EULAR (European League Against Rheumatism): 2016 Congress

LONDON – Tobacco use and excess weight can make it harder to achieve sustained remission in the treatment of early rheumatoid arthritis, according to findings from more than 1,000 patients in the Canadian Early Arthritis Cohort (CATCH) multicenter, prospective study.

Aggressive treatment that starts soon after diagnosis of rheumatoid arthritis (RA) is important for the absence of disease activity, which is the hallmark of sustained remission. But the reality is a success rate of less than 50% in the first 3 years with physical deterioration continuing thereafter. “Excess weight and smoking are two risk factors for developing RA. We were interested in seeing if they might also affect how well people responded to treatment,” said Susan Bartlett, Ph.D., a clinical psychologist at McGill University in Montreal.

At the annual European Congress of Rheumatology, Dr. Bartlett and colleagues reported on a cohort of 1,008 early RA patients who were enrolled in the Canadian Early Arthritis Cohort (CATCH) multicenter, prospective study and followed from around the time of diagnosis through the first 3 years of treatment to estimate the time it took until they achieved sustained remission, defined as having a 28-joint Disease Activity Score less than 2.6 for two consecutive visits.

Mean age of the patients (72% female, 81% white) was early 50s. Overall, 30% of females and 47% of males were overweight, one-third of both genders were obese, and 15%-20% smoked. Treatment at entry included methotrexate in mono- or combination therapy in about three-quarters of the patients, with steroids used in about half and biologics used sparingly.

The proportion of patients in sustained remission was 38% at 3 years, with a median time to remission of 11.3 months. “That finding wasn’t surprising because that is generally what is found in most studies of early RA. However, when we looked more closely at who was and wasn’t achieving remission, we found that people who smoked and those who were overweight or obese were much less likely than their nonsmoking, normal-weight peers to be in sustained remission,” Dr. Bartlett said in a pre-congress interview.

After adjustment for factors that could affect response to treatment – including age, race, disability status, pain, and early medications used – smoking (P = .046) and excess weight (P = .003) were associated with a poorer likelihood of achieving sustained remission. While more men than women were overweight or obese, the effects of weight and smoking appeared to be more problematic for women (P = .02).

An average nonsmoking male with a healthy body mass index (BMI; 25 kg/m² or less) had about a 41% probability of achieving sustained remission within 3 years, compared with 15% for an obese male smoker. A nonsmoking female with a healthy BMI had a 27% probability of achieving sustained remission within 3 years, compared with 10% for an obese female smoker. Probabilities of sustained remission were also lower for overweight men and women, Dr. Bartlett reported.

Smoking and obesity have already been linked with an increased likelihood of developing RA, which in turn increases the risk of cardiovascular disease and premature death. The latest data suggest that both smoking and extra weight – including overweight and obese as defined by BMI – may also independently influence the success of treatment. “Our data suggest that if you have RA, it’s important to take the medications that your doctor has prescribed. If you smoke, you need to stop. And if you’re carrying extra weight, not only is that placing a greater demand on already vulnerable joints, it may also be making your RA treatment less effective,” Dr. Bartlett said.

These lifestyle modifications can be challenging for some people with RA, she said in the interview. Clinicians can help by considering lifestyle behaviors that lead to chronic diseases and poorer outcomes in addition to their more traditional view of diagnosis and treatment, she said, adding that patients and clinicians should know that even a small amount of weight loss can improve health and may improve response to therapy.

Well controlled clinical trials will be needed to better understand the benefits of weight control and smoking cessation on response to RA treatment. Also, why women who smoke and are overweight are at more of a disadvantage than their male counterparts is unknown. “As we begin putting these pieces together, we may learn valuable information that helps us to better control and ultimately cure RA,” said Dr. Bartlett.

The researchers had no conflicts of interest to declare.

LONDON – Tobacco use and excess weight can make it harder to achieve sustained remission in the treatment of early rheumatoid arthritis, according to findings from more than 1,000 patients in the Canadian Early Arthritis Cohort (CATCH) multicenter, prospective study.

Aggressive treatment that starts soon after diagnosis of rheumatoid arthritis (RA) is important for the absence of disease activity, which is the hallmark of sustained remission. But the reality is a success rate of less than 50% in the first 3 years with physical deterioration continuing thereafter. “Excess weight and smoking are two risk factors for developing RA. We were interested in seeing if they might also affect how well people responded to treatment,” said Susan Bartlett, Ph.D., a clinical psychologist at McGill University in Montreal.

At the annual European Congress of Rheumatology, Dr. Bartlett and colleagues reported on a cohort of 1,008 early RA patients who were enrolled in the Canadian Early Arthritis Cohort (CATCH) multicenter, prospective study and followed from around the time of diagnosis through the first 3 years of treatment to estimate the time it took until they achieved sustained remission, defined as having a 28-joint Disease Activity Score less than 2.6 for two consecutive visits.

Mean age of the patients (72% female, 81% white) was early 50s. Overall, 30% of females and 47% of males were overweight, one-third of both genders were obese, and 15%-20% smoked. Treatment at entry included methotrexate in mono- or combination therapy in about three-quarters of the patients, with steroids used in about half and biologics used sparingly.

The proportion of patients in sustained remission was 38% at 3 years, with a median time to remission of 11.3 months. “That finding wasn’t surprising because that is generally what is found in most studies of early RA. However, when we looked more closely at who was and wasn’t achieving remission, we found that people who smoked and those who were overweight or obese were much less likely than their nonsmoking, normal-weight peers to be in sustained remission,” Dr. Bartlett said in a pre-congress interview.

After adjustment for factors that could affect response to treatment – including age, race, disability status, pain, and early medications used – smoking (P = .046) and excess weight (P = .003) were associated with a poorer likelihood of achieving sustained remission. While more men than women were overweight or obese, the effects of weight and smoking appeared to be more problematic for women (P = .02).

An average nonsmoking male with a healthy body mass index (BMI; 25 kg/m² or less) had about a 41% probability of achieving sustained remission within 3 years, compared with 15% for an obese male smoker. A nonsmoking female with a healthy BMI had a 27% probability of achieving sustained remission within 3 years, compared with 10% for an obese female smoker. Probabilities of sustained remission were also lower for overweight men and women, Dr. Bartlett reported.

Smoking and obesity have already been linked with an increased likelihood of developing RA, which in turn increases the risk of cardiovascular disease and premature death. The latest data suggest that both smoking and extra weight – including overweight and obese as defined by BMI – may also independently influence the success of treatment. “Our data suggest that if you have RA, it’s important to take the medications that your doctor has prescribed. If you smoke, you need to stop. And if you’re carrying extra weight, not only is that placing a greater demand on already vulnerable joints, it may also be making your RA treatment less effective,” Dr. Bartlett said.

These lifestyle modifications can be challenging for some people with RA, she said in the interview. Clinicians can help by considering lifestyle behaviors that lead to chronic diseases and poorer outcomes in addition to their more traditional view of diagnosis and treatment, she said, adding that patients and clinicians should know that even a small amount of weight loss can improve health and may improve response to therapy.

Well controlled clinical trials will be needed to better understand the benefits of weight control and smoking cessation on response to RA treatment. Also, why women who smoke and are overweight are at more of a disadvantage than their male counterparts is unknown. “As we begin putting these pieces together, we may learn valuable information that helps us to better control and ultimately cure RA,” said Dr. Bartlett.

The researchers had no conflicts of interest to declare.

LONDON – Tobacco use and excess weight can make it harder to achieve sustained remission in the treatment of early rheumatoid arthritis, according to findings from more than 1,000 patients in the Canadian Early Arthritis Cohort (CATCH) multicenter, prospective study.

Aggressive treatment that starts soon after diagnosis of rheumatoid arthritis (RA) is important for the absence of disease activity, which is the hallmark of sustained remission. But the reality is a success rate of less than 50% in the first 3 years with physical deterioration continuing thereafter. “Excess weight and smoking are two risk factors for developing RA. We were interested in seeing if they might also affect how well people responded to treatment,” said Susan Bartlett, Ph.D., a clinical psychologist at McGill University in Montreal.

At the annual European Congress of Rheumatology, Dr. Bartlett and colleagues reported on a cohort of 1,008 early RA patients who were enrolled in the Canadian Early Arthritis Cohort (CATCH) multicenter, prospective study and followed from around the time of diagnosis through the first 3 years of treatment to estimate the time it took until they achieved sustained remission, defined as having a 28-joint Disease Activity Score less than 2.6 for two consecutive visits.

Mean age of the patients (72% female, 81% white) was early 50s. Overall, 30% of females and 47% of males were overweight, one-third of both genders were obese, and 15%-20% smoked. Treatment at entry included methotrexate in mono- or combination therapy in about three-quarters of the patients, with steroids used in about half and biologics used sparingly.

The proportion of patients in sustained remission was 38% at 3 years, with a median time to remission of 11.3 months. “That finding wasn’t surprising because that is generally what is found in most studies of early RA. However, when we looked more closely at who was and wasn’t achieving remission, we found that people who smoked and those who were overweight or obese were much less likely than their nonsmoking, normal-weight peers to be in sustained remission,” Dr. Bartlett said in a pre-congress interview.

After adjustment for factors that could affect response to treatment – including age, race, disability status, pain, and early medications used – smoking (P = .046) and excess weight (P = .003) were associated with a poorer likelihood of achieving sustained remission. While more men than women were overweight or obese, the effects of weight and smoking appeared to be more problematic for women (P = .02).

An average nonsmoking male with a healthy body mass index (BMI; 25 kg/m² or less) had about a 41% probability of achieving sustained remission within 3 years, compared with 15% for an obese male smoker. A nonsmoking female with a healthy BMI had a 27% probability of achieving sustained remission within 3 years, compared with 10% for an obese female smoker. Probabilities of sustained remission were also lower for overweight men and women, Dr. Bartlett reported.

Smoking and obesity have already been linked with an increased likelihood of developing RA, which in turn increases the risk of cardiovascular disease and premature death. The latest data suggest that both smoking and extra weight – including overweight and obese as defined by BMI – may also independently influence the success of treatment. “Our data suggest that if you have RA, it’s important to take the medications that your doctor has prescribed. If you smoke, you need to stop. And if you’re carrying extra weight, not only is that placing a greater demand on already vulnerable joints, it may also be making your RA treatment less effective,” Dr. Bartlett said.

These lifestyle modifications can be challenging for some people with RA, she said in the interview. Clinicians can help by considering lifestyle behaviors that lead to chronic diseases and poorer outcomes in addition to their more traditional view of diagnosis and treatment, she said, adding that patients and clinicians should know that even a small amount of weight loss can improve health and may improve response to therapy.

Well controlled clinical trials will be needed to better understand the benefits of weight control and smoking cessation on response to RA treatment. Also, why women who smoke and are overweight are at more of a disadvantage than their male counterparts is unknown. “As we begin putting these pieces together, we may learn valuable information that helps us to better control and ultimately cure RA,” said Dr. Bartlett.

The researchers had no conflicts of interest to declare.

LONDON – The prevalence of gout is increasing and to prevent an epidemic, rheumatologists and other physicians need to diagnose and treat cases promptly and better explain the treatment process to their patients, according to a Swedish expert on the disease.

“It’s a disease for which we understand the mechanisms, we know how to diagnose it, and we have had good treatments for the last 50 years,” said Dr. Lennart Jacobsson, professor of rheumatology at the University of Gothenburg in Sweden. “Despite that, we don’t treat it properly. It’s difficult to understand why that is the case, why there is such a lack of knowledge and such a lack of willingness to pursue treatment.”

Gout is the most common nondegenerative inflammatory joint disease, exemplified by a prevalence of 0.9%-2.5% in Europe and 3.9% in the United States. The incidence is increasing along with factors such as the aging population, as well as lifestyle changes such as rising body mass index and physical inactivity, Dr. Jacobsson said at the European Congress of Rheumatology.

“It’s the same story everywhere,” he said. “Gout is underdiagnosed, it’s diagnosed late, and once it’s diagnosed people don’t get treated with urate-lowering therapy, which aims at the heart of the disease. If they are treated, treatment often is discontinued, which we think is largely due to lack of education and information to patients.”

Urate crystals can build up over as much as a decade before a person experiences a first gout attack, Dr. Jacobsson said. “It can take 3-5 years of effective treatment to get rid of those masses within the body. Over that time, especially at the beginning, patients may still have gout attacks, which they often interpret as side effects of the medication or a misinterpretation that it doesn’t work because they’re not properly informed that medication needs to be a long-term treatment.”

Close to 10% of men aged 70-80 years have gout, he said, but it’s still unclear how many of those have mild, moderate, or severe disease. It’s also not well studied how gout itself can affect health-related quality of life and costs to society. “You can easily imagine that the costs are pretty large, however, and they will increase,” he said.

Gout is interrelated with several metabolic syndrome disorders such as obesity, hypertension, and diabetes, Dr. Jacobsson said: “If you have renal disease, you have higher uric acid levels and can more easily get gout, but from having high uric acid levels you may also get decreased renal function, so it’s sort of circular. The same is true of gout and hypertension.”

Once considered a disease of the wealthy, Dr. Jacobsson said, gout has recently been shown to be associated with lower income and socioeconomic class, as is the case for many other chronic diseases. There are still large opportunities for improvements regarding early detection and the initiation of urate-lowering therapy, he said, as well as counseling patients on lifestyle improvements.

“We know what to do, we have the tools, and we should start using them more effectively,” he said. “It’s really very simple, but that message has to get through. It’s an increasing problem, and it’s bad not just for the joints but also for quality of life and comorbidities.”

Dr. Jacobsson reported no relevant financial disclosures.

LONDON – The prevalence of gout is increasing and to prevent an epidemic, rheumatologists and other physicians need to diagnose and treat cases promptly and better explain the treatment process to their patients, according to a Swedish expert on the disease.

“It’s a disease for which we understand the mechanisms, we know how to diagnose it, and we have had good treatments for the last 50 years,” said Dr. Lennart Jacobsson, professor of rheumatology at the University of Gothenburg in Sweden. “Despite that, we don’t treat it properly. It’s difficult to understand why that is the case, why there is such a lack of knowledge and such a lack of willingness to pursue treatment.”

Gout is the most common nondegenerative inflammatory joint disease, exemplified by a prevalence of 0.9%-2.5% in Europe and 3.9% in the United States. The incidence is increasing along with factors such as the aging population, as well as lifestyle changes such as rising body mass index and physical inactivity, Dr. Jacobsson said at the European Congress of Rheumatology.

“It’s the same story everywhere,” he said. “Gout is underdiagnosed, it’s diagnosed late, and once it’s diagnosed people don’t get treated with urate-lowering therapy, which aims at the heart of the disease. If they are treated, treatment often is discontinued, which we think is largely due to lack of education and information to patients.”

Urate crystals can build up over as much as a decade before a person experiences a first gout attack, Dr. Jacobsson said. “It can take 3-5 years of effective treatment to get rid of those masses within the body. Over that time, especially at the beginning, patients may still have gout attacks, which they often interpret as side effects of the medication or a misinterpretation that it doesn’t work because they’re not properly informed that medication needs to be a long-term treatment.”

Close to 10% of men aged 70-80 years have gout, he said, but it’s still unclear how many of those have mild, moderate, or severe disease. It’s also not well studied how gout itself can affect health-related quality of life and costs to society. “You can easily imagine that the costs are pretty large, however, and they will increase,” he said.

Gout is interrelated with several metabolic syndrome disorders such as obesity, hypertension, and diabetes, Dr. Jacobsson said: “If you have renal disease, you have higher uric acid levels and can more easily get gout, but from having high uric acid levels you may also get decreased renal function, so it’s sort of circular. The same is true of gout and hypertension.”

Once considered a disease of the wealthy, Dr. Jacobsson said, gout has recently been shown to be associated with lower income and socioeconomic class, as is the case for many other chronic diseases. There are still large opportunities for improvements regarding early detection and the initiation of urate-lowering therapy, he said, as well as counseling patients on lifestyle improvements.

“We know what to do, we have the tools, and we should start using them more effectively,” he said. “It’s really very simple, but that message has to get through. It’s an increasing problem, and it’s bad not just for the joints but also for quality of life and comorbidities.”

Dr. Jacobsson reported no relevant financial disclosures.

LONDON – The prevalence of gout is increasing and to prevent an epidemic, rheumatologists and other physicians need to diagnose and treat cases promptly and better explain the treatment process to their patients, according to a Swedish expert on the disease.

“It’s a disease for which we understand the mechanisms, we know how to diagnose it, and we have had good treatments for the last 50 years,” said Dr. Lennart Jacobsson, professor of rheumatology at the University of Gothenburg in Sweden. “Despite that, we don’t treat it properly. It’s difficult to understand why that is the case, why there is such a lack of knowledge and such a lack of willingness to pursue treatment.”

Gout is the most common nondegenerative inflammatory joint disease, exemplified by a prevalence of 0.9%-2.5% in Europe and 3.9% in the United States. The incidence is increasing along with factors such as the aging population, as well as lifestyle changes such as rising body mass index and physical inactivity, Dr. Jacobsson said at the European Congress of Rheumatology.

“It’s the same story everywhere,” he said. “Gout is underdiagnosed, it’s diagnosed late, and once it’s diagnosed people don’t get treated with urate-lowering therapy, which aims at the heart of the disease. If they are treated, treatment often is discontinued, which we think is largely due to lack of education and information to patients.”

Urate crystals can build up over as much as a decade before a person experiences a first gout attack, Dr. Jacobsson said. “It can take 3-5 years of effective treatment to get rid of those masses within the body. Over that time, especially at the beginning, patients may still have gout attacks, which they often interpret as side effects of the medication or a misinterpretation that it doesn’t work because they’re not properly informed that medication needs to be a long-term treatment.”

Close to 10% of men aged 70-80 years have gout, he said, but it’s still unclear how many of those have mild, moderate, or severe disease. It’s also not well studied how gout itself can affect health-related quality of life and costs to society. “You can easily imagine that the costs are pretty large, however, and they will increase,” he said.

Gout is interrelated with several metabolic syndrome disorders such as obesity, hypertension, and diabetes, Dr. Jacobsson said: “If you have renal disease, you have higher uric acid levels and can more easily get gout, but from having high uric acid levels you may also get decreased renal function, so it’s sort of circular. The same is true of gout and hypertension.”

Once considered a disease of the wealthy, Dr. Jacobsson said, gout has recently been shown to be associated with lower income and socioeconomic class, as is the case for many other chronic diseases. There are still large opportunities for improvements regarding early detection and the initiation of urate-lowering therapy, he said, as well as counseling patients on lifestyle improvements.

“We know what to do, we have the tools, and we should start using them more effectively,” he said. “It’s really very simple, but that message has to get through. It’s an increasing problem, and it’s bad not just for the joints but also for quality of life and comorbidities.”

Dr. Jacobsson reported no relevant financial disclosures.

LONDON – U.S. rheumatoid arthritis patients had a significantly reduced incidence of type 2 diabetes when on treatment with either hydroxychloroquine or abatacept in an analysis of more than 13,000 patients enrolled in a U.S. national registry during 2000-2015.

The same analysis also showed statistically significant increases in the risk for new-onset type 2 diabetes in rheumatoid arthritis (RA) patients treated with a glucocorticoid or a statin, Kaleb Michaud, Ph.D., reported in a poster at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

“Our findings can inform clinicians about determining appropriate treatment decisions in rheumatoid arthritis patients at increased risk for developing type 2 diabetes,” said Dr. Michaud, an epidemiologist at the University of Nebraska in Omaha and also codirector of the National Data Bank for Rheumatic Diseases in Wichita, Kan., the source of the data used in his study.

Hydroxychloroquine, a relatively inexpensive drug that’s often used in RA patients in combination with other drugs, might be a good agent to consider adding to the therapeutic mix of RA patients at risk for developing type 2 diabetes, he said in an interview. Although the implications of this finding for the use of abatacept (Orencia) are less clear, it is a signal of a novel benefit from the drug that merits further study, Dr. Michaud said.

The findings also suggest that, when rheumatoid arthritis patients receive statin treatment, they are candidates for more intensive monitoring of diabetes onset, he added.

His analysis focused on the 13,669 RA patients who participated in the National Data Bank for Rheumatic Diseases for at least a year during 2000-2015 and had not been diagnosed as having diabetes of any type at the time they entered the registry. During a median 4.6 years of follow-up, 1,139 patients either self-reported receiving a new diagnosis of type 2 diabetes or began treatment with a hypoglycemic medication. Patients averaged about 59 years old at the time they entered the registry, and about 80% were women.

Dr. Michaud and his associates assessed the incidence rate of type 2 diabetes according to six categories of RA treatment: methotrexate monotherapy, which they used as the reference group; any treatment with abatacept with or without methotrexate; any treatment with hydroxychloroquine; any treatment with a glucocorticoid; treatment with any other disease-modifying antirheumatic drug (DMARD) with methotrexate; and treatment with any other DMARD without methotrexate or no DMARD treatment. A seventh treatment category was treatment with a statin.

A series of time-varying Cox proportional hazard models that adjusted for sociodemographic variables, comorbidities, body mass index, and measures of RA severity showed that, when compared with methotrexate monotherapy, patients treated with abatacept had a statistically significant 48% reduced rate of developing diabetes, and those treated with hydroxychloroquine had a statistically significant 33% reduced diabetes incidence, they reported.

In contrast, compared with methotrexate monotherapy, treatment with a glucocorticoid linked with a statistically significant 31% increased rate of type 2 diabetes, and treatment with a statin linked with a statistically significant 56% increased rate of diabetes. Other forms of DMARD treatment, including tumor necrosis factor inhibitors and other biologic DMARDs, had no statistically significant link with diabetes development.

Dr. Michaud also reported additional analyses that further defined the associations between hydroxychloroquine treatment and reduced diabetes incidence: The reduction in diabetes incidence became statistically significant in patients only when they had received the drug for at least 2 years. The link with reduced diabetes incidence seemed dose dependent, with a stronger protective effect in patients who received at least 400 mg/day. Also, the strength of the protection waned in patients who had discontinued hydroxychloroquine for at least 6 months, and the protective effect completely disappeared once patients were off hydroxychloroquine for at least 1 year. Finally, the link between hydroxychloroquine use and reduced diabetes incidence also was statistically significant in patients who concurrently received a glucocorticoid, but a significant protective association disappeared in patients who received a statin as well as hydroxychloroquine.

Dr. Michaud had no disclosures. The study received no commercial support.

[email protected]

On Twitter @mitchelzoler

LONDON – U.S. rheumatoid arthritis patients had a significantly reduced incidence of type 2 diabetes when on treatment with either hydroxychloroquine or abatacept in an analysis of more than 13,000 patients enrolled in a U.S. national registry during 2000-2015.

The same analysis also showed statistically significant increases in the risk for new-onset type 2 diabetes in rheumatoid arthritis (RA) patients treated with a glucocorticoid or a statin, Kaleb Michaud, Ph.D., reported in a poster at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

“Our findings can inform clinicians about determining appropriate treatment decisions in rheumatoid arthritis patients at increased risk for developing type 2 diabetes,” said Dr. Michaud, an epidemiologist at the University of Nebraska in Omaha and also codirector of the National Data Bank for Rheumatic Diseases in Wichita, Kan., the source of the data used in his study.

Hydroxychloroquine, a relatively inexpensive drug that’s often used in RA patients in combination with other drugs, might be a good agent to consider adding to the therapeutic mix of RA patients at risk for developing type 2 diabetes, he said in an interview. Although the implications of this finding for the use of abatacept (Orencia) are less clear, it is a signal of a novel benefit from the drug that merits further study, Dr. Michaud said.

The findings also suggest that, when rheumatoid arthritis patients receive statin treatment, they are candidates for more intensive monitoring of diabetes onset, he added.

His analysis focused on the 13,669 RA patients who participated in the National Data Bank for Rheumatic Diseases for at least a year during 2000-2015 and had not been diagnosed as having diabetes of any type at the time they entered the registry. During a median 4.6 years of follow-up, 1,139 patients either self-reported receiving a new diagnosis of type 2 diabetes or began treatment with a hypoglycemic medication. Patients averaged about 59 years old at the time they entered the registry, and about 80% were women.

Dr. Michaud and his associates assessed the incidence rate of type 2 diabetes according to six categories of RA treatment: methotrexate monotherapy, which they used as the reference group; any treatment with abatacept with or without methotrexate; any treatment with hydroxychloroquine; any treatment with a glucocorticoid; treatment with any other disease-modifying antirheumatic drug (DMARD) with methotrexate; and treatment with any other DMARD without methotrexate or no DMARD treatment. A seventh treatment category was treatment with a statin.

A series of time-varying Cox proportional hazard models that adjusted for sociodemographic variables, comorbidities, body mass index, and measures of RA severity showed that, when compared with methotrexate monotherapy, patients treated with abatacept had a statistically significant 48% reduced rate of developing diabetes, and those treated with hydroxychloroquine had a statistically significant 33% reduced diabetes incidence, they reported.

In contrast, compared with methotrexate monotherapy, treatment with a glucocorticoid linked with a statistically significant 31% increased rate of type 2 diabetes, and treatment with a statin linked with a statistically significant 56% increased rate of diabetes. Other forms of DMARD treatment, including tumor necrosis factor inhibitors and other biologic DMARDs, had no statistically significant link with diabetes development.

Dr. Michaud also reported additional analyses that further defined the associations between hydroxychloroquine treatment and reduced diabetes incidence: The reduction in diabetes incidence became statistically significant in patients only when they had received the drug for at least 2 years. The link with reduced diabetes incidence seemed dose dependent, with a stronger protective effect in patients who received at least 400 mg/day. Also, the strength of the protection waned in patients who had discontinued hydroxychloroquine for at least 6 months, and the protective effect completely disappeared once patients were off hydroxychloroquine for at least 1 year. Finally, the link between hydroxychloroquine use and reduced diabetes incidence also was statistically significant in patients who concurrently received a glucocorticoid, but a significant protective association disappeared in patients who received a statin as well as hydroxychloroquine.

Dr. Michaud had no disclosures. The study received no commercial support.

[email protected]

On Twitter @mitchelzoler

LONDON – U.S. rheumatoid arthritis patients had a significantly reduced incidence of type 2 diabetes when on treatment with either hydroxychloroquine or abatacept in an analysis of more than 13,000 patients enrolled in a U.S. national registry during 2000-2015.

The same analysis also showed statistically significant increases in the risk for new-onset type 2 diabetes in rheumatoid arthritis (RA) patients treated with a glucocorticoid or a statin, Kaleb Michaud, Ph.D., reported in a poster at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

“Our findings can inform clinicians about determining appropriate treatment decisions in rheumatoid arthritis patients at increased risk for developing type 2 diabetes,” said Dr. Michaud, an epidemiologist at the University of Nebraska in Omaha and also codirector of the National Data Bank for Rheumatic Diseases in Wichita, Kan., the source of the data used in his study.

Hydroxychloroquine, a relatively inexpensive drug that’s often used in RA patients in combination with other drugs, might be a good agent to consider adding to the therapeutic mix of RA patients at risk for developing type 2 diabetes, he said in an interview. Although the implications of this finding for the use of abatacept (Orencia) are less clear, it is a signal of a novel benefit from the drug that merits further study, Dr. Michaud said.

The findings also suggest that, when rheumatoid arthritis patients receive statin treatment, they are candidates for more intensive monitoring of diabetes onset, he added.

His analysis focused on the 13,669 RA patients who participated in the National Data Bank for Rheumatic Diseases for at least a year during 2000-2015 and had not been diagnosed as having diabetes of any type at the time they entered the registry. During a median 4.6 years of follow-up, 1,139 patients either self-reported receiving a new diagnosis of type 2 diabetes or began treatment with a hypoglycemic medication. Patients averaged about 59 years old at the time they entered the registry, and about 80% were women.

Dr. Michaud and his associates assessed the incidence rate of type 2 diabetes according to six categories of RA treatment: methotrexate monotherapy, which they used as the reference group; any treatment with abatacept with or without methotrexate; any treatment with hydroxychloroquine; any treatment with a glucocorticoid; treatment with any other disease-modifying antirheumatic drug (DMARD) with methotrexate; and treatment with any other DMARD without methotrexate or no DMARD treatment. A seventh treatment category was treatment with a statin.

A series of time-varying Cox proportional hazard models that adjusted for sociodemographic variables, comorbidities, body mass index, and measures of RA severity showed that, when compared with methotrexate monotherapy, patients treated with abatacept had a statistically significant 48% reduced rate of developing diabetes, and those treated with hydroxychloroquine had a statistically significant 33% reduced diabetes incidence, they reported.

In contrast, compared with methotrexate monotherapy, treatment with a glucocorticoid linked with a statistically significant 31% increased rate of type 2 diabetes, and treatment with a statin linked with a statistically significant 56% increased rate of diabetes. Other forms of DMARD treatment, including tumor necrosis factor inhibitors and other biologic DMARDs, had no statistically significant link with diabetes development.

Dr. Michaud also reported additional analyses that further defined the associations between hydroxychloroquine treatment and reduced diabetes incidence: The reduction in diabetes incidence became statistically significant in patients only when they had received the drug for at least 2 years. The link with reduced diabetes incidence seemed dose dependent, with a stronger protective effect in patients who received at least 400 mg/day. Also, the strength of the protection waned in patients who had discontinued hydroxychloroquine for at least 6 months, and the protective effect completely disappeared once patients were off hydroxychloroquine for at least 1 year. Finally, the link between hydroxychloroquine use and reduced diabetes incidence also was statistically significant in patients who concurrently received a glucocorticoid, but a significant protective association disappeared in patients who received a statin as well as hydroxychloroquine.

Dr. Michaud had no disclosures. The study received no commercial support.

[email protected]

On Twitter @mitchelzoler

LONDON – Tumor necrosis factor may play a role in erosive hand osteoarthritis, and treatments such as etanercept that target this cytokine may help prevent progression of the condition, according to the results of two studies presented at the European Congress of Rheumatology.

In one of the studies, immunoscintigraphic detection of radiolabeled certolizumab pegol was used to show that tumor necrosis factor (TNF) was present in swollen finger joints. In another study, researchers looked to see if treatment with etanercept would have any specific effects on the joints of patients with erosive hand osteoarthritis (OA) and performed a separate analysis of the potential effect on synovitis and the effect on bone marrow lesions.

“We previously had the idea that TNF is an important cytokine in the pathogenesis of erosive [hand] osteoarthritis; but there have been no animal studies, and it’s very difficult to take biopsies or fluid aspiration from these small finger joints,” Dr. Ruth Wittoek, a staff rheumatologist at Ghent University Hospital in Belgium and a coauthor of all three studies, explained in a precongress interview. “We needed to look for other possibilities to really identify the presence of TNF in those affected joints.”

Dr. Wittoek and her associates used immunoscintigraphy to take static images of both hands of five patients with erosive OA immediately (less than 15 minutes) after administration of radiolabeled certolizumab pegol (early phase) and 4-6 hours following the injection (late phase).

The patients studied had erosive OA for a median of 8.4 years, and their median age was 55.6 years. All patients underwent clinical examination for presence of tenderness and palpable swelling of the joints and ultrasound 1 day prior to undergoing immunoscintigraphy.

All 18 interphalangeal (IP) finger joints were scored according to the anatomical phase scoring system on x-ray, and 90 IP finger joints were studied in total. The uptake of radiolabeled certolizumab pegol was semiquantitatively described as being absent, weak, or strong.

During the early phase following administration, uptake of the radiolabeled TNF inhibitor was seen in seven (7.8%) joints, although the uptake was described as weak in all cases. The radiolabeled TNF inhibitor was seen in 24 (26.7%) joints during the late phase following administration, with five instances described as strong uptake and the remaining 19 instances being weak uptake. No uptake of the radiolabeled TNF inhibitor was seen in metacarpophalangeal joints.

Uptake of the radiolabeled TNF inhibitor was linked to signs of disease activity, including tender, swollen, and radiographically active joints.

Late uptake was present in 12 (36.4%) of 33 tender joints and in 12 (21.1%) of 57 nontender joints (odds ratio, 2.1; 95% confidence interval, 0.8-5.6; P was nonsignificant).

The relationship was most pronounced with palpable joint swelling: Late uptake was present in 14 (61%) of 23 swollen joints and 10 (14.9%) of 67 nonswollen joints (OR, 8.9; 95% CI, 3.3-26.0; P less than .001).

Late uptake was present in 18 (29%) of 62 sonographically active joints (defined as any presence of effusion or synovial proliferation) but just 6 (21.4%) of 28 noninflamed joints (OR, 1.5; 95% CI, 0.5-4.3; P was nonsignificant).

Uptake of the radiolabeled TNF inhibitor was observed in all anatomical phases of erosive hand OA, Dr. Wittoek noted, but the strongest association was found during the final remodeling (R) phase.

“Soft-tissue swelling strongly correlated with uptake of certolizumab, meaning in these joints a lot of TNF was present,” Dr. Wittoek said. “These data further solidify the rationale for cytokine-directed therapies in erosive OA.”

Although the data provide proof of concept that TNF may be involved in erosive hand OA, the lack of a control tracer was noted as a limitation of the study after the investigator’s presentation. Dr. Wittoek conceded that it would be interesting to examine that in a future study.

So, if TNF is present, what effect does anti-TNF therapy have on the joints in erosive hand OA?

That question was addressed in a multicenter, double-blind, randomized, placebo-controlled trial involving 90 patients who were randomized to receive either 50 mg of subcutaneous etanercept weekly for 24 weeks, then 25 mg weekly for the remainder of 1 year (45 patients), or placebo (45 patients). Participants were a mean age of 60 years, 81% were women, and 96% fulfilled the American College of Rheumatology hand OA criteria.

“Synovial inflammation is often present in erosive hand OA; moreover, synovitis is associated with pain and with structural damage after around 2 and a half years,” the lead study author, Dr. Margreet Kloppenburg, a professor of rheumatology at Leiden University Medical Centre in the Netherlands, said in an interview.

“Therefore, we wanted to know whether blocking of synovial inflammation by a well-known drug such as etanercept would also have a positive effect on outcomes in erosive hand OA,” Dr. Kloppenburg explained.

The primary outcome measure was the level of OA pain assessed on a visual analog scale (VAS) at 24 weeks.

Secondary endpoints included assessment of hand function, quality of life, the number of tender joints, and grip strength after 4, 8, 12, 24, and 36 weeks, and after 1 year. Radiographic progression of IP joints was scored blindly at baseline, 24 weeks, and 1 year following the quantitative Ghent University Scoring System (GUSS). VAS pain was compared between treatment groups at 24 weeks and 1 year in intention-to-treat analyses.

Although etanercept was not superior to placebo on VAS pain at 24 weeks, it was superior to placebo both on pain and structural damage assessed by GUSS in the symptomatic and inflammatory patients who completed the study. The drug was especially effective in joints with signs of inflammation.

Overall, VAS pain in all patients decreased by 24.8 mm (95% CI, –29.2 to –20.5; P less than .001) at 24 weeks. In intention-to-treat analysis, differences in pain between the groups were in favor of etanercept but did not reach statistical significance. The per-protocol analysis of GUSS showed a mean difference in favor of etanercept, indicating more remodeling in the etanercept group.

Additional analyses showed an interaction between soft swelling/erythema and etanercept treatment on GUSS, resulting in a statistically significant (P less than .05) mean difference between the two treatment groups. More patients dropped out on placebo than on etanercept (six vs. three) because of inefficacy, whereas more dropped out on etanercept than on placebo (six vs. one) because of adverse effects.

“Synovial inflammation is an interesting target for treatment in OA patients with an inflammatory hand osteoarthritis phenotype,” Dr. Kloppenburg said.

A separate analysis of the same multicenter study suggests that etanercept is effective in inhibiting bone marrow lesions (BMLs) in patients with erosive hand OA.

The researchers studied 20 participants with symptomatic erosive OA with clinical and ultrasonographic signs of inflammation in at least one IP joint. The patients underwent contrast-enhanced MRI of the eight distal and proximal IP joints of one hand at baseline and 1 year. Images were scored for synovitis and BMLs (0-3 per joint, total score 0-24), blinded for patient characteristics.

Radiographs of the same hand were scored according to the Verbruggen-Veys system. Logistic regression was used to associate the presence of an MRI feature in a joint with being in an erosive versus nonerosive anatomical phase.

“Although erosive hand OA is a condition with a high disease burden, no disease-modifying treatments are available yet,” explained Féline Kroon, a PhD student in the department of rheumatology at Leiden University Medical Center in the Netherlands, in an interview. “Research to find a new form of therapy is partly hindered by our limited knowledge on the pathophysiology of the disease.”

However, “new imaging modalities like MRI enable us to study the pathophysiology of erosive OA more closely,” she said. “This study also gave us the unique opportunity to investigate whether anti-TNF, which is known to lead to clinical improvement and improvement of inflammatory lesions on MRI in other rheumatic diseases like rheumatoid arthritis, might also be effective in erosive OA.”

The presence of BMLs, but not synovitis, was associated with the presence of an erosive anatomical phase in a joint, and treatment with etanercept appeared to be effective in inhibiting these lesions. That suggests a role for TNF in the pathophysiology of erosive OA.

The inhibitory effect of etanercept on BMLs was more pronounced in IP joints with severe synovitis at baseline, suggesting that inflamed synovial tissue could be a source of TNF production in erosive OA.

The total synovitis score was similar at baseline and 1 year in both study groups. For BMLs, the median total score at baseline was 5.4 (range 2-9) and 7.0 (0-9) at 1 year in the placebo group, versus 4.5 (3-9) and 3.7 (0-8), respectively, in the etanercept group.

The presence of BMLs was associated with being in the erosive and remodeling anatomical phases of erosive hand OA. Synovitis was not associated with those phases.

“We think that TNF-alpha plays a role in the pathophysiology of erosive OA via an effect on the subchondral bone,” Ms. Kroon said. “Because we saw that the beneficial effect of etanercept on BMLs was more pronounced in joints with synovitis at baseline, we think that, in an inflamed synovial hand joint, an interaction takes place between synovium and subchondral bone, which could be influenced by blocking TNF.”

Pfizer and UCB supported the investigator-initiated studies and provided the study drugs. Dr. Kloppenburg has received lecturing, consultancy, and investigator fees or grants from AbbVie, APPROACH, GlaxoSmithKline, Levicept, Pfizer, Servier, and UCB, all paid to her institution. All other authors declared no conflicts of interests.

[email protected]

LONDON – Tumor necrosis factor may play a role in erosive hand osteoarthritis, and treatments such as etanercept that target this cytokine may help prevent progression of the condition, according to the results of two studies presented at the European Congress of Rheumatology.

In one of the studies, immunoscintigraphic detection of radiolabeled certolizumab pegol was used to show that tumor necrosis factor (TNF) was present in swollen finger joints. In another study, researchers looked to see if treatment with etanercept would have any specific effects on the joints of patients with erosive hand osteoarthritis (OA) and performed a separate analysis of the potential effect on synovitis and the effect on bone marrow lesions.

“We previously had the idea that TNF is an important cytokine in the pathogenesis of erosive [hand] osteoarthritis; but there have been no animal studies, and it’s very difficult to take biopsies or fluid aspiration from these small finger joints,” Dr. Ruth Wittoek, a staff rheumatologist at Ghent University Hospital in Belgium and a coauthor of all three studies, explained in a precongress interview. “We needed to look for other possibilities to really identify the presence of TNF in those affected joints.”

Dr. Wittoek and her associates used immunoscintigraphy to take static images of both hands of five patients with erosive OA immediately (less than 15 minutes) after administration of radiolabeled certolizumab pegol (early phase) and 4-6 hours following the injection (late phase).

The patients studied had erosive OA for a median of 8.4 years, and their median age was 55.6 years. All patients underwent clinical examination for presence of tenderness and palpable swelling of the joints and ultrasound 1 day prior to undergoing immunoscintigraphy.

All 18 interphalangeal (IP) finger joints were scored according to the anatomical phase scoring system on x-ray, and 90 IP finger joints were studied in total. The uptake of radiolabeled certolizumab pegol was semiquantitatively described as being absent, weak, or strong.

During the early phase following administration, uptake of the radiolabeled TNF inhibitor was seen in seven (7.8%) joints, although the uptake was described as weak in all cases. The radiolabeled TNF inhibitor was seen in 24 (26.7%) joints during the late phase following administration, with five instances described as strong uptake and the remaining 19 instances being weak uptake. No uptake of the radiolabeled TNF inhibitor was seen in metacarpophalangeal joints.

Uptake of the radiolabeled TNF inhibitor was linked to signs of disease activity, including tender, swollen, and radiographically active joints.

Late uptake was present in 12 (36.4%) of 33 tender joints and in 12 (21.1%) of 57 nontender joints (odds ratio, 2.1; 95% confidence interval, 0.8-5.6; P was nonsignificant).

The relationship was most pronounced with palpable joint swelling: Late uptake was present in 14 (61%) of 23 swollen joints and 10 (14.9%) of 67 nonswollen joints (OR, 8.9; 95% CI, 3.3-26.0; P less than .001).

Late uptake was present in 18 (29%) of 62 sonographically active joints (defined as any presence of effusion or synovial proliferation) but just 6 (21.4%) of 28 noninflamed joints (OR, 1.5; 95% CI, 0.5-4.3; P was nonsignificant).

Uptake of the radiolabeled TNF inhibitor was observed in all anatomical phases of erosive hand OA, Dr. Wittoek noted, but the strongest association was found during the final remodeling (R) phase.

“Soft-tissue swelling strongly correlated with uptake of certolizumab, meaning in these joints a lot of TNF was present,” Dr. Wittoek said. “These data further solidify the rationale for cytokine-directed therapies in erosive OA.”

Although the data provide proof of concept that TNF may be involved in erosive hand OA, the lack of a control tracer was noted as a limitation of the study after the investigator’s presentation. Dr. Wittoek conceded that it would be interesting to examine that in a future study.

So, if TNF is present, what effect does anti-TNF therapy have on the joints in erosive hand OA?

That question was addressed in a multicenter, double-blind, randomized, placebo-controlled trial involving 90 patients who were randomized to receive either 50 mg of subcutaneous etanercept weekly for 24 weeks, then 25 mg weekly for the remainder of 1 year (45 patients), or placebo (45 patients). Participants were a mean age of 60 years, 81% were women, and 96% fulfilled the American College of Rheumatology hand OA criteria.

“Synovial inflammation is often present in erosive hand OA; moreover, synovitis is associated with pain and with structural damage after around 2 and a half years,” the lead study author, Dr. Margreet Kloppenburg, a professor of rheumatology at Leiden University Medical Centre in the Netherlands, said in an interview.

“Therefore, we wanted to know whether blocking of synovial inflammation by a well-known drug such as etanercept would also have a positive effect on outcomes in erosive hand OA,” Dr. Kloppenburg explained.

The primary outcome measure was the level of OA pain assessed on a visual analog scale (VAS) at 24 weeks.

Secondary endpoints included assessment of hand function, quality of life, the number of tender joints, and grip strength after 4, 8, 12, 24, and 36 weeks, and after 1 year. Radiographic progression of IP joints was scored blindly at baseline, 24 weeks, and 1 year following the quantitative Ghent University Scoring System (GUSS). VAS pain was compared between treatment groups at 24 weeks and 1 year in intention-to-treat analyses.

Although etanercept was not superior to placebo on VAS pain at 24 weeks, it was superior to placebo both on pain and structural damage assessed by GUSS in the symptomatic and inflammatory patients who completed the study. The drug was especially effective in joints with signs of inflammation.

Overall, VAS pain in all patients decreased by 24.8 mm (95% CI, –29.2 to –20.5; P less than .001) at 24 weeks. In intention-to-treat analysis, differences in pain between the groups were in favor of etanercept but did not reach statistical significance. The per-protocol analysis of GUSS showed a mean difference in favor of etanercept, indicating more remodeling in the etanercept group.

Additional analyses showed an interaction between soft swelling/erythema and etanercept treatment on GUSS, resulting in a statistically significant (P less than .05) mean difference between the two treatment groups. More patients dropped out on placebo than on etanercept (six vs. three) because of inefficacy, whereas more dropped out on etanercept than on placebo (six vs. one) because of adverse effects.

“Synovial inflammation is an interesting target for treatment in OA patients with an inflammatory hand osteoarthritis phenotype,” Dr. Kloppenburg said.

A separate analysis of the same multicenter study suggests that etanercept is effective in inhibiting bone marrow lesions (BMLs) in patients with erosive hand OA.

The researchers studied 20 participants with symptomatic erosive OA with clinical and ultrasonographic signs of inflammation in at least one IP joint. The patients underwent contrast-enhanced MRI of the eight distal and proximal IP joints of one hand at baseline and 1 year. Images were scored for synovitis and BMLs (0-3 per joint, total score 0-24), blinded for patient characteristics.

Radiographs of the same hand were scored according to the Verbruggen-Veys system. Logistic regression was used to associate the presence of an MRI feature in a joint with being in an erosive versus nonerosive anatomical phase.

“Although erosive hand OA is a condition with a high disease burden, no disease-modifying treatments are available yet,” explained Féline Kroon, a PhD student in the department of rheumatology at Leiden University Medical Center in the Netherlands, in an interview. “Research to find a new form of therapy is partly hindered by our limited knowledge on the pathophysiology of the disease.”

However, “new imaging modalities like MRI enable us to study the pathophysiology of erosive OA more closely,” she said. “This study also gave us the unique opportunity to investigate whether anti-TNF, which is known to lead to clinical improvement and improvement of inflammatory lesions on MRI in other rheumatic diseases like rheumatoid arthritis, might also be effective in erosive OA.”

The presence of BMLs, but not synovitis, was associated with the presence of an erosive anatomical phase in a joint, and treatment with etanercept appeared to be effective in inhibiting these lesions. That suggests a role for TNF in the pathophysiology of erosive OA.

The inhibitory effect of etanercept on BMLs was more pronounced in IP joints with severe synovitis at baseline, suggesting that inflamed synovial tissue could be a source of TNF production in erosive OA.

The total synovitis score was similar at baseline and 1 year in both study groups. For BMLs, the median total score at baseline was 5.4 (range 2-9) and 7.0 (0-9) at 1 year in the placebo group, versus 4.5 (3-9) and 3.7 (0-8), respectively, in the etanercept group.

The presence of BMLs was associated with being in the erosive and remodeling anatomical phases of erosive hand OA. Synovitis was not associated with those phases.

“We think that TNF-alpha plays a role in the pathophysiology of erosive OA via an effect on the subchondral bone,” Ms. Kroon said. “Because we saw that the beneficial effect of etanercept on BMLs was more pronounced in joints with synovitis at baseline, we think that, in an inflamed synovial hand joint, an interaction takes place between synovium and subchondral bone, which could be influenced by blocking TNF.”

Pfizer and UCB supported the investigator-initiated studies and provided the study drugs. Dr. Kloppenburg has received lecturing, consultancy, and investigator fees or grants from AbbVie, APPROACH, GlaxoSmithKline, Levicept, Pfizer, Servier, and UCB, all paid to her institution. All other authors declared no conflicts of interests.

[email protected]

LONDON – Tumor necrosis factor may play a role in erosive hand osteoarthritis, and treatments such as etanercept that target this cytokine may help prevent progression of the condition, according to the results of two studies presented at the European Congress of Rheumatology.

In one of the studies, immunoscintigraphic detection of radiolabeled certolizumab pegol was used to show that tumor necrosis factor (TNF) was present in swollen finger joints. In another study, researchers looked to see if treatment with etanercept would have any specific effects on the joints of patients with erosive hand osteoarthritis (OA) and performed a separate analysis of the potential effect on synovitis and the effect on bone marrow lesions.

“We previously had the idea that TNF is an important cytokine in the pathogenesis of erosive [hand] osteoarthritis; but there have been no animal studies, and it’s very difficult to take biopsies or fluid aspiration from these small finger joints,” Dr. Ruth Wittoek, a staff rheumatologist at Ghent University Hospital in Belgium and a coauthor of all three studies, explained in a precongress interview. “We needed to look for other possibilities to really identify the presence of TNF in those affected joints.”

Dr. Wittoek and her associates used immunoscintigraphy to take static images of both hands of five patients with erosive OA immediately (less than 15 minutes) after administration of radiolabeled certolizumab pegol (early phase) and 4-6 hours following the injection (late phase).

The patients studied had erosive OA for a median of 8.4 years, and their median age was 55.6 years. All patients underwent clinical examination for presence of tenderness and palpable swelling of the joints and ultrasound 1 day prior to undergoing immunoscintigraphy.

All 18 interphalangeal (IP) finger joints were scored according to the anatomical phase scoring system on x-ray, and 90 IP finger joints were studied in total. The uptake of radiolabeled certolizumab pegol was semiquantitatively described as being absent, weak, or strong.

During the early phase following administration, uptake of the radiolabeled TNF inhibitor was seen in seven (7.8%) joints, although the uptake was described as weak in all cases. The radiolabeled TNF inhibitor was seen in 24 (26.7%) joints during the late phase following administration, with five instances described as strong uptake and the remaining 19 instances being weak uptake. No uptake of the radiolabeled TNF inhibitor was seen in metacarpophalangeal joints.

Uptake of the radiolabeled TNF inhibitor was linked to signs of disease activity, including tender, swollen, and radiographically active joints.

Late uptake was present in 12 (36.4%) of 33 tender joints and in 12 (21.1%) of 57 nontender joints (odds ratio, 2.1; 95% confidence interval, 0.8-5.6; P was nonsignificant).

The relationship was most pronounced with palpable joint swelling: Late uptake was present in 14 (61%) of 23 swollen joints and 10 (14.9%) of 67 nonswollen joints (OR, 8.9; 95% CI, 3.3-26.0; P less than .001).

Late uptake was present in 18 (29%) of 62 sonographically active joints (defined as any presence of effusion or synovial proliferation) but just 6 (21.4%) of 28 noninflamed joints (OR, 1.5; 95% CI, 0.5-4.3; P was nonsignificant).

Uptake of the radiolabeled TNF inhibitor was observed in all anatomical phases of erosive hand OA, Dr. Wittoek noted, but the strongest association was found during the final remodeling (R) phase.

“Soft-tissue swelling strongly correlated with uptake of certolizumab, meaning in these joints a lot of TNF was present,” Dr. Wittoek said. “These data further solidify the rationale for cytokine-directed therapies in erosive OA.”

Although the data provide proof of concept that TNF may be involved in erosive hand OA, the lack of a control tracer was noted as a limitation of the study after the investigator’s presentation. Dr. Wittoek conceded that it would be interesting to examine that in a future study.

So, if TNF is present, what effect does anti-TNF therapy have on the joints in erosive hand OA?

That question was addressed in a multicenter, double-blind, randomized, placebo-controlled trial involving 90 patients who were randomized to receive either 50 mg of subcutaneous etanercept weekly for 24 weeks, then 25 mg weekly for the remainder of 1 year (45 patients), or placebo (45 patients). Participants were a mean age of 60 years, 81% were women, and 96% fulfilled the American College of Rheumatology hand OA criteria.

“Synovial inflammation is often present in erosive hand OA; moreover, synovitis is associated with pain and with structural damage after around 2 and a half years,” the lead study author, Dr. Margreet Kloppenburg, a professor of rheumatology at Leiden University Medical Centre in the Netherlands, said in an interview.

“Therefore, we wanted to know whether blocking of synovial inflammation by a well-known drug such as etanercept would also have a positive effect on outcomes in erosive hand OA,” Dr. Kloppenburg explained.

The primary outcome measure was the level of OA pain assessed on a visual analog scale (VAS) at 24 weeks.

Secondary endpoints included assessment of hand function, quality of life, the number of tender joints, and grip strength after 4, 8, 12, 24, and 36 weeks, and after 1 year. Radiographic progression of IP joints was scored blindly at baseline, 24 weeks, and 1 year following the quantitative Ghent University Scoring System (GUSS). VAS pain was compared between treatment groups at 24 weeks and 1 year in intention-to-treat analyses.

Although etanercept was not superior to placebo on VAS pain at 24 weeks, it was superior to placebo both on pain and structural damage assessed by GUSS in the symptomatic and inflammatory patients who completed the study. The drug was especially effective in joints with signs of inflammation.

Overall, VAS pain in all patients decreased by 24.8 mm (95% CI, –29.2 to –20.5; P less than .001) at 24 weeks. In intention-to-treat analysis, differences in pain between the groups were in favor of etanercept but did not reach statistical significance. The per-protocol analysis of GUSS showed a mean difference in favor of etanercept, indicating more remodeling in the etanercept group.

Additional analyses showed an interaction between soft swelling/erythema and etanercept treatment on GUSS, resulting in a statistically significant (P less than .05) mean difference between the two treatment groups. More patients dropped out on placebo than on etanercept (six vs. three) because of inefficacy, whereas more dropped out on etanercept than on placebo (six vs. one) because of adverse effects.

“Synovial inflammation is an interesting target for treatment in OA patients with an inflammatory hand osteoarthritis phenotype,” Dr. Kloppenburg said.

A separate analysis of the same multicenter study suggests that etanercept is effective in inhibiting bone marrow lesions (BMLs) in patients with erosive hand OA.

The researchers studied 20 participants with symptomatic erosive OA with clinical and ultrasonographic signs of inflammation in at least one IP joint. The patients underwent contrast-enhanced MRI of the eight distal and proximal IP joints of one hand at baseline and 1 year. Images were scored for synovitis and BMLs (0-3 per joint, total score 0-24), blinded for patient characteristics.

Radiographs of the same hand were scored according to the Verbruggen-Veys system. Logistic regression was used to associate the presence of an MRI feature in a joint with being in an erosive versus nonerosive anatomical phase.

“Although erosive hand OA is a condition with a high disease burden, no disease-modifying treatments are available yet,” explained Féline Kroon, a PhD student in the department of rheumatology at Leiden University Medical Center in the Netherlands, in an interview. “Research to find a new form of therapy is partly hindered by our limited knowledge on the pathophysiology of the disease.”

However, “new imaging modalities like MRI enable us to study the pathophysiology of erosive OA more closely,” she said. “This study also gave us the unique opportunity to investigate whether anti-TNF, which is known to lead to clinical improvement and improvement of inflammatory lesions on MRI in other rheumatic diseases like rheumatoid arthritis, might also be effective in erosive OA.”

The presence of BMLs, but not synovitis, was associated with the presence of an erosive anatomical phase in a joint, and treatment with etanercept appeared to be effective in inhibiting these lesions. That suggests a role for TNF in the pathophysiology of erosive OA.

The inhibitory effect of etanercept on BMLs was more pronounced in IP joints with severe synovitis at baseline, suggesting that inflamed synovial tissue could be a source of TNF production in erosive OA.

The total synovitis score was similar at baseline and 1 year in both study groups. For BMLs, the median total score at baseline was 5.4 (range 2-9) and 7.0 (0-9) at 1 year in the placebo group, versus 4.5 (3-9) and 3.7 (0-8), respectively, in the etanercept group.

The presence of BMLs was associated with being in the erosive and remodeling anatomical phases of erosive hand OA. Synovitis was not associated with those phases.

“We think that TNF-alpha plays a role in the pathophysiology of erosive OA via an effect on the subchondral bone,” Ms. Kroon said. “Because we saw that the beneficial effect of etanercept on BMLs was more pronounced in joints with synovitis at baseline, we think that, in an inflamed synovial hand joint, an interaction takes place between synovium and subchondral bone, which could be influenced by blocking TNF.”

Pfizer and UCB supported the investigator-initiated studies and provided the study drugs. Dr. Kloppenburg has received lecturing, consultancy, and investigator fees or grants from AbbVie, APPROACH, GlaxoSmithKline, Levicept, Pfizer, Servier, and UCB, all paid to her institution. All other authors declared no conflicts of interests.

[email protected]

LONDON – Long-term treatment with the interleukin 17A inhibitor secukinumab showed suggestive evidence of inhibiting structural progression of spinal disease in 168 patients with ankylosing spondylitis, the first time any evidence for an effect like this has been seen with a biologic drug or any other agent used to treat ankylosing spondylitis.

However, the effect occurred in uncontrolled, 2-year open-label treatment of patients originally enrolled in one of the secukinumab pivotal trials, and the analysis did not include comparison against a historical control group, caveats that demand confirmation of this effect in additional studies, Dr. Jürgen Braun said at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

In a second, unrelated study, the oral Janus kinase inhibitor tofacitinib showed promising efficacy for controlling clinical symptoms in patients with active ankylosing spondylitis (AS) during 12 weeks of treatment in a placebo-controlled, dose-ranging phase II study.

The open-label secukinumab extension study involved patients who had been enrolled in the MEASURE 1 study, one of the pivotal trials that had established secukinumab as safe and effective for improving the clinical status of patients with active AS. The primary endpoint of MEASURE 1 had been the percentage of patients achieving at least a 20% improvement in their Assessment of Spondyloarthritis international Society (ASAS20) response after 16 weeks of treatment (New Engl J Med. 2015 Dec 24;373[26]:2534-48).

Based in part on these data the Food and Drug Administration approved secukinumab (Cosentyx) for the treatment of ankylosing spondylitis in January 2016. The new data reported by Dr. Braun assessed the level of spinal pathology in a subgroup of the MEASURE 1 patients when measured by radiography using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) at baseline and after 104 weeks on secukinumab treatment.

Patients in MEASURE 1 who began on active treatment received 10 mg/kg intravenous secukinumab for 4 weeks, followed by subcutaneous dosages of either 75 mg or 150 mg every 4 weeks for 104 weeks. His analysis also included some patients who entered MEASURE 1 in the placebo group and then switched to open-label, subcutaneous secukinumab treatment after 16 or 24 weeks on placebo.

Analysis of 168 patients who started on intravenous secukinumab and later received any subcutaneous secukinumab treatment out to 104 weeks showed an average increase in mSASSS of 0.30 after 104 weeks when compared against their baseline scores, reported Dr. Braun, professor and medical director of the Ruhr Rheumatology Center of the University of Bochum, Germany.

Among an additional 89 patients who began in the placebo group and then switched to subcutaneous secukinumab, the average change in mSASSS from baseline to 104 weeks was 0.54. By comparison, Dr. Braun noted that AS patients treated with a tumor necrosis factor inhibitor have shown 2-year progression in their mSASSS of about 0.8-0.9, and AS patients not treated with an active biologic drug have shown 2-year mSASSS progression of about 1.0.

A second analysis of the data reported by Dr. Braun showed that among the 168 patients treated for the full 104 weeks with secukinumab about 80% showed no mSASSS progression, but about 20% did have some level of detectable mSASSS progression.

The phase II study of tofacitinib (Xeljanz) randomized 208 patients with active AS to either tofacitinib at daily dosages of 2 mg bid, 5 mg bid, 10 mg bid, or placebo. The study’s primary endpoint was their ASAS20 response after 12 weeks that underwent a Bayesian Emax model analysis to estimate incremental efficacy when compared against placebo.

The primary efficacy analysis showed the greatest EmaxASAS20 response among patients treated with 5 mg bid daily, 63%, which was about 23% above the placebo level, reportedDr. Désirée van der Heijde, professor of rheumatology at the Leiden University Medical Center, The Netherlands. The absolute ASAS20 response rate of the 52 patients randomized to this tofacitinib dosage was about 81%, about 40% higher than the response rate seen in the 51 patients in the placebo arm.

All dosages of tofacitinib tested were well tolerated, with safety data similar to what has previously been shown for tofacitinib, a drug that has Food and Drug Administration approval for treating rheumatoid arthritis.

[email protected]

On Twitter @mitchelzoler

LONDON – Long-term treatment with the interleukin 17A inhibitor secukinumab showed suggestive evidence of inhibiting structural progression of spinal disease in 168 patients with ankylosing spondylitis, the first time any evidence for an effect like this has been seen with a biologic drug or any other agent used to treat ankylosing spondylitis.

However, the effect occurred in uncontrolled, 2-year open-label treatment of patients originally enrolled in one of the secukinumab pivotal trials, and the analysis did not include comparison against a historical control group, caveats that demand confirmation of this effect in additional studies, Dr. Jürgen Braun said at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

In a second, unrelated study, the oral Janus kinase inhibitor tofacitinib showed promising efficacy for controlling clinical symptoms in patients with active ankylosing spondylitis (AS) during 12 weeks of treatment in a placebo-controlled, dose-ranging phase II study.

The open-label secukinumab extension study involved patients who had been enrolled in the MEASURE 1 study, one of the pivotal trials that had established secukinumab as safe and effective for improving the clinical status of patients with active AS. The primary endpoint of MEASURE 1 had been the percentage of patients achieving at least a 20% improvement in their Assessment of Spondyloarthritis international Society (ASAS20) response after 16 weeks of treatment (New Engl J Med. 2015 Dec 24;373[26]:2534-48).

Based in part on these data the Food and Drug Administration approved secukinumab (Cosentyx) for the treatment of ankylosing spondylitis in January 2016. The new data reported by Dr. Braun assessed the level of spinal pathology in a subgroup of the MEASURE 1 patients when measured by radiography using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) at baseline and after 104 weeks on secukinumab treatment.

Patients in MEASURE 1 who began on active treatment received 10 mg/kg intravenous secukinumab for 4 weeks, followed by subcutaneous dosages of either 75 mg or 150 mg every 4 weeks for 104 weeks. His analysis also included some patients who entered MEASURE 1 in the placebo group and then switched to open-label, subcutaneous secukinumab treatment after 16 or 24 weeks on placebo.

Analysis of 168 patients who started on intravenous secukinumab and later received any subcutaneous secukinumab treatment out to 104 weeks showed an average increase in mSASSS of 0.30 after 104 weeks when compared against their baseline scores, reported Dr. Braun, professor and medical director of the Ruhr Rheumatology Center of the University of Bochum, Germany.

Among an additional 89 patients who began in the placebo group and then switched to subcutaneous secukinumab, the average change in mSASSS from baseline to 104 weeks was 0.54. By comparison, Dr. Braun noted that AS patients treated with a tumor necrosis factor inhibitor have shown 2-year progression in their mSASSS of about 0.8-0.9, and AS patients not treated with an active biologic drug have shown 2-year mSASSS progression of about 1.0.

A second analysis of the data reported by Dr. Braun showed that among the 168 patients treated for the full 104 weeks with secukinumab about 80% showed no mSASSS progression, but about 20% did have some level of detectable mSASSS progression.

The phase II study of tofacitinib (Xeljanz) randomized 208 patients with active AS to either tofacitinib at daily dosages of 2 mg bid, 5 mg bid, 10 mg bid, or placebo. The study’s primary endpoint was their ASAS20 response after 12 weeks that underwent a Bayesian Emax model analysis to estimate incremental efficacy when compared against placebo.

The primary efficacy analysis showed the greatest EmaxASAS20 response among patients treated with 5 mg bid daily, 63%, which was about 23% above the placebo level, reportedDr. Désirée van der Heijde, professor of rheumatology at the Leiden University Medical Center, The Netherlands. The absolute ASAS20 response rate of the 52 patients randomized to this tofacitinib dosage was about 81%, about 40% higher than the response rate seen in the 51 patients in the placebo arm.

All dosages of tofacitinib tested were well tolerated, with safety data similar to what has previously been shown for tofacitinib, a drug that has Food and Drug Administration approval for treating rheumatoid arthritis.

[email protected]

On Twitter @mitchelzoler

LONDON – Long-term treatment with the interleukin 17A inhibitor secukinumab showed suggestive evidence of inhibiting structural progression of spinal disease in 168 patients with ankylosing spondylitis, the first time any evidence for an effect like this has been seen with a biologic drug or any other agent used to treat ankylosing spondylitis.

However, the effect occurred in uncontrolled, 2-year open-label treatment of patients originally enrolled in one of the secukinumab pivotal trials, and the analysis did not include comparison against a historical control group, caveats that demand confirmation of this effect in additional studies, Dr. Jürgen Braun said at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

In a second, unrelated study, the oral Janus kinase inhibitor tofacitinib showed promising efficacy for controlling clinical symptoms in patients with active ankylosing spondylitis (AS) during 12 weeks of treatment in a placebo-controlled, dose-ranging phase II study.

The open-label secukinumab extension study involved patients who had been enrolled in the MEASURE 1 study, one of the pivotal trials that had established secukinumab as safe and effective for improving the clinical status of patients with active AS. The primary endpoint of MEASURE 1 had been the percentage of patients achieving at least a 20% improvement in their Assessment of Spondyloarthritis international Society (ASAS20) response after 16 weeks of treatment (New Engl J Med. 2015 Dec 24;373[26]:2534-48).

Based in part on these data the Food and Drug Administration approved secukinumab (Cosentyx) for the treatment of ankylosing spondylitis in January 2016. The new data reported by Dr. Braun assessed the level of spinal pathology in a subgroup of the MEASURE 1 patients when measured by radiography using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) at baseline and after 104 weeks on secukinumab treatment.

Patients in MEASURE 1 who began on active treatment received 10 mg/kg intravenous secukinumab for 4 weeks, followed by subcutaneous dosages of either 75 mg or 150 mg every 4 weeks for 104 weeks. His analysis also included some patients who entered MEASURE 1 in the placebo group and then switched to open-label, subcutaneous secukinumab treatment after 16 or 24 weeks on placebo.

Analysis of 168 patients who started on intravenous secukinumab and later received any subcutaneous secukinumab treatment out to 104 weeks showed an average increase in mSASSS of 0.30 after 104 weeks when compared against their baseline scores, reported Dr. Braun, professor and medical director of the Ruhr Rheumatology Center of the University of Bochum, Germany.

Among an additional 89 patients who began in the placebo group and then switched to subcutaneous secukinumab, the average change in mSASSS from baseline to 104 weeks was 0.54. By comparison, Dr. Braun noted that AS patients treated with a tumor necrosis factor inhibitor have shown 2-year progression in their mSASSS of about 0.8-0.9, and AS patients not treated with an active biologic drug have shown 2-year mSASSS progression of about 1.0.

A second analysis of the data reported by Dr. Braun showed that among the 168 patients treated for the full 104 weeks with secukinumab about 80% showed no mSASSS progression, but about 20% did have some level of detectable mSASSS progression.

The phase II study of tofacitinib (Xeljanz) randomized 208 patients with active AS to either tofacitinib at daily dosages of 2 mg bid, 5 mg bid, 10 mg bid, or placebo. The study’s primary endpoint was their ASAS20 response after 12 weeks that underwent a Bayesian Emax model analysis to estimate incremental efficacy when compared against placebo.

The primary efficacy analysis showed the greatest EmaxASAS20 response among patients treated with 5 mg bid daily, 63%, which was about 23% above the placebo level, reportedDr. Désirée van der Heijde, professor of rheumatology at the Leiden University Medical Center, The Netherlands. The absolute ASAS20 response rate of the 52 patients randomized to this tofacitinib dosage was about 81%, about 40% higher than the response rate seen in the 51 patients in the placebo arm.

All dosages of tofacitinib tested were well tolerated, with safety data similar to what has previously been shown for tofacitinib, a drug that has Food and Drug Administration approval for treating rheumatoid arthritis.

[email protected]

On Twitter @mitchelzoler