clarify its natural history, clinical implications, and the potential to modify outcomes with effective therapy. Although these new data are striking, they aren’t enough to recommend that newly diagnosed patients get routine cardiac imaging, Dr. Buch said.
“The study clearly implies that subclinical cardiovascular pathology exists at the early stage. Screening wouldn’t be appropriate at this stage – the clinical outcome and relevance of subclinical disease is not yet clear. However further evaluation will clarify whether additional benefits of RA disease control – for example, improving the cardiovascular risk and abnormalities seen here – are possible. This could influence future management approach.”
Patients with newly diagnosed rheumatoid arthritis already show increased aortic stiffness as well as lower left and right ventricular, end-systolic, and end-diastolic volumes, Dr. Maya Buch reported at the European Congress of Rheumatology.
The imaging findings lend support to a growing view that inflammation may underlie cardiovascular as well as rheumatic disease, Dr. Buch said in an interview.
“Rheumatoid arthritis is associated with increased cardiovascular disease and death. This is thought to be due to the inflammatory drive as well as traditional risk factors,” said Dr. Buch of the University of Leeds (England). “There is also a significant literature base suggesting atherosclerosis is inflammation driven, thus, shared mechanisms are likely.”
Dr. Buch and her colleagues conducted cardiac magnetic resonance imaging studies on 66 patients with early rheumatoid arthritis; all were treatment naive and had symptoms of less than 1 year in duration. They were matched for age, gender, and blood pressure with 30 healthy controls.
Patients had a mean age of about 48 years; mean systolic blood pressures were similar – 122 mm Hg for patients and 126 mm Hg for controls.
In the patients, the median erythrocyte sedimentation rate was 39.5 mm/hr; C-reactive protein was 18.9 mg/L. The mean Disease Activity Score 28 was 5.65. Most (82%) were positive for anticitrullinated protein antibodies; 73% were positive for rheumatoid factors.
Patients showed significantly reduced aortic distensibility, compared with controls. Aortic compliance and aortic strain were also significantly lower in patients, while aortic stiffness was significantly higher.
Evidence of early cardiac remodeling was present. Left ventricular and right ventricular end-systolic and end-diastolic volumes were all lower in the patients. A trend for lower left ventricular mass index seemed to be associated with seropositivity, Dr. Buch noted. Four patients showed evidence of overt inflammation or fibrosis with focal nonischemic patterns of late gadolinium enhancement.
These changes suggest an early cardiomyopathy, Dr. Buch said, and could imply a higher risk for cardiovascular morbidity and mortality at time of diagnosis. She added that the next steps in learning about this association will be to clarify its natural history, clinical implications, and the potential to modify outcomes with effective therapy. Although these new data are striking, they aren’t enough to recommend that newly diagnosed patients get routine cardiac imaging, Dr. Buch said.
“The study clearly implies that subclinical cardiovascular pathology exists at the early stage. Screening wouldn’t be appropriate at this stage – the clinical outcome and relevance of subclinical disease is not yet clear. However further evaluation will clarify whether additional benefits of RA disease control – for example, improving the cardiovascular risk and abnormalities seen here – are possible. This could influence future management approach.”
FROM THE EULAR 2015 CONGRESS
Key clinical point: Cardiomyopathy may be already developing in patients with early rheumatoid arthritis.
Major finding: Patients with untreated early RA showed radiologic findings of increased arterial stiffness, decreased distensibility, and early ventricular remodeling.
Data source: The prospective study comprises 66 patients and 30 controls.
Disclosures: Dr. Buch had no financial disclosures.
Is citrulline-specific ACPA key to bronchiectasis-RA link?
In bronchiectasis patients who develop rheumatoid arthritis, the responses of anticitrullinated peptide antibodies become more citrulline specific, according to results of a British study.
The study investigators measured anticitrullinated peptide antibodies (ACPA) and rheumatoid factors (RF) in 122 patients with bronchiectasis (BR) alone, 50 patients with BR and RA (BRRA), 50 patients with RA without lung disease, 87 patients with asthma, and 79 healthy patients.
The citrulline specificity of ACPA in patients with BRRA was increased, compared with patients with BR alone and RA without any lung disease. While the study showed significantly elevated levels of ACPA in patients with BR alone, the ACPA response was not citrulline specific.
“Bronchiectasis is an unusual but potent model for the induction of autoimmunity in RA by bacterial infection in the lung,” according to Anne-Marie Quirke, Ph.D., and her colleagues. “Our study suggests that in the early stages of tolerance breakdown, the ACPA response is not citrulline specific, but becomes more so in those patients with BR that develop BRRA.”
In contrast to patients with BR alone, patients with BRRA showed no correlation between antibody responses to citrullinated peptides and arginine-containing peptides, with the exception of the citrullinated peptide cVim and the arginine-containing peptide Vim.
Rheumatoid factors were found significantly more often in BRRA patients, compared with patients with RA without any lung disease, with percent serum antibody positivity for RF vs. controls having been 82 and 52, respectively. For patients with BR alone, the percent serum positivity of RF, compared with controls, was 25.
“Further prospective investigations will need to be carried out of BR patients at risk for RA in order to confirm the evolution of citrulline specificity of ACPA in patients with BR who subsequently develop [RA],” according to the researchers.
Read the full study in Arthritis & Rheumatology (doi:10.1002/art.39226).
In bronchiectasis patients who develop rheumatoid arthritis, the responses of anticitrullinated peptide antibodies become more citrulline specific, according to results of a British study.
The study investigators measured anticitrullinated peptide antibodies (ACPA) and rheumatoid factors (RF) in 122 patients with bronchiectasis (BR) alone, 50 patients with BR and RA (BRRA), 50 patients with RA without lung disease, 87 patients with asthma, and 79 healthy patients.
The citrulline specificity of ACPA in patients with BRRA was increased, compared with patients with BR alone and RA without any lung disease. While the study showed significantly elevated levels of ACPA in patients with BR alone, the ACPA response was not citrulline specific.
“Bronchiectasis is an unusual but potent model for the induction of autoimmunity in RA by bacterial infection in the lung,” according to Anne-Marie Quirke, Ph.D., and her colleagues. “Our study suggests that in the early stages of tolerance breakdown, the ACPA response is not citrulline specific, but becomes more so in those patients with BR that develop BRRA.”
In contrast to patients with BR alone, patients with BRRA showed no correlation between antibody responses to citrullinated peptides and arginine-containing peptides, with the exception of the citrullinated peptide cVim and the arginine-containing peptide Vim.
Rheumatoid factors were found significantly more often in BRRA patients, compared with patients with RA without any lung disease, with percent serum antibody positivity for RF vs. controls having been 82 and 52, respectively. For patients with BR alone, the percent serum positivity of RF, compared with controls, was 25.
“Further prospective investigations will need to be carried out of BR patients at risk for RA in order to confirm the evolution of citrulline specificity of ACPA in patients with BR who subsequently develop [RA],” according to the researchers.
Read the full study in Arthritis & Rheumatology (doi:10.1002/art.39226).
In bronchiectasis patients who develop rheumatoid arthritis, the responses of anticitrullinated peptide antibodies become more citrulline specific, according to results of a British study.
The study investigators measured anticitrullinated peptide antibodies (ACPA) and rheumatoid factors (RF) in 122 patients with bronchiectasis (BR) alone, 50 patients with BR and RA (BRRA), 50 patients with RA without lung disease, 87 patients with asthma, and 79 healthy patients.
The citrulline specificity of ACPA in patients with BRRA was increased, compared with patients with BR alone and RA without any lung disease. While the study showed significantly elevated levels of ACPA in patients with BR alone, the ACPA response was not citrulline specific.
“Bronchiectasis is an unusual but potent model for the induction of autoimmunity in RA by bacterial infection in the lung,” according to Anne-Marie Quirke, Ph.D., and her colleagues. “Our study suggests that in the early stages of tolerance breakdown, the ACPA response is not citrulline specific, but becomes more so in those patients with BR that develop BRRA.”
In contrast to patients with BR alone, patients with BRRA showed no correlation between antibody responses to citrullinated peptides and arginine-containing peptides, with the exception of the citrullinated peptide cVim and the arginine-containing peptide Vim.
Rheumatoid factors were found significantly more often in BRRA patients, compared with patients with RA without any lung disease, with percent serum antibody positivity for RF vs. controls having been 82 and 52, respectively. For patients with BR alone, the percent serum positivity of RF, compared with controls, was 25.
“Further prospective investigations will need to be carried out of BR patients at risk for RA in order to confirm the evolution of citrulline specificity of ACPA in patients with BR who subsequently develop [RA],” according to the researchers.
Read the full study in Arthritis & Rheumatology (doi:10.1002/art.39226).
FROM ARTHRITIS & RHEUMATOLOGY
Ultrasound-detected tenosynovitis signals early RA
ROME – A quick ultrasound scan of the hand may be all that is needed to help determine if a patient with early inflammatory arthritis will go on to develop rheumatoid arthritis (RA).
Adjusted odds ratios (OR) for making a diagnosis of RA were 7.1 for having cyclic citrullinated peptide or rheumatoid factor antibodies (P < .0001), 7.9 for having 10 or more joints involved (P < .0001), and 6.6 for having tenosynovitis in the hand or wrist (P < .0001). The association held in patients with seronegative disease, with an OR of 7.6 for having 10 or more involved joints (P < .0001) and 4.8 for hand/wrist tenosynovitis (P = .003).
Rheumatologists are challenged to diagnose rheumatoid arthritis early, particularly in patients who may have had symptoms for only a few weeks, said Dr. Andrew Filer, senior lecturer at the University of Birmingham (England).
“One of the problems is that, in the first 3 months of the disease, it really is undifferentiated in a lot of patients, even using the 2010 [American College of Rheumatology/European League Against Rheumatism response] criteria for rheumatoid arthritis,” he said. While about a third of patients with inflammatory arthritis will go on to develop RA, the net has been cast so wide that there are patients whose inflammatory arthritis will resolve without treatment, he added.
Dr. Filer and his associates have been working for the past 15 years to find ways to help clinicians identify RA as early as possible. Some of their most recent research has focused on using musculoskeletal ultrasound to examine the small joints (Ann. Rheum. Dis. 2011;70:500-7) and has already shown that it is more accurate than traditional clinical assessment at predicting patient outcomes in very early arthritis.
Results from the Birmingham Early Arthritis Cohort (BEACON) presented at the European Congress of Rheumatology show that ultrasound-detected tenosynovitis can independently identify patients who will go on to develop RA.
The study involved 107 patients with at least one swollen joint and whose symptoms had started in the last 3 months. Of these, 43 developed very early RA, 20 had non-RA persistent disease, and the remaining 44 had resolving disease at 18-month follow-up.
Although a wide variety of tendons throughout the body was examined, including those in the shoulders, ankles, hands, and wrists, it was the extensor carpi ulnaris (ECU) tendon in the wrists and flexor tendons in the fingers that were found to be the most important to examine. The ECU tendon is responsible for straightening and rotating the wrist, as well as integral for gripping and pulling.
“Looking at the tendons was a new area for us, and it’s taken a while for organizations like OMERACT [Outcome Measures in Rheumatology] to come up with some usable criteria and grading,” Dr. Filer observed. Now that these exist and show that ultrasound is a reproducible tool for evaluating tenosynovitis in RA (Ann. Rheum. Dis. 2013;72:1328-34), it was possible to conduct the current prospective study.
Dr. Filer discussed the findings in a press briefing ahead of their scientific presentation by clinical research fellow Dr. Ilfita Sahbudin and noted that tenosynovitis was more difficult to assess clinically than joint inflammation as it was more “hidden.”“Even if it’s really established rheumatoid disease it’s quite difficult for even experienced rheumatologists to detect swelling of tendons; [we] really have to use imaging like ultrasound or MRI to detect this reliably,” he said at the briefing. “Scanning of wrist ECU and finger flexor tendons adds robust diagnostic data for RA in that first window of very early disease.”
Dr. Filer suggested that early arthritis clinics should start to integrate these scans into their protocols to validate the findings.
He reported having no financial disclosures.
ROME – A quick ultrasound scan of the hand may be all that is needed to help determine if a patient with early inflammatory arthritis will go on to develop rheumatoid arthritis (RA).
Adjusted odds ratios (OR) for making a diagnosis of RA were 7.1 for having cyclic citrullinated peptide or rheumatoid factor antibodies (P < .0001), 7.9 for having 10 or more joints involved (P < .0001), and 6.6 for having tenosynovitis in the hand or wrist (P < .0001). The association held in patients with seronegative disease, with an OR of 7.6 for having 10 or more involved joints (P < .0001) and 4.8 for hand/wrist tenosynovitis (P = .003).
Rheumatologists are challenged to diagnose rheumatoid arthritis early, particularly in patients who may have had symptoms for only a few weeks, said Dr. Andrew Filer, senior lecturer at the University of Birmingham (England).
“One of the problems is that, in the first 3 months of the disease, it really is undifferentiated in a lot of patients, even using the 2010 [American College of Rheumatology/European League Against Rheumatism response] criteria for rheumatoid arthritis,” he said. While about a third of patients with inflammatory arthritis will go on to develop RA, the net has been cast so wide that there are patients whose inflammatory arthritis will resolve without treatment, he added.
Dr. Filer and his associates have been working for the past 15 years to find ways to help clinicians identify RA as early as possible. Some of their most recent research has focused on using musculoskeletal ultrasound to examine the small joints (Ann. Rheum. Dis. 2011;70:500-7) and has already shown that it is more accurate than traditional clinical assessment at predicting patient outcomes in very early arthritis.
Results from the Birmingham Early Arthritis Cohort (BEACON) presented at the European Congress of Rheumatology show that ultrasound-detected tenosynovitis can independently identify patients who will go on to develop RA.
The study involved 107 patients with at least one swollen joint and whose symptoms had started in the last 3 months. Of these, 43 developed very early RA, 20 had non-RA persistent disease, and the remaining 44 had resolving disease at 18-month follow-up.
Although a wide variety of tendons throughout the body was examined, including those in the shoulders, ankles, hands, and wrists, it was the extensor carpi ulnaris (ECU) tendon in the wrists and flexor tendons in the fingers that were found to be the most important to examine. The ECU tendon is responsible for straightening and rotating the wrist, as well as integral for gripping and pulling.
“Looking at the tendons was a new area for us, and it’s taken a while for organizations like OMERACT [Outcome Measures in Rheumatology] to come up with some usable criteria and grading,” Dr. Filer observed. Now that these exist and show that ultrasound is a reproducible tool for evaluating tenosynovitis in RA (Ann. Rheum. Dis. 2013;72:1328-34), it was possible to conduct the current prospective study.
Dr. Filer discussed the findings in a press briefing ahead of their scientific presentation by clinical research fellow Dr. Ilfita Sahbudin and noted that tenosynovitis was more difficult to assess clinically than joint inflammation as it was more “hidden.”“Even if it’s really established rheumatoid disease it’s quite difficult for even experienced rheumatologists to detect swelling of tendons; [we] really have to use imaging like ultrasound or MRI to detect this reliably,” he said at the briefing. “Scanning of wrist ECU and finger flexor tendons adds robust diagnostic data for RA in that first window of very early disease.”
Dr. Filer suggested that early arthritis clinics should start to integrate these scans into their protocols to validate the findings.
He reported having no financial disclosures.
ROME – A quick ultrasound scan of the hand may be all that is needed to help determine if a patient with early inflammatory arthritis will go on to develop rheumatoid arthritis (RA).
Adjusted odds ratios (OR) for making a diagnosis of RA were 7.1 for having cyclic citrullinated peptide or rheumatoid factor antibodies (P < .0001), 7.9 for having 10 or more joints involved (P < .0001), and 6.6 for having tenosynovitis in the hand or wrist (P < .0001). The association held in patients with seronegative disease, with an OR of 7.6 for having 10 or more involved joints (P < .0001) and 4.8 for hand/wrist tenosynovitis (P = .003).
Rheumatologists are challenged to diagnose rheumatoid arthritis early, particularly in patients who may have had symptoms for only a few weeks, said Dr. Andrew Filer, senior lecturer at the University of Birmingham (England).
“One of the problems is that, in the first 3 months of the disease, it really is undifferentiated in a lot of patients, even using the 2010 [American College of Rheumatology/European League Against Rheumatism response] criteria for rheumatoid arthritis,” he said. While about a third of patients with inflammatory arthritis will go on to develop RA, the net has been cast so wide that there are patients whose inflammatory arthritis will resolve without treatment, he added.
Dr. Filer and his associates have been working for the past 15 years to find ways to help clinicians identify RA as early as possible. Some of their most recent research has focused on using musculoskeletal ultrasound to examine the small joints (Ann. Rheum. Dis. 2011;70:500-7) and has already shown that it is more accurate than traditional clinical assessment at predicting patient outcomes in very early arthritis.
Results from the Birmingham Early Arthritis Cohort (BEACON) presented at the European Congress of Rheumatology show that ultrasound-detected tenosynovitis can independently identify patients who will go on to develop RA.
The study involved 107 patients with at least one swollen joint and whose symptoms had started in the last 3 months. Of these, 43 developed very early RA, 20 had non-RA persistent disease, and the remaining 44 had resolving disease at 18-month follow-up.
Although a wide variety of tendons throughout the body was examined, including those in the shoulders, ankles, hands, and wrists, it was the extensor carpi ulnaris (ECU) tendon in the wrists and flexor tendons in the fingers that were found to be the most important to examine. The ECU tendon is responsible for straightening and rotating the wrist, as well as integral for gripping and pulling.
“Looking at the tendons was a new area for us, and it’s taken a while for organizations like OMERACT [Outcome Measures in Rheumatology] to come up with some usable criteria and grading,” Dr. Filer observed. Now that these exist and show that ultrasound is a reproducible tool for evaluating tenosynovitis in RA (Ann. Rheum. Dis. 2013;72:1328-34), it was possible to conduct the current prospective study.
Dr. Filer discussed the findings in a press briefing ahead of their scientific presentation by clinical research fellow Dr. Ilfita Sahbudin and noted that tenosynovitis was more difficult to assess clinically than joint inflammation as it was more “hidden.”“Even if it’s really established rheumatoid disease it’s quite difficult for even experienced rheumatologists to detect swelling of tendons; [we] really have to use imaging like ultrasound or MRI to detect this reliably,” he said at the briefing. “Scanning of wrist ECU and finger flexor tendons adds robust diagnostic data for RA in that first window of very early disease.”
Dr. Filer suggested that early arthritis clinics should start to integrate these scans into their protocols to validate the findings.
He reported having no financial disclosures.
AT THE EULAR 2015 CONGRESS
Key clinical point: Ultrasound scanning of the hand and wrist can detect tenosynovitis, which is a strong predictor of early rheumatoid arthritis.
Major finding: The adjusted odds ratio for making a diagnosis of RA was 6.6 for having tenosynovitis in the hand or wrist (P < .0001), which compared favorably to having seropositive disease (OR, 7.1) and more than 10 hand joints involved (OR, 7.9).
Data source: 107 patients from the Birmingham Early Arthritis Cohort who had one or more swollen joints and symptom onset within the preceding 3 months.
Disclosures: Dr. Filer reported having no financial disclosures.
VIDEO: EULAR updates cardiovascular-disease risk recommendations
ROME – The European League Against Rheumatism introduced an update to its 2009 recommendations on assessing and managing cardiovascular-disease risk in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
The update features an expanded evidence base for the recommendations, especially for psoriatic arthritis and ankylosing spondylitis, Dr. Michael T. Nurmohamed said in an interview at the European Congress of Rheumatology. One new element in the revision included a scaling down of the previously suggested annual assessment to a more flexible approach to the timing of serial assessments based on the risk level of individual patients. Another addition is the possible use of carotid ultrasound to measure atherosclerotic burden as a complement to more routinely-measured risk factors such as blood pressure and serum lipids, said Dr. Nurmohamed, convener of the current task force as well as the panel that formulated the first version (Ann. Rheum. Dis. 2010;69:325-31).
A second EULAR task force recently developed new recommendations on assessing and managing other comorbidities in patients with rheumatologic diseases, such as osteoporosis, cancer, peptic ulcers, and renal dysfunction. Chronic kidney disease is an important modifier of cardiovascular-disease risk, and hence the new comorbidity recommendations complement the new cardiovascular-disease statement, said Dr. Nurmohamed, professor and head of the rheumatology research department at VU University Medical Center in Amsterdam.
Dr. Nurmohamed had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
ROME – The European League Against Rheumatism introduced an update to its 2009 recommendations on assessing and managing cardiovascular-disease risk in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
The update features an expanded evidence base for the recommendations, especially for psoriatic arthritis and ankylosing spondylitis, Dr. Michael T. Nurmohamed said in an interview at the European Congress of Rheumatology. One new element in the revision included a scaling down of the previously suggested annual assessment to a more flexible approach to the timing of serial assessments based on the risk level of individual patients. Another addition is the possible use of carotid ultrasound to measure atherosclerotic burden as a complement to more routinely-measured risk factors such as blood pressure and serum lipids, said Dr. Nurmohamed, convener of the current task force as well as the panel that formulated the first version (Ann. Rheum. Dis. 2010;69:325-31).
A second EULAR task force recently developed new recommendations on assessing and managing other comorbidities in patients with rheumatologic diseases, such as osteoporosis, cancer, peptic ulcers, and renal dysfunction. Chronic kidney disease is an important modifier of cardiovascular-disease risk, and hence the new comorbidity recommendations complement the new cardiovascular-disease statement, said Dr. Nurmohamed, professor and head of the rheumatology research department at VU University Medical Center in Amsterdam.
Dr. Nurmohamed had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
ROME – The European League Against Rheumatism introduced an update to its 2009 recommendations on assessing and managing cardiovascular-disease risk in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
The update features an expanded evidence base for the recommendations, especially for psoriatic arthritis and ankylosing spondylitis, Dr. Michael T. Nurmohamed said in an interview at the European Congress of Rheumatology. One new element in the revision included a scaling down of the previously suggested annual assessment to a more flexible approach to the timing of serial assessments based on the risk level of individual patients. Another addition is the possible use of carotid ultrasound to measure atherosclerotic burden as a complement to more routinely-measured risk factors such as blood pressure and serum lipids, said Dr. Nurmohamed, convener of the current task force as well as the panel that formulated the first version (Ann. Rheum. Dis. 2010;69:325-31).
A second EULAR task force recently developed new recommendations on assessing and managing other comorbidities in patients with rheumatologic diseases, such as osteoporosis, cancer, peptic ulcers, and renal dysfunction. Chronic kidney disease is an important modifier of cardiovascular-disease risk, and hence the new comorbidity recommendations complement the new cardiovascular-disease statement, said Dr. Nurmohamed, professor and head of the rheumatology research department at VU University Medical Center in Amsterdam.
Dr. Nurmohamed had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
AT THE EULAR 2015 CONGRESS
VIDEO: Ultrasound of tendons detects early rheumatoid arthritis
ROME – Tenosynovitis on ultrasound might be the next criterion added to the diagnostic criteria for rheumatoid arthritis if it is confirmed as a valid marker for early disease detection, according to Dr. Andrew Filer.
He and his colleagues performed ultrasound assessments of 16 tendon regions in 107 patients in the Birmingham Early Arthritis Cohort Study (BEACON) who had clinically apparent synovitis involving at least one joint with a symptom duration of 3 months or less. They examined patient outcomes at 18 months.
Tenosynovitis in either the extensor carpi ulnaris tendons or the hand flexor tendons independently predicted early RA, and both were still significant independent predictors of early RA in seronegative patients, Dr. Filer of the University of Birmingham (England) said in this video interview at the European Congress of Rheumatology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ROME – Tenosynovitis on ultrasound might be the next criterion added to the diagnostic criteria for rheumatoid arthritis if it is confirmed as a valid marker for early disease detection, according to Dr. Andrew Filer.
He and his colleagues performed ultrasound assessments of 16 tendon regions in 107 patients in the Birmingham Early Arthritis Cohort Study (BEACON) who had clinically apparent synovitis involving at least one joint with a symptom duration of 3 months or less. They examined patient outcomes at 18 months.
Tenosynovitis in either the extensor carpi ulnaris tendons or the hand flexor tendons independently predicted early RA, and both were still significant independent predictors of early RA in seronegative patients, Dr. Filer of the University of Birmingham (England) said in this video interview at the European Congress of Rheumatology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ROME – Tenosynovitis on ultrasound might be the next criterion added to the diagnostic criteria for rheumatoid arthritis if it is confirmed as a valid marker for early disease detection, according to Dr. Andrew Filer.
He and his colleagues performed ultrasound assessments of 16 tendon regions in 107 patients in the Birmingham Early Arthritis Cohort Study (BEACON) who had clinically apparent synovitis involving at least one joint with a symptom duration of 3 months or less. They examined patient outcomes at 18 months.
Tenosynovitis in either the extensor carpi ulnaris tendons or the hand flexor tendons independently predicted early RA, and both were still significant independent predictors of early RA in seronegative patients, Dr. Filer of the University of Birmingham (England) said in this video interview at the European Congress of Rheumatology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE EULAR 2015 CONGRESS
First in-human RA vaccine trial yields positive results
A single intradermal injection of autologous modified dendritic cells exposed to citrullinated peptides is safe and has immunoregulatory and anti-inflammatory effects, results of a phase I first in-human trial showed.
Dr. Helen Benham of the University of Queensland Diamantina Institute, Woolloongabba, Australia, and her colleagues gave 34 anticitrullinated peptide antibody (ACPA)-positive RA patients carrying HLA-DRB1 shared epitope alleles the immunotherapy treatment Rheumavax at either a high or low dose. They then compared results 1 month after treatment with 16 RA patients who served as controls.
Patients who received the treatment had a reduced number of effector T cells and a decreased production of proinflammatory cytokines, compared with controls, the researchers reported (Sci. Transl. Med. 2015;7:290ra87 [doi: 10.1126/scitranslmed.aaa9301]).
Rheumavax did not induce disease flares in patients recruited with minimal disease activity, and the 28-joint disease activity score (DAS28) decreased in treated patients with active disease. Adverse events were a grade 1 out of a maximum of 4 and were similar between the low- and high-dose groups.
“The exploratory study demonstrates safety and biological activity of a single intradermal injection of autologous modified dendritic cells exposed to citrullinated peptides and provides rationale for further studies to assess clinical efficacy and antigen specific effects of autoantigen immunomodulatory therapy in RA,” concluded senior investigator Ranjeny Thomas, also of the University of Queensland, and associates.
All of the study patients were being treated with disease-modifying antirheumatic drugs. Median disease duration in the low-dose group was 3 years and baseline DAS28 based on C-reactive protein was 2.43. The high-dose group had a median disease duration of 2 years and a DAS28-CRP score of 2.2.
The authors reported no conflicts of interest.
rhnews@frontlinemedcom.com
A single intradermal injection of autologous modified dendritic cells exposed to citrullinated peptides is safe and has immunoregulatory and anti-inflammatory effects, results of a phase I first in-human trial showed.
Dr. Helen Benham of the University of Queensland Diamantina Institute, Woolloongabba, Australia, and her colleagues gave 34 anticitrullinated peptide antibody (ACPA)-positive RA patients carrying HLA-DRB1 shared epitope alleles the immunotherapy treatment Rheumavax at either a high or low dose. They then compared results 1 month after treatment with 16 RA patients who served as controls.
Patients who received the treatment had a reduced number of effector T cells and a decreased production of proinflammatory cytokines, compared with controls, the researchers reported (Sci. Transl. Med. 2015;7:290ra87 [doi: 10.1126/scitranslmed.aaa9301]).
Rheumavax did not induce disease flares in patients recruited with minimal disease activity, and the 28-joint disease activity score (DAS28) decreased in treated patients with active disease. Adverse events were a grade 1 out of a maximum of 4 and were similar between the low- and high-dose groups.
“The exploratory study demonstrates safety and biological activity of a single intradermal injection of autologous modified dendritic cells exposed to citrullinated peptides and provides rationale for further studies to assess clinical efficacy and antigen specific effects of autoantigen immunomodulatory therapy in RA,” concluded senior investigator Ranjeny Thomas, also of the University of Queensland, and associates.
All of the study patients were being treated with disease-modifying antirheumatic drugs. Median disease duration in the low-dose group was 3 years and baseline DAS28 based on C-reactive protein was 2.43. The high-dose group had a median disease duration of 2 years and a DAS28-CRP score of 2.2.
The authors reported no conflicts of interest.
rhnews@frontlinemedcom.com
A single intradermal injection of autologous modified dendritic cells exposed to citrullinated peptides is safe and has immunoregulatory and anti-inflammatory effects, results of a phase I first in-human trial showed.
Dr. Helen Benham of the University of Queensland Diamantina Institute, Woolloongabba, Australia, and her colleagues gave 34 anticitrullinated peptide antibody (ACPA)-positive RA patients carrying HLA-DRB1 shared epitope alleles the immunotherapy treatment Rheumavax at either a high or low dose. They then compared results 1 month after treatment with 16 RA patients who served as controls.
Patients who received the treatment had a reduced number of effector T cells and a decreased production of proinflammatory cytokines, compared with controls, the researchers reported (Sci. Transl. Med. 2015;7:290ra87 [doi: 10.1126/scitranslmed.aaa9301]).
Rheumavax did not induce disease flares in patients recruited with minimal disease activity, and the 28-joint disease activity score (DAS28) decreased in treated patients with active disease. Adverse events were a grade 1 out of a maximum of 4 and were similar between the low- and high-dose groups.
“The exploratory study demonstrates safety and biological activity of a single intradermal injection of autologous modified dendritic cells exposed to citrullinated peptides and provides rationale for further studies to assess clinical efficacy and antigen specific effects of autoantigen immunomodulatory therapy in RA,” concluded senior investigator Ranjeny Thomas, also of the University of Queensland, and associates.
All of the study patients were being treated with disease-modifying antirheumatic drugs. Median disease duration in the low-dose group was 3 years and baseline DAS28 based on C-reactive protein was 2.43. The high-dose group had a median disease duration of 2 years and a DAS28-CRP score of 2.2.
The authors reported no conflicts of interest.
rhnews@frontlinemedcom.com
FROM SCIENCE TRANSLATIONAL MEDICINE
Key clinical point: A single intradermal injection of autologous modified dendritic cells exposed to citrullinated peptides was safe and had immunoregulatory and anti-inflammatory effects in HLA risk genotype–positive RA patients.
Major finding: Patients who received Rheumavax treatment had a reduced number of effector T cells and a decreased production of proinflammatory cytokines 1 month after treatment, compared with controls.
Data source: Single-center, open-label, first in-human phase I study of 34 ACPA-positive RA patients and 16 control RA patients.
Disclosures: The authors reported no conflicts of interest.
