Lupus & Connective Tissue Diseases

Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.

The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.

Now rheumatologists are trying to reassure patients with lupus or other rheumatic diseases who take the antimalarials that they will be available and are relatively easy for manufacturers to produce.

In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.

Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity. 
 

Questions about hydroxychloroquine shortage

Q: What is the current situation with hydroxychloroquine in your practice?

A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.

Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
 

Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?

A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.

Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.

Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.

The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.

Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
 

Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?

A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.

Q: Are there pharmacy restrictions on prescription amounts?

A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
 

Colchicine COVID-19 trial underway

Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too. 

Q: What is the general availability of colchicine and its susceptibility to shortage?

A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.

The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.

Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
 

Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?

A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.

The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.

While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.

Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.

The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.

Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.

So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.

Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.

[email protected]

This article was reformatted on 3/30/2020 for clarity. 

Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.

The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.

Now rheumatologists are trying to reassure patients with lupus or other rheumatic diseases who take the antimalarials that they will be available and are relatively easy for manufacturers to produce.

In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.

Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity. 
 

Questions about hydroxychloroquine shortage

Q: What is the current situation with hydroxychloroquine in your practice?

A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.

Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
 

Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?

A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.

Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.

Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.

The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.

Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
 

Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?

A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.

Q: Are there pharmacy restrictions on prescription amounts?

A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
 

Colchicine COVID-19 trial underway

Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too. 

Q: What is the general availability of colchicine and its susceptibility to shortage?

A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.

The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.

Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
 

Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?

A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.

The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.

While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.

Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.

The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.

Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.

So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.

Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.

[email protected]

This article was reformatted on 3/30/2020 for clarity. 

Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.

The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.

Now rheumatologists are trying to reassure patients with lupus or other rheumatic diseases who take the antimalarials that they will be available and are relatively easy for manufacturers to produce.

In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.

Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity. 
 

Questions about hydroxychloroquine shortage

Q: What is the current situation with hydroxychloroquine in your practice?

A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.

Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
 

Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?

A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.

Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.

Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.

The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.

Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
 

Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?

A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.

Q: Are there pharmacy restrictions on prescription amounts?

A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
 

Colchicine COVID-19 trial underway

Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too. 

Q: What is the general availability of colchicine and its susceptibility to shortage?

A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.

The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.

Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
 

Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?

A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.

The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.

While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.

Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.

The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.

Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.

So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.

Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.

[email protected]

This article was reformatted on 3/30/2020 for clarity. 

For almost a quarter century, Julie Powers, a 48-year-old non-profit professional from Maryland, has been taking the same medication for her lupus — and until recently, she never worried that her supply would run out. Now she’s terrified that she might lose access to a drug that prevents her immune system from attacking her heart, lungs, and skin. She describes a feeling akin to being underwater, near drowning: “That’s what my life would be like,” she said. “I’ll suffocate.”

Powers’ concerns began roughly a week ago when she learned that her lupus drug, hydroxychloroquine (hi-DROCK-see-KLORA-quin), may be helpful in the treatment of Covid-19, the illness caused by the SARS-CoV-2 virus now racing across the planet. The medication was already being used around world to treat Covid-19 patients, but evidence of its effectiveness was largely anecdotal. Then, on March 16, a renowned infectious disease specialist, Didier Raoult, announced the results of a small clinical trial in France showing that patients receiving a combination of hydroxychloroquine and the common antibiotic azithromycin had notably lower levels of the virus in their bloodstream than those who did not receive the medication.

In the last week, this once obscure drug has been thrust into the national spotlight with everyone from doctors, to laypeople, to the U.S. president weighing in. The attention has so dramatically driven up demand that pharmacists are reporting depleted stocks of the drug, leaving many of the roughly 1.5 million lupus patients across the country unable to get their prescriptions filled. They now face an uncertain future as the public clings to one of the first signs of hope to appear since the coronavirus began sweeping across the U.S.

But scientists and physicians caution that this hope is based on studies that have been conducted outside of traditional scientific timelines. “The paper is interesting and certainly would warrant future more definitive studies,” Jeff Sparks, a rheumatologist and researcher at Harvard Medical School, said of the French study. “It might even be enough data to use the regimen off-label for sick and hospitalized patients.

“However,” he added, “it does not prove that the regimen actually works.”

Despite efforts to pin blame for the shortages on Trump alone, however, hydroxychloroquine scarcity was already setting in weeks ago, as doctors began responding on their own to percolating and preliminary research. Some evidence suggests that many doctors are now writing prescriptions prophylactically for patients with no known illness — as well as for themselves and family members — prompting at least one state pharmacy board to call an emergency meeting, scheduled for Sunday morning. The board planned to bar pharmacists from dispensing chloroquine or hydroxychloroquine for anyone other than confirmed Covid-19 patients without approval of the board's director.

A prolonged shortfall in supplies would likely have grave implications for people who depend on it — including Powers, who believes that she would not be alive today without the drug. “I guarantee you, it has saved my life,” she said. “It’s the only thing that’s protecting my organs. There’s nothing else.” Like others, she hopes that pharmaceutical companies that manufacture versions of the drug will be able to quickly ramp up production — something several have already promised to do. In the meantime, Powers has a message for the American public — one echoed by most lupus doctors: When it comes to hydroxychloroquine: “If you don’t need it, don’t get it.”

The origins of hydroxychloroquine can be traced back hundreds of years to South America, where the bark of the cinchona tree appears to have been used by Andean populations to treat shivering. European missionaries eventually brought the bark to Europe, where it was used to treat malaria. In 1820, French researchers isolated the substance in the bark responsible for its beneficial effects. They named it “quinine.” When the supply from South America began to dry up, the British and Dutch decided to grow the tree on plantations.

Over time, synthetic versions were developed, including a drug called chloroquine, which was created in the midst of World War II in an effort to spare overseas American troops from malaria. As it turned out, troops with rashes and arthritis saw an improvement in symptoms after using this anti-malarial medication. After the war, a related drug was created, one with fewer side-effects when taken long-term: hydroxychloroquine. It went on to be used to treat many types of autoimmune diseases, including rheumatoid arthritis and lupus. The latter, which disproportionately affects women, used to cut lives short — typically from failure of the kidneys. Those numbers have been reduced with strict management of the disease, but the Lupus Foundation of America estimates that 10 to 15 percent of patients die prematurely due to complications of the disease.

For almost a quarter century, Julie Powers, a 48-year-old non-profit professional from Maryland, has been taking the same medication for her lupus — and until recently, she never worried that her supply would run out. Now she’s terrified that she might lose access to a drug that prevents her immune system from attacking her heart, lungs, and skin. She describes a feeling akin to being underwater, near drowning: “That’s what my life would be like,” she said. “I’ll suffocate.”

Powers’ concerns began roughly a week ago when she learned that her lupus drug, hydroxychloroquine (hi-DROCK-see-KLORA-quin), may be helpful in the treatment of Covid-19, the illness caused by the SARS-CoV-2 virus now racing across the planet. The medication was already being used around world to treat Covid-19 patients, but evidence of its effectiveness was largely anecdotal. Then, on March 16, a renowned infectious disease specialist, Didier Raoult, announced the results of a small clinical trial in France showing that patients receiving a combination of hydroxychloroquine and the common antibiotic azithromycin had notably lower levels of the virus in their bloodstream than those who did not receive the medication.

In the last week, this once obscure drug has been thrust into the national spotlight with everyone from doctors, to laypeople, to the U.S. president weighing in. The attention has so dramatically driven up demand that pharmacists are reporting depleted stocks of the drug, leaving many of the roughly 1.5 million lupus patients across the country unable to get their prescriptions filled. They now face an uncertain future as the public clings to one of the first signs of hope to appear since the coronavirus began sweeping across the U.S.

But scientists and physicians caution that this hope is based on studies that have been conducted outside of traditional scientific timelines. “The paper is interesting and certainly would warrant future more definitive studies,” Jeff Sparks, a rheumatologist and researcher at Harvard Medical School, said of the French study. “It might even be enough data to use the regimen off-label for sick and hospitalized patients.

“However,” he added, “it does not prove that the regimen actually works.”

Despite efforts to pin blame for the shortages on Trump alone, however, hydroxychloroquine scarcity was already setting in weeks ago, as doctors began responding on their own to percolating and preliminary research. Some evidence suggests that many doctors are now writing prescriptions prophylactically for patients with no known illness — as well as for themselves and family members — prompting at least one state pharmacy board to call an emergency meeting, scheduled for Sunday morning. The board planned to bar pharmacists from dispensing chloroquine or hydroxychloroquine for anyone other than confirmed Covid-19 patients without approval of the board's director.

A prolonged shortfall in supplies would likely have grave implications for people who depend on it — including Powers, who believes that she would not be alive today without the drug. “I guarantee you, it has saved my life,” she said. “It’s the only thing that’s protecting my organs. There’s nothing else.” Like others, she hopes that pharmaceutical companies that manufacture versions of the drug will be able to quickly ramp up production — something several have already promised to do. In the meantime, Powers has a message for the American public — one echoed by most lupus doctors: When it comes to hydroxychloroquine: “If you don’t need it, don’t get it.”

The origins of hydroxychloroquine can be traced back hundreds of years to South America, where the bark of the cinchona tree appears to have been used by Andean populations to treat shivering. European missionaries eventually brought the bark to Europe, where it was used to treat malaria. In 1820, French researchers isolated the substance in the bark responsible for its beneficial effects. They named it “quinine.” When the supply from South America began to dry up, the British and Dutch decided to grow the tree on plantations.

Over time, synthetic versions were developed, including a drug called chloroquine, which was created in the midst of World War II in an effort to spare overseas American troops from malaria. As it turned out, troops with rashes and arthritis saw an improvement in symptoms after using this anti-malarial medication. After the war, a related drug was created, one with fewer side-effects when taken long-term: hydroxychloroquine. It went on to be used to treat many types of autoimmune diseases, including rheumatoid arthritis and lupus. The latter, which disproportionately affects women, used to cut lives short — typically from failure of the kidneys. Those numbers have been reduced with strict management of the disease, but the Lupus Foundation of America estimates that 10 to 15 percent of patients die prematurely due to complications of the disease.

For almost a quarter century, Julie Powers, a 48-year-old non-profit professional from Maryland, has been taking the same medication for her lupus — and until recently, she never worried that her supply would run out. Now she’s terrified that she might lose access to a drug that prevents her immune system from attacking her heart, lungs, and skin. She describes a feeling akin to being underwater, near drowning: “That’s what my life would be like,” she said. “I’ll suffocate.”

Powers’ concerns began roughly a week ago when she learned that her lupus drug, hydroxychloroquine (hi-DROCK-see-KLORA-quin), may be helpful in the treatment of Covid-19, the illness caused by the SARS-CoV-2 virus now racing across the planet. The medication was already being used around world to treat Covid-19 patients, but evidence of its effectiveness was largely anecdotal. Then, on March 16, a renowned infectious disease specialist, Didier Raoult, announced the results of a small clinical trial in France showing that patients receiving a combination of hydroxychloroquine and the common antibiotic azithromycin had notably lower levels of the virus in their bloodstream than those who did not receive the medication.

In the last week, this once obscure drug has been thrust into the national spotlight with everyone from doctors, to laypeople, to the U.S. president weighing in. The attention has so dramatically driven up demand that pharmacists are reporting depleted stocks of the drug, leaving many of the roughly 1.5 million lupus patients across the country unable to get their prescriptions filled. They now face an uncertain future as the public clings to one of the first signs of hope to appear since the coronavirus began sweeping across the U.S.

But scientists and physicians caution that this hope is based on studies that have been conducted outside of traditional scientific timelines. “The paper is interesting and certainly would warrant future more definitive studies,” Jeff Sparks, a rheumatologist and researcher at Harvard Medical School, said of the French study. “It might even be enough data to use the regimen off-label for sick and hospitalized patients.

“However,” he added, “it does not prove that the regimen actually works.”

Despite efforts to pin blame for the shortages on Trump alone, however, hydroxychloroquine scarcity was already setting in weeks ago, as doctors began responding on their own to percolating and preliminary research. Some evidence suggests that many doctors are now writing prescriptions prophylactically for patients with no known illness — as well as for themselves and family members — prompting at least one state pharmacy board to call an emergency meeting, scheduled for Sunday morning. The board planned to bar pharmacists from dispensing chloroquine or hydroxychloroquine for anyone other than confirmed Covid-19 patients without approval of the board's director.

A prolonged shortfall in supplies would likely have grave implications for people who depend on it — including Powers, who believes that she would not be alive today without the drug. “I guarantee you, it has saved my life,” she said. “It’s the only thing that’s protecting my organs. There’s nothing else.” Like others, she hopes that pharmaceutical companies that manufacture versions of the drug will be able to quickly ramp up production — something several have already promised to do. In the meantime, Powers has a message for the American public — one echoed by most lupus doctors: When it comes to hydroxychloroquine: “If you don’t need it, don’t get it.”

The origins of hydroxychloroquine can be traced back hundreds of years to South America, where the bark of the cinchona tree appears to have been used by Andean populations to treat shivering. European missionaries eventually brought the bark to Europe, where it was used to treat malaria. In 1820, French researchers isolated the substance in the bark responsible for its beneficial effects. They named it “quinine.” When the supply from South America began to dry up, the British and Dutch decided to grow the tree on plantations.

Over time, synthetic versions were developed, including a drug called chloroquine, which was created in the midst of World War II in an effort to spare overseas American troops from malaria. As it turned out, troops with rashes and arthritis saw an improvement in symptoms after using this anti-malarial medication. After the war, a related drug was created, one with fewer side-effects when taken long-term: hydroxychloroquine. It went on to be used to treat many types of autoimmune diseases, including rheumatoid arthritis and lupus. The latter, which disproportionately affects women, used to cut lives short — typically from failure of the kidneys. Those numbers have been reduced with strict management of the disease, but the Lupus Foundation of America estimates that 10 to 15 percent of patients die prematurely due to complications of the disease.

MAUI, HAWAII – An underlying primary immunodeficiency is far more common among patients in rheumatologists’ offices than is generally appreciated, Anna Postolova, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“Autoimmunity and immunodeficiency are often incorrectly thought to be mutually exclusive, but I hope to convey to you that they actually run together more than we think, and more than you realize. In the immunodeficiency community, we’re now realizing that autoimmunity can be the first presentation of an immunodeficiency disease,” according to Dr. Postolova, a dual rheumatologist and allergist/immunologist at Stanford (Calif.) University.

She cited a major retrospective study of 2,183 consecutive patients with primary immunodeficiencies (PIDs), mean age 25.8 years, enrolled in a French national PID registry. Of these patients, 26% had at least one autoimmune or inflammatory condition. The French investigators, all immunologists, categorized 12.8% of the PID patients as having rheumatologic disorders, but Dr. Postolova is convinced this figure would have been substantially higher had a rheumatologist been on the research team. That’s because vasculitis and inflammatory eye disorders weren’t included in the rheumatologic disease category, and psoriatic arthritis was probably present but undiagnosed in some psoriasis patients grouped in the skin disease category.

“Our results demonstrate that autoimmune and inflammatory diseases are much more frequent by a factor of at least 10 in patients with PIDs than in the general population,” the French investigators observed.

Indeed, the relative risks of vasculitis, inflammatory eye disease, and skin disease in patients with PID were increased 13-, 7-, and 10-fold, respectively. French children with PID were at 40-fold increased risk for rheumatoid arthritis and 80-fold elevated risk for inflammatory bowel disease.

Among the PID patients with at least one autoimmune or inflammatory condition, 31.6% had more than one. And therein lies a clue for rheumatologists.

“You might have some patients in your panel who have both arthritis and vasculitis, for example. It’s not that common for our patients to have two of our diseases, but those are the ones who might have an immune dysregulatory inborn error of metabolism mutation that’s driving their disease – and we’re now able to look into that,” Dr. Postolova explained.

At present, more than 300 identified single-gene inborn errors of immunity have been identified, some of which can manifest variously as systemic lupus erythematosus (SLE), arthritis, vasculitis, and/or cytopenias, she noted.

In the French study, onset of autoimmune or inflammatory manifestations of PID occurred across the age spectrum. The age of onset was earlier with T-cell and innate immunity deficiencies than in patients with B-cell deficiencies. The prevalence of an autoimmune or inflammatory disorder was greater than 40% in PID patients age 50 years or older.

“What I want to hammer home is these patients with PID are no longer succumbing to their infections. They’re being identified as having an immunodeficiency, they’re going on antibiotics, they’re strictly monitored, and they’re growing older. And as their aberrant immune system fights an infection, they have more and more time to dysregulate and develop one of our diseases. So in the coming years I think you’re going to see a lot more of these patients show up in your rheumatology clinic because they are getting older,” Dr. Postolova said.
 

Red flags for underlying PID

Recurrent infections are a hallmark of PIDs. And mutations that cause increased infections can alter central and peripheral tolerance, affecting cell growth, signaling, and survival, which in turn affects immunity.

“As we use biologics in our patients with rheumatologic diseases, I think there’s a cohort of patients we’re starting to identify who are getting very serious recurrent infections. It’s not every patient. But that patient who’s had three or four serious infections, that’s the patient who I think we’ll be able to identify in our clinics through an immunodeficiency evaluation. Likewise, the patients who are not responding to multiple different drugs, that’s where I’d stop and think about an underlying immune deficiency,” she said.

A show of hands indicated only about 25% of her audience of rheumatologists routinely ask new patients if they have a personal or family history of recurrent infections. That should be routine practice, in Dr. Postolova’s view. The 10 warning signs of PID for adults put forth by the Jeffrey Modell Foundation focus on a family or personal history of recurrent ear or sinus infections, deep skin abscesses, pneumonia, viral infections, persistent thrush, or chronic diarrhea with weight loss.
 

Testing for PID

It’s “absolutely appropriate” to start a work-up for suspected immunodeficiency in a rheumatology clinic, according to Dr. Postolova.

“I think every allergist/immunologist would be grateful if you can just order a quantitative immunoglobulin panel as well as specific antibody titer responses to tetanus, diphtheria, pneumococcal vaccine, and an IgG subclass analysis. That’s half of an immunologist’s initial assessment,” she said.

Corticosteroids and other disease-modifying antirheumatic drugs (DMARDs) affect flow cytometry test results. It’s best to hold off on testing until after a patient has been off therapy for 2-3 months. Similarly, treatment with intravenous immunoglobulin (IVIg) will confound measurement of vaccine antibody titers, so it’s recommended to wait for 3-6 months off IVIg before testing.

Genetic testing for PID has become a lot simpler and more affordable. Numerous companies have developed test kits featuring relatively small panels of selected genes of interest. Dr. Postolova often uses Invitae, a Bay Area company that has a 207-gene panel covered by most insurers with an out-of-pocket cost to the patient of $250.

“Upfront when I have a complicated patient where I am concerned about the possibility of immunodeficiency, I will ask if that’s something they can afford and if they want to move forward with it. Also, Invitae has a patient assistance program. I’ve found this helpful in some of my very complicated patients,” she said.
 

Get to know your local allergist/immunologist

Many allergist/immunologists have overcome their traditional reservations about immunosuppressing an immunosuppressed individual and are now treating PID/autoimmune disease–overlap patients with the very drugs rheumatologists use every day, including standard DMARDs, rituximab, abatacept, anakinra, and tumor necrosis factor inhibitors.

“I encourage you to work with your allergist/immunologist for these patients because they’re going to need help,” according to Dr. Postolova. “The people in this room are the most equipped to treat the overlap patients because allergists and immunologists don’t really have the training to use these drugs. A lot of them do use them, but you have a better handle on these drugs than other people.”

Dr. Postolova reported having no financial conflicts regarding her presentation.

[email protected]

MAUI, HAWAII – An underlying primary immunodeficiency is far more common among patients in rheumatologists’ offices than is generally appreciated, Anna Postolova, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“Autoimmunity and immunodeficiency are often incorrectly thought to be mutually exclusive, but I hope to convey to you that they actually run together more than we think, and more than you realize. In the immunodeficiency community, we’re now realizing that autoimmunity can be the first presentation of an immunodeficiency disease,” according to Dr. Postolova, a dual rheumatologist and allergist/immunologist at Stanford (Calif.) University.

She cited a major retrospective study of 2,183 consecutive patients with primary immunodeficiencies (PIDs), mean age 25.8 years, enrolled in a French national PID registry. Of these patients, 26% had at least one autoimmune or inflammatory condition. The French investigators, all immunologists, categorized 12.8% of the PID patients as having rheumatologic disorders, but Dr. Postolova is convinced this figure would have been substantially higher had a rheumatologist been on the research team. That’s because vasculitis and inflammatory eye disorders weren’t included in the rheumatologic disease category, and psoriatic arthritis was probably present but undiagnosed in some psoriasis patients grouped in the skin disease category.

“Our results demonstrate that autoimmune and inflammatory diseases are much more frequent by a factor of at least 10 in patients with PIDs than in the general population,” the French investigators observed.

Indeed, the relative risks of vasculitis, inflammatory eye disease, and skin disease in patients with PID were increased 13-, 7-, and 10-fold, respectively. French children with PID were at 40-fold increased risk for rheumatoid arthritis and 80-fold elevated risk for inflammatory bowel disease.

Among the PID patients with at least one autoimmune or inflammatory condition, 31.6% had more than one. And therein lies a clue for rheumatologists.

“You might have some patients in your panel who have both arthritis and vasculitis, for example. It’s not that common for our patients to have two of our diseases, but those are the ones who might have an immune dysregulatory inborn error of metabolism mutation that’s driving their disease – and we’re now able to look into that,” Dr. Postolova explained.

At present, more than 300 identified single-gene inborn errors of immunity have been identified, some of which can manifest variously as systemic lupus erythematosus (SLE), arthritis, vasculitis, and/or cytopenias, she noted.

In the French study, onset of autoimmune or inflammatory manifestations of PID occurred across the age spectrum. The age of onset was earlier with T-cell and innate immunity deficiencies than in patients with B-cell deficiencies. The prevalence of an autoimmune or inflammatory disorder was greater than 40% in PID patients age 50 years or older.

“What I want to hammer home is these patients with PID are no longer succumbing to their infections. They’re being identified as having an immunodeficiency, they’re going on antibiotics, they’re strictly monitored, and they’re growing older. And as their aberrant immune system fights an infection, they have more and more time to dysregulate and develop one of our diseases. So in the coming years I think you’re going to see a lot more of these patients show up in your rheumatology clinic because they are getting older,” Dr. Postolova said.
 

Red flags for underlying PID

Recurrent infections are a hallmark of PIDs. And mutations that cause increased infections can alter central and peripheral tolerance, affecting cell growth, signaling, and survival, which in turn affects immunity.

“As we use biologics in our patients with rheumatologic diseases, I think there’s a cohort of patients we’re starting to identify who are getting very serious recurrent infections. It’s not every patient. But that patient who’s had three or four serious infections, that’s the patient who I think we’ll be able to identify in our clinics through an immunodeficiency evaluation. Likewise, the patients who are not responding to multiple different drugs, that’s where I’d stop and think about an underlying immune deficiency,” she said.

A show of hands indicated only about 25% of her audience of rheumatologists routinely ask new patients if they have a personal or family history of recurrent infections. That should be routine practice, in Dr. Postolova’s view. The 10 warning signs of PID for adults put forth by the Jeffrey Modell Foundation focus on a family or personal history of recurrent ear or sinus infections, deep skin abscesses, pneumonia, viral infections, persistent thrush, or chronic diarrhea with weight loss.
 

Testing for PID

It’s “absolutely appropriate” to start a work-up for suspected immunodeficiency in a rheumatology clinic, according to Dr. Postolova.

“I think every allergist/immunologist would be grateful if you can just order a quantitative immunoglobulin panel as well as specific antibody titer responses to tetanus, diphtheria, pneumococcal vaccine, and an IgG subclass analysis. That’s half of an immunologist’s initial assessment,” she said.

Corticosteroids and other disease-modifying antirheumatic drugs (DMARDs) affect flow cytometry test results. It’s best to hold off on testing until after a patient has been off therapy for 2-3 months. Similarly, treatment with intravenous immunoglobulin (IVIg) will confound measurement of vaccine antibody titers, so it’s recommended to wait for 3-6 months off IVIg before testing.

Genetic testing for PID has become a lot simpler and more affordable. Numerous companies have developed test kits featuring relatively small panels of selected genes of interest. Dr. Postolova often uses Invitae, a Bay Area company that has a 207-gene panel covered by most insurers with an out-of-pocket cost to the patient of $250.

“Upfront when I have a complicated patient where I am concerned about the possibility of immunodeficiency, I will ask if that’s something they can afford and if they want to move forward with it. Also, Invitae has a patient assistance program. I’ve found this helpful in some of my very complicated patients,” she said.
 

Get to know your local allergist/immunologist

Many allergist/immunologists have overcome their traditional reservations about immunosuppressing an immunosuppressed individual and are now treating PID/autoimmune disease–overlap patients with the very drugs rheumatologists use every day, including standard DMARDs, rituximab, abatacept, anakinra, and tumor necrosis factor inhibitors.

“I encourage you to work with your allergist/immunologist for these patients because they’re going to need help,” according to Dr. Postolova. “The people in this room are the most equipped to treat the overlap patients because allergists and immunologists don’t really have the training to use these drugs. A lot of them do use them, but you have a better handle on these drugs than other people.”

Dr. Postolova reported having no financial conflicts regarding her presentation.

[email protected]

MAUI, HAWAII – An underlying primary immunodeficiency is far more common among patients in rheumatologists’ offices than is generally appreciated, Anna Postolova, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“Autoimmunity and immunodeficiency are often incorrectly thought to be mutually exclusive, but I hope to convey to you that they actually run together more than we think, and more than you realize. In the immunodeficiency community, we’re now realizing that autoimmunity can be the first presentation of an immunodeficiency disease,” according to Dr. Postolova, a dual rheumatologist and allergist/immunologist at Stanford (Calif.) University.

She cited a major retrospective study of 2,183 consecutive patients with primary immunodeficiencies (PIDs), mean age 25.8 years, enrolled in a French national PID registry. Of these patients, 26% had at least one autoimmune or inflammatory condition. The French investigators, all immunologists, categorized 12.8% of the PID patients as having rheumatologic disorders, but Dr. Postolova is convinced this figure would have been substantially higher had a rheumatologist been on the research team. That’s because vasculitis and inflammatory eye disorders weren’t included in the rheumatologic disease category, and psoriatic arthritis was probably present but undiagnosed in some psoriasis patients grouped in the skin disease category.

“Our results demonstrate that autoimmune and inflammatory diseases are much more frequent by a factor of at least 10 in patients with PIDs than in the general population,” the French investigators observed.

Indeed, the relative risks of vasculitis, inflammatory eye disease, and skin disease in patients with PID were increased 13-, 7-, and 10-fold, respectively. French children with PID were at 40-fold increased risk for rheumatoid arthritis and 80-fold elevated risk for inflammatory bowel disease.

Among the PID patients with at least one autoimmune or inflammatory condition, 31.6% had more than one. And therein lies a clue for rheumatologists.

“You might have some patients in your panel who have both arthritis and vasculitis, for example. It’s not that common for our patients to have two of our diseases, but those are the ones who might have an immune dysregulatory inborn error of metabolism mutation that’s driving their disease – and we’re now able to look into that,” Dr. Postolova explained.

At present, more than 300 identified single-gene inborn errors of immunity have been identified, some of which can manifest variously as systemic lupus erythematosus (SLE), arthritis, vasculitis, and/or cytopenias, she noted.

In the French study, onset of autoimmune or inflammatory manifestations of PID occurred across the age spectrum. The age of onset was earlier with T-cell and innate immunity deficiencies than in patients with B-cell deficiencies. The prevalence of an autoimmune or inflammatory disorder was greater than 40% in PID patients age 50 years or older.

“What I want to hammer home is these patients with PID are no longer succumbing to their infections. They’re being identified as having an immunodeficiency, they’re going on antibiotics, they’re strictly monitored, and they’re growing older. And as their aberrant immune system fights an infection, they have more and more time to dysregulate and develop one of our diseases. So in the coming years I think you’re going to see a lot more of these patients show up in your rheumatology clinic because they are getting older,” Dr. Postolova said.
 

Red flags for underlying PID

Recurrent infections are a hallmark of PIDs. And mutations that cause increased infections can alter central and peripheral tolerance, affecting cell growth, signaling, and survival, which in turn affects immunity.

“As we use biologics in our patients with rheumatologic diseases, I think there’s a cohort of patients we’re starting to identify who are getting very serious recurrent infections. It’s not every patient. But that patient who’s had three or four serious infections, that’s the patient who I think we’ll be able to identify in our clinics through an immunodeficiency evaluation. Likewise, the patients who are not responding to multiple different drugs, that’s where I’d stop and think about an underlying immune deficiency,” she said.

A show of hands indicated only about 25% of her audience of rheumatologists routinely ask new patients if they have a personal or family history of recurrent infections. That should be routine practice, in Dr. Postolova’s view. The 10 warning signs of PID for adults put forth by the Jeffrey Modell Foundation focus on a family or personal history of recurrent ear or sinus infections, deep skin abscesses, pneumonia, viral infections, persistent thrush, or chronic diarrhea with weight loss.
 

Testing for PID

It’s “absolutely appropriate” to start a work-up for suspected immunodeficiency in a rheumatology clinic, according to Dr. Postolova.

“I think every allergist/immunologist would be grateful if you can just order a quantitative immunoglobulin panel as well as specific antibody titer responses to tetanus, diphtheria, pneumococcal vaccine, and an IgG subclass analysis. That’s half of an immunologist’s initial assessment,” she said.

Corticosteroids and other disease-modifying antirheumatic drugs (DMARDs) affect flow cytometry test results. It’s best to hold off on testing until after a patient has been off therapy for 2-3 months. Similarly, treatment with intravenous immunoglobulin (IVIg) will confound measurement of vaccine antibody titers, so it’s recommended to wait for 3-6 months off IVIg before testing.

Genetic testing for PID has become a lot simpler and more affordable. Numerous companies have developed test kits featuring relatively small panels of selected genes of interest. Dr. Postolova often uses Invitae, a Bay Area company that has a 207-gene panel covered by most insurers with an out-of-pocket cost to the patient of $250.

“Upfront when I have a complicated patient where I am concerned about the possibility of immunodeficiency, I will ask if that’s something they can afford and if they want to move forward with it. Also, Invitae has a patient assistance program. I’ve found this helpful in some of my very complicated patients,” she said.
 

Get to know your local allergist/immunologist

Many allergist/immunologists have overcome their traditional reservations about immunosuppressing an immunosuppressed individual and are now treating PID/autoimmune disease–overlap patients with the very drugs rheumatologists use every day, including standard DMARDs, rituximab, abatacept, anakinra, and tumor necrosis factor inhibitors.

“I encourage you to work with your allergist/immunologist for these patients because they’re going to need help,” according to Dr. Postolova. “The people in this room are the most equipped to treat the overlap patients because allergists and immunologists don’t really have the training to use these drugs. A lot of them do use them, but you have a better handle on these drugs than other people.”

Dr. Postolova reported having no financial conflicts regarding her presentation.

[email protected]

PHOENIX – African Americans with systemic lupus erythematosus are more likely to experience recurrent hospitalizations for cardiovascular disease, compared with other racial/ethnic groups, results from a single-state registry study found.

Doug Brunk/MDedge News

“SLE is an autoimmune disease that causes inflammation affecting multiple organ systems including the cardiovascular system,” Meghan Angley, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “Therefore, individuals with SLE are at risk for early CVD. African Americans represent the racial group at greatest risk for SLE.”

According to Ms. Angley, with the department of epidemiology at Emory University, Atlanta, white women with SLE have CVD associated mortality 12 years earlier than their non-SLE counterparts, while African American women with SLE have CVD-associated mortality 19 years earlier than their non-SLE counterparts. “We know that recurrent hospitalizations for CVD are associated with mortality,” she said. “These represent potential points of identification of high-risk individuals and also points of interventions.”

In order to study racial disparities across recurrent hospitalizations for cardiovascular disease in an SLE population, Ms. Angley and her colleagues drew from the Georgia Lupus Registry, which is a population-based registry of patients with validated SLE in two Georgia counties. They included all cases diagnosed between 2000 and 2004. The registry was linked to records of all inpatient hospitalizations in Georgia between 2000 and 2013. The researchers used ICD-9 codes to identify hospitalizations for coronary heart disease, peripheral artery disease, cerebrovascular disease, and heart failure and used the Prentice-Williams-Peterson model for recurrent time-to-event analysis. Specifically, they looked at the total time scale from the point of diagnosis to each of the subsequent CVD hospitalizations and truncated the number of hospitalizations at three to maintain stable modeling estimates. The analysis was censored at the time of patient death or at the end of 2013 and adjusted for sex and age at diagnosis.

The sample included 417 African Americans with SLE and 149 non–African Americans with the disease. Most (86%) were female, and the non–African American group was slightly more likely to have been diagnosed with SLE after the age of 45 years, compared with the African American group (36% vs. 30%, respectively).

Ms. Angley and her colleagues found that 24% of African Americans had at least one CVD hospitalization, and 14% had at least two, while 13% of non–African Americans had at least one CVD hospitalization, and 5% had at least two. Among those in the African American group, reasons for hospitalizations were congestive heart failure, (58%), cerebrovascular disease (27%), coronary heart disease (18%), and peripheral artery disease (2%). Among those in the non–African American group, reasons for hospitalizations were congestive heart failure (38%), coronary heart disease (38%), cerebrovascular disease (25%), and peripheral artery disease (6%).

Overall, African American race was associated with recurrent hospitalizations (adjusted hazard ratio, 1.9). In an event-specific stratified analysis, the association between African American race and the hazard of recurrence became even more pronounced with each event (hospitalization 1 aHR, 1.2; hospitalization 2 aHR, 1.5; hospitalization 3 aHR, 1.9). The researchers also observed that African Americans were hospitalized sooner, compared with non–African Americans: a median of 3.68 versus 4.61 years for hospitalization 1, 3.73 years versus 5.98 years for hospitalization 2, and 4.84 years versus 8.14 years for hospitalization 3.

“African Americans with SLE are more likely to experience recurrent hospitalizations for CVD,” Ms. Angley concluded at the meeting, which was sponsored by the American Heart Association. “The events occur sooner after diagnosis than in non–African Americans, suggesting that African Americans may be more vulnerable to the cardiovascular complications of SLE. Our next steps include examining potential reasons for these disparities, such as looking at primary care patterns over time, SLE severity over time, and treatment at CVD hospitalizations.”

In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, called for additional research to determine the reasons for disparities that were observed between African Americans with SLE and their non–African American counterparts. “We need to figure out why and address it,” said Dr. Brown, who is a cardiologist and physician-scientist at Mayo Clinic, Rochester, Minn. “We recognize that social determinants of health, such as insurance, socioeconomic factors, and psychosocial factors, can contribute. We need to figure out the additional steps we need to take in order to close that gap.”

Ms. Angley reported having no disclosures. The study was funded by grants from the Centers for Disease Control and Prevention and by the National Institutes of Health.

[email protected]

SOURCE: Angley M et al. Epi/Lifestyle 2020, Abstract 5.

PHOENIX – African Americans with systemic lupus erythematosus are more likely to experience recurrent hospitalizations for cardiovascular disease, compared with other racial/ethnic groups, results from a single-state registry study found.

Doug Brunk/MDedge News

“SLE is an autoimmune disease that causes inflammation affecting multiple organ systems including the cardiovascular system,” Meghan Angley, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “Therefore, individuals with SLE are at risk for early CVD. African Americans represent the racial group at greatest risk for SLE.”

According to Ms. Angley, with the department of epidemiology at Emory University, Atlanta, white women with SLE have CVD associated mortality 12 years earlier than their non-SLE counterparts, while African American women with SLE have CVD-associated mortality 19 years earlier than their non-SLE counterparts. “We know that recurrent hospitalizations for CVD are associated with mortality,” she said. “These represent potential points of identification of high-risk individuals and also points of interventions.”

In order to study racial disparities across recurrent hospitalizations for cardiovascular disease in an SLE population, Ms. Angley and her colleagues drew from the Georgia Lupus Registry, which is a population-based registry of patients with validated SLE in two Georgia counties. They included all cases diagnosed between 2000 and 2004. The registry was linked to records of all inpatient hospitalizations in Georgia between 2000 and 2013. The researchers used ICD-9 codes to identify hospitalizations for coronary heart disease, peripheral artery disease, cerebrovascular disease, and heart failure and used the Prentice-Williams-Peterson model for recurrent time-to-event analysis. Specifically, they looked at the total time scale from the point of diagnosis to each of the subsequent CVD hospitalizations and truncated the number of hospitalizations at three to maintain stable modeling estimates. The analysis was censored at the time of patient death or at the end of 2013 and adjusted for sex and age at diagnosis.

The sample included 417 African Americans with SLE and 149 non–African Americans with the disease. Most (86%) were female, and the non–African American group was slightly more likely to have been diagnosed with SLE after the age of 45 years, compared with the African American group (36% vs. 30%, respectively).

Ms. Angley and her colleagues found that 24% of African Americans had at least one CVD hospitalization, and 14% had at least two, while 13% of non–African Americans had at least one CVD hospitalization, and 5% had at least two. Among those in the African American group, reasons for hospitalizations were congestive heart failure, (58%), cerebrovascular disease (27%), coronary heart disease (18%), and peripheral artery disease (2%). Among those in the non–African American group, reasons for hospitalizations were congestive heart failure (38%), coronary heart disease (38%), cerebrovascular disease (25%), and peripheral artery disease (6%).

Overall, African American race was associated with recurrent hospitalizations (adjusted hazard ratio, 1.9). In an event-specific stratified analysis, the association between African American race and the hazard of recurrence became even more pronounced with each event (hospitalization 1 aHR, 1.2; hospitalization 2 aHR, 1.5; hospitalization 3 aHR, 1.9). The researchers also observed that African Americans were hospitalized sooner, compared with non–African Americans: a median of 3.68 versus 4.61 years for hospitalization 1, 3.73 years versus 5.98 years for hospitalization 2, and 4.84 years versus 8.14 years for hospitalization 3.

“African Americans with SLE are more likely to experience recurrent hospitalizations for CVD,” Ms. Angley concluded at the meeting, which was sponsored by the American Heart Association. “The events occur sooner after diagnosis than in non–African Americans, suggesting that African Americans may be more vulnerable to the cardiovascular complications of SLE. Our next steps include examining potential reasons for these disparities, such as looking at primary care patterns over time, SLE severity over time, and treatment at CVD hospitalizations.”

In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, called for additional research to determine the reasons for disparities that were observed between African Americans with SLE and their non–African American counterparts. “We need to figure out why and address it,” said Dr. Brown, who is a cardiologist and physician-scientist at Mayo Clinic, Rochester, Minn. “We recognize that social determinants of health, such as insurance, socioeconomic factors, and psychosocial factors, can contribute. We need to figure out the additional steps we need to take in order to close that gap.”

Ms. Angley reported having no disclosures. The study was funded by grants from the Centers for Disease Control and Prevention and by the National Institutes of Health.

[email protected]

SOURCE: Angley M et al. Epi/Lifestyle 2020, Abstract 5.

PHOENIX – African Americans with systemic lupus erythematosus are more likely to experience recurrent hospitalizations for cardiovascular disease, compared with other racial/ethnic groups, results from a single-state registry study found.

Doug Brunk/MDedge News

“SLE is an autoimmune disease that causes inflammation affecting multiple organ systems including the cardiovascular system,” Meghan Angley, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “Therefore, individuals with SLE are at risk for early CVD. African Americans represent the racial group at greatest risk for SLE.”

According to Ms. Angley, with the department of epidemiology at Emory University, Atlanta, white women with SLE have CVD associated mortality 12 years earlier than their non-SLE counterparts, while African American women with SLE have CVD-associated mortality 19 years earlier than their non-SLE counterparts. “We know that recurrent hospitalizations for CVD are associated with mortality,” she said. “These represent potential points of identification of high-risk individuals and also points of interventions.”

In order to study racial disparities across recurrent hospitalizations for cardiovascular disease in an SLE population, Ms. Angley and her colleagues drew from the Georgia Lupus Registry, which is a population-based registry of patients with validated SLE in two Georgia counties. They included all cases diagnosed between 2000 and 2004. The registry was linked to records of all inpatient hospitalizations in Georgia between 2000 and 2013. The researchers used ICD-9 codes to identify hospitalizations for coronary heart disease, peripheral artery disease, cerebrovascular disease, and heart failure and used the Prentice-Williams-Peterson model for recurrent time-to-event analysis. Specifically, they looked at the total time scale from the point of diagnosis to each of the subsequent CVD hospitalizations and truncated the number of hospitalizations at three to maintain stable modeling estimates. The analysis was censored at the time of patient death or at the end of 2013 and adjusted for sex and age at diagnosis.

The sample included 417 African Americans with SLE and 149 non–African Americans with the disease. Most (86%) were female, and the non–African American group was slightly more likely to have been diagnosed with SLE after the age of 45 years, compared with the African American group (36% vs. 30%, respectively).

Ms. Angley and her colleagues found that 24% of African Americans had at least one CVD hospitalization, and 14% had at least two, while 13% of non–African Americans had at least one CVD hospitalization, and 5% had at least two. Among those in the African American group, reasons for hospitalizations were congestive heart failure, (58%), cerebrovascular disease (27%), coronary heart disease (18%), and peripheral artery disease (2%). Among those in the non–African American group, reasons for hospitalizations were congestive heart failure (38%), coronary heart disease (38%), cerebrovascular disease (25%), and peripheral artery disease (6%).

Overall, African American race was associated with recurrent hospitalizations (adjusted hazard ratio, 1.9). In an event-specific stratified analysis, the association between African American race and the hazard of recurrence became even more pronounced with each event (hospitalization 1 aHR, 1.2; hospitalization 2 aHR, 1.5; hospitalization 3 aHR, 1.9). The researchers also observed that African Americans were hospitalized sooner, compared with non–African Americans: a median of 3.68 versus 4.61 years for hospitalization 1, 3.73 years versus 5.98 years for hospitalization 2, and 4.84 years versus 8.14 years for hospitalization 3.

“African Americans with SLE are more likely to experience recurrent hospitalizations for CVD,” Ms. Angley concluded at the meeting, which was sponsored by the American Heart Association. “The events occur sooner after diagnosis than in non–African Americans, suggesting that African Americans may be more vulnerable to the cardiovascular complications of SLE. Our next steps include examining potential reasons for these disparities, such as looking at primary care patterns over time, SLE severity over time, and treatment at CVD hospitalizations.”

In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, called for additional research to determine the reasons for disparities that were observed between African Americans with SLE and their non–African American counterparts. “We need to figure out why and address it,” said Dr. Brown, who is a cardiologist and physician-scientist at Mayo Clinic, Rochester, Minn. “We recognize that social determinants of health, such as insurance, socioeconomic factors, and psychosocial factors, can contribute. We need to figure out the additional steps we need to take in order to close that gap.”

Ms. Angley reported having no disclosures. The study was funded by grants from the Centers for Disease Control and Prevention and by the National Institutes of Health.

[email protected]

SOURCE: Angley M et al. Epi/Lifestyle 2020, Abstract 5.

Patients with lupus who have sustained high blood pressure may be at significantly increased risk of cardiovascular events, compared with those patients whose blood pressure is in the range now considered to be normal, results of a retrospective, single-center investigation suggest.

FatCamera/E+/Getty Images

Risk of atherosclerotic vascular events was increased by 73% for patients with systemic lupus erythematosus (SLE) who sustained a mean blood pressure of 130/80 to 139/89 mm Hg over 2 years in the study, which included 1,532 patients treated at a clinic in Toronto.

Management of hypertension in SLE patients should start early, and should aim to achieve levels below 130/80 mm Hg, according to the investigators, led by Konstantinos Tselios, MD, PhD, of the Centre for Prognosis Studies in the Rheumatic Diseases at the University of Toronto.

“The findings of the present study support that the target BP should be less than 130/80 mm Hg in all patients with lupus in order to minimize their cardiovascular risk,” Dr. Tselios and coauthors said in their study, which appears in Annals of the Rheumatic Diseases.

Despite the limitations inherent in a retrospective, observational study, this work by Dr. Tselios and colleagues may help inform the care of patients with SLE, according to C. Michael Stein, MBChB, professor of medicine at Vanderbilt University in Nashville, Tenn.

“It’s really interesting data that’s important and helps us think in terms of figuring out what may be reasonable to do for a particular patient,” Dr. Stein said in an interview.

Starting antihypertensive management early and aiming at levels below 130/80 mm Hg is a strategy that should be “reasonable” for most patients with SLE, said Dr. Stein, adding that the approach specified in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines are appropriate to follow. In those guidelines, the threshold for diagnosis of hypertension was lowered to 130/80 mm Hg.

“You can start with risk factor modification, in terms of losing weight, exercising, stopping alcohol, and decreasing salt in the diet to see if you can get the blood pressure down, though it may come down to drug therapy for many patients, I believe,” Dr. Stein said.

Authors of those 2017 ACC/AHA guidelines made no recommendations for patients with SLE or other connective tissue diseases, despite including a section devoted to specific patient subgroups and comorbidities of interest, Dr. Tselios and coauthors noted in their report.

Management of hypertension in patients with lupus may be “delayed” in patients with blood pressures reaching the current hypertension threshold, according to Dr. Tselios and colleagues, due in part to difficulties in cardiovascular risk calculation in SLE patients, as well as current risk considerations outlined in the guidelines.

“On the basis of the recent guidelines, the patient with typical lupus (young female with no traditional atherosclerotic risk factors) would be considered as a low-risk individual and not offered treatment for a BP of 130-139/80-89 mm Hg,” they said in their report.

Accordingly, Dr. Tselios and colleagues sought to determine whether the new hypertension definition predicted atherosclerotic vascular events, including new-onset angina, acute myocardial infarction, cerebrovascular events, revascularization procedures, heart failure, or peripheral vascular disease requiring angioplasty, in patients with SLE treated at a Canadian clinic.

Their analysis comprised 1,532 patients with SLE who had at least 2 years of follow-up and had no prior atherosclerotic events on record. Over a mean follow-up of nearly 11 years, there were 124 such events documented in those patients.

With a mean follow-up of nearly 11 years, the incidence of atherosclerotic events was 18.9 per 1,000 patient-years for patients with blood pressure ≥ 140/90 mm Hg, 11.5 per 1,000 patient-years for the 130-139/80-89 mm Hg group, and 4.5 per 1,000 patient-years for those with blood pressures of 130/80 mm Hg or lower, with differences that were statistically significant between groups, according to the report.

An adjusted blood pressure of 130-139/80-89 mm Hg over the first 2 years since enrollment in the clinic was independently associated with the occurrence of an atherosclerotic event, with a hazard ratio of 1.73 (95% confidence interval, 1.13-2.69, P = 0.011), according to results of a multivariable analysis.

Those findings support targeting a blood pressure below 130/80 mm Hg in all patients with lupus, according to Dr. Tselios and coauthors.

“It seems reasonable that clinicians should not rely on CV risk calculators in SLE and commence treatment as soon as possible in cases of sustained BP elevation above the threshold of 130/80 mm Hg,” they wrote in their report.

How low to go remains unclear, however, as targeting lower levels of blood pressure might be unsafe in certain groups, such as those SLE patients with prior heart disease or heart failure; nevertheless, recent observational data from non-SLE populations suggest that effective treatment to levels lower than 130/80 mm Hg would “further reduce the incidence of atherosclerotic events in SLE,” the authors said in a discussion of their results.

Dr. Tselios and coauthors said they had no competing interests relative to the study. They reported funding for the University of Toronto Lupus Clinic from the University Health Network, Lou & Marissa Rocca, Mark & Diana Bozzo, and the Lupus Foundation of Ontario.

SOURCE: Tselios K et al. Ann Rheum Dis. 2020 Mar 10. doi: 10.1136/annrheumdis-2019-216764

Patients with lupus who have sustained high blood pressure may be at significantly increased risk of cardiovascular events, compared with those patients whose blood pressure is in the range now considered to be normal, results of a retrospective, single-center investigation suggest.

FatCamera/E+/Getty Images

Risk of atherosclerotic vascular events was increased by 73% for patients with systemic lupus erythematosus (SLE) who sustained a mean blood pressure of 130/80 to 139/89 mm Hg over 2 years in the study, which included 1,532 patients treated at a clinic in Toronto.

Management of hypertension in SLE patients should start early, and should aim to achieve levels below 130/80 mm Hg, according to the investigators, led by Konstantinos Tselios, MD, PhD, of the Centre for Prognosis Studies in the Rheumatic Diseases at the University of Toronto.

“The findings of the present study support that the target BP should be less than 130/80 mm Hg in all patients with lupus in order to minimize their cardiovascular risk,” Dr. Tselios and coauthors said in their study, which appears in Annals of the Rheumatic Diseases.

Despite the limitations inherent in a retrospective, observational study, this work by Dr. Tselios and colleagues may help inform the care of patients with SLE, according to C. Michael Stein, MBChB, professor of medicine at Vanderbilt University in Nashville, Tenn.

“It’s really interesting data that’s important and helps us think in terms of figuring out what may be reasonable to do for a particular patient,” Dr. Stein said in an interview.

Starting antihypertensive management early and aiming at levels below 130/80 mm Hg is a strategy that should be “reasonable” for most patients with SLE, said Dr. Stein, adding that the approach specified in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines are appropriate to follow. In those guidelines, the threshold for diagnosis of hypertension was lowered to 130/80 mm Hg.

“You can start with risk factor modification, in terms of losing weight, exercising, stopping alcohol, and decreasing salt in the diet to see if you can get the blood pressure down, though it may come down to drug therapy for many patients, I believe,” Dr. Stein said.

Authors of those 2017 ACC/AHA guidelines made no recommendations for patients with SLE or other connective tissue diseases, despite including a section devoted to specific patient subgroups and comorbidities of interest, Dr. Tselios and coauthors noted in their report.

Management of hypertension in patients with lupus may be “delayed” in patients with blood pressures reaching the current hypertension threshold, according to Dr. Tselios and colleagues, due in part to difficulties in cardiovascular risk calculation in SLE patients, as well as current risk considerations outlined in the guidelines.

“On the basis of the recent guidelines, the patient with typical lupus (young female with no traditional atherosclerotic risk factors) would be considered as a low-risk individual and not offered treatment for a BP of 130-139/80-89 mm Hg,” they said in their report.

Accordingly, Dr. Tselios and colleagues sought to determine whether the new hypertension definition predicted atherosclerotic vascular events, including new-onset angina, acute myocardial infarction, cerebrovascular events, revascularization procedures, heart failure, or peripheral vascular disease requiring angioplasty, in patients with SLE treated at a Canadian clinic.

Their analysis comprised 1,532 patients with SLE who had at least 2 years of follow-up and had no prior atherosclerotic events on record. Over a mean follow-up of nearly 11 years, there were 124 such events documented in those patients.

With a mean follow-up of nearly 11 years, the incidence of atherosclerotic events was 18.9 per 1,000 patient-years for patients with blood pressure ≥ 140/90 mm Hg, 11.5 per 1,000 patient-years for the 130-139/80-89 mm Hg group, and 4.5 per 1,000 patient-years for those with blood pressures of 130/80 mm Hg or lower, with differences that were statistically significant between groups, according to the report.

An adjusted blood pressure of 130-139/80-89 mm Hg over the first 2 years since enrollment in the clinic was independently associated with the occurrence of an atherosclerotic event, with a hazard ratio of 1.73 (95% confidence interval, 1.13-2.69, P = 0.011), according to results of a multivariable analysis.

Those findings support targeting a blood pressure below 130/80 mm Hg in all patients with lupus, according to Dr. Tselios and coauthors.

“It seems reasonable that clinicians should not rely on CV risk calculators in SLE and commence treatment as soon as possible in cases of sustained BP elevation above the threshold of 130/80 mm Hg,” they wrote in their report.

How low to go remains unclear, however, as targeting lower levels of blood pressure might be unsafe in certain groups, such as those SLE patients with prior heart disease or heart failure; nevertheless, recent observational data from non-SLE populations suggest that effective treatment to levels lower than 130/80 mm Hg would “further reduce the incidence of atherosclerotic events in SLE,” the authors said in a discussion of their results.

Dr. Tselios and coauthors said they had no competing interests relative to the study. They reported funding for the University of Toronto Lupus Clinic from the University Health Network, Lou & Marissa Rocca, Mark & Diana Bozzo, and the Lupus Foundation of Ontario.

SOURCE: Tselios K et al. Ann Rheum Dis. 2020 Mar 10. doi: 10.1136/annrheumdis-2019-216764

Patients with lupus who have sustained high blood pressure may be at significantly increased risk of cardiovascular events, compared with those patients whose blood pressure is in the range now considered to be normal, results of a retrospective, single-center investigation suggest.

FatCamera/E+/Getty Images

Risk of atherosclerotic vascular events was increased by 73% for patients with systemic lupus erythematosus (SLE) who sustained a mean blood pressure of 130/80 to 139/89 mm Hg over 2 years in the study, which included 1,532 patients treated at a clinic in Toronto.

Management of hypertension in SLE patients should start early, and should aim to achieve levels below 130/80 mm Hg, according to the investigators, led by Konstantinos Tselios, MD, PhD, of the Centre for Prognosis Studies in the Rheumatic Diseases at the University of Toronto.

“The findings of the present study support that the target BP should be less than 130/80 mm Hg in all patients with lupus in order to minimize their cardiovascular risk,” Dr. Tselios and coauthors said in their study, which appears in Annals of the Rheumatic Diseases.

Despite the limitations inherent in a retrospective, observational study, this work by Dr. Tselios and colleagues may help inform the care of patients with SLE, according to C. Michael Stein, MBChB, professor of medicine at Vanderbilt University in Nashville, Tenn.

“It’s really interesting data that’s important and helps us think in terms of figuring out what may be reasonable to do for a particular patient,” Dr. Stein said in an interview.

Starting antihypertensive management early and aiming at levels below 130/80 mm Hg is a strategy that should be “reasonable” for most patients with SLE, said Dr. Stein, adding that the approach specified in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines are appropriate to follow. In those guidelines, the threshold for diagnosis of hypertension was lowered to 130/80 mm Hg.

“You can start with risk factor modification, in terms of losing weight, exercising, stopping alcohol, and decreasing salt in the diet to see if you can get the blood pressure down, though it may come down to drug therapy for many patients, I believe,” Dr. Stein said.

Authors of those 2017 ACC/AHA guidelines made no recommendations for patients with SLE or other connective tissue diseases, despite including a section devoted to specific patient subgroups and comorbidities of interest, Dr. Tselios and coauthors noted in their report.

Management of hypertension in patients with lupus may be “delayed” in patients with blood pressures reaching the current hypertension threshold, according to Dr. Tselios and colleagues, due in part to difficulties in cardiovascular risk calculation in SLE patients, as well as current risk considerations outlined in the guidelines.

“On the basis of the recent guidelines, the patient with typical lupus (young female with no traditional atherosclerotic risk factors) would be considered as a low-risk individual and not offered treatment for a BP of 130-139/80-89 mm Hg,” they said in their report.

Accordingly, Dr. Tselios and colleagues sought to determine whether the new hypertension definition predicted atherosclerotic vascular events, including new-onset angina, acute myocardial infarction, cerebrovascular events, revascularization procedures, heart failure, or peripheral vascular disease requiring angioplasty, in patients with SLE treated at a Canadian clinic.

Their analysis comprised 1,532 patients with SLE who had at least 2 years of follow-up and had no prior atherosclerotic events on record. Over a mean follow-up of nearly 11 years, there were 124 such events documented in those patients.

With a mean follow-up of nearly 11 years, the incidence of atherosclerotic events was 18.9 per 1,000 patient-years for patients with blood pressure ≥ 140/90 mm Hg, 11.5 per 1,000 patient-years for the 130-139/80-89 mm Hg group, and 4.5 per 1,000 patient-years for those with blood pressures of 130/80 mm Hg or lower, with differences that were statistically significant between groups, according to the report.

An adjusted blood pressure of 130-139/80-89 mm Hg over the first 2 years since enrollment in the clinic was independently associated with the occurrence of an atherosclerotic event, with a hazard ratio of 1.73 (95% confidence interval, 1.13-2.69, P = 0.011), according to results of a multivariable analysis.

Those findings support targeting a blood pressure below 130/80 mm Hg in all patients with lupus, according to Dr. Tselios and coauthors.

“It seems reasonable that clinicians should not rely on CV risk calculators in SLE and commence treatment as soon as possible in cases of sustained BP elevation above the threshold of 130/80 mm Hg,” they wrote in their report.

How low to go remains unclear, however, as targeting lower levels of blood pressure might be unsafe in certain groups, such as those SLE patients with prior heart disease or heart failure; nevertheless, recent observational data from non-SLE populations suggest that effective treatment to levels lower than 130/80 mm Hg would “further reduce the incidence of atherosclerotic events in SLE,” the authors said in a discussion of their results.

Dr. Tselios and coauthors said they had no competing interests relative to the study. They reported funding for the University of Toronto Lupus Clinic from the University Health Network, Lou & Marissa Rocca, Mark & Diana Bozzo, and the Lupus Foundation of Ontario.

SOURCE: Tselios K et al. Ann Rheum Dis. 2020 Mar 10. doi: 10.1136/annrheumdis-2019-216764

Mobile health technologies currently available for patients with systemic lupus erythematosus (SLE), particularly mobile health (mHealth) apps, are poor quality and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”

[email protected]

SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.

Mobile health technologies currently available for patients with systemic lupus erythematosus (SLE), particularly mobile health (mHealth) apps, are poor quality and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”

[email protected]

SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.

Mobile health technologies currently available for patients with systemic lupus erythematosus (SLE), particularly mobile health (mHealth) apps, are poor quality and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”

[email protected]

SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.

MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.

“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.

Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.

“It’s a good little rule of thumb,” Dr. Pope commented.

The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.

And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.

Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.

Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.

Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.

[email protected]

MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.

“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.

Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.

“It’s a good little rule of thumb,” Dr. Pope commented.

The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.

And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.

Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.

Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.

Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.

[email protected]

MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.

“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.

Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.

“It’s a good little rule of thumb,” Dr. Pope commented.

The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.

And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.

Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.

Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.

Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.

[email protected]

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

Low serum levels of hydroxychloroquine (HCQ) among patients with systemic lupus erythematosus are associated with a threefold increased likelihood of physician- and patient-reported nonadherence to the medication. In addition, routine monitoring of HCQ levels are associated with improvements in adherence and disease activity.

Alexander Raths/ThinkStock

Those are two key findings from a systematic review and meta-analysis published in Arthritis Care & Research.

“HCQ is recommended for all patients with systemic lupus erythematosus (SLE, or lupus) to reduce disease activity and improve damage-free-survival,” the authors, led by Shivani Garg, MD, of the University of Wisconsin–Madison, wrote in the article. “Yet, up to 83% of lupus patients are nonadherent to HCQ commonly because of poor understanding of benefits of HCQ, lack of motivation to continue therapy, and inflated concerns regarding side effects from HCQ use.”

For their analysis, the researchers drew from 17 published observational and interventional studies that measured HCQ levels and assessed adherence or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in adults with SLE. They used forest plots to compare pooled estimates of correlations between HCQ levels and reported nonadherence, or SLEDAI scores. Patient-reported nonadherence was defined as less than 80% medication adherence reported, and physician-reported adherence was estimated based on physicians’ interpretations of the previous month’s adherence as reported by patients during clinic visits.

The study population consisted of 1,223 patients. Dr. Garg and colleagues found a threefold higher odds of reported nonadherence in patients with low HCQ levels (odds ratio, 2.95; P less than .001). The mean SLEDAI score was 3.14 points higher in a group with below-threshold HCQ levels on a priori analysis (P = .053), and 1.4 points higher in a group with HCQ levels below 500 ng/mL (P = .039). Among all patients, those with HCQ levels 750 ng/mL or greater had a 58% lower risk of active disease, and their SLEDAI score was 3.2 points lower. “Our study support levels greater than or equal to 750 ng/mL to be clinically meaningful and statistically significant to identify disease flare (change in SLEDAI greater than or equal to 3 points) and predict active disease (SLEDAI greater than or equal to 6),” the authors wrote.

In an interview, Michelle A. Petri, MD, MPH, took issue with the HCQ goal of 750 ng/mL or greater recommended by the authors. “I think that was premature,” said Dr. Petri, professor of medicine at Johns Hopkins University, Baltimore. “We presented data at last year’s ACR [which showed] that the level needs to be higher than that to prevent thrombosis. But it is important to open the discussion that HCQ blood levels are not just for nonadherence. I believe they will help us to reduce retinopathy, and also to make sure the dose remains in an efficacious range, such as what is needed to prevent thrombosis.”

Dr. Petri, who also directs the Hopkins Lupus Center, said that the study’s overall conclusions confirms the need for blood testing for HCQ to identify nonadherence. “Everyone remembers the saying of the [former] Surgeon General Dr. C. Everett Koop: ‘Drugs can’t work if patients don’t take them!’ – in particular, blood levels which represent what the patient has taken in the last month. I call blood levels the ‘lupus A_1C.’ ”

She added that HCQ blood levels have utility for nonadherence, prediction of retinopathy, and prevention of thrombosis. Such tests “are now much more widely available, including by some large national laboratories such as Quest Diagnostics, as well as by Exagen. No more excuses.” LabCorp plans to start offering HCQ blood level testing by the middle of 2020, she said.

In their manuscript, the study authors acknowledged certain limitations of their analysis, including the fact that there were only four studies that measured HCQ levels and nonadherence or SLEDAI. “Second, most of the studies that examined the correlation between reported adherence and HCQ blood levels were performed in Europe, and there was only one small U.S. study,” they wrote. “Therefore, generalizability for our findings could be limited because of differences in cultural beliefs, social issues, and insurance/medical coverage in populations from diverse countries.”

The study authors reported having no disclosures. Dr. Petri disclosed that she has conducted research on HCQ that was funded by the National Institutes of Health. She has also conducted research for Exagen.

[email protected]

SOURCE: Garg S et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24155.

Low serum levels of hydroxychloroquine (HCQ) among patients with systemic lupus erythematosus are associated with a threefold increased likelihood of physician- and patient-reported nonadherence to the medication. In addition, routine monitoring of HCQ levels are associated with improvements in adherence and disease activity.

Alexander Raths/ThinkStock

Those are two key findings from a systematic review and meta-analysis published in Arthritis Care & Research.

“HCQ is recommended for all patients with systemic lupus erythematosus (SLE, or lupus) to reduce disease activity and improve damage-free-survival,” the authors, led by Shivani Garg, MD, of the University of Wisconsin–Madison, wrote in the article. “Yet, up to 83% of lupus patients are nonadherent to HCQ commonly because of poor understanding of benefits of HCQ, lack of motivation to continue therapy, and inflated concerns regarding side effects from HCQ use.”

For their analysis, the researchers drew from 17 published observational and interventional studies that measured HCQ levels and assessed adherence or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in adults with SLE. They used forest plots to compare pooled estimates of correlations between HCQ levels and reported nonadherence, or SLEDAI scores. Patient-reported nonadherence was defined as less than 80% medication adherence reported, and physician-reported adherence was estimated based on physicians’ interpretations of the previous month’s adherence as reported by patients during clinic visits.

The study population consisted of 1,223 patients. Dr. Garg and colleagues found a threefold higher odds of reported nonadherence in patients with low HCQ levels (odds ratio, 2.95; P less than .001). The mean SLEDAI score was 3.14 points higher in a group with below-threshold HCQ levels on a priori analysis (P = .053), and 1.4 points higher in a group with HCQ levels below 500 ng/mL (P = .039). Among all patients, those with HCQ levels 750 ng/mL or greater had a 58% lower risk of active disease, and their SLEDAI score was 3.2 points lower. “Our study support levels greater than or equal to 750 ng/mL to be clinically meaningful and statistically significant to identify disease flare (change in SLEDAI greater than or equal to 3 points) and predict active disease (SLEDAI greater than or equal to 6),” the authors wrote.

In an interview, Michelle A. Petri, MD, MPH, took issue with the HCQ goal of 750 ng/mL or greater recommended by the authors. “I think that was premature,” said Dr. Petri, professor of medicine at Johns Hopkins University, Baltimore. “We presented data at last year’s ACR [which showed] that the level needs to be higher than that to prevent thrombosis. But it is important to open the discussion that HCQ blood levels are not just for nonadherence. I believe they will help us to reduce retinopathy, and also to make sure the dose remains in an efficacious range, such as what is needed to prevent thrombosis.”

Dr. Petri, who also directs the Hopkins Lupus Center, said that the study’s overall conclusions confirms the need for blood testing for HCQ to identify nonadherence. “Everyone remembers the saying of the [former] Surgeon General Dr. C. Everett Koop: ‘Drugs can’t work if patients don’t take them!’ – in particular, blood levels which represent what the patient has taken in the last month. I call blood levels the ‘lupus A_1C.’ ”

She added that HCQ blood levels have utility for nonadherence, prediction of retinopathy, and prevention of thrombosis. Such tests “are now much more widely available, including by some large national laboratories such as Quest Diagnostics, as well as by Exagen. No more excuses.” LabCorp plans to start offering HCQ blood level testing by the middle of 2020, she said.

In their manuscript, the study authors acknowledged certain limitations of their analysis, including the fact that there were only four studies that measured HCQ levels and nonadherence or SLEDAI. “Second, most of the studies that examined the correlation between reported adherence and HCQ blood levels were performed in Europe, and there was only one small U.S. study,” they wrote. “Therefore, generalizability for our findings could be limited because of differences in cultural beliefs, social issues, and insurance/medical coverage in populations from diverse countries.”

The study authors reported having no disclosures. Dr. Petri disclosed that she has conducted research on HCQ that was funded by the National Institutes of Health. She has also conducted research for Exagen.

[email protected]

SOURCE: Garg S et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24155.

Low serum levels of hydroxychloroquine (HCQ) among patients with systemic lupus erythematosus are associated with a threefold increased likelihood of physician- and patient-reported nonadherence to the medication. In addition, routine monitoring of HCQ levels are associated with improvements in adherence and disease activity.

Alexander Raths/ThinkStock

Those are two key findings from a systematic review and meta-analysis published in Arthritis Care & Research.

“HCQ is recommended for all patients with systemic lupus erythematosus (SLE, or lupus) to reduce disease activity and improve damage-free-survival,” the authors, led by Shivani Garg, MD, of the University of Wisconsin–Madison, wrote in the article. “Yet, up to 83% of lupus patients are nonadherent to HCQ commonly because of poor understanding of benefits of HCQ, lack of motivation to continue therapy, and inflated concerns regarding side effects from HCQ use.”

For their analysis, the researchers drew from 17 published observational and interventional studies that measured HCQ levels and assessed adherence or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in adults with SLE. They used forest plots to compare pooled estimates of correlations between HCQ levels and reported nonadherence, or SLEDAI scores. Patient-reported nonadherence was defined as less than 80% medication adherence reported, and physician-reported adherence was estimated based on physicians’ interpretations of the previous month’s adherence as reported by patients during clinic visits.

The study population consisted of 1,223 patients. Dr. Garg and colleagues found a threefold higher odds of reported nonadherence in patients with low HCQ levels (odds ratio, 2.95; P less than .001). The mean SLEDAI score was 3.14 points higher in a group with below-threshold HCQ levels on a priori analysis (P = .053), and 1.4 points higher in a group with HCQ levels below 500 ng/mL (P = .039). Among all patients, those with HCQ levels 750 ng/mL or greater had a 58% lower risk of active disease, and their SLEDAI score was 3.2 points lower. “Our study support levels greater than or equal to 750 ng/mL to be clinically meaningful and statistically significant to identify disease flare (change in SLEDAI greater than or equal to 3 points) and predict active disease (SLEDAI greater than or equal to 6),” the authors wrote.

In an interview, Michelle A. Petri, MD, MPH, took issue with the HCQ goal of 750 ng/mL or greater recommended by the authors. “I think that was premature,” said Dr. Petri, professor of medicine at Johns Hopkins University, Baltimore. “We presented data at last year’s ACR [which showed] that the level needs to be higher than that to prevent thrombosis. But it is important to open the discussion that HCQ blood levels are not just for nonadherence. I believe they will help us to reduce retinopathy, and also to make sure the dose remains in an efficacious range, such as what is needed to prevent thrombosis.”

Dr. Petri, who also directs the Hopkins Lupus Center, said that the study’s overall conclusions confirms the need for blood testing for HCQ to identify nonadherence. “Everyone remembers the saying of the [former] Surgeon General Dr. C. Everett Koop: ‘Drugs can’t work if patients don’t take them!’ – in particular, blood levels which represent what the patient has taken in the last month. I call blood levels the ‘lupus A_1C.’ ”

She added that HCQ blood levels have utility for nonadherence, prediction of retinopathy, and prevention of thrombosis. Such tests “are now much more widely available, including by some large national laboratories such as Quest Diagnostics, as well as by Exagen. No more excuses.” LabCorp plans to start offering HCQ blood level testing by the middle of 2020, she said.

In their manuscript, the study authors acknowledged certain limitations of their analysis, including the fact that there were only four studies that measured HCQ levels and nonadherence or SLEDAI. “Second, most of the studies that examined the correlation between reported adherence and HCQ blood levels were performed in Europe, and there was only one small U.S. study,” they wrote. “Therefore, generalizability for our findings could be limited because of differences in cultural beliefs, social issues, and insurance/medical coverage in populations from diverse countries.”

The study authors reported having no disclosures. Dr. Petri disclosed that she has conducted research on HCQ that was funded by the National Institutes of Health. She has also conducted research for Exagen.

[email protected]

SOURCE: Garg S et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24155.

Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.

“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.

To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.

During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.

The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”

HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.

Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.

[email protected]

SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.

Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.

“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.

To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.

During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.

The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”

HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.

Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.

[email protected]

SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.

Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.

“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.

To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.

During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.

The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”

HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.

Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.

[email protected]

SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.