EULAR (European League Against Rheumatism): 2015 Congress

ROME – Patients with psoriasis were more likely to develop psoriatic arthritis if they had experienced physical trauma, based on data from a large, population-based study.

The crude incidence of psoriatic arthritis was 30 per 10,000 person-years in psoriasis patients exposed to trauma, compared with 22 per 10,000 person years in those who were not.

The hazard ratio (HR) for increased psoriatic arthritis risk with any trauma was 1.32 after adjusting for multiple factors, including patient age, gender, and the duration of psoriasis, senior study author Dr. Thorvardur Love said during a press briefing at the European Congress of Rheumatology.

“Patients with psoriasis are an easily identifiable group [to study] as they have skin disease on their body,” he noted. They also have a high risk of developing arthritis, at around 10%-30% of patients. This makes them an ideal population to study to try to find factors that might mitigate the risk and potentially have a large impact in clinical practice.

“The idea that trauma precipitates psoriatic arthritis is not new,” observed Dr. Love of Landspitali University Hospital in Reykjavik, Iceland. “It comes a little bit from the Koebner phenomenon, which is when psoriasis patients develop a new lesion in the skin where an injury has been.”

A few small studies had given rise to the idea that trauma could perhaps trigger a deep Koebner phenomenon in patients with psoriasis, and so the aim of the present analysis was to look at this idea in a larger population. Electronic health records of more than 10 million individuals living in the United Kingdom between 1995 and 2013 were analyzed from the Health Improvement Network (THIN) database. Of 70,646 patients with psoriasis who were identified, 15,416 had been exposed to some form of trauma, which was stratified as trauma involving the joints, bones, nerves, or skin.

After 425,120 person-years of follow-up, 1,010 incident cases of psoriatic arthritis had been recorded.

Having bone or joint trauma was found to increase the risk for psoriatic arthritis by 46% (HR, 1.46; 95% confidence interval, 1.13-1.54) and 50% (HR, 1.50; 95% CI. 1.19-1.90), respectively. This was after adjusting for age, gender, date of entry into the THIN database, duration of psoriasis, body mass index, smoking, alcohol consumption, and the number of visits to the general practitioner.

Neither nerve nor skin trauma were associated with an increased risk for psoriatic arthritis. Dr. Love and his fellow researchers also looked to see if patients with psoriasis had an increased risk of rheumatoid arthritis but found no significant association (HR, 1.04; 95% 0.99-1.10).

“The conclusion is that physical trauma is a risk factor for psoriatic arthritis among patients with psoriasis,” Dr. Love said. “We believe this is very important as the baseline risk is so high.”The effect is specific to psoriatic arthritis, as it is not seen in rheumatoid arthritis, which might provide clues for further research, he added. Why trauma might up the risk for developing psoriatic but not other types of inflammatory arthritis remains unclear, but the hypothesis is that patients would need to have a genetic predisposition and the “right types” of T cells in and around the joint that get disturbed in some way, perhaps by infection or by trauma. “I think it’s important to note that at this point we are not making any recommendations to the psoriasis community,” Dr. Love said. He suggested that, before any recommendations could be made, there needed to be a “really robust” conversation between patients, researchers, and physicians to determine exactly what these findings might mean. Certainly more research is needed before suggesting any lifestyle modifications that might help avoid situations associated with certain types of trauma, he said.

A literature review in the journal Clinical Rheumatology provided additional explanation of the deep Koebner effect. The investigators noted in their abstract that “the role of neuropeptides such as substance P and vasoactive intestinal peptide has been highlighted in the synovium after trauma.”

An editorial in the Journal of Rheumatology also suggested areas for additional research. Dr. Ignazio Olivieri of San Carlo Hospital in Potenza, Italy, wrote that “criteria of imputability” that should be met include “single and significant trauma; absence of joint lesion before trauma; localization of arthritis in the area of trauma; and absence or short delay between trauma and onset of arthritis.”

“You might envision treating [psoriasis] patients early [for psoriatic arthritis] if they break a leg or get a joint dislocation, but we are not there yet,” Dr. Love stressed. “This is an idea of where we could take this and where we might actually be able to have an effect.”

The research was performed by researchers at the University of Iceland (Reykjavik) in collaboration with researchers at Harvard Medical School in Boston and the University of Pennsylvania in Philadelphia. It was partially funded by the Icelandic Centre for Research (RANNIS) and the National Institutes of Health. Dr. Love’s associate, Dr. Stefan Thorarensen of the division of public health at the University of Iceland, presented the findings during the clinical science session at the congress.

Dr. Love and his coauthors reported having no financial disclosures.

ROME – Patients with psoriasis were more likely to develop psoriatic arthritis if they had experienced physical trauma, based on data from a large, population-based study.

The crude incidence of psoriatic arthritis was 30 per 10,000 person-years in psoriasis patients exposed to trauma, compared with 22 per 10,000 person years in those who were not.

The hazard ratio (HR) for increased psoriatic arthritis risk with any trauma was 1.32 after adjusting for multiple factors, including patient age, gender, and the duration of psoriasis, senior study author Dr. Thorvardur Love said during a press briefing at the European Congress of Rheumatology.

“Patients with psoriasis are an easily identifiable group [to study] as they have skin disease on their body,” he noted. They also have a high risk of developing arthritis, at around 10%-30% of patients. This makes them an ideal population to study to try to find factors that might mitigate the risk and potentially have a large impact in clinical practice.

“The idea that trauma precipitates psoriatic arthritis is not new,” observed Dr. Love of Landspitali University Hospital in Reykjavik, Iceland. “It comes a little bit from the Koebner phenomenon, which is when psoriasis patients develop a new lesion in the skin where an injury has been.”

A few small studies had given rise to the idea that trauma could perhaps trigger a deep Koebner phenomenon in patients with psoriasis, and so the aim of the present analysis was to look at this idea in a larger population. Electronic health records of more than 10 million individuals living in the United Kingdom between 1995 and 2013 were analyzed from the Health Improvement Network (THIN) database. Of 70,646 patients with psoriasis who were identified, 15,416 had been exposed to some form of trauma, which was stratified as trauma involving the joints, bones, nerves, or skin.

After 425,120 person-years of follow-up, 1,010 incident cases of psoriatic arthritis had been recorded.

Having bone or joint trauma was found to increase the risk for psoriatic arthritis by 46% (HR, 1.46; 95% confidence interval, 1.13-1.54) and 50% (HR, 1.50; 95% CI. 1.19-1.90), respectively. This was after adjusting for age, gender, date of entry into the THIN database, duration of psoriasis, body mass index, smoking, alcohol consumption, and the number of visits to the general practitioner.

Neither nerve nor skin trauma were associated with an increased risk for psoriatic arthritis. Dr. Love and his fellow researchers also looked to see if patients with psoriasis had an increased risk of rheumatoid arthritis but found no significant association (HR, 1.04; 95% 0.99-1.10).

“The conclusion is that physical trauma is a risk factor for psoriatic arthritis among patients with psoriasis,” Dr. Love said. “We believe this is very important as the baseline risk is so high.”The effect is specific to psoriatic arthritis, as it is not seen in rheumatoid arthritis, which might provide clues for further research, he added. Why trauma might up the risk for developing psoriatic but not other types of inflammatory arthritis remains unclear, but the hypothesis is that patients would need to have a genetic predisposition and the “right types” of T cells in and around the joint that get disturbed in some way, perhaps by infection or by trauma. “I think it’s important to note that at this point we are not making any recommendations to the psoriasis community,” Dr. Love said. He suggested that, before any recommendations could be made, there needed to be a “really robust” conversation between patients, researchers, and physicians to determine exactly what these findings might mean. Certainly more research is needed before suggesting any lifestyle modifications that might help avoid situations associated with certain types of trauma, he said.

A literature review in the journal Clinical Rheumatology provided additional explanation of the deep Koebner effect. The investigators noted in their abstract that “the role of neuropeptides such as substance P and vasoactive intestinal peptide has been highlighted in the synovium after trauma.”

An editorial in the Journal of Rheumatology also suggested areas for additional research. Dr. Ignazio Olivieri of San Carlo Hospital in Potenza, Italy, wrote that “criteria of imputability” that should be met include “single and significant trauma; absence of joint lesion before trauma; localization of arthritis in the area of trauma; and absence or short delay between trauma and onset of arthritis.”

“You might envision treating [psoriasis] patients early [for psoriatic arthritis] if they break a leg or get a joint dislocation, but we are not there yet,” Dr. Love stressed. “This is an idea of where we could take this and where we might actually be able to have an effect.”

The research was performed by researchers at the University of Iceland (Reykjavik) in collaboration with researchers at Harvard Medical School in Boston and the University of Pennsylvania in Philadelphia. It was partially funded by the Icelandic Centre for Research (RANNIS) and the National Institutes of Health. Dr. Love’s associate, Dr. Stefan Thorarensen of the division of public health at the University of Iceland, presented the findings during the clinical science session at the congress.

Dr. Love and his coauthors reported having no financial disclosures.

ROME – Patients with psoriasis were more likely to develop psoriatic arthritis if they had experienced physical trauma, based on data from a large, population-based study.

The crude incidence of psoriatic arthritis was 30 per 10,000 person-years in psoriasis patients exposed to trauma, compared with 22 per 10,000 person years in those who were not.

The hazard ratio (HR) for increased psoriatic arthritis risk with any trauma was 1.32 after adjusting for multiple factors, including patient age, gender, and the duration of psoriasis, senior study author Dr. Thorvardur Love said during a press briefing at the European Congress of Rheumatology.

“Patients with psoriasis are an easily identifiable group [to study] as they have skin disease on their body,” he noted. They also have a high risk of developing arthritis, at around 10%-30% of patients. This makes them an ideal population to study to try to find factors that might mitigate the risk and potentially have a large impact in clinical practice.

“The idea that trauma precipitates psoriatic arthritis is not new,” observed Dr. Love of Landspitali University Hospital in Reykjavik, Iceland. “It comes a little bit from the Koebner phenomenon, which is when psoriasis patients develop a new lesion in the skin where an injury has been.”

A few small studies had given rise to the idea that trauma could perhaps trigger a deep Koebner phenomenon in patients with psoriasis, and so the aim of the present analysis was to look at this idea in a larger population. Electronic health records of more than 10 million individuals living in the United Kingdom between 1995 and 2013 were analyzed from the Health Improvement Network (THIN) database. Of 70,646 patients with psoriasis who were identified, 15,416 had been exposed to some form of trauma, which was stratified as trauma involving the joints, bones, nerves, or skin.

After 425,120 person-years of follow-up, 1,010 incident cases of psoriatic arthritis had been recorded.

Having bone or joint trauma was found to increase the risk for psoriatic arthritis by 46% (HR, 1.46; 95% confidence interval, 1.13-1.54) and 50% (HR, 1.50; 95% CI. 1.19-1.90), respectively. This was after adjusting for age, gender, date of entry into the THIN database, duration of psoriasis, body mass index, smoking, alcohol consumption, and the number of visits to the general practitioner.

Neither nerve nor skin trauma were associated with an increased risk for psoriatic arthritis. Dr. Love and his fellow researchers also looked to see if patients with psoriasis had an increased risk of rheumatoid arthritis but found no significant association (HR, 1.04; 95% 0.99-1.10).

“The conclusion is that physical trauma is a risk factor for psoriatic arthritis among patients with psoriasis,” Dr. Love said. “We believe this is very important as the baseline risk is so high.”The effect is specific to psoriatic arthritis, as it is not seen in rheumatoid arthritis, which might provide clues for further research, he added. Why trauma might up the risk for developing psoriatic but not other types of inflammatory arthritis remains unclear, but the hypothesis is that patients would need to have a genetic predisposition and the “right types” of T cells in and around the joint that get disturbed in some way, perhaps by infection or by trauma. “I think it’s important to note that at this point we are not making any recommendations to the psoriasis community,” Dr. Love said. He suggested that, before any recommendations could be made, there needed to be a “really robust” conversation between patients, researchers, and physicians to determine exactly what these findings might mean. Certainly more research is needed before suggesting any lifestyle modifications that might help avoid situations associated with certain types of trauma, he said.

A literature review in the journal Clinical Rheumatology provided additional explanation of the deep Koebner effect. The investigators noted in their abstract that “the role of neuropeptides such as substance P and vasoactive intestinal peptide has been highlighted in the synovium after trauma.”

An editorial in the Journal of Rheumatology also suggested areas for additional research. Dr. Ignazio Olivieri of San Carlo Hospital in Potenza, Italy, wrote that “criteria of imputability” that should be met include “single and significant trauma; absence of joint lesion before trauma; localization of arthritis in the area of trauma; and absence or short delay between trauma and onset of arthritis.”

“You might envision treating [psoriasis] patients early [for psoriatic arthritis] if they break a leg or get a joint dislocation, but we are not there yet,” Dr. Love stressed. “This is an idea of where we could take this and where we might actually be able to have an effect.”

The research was performed by researchers at the University of Iceland (Reykjavik) in collaboration with researchers at Harvard Medical School in Boston and the University of Pennsylvania in Philadelphia. It was partially funded by the Icelandic Centre for Research (RANNIS) and the National Institutes of Health. Dr. Love’s associate, Dr. Stefan Thorarensen of the division of public health at the University of Iceland, presented the findings during the clinical science session at the congress.

Dr. Love and his coauthors reported having no financial disclosures.

ROME – Hydroxychloroquine should not be prescribed for patients with mild to moderate hand osteoarthritis (OA) according to data from a 24-week, randomized, multicenter, placebo-controlled trial.

The results of the Dutch study, presented at the European Congress of Rheumatology by Dr. Natalja M. Basoski of Maasstad Hospital, Rotterdam, the Netherlands, showed that hydroxychloroquine was no better than placebo at reducing patients’ pain and disability, or for improving their physical, social, or emotional well-being.

The primary outcome measure used was reduction in OA hand pain in the preceding 24 hours measured using a 100-mm visual analog scale (VAS) at the end of the study. The mean change in pain using the VAS over 24 weeks was a reduction of 1.3 mm in the hydroxychloroquine-treated patients versus a 0.10-mm rise in the patients who received placebo (P = .82).

There also was no change in the two secondary endpoints of change in total score of the Australian/Canadian Hand Osteoarthritis Index (AUSCAN) and the Arthritis Impact Measurement Scale 2 SF (AIMS2-SF) by the end of the treatment period. Mean changes in AUSCAN total scores were –0.42 and –0.25 (P = .49) and mean reductions in total AIMS2-SF scores were –0.17 and –0.076 (P = .68), comparing hydroxychloroquine with placebo, respectively.

“Osteoarthritis of the hand is one of the most common types of osteoarthritis, leading to pain, stiffness, and loss of function,” Dr. Basoski explained during a clinical science session looking at manifestations of the disease beyond the knee. “Unfortunately, current pharmacological treatment options are limited,” she added.

The underlying pathophysiological mechanisms of OA that primarily affect the hand are not clear, although inflammation is known to have a role, as in knee OA. Hydroxychloroquine is an established disease-modifying antirheumatoid drug that has shown benefit in patients with mild rheumatoid arthritis, which has led many rheumatologists to prescribe off label for the treatment of hand OA as well, Dr. Basoski observed in an interview. Data to support this are lacking, however, so this trial aimed to look at the potential symptom-modifying effects of the drug specifically in OA.

Over a 3-year period starting in July 2010, 202 patients with symptoms of primary mild to moderate hand OA of at least 1 years’ duration were recruited at six hospitals in the Netherlands and randomized to hydroxychloroquine 400 mg/day or matching placebo for 24 weeks. Six patients were lost to follow-up early on in the study, leaving 98 patients in each study arm who could be included in the intent-to-treat analysis. Of these, 22 hydroxychloroquine-treated and nine placebo-treated patients discontinued treatment, 10 and 5 in each group, respectively, because of adverse effects.

Dr. Basoski noted that patient characteristics were similar at baseline. Mean age was 57 years, and about 86% of participants were women. Hand OA was defined via American College of Rheumatology criteria and 86% and 91% of hydroxychloroquine- and placebo-treated patients had at least one joint with radiographic evidence of joint disease defined as a Kellgren-Lawrence score of ≥2.

“This is one of the studies that does not support the use of hydroxychloroquine in patients with OA of the hands and mild complaints,” she said in an interview. “It means that you should not prescribe it anymore, at least based on the results of this study.”

Further research is needed to see if there are some patients who might benefit or if it applies to other OA phenotypes, such as erosive hand OA. “More studies should be done, although in our second analysis after the study we tried to differentiate between very low pain and high pain and we still didn’t really see a difference,” she observed.

Erosive hand OA could be a different case, and results of an ongoing UK study should provide insight on whether hydroxychloroquine could be beneficial in these patients.

Although a similar number of patients treated with hydroxychloroquine or placebo in the trial experienced adverse events (21 vs. 24, respectively), there was an increase in allergic reactions (3 vs. 0) and rash or itching (8 vs. 3) with the active treatment.

With hydroxychloroquine seemingly out of the picture, at least in mild to moderate cases, Dr. Basoski advised on how she might treat a patient with primary hand OA. “I would try to start with paracetamol [acetaminophen] at the dose that is currently recommended, like 4 g/day, then eventually try to use opioids, as NSAIDs are not such a good thing to use in the long term.”

Dr. Basoski did not have any conflicts of interest to disclose.

ROME – Hydroxychloroquine should not be prescribed for patients with mild to moderate hand osteoarthritis (OA) according to data from a 24-week, randomized, multicenter, placebo-controlled trial.

The results of the Dutch study, presented at the European Congress of Rheumatology by Dr. Natalja M. Basoski of Maasstad Hospital, Rotterdam, the Netherlands, showed that hydroxychloroquine was no better than placebo at reducing patients’ pain and disability, or for improving their physical, social, or emotional well-being.

The primary outcome measure used was reduction in OA hand pain in the preceding 24 hours measured using a 100-mm visual analog scale (VAS) at the end of the study. The mean change in pain using the VAS over 24 weeks was a reduction of 1.3 mm in the hydroxychloroquine-treated patients versus a 0.10-mm rise in the patients who received placebo (P = .82).

There also was no change in the two secondary endpoints of change in total score of the Australian/Canadian Hand Osteoarthritis Index (AUSCAN) and the Arthritis Impact Measurement Scale 2 SF (AIMS2-SF) by the end of the treatment period. Mean changes in AUSCAN total scores were –0.42 and –0.25 (P = .49) and mean reductions in total AIMS2-SF scores were –0.17 and –0.076 (P = .68), comparing hydroxychloroquine with placebo, respectively.

“Osteoarthritis of the hand is one of the most common types of osteoarthritis, leading to pain, stiffness, and loss of function,” Dr. Basoski explained during a clinical science session looking at manifestations of the disease beyond the knee. “Unfortunately, current pharmacological treatment options are limited,” she added.

The underlying pathophysiological mechanisms of OA that primarily affect the hand are not clear, although inflammation is known to have a role, as in knee OA. Hydroxychloroquine is an established disease-modifying antirheumatoid drug that has shown benefit in patients with mild rheumatoid arthritis, which has led many rheumatologists to prescribe off label for the treatment of hand OA as well, Dr. Basoski observed in an interview. Data to support this are lacking, however, so this trial aimed to look at the potential symptom-modifying effects of the drug specifically in OA.

Over a 3-year period starting in July 2010, 202 patients with symptoms of primary mild to moderate hand OA of at least 1 years’ duration were recruited at six hospitals in the Netherlands and randomized to hydroxychloroquine 400 mg/day or matching placebo for 24 weeks. Six patients were lost to follow-up early on in the study, leaving 98 patients in each study arm who could be included in the intent-to-treat analysis. Of these, 22 hydroxychloroquine-treated and nine placebo-treated patients discontinued treatment, 10 and 5 in each group, respectively, because of adverse effects.

Dr. Basoski noted that patient characteristics were similar at baseline. Mean age was 57 years, and about 86% of participants were women. Hand OA was defined via American College of Rheumatology criteria and 86% and 91% of hydroxychloroquine- and placebo-treated patients had at least one joint with radiographic evidence of joint disease defined as a Kellgren-Lawrence score of ≥2.

“This is one of the studies that does not support the use of hydroxychloroquine in patients with OA of the hands and mild complaints,” she said in an interview. “It means that you should not prescribe it anymore, at least based on the results of this study.”

Further research is needed to see if there are some patients who might benefit or if it applies to other OA phenotypes, such as erosive hand OA. “More studies should be done, although in our second analysis after the study we tried to differentiate between very low pain and high pain and we still didn’t really see a difference,” she observed.

Erosive hand OA could be a different case, and results of an ongoing UK study should provide insight on whether hydroxychloroquine could be beneficial in these patients.

Although a similar number of patients treated with hydroxychloroquine or placebo in the trial experienced adverse events (21 vs. 24, respectively), there was an increase in allergic reactions (3 vs. 0) and rash or itching (8 vs. 3) with the active treatment.

With hydroxychloroquine seemingly out of the picture, at least in mild to moderate cases, Dr. Basoski advised on how she might treat a patient with primary hand OA. “I would try to start with paracetamol [acetaminophen] at the dose that is currently recommended, like 4 g/day, then eventually try to use opioids, as NSAIDs are not such a good thing to use in the long term.”

Dr. Basoski did not have any conflicts of interest to disclose.

ROME – Hydroxychloroquine should not be prescribed for patients with mild to moderate hand osteoarthritis (OA) according to data from a 24-week, randomized, multicenter, placebo-controlled trial.

The results of the Dutch study, presented at the European Congress of Rheumatology by Dr. Natalja M. Basoski of Maasstad Hospital, Rotterdam, the Netherlands, showed that hydroxychloroquine was no better than placebo at reducing patients’ pain and disability, or for improving their physical, social, or emotional well-being.

The primary outcome measure used was reduction in OA hand pain in the preceding 24 hours measured using a 100-mm visual analog scale (VAS) at the end of the study. The mean change in pain using the VAS over 24 weeks was a reduction of 1.3 mm in the hydroxychloroquine-treated patients versus a 0.10-mm rise in the patients who received placebo (P = .82).

There also was no change in the two secondary endpoints of change in total score of the Australian/Canadian Hand Osteoarthritis Index (AUSCAN) and the Arthritis Impact Measurement Scale 2 SF (AIMS2-SF) by the end of the treatment period. Mean changes in AUSCAN total scores were –0.42 and –0.25 (P = .49) and mean reductions in total AIMS2-SF scores were –0.17 and –0.076 (P = .68), comparing hydroxychloroquine with placebo, respectively.

“Osteoarthritis of the hand is one of the most common types of osteoarthritis, leading to pain, stiffness, and loss of function,” Dr. Basoski explained during a clinical science session looking at manifestations of the disease beyond the knee. “Unfortunately, current pharmacological treatment options are limited,” she added.

The underlying pathophysiological mechanisms of OA that primarily affect the hand are not clear, although inflammation is known to have a role, as in knee OA. Hydroxychloroquine is an established disease-modifying antirheumatoid drug that has shown benefit in patients with mild rheumatoid arthritis, which has led many rheumatologists to prescribe off label for the treatment of hand OA as well, Dr. Basoski observed in an interview. Data to support this are lacking, however, so this trial aimed to look at the potential symptom-modifying effects of the drug specifically in OA.

Over a 3-year period starting in July 2010, 202 patients with symptoms of primary mild to moderate hand OA of at least 1 years’ duration were recruited at six hospitals in the Netherlands and randomized to hydroxychloroquine 400 mg/day or matching placebo for 24 weeks. Six patients were lost to follow-up early on in the study, leaving 98 patients in each study arm who could be included in the intent-to-treat analysis. Of these, 22 hydroxychloroquine-treated and nine placebo-treated patients discontinued treatment, 10 and 5 in each group, respectively, because of adverse effects.

Dr. Basoski noted that patient characteristics were similar at baseline. Mean age was 57 years, and about 86% of participants were women. Hand OA was defined via American College of Rheumatology criteria and 86% and 91% of hydroxychloroquine- and placebo-treated patients had at least one joint with radiographic evidence of joint disease defined as a Kellgren-Lawrence score of ≥2.

“This is one of the studies that does not support the use of hydroxychloroquine in patients with OA of the hands and mild complaints,” she said in an interview. “It means that you should not prescribe it anymore, at least based on the results of this study.”

Further research is needed to see if there are some patients who might benefit or if it applies to other OA phenotypes, such as erosive hand OA. “More studies should be done, although in our second analysis after the study we tried to differentiate between very low pain and high pain and we still didn’t really see a difference,” she observed.

Erosive hand OA could be a different case, and results of an ongoing UK study should provide insight on whether hydroxychloroquine could be beneficial in these patients.

Although a similar number of patients treated with hydroxychloroquine or placebo in the trial experienced adverse events (21 vs. 24, respectively), there was an increase in allergic reactions (3 vs. 0) and rash or itching (8 vs. 3) with the active treatment.

With hydroxychloroquine seemingly out of the picture, at least in mild to moderate cases, Dr. Basoski advised on how she might treat a patient with primary hand OA. “I would try to start with paracetamol [acetaminophen] at the dose that is currently recommended, like 4 g/day, then eventually try to use opioids, as NSAIDs are not such a good thing to use in the long term.”

Dr. Basoski did not have any conflicts of interest to disclose.

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.

msullivan@frontlinemedcom.com

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.

msullivan@frontlinemedcom.com

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.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

ROME – A program of inspiratory muscle training combined with standard muscular rehabilitation exercise significantly improved lung function in patients with ankylosing spondylitis.

Compared to patients who engaged only in the rehabilitation exercise, the combination program resulted in significantly greater gains in both physical and physiologic measures of pulmonary function, Dr. Razvan Dragoi reported at the annual meeting of the European League Against Rheumatism.

“We assessed resting pulmonary function and ran cardiopulmonary exercise tests at the start and end of the study and saw significant improvements across all measures of lung function in the group undergoing inspiratory muscle training,” said Dr. Dragoi of the Victor Babes University of Medicine and Pharmacy, Romania. “When you compare these findings with the conventional exercise group – which saw small, nonsignificant improvements – it’s clear that adding inspiratory training to an exercise program has clear health benefits for patients.”

The study randomized 54 patients with ankylosing spondylitis to two exercise interventions, Dr. Dragoi said in an interview. “Both groups in our study performed a weekly group session for about 40 minutes per session, managed by a physiotherapist. They were then provided with simple, step-by-step written instructions with illustrations in order to practice these exercises at home,” 5 days each week, for 40 minutes at a time.

The program consisted of 20 exercises: motion and flexibility exercises of the cervical, thoracic, and lumbar spine; stretching of the hamstring muscles, erector spine muscle, and shoulder muscles; abdominal and diaphragm breathing exercises, and chest expansion exercises. The patients were required to achieve a level of perceived exertion of “somewhat hard.”

They also completed an exercise training diary in order to assess their compliance with the recommended program.

The investigational group, however, added another level of training. “In addition to the conventional exercise training, patients performed supervised inspiratory muscle training, three times a week, totaling 24 sessions. This used a real-time computer-assisted device (Trainair, Project Electronics Limited, United Kingdom).”

The training load was based on 80% of the patient’s sustained maximum inspiratory pressure. The patients started by performing six loaded inspiration with a 60-second rest period between each inspiration. This sequence of six exercises continued with 45-, 30-, and 15-, 10- and 5-second rest periods up to 36 loaded inspirations. The training session duration was about 30 minutes.

The study assessed a number of physical and physiologic endpoints, including chest expansion, forced vital capacity and expiratory volumes, and measures of oxygen and carbon dioxide exchange.

Only one outcome – chest expansion – improved significantly in the control arm, increasing from 69 cm at baseline to 72 cm by 8 weeks. In the intensified arm, however, every outcome improved significantly, including chest expansion (66 cm-94 cm), forced vital capacity (78.6%-82.7%), forced expiratory volume (71%-74.6%), and peak oxygen uptake (1.7-2 L/min). The measures of oxygen and carbon dioxide exchange also showed significant improvements.

Dr. Dragoi didn’t follow the patients to assess how long the exercise-related improvements lasted, but like all exercise, he said, the program would have to be repeated to maintain them. “We do have a follow-up in mind, and will be conducting that soon, but we do not know how many patients will be available for the follow-up.”

He had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

ROME – A program of inspiratory muscle training combined with standard muscular rehabilitation exercise significantly improved lung function in patients with ankylosing spondylitis.

Compared to patients who engaged only in the rehabilitation exercise, the combination program resulted in significantly greater gains in both physical and physiologic measures of pulmonary function, Dr. Razvan Dragoi reported at the annual meeting of the European League Against Rheumatism.

“We assessed resting pulmonary function and ran cardiopulmonary exercise tests at the start and end of the study and saw significant improvements across all measures of lung function in the group undergoing inspiratory muscle training,” said Dr. Dragoi of the Victor Babes University of Medicine and Pharmacy, Romania. “When you compare these findings with the conventional exercise group – which saw small, nonsignificant improvements – it’s clear that adding inspiratory training to an exercise program has clear health benefits for patients.”

The study randomized 54 patients with ankylosing spondylitis to two exercise interventions, Dr. Dragoi said in an interview. “Both groups in our study performed a weekly group session for about 40 minutes per session, managed by a physiotherapist. They were then provided with simple, step-by-step written instructions with illustrations in order to practice these exercises at home,” 5 days each week, for 40 minutes at a time.

The program consisted of 20 exercises: motion and flexibility exercises of the cervical, thoracic, and lumbar spine; stretching of the hamstring muscles, erector spine muscle, and shoulder muscles; abdominal and diaphragm breathing exercises, and chest expansion exercises. The patients were required to achieve a level of perceived exertion of “somewhat hard.”

They also completed an exercise training diary in order to assess their compliance with the recommended program.

The investigational group, however, added another level of training. “In addition to the conventional exercise training, patients performed supervised inspiratory muscle training, three times a week, totaling 24 sessions. This used a real-time computer-assisted device (Trainair, Project Electronics Limited, United Kingdom).”

The training load was based on 80% of the patient’s sustained maximum inspiratory pressure. The patients started by performing six loaded inspiration with a 60-second rest period between each inspiration. This sequence of six exercises continued with 45-, 30-, and 15-, 10- and 5-second rest periods up to 36 loaded inspirations. The training session duration was about 30 minutes.

The study assessed a number of physical and physiologic endpoints, including chest expansion, forced vital capacity and expiratory volumes, and measures of oxygen and carbon dioxide exchange.

Only one outcome – chest expansion – improved significantly in the control arm, increasing from 69 cm at baseline to 72 cm by 8 weeks. In the intensified arm, however, every outcome improved significantly, including chest expansion (66 cm-94 cm), forced vital capacity (78.6%-82.7%), forced expiratory volume (71%-74.6%), and peak oxygen uptake (1.7-2 L/min). The measures of oxygen and carbon dioxide exchange also showed significant improvements.

Dr. Dragoi didn’t follow the patients to assess how long the exercise-related improvements lasted, but like all exercise, he said, the program would have to be repeated to maintain them. “We do have a follow-up in mind, and will be conducting that soon, but we do not know how many patients will be available for the follow-up.”

He had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

ROME – A program of inspiratory muscle training combined with standard muscular rehabilitation exercise significantly improved lung function in patients with ankylosing spondylitis.

Compared to patients who engaged only in the rehabilitation exercise, the combination program resulted in significantly greater gains in both physical and physiologic measures of pulmonary function, Dr. Razvan Dragoi reported at the annual meeting of the European League Against Rheumatism.

“We assessed resting pulmonary function and ran cardiopulmonary exercise tests at the start and end of the study and saw significant improvements across all measures of lung function in the group undergoing inspiratory muscle training,” said Dr. Dragoi of the Victor Babes University of Medicine and Pharmacy, Romania. “When you compare these findings with the conventional exercise group – which saw small, nonsignificant improvements – it’s clear that adding inspiratory training to an exercise program has clear health benefits for patients.”

The study randomized 54 patients with ankylosing spondylitis to two exercise interventions, Dr. Dragoi said in an interview. “Both groups in our study performed a weekly group session for about 40 minutes per session, managed by a physiotherapist. They were then provided with simple, step-by-step written instructions with illustrations in order to practice these exercises at home,” 5 days each week, for 40 minutes at a time.

The program consisted of 20 exercises: motion and flexibility exercises of the cervical, thoracic, and lumbar spine; stretching of the hamstring muscles, erector spine muscle, and shoulder muscles; abdominal and diaphragm breathing exercises, and chest expansion exercises. The patients were required to achieve a level of perceived exertion of “somewhat hard.”

They also completed an exercise training diary in order to assess their compliance with the recommended program.

The investigational group, however, added another level of training. “In addition to the conventional exercise training, patients performed supervised inspiratory muscle training, three times a week, totaling 24 sessions. This used a real-time computer-assisted device (Trainair, Project Electronics Limited, United Kingdom).”

The training load was based on 80% of the patient’s sustained maximum inspiratory pressure. The patients started by performing six loaded inspiration with a 60-second rest period between each inspiration. This sequence of six exercises continued with 45-, 30-, and 15-, 10- and 5-second rest periods up to 36 loaded inspirations. The training session duration was about 30 minutes.

The study assessed a number of physical and physiologic endpoints, including chest expansion, forced vital capacity and expiratory volumes, and measures of oxygen and carbon dioxide exchange.

Only one outcome – chest expansion – improved significantly in the control arm, increasing from 69 cm at baseline to 72 cm by 8 weeks. In the intensified arm, however, every outcome improved significantly, including chest expansion (66 cm-94 cm), forced vital capacity (78.6%-82.7%), forced expiratory volume (71%-74.6%), and peak oxygen uptake (1.7-2 L/min). The measures of oxygen and carbon dioxide exchange also showed significant improvements.

Dr. Dragoi didn’t follow the patients to assess how long the exercise-related improvements lasted, but like all exercise, he said, the program would have to be repeated to maintain them. “We do have a follow-up in mind, and will be conducting that soon, but we do not know how many patients will be available for the follow-up.”

He had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

ROME – Ultrasound identification of subclinical synovitis allowed clinicians to get the upper hand on early joint damage in rheumatoid arthritis patients who were in remission.

When these patients increased their methotrexate for 52 weeks, follow-up imaging showed that burgeoning joint damage had arrested, Dr. Tadashi Okano said at the annual meeting of the European League Against Rheumatism. The findings suggest that even patients in clinical remission can have subclinically active disease, which can be identified and effectively managed.

“Although the latest recommendations for the treatment of rheumatoid arthritis focus on the achievement of clinical remission, we have demonstrated that patients with subclinical synovitis...should be treated more intensively to reduce the risk of further joint destruction, even when the patient is currently symptom free,” said Dr. Okano of the Osaka City University Graduate School of Medicine, Japan.

Dr. Okano investigated the potential benefit of intensifying treatment for patients who, although in remission, had ultrasound-diagnosed synovitis. The study comprised 134 patients; most (101) had subclinical synovitis as graded by the power Doppler ultrasound score (PDUS). They were randomized to either maintain their methotrexate dosage or to an increased dosage, for 52 weeks. The 33 patients without synovitis served as a control group. Standard radiographs of hands and feet were obtained at baseline, and weeks 24 and 52. Radiological joint damage was assessed according to the modified total Sharp score (mTSS).

By 52 weeks, the total PDUS had decreased significantly more in the intensified methotrexate group than in the stable methotrexate group (–3.9 vs. –2.0 points). Synovitis progression as graded by the mTSS was significantly suppressed in the intensified treatment group as well, both at week 24 (0.27 vs. 1.02) and week 52 (1.03 vs. 2.02).

The improvement was even more pronounced in the subset of 16 patients who were also taking biologics, Dr. Okano said. Joint damage in these patients was suppressed to the point where they resembled patients free of synovitis, with mTSS scores of 0.75 and 0.80, respectively.

“Subclinical active synovitis should be controlled by additional treatment, as this results in the prevention of the joint damage progression, Dr. Okano noted. High-resolution ultrasound offers the chance to identify these patients for early, aggressive management.

Dr. Okano had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

ROME – Ultrasound identification of subclinical synovitis allowed clinicians to get the upper hand on early joint damage in rheumatoid arthritis patients who were in remission.

When these patients increased their methotrexate for 52 weeks, follow-up imaging showed that burgeoning joint damage had arrested, Dr. Tadashi Okano said at the annual meeting of the European League Against Rheumatism. The findings suggest that even patients in clinical remission can have subclinically active disease, which can be identified and effectively managed.

“Although the latest recommendations for the treatment of rheumatoid arthritis focus on the achievement of clinical remission, we have demonstrated that patients with subclinical synovitis...should be treated more intensively to reduce the risk of further joint destruction, even when the patient is currently symptom free,” said Dr. Okano of the Osaka City University Graduate School of Medicine, Japan.

Dr. Okano investigated the potential benefit of intensifying treatment for patients who, although in remission, had ultrasound-diagnosed synovitis. The study comprised 134 patients; most (101) had subclinical synovitis as graded by the power Doppler ultrasound score (PDUS). They were randomized to either maintain their methotrexate dosage or to an increased dosage, for 52 weeks. The 33 patients without synovitis served as a control group. Standard radiographs of hands and feet were obtained at baseline, and weeks 24 and 52. Radiological joint damage was assessed according to the modified total Sharp score (mTSS).

By 52 weeks, the total PDUS had decreased significantly more in the intensified methotrexate group than in the stable methotrexate group (–3.9 vs. –2.0 points). Synovitis progression as graded by the mTSS was significantly suppressed in the intensified treatment group as well, both at week 24 (0.27 vs. 1.02) and week 52 (1.03 vs. 2.02).

The improvement was even more pronounced in the subset of 16 patients who were also taking biologics, Dr. Okano said. Joint damage in these patients was suppressed to the point where they resembled patients free of synovitis, with mTSS scores of 0.75 and 0.80, respectively.

“Subclinical active synovitis should be controlled by additional treatment, as this results in the prevention of the joint damage progression, Dr. Okano noted. High-resolution ultrasound offers the chance to identify these patients for early, aggressive management.

Dr. Okano had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

ROME – Ultrasound identification of subclinical synovitis allowed clinicians to get the upper hand on early joint damage in rheumatoid arthritis patients who were in remission.

When these patients increased their methotrexate for 52 weeks, follow-up imaging showed that burgeoning joint damage had arrested, Dr. Tadashi Okano said at the annual meeting of the European League Against Rheumatism. The findings suggest that even patients in clinical remission can have subclinically active disease, which can be identified and effectively managed.

“Although the latest recommendations for the treatment of rheumatoid arthritis focus on the achievement of clinical remission, we have demonstrated that patients with subclinical synovitis...should be treated more intensively to reduce the risk of further joint destruction, even when the patient is currently symptom free,” said Dr. Okano of the Osaka City University Graduate School of Medicine, Japan.

Dr. Okano investigated the potential benefit of intensifying treatment for patients who, although in remission, had ultrasound-diagnosed synovitis. The study comprised 134 patients; most (101) had subclinical synovitis as graded by the power Doppler ultrasound score (PDUS). They were randomized to either maintain their methotrexate dosage or to an increased dosage, for 52 weeks. The 33 patients without synovitis served as a control group. Standard radiographs of hands and feet were obtained at baseline, and weeks 24 and 52. Radiological joint damage was assessed according to the modified total Sharp score (mTSS).

By 52 weeks, the total PDUS had decreased significantly more in the intensified methotrexate group than in the stable methotrexate group (–3.9 vs. –2.0 points). Synovitis progression as graded by the mTSS was significantly suppressed in the intensified treatment group as well, both at week 24 (0.27 vs. 1.02) and week 52 (1.03 vs. 2.02).

The improvement was even more pronounced in the subset of 16 patients who were also taking biologics, Dr. Okano said. Joint damage in these patients was suppressed to the point where they resembled patients free of synovitis, with mTSS scores of 0.75 and 0.80, respectively.

“Subclinical active synovitis should be controlled by additional treatment, as this results in the prevention of the joint damage progression, Dr. Okano noted. High-resolution ultrasound offers the chance to identify these patients for early, aggressive management.

Dr. Okano had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

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.”

msullivan@frontlinemedcom.com

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.”

msullivan@frontlinemedcom.com

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.”

msullivan@frontlinemedcom.com

ROME – Tumor necrosis factor–alpha (TNF-alpha) inhibitors are well established as a treatment for psoriatic arthritis patients, but efficacy can vary greatly within that population. New work from Canadian researchers demonstrates that the global DNA methylation pattern differs between TNF-alpha–inhibitor responders and secondary failures, which could help explain the variability in medication success rates.

“Although TNF inhibitors [TNFi] work very well in certain individuals with psoriatic arthritis [PsA], up to 40% of individuals receiving this treatment fail to achieve a therapeutic response, and 20%-50% of individuals who have an initial response to treatment become refractory weeks or months after receiving therapy.” lead study author Darren O’Rielly, Ph.D., said at the European Congress of Rheumatology.

The preliminary study findings eventually could lead to the identification of biomarkers that would indicate patients who are not good candidates for TNFi medications, said Dr. O’Rielly of Memorial University, St. John’s, Nfld.

Given recent advances in epigenetics and that the epigenetic signature is affected by environmental factors, the investigators set out to determine if methylation alterations could help explain why PsA patients respond or fail with TNFi. The researchers performed genome-wide DNA methylation profiling on blood samples from 41 PsA patients, using machinery that measures about 480,000 CpG sites per sample and covers 96% of RefSeq genes. A total of 21 patients were considered TNFi responders, of whom 13 were treated with etanercept and 8 with adalimumab; median follow-up duration was 18 months. Twenty patients were considered secondary TNFi failures, of whom 15 were treated with etanercept and 5 with adalimumab; median follow-up duration was 36 months.

Dr. O’Rielly, a senior research scientist at Memorial and director of the Molecular Genetics Laboratory at Eastern Health in St. John’s, and his associates measured the methylation level at CpG sites using a genome-wide approach and selected regions of interest based on functional relevance to TNF-mediated signaling pathways with methylation level differences of 5% or greater and an adjusted P-value less than .05.

After quality-control filtering, investigators evaluated 384,599 CpG sites for TNFi responders and 368,863 CpG sites for TNFi failures. Researchers found 72 CpG sites of interest in the TNFi responder group and 91 CpG sites of interest in the TNFi failure group. Top candidate genes for TNFi responders included TRAPPC9 (which functions as an activator of NF-kB), CCR6 (which regulates the migration and recruitment of dendritic and T cells), and PSORS1C3 (psoriasis susceptibility 1 candidate 3), while top candidate genes for TNFi secondary failures included CD70 (an encoded protein that is a ligand for TNFRSF27/CD27) and TNFRSF1B (a member of the TNF receptor ‘superfamily’ that mediates most of the metabolic effects of TNF-alpha).

“We are very encouraged by these findings,” Dr. O’Rielly said. “We were a little surprised that several of our best candidate genes, such as TNFRSF1B and CD70, appear to play a role in TNF-alpha signaling, and that their methylation change occurs in a gene region that is consistent with a possible functional effect. We were expecting to find some methylation changes in genes but not necessarily in pathways with a direct connection with TNF-alpha–mediated signaling.”

The group plans to confirm these findings for the best candidate genes using other methylation-specific polymerase chain reaction technology, he said, and will investigate additional CpG sites adjacent to the region of interest, including promoters and enhancers, in the best candidate genes to better characterize the full extent of methylation changes in these regions. They also would like to replicate the findings in a prospective, independent cohort.

Dr. O’Rielly reported no relevant financial conflicts.

ROME – Tumor necrosis factor–alpha (TNF-alpha) inhibitors are well established as a treatment for psoriatic arthritis patients, but efficacy can vary greatly within that population. New work from Canadian researchers demonstrates that the global DNA methylation pattern differs between TNF-alpha–inhibitor responders and secondary failures, which could help explain the variability in medication success rates.

“Although TNF inhibitors [TNFi] work very well in certain individuals with psoriatic arthritis [PsA], up to 40% of individuals receiving this treatment fail to achieve a therapeutic response, and 20%-50% of individuals who have an initial response to treatment become refractory weeks or months after receiving therapy.” lead study author Darren O’Rielly, Ph.D., said at the European Congress of Rheumatology.

The preliminary study findings eventually could lead to the identification of biomarkers that would indicate patients who are not good candidates for TNFi medications, said Dr. O’Rielly of Memorial University, St. John’s, Nfld.

Given recent advances in epigenetics and that the epigenetic signature is affected by environmental factors, the investigators set out to determine if methylation alterations could help explain why PsA patients respond or fail with TNFi. The researchers performed genome-wide DNA methylation profiling on blood samples from 41 PsA patients, using machinery that measures about 480,000 CpG sites per sample and covers 96% of RefSeq genes. A total of 21 patients were considered TNFi responders, of whom 13 were treated with etanercept and 8 with adalimumab; median follow-up duration was 18 months. Twenty patients were considered secondary TNFi failures, of whom 15 were treated with etanercept and 5 with adalimumab; median follow-up duration was 36 months.

Dr. O’Rielly, a senior research scientist at Memorial and director of the Molecular Genetics Laboratory at Eastern Health in St. John’s, and his associates measured the methylation level at CpG sites using a genome-wide approach and selected regions of interest based on functional relevance to TNF-mediated signaling pathways with methylation level differences of 5% or greater and an adjusted P-value less than .05.

After quality-control filtering, investigators evaluated 384,599 CpG sites for TNFi responders and 368,863 CpG sites for TNFi failures. Researchers found 72 CpG sites of interest in the TNFi responder group and 91 CpG sites of interest in the TNFi failure group. Top candidate genes for TNFi responders included TRAPPC9 (which functions as an activator of NF-kB), CCR6 (which regulates the migration and recruitment of dendritic and T cells), and PSORS1C3 (psoriasis susceptibility 1 candidate 3), while top candidate genes for TNFi secondary failures included CD70 (an encoded protein that is a ligand for TNFRSF27/CD27) and TNFRSF1B (a member of the TNF receptor ‘superfamily’ that mediates most of the metabolic effects of TNF-alpha).

“We are very encouraged by these findings,” Dr. O’Rielly said. “We were a little surprised that several of our best candidate genes, such as TNFRSF1B and CD70, appear to play a role in TNF-alpha signaling, and that their methylation change occurs in a gene region that is consistent with a possible functional effect. We were expecting to find some methylation changes in genes but not necessarily in pathways with a direct connection with TNF-alpha–mediated signaling.”

The group plans to confirm these findings for the best candidate genes using other methylation-specific polymerase chain reaction technology, he said, and will investigate additional CpG sites adjacent to the region of interest, including promoters and enhancers, in the best candidate genes to better characterize the full extent of methylation changes in these regions. They also would like to replicate the findings in a prospective, independent cohort.

Dr. O’Rielly reported no relevant financial conflicts.

ROME – Tumor necrosis factor–alpha (TNF-alpha) inhibitors are well established as a treatment for psoriatic arthritis patients, but efficacy can vary greatly within that population. New work from Canadian researchers demonstrates that the global DNA methylation pattern differs between TNF-alpha–inhibitor responders and secondary failures, which could help explain the variability in medication success rates.

“Although TNF inhibitors [TNFi] work very well in certain individuals with psoriatic arthritis [PsA], up to 40% of individuals receiving this treatment fail to achieve a therapeutic response, and 20%-50% of individuals who have an initial response to treatment become refractory weeks or months after receiving therapy.” lead study author Darren O’Rielly, Ph.D., said at the European Congress of Rheumatology.

The preliminary study findings eventually could lead to the identification of biomarkers that would indicate patients who are not good candidates for TNFi medications, said Dr. O’Rielly of Memorial University, St. John’s, Nfld.

Given recent advances in epigenetics and that the epigenetic signature is affected by environmental factors, the investigators set out to determine if methylation alterations could help explain why PsA patients respond or fail with TNFi. The researchers performed genome-wide DNA methylation profiling on blood samples from 41 PsA patients, using machinery that measures about 480,000 CpG sites per sample and covers 96% of RefSeq genes. A total of 21 patients were considered TNFi responders, of whom 13 were treated with etanercept and 8 with adalimumab; median follow-up duration was 18 months. Twenty patients were considered secondary TNFi failures, of whom 15 were treated with etanercept and 5 with adalimumab; median follow-up duration was 36 months.

Dr. O’Rielly, a senior research scientist at Memorial and director of the Molecular Genetics Laboratory at Eastern Health in St. John’s, and his associates measured the methylation level at CpG sites using a genome-wide approach and selected regions of interest based on functional relevance to TNF-mediated signaling pathways with methylation level differences of 5% or greater and an adjusted P-value less than .05.

After quality-control filtering, investigators evaluated 384,599 CpG sites for TNFi responders and 368,863 CpG sites for TNFi failures. Researchers found 72 CpG sites of interest in the TNFi responder group and 91 CpG sites of interest in the TNFi failure group. Top candidate genes for TNFi responders included TRAPPC9 (which functions as an activator of NF-kB), CCR6 (which regulates the migration and recruitment of dendritic and T cells), and PSORS1C3 (psoriasis susceptibility 1 candidate 3), while top candidate genes for TNFi secondary failures included CD70 (an encoded protein that is a ligand for TNFRSF27/CD27) and TNFRSF1B (a member of the TNF receptor ‘superfamily’ that mediates most of the metabolic effects of TNF-alpha).

“We are very encouraged by these findings,” Dr. O’Rielly said. “We were a little surprised that several of our best candidate genes, such as TNFRSF1B and CD70, appear to play a role in TNF-alpha signaling, and that their methylation change occurs in a gene region that is consistent with a possible functional effect. We were expecting to find some methylation changes in genes but not necessarily in pathways with a direct connection with TNF-alpha–mediated signaling.”

The group plans to confirm these findings for the best candidate genes using other methylation-specific polymerase chain reaction technology, he said, and will investigate additional CpG sites adjacent to the region of interest, including promoters and enhancers, in the best candidate genes to better characterize the full extent of methylation changes in these regions. They also would like to replicate the findings in a prospective, independent cohort.

Dr. O’Rielly reported no relevant financial conflicts.

ROME – Changes in the methylation status of particular genes in psoriatic arthritis patients might provide the ability to predict failure to respond to tumor necrosis factor-alpha inhibitors, according to preliminary research in 41 psoriatic arthritis patients.

Two genes stood out to the researchers from Memorial University of Newfoundland, St. John’s: TNFRSF1B and CD70. Patients who had methylation changes to those genes were more likely to have secondary failure of TNF inhibitors, said Dr. Proton Rahman, professor of internal medicine at the university and coinvestigator on the study.

It will be necessary to conduct validation studies of the results in larger numbers of patients, as well as functional studies of the effects of methylation changes on the expression of those genes and their proteins, he said in a video interview at the European Congress of Rheumatology.

jevans@frontlinemedcom.com

ROME – Changes in the methylation status of particular genes in psoriatic arthritis patients might provide the ability to predict failure to respond to tumor necrosis factor-alpha inhibitors, according to preliminary research in 41 psoriatic arthritis patients.

Two genes stood out to the researchers from Memorial University of Newfoundland, St. John’s: TNFRSF1B and CD70. Patients who had methylation changes to those genes were more likely to have secondary failure of TNF inhibitors, said Dr. Proton Rahman, professor of internal medicine at the university and coinvestigator on the study.

It will be necessary to conduct validation studies of the results in larger numbers of patients, as well as functional studies of the effects of methylation changes on the expression of those genes and their proteins, he said in a video interview at the European Congress of Rheumatology.

jevans@frontlinemedcom.com

ROME – Changes in the methylation status of particular genes in psoriatic arthritis patients might provide the ability to predict failure to respond to tumor necrosis factor-alpha inhibitors, according to preliminary research in 41 psoriatic arthritis patients.

Two genes stood out to the researchers from Memorial University of Newfoundland, St. John’s: TNFRSF1B and CD70. Patients who had methylation changes to those genes were more likely to have secondary failure of TNF inhibitors, said Dr. Proton Rahman, professor of internal medicine at the university and coinvestigator on the study.

It will be necessary to conduct validation studies of the results in larger numbers of patients, as well as functional studies of the effects of methylation changes on the expression of those genes and their proteins, he said in a video interview at the European Congress of Rheumatology.

jevans@frontlinemedcom.com

ROME – Biologic drug use in combination with methotrexate appears to carry the greatest risk for serious adverse events in patients with juvenile idiopathic arthritis when different biologics are tried sequentially, according to findings from a study of nearly 6,000 patients in the Pharmachild registry.

The results from the registry, the largest international pharmacovigilance juvenile idiopathic arthritis (JIA) database in the world, showed that patients who had used more than one biologic while on methotrexate had nearly twice the rate of adverse events as did those on methotrexate alone and more than three times the rate of serious adverse events, Dr. Joost F. Swart reported at the European Congress of Rheumatology.

The timing of “when to switch to a biological or even to a second one should not only be based on the activity of the joints as it is recommended nowadays, but should also take into account the different risk profiles of the drugs,” Dr. Swart, a pediatric rheumatologist/immunologist in the department of pediatric immunology and rheumatology in the Wilhelmina Children’s Hospital at University Medical Center Utrecht (the Netherlands), said in an interview. He received a clinical research abstract award for the research at the congress.

The study involved 5,862 JIA patients in the registry who continued methotrexate and either stayed on it alone (1,674) or also added one (3,025) or more biologics over time (1,163). The registry includes 93 centers of the Paediatric Rheumatology International Trials Organization (PRINTO) from more than 30 countries.

Most of the patients who had been treated with one biologic in addition to methotrexate had taken etanercept (66%), followed by adalimumab (19%), infliximab/tocilizumab (about 5% each), and other biologic agents (5%). Treatment experience with multiple biologics was most often with etanercept (30%), adalimumab (27%), infliximab (14%), tocilizumab (9%), abatacept (7%), anakinra (4%), golimumab (4%), and other biologic agents (5%). A total of 40% of children also were treated with corticosteroids (82% of those with systemic JIA); another 20% received other disease-modifying antirheumatic drugs. The patients’ JIA subtypes included systemic (10%), persistent oligoarticular (20%), polyarticular rheumatoid factor positive or negative (50%), and other JIA categories (20%).

Dr. Swart and his coauthors determined that the overall adverse event incidence rate per 100 patient-years was lowest in JIA patients who took methotrexate alone (10.7), intermediate in those who took methotrexate plus one biologic (13.9), and highest among patients who took methotrexate in combination with more than one biologic in sequence over time (19.5). Similar trends were observed for serious adverse events with methotrexate alone (3.0), with one biologic (4.7), and with more than one biologic (9.2).

Although the infection rate was higher for patients who took one biologic (4.6) in comparison with methotrexate alone (2.9), the rate did not increase significantly with more than one biologic (4.8). The same trend applied for serious infections (0.7, 1.4, and 2.0, respectively).

The median disease duration increased from methotrexate-only users (3.6 years) to those who used one biologic with methotrexate (5.4 years) and those who used more than one biologic (7.6 years). The investigators tracked more patient-years of use of one biologic (about 9,000) than two (about 2,800). The number of patient-years on methotrexate for those who took a biologic were not counted in the study.

The proportion of patients who discontinued treatment because of an adverse event or drug intolerance rose along with exposure to greater numbers of drugs, from 4% of methotrexate-only users to 16% of those exposed to a single biologic and 18% of those who took more than one biologic.

The group treated with more than one biologic had higher incidence rates for injury, poisoning and procedural complications, blood and lymphatic system disorders, and eye disorders than did the other groups, whereas methotrexate-only users had a higher incidence of hepatobiliary disorders.

“In due time, we will be able to predict which patients [age, sex, subcategory of JIA, disease activity score, which drugs/drug-combinations, etc.] have the highest risk for certain adverse events and make prediction rules for that. In that way, you might be able to prevent adverse events by specifically avoiding some drugs or drug combinations in certain patient categories or by taking precautionary measures” such as vaccination and antibiotic prophylaxis, Dr. Swart said in an interview.

Analyses are in progress for determining the relationships between individual biologics and adverse events and for differences in adverse events according to geographic area, he said.

Dr. Swart had no conflicts of interest to disclose, but many of his 28 coauthors disclosed relationships with companies that market the drugs used by patients in the registry.

jevans@frontlinemedcom.com

ROME – Biologic drug use in combination with methotrexate appears to carry the greatest risk for serious adverse events in patients with juvenile idiopathic arthritis when different biologics are tried sequentially, according to findings from a study of nearly 6,000 patients in the Pharmachild registry.

The results from the registry, the largest international pharmacovigilance juvenile idiopathic arthritis (JIA) database in the world, showed that patients who had used more than one biologic while on methotrexate had nearly twice the rate of adverse events as did those on methotrexate alone and more than three times the rate of serious adverse events, Dr. Joost F. Swart reported at the European Congress of Rheumatology.

The timing of “when to switch to a biological or even to a second one should not only be based on the activity of the joints as it is recommended nowadays, but should also take into account the different risk profiles of the drugs,” Dr. Swart, a pediatric rheumatologist/immunologist in the department of pediatric immunology and rheumatology in the Wilhelmina Children’s Hospital at University Medical Center Utrecht (the Netherlands), said in an interview. He received a clinical research abstract award for the research at the congress.

The study involved 5,862 JIA patients in the registry who continued methotrexate and either stayed on it alone (1,674) or also added one (3,025) or more biologics over time (1,163). The registry includes 93 centers of the Paediatric Rheumatology International Trials Organization (PRINTO) from more than 30 countries.

Most of the patients who had been treated with one biologic in addition to methotrexate had taken etanercept (66%), followed by adalimumab (19%), infliximab/tocilizumab (about 5% each), and other biologic agents (5%). Treatment experience with multiple biologics was most often with etanercept (30%), adalimumab (27%), infliximab (14%), tocilizumab (9%), abatacept (7%), anakinra (4%), golimumab (4%), and other biologic agents (5%). A total of 40% of children also were treated with corticosteroids (82% of those with systemic JIA); another 20% received other disease-modifying antirheumatic drugs. The patients’ JIA subtypes included systemic (10%), persistent oligoarticular (20%), polyarticular rheumatoid factor positive or negative (50%), and other JIA categories (20%).

Dr. Swart and his coauthors determined that the overall adverse event incidence rate per 100 patient-years was lowest in JIA patients who took methotrexate alone (10.7), intermediate in those who took methotrexate plus one biologic (13.9), and highest among patients who took methotrexate in combination with more than one biologic in sequence over time (19.5). Similar trends were observed for serious adverse events with methotrexate alone (3.0), with one biologic (4.7), and with more than one biologic (9.2).

Although the infection rate was higher for patients who took one biologic (4.6) in comparison with methotrexate alone (2.9), the rate did not increase significantly with more than one biologic (4.8). The same trend applied for serious infections (0.7, 1.4, and 2.0, respectively).

The median disease duration increased from methotrexate-only users (3.6 years) to those who used one biologic with methotrexate (5.4 years) and those who used more than one biologic (7.6 years). The investigators tracked more patient-years of use of one biologic (about 9,000) than two (about 2,800). The number of patient-years on methotrexate for those who took a biologic were not counted in the study.

The proportion of patients who discontinued treatment because of an adverse event or drug intolerance rose along with exposure to greater numbers of drugs, from 4% of methotrexate-only users to 16% of those exposed to a single biologic and 18% of those who took more than one biologic.

The group treated with more than one biologic had higher incidence rates for injury, poisoning and procedural complications, blood and lymphatic system disorders, and eye disorders than did the other groups, whereas methotrexate-only users had a higher incidence of hepatobiliary disorders.

“In due time, we will be able to predict which patients [age, sex, subcategory of JIA, disease activity score, which drugs/drug-combinations, etc.] have the highest risk for certain adverse events and make prediction rules for that. In that way, you might be able to prevent adverse events by specifically avoiding some drugs or drug combinations in certain patient categories or by taking precautionary measures” such as vaccination and antibiotic prophylaxis, Dr. Swart said in an interview.

Analyses are in progress for determining the relationships between individual biologics and adverse events and for differences in adverse events according to geographic area, he said.

Dr. Swart had no conflicts of interest to disclose, but many of his 28 coauthors disclosed relationships with companies that market the drugs used by patients in the registry.

jevans@frontlinemedcom.com

ROME – Biologic drug use in combination with methotrexate appears to carry the greatest risk for serious adverse events in patients with juvenile idiopathic arthritis when different biologics are tried sequentially, according to findings from a study of nearly 6,000 patients in the Pharmachild registry.

The results from the registry, the largest international pharmacovigilance juvenile idiopathic arthritis (JIA) database in the world, showed that patients who had used more than one biologic while on methotrexate had nearly twice the rate of adverse events as did those on methotrexate alone and more than three times the rate of serious adverse events, Dr. Joost F. Swart reported at the European Congress of Rheumatology.

The timing of “when to switch to a biological or even to a second one should not only be based on the activity of the joints as it is recommended nowadays, but should also take into account the different risk profiles of the drugs,” Dr. Swart, a pediatric rheumatologist/immunologist in the department of pediatric immunology and rheumatology in the Wilhelmina Children’s Hospital at University Medical Center Utrecht (the Netherlands), said in an interview. He received a clinical research abstract award for the research at the congress.

The study involved 5,862 JIA patients in the registry who continued methotrexate and either stayed on it alone (1,674) or also added one (3,025) or more biologics over time (1,163). The registry includes 93 centers of the Paediatric Rheumatology International Trials Organization (PRINTO) from more than 30 countries.

Most of the patients who had been treated with one biologic in addition to methotrexate had taken etanercept (66%), followed by adalimumab (19%), infliximab/tocilizumab (about 5% each), and other biologic agents (5%). Treatment experience with multiple biologics was most often with etanercept (30%), adalimumab (27%), infliximab (14%), tocilizumab (9%), abatacept (7%), anakinra (4%), golimumab (4%), and other biologic agents (5%). A total of 40% of children also were treated with corticosteroids (82% of those with systemic JIA); another 20% received other disease-modifying antirheumatic drugs. The patients’ JIA subtypes included systemic (10%), persistent oligoarticular (20%), polyarticular rheumatoid factor positive or negative (50%), and other JIA categories (20%).

Dr. Swart and his coauthors determined that the overall adverse event incidence rate per 100 patient-years was lowest in JIA patients who took methotrexate alone (10.7), intermediate in those who took methotrexate plus one biologic (13.9), and highest among patients who took methotrexate in combination with more than one biologic in sequence over time (19.5). Similar trends were observed for serious adverse events with methotrexate alone (3.0), with one biologic (4.7), and with more than one biologic (9.2).

Although the infection rate was higher for patients who took one biologic (4.6) in comparison with methotrexate alone (2.9), the rate did not increase significantly with more than one biologic (4.8). The same trend applied for serious infections (0.7, 1.4, and 2.0, respectively).

The median disease duration increased from methotrexate-only users (3.6 years) to those who used one biologic with methotrexate (5.4 years) and those who used more than one biologic (7.6 years). The investigators tracked more patient-years of use of one biologic (about 9,000) than two (about 2,800). The number of patient-years on methotrexate for those who took a biologic were not counted in the study.

The proportion of patients who discontinued treatment because of an adverse event or drug intolerance rose along with exposure to greater numbers of drugs, from 4% of methotrexate-only users to 16% of those exposed to a single biologic and 18% of those who took more than one biologic.

The group treated with more than one biologic had higher incidence rates for injury, poisoning and procedural complications, blood and lymphatic system disorders, and eye disorders than did the other groups, whereas methotrexate-only users had a higher incidence of hepatobiliary disorders.

“In due time, we will be able to predict which patients [age, sex, subcategory of JIA, disease activity score, which drugs/drug-combinations, etc.] have the highest risk for certain adverse events and make prediction rules for that. In that way, you might be able to prevent adverse events by specifically avoiding some drugs or drug combinations in certain patient categories or by taking precautionary measures” such as vaccination and antibiotic prophylaxis, Dr. Swart said in an interview.

Analyses are in progress for determining the relationships between individual biologics and adverse events and for differences in adverse events according to geographic area, he said.

Dr. Swart had no conflicts of interest to disclose, but many of his 28 coauthors disclosed relationships with companies that market the drugs used by patients in the registry.

jevans@frontlinemedcom.com