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NEW YORK — Patients with rheumatoid arthritis (RA) carry a high risk for cardiovascular events, but mounting clinical evidence suggests they’re being undertreated to manage that risk. Rheumatologists should consider a patient with RA’s cardiovascular disease (CVD) status before deciding on RA treatments, a researcher of cardiometabolic disorders advised.
“The ORAL Surveillance trial suggests that we need to consider cardiovascular risk factors and maybe do additional screening in these patients before we use RA therapies,” Jon T. Giles, MD, PhD, director of the Cedars-Sinai Inflammatory Arthritis Clinical Center at Cedars-Sinai in Los Angeles, told attendees at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.
Underuse of Statins
ORAL Surveillance enrolled 4362 patients with RA aged 50 years and older with at least one cardiovascular risk factor. About 23% of all patients were taking statins, as were about half of patients with a history of atherosclerotic CVD (ASCVD).
“A lot of those people should have been on statins,” Dr. Giles said in an interview. “Not because of their RA but because of their risk factors, and then RA brings it up another notch.” In the population with ASCVD, Dr. Giles added, “It should have been more like 70% and 80%. If we’re talking about a disease that has enhanced cardiovascular risk, then the adoption of standard care that you would do for anybody in the general population should be at that standard and maybe above.”
Multiple studies have documented the underlying risk for CVD events, CV mortality, and subclinical atherosclerosis in people with RA, Dr. Giles noted in his presentation. Physiologically, the RA-specific risk factors most linked to CVD risk are systemic inflammation/cytokine excess and specific circulating T-cell and intermediate monocyte subsets, or both, Dr. Giles said.
Disease-Modifying Antirheumatic Drugs (DMARDs) and CVD Risk
Likewise, research in the past decade has linked methotrexate and tumor necrosis factor (TNF) inhibitors to reduced ASCVD events in RA. Another study showed that abatacept had an effect similar to that of etanercept in patients with RA, and the ENTRACTE trial, for which Dr. Giles was the lead author, demonstrated that tocilizumab matched etanercept in reducing CV events.
The ORAL Surveillance investigators also reported that patients with RA who were receiving the Janus kinase (JAK) inhibitor tofacitinib had a higher risk for major adverse cardiovascular events and cancers than those on TNF therapy, Dr. Giles noted. While statins in combination with JAK inhibitors may have the potential to provide a balance for controlling CV risk in patients with RA, he said later that the potential of JAK inhibitors in reducing CVD risk in RA “is still unsettled.”
The ongoing TARGET trial is further evaluating the impact of DMARDs on vascular inflammation in RA, said Dr. Giles, who’s also a trial principal investigator. TARGET is randomizing 115 patients with RA who didn’t respond to methotrexate to a TNF inhibitor or the addition of sulfasalazine and hydroxychloroquine to their methotrexate. Patients can be on low-intensity but not high-intensity statin therapy, Dr. Giles said.
TARGET results reported last year demonstrated an 8% decrease in arterial fluorodeoxyglucose (FDG) uptake on PET-CT in both treatment arms. Previous studies, Dr. Giles noted, have shown a potential link between FDG and histologic markers of inflammation. “An 8% decrease in vascular FDG is in line with what you would expect from statin treatment,” he said.
TARGET results published in April showed that a measure of a cluster of 12 cytokines and other inflammatory mediators, known as the multibiomarker disease activity (MBDA) score and marketed under the brand name Vectra DA, may help determine arterial FDG uptake. “Those who had a low MBDA score at week 24 actually had the greatest reduction in the arterial FDG,” he said.
Those results were driven entirely by low serum amyloid A (SAA) levels, Dr. Giles said. Those same results didn’t hold for patients in whom SAA and C-reactive protein were correlated.
“So, there’s more to come here,” Dr. Giles said. “We’re looking at other, much larger biomarker panels.”
Nonetheless, he said, sufficient evidence exists to conclude that treating RA to target reduces CV events. “The idea is that at every visit that you see an RA patient, you measure their disease activity, and if they’re not at the target of low disease activity or remission, then you change their therapy to improve that,” he said in an interview.
But an evidence-based guideline is needed to improve coverage of CVD risks in patients with RA, Dr. Giles said. “There is a movement afoot” for a guideline, he said. “If you just did what is supposed to happen for a general population, you would make some improvements. The risk-benefit [ratio] for statins for people with RA has been looked at, and it’s very favorable.”
Unanswered Questions
Dr. Giles noted that the ORAL Surveillance trial has left a number of questions unanswered about the role of JAK inhibitors in managing CVD risk in patients with RA. “The issue that we’re trying to ask is, is it just the TNF inhibitors may be better? Is this a subpopulation issue, or was it just bad luck from the purposes of this one trial? Granted, it was a very large trial, but you can still have luck in terms of getting an effect that’s not accurate.”
Dr. Giles’ “gut feeling” on JAK inhibitors is that they’re not causing harm, but that they’re not as effective as TNF inhibitors in ameliorating CV risks in patients with RA.
Michael S. Garshick, MD, who attended the conference and is head of the cardio-rheumatology program at NYU Langone Health, concurred that a number of unanswered questions persist over the treatment of CVD risk in RA — and autoimmune disease in general.
“I think we’re still trying to prove that DMARDs reduce cardiovascular risk in autoimmune conditions,” he said. “The epidemiologic data would suggest, yes, that inflammation prevention is beneficial for cardiovascular disease, but the TARGET trial suggested that vascular inflammation improved by treating RA, but that biologic therapy wasn’t better than traditional triple therapy.”
Other questions remain unanswered, Dr. Garshick said.
“Is there a specific immunotherapy that is most beneficial to reduce heart disease in patients with an autoimmune condition, whether it’s rheumatoid arthritis, psoriasis, or lupus?”
Dr. Garshick said he’s specifically interested in the residual risk that exists after treating the autoimmunity. “Do you still have a higher risk for heart disease, and if so, why? Is there something else going on that we can’t see?”
The biggest unanswered question, he said, is “How can we do a better job of recognizing heart disease risk in these patients? That’s the low-hanging fruit that people are studying, but across many of those studies, patients have higher rates of blood pressure, cholesterol issues, obesity, diabetes, and many times, we’re not adequately treating these comorbidities.”
That, Dr. Garshick said, may be a result of physician fatigue. “And so [treatment of these comorbidities is] kicked down the road for a year or years,” he added.
Dr. Giles disclosed financial relationships with Pfizer, AbbVie, Eli Lilly, and Novartis. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.
A version of this article appeared on Medscape.com.
NEW YORK — Patients with rheumatoid arthritis (RA) carry a high risk for cardiovascular events, but mounting clinical evidence suggests they’re being undertreated to manage that risk. Rheumatologists should consider a patient with RA’s cardiovascular disease (CVD) status before deciding on RA treatments, a researcher of cardiometabolic disorders advised.
“The ORAL Surveillance trial suggests that we need to consider cardiovascular risk factors and maybe do additional screening in these patients before we use RA therapies,” Jon T. Giles, MD, PhD, director of the Cedars-Sinai Inflammatory Arthritis Clinical Center at Cedars-Sinai in Los Angeles, told attendees at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.
Underuse of Statins
ORAL Surveillance enrolled 4362 patients with RA aged 50 years and older with at least one cardiovascular risk factor. About 23% of all patients were taking statins, as were about half of patients with a history of atherosclerotic CVD (ASCVD).
“A lot of those people should have been on statins,” Dr. Giles said in an interview. “Not because of their RA but because of their risk factors, and then RA brings it up another notch.” In the population with ASCVD, Dr. Giles added, “It should have been more like 70% and 80%. If we’re talking about a disease that has enhanced cardiovascular risk, then the adoption of standard care that you would do for anybody in the general population should be at that standard and maybe above.”
Multiple studies have documented the underlying risk for CVD events, CV mortality, and subclinical atherosclerosis in people with RA, Dr. Giles noted in his presentation. Physiologically, the RA-specific risk factors most linked to CVD risk are systemic inflammation/cytokine excess and specific circulating T-cell and intermediate monocyte subsets, or both, Dr. Giles said.
Disease-Modifying Antirheumatic Drugs (DMARDs) and CVD Risk
Likewise, research in the past decade has linked methotrexate and tumor necrosis factor (TNF) inhibitors to reduced ASCVD events in RA. Another study showed that abatacept had an effect similar to that of etanercept in patients with RA, and the ENTRACTE trial, for which Dr. Giles was the lead author, demonstrated that tocilizumab matched etanercept in reducing CV events.
The ORAL Surveillance investigators also reported that patients with RA who were receiving the Janus kinase (JAK) inhibitor tofacitinib had a higher risk for major adverse cardiovascular events and cancers than those on TNF therapy, Dr. Giles noted. While statins in combination with JAK inhibitors may have the potential to provide a balance for controlling CV risk in patients with RA, he said later that the potential of JAK inhibitors in reducing CVD risk in RA “is still unsettled.”
The ongoing TARGET trial is further evaluating the impact of DMARDs on vascular inflammation in RA, said Dr. Giles, who’s also a trial principal investigator. TARGET is randomizing 115 patients with RA who didn’t respond to methotrexate to a TNF inhibitor or the addition of sulfasalazine and hydroxychloroquine to their methotrexate. Patients can be on low-intensity but not high-intensity statin therapy, Dr. Giles said.
TARGET results reported last year demonstrated an 8% decrease in arterial fluorodeoxyglucose (FDG) uptake on PET-CT in both treatment arms. Previous studies, Dr. Giles noted, have shown a potential link between FDG and histologic markers of inflammation. “An 8% decrease in vascular FDG is in line with what you would expect from statin treatment,” he said.
TARGET results published in April showed that a measure of a cluster of 12 cytokines and other inflammatory mediators, known as the multibiomarker disease activity (MBDA) score and marketed under the brand name Vectra DA, may help determine arterial FDG uptake. “Those who had a low MBDA score at week 24 actually had the greatest reduction in the arterial FDG,” he said.
Those results were driven entirely by low serum amyloid A (SAA) levels, Dr. Giles said. Those same results didn’t hold for patients in whom SAA and C-reactive protein were correlated.
“So, there’s more to come here,” Dr. Giles said. “We’re looking at other, much larger biomarker panels.”
Nonetheless, he said, sufficient evidence exists to conclude that treating RA to target reduces CV events. “The idea is that at every visit that you see an RA patient, you measure their disease activity, and if they’re not at the target of low disease activity or remission, then you change their therapy to improve that,” he said in an interview.
But an evidence-based guideline is needed to improve coverage of CVD risks in patients with RA, Dr. Giles said. “There is a movement afoot” for a guideline, he said. “If you just did what is supposed to happen for a general population, you would make some improvements. The risk-benefit [ratio] for statins for people with RA has been looked at, and it’s very favorable.”
Unanswered Questions
Dr. Giles noted that the ORAL Surveillance trial has left a number of questions unanswered about the role of JAK inhibitors in managing CVD risk in patients with RA. “The issue that we’re trying to ask is, is it just the TNF inhibitors may be better? Is this a subpopulation issue, or was it just bad luck from the purposes of this one trial? Granted, it was a very large trial, but you can still have luck in terms of getting an effect that’s not accurate.”
Dr. Giles’ “gut feeling” on JAK inhibitors is that they’re not causing harm, but that they’re not as effective as TNF inhibitors in ameliorating CV risks in patients with RA.
Michael S. Garshick, MD, who attended the conference and is head of the cardio-rheumatology program at NYU Langone Health, concurred that a number of unanswered questions persist over the treatment of CVD risk in RA — and autoimmune disease in general.
“I think we’re still trying to prove that DMARDs reduce cardiovascular risk in autoimmune conditions,” he said. “The epidemiologic data would suggest, yes, that inflammation prevention is beneficial for cardiovascular disease, but the TARGET trial suggested that vascular inflammation improved by treating RA, but that biologic therapy wasn’t better than traditional triple therapy.”
Other questions remain unanswered, Dr. Garshick said.
“Is there a specific immunotherapy that is most beneficial to reduce heart disease in patients with an autoimmune condition, whether it’s rheumatoid arthritis, psoriasis, or lupus?”
Dr. Garshick said he’s specifically interested in the residual risk that exists after treating the autoimmunity. “Do you still have a higher risk for heart disease, and if so, why? Is there something else going on that we can’t see?”
The biggest unanswered question, he said, is “How can we do a better job of recognizing heart disease risk in these patients? That’s the low-hanging fruit that people are studying, but across many of those studies, patients have higher rates of blood pressure, cholesterol issues, obesity, diabetes, and many times, we’re not adequately treating these comorbidities.”
That, Dr. Garshick said, may be a result of physician fatigue. “And so [treatment of these comorbidities is] kicked down the road for a year or years,” he added.
Dr. Giles disclosed financial relationships with Pfizer, AbbVie, Eli Lilly, and Novartis. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.
A version of this article appeared on Medscape.com.
NEW YORK — Patients with rheumatoid arthritis (RA) carry a high risk for cardiovascular events, but mounting clinical evidence suggests they’re being undertreated to manage that risk. Rheumatologists should consider a patient with RA’s cardiovascular disease (CVD) status before deciding on RA treatments, a researcher of cardiometabolic disorders advised.
“The ORAL Surveillance trial suggests that we need to consider cardiovascular risk factors and maybe do additional screening in these patients before we use RA therapies,” Jon T. Giles, MD, PhD, director of the Cedars-Sinai Inflammatory Arthritis Clinical Center at Cedars-Sinai in Los Angeles, told attendees at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.
Underuse of Statins
ORAL Surveillance enrolled 4362 patients with RA aged 50 years and older with at least one cardiovascular risk factor. About 23% of all patients were taking statins, as were about half of patients with a history of atherosclerotic CVD (ASCVD).
“A lot of those people should have been on statins,” Dr. Giles said in an interview. “Not because of their RA but because of their risk factors, and then RA brings it up another notch.” In the population with ASCVD, Dr. Giles added, “It should have been more like 70% and 80%. If we’re talking about a disease that has enhanced cardiovascular risk, then the adoption of standard care that you would do for anybody in the general population should be at that standard and maybe above.”
Multiple studies have documented the underlying risk for CVD events, CV mortality, and subclinical atherosclerosis in people with RA, Dr. Giles noted in his presentation. Physiologically, the RA-specific risk factors most linked to CVD risk are systemic inflammation/cytokine excess and specific circulating T-cell and intermediate monocyte subsets, or both, Dr. Giles said.
Disease-Modifying Antirheumatic Drugs (DMARDs) and CVD Risk
Likewise, research in the past decade has linked methotrexate and tumor necrosis factor (TNF) inhibitors to reduced ASCVD events in RA. Another study showed that abatacept had an effect similar to that of etanercept in patients with RA, and the ENTRACTE trial, for which Dr. Giles was the lead author, demonstrated that tocilizumab matched etanercept in reducing CV events.
The ORAL Surveillance investigators also reported that patients with RA who were receiving the Janus kinase (JAK) inhibitor tofacitinib had a higher risk for major adverse cardiovascular events and cancers than those on TNF therapy, Dr. Giles noted. While statins in combination with JAK inhibitors may have the potential to provide a balance for controlling CV risk in patients with RA, he said later that the potential of JAK inhibitors in reducing CVD risk in RA “is still unsettled.”
The ongoing TARGET trial is further evaluating the impact of DMARDs on vascular inflammation in RA, said Dr. Giles, who’s also a trial principal investigator. TARGET is randomizing 115 patients with RA who didn’t respond to methotrexate to a TNF inhibitor or the addition of sulfasalazine and hydroxychloroquine to their methotrexate. Patients can be on low-intensity but not high-intensity statin therapy, Dr. Giles said.
TARGET results reported last year demonstrated an 8% decrease in arterial fluorodeoxyglucose (FDG) uptake on PET-CT in both treatment arms. Previous studies, Dr. Giles noted, have shown a potential link between FDG and histologic markers of inflammation. “An 8% decrease in vascular FDG is in line with what you would expect from statin treatment,” he said.
TARGET results published in April showed that a measure of a cluster of 12 cytokines and other inflammatory mediators, known as the multibiomarker disease activity (MBDA) score and marketed under the brand name Vectra DA, may help determine arterial FDG uptake. “Those who had a low MBDA score at week 24 actually had the greatest reduction in the arterial FDG,” he said.
Those results were driven entirely by low serum amyloid A (SAA) levels, Dr. Giles said. Those same results didn’t hold for patients in whom SAA and C-reactive protein were correlated.
“So, there’s more to come here,” Dr. Giles said. “We’re looking at other, much larger biomarker panels.”
Nonetheless, he said, sufficient evidence exists to conclude that treating RA to target reduces CV events. “The idea is that at every visit that you see an RA patient, you measure their disease activity, and if they’re not at the target of low disease activity or remission, then you change their therapy to improve that,” he said in an interview.
But an evidence-based guideline is needed to improve coverage of CVD risks in patients with RA, Dr. Giles said. “There is a movement afoot” for a guideline, he said. “If you just did what is supposed to happen for a general population, you would make some improvements. The risk-benefit [ratio] for statins for people with RA has been looked at, and it’s very favorable.”
Unanswered Questions
Dr. Giles noted that the ORAL Surveillance trial has left a number of questions unanswered about the role of JAK inhibitors in managing CVD risk in patients with RA. “The issue that we’re trying to ask is, is it just the TNF inhibitors may be better? Is this a subpopulation issue, or was it just bad luck from the purposes of this one trial? Granted, it was a very large trial, but you can still have luck in terms of getting an effect that’s not accurate.”
Dr. Giles’ “gut feeling” on JAK inhibitors is that they’re not causing harm, but that they’re not as effective as TNF inhibitors in ameliorating CV risks in patients with RA.
Michael S. Garshick, MD, who attended the conference and is head of the cardio-rheumatology program at NYU Langone Health, concurred that a number of unanswered questions persist over the treatment of CVD risk in RA — and autoimmune disease in general.
“I think we’re still trying to prove that DMARDs reduce cardiovascular risk in autoimmune conditions,” he said. “The epidemiologic data would suggest, yes, that inflammation prevention is beneficial for cardiovascular disease, but the TARGET trial suggested that vascular inflammation improved by treating RA, but that biologic therapy wasn’t better than traditional triple therapy.”
Other questions remain unanswered, Dr. Garshick said.
“Is there a specific immunotherapy that is most beneficial to reduce heart disease in patients with an autoimmune condition, whether it’s rheumatoid arthritis, psoriasis, or lupus?”
Dr. Garshick said he’s specifically interested in the residual risk that exists after treating the autoimmunity. “Do you still have a higher risk for heart disease, and if so, why? Is there something else going on that we can’t see?”
The biggest unanswered question, he said, is “How can we do a better job of recognizing heart disease risk in these patients? That’s the low-hanging fruit that people are studying, but across many of those studies, patients have higher rates of blood pressure, cholesterol issues, obesity, diabetes, and many times, we’re not adequately treating these comorbidities.”
That, Dr. Garshick said, may be a result of physician fatigue. “And so [treatment of these comorbidities is] kicked down the road for a year or years,” he added.
Dr. Giles disclosed financial relationships with Pfizer, AbbVie, Eli Lilly, and Novartis. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>NEW YORK — Patients with rheumatoid arthritis (RA) carry a high risk for cardiovascular events, but mounting clinical evidence suggests they’re being undertreat</metaDescription> <articlePDF/> <teaserImage>174233</teaserImage> <teaser>Disease-modifying antirheumatic drugs can reduce some cardiovascular risk in patients with rheumatoid arthritis, but questions remain whether that’s enough when statin use lags.</teaser> <title>Don’t Leave CVD Risk in RA Undertreated Despite Unresolved Questions</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> <term>15</term> </publications> <sections> <term>68512</term> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">289</term> <term>290</term> <term>194</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24006725.jpg</altRep> <description role="drol:caption">Dr. Jon T. Giles</description> <description role="drol:credit"/> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240106ac.jpg</altRep> <description role="drol:caption">Dr. Michael S. Garshick</description> <description role="drol:credit">NYU Langone</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Don’t Leave CVD Risk in RA Undertreated Despite Unresolved Questions</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">NEW YORK</span> — Patients with rheumatoid arthritis (RA) carry a high risk for cardiovascular events, but mounting clinical evidence suggests they’re being undertreated to manage that risk. Rheumatologists should consider a patient with RA’s cardiovascular disease (CVD) status before deciding on RA treatments, a researcher of cardiometabolic disorders advised.</p> <p>“The <span class="Hyperlink"><a href="https://ard.bmj.com/content/82/1/119.long">ORAL Surveillance trial</a></span> suggests that we need to consider cardiovascular risk factors and maybe do additional screening in these patients before we use RA therapies,” Jon T. Giles, MD, PhD, director of the Cedars-Sinai Inflammatory Arthritis Clinical Center at Cedars-Sinai in Los Angeles, told attendees at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.<br/><br/></p> <h2>Underuse of Statins</h2> <p>ORAL Surveillance enrolled 4362 patients with RA aged 50 years and older with at least one cardiovascular risk factor. About 23% of all patients were taking statins, as were about half of patients with a history of atherosclerotic CVD (ASCVD).</p> <p>[[{"fid":"174233","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Jon T. Giles, Columbia University, New York","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Jon T. Giles"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]“A lot of those people should have been on statins,” Dr. Giles said in an interview. “Not because of their RA but because of their risk factors, and then RA brings it up another notch.” In the population with ASCVD, Dr. Giles added, “It should have been more like 70% and 80%. If we’re talking about a disease that has enhanced cardiovascular risk, then the adoption of standard care that you would do for anybody in the general population should be at that standard and maybe above.”<br/><br/>Multiple studies have documented the underlying risk for CVD events, CV mortality, and subclinical atherosclerosis in people with RA, Dr. Giles noted in his presentation. Physiologically, the RA-specific risk factors most linked to CVD risk are systemic inflammation/cytokine excess and specific circulating T-cell and intermediate monocyte subsets, or both, Dr. Giles said.<br/><br/></p> <h2>Disease-Modifying Antirheumatic Drugs (DMARDs) and CVD Risk</h2> <p>Likewise, <span class="Hyperlink"><a href="https://ard.bmj.com/content/74/3/480.long">research</a></span> in the past decade has linked methotrexate and tumor necrosis factor (TNF) inhibitors to reduced ASCVD events in RA. <span class="Hyperlink"><a href="https://www.ahajournals.org/doi/full/10.1161/JAHA.117.007393?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org">Another study</a></span> showed that abatacept had an effect similar to that of etanercept in patients with RA, and the <span class="Hyperlink"><a href="https://acrjournals.onlinelibrary.wiley.com/doi/ftr/10.1002/art.41095">ENTRACTE trial</a></span>, for which Dr. Giles was the lead author, demonstrated that tocilizumab matched etanercept in reducing CV events.</p> <p>The <span class="Hyperlink"><a href="https://www.nejm.org/doi/10.1056/NEJMoa2109927">ORAL Surveillance investigators also reported</a></span> that patients with RA who were receiving the Janus kinase (JAK) inhibitor tofacitinib had a higher risk for major adverse cardiovascular events and cancers than those on TNF therapy, Dr. Giles noted. While statins in combination with JAK inhibitors may have the potential to provide a balance for controlling CV risk in patients with RA, he said later that the potential of JAK inhibitors in reducing CVD risk in RA “is still unsettled.”<br/><br/>The ongoing <span class="Hyperlink"><a href="https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr2.11256">TARGET trial</a></span> is further evaluating the impact of DMARDs on vascular inflammation in RA, said Dr. Giles, who’s also a trial principal investigator. TARGET is randomizing 115 patients with RA who didn’t respond to methotrexate to a TNF inhibitor or the addition of sulfasalazine and hydroxychloroquine to their methotrexate. Patients can be on low-intensity but not high-intensity statin therapy, Dr. Giles said.<br/><br/><span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/985277">TARGET results reported last year</a></span> demonstrated an 8% decrease in arterial fluorodeoxyglucose (FDG) uptake on PET-CT in both treatment arms. <span class="Hyperlink"><a href="https://www.sciencedirect.com/science/article/pii/S1936878X11005900?via%3Dihub">Previous studies</a></span>, Dr. Giles noted, have shown a potential link between FDG and histologic markers of inflammation. “An 8% decrease in vascular FDG is in line with what you would expect from statin treatment,” he said.<br/><br/><span class="Hyperlink"><a href="https://academic.oup.com/rheumatology/advance-article-abstract/doi/10.1093/rheumatology/keae242/7656782?redirectedFrom=fulltext&login=false">TARGET results published in April</a></span> showed that a measure of a cluster of 12 cytokines and other inflammatory mediators, known as the multibiomarker disease activity (MBDA) score and marketed under the brand name Vectra DA, may help determine arterial FDG uptake. “Those who had a low MBDA score at week 24 actually had the greatest reduction in the arterial FDG,” he said.<br/><br/>Those results were driven entirely by low serum amyloid A (SAA) levels, Dr. Giles said. Those same results didn’t hold for patients in whom SAA and C-reactive protein were correlated.<br/><br/>“So, there’s more to come here,” Dr. Giles said. “We’re looking at other, much larger biomarker panels.”<br/><br/>Nonetheless, he said, sufficient evidence exists to conclude that treating RA to target reduces CV events. “The idea is that at every visit that you see an RA patient, you measure their disease activity, and if they’re not at the target of low disease activity or remission, then you change their therapy to improve that,” he said in an interview.<br/><br/>But an evidence-based guideline is needed to improve coverage of CVD risks in patients with RA, Dr. Giles said. “There is a movement afoot” for a guideline, he said. “If you just did what is supposed to happen for a general population, you would make some improvements. The risk-benefit [ratio] for statins for people with RA has been looked at, and it’s very favorable.”<br/><br/></p> <h2>Unanswered Questions</h2> <p>Dr. Giles noted that the ORAL Surveillance trial has left a number of questions unanswered about the role of JAK inhibitors in managing CVD risk in patients with RA. “The issue that we’re trying to ask is, is it just the TNF inhibitors may be better? Is this a subpopulation issue, or was it just bad luck from the purposes of this one trial? Granted, it was a very large trial, but you can still have luck in terms of getting an effect that’s not accurate.”</p> <p>Dr. Giles’ “gut feeling” on JAK inhibitors is that they’re not causing harm, but that they’re not as effective as TNF inhibitors in ameliorating CV risks in patients with RA.<br/><br/>Michael S. Garshick, MD, who attended the conference and is head of the cardio-rheumatology program at NYU Langone Health, concurred that a number of unanswered questions persist over the treatment of CVD risk in RA — and autoimmune disease in general.<br/><br/>[[{"fid":"283534","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Michael S. Garshick, caridiologist, New York University, NYU Langone","field_file_image_credit[und][0][value]":"NYU Langone","field_file_image_caption[und][0][value]":"Dr. Michael S. Garshick"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]“I think we’re still trying to prove that DMARDs reduce cardiovascular risk in autoimmune conditions,” he said. “The epidemiologic data would suggest, yes, that inflammation prevention is beneficial for cardiovascular disease, but the TARGET trial suggested that vascular inflammation improved by treating RA, but that biologic therapy wasn’t better than traditional triple therapy.”<br/><br/>Other questions remain unanswered, Dr. Garshick said.<br/><br/>“Is there a specific immunotherapy that is most beneficial to reduce heart disease in patients with an autoimmune condition, whether it’s rheumatoid arthritis, psoriasis, or lupus?”<br/><br/>Dr. Garshick said he’s specifically interested in the residual risk that exists after treating the autoimmunity. “Do you still have a higher risk for heart disease, and if so, why? Is there something else going on that we can’t see?”<br/><br/>The biggest unanswered question, he said, is “How can we do a better job of recognizing heart disease risk in these patients? That’s the low-hanging fruit that people are studying, but across many of those studies, patients have higher rates of blood pressure, cholesterol issues, obesity, diabetes, and many times, we’re not adequately treating these comorbidities.”<br/><br/>That, Dr. Garshick said, may be a result of physician fatigue. “And so [treatment of these comorbidities is] kicked down the road for a year or years,” he added.<br/><br/>Dr. Giles disclosed financial relationships with Pfizer, AbbVie, Eli Lilly, and Novartis. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.<span class="end"/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/ra-treatment-dont-overlook-underlying-cv-risks-2024a10009b7">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
