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FDA approves second adalimumab biosimilar for multiple conditions
The Food and Drug Administration has approved Cyltezo (adalimumab-adbm) for multiple conditions.
Cyltezo is an injectable tumor necrosis factor blocker, and is a biosimilar to adalimumab (Humira). The drug is indicated to treat moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active Crohn’s disease, moderate to severe active ulcerative colitis, moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older, and moderate to severe plaque psoriasis.
Find the Cyltezo labeling information here.
The Food and Drug Administration has approved Cyltezo (adalimumab-adbm) for multiple conditions.
Cyltezo is an injectable tumor necrosis factor blocker, and is a biosimilar to adalimumab (Humira). The drug is indicated to treat moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active Crohn’s disease, moderate to severe active ulcerative colitis, moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older, and moderate to severe plaque psoriasis.
Find the Cyltezo labeling information here.
The Food and Drug Administration has approved Cyltezo (adalimumab-adbm) for multiple conditions.
Cyltezo is an injectable tumor necrosis factor blocker, and is a biosimilar to adalimumab (Humira). The drug is indicated to treat moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active Crohn’s disease, moderate to severe active ulcerative colitis, moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older, and moderate to severe plaque psoriasis.
Find the Cyltezo labeling information here.
Musculoskeletal ultrasound training now offered in nearly all U.S. rheumatology fellowships
Musculoskeletal ultrasound (MSUS) fellowship opportunities are growing among rheumatology programs across the country as professionals push for more standardized education, according to a survey of fellowship program directors.
Rise in use of MSUS among rheumatologists is spurring more comprehensive education for providers to acquire these skill sets, which researchers have gathered will only become more prevalent.
The investigators sent two surveys to 113 rheumatology fellowship program directors. In the first survey, responses from the directors of 108 programs indicated that 101 (94%) offered MSUS programs (Arthritis Care Res. 2017 Aug 4. doi: 10.1002/acr.23336).
While this number has increased dramatically since a 2013 survey showed that 60% offered MSUS programs, the new survey found that 66% of respondents would prefer for the program to be optional, as opposed to a formal part of the fellowship program.
This sentiment for nonformal education programs was mirrored in the second survey specifically targeting the 101 programs that were known to provide some sort of MSUS education.
Among the 74 program directors who responded, 30 (41%) reported having a formal curriculum, while 44 (59%) did not, citing a major barrier being a lack of interested fellows to learn the material (P = .012)
Another major barrier, according to Dr. Torralba and her colleagues, is access to faculty with enough teaching experience to properly teach MSUS skills, with 62 (84%) reporting having no or only one faculty member with MSUS certification (P = .049).
Programs without proper faculty available and even those with available faculty are choosing to outsource lessons to expensive teaching programs such as the Ultrasound School of North American Rheumatologists (USSONAR) fellowship course, according to Dr. Torralba and her associates.
“While cost of external courses can be prohibitive, (expenses for a 2- to 4-day course costs between $1,500 and $4,000), programs may augment MSUS teaching using these courses for several reasons,” according to Dr. Torralba and her colleagues. [These include] insufficient number of teaching faculty, limited time or support for faculty to deliver all educational content, inadequate confidence or competency for faculty to teach content, and utilization of external materials to bolster resources.”
While these barriers will still need addressing, according to Dr. Torralba and her colleagues, half of responders noted previous barriers such as political pushback and lack of fellow interest are starting to recede, giving more room for programs to start developing MSUS programs that researchers assert are necessary for future developing rheumatologists.
“A standardized MSUS curriculum developed and endorsed by program directors and MSUS lead educators is now reasonably within sights,” the investigators wrote. “We need to work together to proactively champion MSUS education for both faculty and fellows who desire to attain this skill set.”
This study was limited by the self-reporting nature of the survey sent, as well as the small population of the sample. Researchers were also forced to rely on program directors’ perception of how effective their MSUS programs were instead of asking those participating in the programs directly.
The researchers reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
Musculoskeletal ultrasound (MSUS) fellowship opportunities are growing among rheumatology programs across the country as professionals push for more standardized education, according to a survey of fellowship program directors.
Rise in use of MSUS among rheumatologists is spurring more comprehensive education for providers to acquire these skill sets, which researchers have gathered will only become more prevalent.
The investigators sent two surveys to 113 rheumatology fellowship program directors. In the first survey, responses from the directors of 108 programs indicated that 101 (94%) offered MSUS programs (Arthritis Care Res. 2017 Aug 4. doi: 10.1002/acr.23336).
While this number has increased dramatically since a 2013 survey showed that 60% offered MSUS programs, the new survey found that 66% of respondents would prefer for the program to be optional, as opposed to a formal part of the fellowship program.
This sentiment for nonformal education programs was mirrored in the second survey specifically targeting the 101 programs that were known to provide some sort of MSUS education.
Among the 74 program directors who responded, 30 (41%) reported having a formal curriculum, while 44 (59%) did not, citing a major barrier being a lack of interested fellows to learn the material (P = .012)
Another major barrier, according to Dr. Torralba and her colleagues, is access to faculty with enough teaching experience to properly teach MSUS skills, with 62 (84%) reporting having no or only one faculty member with MSUS certification (P = .049).
Programs without proper faculty available and even those with available faculty are choosing to outsource lessons to expensive teaching programs such as the Ultrasound School of North American Rheumatologists (USSONAR) fellowship course, according to Dr. Torralba and her associates.
“While cost of external courses can be prohibitive, (expenses for a 2- to 4-day course costs between $1,500 and $4,000), programs may augment MSUS teaching using these courses for several reasons,” according to Dr. Torralba and her colleagues. [These include] insufficient number of teaching faculty, limited time or support for faculty to deliver all educational content, inadequate confidence or competency for faculty to teach content, and utilization of external materials to bolster resources.”
While these barriers will still need addressing, according to Dr. Torralba and her colleagues, half of responders noted previous barriers such as political pushback and lack of fellow interest are starting to recede, giving more room for programs to start developing MSUS programs that researchers assert are necessary for future developing rheumatologists.
“A standardized MSUS curriculum developed and endorsed by program directors and MSUS lead educators is now reasonably within sights,” the investigators wrote. “We need to work together to proactively champion MSUS education for both faculty and fellows who desire to attain this skill set.”
This study was limited by the self-reporting nature of the survey sent, as well as the small population of the sample. Researchers were also forced to rely on program directors’ perception of how effective their MSUS programs were instead of asking those participating in the programs directly.
The researchers reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
Musculoskeletal ultrasound (MSUS) fellowship opportunities are growing among rheumatology programs across the country as professionals push for more standardized education, according to a survey of fellowship program directors.
Rise in use of MSUS among rheumatologists is spurring more comprehensive education for providers to acquire these skill sets, which researchers have gathered will only become more prevalent.
The investigators sent two surveys to 113 rheumatology fellowship program directors. In the first survey, responses from the directors of 108 programs indicated that 101 (94%) offered MSUS programs (Arthritis Care Res. 2017 Aug 4. doi: 10.1002/acr.23336).
While this number has increased dramatically since a 2013 survey showed that 60% offered MSUS programs, the new survey found that 66% of respondents would prefer for the program to be optional, as opposed to a formal part of the fellowship program.
This sentiment for nonformal education programs was mirrored in the second survey specifically targeting the 101 programs that were known to provide some sort of MSUS education.
Among the 74 program directors who responded, 30 (41%) reported having a formal curriculum, while 44 (59%) did not, citing a major barrier being a lack of interested fellows to learn the material (P = .012)
Another major barrier, according to Dr. Torralba and her colleagues, is access to faculty with enough teaching experience to properly teach MSUS skills, with 62 (84%) reporting having no or only one faculty member with MSUS certification (P = .049).
Programs without proper faculty available and even those with available faculty are choosing to outsource lessons to expensive teaching programs such as the Ultrasound School of North American Rheumatologists (USSONAR) fellowship course, according to Dr. Torralba and her associates.
“While cost of external courses can be prohibitive, (expenses for a 2- to 4-day course costs between $1,500 and $4,000), programs may augment MSUS teaching using these courses for several reasons,” according to Dr. Torralba and her colleagues. [These include] insufficient number of teaching faculty, limited time or support for faculty to deliver all educational content, inadequate confidence or competency for faculty to teach content, and utilization of external materials to bolster resources.”
While these barriers will still need addressing, according to Dr. Torralba and her colleagues, half of responders noted previous barriers such as political pushback and lack of fellow interest are starting to recede, giving more room for programs to start developing MSUS programs that researchers assert are necessary for future developing rheumatologists.
“A standardized MSUS curriculum developed and endorsed by program directors and MSUS lead educators is now reasonably within sights,” the investigators wrote. “We need to work together to proactively champion MSUS education for both faculty and fellows who desire to attain this skill set.”
This study was limited by the self-reporting nature of the survey sent, as well as the small population of the sample. Researchers were also forced to rely on program directors’ perception of how effective their MSUS programs were instead of asking those participating in the programs directly.
The researchers reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
FROM ARTHRITIS CARE & RESEARCH
Key clinical point:
Major finding: Of 108 program directors who responded to a survey, 101 (94%) offered a musculoskeletal ultrasound fellowship.
Data source: Survey of 113 rheumatology fellowship program directors gathered from the Fellowship and Residency Electronic Interactive Database Access (FREIDA) online database.
Disclosures: The investigators reported no relevant financial disclosures.
Oral contraceptive use linked to lower rheumatoid arthritis risk
The use of oral contraceptives may be associated with a reduced risk of rheumatoid arthritis based on findings from a large, population-based, case-control study in Sweden.
The lowered risk for rheumatoid arthritis in the study conducted by Cecilia Orellana, PhD, of the Institute of Environmental Medicine at the Karolinska Institute, Stockholm, and her coauthors applied only to patients who tested positive for anticitrullinated protein antibodies (ACPA) and to those who used oral contraceptives for 7 or more years. The investigators also found a significant reduction in RA risk for women who breastfed their children.
“All of these findings together support the notion of RA as two different disease entities with different risk factors patterns,” the authors wrote.
The researchers looked at 2,578 women with RA and 4,129 female controls from the Swedish Epidemiological Investigation of RA study and found that women who had ever used OCs had 13% lower odds of developing RA than did women who had never used OCs, even after adjusting for age, residential area, smoking, and alcohol consumption. However, this association was significant only for ACPA-positive RA – where the risk was 16% lower – and not for ACPA-negative disease (Ann Rheum Dis. 2017 Aug 17. doi: 10.1136/annrheumdis-2017-211620).
Duration of oral contraceptive use was also positively associated with a decreased risk of RA; women who had taken OCs for 7 or more years had a 19% lower risk of RA, compared with never users.
However, the authors noted that they only collected information on the use of OCs as a whole and not on particular preparations or doses.
Women who had never used OCs and who had also smoked had more than twofold higher odds of developing RA than did women who had used OCs and who had never smoked. Women who had used OCs but who also smoked were 71% more likely to develop RA.
“Since both smoking and the use of OC have been linked to an increased predisposition to venous thrombotic events (VTE), women with a history of VTEs (especially if they smoke) might be recommended not to use OC by their physician. We can therefore not exclude the possibility that our findings on an interaction between non-OC use and smoking merely reflects that smoking women, who have an increased RA risk, do not receive OC prescription as often. The physiopathology of RA is complex and not fully understood, but our findings may contribute to the knowledge regarding mechanisms of importance for the development of RA,” the authors wrote.
The investigators also saw an influence of breastfeeding on the likelihood of developing RA, with a significant 23% lower odds for the disease among women who breastfed their children for 13 months or more and 7% lower odds in women who had breastfed their children for 7-12 months, compared with those who had breastfed for 0-6 months. Once again, this effect was only significant for ACPA-positive RA.
The study was supported by the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, King Gustav V’s 80-Year Foundation, Vinnova, the Swedish Foundation for Strategic Research, the Swedish Rheumatic Foundation, the Stockholm County Council, the Insurance Company AFA, the Innovative Medicines Initiative, and the National Institutes of Health. The authors said that they had no competing interests.
The use of oral contraceptives may be associated with a reduced risk of rheumatoid arthritis based on findings from a large, population-based, case-control study in Sweden.
The lowered risk for rheumatoid arthritis in the study conducted by Cecilia Orellana, PhD, of the Institute of Environmental Medicine at the Karolinska Institute, Stockholm, and her coauthors applied only to patients who tested positive for anticitrullinated protein antibodies (ACPA) and to those who used oral contraceptives for 7 or more years. The investigators also found a significant reduction in RA risk for women who breastfed their children.
“All of these findings together support the notion of RA as two different disease entities with different risk factors patterns,” the authors wrote.
The researchers looked at 2,578 women with RA and 4,129 female controls from the Swedish Epidemiological Investigation of RA study and found that women who had ever used OCs had 13% lower odds of developing RA than did women who had never used OCs, even after adjusting for age, residential area, smoking, and alcohol consumption. However, this association was significant only for ACPA-positive RA – where the risk was 16% lower – and not for ACPA-negative disease (Ann Rheum Dis. 2017 Aug 17. doi: 10.1136/annrheumdis-2017-211620).
Duration of oral contraceptive use was also positively associated with a decreased risk of RA; women who had taken OCs for 7 or more years had a 19% lower risk of RA, compared with never users.
However, the authors noted that they only collected information on the use of OCs as a whole and not on particular preparations or doses.
Women who had never used OCs and who had also smoked had more than twofold higher odds of developing RA than did women who had used OCs and who had never smoked. Women who had used OCs but who also smoked were 71% more likely to develop RA.
“Since both smoking and the use of OC have been linked to an increased predisposition to venous thrombotic events (VTE), women with a history of VTEs (especially if they smoke) might be recommended not to use OC by their physician. We can therefore not exclude the possibility that our findings on an interaction between non-OC use and smoking merely reflects that smoking women, who have an increased RA risk, do not receive OC prescription as often. The physiopathology of RA is complex and not fully understood, but our findings may contribute to the knowledge regarding mechanisms of importance for the development of RA,” the authors wrote.
The investigators also saw an influence of breastfeeding on the likelihood of developing RA, with a significant 23% lower odds for the disease among women who breastfed their children for 13 months or more and 7% lower odds in women who had breastfed their children for 7-12 months, compared with those who had breastfed for 0-6 months. Once again, this effect was only significant for ACPA-positive RA.
The study was supported by the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, King Gustav V’s 80-Year Foundation, Vinnova, the Swedish Foundation for Strategic Research, the Swedish Rheumatic Foundation, the Stockholm County Council, the Insurance Company AFA, the Innovative Medicines Initiative, and the National Institutes of Health. The authors said that they had no competing interests.
The use of oral contraceptives may be associated with a reduced risk of rheumatoid arthritis based on findings from a large, population-based, case-control study in Sweden.
The lowered risk for rheumatoid arthritis in the study conducted by Cecilia Orellana, PhD, of the Institute of Environmental Medicine at the Karolinska Institute, Stockholm, and her coauthors applied only to patients who tested positive for anticitrullinated protein antibodies (ACPA) and to those who used oral contraceptives for 7 or more years. The investigators also found a significant reduction in RA risk for women who breastfed their children.
“All of these findings together support the notion of RA as two different disease entities with different risk factors patterns,” the authors wrote.
The researchers looked at 2,578 women with RA and 4,129 female controls from the Swedish Epidemiological Investigation of RA study and found that women who had ever used OCs had 13% lower odds of developing RA than did women who had never used OCs, even after adjusting for age, residential area, smoking, and alcohol consumption. However, this association was significant only for ACPA-positive RA – where the risk was 16% lower – and not for ACPA-negative disease (Ann Rheum Dis. 2017 Aug 17. doi: 10.1136/annrheumdis-2017-211620).
Duration of oral contraceptive use was also positively associated with a decreased risk of RA; women who had taken OCs for 7 or more years had a 19% lower risk of RA, compared with never users.
However, the authors noted that they only collected information on the use of OCs as a whole and not on particular preparations or doses.
Women who had never used OCs and who had also smoked had more than twofold higher odds of developing RA than did women who had used OCs and who had never smoked. Women who had used OCs but who also smoked were 71% more likely to develop RA.
“Since both smoking and the use of OC have been linked to an increased predisposition to venous thrombotic events (VTE), women with a history of VTEs (especially if they smoke) might be recommended not to use OC by their physician. We can therefore not exclude the possibility that our findings on an interaction between non-OC use and smoking merely reflects that smoking women, who have an increased RA risk, do not receive OC prescription as often. The physiopathology of RA is complex and not fully understood, but our findings may contribute to the knowledge regarding mechanisms of importance for the development of RA,” the authors wrote.
The investigators also saw an influence of breastfeeding on the likelihood of developing RA, with a significant 23% lower odds for the disease among women who breastfed their children for 13 months or more and 7% lower odds in women who had breastfed their children for 7-12 months, compared with those who had breastfed for 0-6 months. Once again, this effect was only significant for ACPA-positive RA.
The study was supported by the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, King Gustav V’s 80-Year Foundation, Vinnova, the Swedish Foundation for Strategic Research, the Swedish Rheumatic Foundation, the Stockholm County Council, the Insurance Company AFA, the Innovative Medicines Initiative, and the National Institutes of Health. The authors said that they had no competing interests.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: The odds of ACPA-positive rheumatoid arthritis were 16% lower in women who had ever used oral contraceptives.
Data source: A population-based, case-control study in 2,578 women with rheumatoid arthritis and 4,129 female controls.
Disclosures: The study was supported by the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, King Gustav V’s 80-Year Foundation, Vinnova, the Swedish Foundation for Strategic Research, the Swedish Rheumatic Foundation, the Stockholm County Council, the Insurance Company AFA, the Innovative Medicines Initiative, and the National Institutes of Health. The authors said that they had no competing interests.
FDA committee rejects sirukumab approval on safety concerns
Citing safety concerns, the Food and Drug Administration’s Arthritis Advisory Committee voted overwhelmingly against recommending FDA approval of the interleukin-6 inhibitor sirukumab for refractory rheumatoid arthritis.
Janssen Biotech submitted a biologics license application (BLA) for the monoclonal antibody, seeking an indication for adults with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response or intolerance to one or more prior disease-modifying antirheumatic drugs, but despite agreeing unanimously that the data presented by the applicant provided substantial evidence of efficacy for this indication, the committee voted 12-1 against approval at an Aug. 2 meeting.
“I’m not sure whether the safety signal is of concern or not. I don’t think there’s enough data here to know that. It’s concerning, and it may be just noise, but it may also be real and I’m not willing to ... be supportive of the notion that it’s safe enough to take its place along with other biologicals,” said temporary voting member David T. Felson, MD, professor of medicine and public health at Boston University.
Similarly, temporary voting member Erica Brittain, PhD, said the mortality concerns swayed her vote.
“It was a very close call for me. I do think there’s a real argument to be made about bias in the analysis that shows some possibility of a difference. On the other hand, I just couldn’t get past the uncertainty, and when we’re talking about mortality it’s hard to dismiss that,” said Dr. Brittain, a mathematical statistician and deputy chief of the Biostatistics Research Branch at the National Institute of Allergy and Infectious Diseases.
Michael H. Weisman, MD, also a temporary voting member and chair of rheumatology at Cedars-Sinai Medical Center in Los Angeles, said that if the indication had been narrowed – perhaps to those who showed a biologic response – he would have voted “yes.”
Temporary voting member James Katz, MD, was the only committee member to vote in favor of approval.
“I actually voted yes because this drug doesn’t scare me any more than all the other drugs I use. I’m very scared by all the biological agents, and this is no different,” said Dr. Katz, director of the Rheumatology Fellowship and Training Branch at the National Institute of Arthritis and Musculoskeletal Diseases.
Sirukumab differs from two other approved monoclonal antibodies that target the IL-6 pathway for the treatment of patients with RA – tocilizumab (Actemra) and sarilumab (Kevzara) – in that it targets IL-6, while the others target the IL-6 receptor. This slight difference could make a difference for some highly refractory patients who had failed to respond to prior treatments, according to applicant presentations at the meeting.
The efficacy and safety of the agent were assessed in a phase 2 dose-ranging study, as well in three pivotal phase 3 studies. Two of the phase 3 studies compared 100 mg twice weekly and 50 mg four times weekly doses of subcutaneous sirukumab to placebo – which were shown to have similar efficacy for reducing the signs and symptoms of RA – and a third compared those two doses against adalimumab (Humira) and showed that it was not superior to adalimumab for efficacy.
One phase 3 placebo-controlled study involving 878 refractory patients was published in February in The Lancet and showed that sirukumab was associated with rapid and sustained improvements in RA signs and symptoms, physical function, and health status, as well as improvement in physical and mental well-being.
However, a safety signal – a trend of increased overall mortality with sirukumab vs. placebo – emerged from the studies. The mortality was mainly associated with major adverse cardiovascular events, infection, and malignancy.
Three speakers, including RA patients or patient representatives, participated in the open public hearing portion of the committee meeting, and all spoke in favor of approval of sirukumab, but ultimately the committee agreed that the limited benefits of the agent – given that it does not involve an entirely new mechanism of action – did not outweigh the unknowns regarding safety.
Committee chairperson Daniel H. Solomon, MD, professor of medicine at Harvard Medical School and chief of the section of clinical sciences at Brigham and Women’s Hospital, both in Boston, said longer-term outcomes data with a clear comparator are needed.
The FDA will now consider the committee’s recommendations in making its final determination regarding the BLA.
All voting advisory committee members were screened and cleared with respect to potential conflicts of interest.
Citing safety concerns, the Food and Drug Administration’s Arthritis Advisory Committee voted overwhelmingly against recommending FDA approval of the interleukin-6 inhibitor sirukumab for refractory rheumatoid arthritis.
Janssen Biotech submitted a biologics license application (BLA) for the monoclonal antibody, seeking an indication for adults with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response or intolerance to one or more prior disease-modifying antirheumatic drugs, but despite agreeing unanimously that the data presented by the applicant provided substantial evidence of efficacy for this indication, the committee voted 12-1 against approval at an Aug. 2 meeting.
“I’m not sure whether the safety signal is of concern or not. I don’t think there’s enough data here to know that. It’s concerning, and it may be just noise, but it may also be real and I’m not willing to ... be supportive of the notion that it’s safe enough to take its place along with other biologicals,” said temporary voting member David T. Felson, MD, professor of medicine and public health at Boston University.
Similarly, temporary voting member Erica Brittain, PhD, said the mortality concerns swayed her vote.
“It was a very close call for me. I do think there’s a real argument to be made about bias in the analysis that shows some possibility of a difference. On the other hand, I just couldn’t get past the uncertainty, and when we’re talking about mortality it’s hard to dismiss that,” said Dr. Brittain, a mathematical statistician and deputy chief of the Biostatistics Research Branch at the National Institute of Allergy and Infectious Diseases.
Michael H. Weisman, MD, also a temporary voting member and chair of rheumatology at Cedars-Sinai Medical Center in Los Angeles, said that if the indication had been narrowed – perhaps to those who showed a biologic response – he would have voted “yes.”
Temporary voting member James Katz, MD, was the only committee member to vote in favor of approval.
“I actually voted yes because this drug doesn’t scare me any more than all the other drugs I use. I’m very scared by all the biological agents, and this is no different,” said Dr. Katz, director of the Rheumatology Fellowship and Training Branch at the National Institute of Arthritis and Musculoskeletal Diseases.
Sirukumab differs from two other approved monoclonal antibodies that target the IL-6 pathway for the treatment of patients with RA – tocilizumab (Actemra) and sarilumab (Kevzara) – in that it targets IL-6, while the others target the IL-6 receptor. This slight difference could make a difference for some highly refractory patients who had failed to respond to prior treatments, according to applicant presentations at the meeting.
The efficacy and safety of the agent were assessed in a phase 2 dose-ranging study, as well in three pivotal phase 3 studies. Two of the phase 3 studies compared 100 mg twice weekly and 50 mg four times weekly doses of subcutaneous sirukumab to placebo – which were shown to have similar efficacy for reducing the signs and symptoms of RA – and a third compared those two doses against adalimumab (Humira) and showed that it was not superior to adalimumab for efficacy.
One phase 3 placebo-controlled study involving 878 refractory patients was published in February in The Lancet and showed that sirukumab was associated with rapid and sustained improvements in RA signs and symptoms, physical function, and health status, as well as improvement in physical and mental well-being.
However, a safety signal – a trend of increased overall mortality with sirukumab vs. placebo – emerged from the studies. The mortality was mainly associated with major adverse cardiovascular events, infection, and malignancy.
Three speakers, including RA patients or patient representatives, participated in the open public hearing portion of the committee meeting, and all spoke in favor of approval of sirukumab, but ultimately the committee agreed that the limited benefits of the agent – given that it does not involve an entirely new mechanism of action – did not outweigh the unknowns regarding safety.
Committee chairperson Daniel H. Solomon, MD, professor of medicine at Harvard Medical School and chief of the section of clinical sciences at Brigham and Women’s Hospital, both in Boston, said longer-term outcomes data with a clear comparator are needed.
The FDA will now consider the committee’s recommendations in making its final determination regarding the BLA.
All voting advisory committee members were screened and cleared with respect to potential conflicts of interest.
Citing safety concerns, the Food and Drug Administration’s Arthritis Advisory Committee voted overwhelmingly against recommending FDA approval of the interleukin-6 inhibitor sirukumab for refractory rheumatoid arthritis.
Janssen Biotech submitted a biologics license application (BLA) for the monoclonal antibody, seeking an indication for adults with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response or intolerance to one or more prior disease-modifying antirheumatic drugs, but despite agreeing unanimously that the data presented by the applicant provided substantial evidence of efficacy for this indication, the committee voted 12-1 against approval at an Aug. 2 meeting.
“I’m not sure whether the safety signal is of concern or not. I don’t think there’s enough data here to know that. It’s concerning, and it may be just noise, but it may also be real and I’m not willing to ... be supportive of the notion that it’s safe enough to take its place along with other biologicals,” said temporary voting member David T. Felson, MD, professor of medicine and public health at Boston University.
Similarly, temporary voting member Erica Brittain, PhD, said the mortality concerns swayed her vote.
“It was a very close call for me. I do think there’s a real argument to be made about bias in the analysis that shows some possibility of a difference. On the other hand, I just couldn’t get past the uncertainty, and when we’re talking about mortality it’s hard to dismiss that,” said Dr. Brittain, a mathematical statistician and deputy chief of the Biostatistics Research Branch at the National Institute of Allergy and Infectious Diseases.
Michael H. Weisman, MD, also a temporary voting member and chair of rheumatology at Cedars-Sinai Medical Center in Los Angeles, said that if the indication had been narrowed – perhaps to those who showed a biologic response – he would have voted “yes.”
Temporary voting member James Katz, MD, was the only committee member to vote in favor of approval.
“I actually voted yes because this drug doesn’t scare me any more than all the other drugs I use. I’m very scared by all the biological agents, and this is no different,” said Dr. Katz, director of the Rheumatology Fellowship and Training Branch at the National Institute of Arthritis and Musculoskeletal Diseases.
Sirukumab differs from two other approved monoclonal antibodies that target the IL-6 pathway for the treatment of patients with RA – tocilizumab (Actemra) and sarilumab (Kevzara) – in that it targets IL-6, while the others target the IL-6 receptor. This slight difference could make a difference for some highly refractory patients who had failed to respond to prior treatments, according to applicant presentations at the meeting.
The efficacy and safety of the agent were assessed in a phase 2 dose-ranging study, as well in three pivotal phase 3 studies. Two of the phase 3 studies compared 100 mg twice weekly and 50 mg four times weekly doses of subcutaneous sirukumab to placebo – which were shown to have similar efficacy for reducing the signs and symptoms of RA – and a third compared those two doses against adalimumab (Humira) and showed that it was not superior to adalimumab for efficacy.
One phase 3 placebo-controlled study involving 878 refractory patients was published in February in The Lancet and showed that sirukumab was associated with rapid and sustained improvements in RA signs and symptoms, physical function, and health status, as well as improvement in physical and mental well-being.
However, a safety signal – a trend of increased overall mortality with sirukumab vs. placebo – emerged from the studies. The mortality was mainly associated with major adverse cardiovascular events, infection, and malignancy.
Three speakers, including RA patients or patient representatives, participated in the open public hearing portion of the committee meeting, and all spoke in favor of approval of sirukumab, but ultimately the committee agreed that the limited benefits of the agent – given that it does not involve an entirely new mechanism of action – did not outweigh the unknowns regarding safety.
Committee chairperson Daniel H. Solomon, MD, professor of medicine at Harvard Medical School and chief of the section of clinical sciences at Brigham and Women’s Hospital, both in Boston, said longer-term outcomes data with a clear comparator are needed.
The FDA will now consider the committee’s recommendations in making its final determination regarding the BLA.
All voting advisory committee members were screened and cleared with respect to potential conflicts of interest.
First interchangeability study for an adalimumab biosimilar has begun
The VOLTAIRE-X study of a biosimilar candidate for adalimumab (Humira) for chronic plaque psoriasis has enrolled its first patient, announced Boehringer Ingelheim, the biosimilar’s developer, on July 27.
This is the first study in the United States to investigate whether a biosimilar candidate should be granted an interchangeability designation with adalimumab. The candidate, BI 695501, is up against adalimumab’s 40-mg injection.
In VOLTAIRE-X, some patients will alternate between adalimumab and BI 695501, and others will take adalimumab continuously. The study will compare the pharmacokinetics, clinical outcomes, safety, immunogenicity, and efficacy between the two groups of patients. The estimated enrollment of adult patients with moderate to severe chronic plaque psoriasis is 240, and the study is expected to conclude in July 2019.
A phase 3 study of BI 695501’s performance for rheumatoid arthritis patients, completed in 2016, demonstrated similar efficacy, safety, and immunogenicity.
The VOLTAIRE-X study of a biosimilar candidate for adalimumab (Humira) for chronic plaque psoriasis has enrolled its first patient, announced Boehringer Ingelheim, the biosimilar’s developer, on July 27.
This is the first study in the United States to investigate whether a biosimilar candidate should be granted an interchangeability designation with adalimumab. The candidate, BI 695501, is up against adalimumab’s 40-mg injection.
In VOLTAIRE-X, some patients will alternate between adalimumab and BI 695501, and others will take adalimumab continuously. The study will compare the pharmacokinetics, clinical outcomes, safety, immunogenicity, and efficacy between the two groups of patients. The estimated enrollment of adult patients with moderate to severe chronic plaque psoriasis is 240, and the study is expected to conclude in July 2019.
A phase 3 study of BI 695501’s performance for rheumatoid arthritis patients, completed in 2016, demonstrated similar efficacy, safety, and immunogenicity.
The VOLTAIRE-X study of a biosimilar candidate for adalimumab (Humira) for chronic plaque psoriasis has enrolled its first patient, announced Boehringer Ingelheim, the biosimilar’s developer, on July 27.
This is the first study in the United States to investigate whether a biosimilar candidate should be granted an interchangeability designation with adalimumab. The candidate, BI 695501, is up against adalimumab’s 40-mg injection.
In VOLTAIRE-X, some patients will alternate between adalimumab and BI 695501, and others will take adalimumab continuously. The study will compare the pharmacokinetics, clinical outcomes, safety, immunogenicity, and efficacy between the two groups of patients. The estimated enrollment of adult patients with moderate to severe chronic plaque psoriasis is 240, and the study is expected to conclude in July 2019.
A phase 3 study of BI 695501’s performance for rheumatoid arthritis patients, completed in 2016, demonstrated similar efficacy, safety, and immunogenicity.
Attitudes and beliefs affecting methotrexate adherence identified
MADRID – Negative beliefs and uncertainty regarding treatment with methotrexate, as well as dislike for the drug, contribute the most to rheumatoid arthritis patients’ nonadherence to the therapy, with one study finding that about one-third were nonadherent at the time they were eligible to start biologic therapy.
The French cross-sectional survey of 244 patients who were not responding to methotrexate found that 34% actually had poor adherence, including 54% who skipped doses and 38% who temporarily stopped treatment without their doctors’ recommendation. In comparison, patients who were deemed adherent had a lower rate of skipping doses (15%) or temporarily stopped treatment without their doctors’ recommendation (4%), both of which were statistically significant differences, Catherine Beauvais, MD, reported at the European Congress of Rheumatology. Nonadherence was defined as taking less than 80% of doses, according to the CQR19 (Compliance Questionnaire for Rheumatology).
“We have identified profiles of adherence,” Dr. Beauvais of Saint-Antoine Hospital in Paris commented in an interview.
“Among nonadherent patients, there are two profiles,” she added. “We have patients who are not responding to methotrexate but they also have negative beliefs, low levels of support, and they have professional impairment. [Then,] there are patients who do not like their treatment [although it is being well tolerated].”
The other profiles identified were of patients with good adherence to methotrexate with a higher or lower impact on patient outcomes.
In a poster presentation, Dr. Beauvais and her coauthors suggested that the “detection of patients’ profiles may allow targeted strategies to improve or maintain adherence.”
The FORGET survey was conducted over a 3-month period starting in July 2016. A total of 78 rheumatologists recruited patients who were inadequately responding to methotrexate and, thus, eligible to start biologic treatment for rheumatoid arthritis. Both the rheumatologists and the patients completed questionnaires, with 200 questionnaires being completed by patients and their rheumatologist.
As might be suspected for an RA population, 72% of respondents were women, with a mean age of 54 years. Over half (58%) had at least one comorbidity, and the mean disease activity score in 28 joints at the time of the survey was 4.07.
Significant factors for nonadherence were feeling constrained about taking treatment, cited by 29% of respondents; feeling “less good” with a change in dosage (31%); and feeling that treatment was “doing me more harm than good” (19% of respondents).
Surprisingly, most rheumatologists seemed to be unaware of their patients’ lack of adherence to their medication, despite saying that they asked about adherence in more than 80% of their patients.
Rheumatologists proposed the addition of a biologic to methotrexate more often if patients were nonadherent than if patients showed good compliance (91% vs. 68%; P less than .01).
Effect of patient attitudes on compliance
A team of U.K. researchers evaluated how attitudes toward treatment with methotrexate affected patients’ compliance in a separate poster presentation at the meeting.
RAMS is a 1-year observational study of patients with RA who are starting treatment with methotrexate. Patients recruited into the study completed weekly diaries, noting whether they took methotrexate (adherence) and, if not, their reasons for not doing so. Patients were deemed nonadherent if they did not take methotrexate correctly for 90% of the time over a period of 6 months.
Lower adherence was significantly associated with negative or uncertain views about treatment, with an odds ratio of 2.7. Conversely, being positive or certain about treatment lowered patients’ odds of being nonadherent (OR, 0.32).
“People who are uncertain about how to attribute illness events are less likely to adhere within the first 6 months of starting methotrexate therapy,” Ms. Hope and her coauthors observed.
“Encouraging patients to actively monitor their progress with therapy and providing them with support to understand likely effects of methotrexate may help optimize disease-modifying antirheumatic drug use,” they concluded.
Ms. Hope and Dr. Beauvais had no conflicts of interest to disclose. The FORGET survey was funded by Chugai Pharma France.
MADRID – Negative beliefs and uncertainty regarding treatment with methotrexate, as well as dislike for the drug, contribute the most to rheumatoid arthritis patients’ nonadherence to the therapy, with one study finding that about one-third were nonadherent at the time they were eligible to start biologic therapy.
The French cross-sectional survey of 244 patients who were not responding to methotrexate found that 34% actually had poor adherence, including 54% who skipped doses and 38% who temporarily stopped treatment without their doctors’ recommendation. In comparison, patients who were deemed adherent had a lower rate of skipping doses (15%) or temporarily stopped treatment without their doctors’ recommendation (4%), both of which were statistically significant differences, Catherine Beauvais, MD, reported at the European Congress of Rheumatology. Nonadherence was defined as taking less than 80% of doses, according to the CQR19 (Compliance Questionnaire for Rheumatology).
“We have identified profiles of adherence,” Dr. Beauvais of Saint-Antoine Hospital in Paris commented in an interview.
“Among nonadherent patients, there are two profiles,” she added. “We have patients who are not responding to methotrexate but they also have negative beliefs, low levels of support, and they have professional impairment. [Then,] there are patients who do not like their treatment [although it is being well tolerated].”
The other profiles identified were of patients with good adherence to methotrexate with a higher or lower impact on patient outcomes.
In a poster presentation, Dr. Beauvais and her coauthors suggested that the “detection of patients’ profiles may allow targeted strategies to improve or maintain adherence.”
The FORGET survey was conducted over a 3-month period starting in July 2016. A total of 78 rheumatologists recruited patients who were inadequately responding to methotrexate and, thus, eligible to start biologic treatment for rheumatoid arthritis. Both the rheumatologists and the patients completed questionnaires, with 200 questionnaires being completed by patients and their rheumatologist.
As might be suspected for an RA population, 72% of respondents were women, with a mean age of 54 years. Over half (58%) had at least one comorbidity, and the mean disease activity score in 28 joints at the time of the survey was 4.07.
Significant factors for nonadherence were feeling constrained about taking treatment, cited by 29% of respondents; feeling “less good” with a change in dosage (31%); and feeling that treatment was “doing me more harm than good” (19% of respondents).
Surprisingly, most rheumatologists seemed to be unaware of their patients’ lack of adherence to their medication, despite saying that they asked about adherence in more than 80% of their patients.
Rheumatologists proposed the addition of a biologic to methotrexate more often if patients were nonadherent than if patients showed good compliance (91% vs. 68%; P less than .01).
Effect of patient attitudes on compliance
A team of U.K. researchers evaluated how attitudes toward treatment with methotrexate affected patients’ compliance in a separate poster presentation at the meeting.
RAMS is a 1-year observational study of patients with RA who are starting treatment with methotrexate. Patients recruited into the study completed weekly diaries, noting whether they took methotrexate (adherence) and, if not, their reasons for not doing so. Patients were deemed nonadherent if they did not take methotrexate correctly for 90% of the time over a period of 6 months.
Lower adherence was significantly associated with negative or uncertain views about treatment, with an odds ratio of 2.7. Conversely, being positive or certain about treatment lowered patients’ odds of being nonadherent (OR, 0.32).
“People who are uncertain about how to attribute illness events are less likely to adhere within the first 6 months of starting methotrexate therapy,” Ms. Hope and her coauthors observed.
“Encouraging patients to actively monitor their progress with therapy and providing them with support to understand likely effects of methotrexate may help optimize disease-modifying antirheumatic drug use,” they concluded.
Ms. Hope and Dr. Beauvais had no conflicts of interest to disclose. The FORGET survey was funded by Chugai Pharma France.
MADRID – Negative beliefs and uncertainty regarding treatment with methotrexate, as well as dislike for the drug, contribute the most to rheumatoid arthritis patients’ nonadherence to the therapy, with one study finding that about one-third were nonadherent at the time they were eligible to start biologic therapy.
The French cross-sectional survey of 244 patients who were not responding to methotrexate found that 34% actually had poor adherence, including 54% who skipped doses and 38% who temporarily stopped treatment without their doctors’ recommendation. In comparison, patients who were deemed adherent had a lower rate of skipping doses (15%) or temporarily stopped treatment without their doctors’ recommendation (4%), both of which were statistically significant differences, Catherine Beauvais, MD, reported at the European Congress of Rheumatology. Nonadherence was defined as taking less than 80% of doses, according to the CQR19 (Compliance Questionnaire for Rheumatology).
“We have identified profiles of adherence,” Dr. Beauvais of Saint-Antoine Hospital in Paris commented in an interview.
“Among nonadherent patients, there are two profiles,” she added. “We have patients who are not responding to methotrexate but they also have negative beliefs, low levels of support, and they have professional impairment. [Then,] there are patients who do not like their treatment [although it is being well tolerated].”
The other profiles identified were of patients with good adherence to methotrexate with a higher or lower impact on patient outcomes.
In a poster presentation, Dr. Beauvais and her coauthors suggested that the “detection of patients’ profiles may allow targeted strategies to improve or maintain adherence.”
The FORGET survey was conducted over a 3-month period starting in July 2016. A total of 78 rheumatologists recruited patients who were inadequately responding to methotrexate and, thus, eligible to start biologic treatment for rheumatoid arthritis. Both the rheumatologists and the patients completed questionnaires, with 200 questionnaires being completed by patients and their rheumatologist.
As might be suspected for an RA population, 72% of respondents were women, with a mean age of 54 years. Over half (58%) had at least one comorbidity, and the mean disease activity score in 28 joints at the time of the survey was 4.07.
Significant factors for nonadherence were feeling constrained about taking treatment, cited by 29% of respondents; feeling “less good” with a change in dosage (31%); and feeling that treatment was “doing me more harm than good” (19% of respondents).
Surprisingly, most rheumatologists seemed to be unaware of their patients’ lack of adherence to their medication, despite saying that they asked about adherence in more than 80% of their patients.
Rheumatologists proposed the addition of a biologic to methotrexate more often if patients were nonadherent than if patients showed good compliance (91% vs. 68%; P less than .01).
Effect of patient attitudes on compliance
A team of U.K. researchers evaluated how attitudes toward treatment with methotrexate affected patients’ compliance in a separate poster presentation at the meeting.
RAMS is a 1-year observational study of patients with RA who are starting treatment with methotrexate. Patients recruited into the study completed weekly diaries, noting whether they took methotrexate (adherence) and, if not, their reasons for not doing so. Patients were deemed nonadherent if they did not take methotrexate correctly for 90% of the time over a period of 6 months.
Lower adherence was significantly associated with negative or uncertain views about treatment, with an odds ratio of 2.7. Conversely, being positive or certain about treatment lowered patients’ odds of being nonadherent (OR, 0.32).
“People who are uncertain about how to attribute illness events are less likely to adhere within the first 6 months of starting methotrexate therapy,” Ms. Hope and her coauthors observed.
“Encouraging patients to actively monitor their progress with therapy and providing them with support to understand likely effects of methotrexate may help optimize disease-modifying antirheumatic drug use,” they concluded.
Ms. Hope and Dr. Beauvais had no conflicts of interest to disclose. The FORGET survey was funded by Chugai Pharma France.
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: One-third (34%) of RA patients were nonadherent to methotrexate at the initiation of biologic therapy; having negative and uncertain beliefs about the effects of treatment increased the odds of nonadherence.
Data source: The cross-sectional FORGET survey of 78 rheumatologists and 269 patients with rheumatoid arthritis conducted in France and the Rheumatoid Arthritis Medications Study (RAMS) of 200 adherent and nonadherent patients.
Disclosures: The authors had no conflicts of interest to disclose. The FORGET survey was funded by Chugai Pharma France.
Selection of strategy for high-risk early RA remission induction hinges on safety
MADRID – Two-year results from the Care in early RA (CareRA) trial demonstrated the sustained effectiveness of a treat-to-target approach in patients with early rheumatoid arthritis at high risk for progression.
The percentage of patients who achieved clinical remission with one of three disease-modifying antirheumatic drug (DMARD) and glucocorticoid-containing regimens ranged from 60% to 65% at 1 year, and the percentage of those patients who were able to maintain their remission at all time points in year 2 ranged from 55% to 70%, none of which were significantly different from each other.
Ms. Stouten added that, according to international guidelines, achieving clinical remission means treating patients early, as soon as possible after the diagnosis of rheumatoid arthritis is made; intensively, with a DMARD, preferably methotrexate if not contraindicated, combined with short-term glucocorticoids; and to target, meaning treatment should be targeted at achieving remission or at least low disease activity in every patient.
The CareRA trial was a prospective, randomized, multicenter trial set up to see which of three methotrexate-based, steroid-containing intensive regimens would be best for inducing remission in patients with high-risk RA. The pragmatic trial was conducted in 13 Belgian rheumatology practices recruiting 400 patients, 300 of whom were designated as high risk for progression based on factors such as their antibody status and presence of joint erosions. CareRA trial investigators defined clinical remission as less than 2.6 on the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP).
The three regimens all contained a weekly 15-mg dose of methotrexate and prednisone 30 mg or 60 mg that was then tapered weekly after the first 6-7 weeks.
In the COBRA Classic regimen, methotrexate was partnered with sulfasalazine, given as a 2-g daily dose. Prednisone was initially given at a dose of 60 mg and then taped to 5.7 mg starting at week 7.
For the COBRA Slim regimen, just methotrexate and prednisone were used, with the latter started at a dose of 30 mg and then tapered to 5 mg starting at week 6.
Lastly, the COBRA Avant-Garde regimen saw methotrexate combined with leflunomide, 10 mg daily, and the same step-down prednisone regimen as COBRA Slim.
In the first year, treatment in each group was adjusted to achieve a target of low disease activity (DAS28-CRP of 3.2 or lower), with measurements taken every 3 months. The steroid component was stepped down further after 28 weeks and stopped altogether by 34 weeks. The aim was also to reduce the number of DMARDs used, such that everyone was on DMARD monotherapy if possible. In the second year, rheumatologists could treat patients at their own discretion, with adjustments to treatment made according to DAS28-CRP at visits every 3 months.
Ms. Stouten reported that all three of the intensive induction regimens “were very effective in our high-risk population and that they showed persistently high remission rates at year 2.”
The percentage of patients with a DAS28-CRP of less than 2.6 at 2 years was 65.3% for the COBRA Classic regimen, 73.5% for COBRA Slim, and 73.1% for COBRA Avant-Garde.
For inducing remission, however, she suggested that the COBRA Slim regimen might have the edge from a benefit-to-risk perspective.
A total of 60.2% of COBRA Slim patients were in remission at year 1, and 67.8% of them remained in remission throughout year 2. Also, fewer COBRA Slim patients needed biologic therapy, both overall (n = 11) and in the first year (n = 2), when compared with the other two regimens. However, in the COBRA Classic arm, 65.3% were in remission at year 1, and 54.7% of those patients maintained it throughout year 2, whereas in the COBRA Avant-Garde arm the rates were 61.3% at year 1, with 70.2% of those maintaining remission throughout year 2. A total of 18 patients in the COBRA Classic group started biologics, including 10 in the first year, compared with 15 in the COBRA Avant-Garde group, 7 of those in the first year.
“For maintaining remission, there were no statistically significant differences observed in remission rates at year 2 between treatment groups,” Ms. Stouten observed. “However, COBRA Avant-Garde had numerically better CDAI [clinical disease activity index] remission rates at year 2 [48.2% vs. 33.7% for COBRA Slim and 34.7% for COBRA Classic; P = .068].”
The total numbers of patients reporting adverse events related to treatment were lower with the COBRA Slim regimen (n = 164) than with COBRA Classic (n = 209) and COBRA Avant-Garde (n = 208). Fewer COBRA Slim patients also had to stop treatment (5 vs. 9 with COBRA Classic and 12 with COBRA Avant-Garde) or have interrupted treatment (12 vs. 17 and 19, respectively) because of adverse events.
Ms. Stouten had no personal disclosures. The study was supported by a Flemish governmental grant provided by IWT (Innovatie door Wetenschap en Technologie).
rhnews@frontlinemedcom.com
On Twitter @rheumnews1
MADRID – Two-year results from the Care in early RA (CareRA) trial demonstrated the sustained effectiveness of a treat-to-target approach in patients with early rheumatoid arthritis at high risk for progression.
The percentage of patients who achieved clinical remission with one of three disease-modifying antirheumatic drug (DMARD) and glucocorticoid-containing regimens ranged from 60% to 65% at 1 year, and the percentage of those patients who were able to maintain their remission at all time points in year 2 ranged from 55% to 70%, none of which were significantly different from each other.
Ms. Stouten added that, according to international guidelines, achieving clinical remission means treating patients early, as soon as possible after the diagnosis of rheumatoid arthritis is made; intensively, with a DMARD, preferably methotrexate if not contraindicated, combined with short-term glucocorticoids; and to target, meaning treatment should be targeted at achieving remission or at least low disease activity in every patient.
The CareRA trial was a prospective, randomized, multicenter trial set up to see which of three methotrexate-based, steroid-containing intensive regimens would be best for inducing remission in patients with high-risk RA. The pragmatic trial was conducted in 13 Belgian rheumatology practices recruiting 400 patients, 300 of whom were designated as high risk for progression based on factors such as their antibody status and presence of joint erosions. CareRA trial investigators defined clinical remission as less than 2.6 on the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP).
The three regimens all contained a weekly 15-mg dose of methotrexate and prednisone 30 mg or 60 mg that was then tapered weekly after the first 6-7 weeks.
In the COBRA Classic regimen, methotrexate was partnered with sulfasalazine, given as a 2-g daily dose. Prednisone was initially given at a dose of 60 mg and then taped to 5.7 mg starting at week 7.
For the COBRA Slim regimen, just methotrexate and prednisone were used, with the latter started at a dose of 30 mg and then tapered to 5 mg starting at week 6.
Lastly, the COBRA Avant-Garde regimen saw methotrexate combined with leflunomide, 10 mg daily, and the same step-down prednisone regimen as COBRA Slim.
In the first year, treatment in each group was adjusted to achieve a target of low disease activity (DAS28-CRP of 3.2 or lower), with measurements taken every 3 months. The steroid component was stepped down further after 28 weeks and stopped altogether by 34 weeks. The aim was also to reduce the number of DMARDs used, such that everyone was on DMARD monotherapy if possible. In the second year, rheumatologists could treat patients at their own discretion, with adjustments to treatment made according to DAS28-CRP at visits every 3 months.
Ms. Stouten reported that all three of the intensive induction regimens “were very effective in our high-risk population and that they showed persistently high remission rates at year 2.”
The percentage of patients with a DAS28-CRP of less than 2.6 at 2 years was 65.3% for the COBRA Classic regimen, 73.5% for COBRA Slim, and 73.1% for COBRA Avant-Garde.
For inducing remission, however, she suggested that the COBRA Slim regimen might have the edge from a benefit-to-risk perspective.
A total of 60.2% of COBRA Slim patients were in remission at year 1, and 67.8% of them remained in remission throughout year 2. Also, fewer COBRA Slim patients needed biologic therapy, both overall (n = 11) and in the first year (n = 2), when compared with the other two regimens. However, in the COBRA Classic arm, 65.3% were in remission at year 1, and 54.7% of those patients maintained it throughout year 2, whereas in the COBRA Avant-Garde arm the rates were 61.3% at year 1, with 70.2% of those maintaining remission throughout year 2. A total of 18 patients in the COBRA Classic group started biologics, including 10 in the first year, compared with 15 in the COBRA Avant-Garde group, 7 of those in the first year.
“For maintaining remission, there were no statistically significant differences observed in remission rates at year 2 between treatment groups,” Ms. Stouten observed. “However, COBRA Avant-Garde had numerically better CDAI [clinical disease activity index] remission rates at year 2 [48.2% vs. 33.7% for COBRA Slim and 34.7% for COBRA Classic; P = .068].”
The total numbers of patients reporting adverse events related to treatment were lower with the COBRA Slim regimen (n = 164) than with COBRA Classic (n = 209) and COBRA Avant-Garde (n = 208). Fewer COBRA Slim patients also had to stop treatment (5 vs. 9 with COBRA Classic and 12 with COBRA Avant-Garde) or have interrupted treatment (12 vs. 17 and 19, respectively) because of adverse events.
Ms. Stouten had no personal disclosures. The study was supported by a Flemish governmental grant provided by IWT (Innovatie door Wetenschap en Technologie).
rhnews@frontlinemedcom.com
On Twitter @rheumnews1
MADRID – Two-year results from the Care in early RA (CareRA) trial demonstrated the sustained effectiveness of a treat-to-target approach in patients with early rheumatoid arthritis at high risk for progression.
The percentage of patients who achieved clinical remission with one of three disease-modifying antirheumatic drug (DMARD) and glucocorticoid-containing regimens ranged from 60% to 65% at 1 year, and the percentage of those patients who were able to maintain their remission at all time points in year 2 ranged from 55% to 70%, none of which were significantly different from each other.
Ms. Stouten added that, according to international guidelines, achieving clinical remission means treating patients early, as soon as possible after the diagnosis of rheumatoid arthritis is made; intensively, with a DMARD, preferably methotrexate if not contraindicated, combined with short-term glucocorticoids; and to target, meaning treatment should be targeted at achieving remission or at least low disease activity in every patient.
The CareRA trial was a prospective, randomized, multicenter trial set up to see which of three methotrexate-based, steroid-containing intensive regimens would be best for inducing remission in patients with high-risk RA. The pragmatic trial was conducted in 13 Belgian rheumatology practices recruiting 400 patients, 300 of whom were designated as high risk for progression based on factors such as their antibody status and presence of joint erosions. CareRA trial investigators defined clinical remission as less than 2.6 on the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP).
The three regimens all contained a weekly 15-mg dose of methotrexate and prednisone 30 mg or 60 mg that was then tapered weekly after the first 6-7 weeks.
In the COBRA Classic regimen, methotrexate was partnered with sulfasalazine, given as a 2-g daily dose. Prednisone was initially given at a dose of 60 mg and then taped to 5.7 mg starting at week 7.
For the COBRA Slim regimen, just methotrexate and prednisone were used, with the latter started at a dose of 30 mg and then tapered to 5 mg starting at week 6.
Lastly, the COBRA Avant-Garde regimen saw methotrexate combined with leflunomide, 10 mg daily, and the same step-down prednisone regimen as COBRA Slim.
In the first year, treatment in each group was adjusted to achieve a target of low disease activity (DAS28-CRP of 3.2 or lower), with measurements taken every 3 months. The steroid component was stepped down further after 28 weeks and stopped altogether by 34 weeks. The aim was also to reduce the number of DMARDs used, such that everyone was on DMARD monotherapy if possible. In the second year, rheumatologists could treat patients at their own discretion, with adjustments to treatment made according to DAS28-CRP at visits every 3 months.
Ms. Stouten reported that all three of the intensive induction regimens “were very effective in our high-risk population and that they showed persistently high remission rates at year 2.”
The percentage of patients with a DAS28-CRP of less than 2.6 at 2 years was 65.3% for the COBRA Classic regimen, 73.5% for COBRA Slim, and 73.1% for COBRA Avant-Garde.
For inducing remission, however, she suggested that the COBRA Slim regimen might have the edge from a benefit-to-risk perspective.
A total of 60.2% of COBRA Slim patients were in remission at year 1, and 67.8% of them remained in remission throughout year 2. Also, fewer COBRA Slim patients needed biologic therapy, both overall (n = 11) and in the first year (n = 2), when compared with the other two regimens. However, in the COBRA Classic arm, 65.3% were in remission at year 1, and 54.7% of those patients maintained it throughout year 2, whereas in the COBRA Avant-Garde arm the rates were 61.3% at year 1, with 70.2% of those maintaining remission throughout year 2. A total of 18 patients in the COBRA Classic group started biologics, including 10 in the first year, compared with 15 in the COBRA Avant-Garde group, 7 of those in the first year.
“For maintaining remission, there were no statistically significant differences observed in remission rates at year 2 between treatment groups,” Ms. Stouten observed. “However, COBRA Avant-Garde had numerically better CDAI [clinical disease activity index] remission rates at year 2 [48.2% vs. 33.7% for COBRA Slim and 34.7% for COBRA Classic; P = .068].”
The total numbers of patients reporting adverse events related to treatment were lower with the COBRA Slim regimen (n = 164) than with COBRA Classic (n = 209) and COBRA Avant-Garde (n = 208). Fewer COBRA Slim patients also had to stop treatment (5 vs. 9 with COBRA Classic and 12 with COBRA Avant-Garde) or have interrupted treatment (12 vs. 17 and 19, respectively) because of adverse events.
Ms. Stouten had no personal disclosures. The study was supported by a Flemish governmental grant provided by IWT (Innovatie door Wetenschap en Technologie).
rhnews@frontlinemedcom.com
On Twitter @rheumnews1
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: The percentage of patients with a DAS28-CRP of less than 2.6 at 2 years was 73.5% for the COBRA Slim regimen, 73.1% for COBRA Avant-Garde, and 65.3% for COBRA Classic.
Data source: The Care in early RA (CareRA) trial, a prospective, randomized, multicenter trial of 379 patients with treatment-naive, early rheumatoid arthritis.
Disclosures: The presenter had no personal disclosures. The study was supported by a Flemish governmental grant provided by IWT (Innovatie door Wetenschap en Technologie).
Studies examine methotrexate starting dose for RA in monotherapy and combinations
MADRID – A low versus high starting dose of methotrexate given as monotherapy or in combination with glucocorticoids or conventional synthetic disease-modifying antirheumatic drugs to newly diagnosed rheumatoid arthritis patients doesn’t seem to make a difference in short-term disease activity and physical functioning responses, but a higher starting dose of at least 15 mg/week may provide a better chance at achieving a good response at 6 months, according to two separate observational studies presented at the European Congress of Rheumatology.
One of the studies looked at 3- to 6-month disease activity and physical functioning responses to methotrexate used as mono- or combination therapy and the other assessed EULAR clinical responses at 6 months in mostly monotherapy-treated patients.
Low vs. high dose in combination treatments
“Methotrexate is the anchor drug in the treatment of rheumatoid arthritis patients. Current guidelines for methotrexate monotherapy recommend initiating 15 mg/week orally then escalating to 25-30 mg/week or the highest tolerable dose, but no recommendations exist for the drug’s use in combination therapy,” said Sytske Anne Bergstra, first author of a study using the international, observational METEOR database, a cohort with real-world clinical data.
The investigators selected 1,404 RA patients from the METEOR database who had a symptom duration of less than 5 years, had less than 2 months between diagnosis and first visit, and did not change medications (only dose adjustments were allowed). They were divided into three groups: methotrexate monotherapy, methotrexate plus conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and methotrexate plus glucocorticoids (and possibly csDMARDs). The investigators defined initial starting doses of methotrexate as low (10 mg/week or less) or high (15 mg/week or more) based on the last reported dose of methotrexate at no later than 8 weeks of follow-up.
In each group, females comprised about 80% of patients, and the mean age was 45-48 years. The group that received methotrexate plus csDMARDs had a median symptom duration nearly twice that of the other groups (730 days vs. 365 for monotherapy and 458 for methotrexate plus glucocorticoids). Rheumatoid factor positivity ranged from 77% to 84% and anticitrullinated peptide autoantibody positivity from 72% to 85%.
The use of a high methotrexate starting dose generally trended upward in patients enrolled in the database through 2015, whereas the high point for use of a low dose was 2010 and declined thereafter. Overall, a high starting dose was used in 28% of monotherapy patients, 14% with methotrexate plus csDMARDs, and 46% with methotrexate plus glucocorticoids.
In propensity score–adjusted analyses that helped to control for confounding by indication, there were no differences in the effectiveness of low or high methotrexate starting doses for all three groups after follow-up between 3 and 6 months on Disease Activity Score (DAS), 28-joint DAS, or the Health Assessment Questionnaire (HAQ).
“Our findings seem to contradict the general trend of starting with high methotrexate doses. They indicate that higher doses did not provide better short-term clinical outcome in either monotherapy or combination therapy,” Ms. Bergstra observed.
She continued: “For the moment, we suggest that rheumatologists consider starting with a lower initial methotrexate dose, especially when prescribing in combination with other synthetic DMARDS or glucocorticoids.”
Effect of initial dose on EULAR response
Rebecca Davies of the Centre for Musculoskeletal Research at the University of Manchester (England) presented data from a separate study that examined the effect of giving a low versus a high dose of methotrexate on patients’ rate of response to EULAR criteria at 6 months.
“Methotrexate is the recommended first line treatment for rheumatoid arthritis; however, we have not yet established [a] clear optimal strategy for the starting dose of this therapy,” Ms. Davies said.
The aim of the study was therefore to assess the two most commonly used methotrexate starting doses used in the United Kingdom (7.5 mg/week or less vs. 15 mg/week or more) and how they affected the DAS28 of patients.
A total of 810 patients with rheumatoid arthritis who were starting methotrexate were recruited from the U.K. national, multicenter, longitudinal, observational Rheumatoid Arthritis Medication Study. For inclusion in the study, patients had to have complete DAS28 data at baseline and at 6 months.
The median age of patients was similar among the low- and high-dose groups, at 58 and 61 years, respectively. Most of the participants were female (70% vs. 60%), with a median disease duration of 6 years. Median baseline DAS28 scores were 4.2 in low- and 4.1 in high-dose groups, and baseline HAQ scores were 1.3 and 0.9, respectively.
Ms. Davies noted that 627 (77%) of the patients newly initiated on methotrexate received 15 mg/week, 10 received 20 mg, and 2 received 25 mg. The low dose of 7.5 mg/week was started by 165 patients (20%), 4 started on 5 mg, and 2 started on 2.5 mg. In more than 90% of patients, methotrexate was given orally in both the low- and high-dose groups.
Patients who were initiated on the lower methotrexate dose were more often prescribed concomitant nonbiologic DMARDs (17% vs. 10% of those in the high-dose group). Half of patients in both high- and low-dose groups used oral steroids, and a quarter used intramuscular steroids.
According to the EULAR response criteria, a good response is seen if the final DAS28 drops to 3.2 or below and there is also an improvement of 1.2 or more from baseline values. This was achieved in 23% of patients in the low-dose group and in 33% of patients in the high-dose group. Moderate EULAR clinical responses were seen in 32% and 25%, and nonresponses seen in a respective 45% and 42%.
However, findings on a multinomial logistic regression model “showed that RA patients starting methotrexate on a higher dose have a higher probability of having a good EULAR clinical response, as opposed to nonresponse, at 6 months,” Ms. Davies said.
The unadjusted relative risk ratio in patients starting a high versus low dose was 0.8 for a moderate EULAR response and 1.5 for a good EULAR response. The respective adjusted RRR was 1.0 and 2.7, suggesting that there is no difference between the doses in achieving a moderate response, but the higher dose has the edge at helping patients achieve a good EULAR response by 6 months.
During the discussion following Ms. Davies’ presentation, Roy Fleischmann, MD, of the department of internal medicine at the University of Texas Southwestern Medical Center, Dallas, asked whether a high dose had actually been used at all in the study. Dr. Fleischmann observed that both 7.5 mg/week and 15 mg/week could be considered low doses.
However, one of the chairs of the session, Peter Taylor, PhD , of the University of Oxford (England) noted that the bioavailability of methotrexate does not change much when the dose is above 15 mg via the oral route.
Kimme Hyrich, MD, of the University of Manchester (England) and senior author on the study, pointed out that the point of the analysis was to compare the starting doses of methotrexate among patients, and there might have been patients who received higher doses (25 mg or more) during the 6-month follow-up period. It is expected that future work will look at the change in the dose response over the 6-month time period, she said.
Ms. Bergstra and Ms. Davies reported that they had no relevant financial disclosures. Several coauthors for the METEOR database study disclosed financial relationships with numerous companies that market drugs for RA.
MADRID – A low versus high starting dose of methotrexate given as monotherapy or in combination with glucocorticoids or conventional synthetic disease-modifying antirheumatic drugs to newly diagnosed rheumatoid arthritis patients doesn’t seem to make a difference in short-term disease activity and physical functioning responses, but a higher starting dose of at least 15 mg/week may provide a better chance at achieving a good response at 6 months, according to two separate observational studies presented at the European Congress of Rheumatology.
One of the studies looked at 3- to 6-month disease activity and physical functioning responses to methotrexate used as mono- or combination therapy and the other assessed EULAR clinical responses at 6 months in mostly monotherapy-treated patients.
Low vs. high dose in combination treatments
“Methotrexate is the anchor drug in the treatment of rheumatoid arthritis patients. Current guidelines for methotrexate monotherapy recommend initiating 15 mg/week orally then escalating to 25-30 mg/week or the highest tolerable dose, but no recommendations exist for the drug’s use in combination therapy,” said Sytske Anne Bergstra, first author of a study using the international, observational METEOR database, a cohort with real-world clinical data.
The investigators selected 1,404 RA patients from the METEOR database who had a symptom duration of less than 5 years, had less than 2 months between diagnosis and first visit, and did not change medications (only dose adjustments were allowed). They were divided into three groups: methotrexate monotherapy, methotrexate plus conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and methotrexate plus glucocorticoids (and possibly csDMARDs). The investigators defined initial starting doses of methotrexate as low (10 mg/week or less) or high (15 mg/week or more) based on the last reported dose of methotrexate at no later than 8 weeks of follow-up.
In each group, females comprised about 80% of patients, and the mean age was 45-48 years. The group that received methotrexate plus csDMARDs had a median symptom duration nearly twice that of the other groups (730 days vs. 365 for monotherapy and 458 for methotrexate plus glucocorticoids). Rheumatoid factor positivity ranged from 77% to 84% and anticitrullinated peptide autoantibody positivity from 72% to 85%.
The use of a high methotrexate starting dose generally trended upward in patients enrolled in the database through 2015, whereas the high point for use of a low dose was 2010 and declined thereafter. Overall, a high starting dose was used in 28% of monotherapy patients, 14% with methotrexate plus csDMARDs, and 46% with methotrexate plus glucocorticoids.
In propensity score–adjusted analyses that helped to control for confounding by indication, there were no differences in the effectiveness of low or high methotrexate starting doses for all three groups after follow-up between 3 and 6 months on Disease Activity Score (DAS), 28-joint DAS, or the Health Assessment Questionnaire (HAQ).
“Our findings seem to contradict the general trend of starting with high methotrexate doses. They indicate that higher doses did not provide better short-term clinical outcome in either monotherapy or combination therapy,” Ms. Bergstra observed.
She continued: “For the moment, we suggest that rheumatologists consider starting with a lower initial methotrexate dose, especially when prescribing in combination with other synthetic DMARDS or glucocorticoids.”
Effect of initial dose on EULAR response
Rebecca Davies of the Centre for Musculoskeletal Research at the University of Manchester (England) presented data from a separate study that examined the effect of giving a low versus a high dose of methotrexate on patients’ rate of response to EULAR criteria at 6 months.
“Methotrexate is the recommended first line treatment for rheumatoid arthritis; however, we have not yet established [a] clear optimal strategy for the starting dose of this therapy,” Ms. Davies said.
The aim of the study was therefore to assess the two most commonly used methotrexate starting doses used in the United Kingdom (7.5 mg/week or less vs. 15 mg/week or more) and how they affected the DAS28 of patients.
A total of 810 patients with rheumatoid arthritis who were starting methotrexate were recruited from the U.K. national, multicenter, longitudinal, observational Rheumatoid Arthritis Medication Study. For inclusion in the study, patients had to have complete DAS28 data at baseline and at 6 months.
The median age of patients was similar among the low- and high-dose groups, at 58 and 61 years, respectively. Most of the participants were female (70% vs. 60%), with a median disease duration of 6 years. Median baseline DAS28 scores were 4.2 in low- and 4.1 in high-dose groups, and baseline HAQ scores were 1.3 and 0.9, respectively.
Ms. Davies noted that 627 (77%) of the patients newly initiated on methotrexate received 15 mg/week, 10 received 20 mg, and 2 received 25 mg. The low dose of 7.5 mg/week was started by 165 patients (20%), 4 started on 5 mg, and 2 started on 2.5 mg. In more than 90% of patients, methotrexate was given orally in both the low- and high-dose groups.
Patients who were initiated on the lower methotrexate dose were more often prescribed concomitant nonbiologic DMARDs (17% vs. 10% of those in the high-dose group). Half of patients in both high- and low-dose groups used oral steroids, and a quarter used intramuscular steroids.
According to the EULAR response criteria, a good response is seen if the final DAS28 drops to 3.2 or below and there is also an improvement of 1.2 or more from baseline values. This was achieved in 23% of patients in the low-dose group and in 33% of patients in the high-dose group. Moderate EULAR clinical responses were seen in 32% and 25%, and nonresponses seen in a respective 45% and 42%.
However, findings on a multinomial logistic regression model “showed that RA patients starting methotrexate on a higher dose have a higher probability of having a good EULAR clinical response, as opposed to nonresponse, at 6 months,” Ms. Davies said.
The unadjusted relative risk ratio in patients starting a high versus low dose was 0.8 for a moderate EULAR response and 1.5 for a good EULAR response. The respective adjusted RRR was 1.0 and 2.7, suggesting that there is no difference between the doses in achieving a moderate response, but the higher dose has the edge at helping patients achieve a good EULAR response by 6 months.
During the discussion following Ms. Davies’ presentation, Roy Fleischmann, MD, of the department of internal medicine at the University of Texas Southwestern Medical Center, Dallas, asked whether a high dose had actually been used at all in the study. Dr. Fleischmann observed that both 7.5 mg/week and 15 mg/week could be considered low doses.
However, one of the chairs of the session, Peter Taylor, PhD , of the University of Oxford (England) noted that the bioavailability of methotrexate does not change much when the dose is above 15 mg via the oral route.
Kimme Hyrich, MD, of the University of Manchester (England) and senior author on the study, pointed out that the point of the analysis was to compare the starting doses of methotrexate among patients, and there might have been patients who received higher doses (25 mg or more) during the 6-month follow-up period. It is expected that future work will look at the change in the dose response over the 6-month time period, she said.
Ms. Bergstra and Ms. Davies reported that they had no relevant financial disclosures. Several coauthors for the METEOR database study disclosed financial relationships with numerous companies that market drugs for RA.
MADRID – A low versus high starting dose of methotrexate given as monotherapy or in combination with glucocorticoids or conventional synthetic disease-modifying antirheumatic drugs to newly diagnosed rheumatoid arthritis patients doesn’t seem to make a difference in short-term disease activity and physical functioning responses, but a higher starting dose of at least 15 mg/week may provide a better chance at achieving a good response at 6 months, according to two separate observational studies presented at the European Congress of Rheumatology.
One of the studies looked at 3- to 6-month disease activity and physical functioning responses to methotrexate used as mono- or combination therapy and the other assessed EULAR clinical responses at 6 months in mostly monotherapy-treated patients.
Low vs. high dose in combination treatments
“Methotrexate is the anchor drug in the treatment of rheumatoid arthritis patients. Current guidelines for methotrexate monotherapy recommend initiating 15 mg/week orally then escalating to 25-30 mg/week or the highest tolerable dose, but no recommendations exist for the drug’s use in combination therapy,” said Sytske Anne Bergstra, first author of a study using the international, observational METEOR database, a cohort with real-world clinical data.
The investigators selected 1,404 RA patients from the METEOR database who had a symptom duration of less than 5 years, had less than 2 months between diagnosis and first visit, and did not change medications (only dose adjustments were allowed). They were divided into three groups: methotrexate monotherapy, methotrexate plus conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and methotrexate plus glucocorticoids (and possibly csDMARDs). The investigators defined initial starting doses of methotrexate as low (10 mg/week or less) or high (15 mg/week or more) based on the last reported dose of methotrexate at no later than 8 weeks of follow-up.
In each group, females comprised about 80% of patients, and the mean age was 45-48 years. The group that received methotrexate plus csDMARDs had a median symptom duration nearly twice that of the other groups (730 days vs. 365 for monotherapy and 458 for methotrexate plus glucocorticoids). Rheumatoid factor positivity ranged from 77% to 84% and anticitrullinated peptide autoantibody positivity from 72% to 85%.
The use of a high methotrexate starting dose generally trended upward in patients enrolled in the database through 2015, whereas the high point for use of a low dose was 2010 and declined thereafter. Overall, a high starting dose was used in 28% of monotherapy patients, 14% with methotrexate plus csDMARDs, and 46% with methotrexate plus glucocorticoids.
In propensity score–adjusted analyses that helped to control for confounding by indication, there were no differences in the effectiveness of low or high methotrexate starting doses for all three groups after follow-up between 3 and 6 months on Disease Activity Score (DAS), 28-joint DAS, or the Health Assessment Questionnaire (HAQ).
“Our findings seem to contradict the general trend of starting with high methotrexate doses. They indicate that higher doses did not provide better short-term clinical outcome in either monotherapy or combination therapy,” Ms. Bergstra observed.
She continued: “For the moment, we suggest that rheumatologists consider starting with a lower initial methotrexate dose, especially when prescribing in combination with other synthetic DMARDS or glucocorticoids.”
Effect of initial dose on EULAR response
Rebecca Davies of the Centre for Musculoskeletal Research at the University of Manchester (England) presented data from a separate study that examined the effect of giving a low versus a high dose of methotrexate on patients’ rate of response to EULAR criteria at 6 months.
“Methotrexate is the recommended first line treatment for rheumatoid arthritis; however, we have not yet established [a] clear optimal strategy for the starting dose of this therapy,” Ms. Davies said.
The aim of the study was therefore to assess the two most commonly used methotrexate starting doses used in the United Kingdom (7.5 mg/week or less vs. 15 mg/week or more) and how they affected the DAS28 of patients.
A total of 810 patients with rheumatoid arthritis who were starting methotrexate were recruited from the U.K. national, multicenter, longitudinal, observational Rheumatoid Arthritis Medication Study. For inclusion in the study, patients had to have complete DAS28 data at baseline and at 6 months.
The median age of patients was similar among the low- and high-dose groups, at 58 and 61 years, respectively. Most of the participants were female (70% vs. 60%), with a median disease duration of 6 years. Median baseline DAS28 scores were 4.2 in low- and 4.1 in high-dose groups, and baseline HAQ scores were 1.3 and 0.9, respectively.
Ms. Davies noted that 627 (77%) of the patients newly initiated on methotrexate received 15 mg/week, 10 received 20 mg, and 2 received 25 mg. The low dose of 7.5 mg/week was started by 165 patients (20%), 4 started on 5 mg, and 2 started on 2.5 mg. In more than 90% of patients, methotrexate was given orally in both the low- and high-dose groups.
Patients who were initiated on the lower methotrexate dose were more often prescribed concomitant nonbiologic DMARDs (17% vs. 10% of those in the high-dose group). Half of patients in both high- and low-dose groups used oral steroids, and a quarter used intramuscular steroids.
According to the EULAR response criteria, a good response is seen if the final DAS28 drops to 3.2 or below and there is also an improvement of 1.2 or more from baseline values. This was achieved in 23% of patients in the low-dose group and in 33% of patients in the high-dose group. Moderate EULAR clinical responses were seen in 32% and 25%, and nonresponses seen in a respective 45% and 42%.
However, findings on a multinomial logistic regression model “showed that RA patients starting methotrexate on a higher dose have a higher probability of having a good EULAR clinical response, as opposed to nonresponse, at 6 months,” Ms. Davies said.
The unadjusted relative risk ratio in patients starting a high versus low dose was 0.8 for a moderate EULAR response and 1.5 for a good EULAR response. The respective adjusted RRR was 1.0 and 2.7, suggesting that there is no difference between the doses in achieving a moderate response, but the higher dose has the edge at helping patients achieve a good EULAR response by 6 months.
During the discussion following Ms. Davies’ presentation, Roy Fleischmann, MD, of the department of internal medicine at the University of Texas Southwestern Medical Center, Dallas, asked whether a high dose had actually been used at all in the study. Dr. Fleischmann observed that both 7.5 mg/week and 15 mg/week could be considered low doses.
However, one of the chairs of the session, Peter Taylor, PhD , of the University of Oxford (England) noted that the bioavailability of methotrexate does not change much when the dose is above 15 mg via the oral route.
Kimme Hyrich, MD, of the University of Manchester (England) and senior author on the study, pointed out that the point of the analysis was to compare the starting doses of methotrexate among patients, and there might have been patients who received higher doses (25 mg or more) during the 6-month follow-up period. It is expected that future work will look at the change in the dose response over the 6-month time period, she said.
Ms. Bergstra and Ms. Davies reported that they had no relevant financial disclosures. Several coauthors for the METEOR database study disclosed financial relationships with numerous companies that market drugs for RA.
AT THE EULAR 2017 CONGRESS
Key clinical point: For newly diagnosed RA, consider using a lower methotrexate starting dose with combination therapy and a higher dose of 15 mg/week or more in monotherapy.
Major finding: In one study, 23% and 33% of patients taking low-dose or high-dose methotrexate, respectively, achieved a good EULAR clinical response.
Data source: Two studies (METEOR and RAMS) evaluating the comparative effects of initiating low versus high doses of methotrexate for newly diagnosed rheumatoid arthritis.
Disclosures: The presenters reported they had no relevant financial disclosures. Several coauthors for the METEOR database study disclosed financial relationships with numerous companies that market drugs for RA.
Three-drug combo keeps early RA at bay long term
MADRID – A triple combination of methotrexate, hydroxychloroquine, and triamcinolone used to induce remission in patients with early rheumatoid arthritis (RA) was associated with higher long-term remission rates than methotrexate used alone in a study presented at the European Congress of Rheumatology.
The percentages of patients in remission were a respective 88.2% versus 72.1% at 1 year, 86.6% versus 81.9% at 2 years, and 88.0% versus 85.8% at 3 years.
“Combination treatment results in a higher remission rate in the first 2 years of treatment and a similar remission rate in the third year,” said Tammo Brunekreef, a medical student at Ziekenhuisgroep Twente in Almelo, the Netherlands, who presented the findings.
“There is no consensus on what the initial treatment should look like, however,” he said. For instance, should remission be induced with methotrexate alone? Or should methotrexate be used in combination with other synthetic disease-modifying antirheumatic drugs (DMARDs)? Or is methotrexate best combined with steroids?
“The early treatment [of RA] is very important because a shorter time to remission is related to sustainability of remission,” Mr. Brunekreef said. “Combination therapy has also been compared in previous studies with methotrexate monotherapy and had been shown to be more effective at 3 and 6 months, although not at 12 months.”
Data on the longer-term follow-up in routine care is lacking, so Mr. Brunekreef and Dutch rheumatologist Hein J. Bernelot Moens, MD, created two historical cohorts of patients with early RA. One cohort of 296 patients had a disease onset between 2006 and 2011 and had received methotrexate monotherapy initiated at 15-20 mg/week. The other cohort of 157 patients had a disease onset between 2012 and 2014 and had been given a combination of oral methotrexate, started at 20 mg/week; oral hydroxychloroquine, started at 200 mg twice daily; and a single 80-120 mg intramuscular injection of triamcinolone that could be repeated after 4 weeks, if necessary.
The mean age of the recruited patients in the monotherapy and combination cohorts was a respective 59.5 and 58.9 years, and 60.5% and 65% were female. More patients in the combination than monotherapy group were rheumatoid factor positive (72.3% vs. 62.2%), with 72.1% and 64.5% being positive for anticitrullinated protein antibodies.
“A number of patients were lost to follow-up due to death (3.7% vs. 1.9%) [or] drug-free remission (1.7% vs. 0.6%) or did not start methotrexate or for other reasons (2.4% vs. 0.6%), but this was not significantly different,” Mr. Brunekreef reported. This left 273 and 124 in each cohort, respectively, who completed 3 years’ of follow-up.
The same percentage of patients in the methotrexate and combination cohorts started a biologic DMARD in the first year (10.8%). A biologic DMARD was recommended if remission was not achieved within 6 months or if there was sustained disease activity after 6 months.
In the second year, however, 6.6% more patients in the methotrexate cohort started a biologic (9.8% vs. 3.2%). Conversely, 1.3% more patients started a biologic in the third year in the combination arm (4% vs. 2.7%). Overall, the receipt of biologics by 21% of monotherapy patients and 14% of combination therapy patients did not differ significantly.
The mean time to the start of the biologic DMARD was similar, however, at around 11-12 months.
Mr. Brunekreef answered that the DAS28-ESR had been used up to 2015 and then the DAS-CRP from 2016 onward, although the latter was only for patients in year 3, a small number of patients. “We’re looking into a way to translate those data to make them comparable,” Brunekreef said.
“That’s a real problem,” Dr. Fleischmann said, as the DAS28-ESR and DAS28-CRP are not interchangeable. He proposed that these data needed to be looked at using another measure, perhaps the Clinical Disease Activity Index.
Further, Dr. Fleischmann observed that the methotrexate monotherapy data were “absolutely incredible, compared to what we’ve seen in randomized, controlled trials, with 40%-50% of patients in remission.” In clinical trials, about 15% on methotrexate alone achieve an American College of Rheumatology 20 Response Criteria.
“These are very, very strong data, but now I wonder whether or not it’s because of that switch” in DAS28 scoring, Dr. Fleischmann said.
Mr. Brunekreef had no disclosures to report. Dr. Fleischmann has received research grants, research support, and consultancy fees from Pfizer and from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Sanofi Genzyme, and UCB.
MADRID – A triple combination of methotrexate, hydroxychloroquine, and triamcinolone used to induce remission in patients with early rheumatoid arthritis (RA) was associated with higher long-term remission rates than methotrexate used alone in a study presented at the European Congress of Rheumatology.
The percentages of patients in remission were a respective 88.2% versus 72.1% at 1 year, 86.6% versus 81.9% at 2 years, and 88.0% versus 85.8% at 3 years.
“Combination treatment results in a higher remission rate in the first 2 years of treatment and a similar remission rate in the third year,” said Tammo Brunekreef, a medical student at Ziekenhuisgroep Twente in Almelo, the Netherlands, who presented the findings.
“There is no consensus on what the initial treatment should look like, however,” he said. For instance, should remission be induced with methotrexate alone? Or should methotrexate be used in combination with other synthetic disease-modifying antirheumatic drugs (DMARDs)? Or is methotrexate best combined with steroids?
“The early treatment [of RA] is very important because a shorter time to remission is related to sustainability of remission,” Mr. Brunekreef said. “Combination therapy has also been compared in previous studies with methotrexate monotherapy and had been shown to be more effective at 3 and 6 months, although not at 12 months.”
Data on the longer-term follow-up in routine care is lacking, so Mr. Brunekreef and Dutch rheumatologist Hein J. Bernelot Moens, MD, created two historical cohorts of patients with early RA. One cohort of 296 patients had a disease onset between 2006 and 2011 and had received methotrexate monotherapy initiated at 15-20 mg/week. The other cohort of 157 patients had a disease onset between 2012 and 2014 and had been given a combination of oral methotrexate, started at 20 mg/week; oral hydroxychloroquine, started at 200 mg twice daily; and a single 80-120 mg intramuscular injection of triamcinolone that could be repeated after 4 weeks, if necessary.
The mean age of the recruited patients in the monotherapy and combination cohorts was a respective 59.5 and 58.9 years, and 60.5% and 65% were female. More patients in the combination than monotherapy group were rheumatoid factor positive (72.3% vs. 62.2%), with 72.1% and 64.5% being positive for anticitrullinated protein antibodies.
“A number of patients were lost to follow-up due to death (3.7% vs. 1.9%) [or] drug-free remission (1.7% vs. 0.6%) or did not start methotrexate or for other reasons (2.4% vs. 0.6%), but this was not significantly different,” Mr. Brunekreef reported. This left 273 and 124 in each cohort, respectively, who completed 3 years’ of follow-up.
The same percentage of patients in the methotrexate and combination cohorts started a biologic DMARD in the first year (10.8%). A biologic DMARD was recommended if remission was not achieved within 6 months or if there was sustained disease activity after 6 months.
In the second year, however, 6.6% more patients in the methotrexate cohort started a biologic (9.8% vs. 3.2%). Conversely, 1.3% more patients started a biologic in the third year in the combination arm (4% vs. 2.7%). Overall, the receipt of biologics by 21% of monotherapy patients and 14% of combination therapy patients did not differ significantly.
The mean time to the start of the biologic DMARD was similar, however, at around 11-12 months.
Mr. Brunekreef answered that the DAS28-ESR had been used up to 2015 and then the DAS-CRP from 2016 onward, although the latter was only for patients in year 3, a small number of patients. “We’re looking into a way to translate those data to make them comparable,” Brunekreef said.
“That’s a real problem,” Dr. Fleischmann said, as the DAS28-ESR and DAS28-CRP are not interchangeable. He proposed that these data needed to be looked at using another measure, perhaps the Clinical Disease Activity Index.
Further, Dr. Fleischmann observed that the methotrexate monotherapy data were “absolutely incredible, compared to what we’ve seen in randomized, controlled trials, with 40%-50% of patients in remission.” In clinical trials, about 15% on methotrexate alone achieve an American College of Rheumatology 20 Response Criteria.
“These are very, very strong data, but now I wonder whether or not it’s because of that switch” in DAS28 scoring, Dr. Fleischmann said.
Mr. Brunekreef had no disclosures to report. Dr. Fleischmann has received research grants, research support, and consultancy fees from Pfizer and from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Sanofi Genzyme, and UCB.
MADRID – A triple combination of methotrexate, hydroxychloroquine, and triamcinolone used to induce remission in patients with early rheumatoid arthritis (RA) was associated with higher long-term remission rates than methotrexate used alone in a study presented at the European Congress of Rheumatology.
The percentages of patients in remission were a respective 88.2% versus 72.1% at 1 year, 86.6% versus 81.9% at 2 years, and 88.0% versus 85.8% at 3 years.
“Combination treatment results in a higher remission rate in the first 2 years of treatment and a similar remission rate in the third year,” said Tammo Brunekreef, a medical student at Ziekenhuisgroep Twente in Almelo, the Netherlands, who presented the findings.
“There is no consensus on what the initial treatment should look like, however,” he said. For instance, should remission be induced with methotrexate alone? Or should methotrexate be used in combination with other synthetic disease-modifying antirheumatic drugs (DMARDs)? Or is methotrexate best combined with steroids?
“The early treatment [of RA] is very important because a shorter time to remission is related to sustainability of remission,” Mr. Brunekreef said. “Combination therapy has also been compared in previous studies with methotrexate monotherapy and had been shown to be more effective at 3 and 6 months, although not at 12 months.”
Data on the longer-term follow-up in routine care is lacking, so Mr. Brunekreef and Dutch rheumatologist Hein J. Bernelot Moens, MD, created two historical cohorts of patients with early RA. One cohort of 296 patients had a disease onset between 2006 and 2011 and had received methotrexate monotherapy initiated at 15-20 mg/week. The other cohort of 157 patients had a disease onset between 2012 and 2014 and had been given a combination of oral methotrexate, started at 20 mg/week; oral hydroxychloroquine, started at 200 mg twice daily; and a single 80-120 mg intramuscular injection of triamcinolone that could be repeated after 4 weeks, if necessary.
The mean age of the recruited patients in the monotherapy and combination cohorts was a respective 59.5 and 58.9 years, and 60.5% and 65% were female. More patients in the combination than monotherapy group were rheumatoid factor positive (72.3% vs. 62.2%), with 72.1% and 64.5% being positive for anticitrullinated protein antibodies.
“A number of patients were lost to follow-up due to death (3.7% vs. 1.9%) [or] drug-free remission (1.7% vs. 0.6%) or did not start methotrexate or for other reasons (2.4% vs. 0.6%), but this was not significantly different,” Mr. Brunekreef reported. This left 273 and 124 in each cohort, respectively, who completed 3 years’ of follow-up.
The same percentage of patients in the methotrexate and combination cohorts started a biologic DMARD in the first year (10.8%). A biologic DMARD was recommended if remission was not achieved within 6 months or if there was sustained disease activity after 6 months.
In the second year, however, 6.6% more patients in the methotrexate cohort started a biologic (9.8% vs. 3.2%). Conversely, 1.3% more patients started a biologic in the third year in the combination arm (4% vs. 2.7%). Overall, the receipt of biologics by 21% of monotherapy patients and 14% of combination therapy patients did not differ significantly.
The mean time to the start of the biologic DMARD was similar, however, at around 11-12 months.
Mr. Brunekreef answered that the DAS28-ESR had been used up to 2015 and then the DAS-CRP from 2016 onward, although the latter was only for patients in year 3, a small number of patients. “We’re looking into a way to translate those data to make them comparable,” Brunekreef said.
“That’s a real problem,” Dr. Fleischmann said, as the DAS28-ESR and DAS28-CRP are not interchangeable. He proposed that these data needed to be looked at using another measure, perhaps the Clinical Disease Activity Index.
Further, Dr. Fleischmann observed that the methotrexate monotherapy data were “absolutely incredible, compared to what we’ve seen in randomized, controlled trials, with 40%-50% of patients in remission.” In clinical trials, about 15% on methotrexate alone achieve an American College of Rheumatology 20 Response Criteria.
“These are very, very strong data, but now I wonder whether or not it’s because of that switch” in DAS28 scoring, Dr. Fleischmann said.
Mr. Brunekreef had no disclosures to report. Dr. Fleischmann has received research grants, research support, and consultancy fees from Pfizer and from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Sanofi Genzyme, and UCB.
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: A DAS28 less than 2.6 was achieved in 88.2% who received a methotrexate-based triple combination versus 72.1% with methotrexate monotherapy at 1 year, 86.6% versus 81.9% at 2 years, and 88.0% versus 85.8% at 3 years.
Data source: Two historical cohorts of early arthritis patients treated with methotrexate alone (n = 296) or a combination of methotrexate, hydroxychloroquine, and triamcinolone (n = 157) in routine care.
Disclosures: The study presenter had no disclosures to report. An independent commentator has received research grants, research support, and consultancy fees from Pfizer and from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Sanofi Genzyme, and UCB.
VIDEO: Cardiovascular events in rheumatoid arthritis have decreased over decades
MADRID – Recent improvements in the management of rheumatoid arthritis may have had a positive impact on common cardiovascular comorbidities, according to the results of a systematic review and meta-analysis.
Risk ratios (RR) for several CV events in rheumatoid arthritis (RA) patients were found to be lower for data published after 2000 and up to March 2016 when compared with data published up until 2000. Indeed, comparing these two time periods, French researchers found that the RR for myocardial infarction (MI) were a respective 1.32 and 1.18, for heart failure a respective 1.25 and 1.17, and for CV mortality a respective 1.21 and 1.07.
“Systemic inflammation is the cornerstone of both rheumatoid arthritis and atherosclerosis,” Cécile Gaujoux-Viala, MD, PhD, professor of rheumatology at Montpellier University, Nîmes, France, and chief of the rheumatology service at Nîmes University Hospital, said during a press briefing at the European Congress of Rheumatology.
“Over the past 15 years, new treatment strategies such as ‘tight control,’ ‘treat-to-target,’ methotrexate optimization, and use of biologic DMARDs [disease-modifying antirheumatic drugs] have led to better control of this inflammation,” Dr. Gaujoux-Viala added.
The aim of the meta-analysis was to look at the overall risk for CV events in RA patients versus the general population, she said, as well as to see if there had been any temporal shift by analyzing data obtained within two time periods – before 2000 and after 2000.
A systematic literature review was performed using the PubMed and Cochrane Library databases to search for observational studies that provided data about the occurrence of CV events in RA patients and controls. Of 5,714 papers that included reports of stroke, MI, heart failure, or CV death, 28 had the necessary data that could be used for the meta-analysis. Overall, the 28 studies included 227,871 RA patients, with a mean age of 55 years.
Results showed that RA patients had a 17% increased risk for stroke versus controls overall (P = .002), with a RR of 1.17. The RRs were 1.12 before 2000 and 1.23 after 2000, making stroke the only CV event that did not appear to show a downward trend.
Compared with the general population, RA patients had a 24% excess risk of MI, a 22% excess risk of heart failure, and a 18% excess risk of dying from a CV event (all P less than .00001).
These data provide “confirmation of an increased CV risk in RA patients compared to the general population,” said Dr. Gaujoux-Viala, who also discussed the study and its implications in a video interview.
Commenting on the study, Philip J. Mease, MD, of the University of Washington, Seattle, wondered where the studies used in the meta-analysis had been performed because of the potential impact that reduced access to CV medications or prevention strategies in certain countries could have on the results. However, the investigators did not determine where each of the studies used in the review took place.
Dr. Gaujoux-Viala had no relevant conflicts of interest to disclose.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – Recent improvements in the management of rheumatoid arthritis may have had a positive impact on common cardiovascular comorbidities, according to the results of a systematic review and meta-analysis.
Risk ratios (RR) for several CV events in rheumatoid arthritis (RA) patients were found to be lower for data published after 2000 and up to March 2016 when compared with data published up until 2000. Indeed, comparing these two time periods, French researchers found that the RR for myocardial infarction (MI) were a respective 1.32 and 1.18, for heart failure a respective 1.25 and 1.17, and for CV mortality a respective 1.21 and 1.07.
“Systemic inflammation is the cornerstone of both rheumatoid arthritis and atherosclerosis,” Cécile Gaujoux-Viala, MD, PhD, professor of rheumatology at Montpellier University, Nîmes, France, and chief of the rheumatology service at Nîmes University Hospital, said during a press briefing at the European Congress of Rheumatology.
“Over the past 15 years, new treatment strategies such as ‘tight control,’ ‘treat-to-target,’ methotrexate optimization, and use of biologic DMARDs [disease-modifying antirheumatic drugs] have led to better control of this inflammation,” Dr. Gaujoux-Viala added.
The aim of the meta-analysis was to look at the overall risk for CV events in RA patients versus the general population, she said, as well as to see if there had been any temporal shift by analyzing data obtained within two time periods – before 2000 and after 2000.
A systematic literature review was performed using the PubMed and Cochrane Library databases to search for observational studies that provided data about the occurrence of CV events in RA patients and controls. Of 5,714 papers that included reports of stroke, MI, heart failure, or CV death, 28 had the necessary data that could be used for the meta-analysis. Overall, the 28 studies included 227,871 RA patients, with a mean age of 55 years.
Results showed that RA patients had a 17% increased risk for stroke versus controls overall (P = .002), with a RR of 1.17. The RRs were 1.12 before 2000 and 1.23 after 2000, making stroke the only CV event that did not appear to show a downward trend.
Compared with the general population, RA patients had a 24% excess risk of MI, a 22% excess risk of heart failure, and a 18% excess risk of dying from a CV event (all P less than .00001).
These data provide “confirmation of an increased CV risk in RA patients compared to the general population,” said Dr. Gaujoux-Viala, who also discussed the study and its implications in a video interview.
Commenting on the study, Philip J. Mease, MD, of the University of Washington, Seattle, wondered where the studies used in the meta-analysis had been performed because of the potential impact that reduced access to CV medications or prevention strategies in certain countries could have on the results. However, the investigators did not determine where each of the studies used in the review took place.
Dr. Gaujoux-Viala had no relevant conflicts of interest to disclose.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – Recent improvements in the management of rheumatoid arthritis may have had a positive impact on common cardiovascular comorbidities, according to the results of a systematic review and meta-analysis.
Risk ratios (RR) for several CV events in rheumatoid arthritis (RA) patients were found to be lower for data published after 2000 and up to March 2016 when compared with data published up until 2000. Indeed, comparing these two time periods, French researchers found that the RR for myocardial infarction (MI) were a respective 1.32 and 1.18, for heart failure a respective 1.25 and 1.17, and for CV mortality a respective 1.21 and 1.07.
“Systemic inflammation is the cornerstone of both rheumatoid arthritis and atherosclerosis,” Cécile Gaujoux-Viala, MD, PhD, professor of rheumatology at Montpellier University, Nîmes, France, and chief of the rheumatology service at Nîmes University Hospital, said during a press briefing at the European Congress of Rheumatology.
“Over the past 15 years, new treatment strategies such as ‘tight control,’ ‘treat-to-target,’ methotrexate optimization, and use of biologic DMARDs [disease-modifying antirheumatic drugs] have led to better control of this inflammation,” Dr. Gaujoux-Viala added.
The aim of the meta-analysis was to look at the overall risk for CV events in RA patients versus the general population, she said, as well as to see if there had been any temporal shift by analyzing data obtained within two time periods – before 2000 and after 2000.
A systematic literature review was performed using the PubMed and Cochrane Library databases to search for observational studies that provided data about the occurrence of CV events in RA patients and controls. Of 5,714 papers that included reports of stroke, MI, heart failure, or CV death, 28 had the necessary data that could be used for the meta-analysis. Overall, the 28 studies included 227,871 RA patients, with a mean age of 55 years.
Results showed that RA patients had a 17% increased risk for stroke versus controls overall (P = .002), with a RR of 1.17. The RRs were 1.12 before 2000 and 1.23 after 2000, making stroke the only CV event that did not appear to show a downward trend.
Compared with the general population, RA patients had a 24% excess risk of MI, a 22% excess risk of heart failure, and a 18% excess risk of dying from a CV event (all P less than .00001).
These data provide “confirmation of an increased CV risk in RA patients compared to the general population,” said Dr. Gaujoux-Viala, who also discussed the study and its implications in a video interview.
Commenting on the study, Philip J. Mease, MD, of the University of Washington, Seattle, wondered where the studies used in the meta-analysis had been performed because of the potential impact that reduced access to CV medications or prevention strategies in certain countries could have on the results. However, the investigators did not determine where each of the studies used in the review took place.
Dr. Gaujoux-Viala had no relevant conflicts of interest to disclose.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Risk ratios for myocardial infarction, heart failure, and CV mortality were lower between the period of 2000-2016 than for the period up to 2000.
Data source: Meta-analysis of 28 studies published up to March 2016 that provided data on CV event rates in RA patients and the general population.
Disclosures: Dr. Gaujoux-Viala had no relevant conflicts of interest to disclose.
