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Omega-3 fatty acid found in fish may reduce RA risk
Consistent dietary intake of long-chain n-3 polyunsaturated fatty acids typically found in fish was associated with a reduced risk of rheumatoid arthritis in a prospective cohort study of Swedish women.
The study of 32,232 middle-aged and older Swedish women included 205 who developed rheumatoid arthritis (RA) during a mean follow-up of 7.5 years. Those who reported intake of more than 0.21 g/day of dietary long-chain n-3 polyunsaturated fatty acids (PUFAs), also called omega-3 fatty acids, at the time of an assessment in 1997 had a 35% reduction in the risk of developing RA, compared with women who reported lower intake (adjusted relative risk, 0.65), reported Dr. Daniela Di Giuseppe of the Karolinska Institute, Stockholm, and her colleagues.
"The population prevented fraction, the equivalent of the population attributable risk when analyzing a protective factor, was 0.28. This indicates that 28% of the hypothetical total load of disease could be prevented by exposure to greater than 0.21 g/day of dietary long-chain n-3 PUFAs," the investigators wrote.
Consistent long-term intake of more than 0.21 g/day was associated with even greater risk reduction. Women who reported intake at that level at assessments in both 1987 and 1997 had a 52% reduction in risk, compared with those with lower intake (adjusted RR, 0.48), they said.
Those who reported consistent long-term consumption of at least one serving of fish weekly had a 29% reduction in risk, compared with those who had less than one serving weekly (adjusted RR, 0.71), they noted (Ann. Rheum. Dis. 2013 Aug. 12 [doi: 10.1136/annrheumdis-2013-203338]).
"The inverse association between fish consumption and RA can be attributed mainly to its content of long-chain n-3 PUFAs," they wrote.
Of note, the use of fish oil supplementation was not associated with the development of RA in this study (relative risk, 1.32 for ever vs. never users). However, there were only 17 users, and information about dose and duration of use was lacking.
Study subjects were participants in the population-based Swedish Mammography Cohort. The women, who were aged 54-89 years at follow-up, completed detailed food-frequency questionnaires at the 1987 and 1997 assessments.
The multivariable relative risks for dietary long-chain n-3 PUFAs were adjusted for cigarette smoking, alcohol intake, aspirin use, and energy intake. The multivariable relative risks for long-term fish consumption were also adjusted for quartiles of red meat and dairy food consumption.
The findings have implications for dietary guidelines with respect to fish consumption, the investigators said.
RA is known to be influenced by both genetic and environmental factors, but little is known about important modifiable risk factors other than smoking and alcohol consumption, they said, noting that the evidence regarding a role for dietary long-chain n-3 PUFAs has been limited, and study results have been conflicting.
However, the current study suggests that intake of at least 0.21 g/day is indeed of benefit. That intake is about the equivalent of at least one serving of fatty fish, such as salmon, or four servings of lean fish, such as cod, each week, the investigators explained. They suggested that dietary long-chain n-3 PUFAs may protect against RA through their anti-inflammatory properties, particularly through the synthesis of eicosanoids.
These intake levels are in line with recommendations from the American Dietary Guideline Advisory Committee, which advised eating fish twice weekly.
"In conclusion, the study indicates a potentially important role for dietary long-chain n-3 PUFAs in the etiology of RA, and that adherence to existing dietary guidelines regarding fish consumption may also be beneficial in terms of RA risk," they wrote.
The study was supported by research grants from the Swedish Research Council/Committee for Research Infrastructure for Maintenance of the Swedish Mammography Cohort, and from the Karolinska Institute’s Award for Ph.D. Students. The authors reported having no disclosures.
Consistent dietary intake of long-chain n-3 polyunsaturated fatty acids typically found in fish was associated with a reduced risk of rheumatoid arthritis in a prospective cohort study of Swedish women.
The study of 32,232 middle-aged and older Swedish women included 205 who developed rheumatoid arthritis (RA) during a mean follow-up of 7.5 years. Those who reported intake of more than 0.21 g/day of dietary long-chain n-3 polyunsaturated fatty acids (PUFAs), also called omega-3 fatty acids, at the time of an assessment in 1997 had a 35% reduction in the risk of developing RA, compared with women who reported lower intake (adjusted relative risk, 0.65), reported Dr. Daniela Di Giuseppe of the Karolinska Institute, Stockholm, and her colleagues.
"The population prevented fraction, the equivalent of the population attributable risk when analyzing a protective factor, was 0.28. This indicates that 28% of the hypothetical total load of disease could be prevented by exposure to greater than 0.21 g/day of dietary long-chain n-3 PUFAs," the investigators wrote.
Consistent long-term intake of more than 0.21 g/day was associated with even greater risk reduction. Women who reported intake at that level at assessments in both 1987 and 1997 had a 52% reduction in risk, compared with those with lower intake (adjusted RR, 0.48), they said.
Those who reported consistent long-term consumption of at least one serving of fish weekly had a 29% reduction in risk, compared with those who had less than one serving weekly (adjusted RR, 0.71), they noted (Ann. Rheum. Dis. 2013 Aug. 12 [doi: 10.1136/annrheumdis-2013-203338]).
"The inverse association between fish consumption and RA can be attributed mainly to its content of long-chain n-3 PUFAs," they wrote.
Of note, the use of fish oil supplementation was not associated with the development of RA in this study (relative risk, 1.32 for ever vs. never users). However, there were only 17 users, and information about dose and duration of use was lacking.
Study subjects were participants in the population-based Swedish Mammography Cohort. The women, who were aged 54-89 years at follow-up, completed detailed food-frequency questionnaires at the 1987 and 1997 assessments.
The multivariable relative risks for dietary long-chain n-3 PUFAs were adjusted for cigarette smoking, alcohol intake, aspirin use, and energy intake. The multivariable relative risks for long-term fish consumption were also adjusted for quartiles of red meat and dairy food consumption.
The findings have implications for dietary guidelines with respect to fish consumption, the investigators said.
RA is known to be influenced by both genetic and environmental factors, but little is known about important modifiable risk factors other than smoking and alcohol consumption, they said, noting that the evidence regarding a role for dietary long-chain n-3 PUFAs has been limited, and study results have been conflicting.
However, the current study suggests that intake of at least 0.21 g/day is indeed of benefit. That intake is about the equivalent of at least one serving of fatty fish, such as salmon, or four servings of lean fish, such as cod, each week, the investigators explained. They suggested that dietary long-chain n-3 PUFAs may protect against RA through their anti-inflammatory properties, particularly through the synthesis of eicosanoids.
These intake levels are in line with recommendations from the American Dietary Guideline Advisory Committee, which advised eating fish twice weekly.
"In conclusion, the study indicates a potentially important role for dietary long-chain n-3 PUFAs in the etiology of RA, and that adherence to existing dietary guidelines regarding fish consumption may also be beneficial in terms of RA risk," they wrote.
The study was supported by research grants from the Swedish Research Council/Committee for Research Infrastructure for Maintenance of the Swedish Mammography Cohort, and from the Karolinska Institute’s Award for Ph.D. Students. The authors reported having no disclosures.
Consistent dietary intake of long-chain n-3 polyunsaturated fatty acids typically found in fish was associated with a reduced risk of rheumatoid arthritis in a prospective cohort study of Swedish women.
The study of 32,232 middle-aged and older Swedish women included 205 who developed rheumatoid arthritis (RA) during a mean follow-up of 7.5 years. Those who reported intake of more than 0.21 g/day of dietary long-chain n-3 polyunsaturated fatty acids (PUFAs), also called omega-3 fatty acids, at the time of an assessment in 1997 had a 35% reduction in the risk of developing RA, compared with women who reported lower intake (adjusted relative risk, 0.65), reported Dr. Daniela Di Giuseppe of the Karolinska Institute, Stockholm, and her colleagues.
"The population prevented fraction, the equivalent of the population attributable risk when analyzing a protective factor, was 0.28. This indicates that 28% of the hypothetical total load of disease could be prevented by exposure to greater than 0.21 g/day of dietary long-chain n-3 PUFAs," the investigators wrote.
Consistent long-term intake of more than 0.21 g/day was associated with even greater risk reduction. Women who reported intake at that level at assessments in both 1987 and 1997 had a 52% reduction in risk, compared with those with lower intake (adjusted RR, 0.48), they said.
Those who reported consistent long-term consumption of at least one serving of fish weekly had a 29% reduction in risk, compared with those who had less than one serving weekly (adjusted RR, 0.71), they noted (Ann. Rheum. Dis. 2013 Aug. 12 [doi: 10.1136/annrheumdis-2013-203338]).
"The inverse association between fish consumption and RA can be attributed mainly to its content of long-chain n-3 PUFAs," they wrote.
Of note, the use of fish oil supplementation was not associated with the development of RA in this study (relative risk, 1.32 for ever vs. never users). However, there were only 17 users, and information about dose and duration of use was lacking.
Study subjects were participants in the population-based Swedish Mammography Cohort. The women, who were aged 54-89 years at follow-up, completed detailed food-frequency questionnaires at the 1987 and 1997 assessments.
The multivariable relative risks for dietary long-chain n-3 PUFAs were adjusted for cigarette smoking, alcohol intake, aspirin use, and energy intake. The multivariable relative risks for long-term fish consumption were also adjusted for quartiles of red meat and dairy food consumption.
The findings have implications for dietary guidelines with respect to fish consumption, the investigators said.
RA is known to be influenced by both genetic and environmental factors, but little is known about important modifiable risk factors other than smoking and alcohol consumption, they said, noting that the evidence regarding a role for dietary long-chain n-3 PUFAs has been limited, and study results have been conflicting.
However, the current study suggests that intake of at least 0.21 g/day is indeed of benefit. That intake is about the equivalent of at least one serving of fatty fish, such as salmon, or four servings of lean fish, such as cod, each week, the investigators explained. They suggested that dietary long-chain n-3 PUFAs may protect against RA through their anti-inflammatory properties, particularly through the synthesis of eicosanoids.
These intake levels are in line with recommendations from the American Dietary Guideline Advisory Committee, which advised eating fish twice weekly.
"In conclusion, the study indicates a potentially important role for dietary long-chain n-3 PUFAs in the etiology of RA, and that adherence to existing dietary guidelines regarding fish consumption may also be beneficial in terms of RA risk," they wrote.
The study was supported by research grants from the Swedish Research Council/Committee for Research Infrastructure for Maintenance of the Swedish Mammography Cohort, and from the Karolinska Institute’s Award for Ph.D. Students. The authors reported having no disclosures.
FROM ANNALS OF THE RHEUMATIC DISEASES
Major finding: More than 0.21 g/day intake of dietary long-chain n-3 PUFAs was associated with a 35% reduction in RA risk (adjusted relative risk, 0.65).
Data source: A population-based, prospective cohort study of 32,232 Swedish women.
Disclosures: The study was supported by research grants from the Swedish Research Council/Committee for Research Infrastructure for Maintenance of the Swedish Mammography Cohort, and from the Karolinska Institute’s Award for Ph.D. Students. The authors reported having no disclosures.
Tofacitinib rapidly improves RA signs and symptoms
Response rates for rheumatoid arthritis patients taking either 5 mg or 10 mg twice-daily of the oral Janus kinase inhibitor tofacitinib were at least 20% greater after 6 months than for those who started on placebo and switched to the therapy, according to a new study.
Lead investigator Dr. Joel Kremer and his colleagues concluded that tofacitinib (Xeljanz) – when taken in combination with a nonbiologic disease-modifying antirheumatic drug (DMARD) – rapidly reduced the signs and symptoms of RA and improved physical functioning. But, they added, since the majority of patients in their study were taking methotrexate, extrapolating the results to other nonbiologic DMARDs should be done with caution.
They also noted that this trial supported findings in previous studies that tofacitinib works well with methotrexate. One such study was published in the Lancet and was also funded by Pfizer (Lancet 2013 [doi:10.1016/S0140-6736(12)61424-X]).
In the trial, paid for by Pfizer and conducted at 114 centers in 19 countries, 792 patients were randomly assigned 4:4:1:1 to twice-daily treatment with 5 mg of tofacitinib; 10 mg of tofacitinib; or placebo. The study was published Aug. 19 in the Annals of Internal Medicine.
At 3 months, placebo patients who did not respond were blindly switched to the 5-mg or 10-mg dose. Patients taking tofacitinib who did not respond at 3 months continued on the same dose. After 6 months, all patients still on placebo were switched blindly to either the 5-mg or 10-mg dose.
At 6 months, the response rates – defined as 20% improvement in the tender or painful and swollen joint count at three months (ACR20) – were 21% greater for patients taking 5 mg, and 26% greater for patients taking 10 mg, when compared with patients who had been on placebo for 3 months and then switched to one of the two doses.
There was a significantly greater improvement (P less than .001) at 3 months in the Health Assessment Questionnaire Disability Index (HAQ-DI) for patients in the treatment arms, and more of those patients had a Disease Activity Score for 28 joints (DAS28-4) of less than 2.6 at 6 months than did the placebo groups.
Patients were enrolled if they were aged 18 years or older and had a rheumatoid arthritis diagnosis consistent with the 1987 American College of Rheumatology criteria, and an inadequate response to treatment with one or more nonbiologic or biologic DMARDs. They were also required to continue treatment with one or more nonbiologic DMARDs throughout the study. Those taking methotrexate had to have been receiving it for at least 4 months and at stable dosing over at least 6 weeks before the study start. Low-dose, oral corticosteroid therapy was also allowed.
Exclusion criteria included previous treatment with lymphocyte-depleting therapies within a year of the study start; a depressed hemoglobin, hematocrit, leukocyte, or platelet count; or a history of autoimmune rheumatic disease or most cancers. Patients were also excluded if they had experienced an infection requiring hospitalization or intravenous antibiotics within 6 months of baseline, oral antibiotics within 2 weeks of baseline, or infection with herpes zoster, hepatitis B or C, or HIV.
Only 651 (82%) of the 792 patients enrolled completed the study. The mean age across the four treatment groups was 51-53 years old, and at least three-quarters of the participants were female. Two-thirds to 73% of patients continued to take background DMARDs during the study, and at least a quarter received two or more DMARDs. Methotrexate was the most frequently prescribed DMARD.
At 3 months, half of the placebo patients did not have a response and were then switched to either 5 mg (38 patients) or 10 mg (40 patients) of tofacitinib. In the treatment group at 3 months, 80 (26%) patients taking 5 mg and 58 (18%) patients taking 10 mg had no response. A total of 27% of those taking placebo had a response according to the ACR20 criteria.
The authors reported statistically significant response rates for ACR20 and ACR50 by the second week for both treatment arms. DAS28-4, DAS28-4 less than 2.6, and Functional Assessment of Chronic Illness Therapy-Fatigue response rates also were statistically significant over time for the tofacitinib treatment groups when compared with placebo.
The authors reported a higher adverse event and serious adverse event rate for patients on placebo, but a higher discontinuation rate for those taking tofacitinib.
Over a year, the adverse event rate was 172/100 patient-years for tofacitinib 5 mg, 176 for the 10 mg group, and 342 for the placebo-to-tofacitinib groups. The most common adverse events in the tofacitinib groups were upper respiratory tract infections and nasopharyngitis. The discontinuation rate from adverse events was 5.4/100 patient-years for placebo, 6.2 for the 5-mg group, and 9.7 for the 10-mg group.
The authors reported four treatment-related opportunistic infections: disseminated herpes zoster, cryptococcal pneumonia, and two cases of pulmonary tuberculosis. There were four deaths during the study, but only one, respiratory failure, was deemed to be treatment related.
The trial’s Cardiovascular Safety Endpoint Adjudication Committee determined that three patients had events that were notable: a transient ischemic attack in a patient taking 5 mg, a cerebrovascular accident in a patient taking 5 mg, and heart failure in a patient taking 10 mg who eventually died.
In patients taking tofacitinib, the authors also reported decreases in mean neutrophil counts at 3 months and increases in high- and low-density lipoprotein levels that were sustained at 12 months after baseline.
These results have not impressed the European Medicines Agency. In July, the EMA’s Committee for Medicinal Products for Human Use (CHMP) reaffirmed an opinion issued in April that tofacitinib’s benefits did not outweigh its risks. The CHMP recommended against approval of the drug. Pfizer said in a release that it is evaluating the opinion and "will determine next steps to resubmit" its approval application.
Dr. Kremer is the founder and president of the Consortium of Rheumatology Researchers of America (CORRONA) registry, which receives funding from Pfizer. He received a research grant from Pfizer to conduct the study and has been a consultant to Pfizer for the development of tofacitinib. Several other authors reported receiving grants from Pfizer and performing consultant work to Pfizer in relation to the trial. Other authors are Pfizer employees.
On Twitter @aliciaault
Dr. Kremer and his associates' report is a good study that will reassure rheumatologists that it is possible to use tofacitinib with nonbiologic DMARDs. It also reinforces that the dose of tofacitinib that is approved in North America is too low for many patients. There is a nice dose response for DAS28 remission (placebo, 2.6%; tofacitinib, 5 mg twice daily, 8.5%; tofacitinib 10 mg twice daily, 12.5%) and HAQ-DI (-0.16, -0.44, and -0.53, respectively). This was less the case for the ACR20 responses (30.8%, 52.1%, and 56.6%, respectively), but even here there is some trend toward a dose response.
On the other hand, there are some aspects of this study that could be clearer. The patients themselves had long disease duration and relatively high disease activity, so it is not clear that the results apply to all patients. Furthermore, about 10% of patients were on biologics prior to entering the study, and it is not clear how long those biologics had actually been stopped. (The inclusion criteria were not very clear on this aspect.) The patients were allowed on more than one DMARD, and it would have been good to know the breakdown of responses by the number of concomitant DMARDs. Also, nearly 60% of the patients were on corticosteroids, and there is no discussion of the effect of this drug on response or toxicity. Finally, the breakdown of patients was about 20% on placebo initially, compared with 80% on initial tofacitinib, thus introducing the possibility of an unbalanced early response.
The bottom line is that this article is generally reassuring and allows rheumatologists to use tofacitinib more broadly. It reinforces the need for sufficient data to allow higher doses of drugs to be approved in the United States, but, like many studies, leaves many questions (especially on how to consider combinations and corticosteroids) and does not allow the degree of generalization that would have been ideal.
Daniel E. Furst, M.D., is the Carl M. Pearson Professor of Rheumatology at the at the University of California, Los Angeles. He has been a consultant to Pfizer and has received travel support and meals from the company. He has also been a consultant to or received grant support from other pharmaceutical companies marketing drugs for rheumatoid arthritis, including Abbott, Amgen, and Bristol-Myers Squibb.
Dr. Kremer and his associates' report is a good study that will reassure rheumatologists that it is possible to use tofacitinib with nonbiologic DMARDs. It also reinforces that the dose of tofacitinib that is approved in North America is too low for many patients. There is a nice dose response for DAS28 remission (placebo, 2.6%; tofacitinib, 5 mg twice daily, 8.5%; tofacitinib 10 mg twice daily, 12.5%) and HAQ-DI (-0.16, -0.44, and -0.53, respectively). This was less the case for the ACR20 responses (30.8%, 52.1%, and 56.6%, respectively), but even here there is some trend toward a dose response.
On the other hand, there are some aspects of this study that could be clearer. The patients themselves had long disease duration and relatively high disease activity, so it is not clear that the results apply to all patients. Furthermore, about 10% of patients were on biologics prior to entering the study, and it is not clear how long those biologics had actually been stopped. (The inclusion criteria were not very clear on this aspect.) The patients were allowed on more than one DMARD, and it would have been good to know the breakdown of responses by the number of concomitant DMARDs. Also, nearly 60% of the patients were on corticosteroids, and there is no discussion of the effect of this drug on response or toxicity. Finally, the breakdown of patients was about 20% on placebo initially, compared with 80% on initial tofacitinib, thus introducing the possibility of an unbalanced early response.
The bottom line is that this article is generally reassuring and allows rheumatologists to use tofacitinib more broadly. It reinforces the need for sufficient data to allow higher doses of drugs to be approved in the United States, but, like many studies, leaves many questions (especially on how to consider combinations and corticosteroids) and does not allow the degree of generalization that would have been ideal.
Daniel E. Furst, M.D., is the Carl M. Pearson Professor of Rheumatology at the at the University of California, Los Angeles. He has been a consultant to Pfizer and has received travel support and meals from the company. He has also been a consultant to or received grant support from other pharmaceutical companies marketing drugs for rheumatoid arthritis, including Abbott, Amgen, and Bristol-Myers Squibb.
Dr. Kremer and his associates' report is a good study that will reassure rheumatologists that it is possible to use tofacitinib with nonbiologic DMARDs. It also reinforces that the dose of tofacitinib that is approved in North America is too low for many patients. There is a nice dose response for DAS28 remission (placebo, 2.6%; tofacitinib, 5 mg twice daily, 8.5%; tofacitinib 10 mg twice daily, 12.5%) and HAQ-DI (-0.16, -0.44, and -0.53, respectively). This was less the case for the ACR20 responses (30.8%, 52.1%, and 56.6%, respectively), but even here there is some trend toward a dose response.
On the other hand, there are some aspects of this study that could be clearer. The patients themselves had long disease duration and relatively high disease activity, so it is not clear that the results apply to all patients. Furthermore, about 10% of patients were on biologics prior to entering the study, and it is not clear how long those biologics had actually been stopped. (The inclusion criteria were not very clear on this aspect.) The patients were allowed on more than one DMARD, and it would have been good to know the breakdown of responses by the number of concomitant DMARDs. Also, nearly 60% of the patients were on corticosteroids, and there is no discussion of the effect of this drug on response or toxicity. Finally, the breakdown of patients was about 20% on placebo initially, compared with 80% on initial tofacitinib, thus introducing the possibility of an unbalanced early response.
The bottom line is that this article is generally reassuring and allows rheumatologists to use tofacitinib more broadly. It reinforces the need for sufficient data to allow higher doses of drugs to be approved in the United States, but, like many studies, leaves many questions (especially on how to consider combinations and corticosteroids) and does not allow the degree of generalization that would have been ideal.
Daniel E. Furst, M.D., is the Carl M. Pearson Professor of Rheumatology at the at the University of California, Los Angeles. He has been a consultant to Pfizer and has received travel support and meals from the company. He has also been a consultant to or received grant support from other pharmaceutical companies marketing drugs for rheumatoid arthritis, including Abbott, Amgen, and Bristol-Myers Squibb.
Response rates for rheumatoid arthritis patients taking either 5 mg or 10 mg twice-daily of the oral Janus kinase inhibitor tofacitinib were at least 20% greater after 6 months than for those who started on placebo and switched to the therapy, according to a new study.
Lead investigator Dr. Joel Kremer and his colleagues concluded that tofacitinib (Xeljanz) – when taken in combination with a nonbiologic disease-modifying antirheumatic drug (DMARD) – rapidly reduced the signs and symptoms of RA and improved physical functioning. But, they added, since the majority of patients in their study were taking methotrexate, extrapolating the results to other nonbiologic DMARDs should be done with caution.
They also noted that this trial supported findings in previous studies that tofacitinib works well with methotrexate. One such study was published in the Lancet and was also funded by Pfizer (Lancet 2013 [doi:10.1016/S0140-6736(12)61424-X]).
In the trial, paid for by Pfizer and conducted at 114 centers in 19 countries, 792 patients were randomly assigned 4:4:1:1 to twice-daily treatment with 5 mg of tofacitinib; 10 mg of tofacitinib; or placebo. The study was published Aug. 19 in the Annals of Internal Medicine.
At 3 months, placebo patients who did not respond were blindly switched to the 5-mg or 10-mg dose. Patients taking tofacitinib who did not respond at 3 months continued on the same dose. After 6 months, all patients still on placebo were switched blindly to either the 5-mg or 10-mg dose.
At 6 months, the response rates – defined as 20% improvement in the tender or painful and swollen joint count at three months (ACR20) – were 21% greater for patients taking 5 mg, and 26% greater for patients taking 10 mg, when compared with patients who had been on placebo for 3 months and then switched to one of the two doses.
There was a significantly greater improvement (P less than .001) at 3 months in the Health Assessment Questionnaire Disability Index (HAQ-DI) for patients in the treatment arms, and more of those patients had a Disease Activity Score for 28 joints (DAS28-4) of less than 2.6 at 6 months than did the placebo groups.
Patients were enrolled if they were aged 18 years or older and had a rheumatoid arthritis diagnosis consistent with the 1987 American College of Rheumatology criteria, and an inadequate response to treatment with one or more nonbiologic or biologic DMARDs. They were also required to continue treatment with one or more nonbiologic DMARDs throughout the study. Those taking methotrexate had to have been receiving it for at least 4 months and at stable dosing over at least 6 weeks before the study start. Low-dose, oral corticosteroid therapy was also allowed.
Exclusion criteria included previous treatment with lymphocyte-depleting therapies within a year of the study start; a depressed hemoglobin, hematocrit, leukocyte, or platelet count; or a history of autoimmune rheumatic disease or most cancers. Patients were also excluded if they had experienced an infection requiring hospitalization or intravenous antibiotics within 6 months of baseline, oral antibiotics within 2 weeks of baseline, or infection with herpes zoster, hepatitis B or C, or HIV.
Only 651 (82%) of the 792 patients enrolled completed the study. The mean age across the four treatment groups was 51-53 years old, and at least three-quarters of the participants were female. Two-thirds to 73% of patients continued to take background DMARDs during the study, and at least a quarter received two or more DMARDs. Methotrexate was the most frequently prescribed DMARD.
At 3 months, half of the placebo patients did not have a response and were then switched to either 5 mg (38 patients) or 10 mg (40 patients) of tofacitinib. In the treatment group at 3 months, 80 (26%) patients taking 5 mg and 58 (18%) patients taking 10 mg had no response. A total of 27% of those taking placebo had a response according to the ACR20 criteria.
The authors reported statistically significant response rates for ACR20 and ACR50 by the second week for both treatment arms. DAS28-4, DAS28-4 less than 2.6, and Functional Assessment of Chronic Illness Therapy-Fatigue response rates also were statistically significant over time for the tofacitinib treatment groups when compared with placebo.
The authors reported a higher adverse event and serious adverse event rate for patients on placebo, but a higher discontinuation rate for those taking tofacitinib.
Over a year, the adverse event rate was 172/100 patient-years for tofacitinib 5 mg, 176 for the 10 mg group, and 342 for the placebo-to-tofacitinib groups. The most common adverse events in the tofacitinib groups were upper respiratory tract infections and nasopharyngitis. The discontinuation rate from adverse events was 5.4/100 patient-years for placebo, 6.2 for the 5-mg group, and 9.7 for the 10-mg group.
The authors reported four treatment-related opportunistic infections: disseminated herpes zoster, cryptococcal pneumonia, and two cases of pulmonary tuberculosis. There were four deaths during the study, but only one, respiratory failure, was deemed to be treatment related.
The trial’s Cardiovascular Safety Endpoint Adjudication Committee determined that three patients had events that were notable: a transient ischemic attack in a patient taking 5 mg, a cerebrovascular accident in a patient taking 5 mg, and heart failure in a patient taking 10 mg who eventually died.
In patients taking tofacitinib, the authors also reported decreases in mean neutrophil counts at 3 months and increases in high- and low-density lipoprotein levels that were sustained at 12 months after baseline.
These results have not impressed the European Medicines Agency. In July, the EMA’s Committee for Medicinal Products for Human Use (CHMP) reaffirmed an opinion issued in April that tofacitinib’s benefits did not outweigh its risks. The CHMP recommended against approval of the drug. Pfizer said in a release that it is evaluating the opinion and "will determine next steps to resubmit" its approval application.
Dr. Kremer is the founder and president of the Consortium of Rheumatology Researchers of America (CORRONA) registry, which receives funding from Pfizer. He received a research grant from Pfizer to conduct the study and has been a consultant to Pfizer for the development of tofacitinib. Several other authors reported receiving grants from Pfizer and performing consultant work to Pfizer in relation to the trial. Other authors are Pfizer employees.
On Twitter @aliciaault
Response rates for rheumatoid arthritis patients taking either 5 mg or 10 mg twice-daily of the oral Janus kinase inhibitor tofacitinib were at least 20% greater after 6 months than for those who started on placebo and switched to the therapy, according to a new study.
Lead investigator Dr. Joel Kremer and his colleagues concluded that tofacitinib (Xeljanz) – when taken in combination with a nonbiologic disease-modifying antirheumatic drug (DMARD) – rapidly reduced the signs and symptoms of RA and improved physical functioning. But, they added, since the majority of patients in their study were taking methotrexate, extrapolating the results to other nonbiologic DMARDs should be done with caution.
They also noted that this trial supported findings in previous studies that tofacitinib works well with methotrexate. One such study was published in the Lancet and was also funded by Pfizer (Lancet 2013 [doi:10.1016/S0140-6736(12)61424-X]).
In the trial, paid for by Pfizer and conducted at 114 centers in 19 countries, 792 patients were randomly assigned 4:4:1:1 to twice-daily treatment with 5 mg of tofacitinib; 10 mg of tofacitinib; or placebo. The study was published Aug. 19 in the Annals of Internal Medicine.
At 3 months, placebo patients who did not respond were blindly switched to the 5-mg or 10-mg dose. Patients taking tofacitinib who did not respond at 3 months continued on the same dose. After 6 months, all patients still on placebo were switched blindly to either the 5-mg or 10-mg dose.
At 6 months, the response rates – defined as 20% improvement in the tender or painful and swollen joint count at three months (ACR20) – were 21% greater for patients taking 5 mg, and 26% greater for patients taking 10 mg, when compared with patients who had been on placebo for 3 months and then switched to one of the two doses.
There was a significantly greater improvement (P less than .001) at 3 months in the Health Assessment Questionnaire Disability Index (HAQ-DI) for patients in the treatment arms, and more of those patients had a Disease Activity Score for 28 joints (DAS28-4) of less than 2.6 at 6 months than did the placebo groups.
Patients were enrolled if they were aged 18 years or older and had a rheumatoid arthritis diagnosis consistent with the 1987 American College of Rheumatology criteria, and an inadequate response to treatment with one or more nonbiologic or biologic DMARDs. They were also required to continue treatment with one or more nonbiologic DMARDs throughout the study. Those taking methotrexate had to have been receiving it for at least 4 months and at stable dosing over at least 6 weeks before the study start. Low-dose, oral corticosteroid therapy was also allowed.
Exclusion criteria included previous treatment with lymphocyte-depleting therapies within a year of the study start; a depressed hemoglobin, hematocrit, leukocyte, or platelet count; or a history of autoimmune rheumatic disease or most cancers. Patients were also excluded if they had experienced an infection requiring hospitalization or intravenous antibiotics within 6 months of baseline, oral antibiotics within 2 weeks of baseline, or infection with herpes zoster, hepatitis B or C, or HIV.
Only 651 (82%) of the 792 patients enrolled completed the study. The mean age across the four treatment groups was 51-53 years old, and at least three-quarters of the participants were female. Two-thirds to 73% of patients continued to take background DMARDs during the study, and at least a quarter received two or more DMARDs. Methotrexate was the most frequently prescribed DMARD.
At 3 months, half of the placebo patients did not have a response and were then switched to either 5 mg (38 patients) or 10 mg (40 patients) of tofacitinib. In the treatment group at 3 months, 80 (26%) patients taking 5 mg and 58 (18%) patients taking 10 mg had no response. A total of 27% of those taking placebo had a response according to the ACR20 criteria.
The authors reported statistically significant response rates for ACR20 and ACR50 by the second week for both treatment arms. DAS28-4, DAS28-4 less than 2.6, and Functional Assessment of Chronic Illness Therapy-Fatigue response rates also were statistically significant over time for the tofacitinib treatment groups when compared with placebo.
The authors reported a higher adverse event and serious adverse event rate for patients on placebo, but a higher discontinuation rate for those taking tofacitinib.
Over a year, the adverse event rate was 172/100 patient-years for tofacitinib 5 mg, 176 for the 10 mg group, and 342 for the placebo-to-tofacitinib groups. The most common adverse events in the tofacitinib groups were upper respiratory tract infections and nasopharyngitis. The discontinuation rate from adverse events was 5.4/100 patient-years for placebo, 6.2 for the 5-mg group, and 9.7 for the 10-mg group.
The authors reported four treatment-related opportunistic infections: disseminated herpes zoster, cryptococcal pneumonia, and two cases of pulmonary tuberculosis. There were four deaths during the study, but only one, respiratory failure, was deemed to be treatment related.
The trial’s Cardiovascular Safety Endpoint Adjudication Committee determined that three patients had events that were notable: a transient ischemic attack in a patient taking 5 mg, a cerebrovascular accident in a patient taking 5 mg, and heart failure in a patient taking 10 mg who eventually died.
In patients taking tofacitinib, the authors also reported decreases in mean neutrophil counts at 3 months and increases in high- and low-density lipoprotein levels that were sustained at 12 months after baseline.
These results have not impressed the European Medicines Agency. In July, the EMA’s Committee for Medicinal Products for Human Use (CHMP) reaffirmed an opinion issued in April that tofacitinib’s benefits did not outweigh its risks. The CHMP recommended against approval of the drug. Pfizer said in a release that it is evaluating the opinion and "will determine next steps to resubmit" its approval application.
Dr. Kremer is the founder and president of the Consortium of Rheumatology Researchers of America (CORRONA) registry, which receives funding from Pfizer. He received a research grant from Pfizer to conduct the study and has been a consultant to Pfizer for the development of tofacitinib. Several other authors reported receiving grants from Pfizer and performing consultant work to Pfizer in relation to the trial. Other authors are Pfizer employees.
On Twitter @aliciaault
FROM ANNALS OF INTERNAL MEDICINE
Major finding: ACR20 response rates were 21% greater in the 5 mg twice-daily tofacitinib arm and 26% greater in the 10 mg twice-daily arm, when compared with a combined placebo arm.
Data source: A 1-year, double-blind, 792-patient study, conducted in 114 centers in 19 countries.
Disclosures: The study was funded by Pfizer. Dr. Kremer is the founder and president of the Consortium of Rheumatology Researchers of North America. (CORRONA) registry, which receives funding from Pfizer. He received a research grant from Pfizer to conduct the study and has been a consultant to Pfizer for the development of tofacitinib. Several other authors reported receiving grants from Pfizer and performing consultant work to Pfizer in relation to the trial. Other authors are Pfizer employees.
Combo of smoking while overweight boosts RA incidence
MADRID – Researchers have begun testing whether immunologic modification can forestall rheumatoid arthritis in people at high risk for the disease and also have identified smoking and overweight as two modifiable risk factors strongly linked to disease onset.
In a group of 55 people without rheumatoid arthritis (RA) who were enrolled because of a family history of RA or a positive RA blood marker, those with an elevated body mass index (BMI) who also smoked had a greater than seven-fold increased rate of incident RA, compared with lower-BMI people and nonsmokers, Dr. Danielle M. Gerlag said at the annual European Congress of Rheumatology.
The finding raises the possibility that weight loss and smoking cessation may be effective tools for preventing RA, said Dr. Gerlag, a rheumatologist at the Academic Medical Center in Amsterdam.
The finding came from 55 people she and her associates recruited because they were either first-degree relatives of RA patients or because they tested positive for either IgM anti-rheumatoid factor or anti-ctirullinated protein antibody or both. Their average age was about 45 years, and two-thirds were women. During a median follow-up of 27 months, 15 people (27%) developed RA. Two baseline characteristics stood out as strongly associated with RA incidence: history of smoking and a BMI of 25 kg/m2 or greater (Ann. Rheum. Dis. 2012;doi:10.1136/annrheumdis-2012-202254).
Patients who had both a history of smoking and an elevated BMI had a statistically significant, 7.5-fold increased rate of RA during follow-up, compared with all the others in the study group, including those who had smoked but were not overweight and those who were overweight but had never smoked.
Dr. Gerlag and her associates also have collected evidence for several specific changes in T and B cell profiles that link with subsequent development of early RA, which led to the hypothesis that a treatment aimed at dampening immune-cell activation might contain RA development. To explore this possibility, they have treated 75 people at high risk for developing RA with a single 1-g dose of rituximab (Rituxan). So far, during a median follow-up of 19 months, 16 patients (21%) have developed RA, she said.
Dr. Gerlag said that she had no disclosures.
On Twitter @mitchelzoler
MADRID – Researchers have begun testing whether immunologic modification can forestall rheumatoid arthritis in people at high risk for the disease and also have identified smoking and overweight as two modifiable risk factors strongly linked to disease onset.
In a group of 55 people without rheumatoid arthritis (RA) who were enrolled because of a family history of RA or a positive RA blood marker, those with an elevated body mass index (BMI) who also smoked had a greater than seven-fold increased rate of incident RA, compared with lower-BMI people and nonsmokers, Dr. Danielle M. Gerlag said at the annual European Congress of Rheumatology.
The finding raises the possibility that weight loss and smoking cessation may be effective tools for preventing RA, said Dr. Gerlag, a rheumatologist at the Academic Medical Center in Amsterdam.
The finding came from 55 people she and her associates recruited because they were either first-degree relatives of RA patients or because they tested positive for either IgM anti-rheumatoid factor or anti-ctirullinated protein antibody or both. Their average age was about 45 years, and two-thirds were women. During a median follow-up of 27 months, 15 people (27%) developed RA. Two baseline characteristics stood out as strongly associated with RA incidence: history of smoking and a BMI of 25 kg/m2 or greater (Ann. Rheum. Dis. 2012;doi:10.1136/annrheumdis-2012-202254).
Patients who had both a history of smoking and an elevated BMI had a statistically significant, 7.5-fold increased rate of RA during follow-up, compared with all the others in the study group, including those who had smoked but were not overweight and those who were overweight but had never smoked.
Dr. Gerlag and her associates also have collected evidence for several specific changes in T and B cell profiles that link with subsequent development of early RA, which led to the hypothesis that a treatment aimed at dampening immune-cell activation might contain RA development. To explore this possibility, they have treated 75 people at high risk for developing RA with a single 1-g dose of rituximab (Rituxan). So far, during a median follow-up of 19 months, 16 patients (21%) have developed RA, she said.
Dr. Gerlag said that she had no disclosures.
On Twitter @mitchelzoler
MADRID – Researchers have begun testing whether immunologic modification can forestall rheumatoid arthritis in people at high risk for the disease and also have identified smoking and overweight as two modifiable risk factors strongly linked to disease onset.
In a group of 55 people without rheumatoid arthritis (RA) who were enrolled because of a family history of RA or a positive RA blood marker, those with an elevated body mass index (BMI) who also smoked had a greater than seven-fold increased rate of incident RA, compared with lower-BMI people and nonsmokers, Dr. Danielle M. Gerlag said at the annual European Congress of Rheumatology.
The finding raises the possibility that weight loss and smoking cessation may be effective tools for preventing RA, said Dr. Gerlag, a rheumatologist at the Academic Medical Center in Amsterdam.
The finding came from 55 people she and her associates recruited because they were either first-degree relatives of RA patients or because they tested positive for either IgM anti-rheumatoid factor or anti-ctirullinated protein antibody or both. Their average age was about 45 years, and two-thirds were women. During a median follow-up of 27 months, 15 people (27%) developed RA. Two baseline characteristics stood out as strongly associated with RA incidence: history of smoking and a BMI of 25 kg/m2 or greater (Ann. Rheum. Dis. 2012;doi:10.1136/annrheumdis-2012-202254).
Patients who had both a history of smoking and an elevated BMI had a statistically significant, 7.5-fold increased rate of RA during follow-up, compared with all the others in the study group, including those who had smoked but were not overweight and those who were overweight but had never smoked.
Dr. Gerlag and her associates also have collected evidence for several specific changes in T and B cell profiles that link with subsequent development of early RA, which led to the hypothesis that a treatment aimed at dampening immune-cell activation might contain RA development. To explore this possibility, they have treated 75 people at high risk for developing RA with a single 1-g dose of rituximab (Rituxan). So far, during a median follow-up of 19 months, 16 patients (21%) have developed RA, she said.
Dr. Gerlag said that she had no disclosures.
On Twitter @mitchelzoler
AT THE EULAR CONGRESS 2013
Major finding: Patients who smoked and a BMI of at least 25 kg/m2 were 7.5-fold more likely to develop rheumatoid arthritis.
Data source: 27-month follow-up of 55 people selected for their high risk for developing rheumatoid arthritis.
Disclosures: Dr. Gerlag said that she had no disclosures.
Infliximab, IV steroid combos with methotrexate appear comparable in early RA
Methotrexate plus infliximab was not superior to methotrexate plus intravenous corticosteroid for inducing remission in treatment-naïve patients in the Infliximab as Induction Therapy in Early Rheumatoid Arthritis (IDEA) Trial.
Participants in the 18-month, phase IV, randomized, controlled, superiority trial were treated using a rapid remission strategy followed by a treat-to-target approach. At week 50 after the start of treatment, the mean change in modified total Sharp-van der Heijde score (mTSS) was 1.20 in 55 patients in the infliximab group, compared with 2.81 in 57 patients in the intravenous corticosteroid group, Dr. Jackie L. Nam of the University of Leeds (England) and her colleagues reported (Ann. Rheum. Dis. 2013 Aug. 2 [doi:10.1136/annrheumdis-2013-203440]).
An mTSS score of less than 2.0, indicating radiographic nonprogression, was achieved by week 78 in 80.6% of patients who received infliximab and in 71% of those who received steroid (odds ratio, 1.77), and an mTSS of less than 0.5 was achieved by week 78 in 61.9% and 46.7% of patients in the groups, respectively.
The clinical and radiographic findings of this study "support the call to treat to target. They confirm benefit of methotrexate and biologic combination therapies in early DMARD [disease-modifying antirheumatic drugs]–naive RA with the potential for drug de-escalation. Additionally, they demonstrate the benefit of combination therapy with methotrexate and steroid given here initially as a single intravenous dose," Dr. Nam and her associates wrote. However, longer-term outcomes could refine the conclusions drawn thus far from the study, and some effects of the treatments remain to be determined, particularly on bone and cardiovascular risk.
An exploratory analysis suggested that more patients in the infliximab group had early remission, which was defined as a Disease Activity Score 44 (DAS44) of less than 1.6 for 6 months. Although early remission occurred in 18.3% of infliximab-treated patients and 7.1% of steroid-treated patients (OR, 5.02), the proportion of patients achieving DAS44 remission did not differ significantly between the groups at weeks 26, 50, or 78. At week 78, for example, 47.7% and 50% in the infliximab and steroid groups, respectively, achieved DAS44 remission (OR, 1.12), the investigators said.
No substantive differences in adverse events were seen between the two groups: 98.2% of patients in the infliximab group and 94.7% in the steroid group reported adverse events. The most common were noninfectious gastrointestinal events and pulmonary/upper respiratory infections. A total of 20 serious AEs occurred in 13 patients in the infliximab group and 9 occurred in 9 patients in the steroid group, and two serious infections occurred in each group, they noted.
Patients in the multicenter trial were adults aged 18-80 years with a DAS44 of 2.4 or greater and symptom duration that ranged from 3 to 12 months. They were recruited from five sites in West Yorkshire, England, from September 2006 to July 2009, and were blinded to their treatment assignment until week 26. Patients in both groups received 10 mg methotrexate weekly, increasing to 20 mg or the maximum tolerated dose by week 6, along with 5 mg folic acid daily except on the methotrexate administration day.
Additionally, the infliximab group received infusions from 250-mL bags over a 2-hour period, receiving 3 mg/kg to a maximum dose of 1,000 mg at weeks 0, 2, 6, 14, and 22. The steroid group received 250 mg intravenous methylprednisolone at week 0, and placebo infusions at weeks 2, 6, 14, and 22.
"Disease activity was measured at weeks 0, 6, 14, 22, 26, 38, 50, 68, and 78. From week 26, during an open label observation period, patients continued therapy according to a pragmatic predetermined study escalation protocol with dose adjustment or DMARD change in the infliximab group, and DMARD escalation in the intravenous steroid group if DAS44 was greater than 2.4," the investigators wrote.
Infliximab was discontinued for sustained remission, defined as DAS44 less than 1.6 for 6 months.
This study was supported by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme. Dr. Nam reported receiving speakers bureau fees from UCB. Several other study authors reported receiving grant funding, consultancy fees, and/or honoraria, and also serving on speakers bureaus or advisory boards for numerous pharmaceutical companies, including AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Roche-Chugai, Sanofi-Aventis, Schering-Plough, UCB, and Vertex.
Methotrexate plus infliximab was not superior to methotrexate plus intravenous corticosteroid for inducing remission in treatment-naïve patients in the Infliximab as Induction Therapy in Early Rheumatoid Arthritis (IDEA) Trial.
Participants in the 18-month, phase IV, randomized, controlled, superiority trial were treated using a rapid remission strategy followed by a treat-to-target approach. At week 50 after the start of treatment, the mean change in modified total Sharp-van der Heijde score (mTSS) was 1.20 in 55 patients in the infliximab group, compared with 2.81 in 57 patients in the intravenous corticosteroid group, Dr. Jackie L. Nam of the University of Leeds (England) and her colleagues reported (Ann. Rheum. Dis. 2013 Aug. 2 [doi:10.1136/annrheumdis-2013-203440]).
An mTSS score of less than 2.0, indicating radiographic nonprogression, was achieved by week 78 in 80.6% of patients who received infliximab and in 71% of those who received steroid (odds ratio, 1.77), and an mTSS of less than 0.5 was achieved by week 78 in 61.9% and 46.7% of patients in the groups, respectively.
The clinical and radiographic findings of this study "support the call to treat to target. They confirm benefit of methotrexate and biologic combination therapies in early DMARD [disease-modifying antirheumatic drugs]–naive RA with the potential for drug de-escalation. Additionally, they demonstrate the benefit of combination therapy with methotrexate and steroid given here initially as a single intravenous dose," Dr. Nam and her associates wrote. However, longer-term outcomes could refine the conclusions drawn thus far from the study, and some effects of the treatments remain to be determined, particularly on bone and cardiovascular risk.
An exploratory analysis suggested that more patients in the infliximab group had early remission, which was defined as a Disease Activity Score 44 (DAS44) of less than 1.6 for 6 months. Although early remission occurred in 18.3% of infliximab-treated patients and 7.1% of steroid-treated patients (OR, 5.02), the proportion of patients achieving DAS44 remission did not differ significantly between the groups at weeks 26, 50, or 78. At week 78, for example, 47.7% and 50% in the infliximab and steroid groups, respectively, achieved DAS44 remission (OR, 1.12), the investigators said.
No substantive differences in adverse events were seen between the two groups: 98.2% of patients in the infliximab group and 94.7% in the steroid group reported adverse events. The most common were noninfectious gastrointestinal events and pulmonary/upper respiratory infections. A total of 20 serious AEs occurred in 13 patients in the infliximab group and 9 occurred in 9 patients in the steroid group, and two serious infections occurred in each group, they noted.
Patients in the multicenter trial were adults aged 18-80 years with a DAS44 of 2.4 or greater and symptom duration that ranged from 3 to 12 months. They were recruited from five sites in West Yorkshire, England, from September 2006 to July 2009, and were blinded to their treatment assignment until week 26. Patients in both groups received 10 mg methotrexate weekly, increasing to 20 mg or the maximum tolerated dose by week 6, along with 5 mg folic acid daily except on the methotrexate administration day.
Additionally, the infliximab group received infusions from 250-mL bags over a 2-hour period, receiving 3 mg/kg to a maximum dose of 1,000 mg at weeks 0, 2, 6, 14, and 22. The steroid group received 250 mg intravenous methylprednisolone at week 0, and placebo infusions at weeks 2, 6, 14, and 22.
"Disease activity was measured at weeks 0, 6, 14, 22, 26, 38, 50, 68, and 78. From week 26, during an open label observation period, patients continued therapy according to a pragmatic predetermined study escalation protocol with dose adjustment or DMARD change in the infliximab group, and DMARD escalation in the intravenous steroid group if DAS44 was greater than 2.4," the investigators wrote.
Infliximab was discontinued for sustained remission, defined as DAS44 less than 1.6 for 6 months.
This study was supported by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme. Dr. Nam reported receiving speakers bureau fees from UCB. Several other study authors reported receiving grant funding, consultancy fees, and/or honoraria, and also serving on speakers bureaus or advisory boards for numerous pharmaceutical companies, including AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Roche-Chugai, Sanofi-Aventis, Schering-Plough, UCB, and Vertex.
Methotrexate plus infliximab was not superior to methotrexate plus intravenous corticosteroid for inducing remission in treatment-naïve patients in the Infliximab as Induction Therapy in Early Rheumatoid Arthritis (IDEA) Trial.
Participants in the 18-month, phase IV, randomized, controlled, superiority trial were treated using a rapid remission strategy followed by a treat-to-target approach. At week 50 after the start of treatment, the mean change in modified total Sharp-van der Heijde score (mTSS) was 1.20 in 55 patients in the infliximab group, compared with 2.81 in 57 patients in the intravenous corticosteroid group, Dr. Jackie L. Nam of the University of Leeds (England) and her colleagues reported (Ann. Rheum. Dis. 2013 Aug. 2 [doi:10.1136/annrheumdis-2013-203440]).
An mTSS score of less than 2.0, indicating radiographic nonprogression, was achieved by week 78 in 80.6% of patients who received infliximab and in 71% of those who received steroid (odds ratio, 1.77), and an mTSS of less than 0.5 was achieved by week 78 in 61.9% and 46.7% of patients in the groups, respectively.
The clinical and radiographic findings of this study "support the call to treat to target. They confirm benefit of methotrexate and biologic combination therapies in early DMARD [disease-modifying antirheumatic drugs]–naive RA with the potential for drug de-escalation. Additionally, they demonstrate the benefit of combination therapy with methotrexate and steroid given here initially as a single intravenous dose," Dr. Nam and her associates wrote. However, longer-term outcomes could refine the conclusions drawn thus far from the study, and some effects of the treatments remain to be determined, particularly on bone and cardiovascular risk.
An exploratory analysis suggested that more patients in the infliximab group had early remission, which was defined as a Disease Activity Score 44 (DAS44) of less than 1.6 for 6 months. Although early remission occurred in 18.3% of infliximab-treated patients and 7.1% of steroid-treated patients (OR, 5.02), the proportion of patients achieving DAS44 remission did not differ significantly between the groups at weeks 26, 50, or 78. At week 78, for example, 47.7% and 50% in the infliximab and steroid groups, respectively, achieved DAS44 remission (OR, 1.12), the investigators said.
No substantive differences in adverse events were seen between the two groups: 98.2% of patients in the infliximab group and 94.7% in the steroid group reported adverse events. The most common were noninfectious gastrointestinal events and pulmonary/upper respiratory infections. A total of 20 serious AEs occurred in 13 patients in the infliximab group and 9 occurred in 9 patients in the steroid group, and two serious infections occurred in each group, they noted.
Patients in the multicenter trial were adults aged 18-80 years with a DAS44 of 2.4 or greater and symptom duration that ranged from 3 to 12 months. They were recruited from five sites in West Yorkshire, England, from September 2006 to July 2009, and were blinded to their treatment assignment until week 26. Patients in both groups received 10 mg methotrexate weekly, increasing to 20 mg or the maximum tolerated dose by week 6, along with 5 mg folic acid daily except on the methotrexate administration day.
Additionally, the infliximab group received infusions from 250-mL bags over a 2-hour period, receiving 3 mg/kg to a maximum dose of 1,000 mg at weeks 0, 2, 6, 14, and 22. The steroid group received 250 mg intravenous methylprednisolone at week 0, and placebo infusions at weeks 2, 6, 14, and 22.
"Disease activity was measured at weeks 0, 6, 14, 22, 26, 38, 50, 68, and 78. From week 26, during an open label observation period, patients continued therapy according to a pragmatic predetermined study escalation protocol with dose adjustment or DMARD change in the infliximab group, and DMARD escalation in the intravenous steroid group if DAS44 was greater than 2.4," the investigators wrote.
Infliximab was discontinued for sustained remission, defined as DAS44 less than 1.6 for 6 months.
This study was supported by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme. Dr. Nam reported receiving speakers bureau fees from UCB. Several other study authors reported receiving grant funding, consultancy fees, and/or honoraria, and also serving on speakers bureaus or advisory boards for numerous pharmaceutical companies, including AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Roche-Chugai, Sanofi-Aventis, Schering-Plough, UCB, and Vertex.
FROM ANNALS OF THE RHEUMATIC DISEASES
Major finding: At week 50 after the start of treatment, the mean change in modified total Sharp-van der Heijde score was 1.20 in 55 patients in the infliximab group, compared with 2.81 in 57 patients in the intravenous corticosteroid group.
Data source: The IDEA study – a double-blind randomized controlled trial involving 112 patients.
Disclosures: This study was supported by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme. Dr. Nam reported receiving speaker bureau fees from UCB. Several other study authors reported receiving grant funding, consultancy fees, and/or honoraria, and also serving on speaker bureaus or advisory boards for numerous pharmaceutical companies, including AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Roche-Chugai, Sanofi-Aventis, Schering-Plough, UCB, and Vertex.
Most American RA patients quit biologics after 2 years
MADRID – Half the patients who successfully start treatment on a biological drug for rheumatoid arthritis are off it within about 2 years, even when treatment was effective and tolerable for the first 6 months, according to U.S. registry data from more than 6,000 patients.
"These findings say to me that there is a fair amount of dissatisfaction even though we have all these treatments," Dr. Vibeke Strand said at the annual European Congress of Rheumatology. "When patients start a biologic treatment, they probably have fairly high expectations, and I might suppose that some of those expectations weren’t met," said Dr. Strand, a rheumatologist and drug consultant affiliated with Stanford (Calif.) University.
The most common reason patients dropped their biologic was lack of efficacy, cited in 36% of the discontinuations, followed by physician preference in 28%, safety in 20%, patient preference in 18%, and treatment access in 9%. (The total exceeds 100% because more than one reason could be cited.)
The strongest correlates of treatment discontinuation were higher disease activity; patient report of anxiety, depression, or both; and starting treatment during 2007-2010, compared with patients who started in 2002-2003.
The data that Dr. Strand and her associates analyzed came from a registry of U.S. rheumatoid arthritis patients kept by the CORRONA (Consortium of Rheumatology Researchers of North America) registry. During 2002-2011, 6,209 American adults with rheumatoid arthritis in the registry received at least 6 months of treatment with a tumor necrosis factor inhibitor (81% of these patients) or another biologic drug (the remaining 19%). The patients had a mean age of 58 years and had rheumatoid arthritis for a mean of 11 years. Many (43%) had not previously been treated with a biologic drug. Patients were followed in the registry for an average of about 3 years.
By 1 year after entry, a third of the patients were off the biologic drug they entered the registry on. Half were off their entry biologic after about 2 years, and during the average 3 years of follow-up 58% of the patients stopped their medication, Dr. Strand and her associates reported (Ann. Rheum. Dis. 2013;72:71). It took a median of 27 months for patients to drop a tumor necrosis factor inhibitor and a median of 21 months for them to come off another type of biologic.
Dr. Strand stressed that because patients had been receiving their biologic drug for at least 6 months to qualify for this analysis, the subsequent dropouts from treatment do not reflect an empiric search for a safe and tolerated agent.
"The guidelines call for figuring out [if a treatment works] in the first 3 months. By requiring patients to be on treatment for at least 6 months, we got away from empiric switching," Dr. Strand said in an interview. That suggests other factors make patients stop treatment. She said she plans to look for what they might be.
The CORRONA registry and related research projects are funded by a consortium of drug companies. Dr. Strand said that she is a consultant to CORRONA and a member of its advisory board.
On Twitter @mitchelzoler
MADRID – Half the patients who successfully start treatment on a biological drug for rheumatoid arthritis are off it within about 2 years, even when treatment was effective and tolerable for the first 6 months, according to U.S. registry data from more than 6,000 patients.
"These findings say to me that there is a fair amount of dissatisfaction even though we have all these treatments," Dr. Vibeke Strand said at the annual European Congress of Rheumatology. "When patients start a biologic treatment, they probably have fairly high expectations, and I might suppose that some of those expectations weren’t met," said Dr. Strand, a rheumatologist and drug consultant affiliated with Stanford (Calif.) University.
The most common reason patients dropped their biologic was lack of efficacy, cited in 36% of the discontinuations, followed by physician preference in 28%, safety in 20%, patient preference in 18%, and treatment access in 9%. (The total exceeds 100% because more than one reason could be cited.)
The strongest correlates of treatment discontinuation were higher disease activity; patient report of anxiety, depression, or both; and starting treatment during 2007-2010, compared with patients who started in 2002-2003.
The data that Dr. Strand and her associates analyzed came from a registry of U.S. rheumatoid arthritis patients kept by the CORRONA (Consortium of Rheumatology Researchers of North America) registry. During 2002-2011, 6,209 American adults with rheumatoid arthritis in the registry received at least 6 months of treatment with a tumor necrosis factor inhibitor (81% of these patients) or another biologic drug (the remaining 19%). The patients had a mean age of 58 years and had rheumatoid arthritis for a mean of 11 years. Many (43%) had not previously been treated with a biologic drug. Patients were followed in the registry for an average of about 3 years.
By 1 year after entry, a third of the patients were off the biologic drug they entered the registry on. Half were off their entry biologic after about 2 years, and during the average 3 years of follow-up 58% of the patients stopped their medication, Dr. Strand and her associates reported (Ann. Rheum. Dis. 2013;72:71). It took a median of 27 months for patients to drop a tumor necrosis factor inhibitor and a median of 21 months for them to come off another type of biologic.
Dr. Strand stressed that because patients had been receiving their biologic drug for at least 6 months to qualify for this analysis, the subsequent dropouts from treatment do not reflect an empiric search for a safe and tolerated agent.
"The guidelines call for figuring out [if a treatment works] in the first 3 months. By requiring patients to be on treatment for at least 6 months, we got away from empiric switching," Dr. Strand said in an interview. That suggests other factors make patients stop treatment. She said she plans to look for what they might be.
The CORRONA registry and related research projects are funded by a consortium of drug companies. Dr. Strand said that she is a consultant to CORRONA and a member of its advisory board.
On Twitter @mitchelzoler
MADRID – Half the patients who successfully start treatment on a biological drug for rheumatoid arthritis are off it within about 2 years, even when treatment was effective and tolerable for the first 6 months, according to U.S. registry data from more than 6,000 patients.
"These findings say to me that there is a fair amount of dissatisfaction even though we have all these treatments," Dr. Vibeke Strand said at the annual European Congress of Rheumatology. "When patients start a biologic treatment, they probably have fairly high expectations, and I might suppose that some of those expectations weren’t met," said Dr. Strand, a rheumatologist and drug consultant affiliated with Stanford (Calif.) University.
The most common reason patients dropped their biologic was lack of efficacy, cited in 36% of the discontinuations, followed by physician preference in 28%, safety in 20%, patient preference in 18%, and treatment access in 9%. (The total exceeds 100% because more than one reason could be cited.)
The strongest correlates of treatment discontinuation were higher disease activity; patient report of anxiety, depression, or both; and starting treatment during 2007-2010, compared with patients who started in 2002-2003.
The data that Dr. Strand and her associates analyzed came from a registry of U.S. rheumatoid arthritis patients kept by the CORRONA (Consortium of Rheumatology Researchers of North America) registry. During 2002-2011, 6,209 American adults with rheumatoid arthritis in the registry received at least 6 months of treatment with a tumor necrosis factor inhibitor (81% of these patients) or another biologic drug (the remaining 19%). The patients had a mean age of 58 years and had rheumatoid arthritis for a mean of 11 years. Many (43%) had not previously been treated with a biologic drug. Patients were followed in the registry for an average of about 3 years.
By 1 year after entry, a third of the patients were off the biologic drug they entered the registry on. Half were off their entry biologic after about 2 years, and during the average 3 years of follow-up 58% of the patients stopped their medication, Dr. Strand and her associates reported (Ann. Rheum. Dis. 2013;72:71). It took a median of 27 months for patients to drop a tumor necrosis factor inhibitor and a median of 21 months for them to come off another type of biologic.
Dr. Strand stressed that because patients had been receiving their biologic drug for at least 6 months to qualify for this analysis, the subsequent dropouts from treatment do not reflect an empiric search for a safe and tolerated agent.
"The guidelines call for figuring out [if a treatment works] in the first 3 months. By requiring patients to be on treatment for at least 6 months, we got away from empiric switching," Dr. Strand said in an interview. That suggests other factors make patients stop treatment. She said she plans to look for what they might be.
The CORRONA registry and related research projects are funded by a consortium of drug companies. Dr. Strand said that she is a consultant to CORRONA and a member of its advisory board.
On Twitter @mitchelzoler
AT THE EULAR CONGRESS 2013
Major finding: Half of U.S. rheumatoid arthritis patients on a biologic drug for at least 6 months stopped it after 2 years.
Data source: Data came from 6,209 U.S. rheumatoid arthritis patients in the CORRONA registry on a biologic drug for at least 6 months.
Disclosures: The CORRONA registry and related research projects are funded by a consortium of drug companies. Dr. Strand said that she is a consultant to CORRONA and a member of its advisory board.
Venous thromboembolism risk increased with rheumatoid arthritis
Having rheumatoid arthritis tripled the risk for developing deep vein thrombosis and doubled the risk for pulmonary embolism in an analysis of data on 146,190 Taiwan residents.
Investigators identified 29,238 people with new diagnoses of rheumatoid arthritis in 1998-2008 in a national database with health records on Taiwan’s entire population of 23.7 million people. They extended the monitoring period for the study to the end of 2010 and compared the rheumatoid arthritis cohort with 116,952 control patients matched by sex and age in the year of diagnosis.
Expressed in person-years of follow-up, the incidence density of deep vein thrombosis was significantly higher in patients with rheumatoid arthritis (11 per 1,000 person-years), compared with the control group patients (3 per 1,000 person-years). The incidence density of pulmonary thromboembolism also was significantly higher in patients with rheumatoid arthritis compared with controls (4 vs. 2 per 1,000 person-years), Dr. Wei-Sheng Chung and his associates reported Aug. 7 in the Annals of the Rheumatic Diseases.
In all, the data included 193,753 person-years of follow-up in the rheumatoid arthritis group and 792,941 person-years of follow-up in the control group.
After adjusting for age, sex, and comorbidities, the rheumatoid arthritis group had a 3.36-fold higher chance of developing deep vein thrombosis and a 2.07-fold higher risk for developing pulmonary embolism, compared with controls, reported Dr. Chung of Taichung (Taiwan) Hospital and his colleagues (Ann. Rheum. Dis. 2013 Aug. 7 [doi:10.1136/annrheumdis-2013-203380]).
The greatest rise in risk was seen in young adults (50 years or younger) with rheumatoid arthritis, who had a nearly six-fold increased risk for deep vein thrombosis and a tripled risk for pulmonary embolism, compared with controls. The increased risk for deep vein thrombosis was seen mainly in the first 4 years after diagnosis of rheumatoid arthritis, which relied on American College of Rheumatology 1987 criteria that may have identified the disease at a later stage, the investigators suggested. The ACR and the European League Against Rheumatism (EULAR) revised their classification criteria in 2010 to focus on features at earlier stages of the disease.
Patients with rheumatoid arthritis were significantly more likely than controls to have comorbidities, including hypertension, diabetes, hyperlipidemia, heart failure, or lower leg fracture or surgery. The presence of both rheumatoid arthritis and a comorbidity multiplied the risk for thromboembolism, with a six-fold increased risk for deep vein thrombosis and a four-fold increased risk for pulmonary embolism, compared with patients with neither rheumatoid arthritis nor a comorbidity.
"Providing adequate care for patients with rheumatoid arthritis with comorbidities is an important step in preventing further development of deep vein thrombosis and pulmonary embolism. Thus, a multidisciplinary team should guide the assessment, treatment and holistic care of patients with rheumatoid arthritis," Dr. Chung and his associates concluded.
In Taiwan, an estimated 0.1% of the population has rheumatoid arthritis, which is lower than rates of 0.5%-1% in Western countries, they noted. In general, venous thromboembolism leads to death within 30 days in 11%-30% of patients, previous data show.
Two recent population-based cohort studies of patients in Sweden (JAMA 2012;308:1350-6) and in the United Kingdom (Ann. Rheum. Dis. 2013;72:1182-7) reported a doubling in risk for venous thromboembolism in people with rheumatoid arthritis. The differences in increased risk seen in the Taiwan and Western studies may be associated with racial differences, the Taiwanese investigators suggested.
The study cohort was 77% female and had a mean age of 52 years.
The findings are limited by the fact that the Taiwanese database did not include information on smoking, body mass index, physical activity, severity of rheumatoid arthritis, and use of drugs that could affect risk, including hormone replacement therapy, anticonceptive drugs, or glucocorticoids.
Chronic inflammation in patients with rheumatoid arthritis has been associated with prothrombotic factors and endothelial dysfunction in the development of atherothrombosis in prior studies.
Dr. Chung reported having no financial disclosures. The Taiwan government and Taichung Hospital funded the study.
On Twitter @sherryboschert
This study is consistent with the findings of our U.S. study of 110,715 patients (Arthritis Care Res. 2013 May 10 [doi:10.1002/acr.22039]) and other published papers. Over the past few years, a number of studies, including ours and this one, have shown an increased risk of venous thromboembolism in patients with rheumatoid arthritis, compared with those without rheumatoid arthritis. This risk may be related to rheumatoid arthritis disease (systemic inflammation) itself or the treatment that patients received for rheumatoid arthritis.
|
|
Regardless, physicians should keep in mind that patients with rheumatoid arthritis are at increased risk of venous thromboembolism. When rheumatoid arthritis patients go through other known risk factors for venous thromboembolism (surgery, cancer diagnosis, hospitalization), they should be properly placed on venous thromboembolism prophylaxis.
According to this Taiwanese study, the risk of deep vein thrombosis was the highest in the first years after rheumatoid arthritis diagnosis.
The Taiwanese study focused on newly diagnosed rheumatoid arthritis, while our study used prevalent cases of rheumatoid arthritis. They were able to look at the risk by time since rheumatoid arthritis diagnosis. Overall, the mean follow-up time was quite long (over 6 years), whereas our study has over 2 years of follow-up on average.
The Taiwanese findings regarding the interaction between rheumatoid arthritis and comorbidity is interesting clinically, but it is important to note that their adjusted hazard ratio was adjusted only for age, sex, and comorbidity, which was made into a dichotomized (yes/no) variable, which may be too simple.
The Taiwanese study reported that around 7% of patients had hypertension, which seems somewhat low, given that the mean age of the cohort was 52 years. Our cohort had the same mean age and 24%-30% had hypertension. We excluded patients with cancer at baseline, and the Taiwanese study included them.
As the Taiwanese investigators write in the discussion section of their report, the lack of data on some known risk factors such as oral contraceptive use, steroids, and other drugs would lead to incomplete adjustment for confounding.
Because both studies used mainly claims data, it is important to adjust for health care use patterns to minimize surveillance bias. In other words, patients without rheumatoid arthritis may not seek medical care as much as rheumatoid arthritis patients. Physicians may behave differently when they have a patient with possible venous thromboembolism symptoms in the presence or absence of rheumatoid arthritis. My guess is that, if the Taiwanese study does further adjustment for health care use, the hazard ratio would get smaller.
Further research is needed to evaluate whether or not the additional venous thromboembolism risk in patients with rheumatoid arthritis can be modified by disease-modifying antirheumatic drugs or other factors (such as physical activity, obesity, or smoking).
Dr. SeoYoung C. Kim is assistant professor of medicine at Brigham and Women’s Hospital, Boston. Her study was funded by the National Institutes of Health. She has received research support from Pfizer and tuition support from the pharmacoepidemiology program at the Harvard School of Public Health, which is funded by Pfizer, Millennium, and ASISA.
This study is consistent with the findings of our U.S. study of 110,715 patients (Arthritis Care Res. 2013 May 10 [doi:10.1002/acr.22039]) and other published papers. Over the past few years, a number of studies, including ours and this one, have shown an increased risk of venous thromboembolism in patients with rheumatoid arthritis, compared with those without rheumatoid arthritis. This risk may be related to rheumatoid arthritis disease (systemic inflammation) itself or the treatment that patients received for rheumatoid arthritis.
|
|
|
Regardless, physicians should keep in mind that patients with rheumatoid arthritis are at increased risk of venous thromboembolism. When rheumatoid arthritis patients go through other known risk factors for venous thromboembolism (surgery, cancer diagnosis, hospitalization), they should be properly placed on venous thromboembolism prophylaxis.
According to this Taiwanese study, the risk of deep vein thrombosis was the highest in the first years after rheumatoid arthritis diagnosis.
The Taiwanese study focused on newly diagnosed rheumatoid arthritis, while our study used prevalent cases of rheumatoid arthritis. They were able to look at the risk by time since rheumatoid arthritis diagnosis. Overall, the mean follow-up time was quite long (over 6 years), whereas our study has over 2 years of follow-up on average.
The Taiwanese findings regarding the interaction between rheumatoid arthritis and comorbidity is interesting clinically, but it is important to note that their adjusted hazard ratio was adjusted only for age, sex, and comorbidity, which was made into a dichotomized (yes/no) variable, which may be too simple.
The Taiwanese study reported that around 7% of patients had hypertension, which seems somewhat low, given that the mean age of the cohort was 52 years. Our cohort had the same mean age and 24%-30% had hypertension. We excluded patients with cancer at baseline, and the Taiwanese study included them.
As the Taiwanese investigators write in the discussion section of their report, the lack of data on some known risk factors such as oral contraceptive use, steroids, and other drugs would lead to incomplete adjustment for confounding.
Because both studies used mainly claims data, it is important to adjust for health care use patterns to minimize surveillance bias. In other words, patients without rheumatoid arthritis may not seek medical care as much as rheumatoid arthritis patients. Physicians may behave differently when they have a patient with possible venous thromboembolism symptoms in the presence or absence of rheumatoid arthritis. My guess is that, if the Taiwanese study does further adjustment for health care use, the hazard ratio would get smaller.
Further research is needed to evaluate whether or not the additional venous thromboembolism risk in patients with rheumatoid arthritis can be modified by disease-modifying antirheumatic drugs or other factors (such as physical activity, obesity, or smoking).
Dr. SeoYoung C. Kim is assistant professor of medicine at Brigham and Women’s Hospital, Boston. Her study was funded by the National Institutes of Health. She has received research support from Pfizer and tuition support from the pharmacoepidemiology program at the Harvard School of Public Health, which is funded by Pfizer, Millennium, and ASISA.
This study is consistent with the findings of our U.S. study of 110,715 patients (Arthritis Care Res. 2013 May 10 [doi:10.1002/acr.22039]) and other published papers. Over the past few years, a number of studies, including ours and this one, have shown an increased risk of venous thromboembolism in patients with rheumatoid arthritis, compared with those without rheumatoid arthritis. This risk may be related to rheumatoid arthritis disease (systemic inflammation) itself or the treatment that patients received for rheumatoid arthritis.
|
|
|
Regardless, physicians should keep in mind that patients with rheumatoid arthritis are at increased risk of venous thromboembolism. When rheumatoid arthritis patients go through other known risk factors for venous thromboembolism (surgery, cancer diagnosis, hospitalization), they should be properly placed on venous thromboembolism prophylaxis.
According to this Taiwanese study, the risk of deep vein thrombosis was the highest in the first years after rheumatoid arthritis diagnosis.
The Taiwanese study focused on newly diagnosed rheumatoid arthritis, while our study used prevalent cases of rheumatoid arthritis. They were able to look at the risk by time since rheumatoid arthritis diagnosis. Overall, the mean follow-up time was quite long (over 6 years), whereas our study has over 2 years of follow-up on average.
The Taiwanese findings regarding the interaction between rheumatoid arthritis and comorbidity is interesting clinically, but it is important to note that their adjusted hazard ratio was adjusted only for age, sex, and comorbidity, which was made into a dichotomized (yes/no) variable, which may be too simple.
The Taiwanese study reported that around 7% of patients had hypertension, which seems somewhat low, given that the mean age of the cohort was 52 years. Our cohort had the same mean age and 24%-30% had hypertension. We excluded patients with cancer at baseline, and the Taiwanese study included them.
As the Taiwanese investigators write in the discussion section of their report, the lack of data on some known risk factors such as oral contraceptive use, steroids, and other drugs would lead to incomplete adjustment for confounding.
Because both studies used mainly claims data, it is important to adjust for health care use patterns to minimize surveillance bias. In other words, patients without rheumatoid arthritis may not seek medical care as much as rheumatoid arthritis patients. Physicians may behave differently when they have a patient with possible venous thromboembolism symptoms in the presence or absence of rheumatoid arthritis. My guess is that, if the Taiwanese study does further adjustment for health care use, the hazard ratio would get smaller.
Further research is needed to evaluate whether or not the additional venous thromboembolism risk in patients with rheumatoid arthritis can be modified by disease-modifying antirheumatic drugs or other factors (such as physical activity, obesity, or smoking).
Dr. SeoYoung C. Kim is assistant professor of medicine at Brigham and Women’s Hospital, Boston. Her study was funded by the National Institutes of Health. She has received research support from Pfizer and tuition support from the pharmacoepidemiology program at the Harvard School of Public Health, which is funded by Pfizer, Millennium, and ASISA.
Having rheumatoid arthritis tripled the risk for developing deep vein thrombosis and doubled the risk for pulmonary embolism in an analysis of data on 146,190 Taiwan residents.
Investigators identified 29,238 people with new diagnoses of rheumatoid arthritis in 1998-2008 in a national database with health records on Taiwan’s entire population of 23.7 million people. They extended the monitoring period for the study to the end of 2010 and compared the rheumatoid arthritis cohort with 116,952 control patients matched by sex and age in the year of diagnosis.
Expressed in person-years of follow-up, the incidence density of deep vein thrombosis was significantly higher in patients with rheumatoid arthritis (11 per 1,000 person-years), compared with the control group patients (3 per 1,000 person-years). The incidence density of pulmonary thromboembolism also was significantly higher in patients with rheumatoid arthritis compared with controls (4 vs. 2 per 1,000 person-years), Dr. Wei-Sheng Chung and his associates reported Aug. 7 in the Annals of the Rheumatic Diseases.
In all, the data included 193,753 person-years of follow-up in the rheumatoid arthritis group and 792,941 person-years of follow-up in the control group.
After adjusting for age, sex, and comorbidities, the rheumatoid arthritis group had a 3.36-fold higher chance of developing deep vein thrombosis and a 2.07-fold higher risk for developing pulmonary embolism, compared with controls, reported Dr. Chung of Taichung (Taiwan) Hospital and his colleagues (Ann. Rheum. Dis. 2013 Aug. 7 [doi:10.1136/annrheumdis-2013-203380]).
The greatest rise in risk was seen in young adults (50 years or younger) with rheumatoid arthritis, who had a nearly six-fold increased risk for deep vein thrombosis and a tripled risk for pulmonary embolism, compared with controls. The increased risk for deep vein thrombosis was seen mainly in the first 4 years after diagnosis of rheumatoid arthritis, which relied on American College of Rheumatology 1987 criteria that may have identified the disease at a later stage, the investigators suggested. The ACR and the European League Against Rheumatism (EULAR) revised their classification criteria in 2010 to focus on features at earlier stages of the disease.
Patients with rheumatoid arthritis were significantly more likely than controls to have comorbidities, including hypertension, diabetes, hyperlipidemia, heart failure, or lower leg fracture or surgery. The presence of both rheumatoid arthritis and a comorbidity multiplied the risk for thromboembolism, with a six-fold increased risk for deep vein thrombosis and a four-fold increased risk for pulmonary embolism, compared with patients with neither rheumatoid arthritis nor a comorbidity.
"Providing adequate care for patients with rheumatoid arthritis with comorbidities is an important step in preventing further development of deep vein thrombosis and pulmonary embolism. Thus, a multidisciplinary team should guide the assessment, treatment and holistic care of patients with rheumatoid arthritis," Dr. Chung and his associates concluded.
In Taiwan, an estimated 0.1% of the population has rheumatoid arthritis, which is lower than rates of 0.5%-1% in Western countries, they noted. In general, venous thromboembolism leads to death within 30 days in 11%-30% of patients, previous data show.
Two recent population-based cohort studies of patients in Sweden (JAMA 2012;308:1350-6) and in the United Kingdom (Ann. Rheum. Dis. 2013;72:1182-7) reported a doubling in risk for venous thromboembolism in people with rheumatoid arthritis. The differences in increased risk seen in the Taiwan and Western studies may be associated with racial differences, the Taiwanese investigators suggested.
The study cohort was 77% female and had a mean age of 52 years.
The findings are limited by the fact that the Taiwanese database did not include information on smoking, body mass index, physical activity, severity of rheumatoid arthritis, and use of drugs that could affect risk, including hormone replacement therapy, anticonceptive drugs, or glucocorticoids.
Chronic inflammation in patients with rheumatoid arthritis has been associated with prothrombotic factors and endothelial dysfunction in the development of atherothrombosis in prior studies.
Dr. Chung reported having no financial disclosures. The Taiwan government and Taichung Hospital funded the study.
On Twitter @sherryboschert
Having rheumatoid arthritis tripled the risk for developing deep vein thrombosis and doubled the risk for pulmonary embolism in an analysis of data on 146,190 Taiwan residents.
Investigators identified 29,238 people with new diagnoses of rheumatoid arthritis in 1998-2008 in a national database with health records on Taiwan’s entire population of 23.7 million people. They extended the monitoring period for the study to the end of 2010 and compared the rheumatoid arthritis cohort with 116,952 control patients matched by sex and age in the year of diagnosis.
Expressed in person-years of follow-up, the incidence density of deep vein thrombosis was significantly higher in patients with rheumatoid arthritis (11 per 1,000 person-years), compared with the control group patients (3 per 1,000 person-years). The incidence density of pulmonary thromboembolism also was significantly higher in patients with rheumatoid arthritis compared with controls (4 vs. 2 per 1,000 person-years), Dr. Wei-Sheng Chung and his associates reported Aug. 7 in the Annals of the Rheumatic Diseases.
In all, the data included 193,753 person-years of follow-up in the rheumatoid arthritis group and 792,941 person-years of follow-up in the control group.
After adjusting for age, sex, and comorbidities, the rheumatoid arthritis group had a 3.36-fold higher chance of developing deep vein thrombosis and a 2.07-fold higher risk for developing pulmonary embolism, compared with controls, reported Dr. Chung of Taichung (Taiwan) Hospital and his colleagues (Ann. Rheum. Dis. 2013 Aug. 7 [doi:10.1136/annrheumdis-2013-203380]).
The greatest rise in risk was seen in young adults (50 years or younger) with rheumatoid arthritis, who had a nearly six-fold increased risk for deep vein thrombosis and a tripled risk for pulmonary embolism, compared with controls. The increased risk for deep vein thrombosis was seen mainly in the first 4 years after diagnosis of rheumatoid arthritis, which relied on American College of Rheumatology 1987 criteria that may have identified the disease at a later stage, the investigators suggested. The ACR and the European League Against Rheumatism (EULAR) revised their classification criteria in 2010 to focus on features at earlier stages of the disease.
Patients with rheumatoid arthritis were significantly more likely than controls to have comorbidities, including hypertension, diabetes, hyperlipidemia, heart failure, or lower leg fracture or surgery. The presence of both rheumatoid arthritis and a comorbidity multiplied the risk for thromboembolism, with a six-fold increased risk for deep vein thrombosis and a four-fold increased risk for pulmonary embolism, compared with patients with neither rheumatoid arthritis nor a comorbidity.
"Providing adequate care for patients with rheumatoid arthritis with comorbidities is an important step in preventing further development of deep vein thrombosis and pulmonary embolism. Thus, a multidisciplinary team should guide the assessment, treatment and holistic care of patients with rheumatoid arthritis," Dr. Chung and his associates concluded.
In Taiwan, an estimated 0.1% of the population has rheumatoid arthritis, which is lower than rates of 0.5%-1% in Western countries, they noted. In general, venous thromboembolism leads to death within 30 days in 11%-30% of patients, previous data show.
Two recent population-based cohort studies of patients in Sweden (JAMA 2012;308:1350-6) and in the United Kingdom (Ann. Rheum. Dis. 2013;72:1182-7) reported a doubling in risk for venous thromboembolism in people with rheumatoid arthritis. The differences in increased risk seen in the Taiwan and Western studies may be associated with racial differences, the Taiwanese investigators suggested.
The study cohort was 77% female and had a mean age of 52 years.
The findings are limited by the fact that the Taiwanese database did not include information on smoking, body mass index, physical activity, severity of rheumatoid arthritis, and use of drugs that could affect risk, including hormone replacement therapy, anticonceptive drugs, or glucocorticoids.
Chronic inflammation in patients with rheumatoid arthritis has been associated with prothrombotic factors and endothelial dysfunction in the development of atherothrombosis in prior studies.
Dr. Chung reported having no financial disclosures. The Taiwan government and Taichung Hospital funded the study.
On Twitter @sherryboschert
FROM ANNALS OF THE RHEUMATIC DISEASES
Major finding: Having rheumatoid arthritis tripled the risk for deep vein thrombosis and doubled the risk for pulmonary embolism after controlling for age, sex, and comorbidities.
Data source: Analysis of data from a registry of all Taiwan residents that compared 29,238 people with rheumatoid arthritis and 116,952 matched control patients.
Disclosures: Dr. Chung reported having no financial disclosures. The Taiwan government and Taichung Hospital funded the study.
Study suggests cardiovascular benefit with TNF-alpha blockade
Patients with rheumatoid arthritis who began taking a tumor necrosis factor–alpha blocking agent had a lower cardiovascular event risk during the subsequent 6 months than did those who took a nonbiologic disease-modifying antirheumatic drug in a large, observational study of several administrative and health plan datasets.
The incidence rate for a composite cardiovascular endpoint through the first 6 months of follow-up was 2.52/100 person-years in 11,587 subjects with rheumatoid arthritis (RA) who added a TNF-alpha blocker to their treatment regimen, compared with a rate of 3.05/100 person-years in 8,656 subjects with RA who added a nonbiologic DMARD, Dr. Daniel H. Solomon of Brigham and Women’s Hospital, Boston, and his colleagues reported.
The findings were most pronounced among those aged 65 years and older (hazard ratio, 0.52), and the benefits waned after 6 months.
"In both the first exposure carried forward and the as-treated analyses, the cardiovascular event–free survival curves diverged over the first 6 months. The hazard ratio for the TNF-alpha blocking agent, compared with the nonbiologic DMARD in the first exposure, carried forward was 0.80, and the as-treated analysis at 6 months was 0.71. However, by 12 months the curves appeared to converge with the hazard ratios approaching the null," the investigators explained (Am. J. Med. 2013;126:730.e9-17).
The study involved participants older than 16 years (mean age of 56 years) in several U.S. insurance programs. Those included in the current study – which was part of a larger study collaborative known as SABER (Safety Assessment of Biologic Therapy) – were RA patients using methotrexate who were either adding or switching to a TNF-alpha blocker or a nonbiologic DMARD.
The study’s primary endpoint consisted of a composite cardiovascular outcome of myocardial infarction, stroke, or coronary revascularization; each of these components alone represented a secondary study endpoint.
"While statins and aspirin may reduce cardiovascular risk in part through their anti-inflammatory properties, targeting cytokines known to be part of cardiovascular disease is an attractive therapeutic option."
"The component cardiovascular outcomes followed a similar pattern (to the composite outcome), except stroke, where the incidence rates were similar across exposures," the investigators noted.
Despite the limitations inherent in an observational study, the findings may have important clinical implications, they said.
"As greater evidence accumulates for the role of inflammation in atherosclerosis, consideration has been given to the use of immunosuppressive treatment regimens in cardiovascular disease. While statins and aspirin may reduce cardiovascular risk in part through their anti-inflammatory properties, targeting cytokines known to be part of cardiovascular disease is an attractive therapeutic option. Because the use of potent immunosuppressive agents is common in a systemic inflammatory condition such as rheumatoid arthritis, studying the effect of these agents on cardiovascular disease may provide important insights into the potential role of this strategy in the general population."
The results of the current study generally agree with prior findings demonstrating a link between TNF-alpha blocker use and reduced risk of cardiovascular outcomes.
"TNF-alpha appears to affect several aspects of cardiovascular disease, such as plaque stabilization, endothelial function, and postinfarct remodeling. Thus, one would anticipate that blockade of TNF-alpha would reduce ischemic cardiovascular outcomes. This finding supports the inflammatory underpinnings of cardiovascular disease and highlights a potential role for immunosuppression in cardiovascular risk reduction," they wrote, concluding that randomized controlled clinical trials testing targeted immunosuppression to reduce cardiovascular risk are warranted.
This study was supported by the Agency for Healthcare Research and Quality and the Food and Drug Administration. Dr. Solomon reported receiving research grants from Abbott, Amgen, and Lilly, and serving in unpaid roles on two Pfizer trials. He also directed an educational course supported by Bristol-Myers Squibb, and serves as a consultant to the Consortium of Rheumatology Researchers of North America Inc. (CORRONA). Other study authors reported receiving research grants from, and/or serving as a consultant for Amgen, Abbott, BMS, Centocor, Genentech/Roche, Janssen, Pfizer, UCB, and CORRONA.
Patients with rheumatoid arthritis who began taking a tumor necrosis factor–alpha blocking agent had a lower cardiovascular event risk during the subsequent 6 months than did those who took a nonbiologic disease-modifying antirheumatic drug in a large, observational study of several administrative and health plan datasets.
The incidence rate for a composite cardiovascular endpoint through the first 6 months of follow-up was 2.52/100 person-years in 11,587 subjects with rheumatoid arthritis (RA) who added a TNF-alpha blocker to their treatment regimen, compared with a rate of 3.05/100 person-years in 8,656 subjects with RA who added a nonbiologic DMARD, Dr. Daniel H. Solomon of Brigham and Women’s Hospital, Boston, and his colleagues reported.
The findings were most pronounced among those aged 65 years and older (hazard ratio, 0.52), and the benefits waned after 6 months.
"In both the first exposure carried forward and the as-treated analyses, the cardiovascular event–free survival curves diverged over the first 6 months. The hazard ratio for the TNF-alpha blocking agent, compared with the nonbiologic DMARD in the first exposure, carried forward was 0.80, and the as-treated analysis at 6 months was 0.71. However, by 12 months the curves appeared to converge with the hazard ratios approaching the null," the investigators explained (Am. J. Med. 2013;126:730.e9-17).
The study involved participants older than 16 years (mean age of 56 years) in several U.S. insurance programs. Those included in the current study – which was part of a larger study collaborative known as SABER (Safety Assessment of Biologic Therapy) – were RA patients using methotrexate who were either adding or switching to a TNF-alpha blocker or a nonbiologic DMARD.
The study’s primary endpoint consisted of a composite cardiovascular outcome of myocardial infarction, stroke, or coronary revascularization; each of these components alone represented a secondary study endpoint.
"While statins and aspirin may reduce cardiovascular risk in part through their anti-inflammatory properties, targeting cytokines known to be part of cardiovascular disease is an attractive therapeutic option."
"The component cardiovascular outcomes followed a similar pattern (to the composite outcome), except stroke, where the incidence rates were similar across exposures," the investigators noted.
Despite the limitations inherent in an observational study, the findings may have important clinical implications, they said.
"As greater evidence accumulates for the role of inflammation in atherosclerosis, consideration has been given to the use of immunosuppressive treatment regimens in cardiovascular disease. While statins and aspirin may reduce cardiovascular risk in part through their anti-inflammatory properties, targeting cytokines known to be part of cardiovascular disease is an attractive therapeutic option. Because the use of potent immunosuppressive agents is common in a systemic inflammatory condition such as rheumatoid arthritis, studying the effect of these agents on cardiovascular disease may provide important insights into the potential role of this strategy in the general population."
The results of the current study generally agree with prior findings demonstrating a link between TNF-alpha blocker use and reduced risk of cardiovascular outcomes.
"TNF-alpha appears to affect several aspects of cardiovascular disease, such as plaque stabilization, endothelial function, and postinfarct remodeling. Thus, one would anticipate that blockade of TNF-alpha would reduce ischemic cardiovascular outcomes. This finding supports the inflammatory underpinnings of cardiovascular disease and highlights a potential role for immunosuppression in cardiovascular risk reduction," they wrote, concluding that randomized controlled clinical trials testing targeted immunosuppression to reduce cardiovascular risk are warranted.
This study was supported by the Agency for Healthcare Research and Quality and the Food and Drug Administration. Dr. Solomon reported receiving research grants from Abbott, Amgen, and Lilly, and serving in unpaid roles on two Pfizer trials. He also directed an educational course supported by Bristol-Myers Squibb, and serves as a consultant to the Consortium of Rheumatology Researchers of North America Inc. (CORRONA). Other study authors reported receiving research grants from, and/or serving as a consultant for Amgen, Abbott, BMS, Centocor, Genentech/Roche, Janssen, Pfizer, UCB, and CORRONA.
Patients with rheumatoid arthritis who began taking a tumor necrosis factor–alpha blocking agent had a lower cardiovascular event risk during the subsequent 6 months than did those who took a nonbiologic disease-modifying antirheumatic drug in a large, observational study of several administrative and health plan datasets.
The incidence rate for a composite cardiovascular endpoint through the first 6 months of follow-up was 2.52/100 person-years in 11,587 subjects with rheumatoid arthritis (RA) who added a TNF-alpha blocker to their treatment regimen, compared with a rate of 3.05/100 person-years in 8,656 subjects with RA who added a nonbiologic DMARD, Dr. Daniel H. Solomon of Brigham and Women’s Hospital, Boston, and his colleagues reported.
The findings were most pronounced among those aged 65 years and older (hazard ratio, 0.52), and the benefits waned after 6 months.
"In both the first exposure carried forward and the as-treated analyses, the cardiovascular event–free survival curves diverged over the first 6 months. The hazard ratio for the TNF-alpha blocking agent, compared with the nonbiologic DMARD in the first exposure, carried forward was 0.80, and the as-treated analysis at 6 months was 0.71. However, by 12 months the curves appeared to converge with the hazard ratios approaching the null," the investigators explained (Am. J. Med. 2013;126:730.e9-17).
The study involved participants older than 16 years (mean age of 56 years) in several U.S. insurance programs. Those included in the current study – which was part of a larger study collaborative known as SABER (Safety Assessment of Biologic Therapy) – were RA patients using methotrexate who were either adding or switching to a TNF-alpha blocker or a nonbiologic DMARD.
The study’s primary endpoint consisted of a composite cardiovascular outcome of myocardial infarction, stroke, or coronary revascularization; each of these components alone represented a secondary study endpoint.
"While statins and aspirin may reduce cardiovascular risk in part through their anti-inflammatory properties, targeting cytokines known to be part of cardiovascular disease is an attractive therapeutic option."
"The component cardiovascular outcomes followed a similar pattern (to the composite outcome), except stroke, where the incidence rates were similar across exposures," the investigators noted.
Despite the limitations inherent in an observational study, the findings may have important clinical implications, they said.
"As greater evidence accumulates for the role of inflammation in atherosclerosis, consideration has been given to the use of immunosuppressive treatment regimens in cardiovascular disease. While statins and aspirin may reduce cardiovascular risk in part through their anti-inflammatory properties, targeting cytokines known to be part of cardiovascular disease is an attractive therapeutic option. Because the use of potent immunosuppressive agents is common in a systemic inflammatory condition such as rheumatoid arthritis, studying the effect of these agents on cardiovascular disease may provide important insights into the potential role of this strategy in the general population."
The results of the current study generally agree with prior findings demonstrating a link between TNF-alpha blocker use and reduced risk of cardiovascular outcomes.
"TNF-alpha appears to affect several aspects of cardiovascular disease, such as plaque stabilization, endothelial function, and postinfarct remodeling. Thus, one would anticipate that blockade of TNF-alpha would reduce ischemic cardiovascular outcomes. This finding supports the inflammatory underpinnings of cardiovascular disease and highlights a potential role for immunosuppression in cardiovascular risk reduction," they wrote, concluding that randomized controlled clinical trials testing targeted immunosuppression to reduce cardiovascular risk are warranted.
This study was supported by the Agency for Healthcare Research and Quality and the Food and Drug Administration. Dr. Solomon reported receiving research grants from Abbott, Amgen, and Lilly, and serving in unpaid roles on two Pfizer trials. He also directed an educational course supported by Bristol-Myers Squibb, and serves as a consultant to the Consortium of Rheumatology Researchers of North America Inc. (CORRONA). Other study authors reported receiving research grants from, and/or serving as a consultant for Amgen, Abbott, BMS, Centocor, Genentech/Roche, Janssen, Pfizer, UCB, and CORRONA.
FROM THE AMERICAN JOURNAL OF MEDICINE
Major finding: Composite cardiovascular endpoint incidence rates were 2.52/100 person-years for TNF-alpha blockers, compared with 3.05 for nonbiologic DMARDs.
Data source: A large, observational study including more than 20,000 RA patients.
Disclosures: This study was supported by the Agency for Healthcare Research and Quality and the Food and Drug Administration. Dr. Solomon reported receiving research grants from Abbott, Amgen, and Lilly, and serves in unpaid roles on two Pfizer trials. He also directed an educational course supported by Bristol-Myers Squibb (BMS), and serves as a consultant to CORRONA. Other study authors reported receiving research grants from, and/or serving as a consultant for Amgen, Abbott, BMS, Centocor, Genentech/Roche, Janssen, Pfizer, UCB, and CORRONA.
FDA approves IV golimumab for RA treatment
The Food and Drug Administration has approved a new infusion-version of golimumab, in combination with methotrexate, for the treatment of adults with moderately to severely active rheumatoid arthritis.
The approval, which was announced on July 18, provides another indication for the RA drug. The FDA originally approved golimumab in 2009 as a once-monthly subcutaneous injection treatment for moderately to severely active RA, active psoriatic arthritis, and active ankylosing spondylitis. The injection version of the drug was marketed under the name Simponi, while the new infusion version will go by the trade name Simponi Aria.
The drug’s manufacturer, Janssen Biotech, recommends a dosing regimen of 2 mg/kg given as an intravenous infusion at weeks 0 and 4, then every 8 weeks after. Infusions are given over a 30-minute period.
The dosing regimen allows for an improved infusion experience, Rob Bazemore, president of Janssen Biotech, said in a statement. "Patients can now receive this form of treatment administration with an anti-TNF therapy via a short infusion time of 30 minutes with a dosing regimen of every 8 weeks," he said.
But Dr. Daniel E. Furst, professor of rheumatology at the University of California, Los Angeles, said the latest approval won’t make a major difference in terms of treatment options for patients. The approval is more of a marketing boon for Janssen, which will be able to tout its availability as an infusion. As for the 30-minute infusion time, Dr. Furst said it is likely to appeal to some patients but is not significantly shorter than other infusion times.
"It really doesn’t make a big difference," said Dr. Furst, who performs clinical trial work for several TNF inhibitor drugs and non-TNF inhibitor drugs.
The latest approval was supported by the results of the phase III trial known as GO-FURTHER (Golimumab, an Anti-TNF-alpha Monoclonal Antibody, Administered Intravenously, in Subjects with Active Rheumatoid Arthritis Despite Methotrexate Therapy). The trial showed that the drug significantly improved the signs and symptoms of RA, improved physical function, and slowed the progression of structural damage, according to a statement from Janssen.
In the multicenter, double-blind, placebo-controlled study, researchers evaluated 592 adults with moderately to severely active RA who had at least six tender and six swollen joints at screening and baseline, as well as elevated C-reactive protein (CRP) levels at screening, and who had been receiving background methotrexate for at least 3 months.
They found that at week 14, nearly 60% of the patients who received golimumab plus methotrexate had significant improvements in their signs and symptoms, as determined by at least a 20% improvement in American College of Rheumatology criteria (ACR 20), the study’s primary endpoint. In comparison, only 25% of patients receiving placebo plus methotrexate had at least an ACR 20 response.
Adverse events were reported slightly more often among patients receiving IV golimumab (53%) than among patients receiving placebo (49%). Serious adverse events involving an infection were observed in 0.9% of IV golimumab patients, including one case of tuberculosis and one death from myocardial infarction secondary to community-acquired pneumonia. No serious infections occurred in placebo-treated patients.
The Food and Drug Administration has approved a new infusion-version of golimumab, in combination with methotrexate, for the treatment of adults with moderately to severely active rheumatoid arthritis.
The approval, which was announced on July 18, provides another indication for the RA drug. The FDA originally approved golimumab in 2009 as a once-monthly subcutaneous injection treatment for moderately to severely active RA, active psoriatic arthritis, and active ankylosing spondylitis. The injection version of the drug was marketed under the name Simponi, while the new infusion version will go by the trade name Simponi Aria.
The drug’s manufacturer, Janssen Biotech, recommends a dosing regimen of 2 mg/kg given as an intravenous infusion at weeks 0 and 4, then every 8 weeks after. Infusions are given over a 30-minute period.
The dosing regimen allows for an improved infusion experience, Rob Bazemore, president of Janssen Biotech, said in a statement. "Patients can now receive this form of treatment administration with an anti-TNF therapy via a short infusion time of 30 minutes with a dosing regimen of every 8 weeks," he said.
But Dr. Daniel E. Furst, professor of rheumatology at the University of California, Los Angeles, said the latest approval won’t make a major difference in terms of treatment options for patients. The approval is more of a marketing boon for Janssen, which will be able to tout its availability as an infusion. As for the 30-minute infusion time, Dr. Furst said it is likely to appeal to some patients but is not significantly shorter than other infusion times.
"It really doesn’t make a big difference," said Dr. Furst, who performs clinical trial work for several TNF inhibitor drugs and non-TNF inhibitor drugs.
The latest approval was supported by the results of the phase III trial known as GO-FURTHER (Golimumab, an Anti-TNF-alpha Monoclonal Antibody, Administered Intravenously, in Subjects with Active Rheumatoid Arthritis Despite Methotrexate Therapy). The trial showed that the drug significantly improved the signs and symptoms of RA, improved physical function, and slowed the progression of structural damage, according to a statement from Janssen.
In the multicenter, double-blind, placebo-controlled study, researchers evaluated 592 adults with moderately to severely active RA who had at least six tender and six swollen joints at screening and baseline, as well as elevated C-reactive protein (CRP) levels at screening, and who had been receiving background methotrexate for at least 3 months.
They found that at week 14, nearly 60% of the patients who received golimumab plus methotrexate had significant improvements in their signs and symptoms, as determined by at least a 20% improvement in American College of Rheumatology criteria (ACR 20), the study’s primary endpoint. In comparison, only 25% of patients receiving placebo plus methotrexate had at least an ACR 20 response.
Adverse events were reported slightly more often among patients receiving IV golimumab (53%) than among patients receiving placebo (49%). Serious adverse events involving an infection were observed in 0.9% of IV golimumab patients, including one case of tuberculosis and one death from myocardial infarction secondary to community-acquired pneumonia. No serious infections occurred in placebo-treated patients.
The Food and Drug Administration has approved a new infusion-version of golimumab, in combination with methotrexate, for the treatment of adults with moderately to severely active rheumatoid arthritis.
The approval, which was announced on July 18, provides another indication for the RA drug. The FDA originally approved golimumab in 2009 as a once-monthly subcutaneous injection treatment for moderately to severely active RA, active psoriatic arthritis, and active ankylosing spondylitis. The injection version of the drug was marketed under the name Simponi, while the new infusion version will go by the trade name Simponi Aria.
The drug’s manufacturer, Janssen Biotech, recommends a dosing regimen of 2 mg/kg given as an intravenous infusion at weeks 0 and 4, then every 8 weeks after. Infusions are given over a 30-minute period.
The dosing regimen allows for an improved infusion experience, Rob Bazemore, president of Janssen Biotech, said in a statement. "Patients can now receive this form of treatment administration with an anti-TNF therapy via a short infusion time of 30 minutes with a dosing regimen of every 8 weeks," he said.
But Dr. Daniel E. Furst, professor of rheumatology at the University of California, Los Angeles, said the latest approval won’t make a major difference in terms of treatment options for patients. The approval is more of a marketing boon for Janssen, which will be able to tout its availability as an infusion. As for the 30-minute infusion time, Dr. Furst said it is likely to appeal to some patients but is not significantly shorter than other infusion times.
"It really doesn’t make a big difference," said Dr. Furst, who performs clinical trial work for several TNF inhibitor drugs and non-TNF inhibitor drugs.
The latest approval was supported by the results of the phase III trial known as GO-FURTHER (Golimumab, an Anti-TNF-alpha Monoclonal Antibody, Administered Intravenously, in Subjects with Active Rheumatoid Arthritis Despite Methotrexate Therapy). The trial showed that the drug significantly improved the signs and symptoms of RA, improved physical function, and slowed the progression of structural damage, according to a statement from Janssen.
In the multicenter, double-blind, placebo-controlled study, researchers evaluated 592 adults with moderately to severely active RA who had at least six tender and six swollen joints at screening and baseline, as well as elevated C-reactive protein (CRP) levels at screening, and who had been receiving background methotrexate for at least 3 months.
They found that at week 14, nearly 60% of the patients who received golimumab plus methotrexate had significant improvements in their signs and symptoms, as determined by at least a 20% improvement in American College of Rheumatology criteria (ACR 20), the study’s primary endpoint. In comparison, only 25% of patients receiving placebo plus methotrexate had at least an ACR 20 response.
Adverse events were reported slightly more often among patients receiving IV golimumab (53%) than among patients receiving placebo (49%). Serious adverse events involving an infection were observed in 0.9% of IV golimumab patients, including one case of tuberculosis and one death from myocardial infarction secondary to community-acquired pneumonia. No serious infections occurred in placebo-treated patients.
Ultrasound speeds new RA diagnoses
MADRID – Routine joint scans by ultrasound in patients with suspected rheumatoid arthritis led to faster diagnoses and quicker initiation of disease-modifying treatment in a multicenter-study of more than 250 patients.
But the results did not address whether this earlier diagnosis and treatment produced better outcomes. "While earlier diagnosis and treatment is known to lead to better outcomes, a large, prospective study is required to explore the long-term clinical impact and cost effectiveness of wider routine use of ultrasound by rheumatologists," Dr. Stephen Kelly said at the annual European Congress of Rheumatology.
Despite this current limitation of the available evidence, Dr. Kelly is convinced of the value of routine ultrasound examinations for joint assessment in patients with possible rheumatoid arthritis (RA). "You can see raging inflammation in joints that are not swollen or tender," he said in an interview. The discrepancy between clinical symptoms and the ultrasound appearance can be "surprising," said Dr. Kelly, a rheumatologist at Mile End Hospital in Barts Health NHS Trust in London.
The current study involved observation of patients referred by primary-care physicians to rheumatologists at four U.K. hospitals. Each of the four sites selected included some rheumatologists who routinely used ultrasound and others who did not. By the end of the study, 134 patients had been assessed with ultrasound joint examinations and 124 had been assessed without ultrasound. All patients were initially seen in the referral rheumatology clinics an average of 5 months after symptom onset. They had a mean age of about 53 years, and about 70% were women.
Among the 134 patients assessed initially with ultrasound, the average time to a formal RA diagnosis was 2.24 months, and the median time was 0.89 months. Among the patients not examined with ultrasound, a formal RA diagnosis was made at a mean of 2.76 months and a median of 2 months. These differences were statistically significant.
The investigators eventually diagnosed RA in 54 of the patients assessed with ultrasound and in 58 patients assessed without ultrasound. The median time to the start of treatment with a disease-modifying antirheumatic drug (DMARD) was 0.62 months among patients routinely examined with ultrasound and 1.41 months among those examined without ultrasound.
Put another way, among the patients eventually diagnosed with RA, 67% were diagnosed within a month of initial referral when their rheumatologists routinely used ultrasound, compared with 37% of the RA patients diagnosed within the first month when ultrasound wasn’t used. Initiation of DMARD treatment for the subgroup eventually diagnosed with RA happened in the first month for 63% of the patients routinely assessed by ultrasound, and in 32% of those worked-up without ultrasound.
In a further analysis, the rheumatologists who assessed 134 patients with ultrasound were asked whether their use of ultrasound made a difference. Fifty-three percent said that the first scan they obtained was instrumental in making their diagnosis, and 39% said that a subsequent ultrasound exam was critical in their diagnostic process.
The researchers also asked the rheumatologists who used ultrasound whether the ultrasound results played an important role in management decisions. Thirty-eight percent of the rheumatologists said that the first ultrasound scan they obtained played an important role in their management decisions, and 57% said that a subsequent ultrasound scan affected management.
The study was sponsored by AbbVie. Dr. Kelly said that he had no personal disclosures.
On Twitter @mitchelzoler
The main issue when imaging joints in patients with suspected rheumatoid arthritis (RA) or early disease is: What does imaging add to a standard clinical examination? Standard x-rays do not show many erosions in patients with early disease; ultrasound, as well as MRI, are much more sensitive. Both ultrasound and MRI can be very helpful for difficult-to-diagnose cases. In my experience, about 5%-10% of early-diagnosis cases benefit from using ultrasound or MRI imaging of joints.
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|
Ultrasound is more widely used than MRI is and also costs less. You can examine multiple joints with ultrasound, you don’t need to inject contrast, and you can also use the ultrasound to guide injections. For all these reasons, ultrasound has rapidly become widely used to aid early diagnoses. But not every clinician has the expertise to perform ultrasound examinations, and it has not yet been definitively proven that using ultrasound routinely for diagnostically challenging cases is cost effective. I suspect it is cost effective to perform ultrasound examinations fairly broadly on patients suspected of having RA, compared with the financial and social costs of delayed RA diagnosis in which the patient goes untreated for an added period of time, but study results are still needed to prove this.
In June, I chaired a task force that issued the European League Against Rheumatism’s first recommendations on using joint imaging in the management of RA (Ann. Rheum. Dis. 2013;72:804-14). The 10 recommendations made by the task force include several that support and encourage the use of ultrasound or MRI for both the initial diagnosis of RA as well as subsequent management. However, because evidence is currently lacking to fully document the feasibility, cost, and training required to use methods like ultrasound in routine practice, our recommendations could not be unqualified. For example, our first recommendation says, "When there is diagnostic doubt, conventional radiography, ultrasound, or MRI can be used to improve the certainty of a diagnosis of RA above clinical criteria alone." The level of evidence for this recommendation is level III, which is not the highest level. In addition, note that the recommendation says "can be used" rather than mandating the use of ultrasound or another imaging method. In the same way, our third recommendation says, "Ultrasound and MRI are superior to clinical examination in the detection of joint inflammation; these techniques should be considered for more accurate assessment of inflammation." Again, the level of evidence, III, precluded us from saying anything more definitive than "should be considered."
The main issue when imaging joints in patients with suspected rheumatoid arthritis (RA) or early disease is: What does imaging add to a standard clinical examination? Standard x-rays do not show many erosions in patients with early disease; ultrasound, as well as MRI, are much more sensitive. Both ultrasound and MRI can be very helpful for difficult-to-diagnose cases. In my experience, about 5%-10% of early-diagnosis cases benefit from using ultrasound or MRI imaging of joints.
|
|
|
Ultrasound is more widely used than MRI is and also costs less. You can examine multiple joints with ultrasound, you don’t need to inject contrast, and you can also use the ultrasound to guide injections. For all these reasons, ultrasound has rapidly become widely used to aid early diagnoses. But not every clinician has the expertise to perform ultrasound examinations, and it has not yet been definitively proven that using ultrasound routinely for diagnostically challenging cases is cost effective. I suspect it is cost effective to perform ultrasound examinations fairly broadly on patients suspected of having RA, compared with the financial and social costs of delayed RA diagnosis in which the patient goes untreated for an added period of time, but study results are still needed to prove this.
In June, I chaired a task force that issued the European League Against Rheumatism’s first recommendations on using joint imaging in the management of RA (Ann. Rheum. Dis. 2013;72:804-14). The 10 recommendations made by the task force include several that support and encourage the use of ultrasound or MRI for both the initial diagnosis of RA as well as subsequent management. However, because evidence is currently lacking to fully document the feasibility, cost, and training required to use methods like ultrasound in routine practice, our recommendations could not be unqualified. For example, our first recommendation says, "When there is diagnostic doubt, conventional radiography, ultrasound, or MRI can be used to improve the certainty of a diagnosis of RA above clinical criteria alone." The level of evidence for this recommendation is level III, which is not the highest level. In addition, note that the recommendation says "can be used" rather than mandating the use of ultrasound or another imaging method. In the same way, our third recommendation says, "Ultrasound and MRI are superior to clinical examination in the detection of joint inflammation; these techniques should be considered for more accurate assessment of inflammation." Again, the level of evidence, III, precluded us from saying anything more definitive than "should be considered."
The main issue when imaging joints in patients with suspected rheumatoid arthritis (RA) or early disease is: What does imaging add to a standard clinical examination? Standard x-rays do not show many erosions in patients with early disease; ultrasound, as well as MRI, are much more sensitive. Both ultrasound and MRI can be very helpful for difficult-to-diagnose cases. In my experience, about 5%-10% of early-diagnosis cases benefit from using ultrasound or MRI imaging of joints.
|
|
|
Ultrasound is more widely used than MRI is and also costs less. You can examine multiple joints with ultrasound, you don’t need to inject contrast, and you can also use the ultrasound to guide injections. For all these reasons, ultrasound has rapidly become widely used to aid early diagnoses. But not every clinician has the expertise to perform ultrasound examinations, and it has not yet been definitively proven that using ultrasound routinely for diagnostically challenging cases is cost effective. I suspect it is cost effective to perform ultrasound examinations fairly broadly on patients suspected of having RA, compared with the financial and social costs of delayed RA diagnosis in which the patient goes untreated for an added period of time, but study results are still needed to prove this.
In June, I chaired a task force that issued the European League Against Rheumatism’s first recommendations on using joint imaging in the management of RA (Ann. Rheum. Dis. 2013;72:804-14). The 10 recommendations made by the task force include several that support and encourage the use of ultrasound or MRI for both the initial diagnosis of RA as well as subsequent management. However, because evidence is currently lacking to fully document the feasibility, cost, and training required to use methods like ultrasound in routine practice, our recommendations could not be unqualified. For example, our first recommendation says, "When there is diagnostic doubt, conventional radiography, ultrasound, or MRI can be used to improve the certainty of a diagnosis of RA above clinical criteria alone." The level of evidence for this recommendation is level III, which is not the highest level. In addition, note that the recommendation says "can be used" rather than mandating the use of ultrasound or another imaging method. In the same way, our third recommendation says, "Ultrasound and MRI are superior to clinical examination in the detection of joint inflammation; these techniques should be considered for more accurate assessment of inflammation." Again, the level of evidence, III, precluded us from saying anything more definitive than "should be considered."
MADRID – Routine joint scans by ultrasound in patients with suspected rheumatoid arthritis led to faster diagnoses and quicker initiation of disease-modifying treatment in a multicenter-study of more than 250 patients.
But the results did not address whether this earlier diagnosis and treatment produced better outcomes. "While earlier diagnosis and treatment is known to lead to better outcomes, a large, prospective study is required to explore the long-term clinical impact and cost effectiveness of wider routine use of ultrasound by rheumatologists," Dr. Stephen Kelly said at the annual European Congress of Rheumatology.
Despite this current limitation of the available evidence, Dr. Kelly is convinced of the value of routine ultrasound examinations for joint assessment in patients with possible rheumatoid arthritis (RA). "You can see raging inflammation in joints that are not swollen or tender," he said in an interview. The discrepancy between clinical symptoms and the ultrasound appearance can be "surprising," said Dr. Kelly, a rheumatologist at Mile End Hospital in Barts Health NHS Trust in London.
The current study involved observation of patients referred by primary-care physicians to rheumatologists at four U.K. hospitals. Each of the four sites selected included some rheumatologists who routinely used ultrasound and others who did not. By the end of the study, 134 patients had been assessed with ultrasound joint examinations and 124 had been assessed without ultrasound. All patients were initially seen in the referral rheumatology clinics an average of 5 months after symptom onset. They had a mean age of about 53 years, and about 70% were women.
Among the 134 patients assessed initially with ultrasound, the average time to a formal RA diagnosis was 2.24 months, and the median time was 0.89 months. Among the patients not examined with ultrasound, a formal RA diagnosis was made at a mean of 2.76 months and a median of 2 months. These differences were statistically significant.
The investigators eventually diagnosed RA in 54 of the patients assessed with ultrasound and in 58 patients assessed without ultrasound. The median time to the start of treatment with a disease-modifying antirheumatic drug (DMARD) was 0.62 months among patients routinely examined with ultrasound and 1.41 months among those examined without ultrasound.
Put another way, among the patients eventually diagnosed with RA, 67% were diagnosed within a month of initial referral when their rheumatologists routinely used ultrasound, compared with 37% of the RA patients diagnosed within the first month when ultrasound wasn’t used. Initiation of DMARD treatment for the subgroup eventually diagnosed with RA happened in the first month for 63% of the patients routinely assessed by ultrasound, and in 32% of those worked-up without ultrasound.
In a further analysis, the rheumatologists who assessed 134 patients with ultrasound were asked whether their use of ultrasound made a difference. Fifty-three percent said that the first scan they obtained was instrumental in making their diagnosis, and 39% said that a subsequent ultrasound exam was critical in their diagnostic process.
The researchers also asked the rheumatologists who used ultrasound whether the ultrasound results played an important role in management decisions. Thirty-eight percent of the rheumatologists said that the first ultrasound scan they obtained played an important role in their management decisions, and 57% said that a subsequent ultrasound scan affected management.
The study was sponsored by AbbVie. Dr. Kelly said that he had no personal disclosures.
On Twitter @mitchelzoler
MADRID – Routine joint scans by ultrasound in patients with suspected rheumatoid arthritis led to faster diagnoses and quicker initiation of disease-modifying treatment in a multicenter-study of more than 250 patients.
But the results did not address whether this earlier diagnosis and treatment produced better outcomes. "While earlier diagnosis and treatment is known to lead to better outcomes, a large, prospective study is required to explore the long-term clinical impact and cost effectiveness of wider routine use of ultrasound by rheumatologists," Dr. Stephen Kelly said at the annual European Congress of Rheumatology.
Despite this current limitation of the available evidence, Dr. Kelly is convinced of the value of routine ultrasound examinations for joint assessment in patients with possible rheumatoid arthritis (RA). "You can see raging inflammation in joints that are not swollen or tender," he said in an interview. The discrepancy between clinical symptoms and the ultrasound appearance can be "surprising," said Dr. Kelly, a rheumatologist at Mile End Hospital in Barts Health NHS Trust in London.
The current study involved observation of patients referred by primary-care physicians to rheumatologists at four U.K. hospitals. Each of the four sites selected included some rheumatologists who routinely used ultrasound and others who did not. By the end of the study, 134 patients had been assessed with ultrasound joint examinations and 124 had been assessed without ultrasound. All patients were initially seen in the referral rheumatology clinics an average of 5 months after symptom onset. They had a mean age of about 53 years, and about 70% were women.
Among the 134 patients assessed initially with ultrasound, the average time to a formal RA diagnosis was 2.24 months, and the median time was 0.89 months. Among the patients not examined with ultrasound, a formal RA diagnosis was made at a mean of 2.76 months and a median of 2 months. These differences were statistically significant.
The investigators eventually diagnosed RA in 54 of the patients assessed with ultrasound and in 58 patients assessed without ultrasound. The median time to the start of treatment with a disease-modifying antirheumatic drug (DMARD) was 0.62 months among patients routinely examined with ultrasound and 1.41 months among those examined without ultrasound.
Put another way, among the patients eventually diagnosed with RA, 67% were diagnosed within a month of initial referral when their rheumatologists routinely used ultrasound, compared with 37% of the RA patients diagnosed within the first month when ultrasound wasn’t used. Initiation of DMARD treatment for the subgroup eventually diagnosed with RA happened in the first month for 63% of the patients routinely assessed by ultrasound, and in 32% of those worked-up without ultrasound.
In a further analysis, the rheumatologists who assessed 134 patients with ultrasound were asked whether their use of ultrasound made a difference. Fifty-three percent said that the first scan they obtained was instrumental in making their diagnosis, and 39% said that a subsequent ultrasound exam was critical in their diagnostic process.
The researchers also asked the rheumatologists who used ultrasound whether the ultrasound results played an important role in management decisions. Thirty-eight percent of the rheumatologists said that the first ultrasound scan they obtained played an important role in their management decisions, and 57% said that a subsequent ultrasound scan affected management.
The study was sponsored by AbbVie. Dr. Kelly said that he had no personal disclosures.
On Twitter @mitchelzoler
AT THE EULAR CONGRESS 2013
Major finding: Rheumatoid arthritis diagnosis using ultrasound took a median of 0.89 months, compared with 2.00 months when ultrasound wasn’t used.
Data source: A prospective study of 258 patients with suspected rheumatoid arthritis who were examined at four U.K. centers.
Disclosures: The study was sponsored by AbbVie. Dr. Kelly said that he had no personal disclosures.
Scoring method assesses large-joint damage in treated RA
MADRID – A new radiographic scoring method successfully assessed damage in the large joints of patients with rheumatoid arthritis who were being treated with biologic therapy, according to research presented at the annual European Congress of Rheumatology.
The ARASHI (Assessment of Rheumatoid Arthritis by Scoring of Large-Joint Destruction and Healing in Radiographic Imaging) method, developed by a team in Japan, was tested over a period of 2 years in 51 patients who were being newly treated with tumor necrosis factor–alpha (TNF-alpha) inhibitors.
"Evaluation of radiographic damage of the small joints in the hands and feet using the van der Heijde total Sharp score in patients with early RA has been established," said Dr. Isao Matsushita, assistant professor in the orthopedic surgery department at the University of Toyama, Japan.
While the Larsen grade is most often used to assess large joints, this radiographic grading system has several limitations, including a "ceiling effect," resulting from the substantial variation found within each of the six Larsen grades (scored 0-5), he said in an interview at the meeting. Dr. Matsushita and his colleagues developed the ARASHI method to offer a more sensitive means of determining radiographic progression in the large joints.
The ARASHI method is composed of two parts (Mod. Rheumatol. 2013 April 27 [doi: 10.1007/s10165-012-0823-6]), Dr. Matsushita explained. First, there is a status score, which takes into account four categories: joint space narrowing (scored 0-3), erosion (scored 0-3), joint surface (0-6), and joint stability (0-4). Second, there is a change score, which assesses the same four categories plus the porosity of the joint.
A total of 57 patients with early RA who were about to be treated with TNF-alpha inhibitors were included in the study, and 51 completed 2 years’ treatment with these agents. The most frequently prescribed TNF-alpha inhibitors were infliximab, in 24 patients, and etanercept, used in 14. Another 7 patients switched from infliximab to etanercept, and 6 patients were treated with adalimumab. The mean age of the patients was 60 years, with a mean RA duration of 10.6 years.
The investigators used the ARASHI status score to assess 96 hip and 86 knee joints at baseline (before TNF-alpha inhibitor treatment was started). They later computed the ARASHI change score for the joints at both 1-year and 2-year follow-up visits. A 1-point or more increase in the ARASHI change score constituted radiographic progression. Higher scores indicated higher levels of joint damage.
All of the hip and knee joints with a status score of greater than 2 showed progression of joint damage under TNF-blocking therapies, Dr. Matsushita said. He added that of the joints with a low baseline ARASHI status score (0-2), only 6.5% showed progressive damage over the course of the study. Furthermore, the joint space narrowing score was more closely related to the joint damage subsequently seen than was the erosion score.
Taken together, these findings demonstrate that the "ARASHI scoring method is useful for the evaluation of radiographic damage in large weight-bearing joints, and to predict the risk for progression in patients with RA," Dr. Matsushita said. The next step is to look at the utility of the score in other large joints, perhaps the shoulder, elbow, and ankle joints, he noted.
Dr. Matsushita had no disclosures.
MADRID – A new radiographic scoring method successfully assessed damage in the large joints of patients with rheumatoid arthritis who were being treated with biologic therapy, according to research presented at the annual European Congress of Rheumatology.
The ARASHI (Assessment of Rheumatoid Arthritis by Scoring of Large-Joint Destruction and Healing in Radiographic Imaging) method, developed by a team in Japan, was tested over a period of 2 years in 51 patients who were being newly treated with tumor necrosis factor–alpha (TNF-alpha) inhibitors.
"Evaluation of radiographic damage of the small joints in the hands and feet using the van der Heijde total Sharp score in patients with early RA has been established," said Dr. Isao Matsushita, assistant professor in the orthopedic surgery department at the University of Toyama, Japan.
While the Larsen grade is most often used to assess large joints, this radiographic grading system has several limitations, including a "ceiling effect," resulting from the substantial variation found within each of the six Larsen grades (scored 0-5), he said in an interview at the meeting. Dr. Matsushita and his colleagues developed the ARASHI method to offer a more sensitive means of determining radiographic progression in the large joints.
The ARASHI method is composed of two parts (Mod. Rheumatol. 2013 April 27 [doi: 10.1007/s10165-012-0823-6]), Dr. Matsushita explained. First, there is a status score, which takes into account four categories: joint space narrowing (scored 0-3), erosion (scored 0-3), joint surface (0-6), and joint stability (0-4). Second, there is a change score, which assesses the same four categories plus the porosity of the joint.
A total of 57 patients with early RA who were about to be treated with TNF-alpha inhibitors were included in the study, and 51 completed 2 years’ treatment with these agents. The most frequently prescribed TNF-alpha inhibitors were infliximab, in 24 patients, and etanercept, used in 14. Another 7 patients switched from infliximab to etanercept, and 6 patients were treated with adalimumab. The mean age of the patients was 60 years, with a mean RA duration of 10.6 years.
The investigators used the ARASHI status score to assess 96 hip and 86 knee joints at baseline (before TNF-alpha inhibitor treatment was started). They later computed the ARASHI change score for the joints at both 1-year and 2-year follow-up visits. A 1-point or more increase in the ARASHI change score constituted radiographic progression. Higher scores indicated higher levels of joint damage.
All of the hip and knee joints with a status score of greater than 2 showed progression of joint damage under TNF-blocking therapies, Dr. Matsushita said. He added that of the joints with a low baseline ARASHI status score (0-2), only 6.5% showed progressive damage over the course of the study. Furthermore, the joint space narrowing score was more closely related to the joint damage subsequently seen than was the erosion score.
Taken together, these findings demonstrate that the "ARASHI scoring method is useful for the evaluation of radiographic damage in large weight-bearing joints, and to predict the risk for progression in patients with RA," Dr. Matsushita said. The next step is to look at the utility of the score in other large joints, perhaps the shoulder, elbow, and ankle joints, he noted.
Dr. Matsushita had no disclosures.
MADRID – A new radiographic scoring method successfully assessed damage in the large joints of patients with rheumatoid arthritis who were being treated with biologic therapy, according to research presented at the annual European Congress of Rheumatology.
The ARASHI (Assessment of Rheumatoid Arthritis by Scoring of Large-Joint Destruction and Healing in Radiographic Imaging) method, developed by a team in Japan, was tested over a period of 2 years in 51 patients who were being newly treated with tumor necrosis factor–alpha (TNF-alpha) inhibitors.
"Evaluation of radiographic damage of the small joints in the hands and feet using the van der Heijde total Sharp score in patients with early RA has been established," said Dr. Isao Matsushita, assistant professor in the orthopedic surgery department at the University of Toyama, Japan.
While the Larsen grade is most often used to assess large joints, this radiographic grading system has several limitations, including a "ceiling effect," resulting from the substantial variation found within each of the six Larsen grades (scored 0-5), he said in an interview at the meeting. Dr. Matsushita and his colleagues developed the ARASHI method to offer a more sensitive means of determining radiographic progression in the large joints.
The ARASHI method is composed of two parts (Mod. Rheumatol. 2013 April 27 [doi: 10.1007/s10165-012-0823-6]), Dr. Matsushita explained. First, there is a status score, which takes into account four categories: joint space narrowing (scored 0-3), erosion (scored 0-3), joint surface (0-6), and joint stability (0-4). Second, there is a change score, which assesses the same four categories plus the porosity of the joint.
A total of 57 patients with early RA who were about to be treated with TNF-alpha inhibitors were included in the study, and 51 completed 2 years’ treatment with these agents. The most frequently prescribed TNF-alpha inhibitors were infliximab, in 24 patients, and etanercept, used in 14. Another 7 patients switched from infliximab to etanercept, and 6 patients were treated with adalimumab. The mean age of the patients was 60 years, with a mean RA duration of 10.6 years.
The investigators used the ARASHI status score to assess 96 hip and 86 knee joints at baseline (before TNF-alpha inhibitor treatment was started). They later computed the ARASHI change score for the joints at both 1-year and 2-year follow-up visits. A 1-point or more increase in the ARASHI change score constituted radiographic progression. Higher scores indicated higher levels of joint damage.
All of the hip and knee joints with a status score of greater than 2 showed progression of joint damage under TNF-blocking therapies, Dr. Matsushita said. He added that of the joints with a low baseline ARASHI status score (0-2), only 6.5% showed progressive damage over the course of the study. Furthermore, the joint space narrowing score was more closely related to the joint damage subsequently seen than was the erosion score.
Taken together, these findings demonstrate that the "ARASHI scoring method is useful for the evaluation of radiographic damage in large weight-bearing joints, and to predict the risk for progression in patients with RA," Dr. Matsushita said. The next step is to look at the utility of the score in other large joints, perhaps the shoulder, elbow, and ankle joints, he noted.
Dr. Matsushita had no disclosures.
AT THE EULAR CONGRESS 2013
Major finding: Only 6.5% of patients with a low (0-2) baseline ARASHI status score showed progressive radiographic damage over the course of the study.
Data source: Study of 51 consecutive patients with active rheumatoid arthritis who underwent 2 years of treatment with TNF-alpha inhibitors.
Disclosures: Dr. Matsushita had no disclosures.