Rheumatology

It’s anything but business as usual for clinicians who oversee office-based infusion centers, as they scramble to maintain services for patients considered to be at heightened risk for severe illness should they become infected with COVID-19.

Courtesy Dr. Alyssa M. Parian

“For many reasons, the guidance for patients right now is that they stay on their medications,” Max I. Hamburger, MD, a managing partner at Rheumatology Associates of Long Island (N.Y.), said in an interview. “Some have decided to stop the drug, and then they call us up to tell us that they’re flaring. The beginning of a flare is tiredness and other things. Now they’re worried: Are they tired because of the disease, or are they tired because they have COVID-19?”

With five office locations located in a region considered to be the epicenter of the COVID-19 pandemic in the United States, Dr. Hamburger and his colleagues are hypervigilant about screening patients for symptoms of the virus before they visit one of the three practice locations that provide infusion services. This starts with an automated phone system that reminds patients of their appointment time. “Part of that robocall now has some questions like, ‘Do you have any symptoms of COVID-19?’ ‘Are you running a fever?’ ‘Do you have any reason to worry about yourself? If so, please call us.’ ” The infusion nurses are also calling the patients in advance of their appointment to check on their status. “When they get to the office location, we ask them again about their general health and check their temperature,” said Dr. Hamburger, who is also founder and executive chairman of United Rheumatology, which is a nationwide rheumatology care management services organization with 650 members in 39 states. “We’re doing everything we can to talk to them about their own state of health and to question them about what I call extended paranoia: like, ‘Who are you living with?’ ‘Who are you hanging out with?’ ‘What are all the six degrees of separation here?’ I want to know what the patient’s husband did last night. I want to know where their kids were over this past week, et cetera. We do everything we can to see if there’s anybody who might have had the slightest [contact with someone who has COVID-19]. Because if I lose my infusion nurse, then I’m up the creek.”

The infusion nurse wears scrubs, a face mask, and latex gloves. She and her staff are using hand sanitizer and cleaning infusion equipment with sanitizing wipes as one might do in a surgical setting. “Every surface is wiped down between patients, and the nurse is changing gloves between patients,” said Dr. Hamburger, who was founding president of the New York State Rheumatology Society before retiring from that post in 2017. “Getting masks has been tough. We’re doing the best we can there. We’re not gloving patients but we’re masking patients.”

As noted in guidance from the American College of Rheumatology and other medical organizations, following the CDC’s recommendation to stay at home during the pandemic has jump-started conversations between physicians and their patients about modifying the time interval between infusions. “If they have been doing well for the last 9 months, we’re having a conversation such as ‘Maybe instead of getting your Orencia every 4 weeks, maybe we’ll push it out to 5 weeks, or maybe we’ll push the Enbrel out to 10 days and the Humira out 3 weeks, et cetera,” Dr. Hamburger said. “One has to be very careful about when you do that, because you don’t want the patient to flare up because it’s hard to get them in, but it is a natural opportunity to look at this. We’re seeing how we can optimize the dose, but I don’t want to send the message that we’re doing this because it changes the patient’s outcome, because there’s zero evidence that it’s a good thing to do in terms of resistance.”

At the infusion centers operated by the Johns Hopkins division of gastroenterology and hepatology, Baltimore, clinicians are not increasing the time interval between infusions for patients at this time. “We’re keeping them as they are, to prevent any flare-ups. Our main goal is to keep patients in remission and out of the hospital,” said Alyssa M. Parian, MD, medical director of the infusion center and associate director of the university’s GI department. “With Remicade specifically, there’s also the risk of developing antibodies if you delay treatment, so we’re basically keeping everyone on track. We’re not recommending a switch from infusions to injectables, and we also are not speeding up infusions, either. Before this pandemic happened, we had already tried to decrease all Remicade infusions from 2 hours to 1 hour for patient satisfaction. The Entyvio is a pretty quick, 30-minute infusion.”

To accommodate patients during this era of physical distancing measures recommended by the Centers for Disease Control and Prevention, Dr. Parian and her infusion nurse manager Elisheva Weiser converted one of their two outpatient GI centers into an infusion-only suite with 12 individual clinic rooms. As soon as patients exit the second-floor elevator, they encounter a workstation prior to entering the office where they are screened for COVID-19 symptoms and their temperature is taken. “If any symptoms or temperature comes back positive, we’re asking them to postpone their treatment and consider COVID testing,” she said.

Instead of one nurse looking after four patients in one room during infusion therapy, now one nurse looks after two patients who are in rooms next to each other. All patients and all staff wear masks while in the center. “We always have physician oversight at our infusion centers,” Dr. Parian said. “We are trying to maintain a ‘COVID-free zone.’ Therefore, no physicians who have served in a hospital ward are allowed in the infusion suite because we don’t want any carriers of COVID-19. Same with the nurses. Additionally, we limit the staff within the suite to only those who are essential and don’t allow anyone to perform telemedicine or urgent clinic visits in this location. Our infusion center staff are on a strict protocol to not come in with any symptoms at all. They are asked to take their temperature before coming in to work.”

She and her colleagues drew from recommendations from the joint GI society message on COVID-19, the Crohn’s and Colitis Foundation, and the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) to inform their approach in serving patients during this unprecedented time. “We went as conservative as possible because these are immunosuppressed patients,” she said. One patient on her panel who receives an infusion every 8 weeks tested positive for COVID-19 between infusions, but was not hospitalized. Dr. Parian said that person will only be treated 14 days after the all symptoms disappear. “That person will wear a mask and will be infused in a separate room,” she said.

In Aventura, Fla., Norman B. Gaylis, MD, and his colleagues at Arthritis & Rheumatic Disease Specialties are looking into shutting down their infusion services during the time period that local public health officials consider to be the peak level of exposure to COVID-19. “We’ve tried to work around that, and bring people in a little early,” said Dr. Gaylis, medical director of rheumatology and infusion services at the practice. “We’ve done our best to mitigate the risk [of exposure] as much as possible.” This includes staggering their caseload by infusing 5 patients at a time, compared with the 15 patients at a time they could treat during prepandemic conditions. “Everyone is at least 20 feet apart,” said Dr. Gaylis, who is a member of the American College of Rheumatology Board of Directors. “While we don’t have the kind of protective garments you might see in an ICU, we still are gowning, gloving, and masking our staff, and trying to practice sterile techniques as much as we can.”

The pandemic has caused him to reflect more broadly on the way he and his colleagues deliver care for patients on infusion therapy. “We see patients who really want their treatment because they feel it’s helpful and beneficial,” he said. “There are also patients who may truly be in remission who could stop [infusion therapy]. We could possibly extend the duration of their therapy, try and push it back.”

Dr. Gaylis emphasized that any discussion about halting infusion therapy requires clinical, serological, and ideally even MRI evidence that the disease is in a dormant state. “You wouldn’t stop treatment in someone who is showing signs in their blood that their disease is still active,” he said. “You’re using all those parameters in that conversation.”

In his clinical opinion, now is not the time to switch patients to self-injectable agents as a perceived matter of convenience. “I don’t really think that’s a good idea because self-injectables are different,” Dr. Gaylis said. “You’re basically switching treatment patterns. The practicality of getting a specialty pharmacy to switch, the insurance companies to cover it, and determine copay for it, is a burden on patients. That’s why I’m against it, because you’re starting a whole new process and problem.”

One patient tested positive for COVID-19 about 3 weeks after an infusion at the facility. “That does lead to a point: Have my staff been tested? We have not had the tests available to us,” Dr. Gaylis said. “One provider had a contact with someone with COVID-19 and stayed home for 2 weeks. That person tested negative. Soon we are going to receive a kit that will allow us to measure IgM and IgG COVID-19 antibodies. Because we’re going to be closed for 2 weeks, measuring us now would be a great way to handle it.”

In rural Western Kentucky, Christopher R. Phillips, MD, and his colleagues at Paducah Rheumatology have arranged for “drive-by” injections for some of their higher-risk patients who require subcutaneous administration of biologic agents. “We have them call us when they’re in the parking lot, and we give them the treatment while they sit in their car,” said Dr. Phillips, who chairs the ACR Insurance Subcommittee and is a member of the ACR COVID-19 Practice and Advocacy Task Force.

For patients who require infusions, they’ve arranged three chairs in the clinic to be at least 6 feet apart, and moved the fourth chair into a separate room. “My infusion nurse knows these patients well; we’re a small community,” he said. “She checks in with them the day before to screen for any symptoms of infection and asks them to call when they get here. A lot of them wait in their car to be brought in. She’ll bring them in, screen for infection symptoms, and check their temperature. She and the receptionist are masked and gloved, and disinfect aggressively between patients. The other thing we are trying to be on top of is making sure that everyone’s insurance coverage is active when they come in, in light of the number of people who have been laid off or had changes in their employment.”

Dr. Phillips has considered increasing the infusion time interval for some patients, but not knowing when current physical distancing guidelines will ease up presents a conundrum. “If I have a patient coming in today, and their next treatment is due in a month, I don’t know how to say that, if we stretch the infusion to 2 months, that things are going to be better,” he said. “For some very well-controlled patients and/or high-risk patients, that is something we’ve done: stretch the interval or skip a treatment. For most patients, our default is to stick with the normal schedule. We feel that, for most patients who have moderate to severe underlying rheumatic disease, the risk of disease flare and subsequent need for steroids may be a larger risk than the treatment itself, though that is an individualized decision.”

To date, Dr. Phillips has not treated a patient who has recovered from COVID-19, but the thought of that scenario gives him pause. “There is some literature suggesting these patients may asymptomatically shed virus for some time after they’ve clinically recovered, but we don’t really know enough about that,” he said. “If I had one of those patients, I’d probably be delaying them for a longer period of time, and I’d be looking for some guidance from the literature on postsymptomatic viral shedding.”

In the meantime, the level of anxiety that many of his patients express during this pandemic is palpable. “They really are between a rock and a hard place,” Dr. Phillips said. “If they come off their effective treatment, they risk flare of a disease that can be life or limb threatening. And yet, because of their disease and their treatment, they’re potentially at increased risk for serious illness if they become infected with COVID-19. We look for ways to try to reassure patients and to comfort them, and work with them to make the best of the situation.”

[email protected]

It’s anything but business as usual for clinicians who oversee office-based infusion centers, as they scramble to maintain services for patients considered to be at heightened risk for severe illness should they become infected with COVID-19.

Courtesy Dr. Alyssa M. Parian

“For many reasons, the guidance for patients right now is that they stay on their medications,” Max I. Hamburger, MD, a managing partner at Rheumatology Associates of Long Island (N.Y.), said in an interview. “Some have decided to stop the drug, and then they call us up to tell us that they’re flaring. The beginning of a flare is tiredness and other things. Now they’re worried: Are they tired because of the disease, or are they tired because they have COVID-19?”

With five office locations located in a region considered to be the epicenter of the COVID-19 pandemic in the United States, Dr. Hamburger and his colleagues are hypervigilant about screening patients for symptoms of the virus before they visit one of the three practice locations that provide infusion services. This starts with an automated phone system that reminds patients of their appointment time. “Part of that robocall now has some questions like, ‘Do you have any symptoms of COVID-19?’ ‘Are you running a fever?’ ‘Do you have any reason to worry about yourself? If so, please call us.’ ” The infusion nurses are also calling the patients in advance of their appointment to check on their status. “When they get to the office location, we ask them again about their general health and check their temperature,” said Dr. Hamburger, who is also founder and executive chairman of United Rheumatology, which is a nationwide rheumatology care management services organization with 650 members in 39 states. “We’re doing everything we can to talk to them about their own state of health and to question them about what I call extended paranoia: like, ‘Who are you living with?’ ‘Who are you hanging out with?’ ‘What are all the six degrees of separation here?’ I want to know what the patient’s husband did last night. I want to know where their kids were over this past week, et cetera. We do everything we can to see if there’s anybody who might have had the slightest [contact with someone who has COVID-19]. Because if I lose my infusion nurse, then I’m up the creek.”

The infusion nurse wears scrubs, a face mask, and latex gloves. She and her staff are using hand sanitizer and cleaning infusion equipment with sanitizing wipes as one might do in a surgical setting. “Every surface is wiped down between patients, and the nurse is changing gloves between patients,” said Dr. Hamburger, who was founding president of the New York State Rheumatology Society before retiring from that post in 2017. “Getting masks has been tough. We’re doing the best we can there. We’re not gloving patients but we’re masking patients.”

As noted in guidance from the American College of Rheumatology and other medical organizations, following the CDC’s recommendation to stay at home during the pandemic has jump-started conversations between physicians and their patients about modifying the time interval between infusions. “If they have been doing well for the last 9 months, we’re having a conversation such as ‘Maybe instead of getting your Orencia every 4 weeks, maybe we’ll push it out to 5 weeks, or maybe we’ll push the Enbrel out to 10 days and the Humira out 3 weeks, et cetera,” Dr. Hamburger said. “One has to be very careful about when you do that, because you don’t want the patient to flare up because it’s hard to get them in, but it is a natural opportunity to look at this. We’re seeing how we can optimize the dose, but I don’t want to send the message that we’re doing this because it changes the patient’s outcome, because there’s zero evidence that it’s a good thing to do in terms of resistance.”

At the infusion centers operated by the Johns Hopkins division of gastroenterology and hepatology, Baltimore, clinicians are not increasing the time interval between infusions for patients at this time. “We’re keeping them as they are, to prevent any flare-ups. Our main goal is to keep patients in remission and out of the hospital,” said Alyssa M. Parian, MD, medical director of the infusion center and associate director of the university’s GI department. “With Remicade specifically, there’s also the risk of developing antibodies if you delay treatment, so we’re basically keeping everyone on track. We’re not recommending a switch from infusions to injectables, and we also are not speeding up infusions, either. Before this pandemic happened, we had already tried to decrease all Remicade infusions from 2 hours to 1 hour for patient satisfaction. The Entyvio is a pretty quick, 30-minute infusion.”

To accommodate patients during this era of physical distancing measures recommended by the Centers for Disease Control and Prevention, Dr. Parian and her infusion nurse manager Elisheva Weiser converted one of their two outpatient GI centers into an infusion-only suite with 12 individual clinic rooms. As soon as patients exit the second-floor elevator, they encounter a workstation prior to entering the office where they are screened for COVID-19 symptoms and their temperature is taken. “If any symptoms or temperature comes back positive, we’re asking them to postpone their treatment and consider COVID testing,” she said.

Instead of one nurse looking after four patients in one room during infusion therapy, now one nurse looks after two patients who are in rooms next to each other. All patients and all staff wear masks while in the center. “We always have physician oversight at our infusion centers,” Dr. Parian said. “We are trying to maintain a ‘COVID-free zone.’ Therefore, no physicians who have served in a hospital ward are allowed in the infusion suite because we don’t want any carriers of COVID-19. Same with the nurses. Additionally, we limit the staff within the suite to only those who are essential and don’t allow anyone to perform telemedicine or urgent clinic visits in this location. Our infusion center staff are on a strict protocol to not come in with any symptoms at all. They are asked to take their temperature before coming in to work.”

She and her colleagues drew from recommendations from the joint GI society message on COVID-19, the Crohn’s and Colitis Foundation, and the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) to inform their approach in serving patients during this unprecedented time. “We went as conservative as possible because these are immunosuppressed patients,” she said. One patient on her panel who receives an infusion every 8 weeks tested positive for COVID-19 between infusions, but was not hospitalized. Dr. Parian said that person will only be treated 14 days after the all symptoms disappear. “That person will wear a mask and will be infused in a separate room,” she said.

In Aventura, Fla., Norman B. Gaylis, MD, and his colleagues at Arthritis & Rheumatic Disease Specialties are looking into shutting down their infusion services during the time period that local public health officials consider to be the peak level of exposure to COVID-19. “We’ve tried to work around that, and bring people in a little early,” said Dr. Gaylis, medical director of rheumatology and infusion services at the practice. “We’ve done our best to mitigate the risk [of exposure] as much as possible.” This includes staggering their caseload by infusing 5 patients at a time, compared with the 15 patients at a time they could treat during prepandemic conditions. “Everyone is at least 20 feet apart,” said Dr. Gaylis, who is a member of the American College of Rheumatology Board of Directors. “While we don’t have the kind of protective garments you might see in an ICU, we still are gowning, gloving, and masking our staff, and trying to practice sterile techniques as much as we can.”

The pandemic has caused him to reflect more broadly on the way he and his colleagues deliver care for patients on infusion therapy. “We see patients who really want their treatment because they feel it’s helpful and beneficial,” he said. “There are also patients who may truly be in remission who could stop [infusion therapy]. We could possibly extend the duration of their therapy, try and push it back.”

Dr. Gaylis emphasized that any discussion about halting infusion therapy requires clinical, serological, and ideally even MRI evidence that the disease is in a dormant state. “You wouldn’t stop treatment in someone who is showing signs in their blood that their disease is still active,” he said. “You’re using all those parameters in that conversation.”

In his clinical opinion, now is not the time to switch patients to self-injectable agents as a perceived matter of convenience. “I don’t really think that’s a good idea because self-injectables are different,” Dr. Gaylis said. “You’re basically switching treatment patterns. The practicality of getting a specialty pharmacy to switch, the insurance companies to cover it, and determine copay for it, is a burden on patients. That’s why I’m against it, because you’re starting a whole new process and problem.”

One patient tested positive for COVID-19 about 3 weeks after an infusion at the facility. “That does lead to a point: Have my staff been tested? We have not had the tests available to us,” Dr. Gaylis said. “One provider had a contact with someone with COVID-19 and stayed home for 2 weeks. That person tested negative. Soon we are going to receive a kit that will allow us to measure IgM and IgG COVID-19 antibodies. Because we’re going to be closed for 2 weeks, measuring us now would be a great way to handle it.”

In rural Western Kentucky, Christopher R. Phillips, MD, and his colleagues at Paducah Rheumatology have arranged for “drive-by” injections for some of their higher-risk patients who require subcutaneous administration of biologic agents. “We have them call us when they’re in the parking lot, and we give them the treatment while they sit in their car,” said Dr. Phillips, who chairs the ACR Insurance Subcommittee and is a member of the ACR COVID-19 Practice and Advocacy Task Force.

For patients who require infusions, they’ve arranged three chairs in the clinic to be at least 6 feet apart, and moved the fourth chair into a separate room. “My infusion nurse knows these patients well; we’re a small community,” he said. “She checks in with them the day before to screen for any symptoms of infection and asks them to call when they get here. A lot of them wait in their car to be brought in. She’ll bring them in, screen for infection symptoms, and check their temperature. She and the receptionist are masked and gloved, and disinfect aggressively between patients. The other thing we are trying to be on top of is making sure that everyone’s insurance coverage is active when they come in, in light of the number of people who have been laid off or had changes in their employment.”

Dr. Phillips has considered increasing the infusion time interval for some patients, but not knowing when current physical distancing guidelines will ease up presents a conundrum. “If I have a patient coming in today, and their next treatment is due in a month, I don’t know how to say that, if we stretch the infusion to 2 months, that things are going to be better,” he said. “For some very well-controlled patients and/or high-risk patients, that is something we’ve done: stretch the interval or skip a treatment. For most patients, our default is to stick with the normal schedule. We feel that, for most patients who have moderate to severe underlying rheumatic disease, the risk of disease flare and subsequent need for steroids may be a larger risk than the treatment itself, though that is an individualized decision.”

To date, Dr. Phillips has not treated a patient who has recovered from COVID-19, but the thought of that scenario gives him pause. “There is some literature suggesting these patients may asymptomatically shed virus for some time after they’ve clinically recovered, but we don’t really know enough about that,” he said. “If I had one of those patients, I’d probably be delaying them for a longer period of time, and I’d be looking for some guidance from the literature on postsymptomatic viral shedding.”

In the meantime, the level of anxiety that many of his patients express during this pandemic is palpable. “They really are between a rock and a hard place,” Dr. Phillips said. “If they come off their effective treatment, they risk flare of a disease that can be life or limb threatening. And yet, because of their disease and their treatment, they’re potentially at increased risk for serious illness if they become infected with COVID-19. We look for ways to try to reassure patients and to comfort them, and work with them to make the best of the situation.”

[email protected]

It’s anything but business as usual for clinicians who oversee office-based infusion centers, as they scramble to maintain services for patients considered to be at heightened risk for severe illness should they become infected with COVID-19.

Courtesy Dr. Alyssa M. Parian

“For many reasons, the guidance for patients right now is that they stay on their medications,” Max I. Hamburger, MD, a managing partner at Rheumatology Associates of Long Island (N.Y.), said in an interview. “Some have decided to stop the drug, and then they call us up to tell us that they’re flaring. The beginning of a flare is tiredness and other things. Now they’re worried: Are they tired because of the disease, or are they tired because they have COVID-19?”

With five office locations located in a region considered to be the epicenter of the COVID-19 pandemic in the United States, Dr. Hamburger and his colleagues are hypervigilant about screening patients for symptoms of the virus before they visit one of the three practice locations that provide infusion services. This starts with an automated phone system that reminds patients of their appointment time. “Part of that robocall now has some questions like, ‘Do you have any symptoms of COVID-19?’ ‘Are you running a fever?’ ‘Do you have any reason to worry about yourself? If so, please call us.’ ” The infusion nurses are also calling the patients in advance of their appointment to check on their status. “When they get to the office location, we ask them again about their general health and check their temperature,” said Dr. Hamburger, who is also founder and executive chairman of United Rheumatology, which is a nationwide rheumatology care management services organization with 650 members in 39 states. “We’re doing everything we can to talk to them about their own state of health and to question them about what I call extended paranoia: like, ‘Who are you living with?’ ‘Who are you hanging out with?’ ‘What are all the six degrees of separation here?’ I want to know what the patient’s husband did last night. I want to know where their kids were over this past week, et cetera. We do everything we can to see if there’s anybody who might have had the slightest [contact with someone who has COVID-19]. Because if I lose my infusion nurse, then I’m up the creek.”

The infusion nurse wears scrubs, a face mask, and latex gloves. She and her staff are using hand sanitizer and cleaning infusion equipment with sanitizing wipes as one might do in a surgical setting. “Every surface is wiped down between patients, and the nurse is changing gloves between patients,” said Dr. Hamburger, who was founding president of the New York State Rheumatology Society before retiring from that post in 2017. “Getting masks has been tough. We’re doing the best we can there. We’re not gloving patients but we’re masking patients.”

As noted in guidance from the American College of Rheumatology and other medical organizations, following the CDC’s recommendation to stay at home during the pandemic has jump-started conversations between physicians and their patients about modifying the time interval between infusions. “If they have been doing well for the last 9 months, we’re having a conversation such as ‘Maybe instead of getting your Orencia every 4 weeks, maybe we’ll push it out to 5 weeks, or maybe we’ll push the Enbrel out to 10 days and the Humira out 3 weeks, et cetera,” Dr. Hamburger said. “One has to be very careful about when you do that, because you don’t want the patient to flare up because it’s hard to get them in, but it is a natural opportunity to look at this. We’re seeing how we can optimize the dose, but I don’t want to send the message that we’re doing this because it changes the patient’s outcome, because there’s zero evidence that it’s a good thing to do in terms of resistance.”

At the infusion centers operated by the Johns Hopkins division of gastroenterology and hepatology, Baltimore, clinicians are not increasing the time interval between infusions for patients at this time. “We’re keeping them as they are, to prevent any flare-ups. Our main goal is to keep patients in remission and out of the hospital,” said Alyssa M. Parian, MD, medical director of the infusion center and associate director of the university’s GI department. “With Remicade specifically, there’s also the risk of developing antibodies if you delay treatment, so we’re basically keeping everyone on track. We’re not recommending a switch from infusions to injectables, and we also are not speeding up infusions, either. Before this pandemic happened, we had already tried to decrease all Remicade infusions from 2 hours to 1 hour for patient satisfaction. The Entyvio is a pretty quick, 30-minute infusion.”

To accommodate patients during this era of physical distancing measures recommended by the Centers for Disease Control and Prevention, Dr. Parian and her infusion nurse manager Elisheva Weiser converted one of their two outpatient GI centers into an infusion-only suite with 12 individual clinic rooms. As soon as patients exit the second-floor elevator, they encounter a workstation prior to entering the office where they are screened for COVID-19 symptoms and their temperature is taken. “If any symptoms or temperature comes back positive, we’re asking them to postpone their treatment and consider COVID testing,” she said.

Instead of one nurse looking after four patients in one room during infusion therapy, now one nurse looks after two patients who are in rooms next to each other. All patients and all staff wear masks while in the center. “We always have physician oversight at our infusion centers,” Dr. Parian said. “We are trying to maintain a ‘COVID-free zone.’ Therefore, no physicians who have served in a hospital ward are allowed in the infusion suite because we don’t want any carriers of COVID-19. Same with the nurses. Additionally, we limit the staff within the suite to only those who are essential and don’t allow anyone to perform telemedicine or urgent clinic visits in this location. Our infusion center staff are on a strict protocol to not come in with any symptoms at all. They are asked to take their temperature before coming in to work.”

She and her colleagues drew from recommendations from the joint GI society message on COVID-19, the Crohn’s and Colitis Foundation, and the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) to inform their approach in serving patients during this unprecedented time. “We went as conservative as possible because these are immunosuppressed patients,” she said. One patient on her panel who receives an infusion every 8 weeks tested positive for COVID-19 between infusions, but was not hospitalized. Dr. Parian said that person will only be treated 14 days after the all symptoms disappear. “That person will wear a mask and will be infused in a separate room,” she said.

In Aventura, Fla., Norman B. Gaylis, MD, and his colleagues at Arthritis & Rheumatic Disease Specialties are looking into shutting down their infusion services during the time period that local public health officials consider to be the peak level of exposure to COVID-19. “We’ve tried to work around that, and bring people in a little early,” said Dr. Gaylis, medical director of rheumatology and infusion services at the practice. “We’ve done our best to mitigate the risk [of exposure] as much as possible.” This includes staggering their caseload by infusing 5 patients at a time, compared with the 15 patients at a time they could treat during prepandemic conditions. “Everyone is at least 20 feet apart,” said Dr. Gaylis, who is a member of the American College of Rheumatology Board of Directors. “While we don’t have the kind of protective garments you might see in an ICU, we still are gowning, gloving, and masking our staff, and trying to practice sterile techniques as much as we can.”

The pandemic has caused him to reflect more broadly on the way he and his colleagues deliver care for patients on infusion therapy. “We see patients who really want their treatment because they feel it’s helpful and beneficial,” he said. “There are also patients who may truly be in remission who could stop [infusion therapy]. We could possibly extend the duration of their therapy, try and push it back.”

Dr. Gaylis emphasized that any discussion about halting infusion therapy requires clinical, serological, and ideally even MRI evidence that the disease is in a dormant state. “You wouldn’t stop treatment in someone who is showing signs in their blood that their disease is still active,” he said. “You’re using all those parameters in that conversation.”

In his clinical opinion, now is not the time to switch patients to self-injectable agents as a perceived matter of convenience. “I don’t really think that’s a good idea because self-injectables are different,” Dr. Gaylis said. “You’re basically switching treatment patterns. The practicality of getting a specialty pharmacy to switch, the insurance companies to cover it, and determine copay for it, is a burden on patients. That’s why I’m against it, because you’re starting a whole new process and problem.”

One patient tested positive for COVID-19 about 3 weeks after an infusion at the facility. “That does lead to a point: Have my staff been tested? We have not had the tests available to us,” Dr. Gaylis said. “One provider had a contact with someone with COVID-19 and stayed home for 2 weeks. That person tested negative. Soon we are going to receive a kit that will allow us to measure IgM and IgG COVID-19 antibodies. Because we’re going to be closed for 2 weeks, measuring us now would be a great way to handle it.”

In rural Western Kentucky, Christopher R. Phillips, MD, and his colleagues at Paducah Rheumatology have arranged for “drive-by” injections for some of their higher-risk patients who require subcutaneous administration of biologic agents. “We have them call us when they’re in the parking lot, and we give them the treatment while they sit in their car,” said Dr. Phillips, who chairs the ACR Insurance Subcommittee and is a member of the ACR COVID-19 Practice and Advocacy Task Force.

For patients who require infusions, they’ve arranged three chairs in the clinic to be at least 6 feet apart, and moved the fourth chair into a separate room. “My infusion nurse knows these patients well; we’re a small community,” he said. “She checks in with them the day before to screen for any symptoms of infection and asks them to call when they get here. A lot of them wait in their car to be brought in. She’ll bring them in, screen for infection symptoms, and check their temperature. She and the receptionist are masked and gloved, and disinfect aggressively between patients. The other thing we are trying to be on top of is making sure that everyone’s insurance coverage is active when they come in, in light of the number of people who have been laid off or had changes in their employment.”

Dr. Phillips has considered increasing the infusion time interval for some patients, but not knowing when current physical distancing guidelines will ease up presents a conundrum. “If I have a patient coming in today, and their next treatment is due in a month, I don’t know how to say that, if we stretch the infusion to 2 months, that things are going to be better,” he said. “For some very well-controlled patients and/or high-risk patients, that is something we’ve done: stretch the interval or skip a treatment. For most patients, our default is to stick with the normal schedule. We feel that, for most patients who have moderate to severe underlying rheumatic disease, the risk of disease flare and subsequent need for steroids may be a larger risk than the treatment itself, though that is an individualized decision.”

To date, Dr. Phillips has not treated a patient who has recovered from COVID-19, but the thought of that scenario gives him pause. “There is some literature suggesting these patients may asymptomatically shed virus for some time after they’ve clinically recovered, but we don’t really know enough about that,” he said. “If I had one of those patients, I’d probably be delaying them for a longer period of time, and I’d be looking for some guidance from the literature on postsymptomatic viral shedding.”

In the meantime, the level of anxiety that many of his patients express during this pandemic is palpable. “They really are between a rock and a hard place,” Dr. Phillips said. “If they come off their effective treatment, they risk flare of a disease that can be life or limb threatening. And yet, because of their disease and their treatment, they’re potentially at increased risk for serious illness if they become infected with COVID-19. We look for ways to try to reassure patients and to comfort them, and work with them to make the best of the situation.”

[email protected]

Approximately 26% of women with inactive or mild lupus at conception experienced flares at some point during pregnancy, based on data from 384 patients.

zoranm/Getty Images

Active systemic lupus erythematosus (SLE) is a known predictor of poor pregnancy outcomes, including preterm birth, growth restriction, and fetal loss, but predictors of flares during and after pregnancy in women with SLE have not been well studied, wrote Julia Davis-Porada, MD, of the Hospital for Special Surgery, New York, and her colleagues.

In a study published in Arthritis Research & Therapy, the investigators reviewed data from the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study, a prospective study of pregnant women aged 18-45 years. The women were enrolled at less than 12 weeks’ gestation, and participants had a baseline hematocrit greater than 26%. Participants met criteria for inactive or mild/stable disease at the time of conception.

Overall, 20.8% of patients experienced at least one mild or moderate flare and 6.25% had one or more severe flares during pregnancy. Mild to moderate flares and severe flares occurred postpartum (2-6 months after the end of pregnancy) in 22.7% and 1.7% of patients, respectively.

Patients who were younger and those who had lower C4 at baseline and higher Physician Global Assessment scores at baseline were significantly more likely to have at least one flare during pregnancy (P = .003, P = .024, P = .0005, respectively).

In the analysis of postpartum flares, the incidence rates for mild to moderate and severe flares were 0.8 and 0.06 per person-year, respectively. “In contrast to the findings observed for flares that occurred during pregnancy, baseline patient characteristics were not correlated with postpartum flares,” the researchers wrote.

No medications were associated with flares during or after pregnancy.

The study findings were limited by several factors, including the exclusion of SLE patients with current nephritis and those who needed high-dose prednisone; the potential for missed flares; and the lack of postpartum data for approximately 10% of patients, the researchers noted. Also, “since many patients presented to this study only after conception, we have no data to review disease activity prior to pregnancy to determine whether pregnancy per se increased the risk for flare,” they said.

However, the results were strengthened by the large, multiethnic population and prospective study design, and support physicians in reassuring patients with SLE that pregnancy and postpartum flares are unlikely if they plan pregnancy during a time of mild or inactive disease, they concluded.

The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers had no financial conflicts to disclose.

SOURCE: Davis-Porada J et al. Arthritis Res Ther. 2020 Mar 19. doi: 10.1186/s13075-020-2139-9.

Approximately 26% of women with inactive or mild lupus at conception experienced flares at some point during pregnancy, based on data from 384 patients.

zoranm/Getty Images

Active systemic lupus erythematosus (SLE) is a known predictor of poor pregnancy outcomes, including preterm birth, growth restriction, and fetal loss, but predictors of flares during and after pregnancy in women with SLE have not been well studied, wrote Julia Davis-Porada, MD, of the Hospital for Special Surgery, New York, and her colleagues.

In a study published in Arthritis Research & Therapy, the investigators reviewed data from the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study, a prospective study of pregnant women aged 18-45 years. The women were enrolled at less than 12 weeks’ gestation, and participants had a baseline hematocrit greater than 26%. Participants met criteria for inactive or mild/stable disease at the time of conception.

Overall, 20.8% of patients experienced at least one mild or moderate flare and 6.25% had one or more severe flares during pregnancy. Mild to moderate flares and severe flares occurred postpartum (2-6 months after the end of pregnancy) in 22.7% and 1.7% of patients, respectively.

Patients who were younger and those who had lower C4 at baseline and higher Physician Global Assessment scores at baseline were significantly more likely to have at least one flare during pregnancy (P = .003, P = .024, P = .0005, respectively).

In the analysis of postpartum flares, the incidence rates for mild to moderate and severe flares were 0.8 and 0.06 per person-year, respectively. “In contrast to the findings observed for flares that occurred during pregnancy, baseline patient characteristics were not correlated with postpartum flares,” the researchers wrote.

No medications were associated with flares during or after pregnancy.

The study findings were limited by several factors, including the exclusion of SLE patients with current nephritis and those who needed high-dose prednisone; the potential for missed flares; and the lack of postpartum data for approximately 10% of patients, the researchers noted. Also, “since many patients presented to this study only after conception, we have no data to review disease activity prior to pregnancy to determine whether pregnancy per se increased the risk for flare,” they said.

However, the results were strengthened by the large, multiethnic population and prospective study design, and support physicians in reassuring patients with SLE that pregnancy and postpartum flares are unlikely if they plan pregnancy during a time of mild or inactive disease, they concluded.

The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers had no financial conflicts to disclose.

SOURCE: Davis-Porada J et al. Arthritis Res Ther. 2020 Mar 19. doi: 10.1186/s13075-020-2139-9.

Approximately 26% of women with inactive or mild lupus at conception experienced flares at some point during pregnancy, based on data from 384 patients.

zoranm/Getty Images

Active systemic lupus erythematosus (SLE) is a known predictor of poor pregnancy outcomes, including preterm birth, growth restriction, and fetal loss, but predictors of flares during and after pregnancy in women with SLE have not been well studied, wrote Julia Davis-Porada, MD, of the Hospital for Special Surgery, New York, and her colleagues.

In a study published in Arthritis Research & Therapy, the investigators reviewed data from the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study, a prospective study of pregnant women aged 18-45 years. The women were enrolled at less than 12 weeks’ gestation, and participants had a baseline hematocrit greater than 26%. Participants met criteria for inactive or mild/stable disease at the time of conception.

Overall, 20.8% of patients experienced at least one mild or moderate flare and 6.25% had one or more severe flares during pregnancy. Mild to moderate flares and severe flares occurred postpartum (2-6 months after the end of pregnancy) in 22.7% and 1.7% of patients, respectively.

Patients who were younger and those who had lower C4 at baseline and higher Physician Global Assessment scores at baseline were significantly more likely to have at least one flare during pregnancy (P = .003, P = .024, P = .0005, respectively).

In the analysis of postpartum flares, the incidence rates for mild to moderate and severe flares were 0.8 and 0.06 per person-year, respectively. “In contrast to the findings observed for flares that occurred during pregnancy, baseline patient characteristics were not correlated with postpartum flares,” the researchers wrote.

No medications were associated with flares during or after pregnancy.

The study findings were limited by several factors, including the exclusion of SLE patients with current nephritis and those who needed high-dose prednisone; the potential for missed flares; and the lack of postpartum data for approximately 10% of patients, the researchers noted. Also, “since many patients presented to this study only after conception, we have no data to review disease activity prior to pregnancy to determine whether pregnancy per se increased the risk for flare,” they said.

However, the results were strengthened by the large, multiethnic population and prospective study design, and support physicians in reassuring patients with SLE that pregnancy and postpartum flares are unlikely if they plan pregnancy during a time of mild or inactive disease, they concluded.

The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers had no financial conflicts to disclose.

SOURCE: Davis-Porada J et al. Arthritis Res Ther. 2020 Mar 19. doi: 10.1186/s13075-020-2139-9.

MAUI, HAWAII – Belimumab shows promise as a novel biologic treatment for skin involvement in early diffuse cutaneous systemic sclerosis, Janet E. Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

She highlighted a single-center, double-blind, placebo-controlled, New York pilot study including 20 patients with early diffuse cutaneous systemic sclerosis and moderate skin involvement. Participants had recently started on background mycophenolate mofetil (MMF) at 1,000 mg twice daily and were then randomized to add-on belimumab (Benlysta) at the dosing approved for systemic lupus erythematosus or to infusions of normal saline.

At 52 weeks, the modified Rodnan skin thickness score (mRSS) decreased by a median of 10 points from a baseline of 27 in the belimumab group, compared with just a 3-point reduction in controls on MMF plus placebo.

This small study raises several key points. It definitely warrants confirmation in a large phase 3 trial, 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 Care, both in London.

For one thing, the pilot study makes a good case for multidrug therapy in scleroderma. “In rheumatoid arthritis, if in general one drug is not as good as two, why would we ever think, in our most difficult-to-treat disease, one drug would be okay?” the rheumatologist observed.

The belimumab study also highlights the role of abnormalities in B-cell function in the pathogenesis of skin involvement in early diffuse cutaneous systemic sclerosis. Belimumab is a fully human monoclonal antibody which binds to soluble B-lymphocyte stimulator and inhibits autoantibody production.

Belimumab’s mechanism of benefit was as expected: The improvement in skin scores in the belimumab group was accompanied by decreased expression of profibrotic genes and B-cell signaling, changes that didn’t occur in the controls on MMF alone.

The belimumab study makes another important point: MMF, despite its growing popularity for treatment of skin manifestations of scleroderma, is actually a wimpy drug for that purpose, achieving a mere 3-point reduction in mRSS.

“To be quite honest, mycophenolate mofetil is not all that great on skin,” Dr. Pope said.

Nonetheless, when she and her coworkers recently polled 170 scleroderma experts as to their favored treatments directed at various target organs impaired by the disease, as she had previously done in 2012, a clear trend was evident. “There’s a shift in that mycophenolate mofetil is moving to first-line treatment across the board for skin,” Dr. Pope observed.

Indeed, in the more recent survey, 71% of the experts agreed upon a scleroderma skin involvement treatment algorithm in which the first-line treatment for severe skin disease as defined by an mRSS of 32 was MMF, with methotrexate as second line, intravenous cyclophosphamide third, and autologous stem cell transplantation as fourth line for the small number of patients who qualify for it.

For moderate skin involvement, with an mRSS of 24, methotrexate was endorsed as first line, although by the narrowest of margins, over MMF, with intravenous cyclophosphamide as third line. For mild disease, with an mRSS of 10, methotrexate again narrowly beat out MMF by expert consensus as the preferred first-line therapy.

When asked about concomitant use of corticosteroids for treatment of skin involvement, 35% of experts said they never prescribe them for that indication, 33% do so occasionally, 19% sometimes, and 13% routinely. There was an even split on dosing among those who prescribe steroids: 49% suggested using prednisone at less than 7.5 mg/day, and 51% recommended 7.5-20 mg/day.

The purpose in polling the experts, who were drawn from the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research Group, was to provide treatment guidance to general rheumatologists and dermatologists who may not see many patients with scleroderma. In contrast, the great majority of the polled experts see more than 50 scleroderma patients per year. And they had a high level of total agreement for treatment algorithms addressing not only skin disease, but also pulmonary arterial hypertension, interstitial lung disease, Raynaud’s phenomenon, renal crisis, digital ulcers, inflammatory arthritis, cardiac involvement, and gastrointestinal disease, Dr. Pope noted.

She attributed the experts’ rising enthusiasm for MMF for scleroderma skin involvement to the results of the Scleroderma Lung Study II, the first randomized, controlled trial to compare MMF and cyclophosphamide for the treatment of symptomatic scleroderma interstitial lung disease. Two years of MMF improved forced vital capacity as much as 1 year of oral cyclophosphamide. At 2 years of follow-up, the mRSS dropped modestly from baseline by an average of 6.1 points in the cyclophosphamide group and 2.9 points with MMF, a nonsignificant difference. But the incidence of serious adverse events was roughly three times higher and deaths were twice as frequent in the cyclophosphamide group.

“I think mycophenolate mofetil is surging for treatment of skin because of the lung protection and it was safer, but it’s hard for me to know if the deaths were more common in the cyclophosphamide group because of the cyclophosphamide or because of no treatment in year 2,” Dr. Pope commented.

She reported receiving research grants from Bristol-Myers Squibb, Merck, Roche, Seattle Genetics, and UCB, and serving as a consultant to more than a dozen pharmaceutical companies.

[email protected]

MAUI, HAWAII – Belimumab shows promise as a novel biologic treatment for skin involvement in early diffuse cutaneous systemic sclerosis, Janet E. Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

She highlighted a single-center, double-blind, placebo-controlled, New York pilot study including 20 patients with early diffuse cutaneous systemic sclerosis and moderate skin involvement. Participants had recently started on background mycophenolate mofetil (MMF) at 1,000 mg twice daily and were then randomized to add-on belimumab (Benlysta) at the dosing approved for systemic lupus erythematosus or to infusions of normal saline.

At 52 weeks, the modified Rodnan skin thickness score (mRSS) decreased by a median of 10 points from a baseline of 27 in the belimumab group, compared with just a 3-point reduction in controls on MMF plus placebo.

This small study raises several key points. It definitely warrants confirmation in a large phase 3 trial, 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 Care, both in London.

For one thing, the pilot study makes a good case for multidrug therapy in scleroderma. “In rheumatoid arthritis, if in general one drug is not as good as two, why would we ever think, in our most difficult-to-treat disease, one drug would be okay?” the rheumatologist observed.

The belimumab study also highlights the role of abnormalities in B-cell function in the pathogenesis of skin involvement in early diffuse cutaneous systemic sclerosis. Belimumab is a fully human monoclonal antibody which binds to soluble B-lymphocyte stimulator and inhibits autoantibody production.

Belimumab’s mechanism of benefit was as expected: The improvement in skin scores in the belimumab group was accompanied by decreased expression of profibrotic genes and B-cell signaling, changes that didn’t occur in the controls on MMF alone.

The belimumab study makes another important point: MMF, despite its growing popularity for treatment of skin manifestations of scleroderma, is actually a wimpy drug for that purpose, achieving a mere 3-point reduction in mRSS.

“To be quite honest, mycophenolate mofetil is not all that great on skin,” Dr. Pope said.

Nonetheless, when she and her coworkers recently polled 170 scleroderma experts as to their favored treatments directed at various target organs impaired by the disease, as she had previously done in 2012, a clear trend was evident. “There’s a shift in that mycophenolate mofetil is moving to first-line treatment across the board for skin,” Dr. Pope observed.

Indeed, in the more recent survey, 71% of the experts agreed upon a scleroderma skin involvement treatment algorithm in which the first-line treatment for severe skin disease as defined by an mRSS of 32 was MMF, with methotrexate as second line, intravenous cyclophosphamide third, and autologous stem cell transplantation as fourth line for the small number of patients who qualify for it.

For moderate skin involvement, with an mRSS of 24, methotrexate was endorsed as first line, although by the narrowest of margins, over MMF, with intravenous cyclophosphamide as third line. For mild disease, with an mRSS of 10, methotrexate again narrowly beat out MMF by expert consensus as the preferred first-line therapy.

When asked about concomitant use of corticosteroids for treatment of skin involvement, 35% of experts said they never prescribe them for that indication, 33% do so occasionally, 19% sometimes, and 13% routinely. There was an even split on dosing among those who prescribe steroids: 49% suggested using prednisone at less than 7.5 mg/day, and 51% recommended 7.5-20 mg/day.

The purpose in polling the experts, who were drawn from the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research Group, was to provide treatment guidance to general rheumatologists and dermatologists who may not see many patients with scleroderma. In contrast, the great majority of the polled experts see more than 50 scleroderma patients per year. And they had a high level of total agreement for treatment algorithms addressing not only skin disease, but also pulmonary arterial hypertension, interstitial lung disease, Raynaud’s phenomenon, renal crisis, digital ulcers, inflammatory arthritis, cardiac involvement, and gastrointestinal disease, Dr. Pope noted.

She attributed the experts’ rising enthusiasm for MMF for scleroderma skin involvement to the results of the Scleroderma Lung Study II, the first randomized, controlled trial to compare MMF and cyclophosphamide for the treatment of symptomatic scleroderma interstitial lung disease. Two years of MMF improved forced vital capacity as much as 1 year of oral cyclophosphamide. At 2 years of follow-up, the mRSS dropped modestly from baseline by an average of 6.1 points in the cyclophosphamide group and 2.9 points with MMF, a nonsignificant difference. But the incidence of serious adverse events was roughly three times higher and deaths were twice as frequent in the cyclophosphamide group.

“I think mycophenolate mofetil is surging for treatment of skin because of the lung protection and it was safer, but it’s hard for me to know if the deaths were more common in the cyclophosphamide group because of the cyclophosphamide or because of no treatment in year 2,” Dr. Pope commented.

She reported receiving research grants from Bristol-Myers Squibb, Merck, Roche, Seattle Genetics, and UCB, and serving as a consultant to more than a dozen pharmaceutical companies.

[email protected]

MAUI, HAWAII – Belimumab shows promise as a novel biologic treatment for skin involvement in early diffuse cutaneous systemic sclerosis, Janet E. Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

She highlighted a single-center, double-blind, placebo-controlled, New York pilot study including 20 patients with early diffuse cutaneous systemic sclerosis and moderate skin involvement. Participants had recently started on background mycophenolate mofetil (MMF) at 1,000 mg twice daily and were then randomized to add-on belimumab (Benlysta) at the dosing approved for systemic lupus erythematosus or to infusions of normal saline.

At 52 weeks, the modified Rodnan skin thickness score (mRSS) decreased by a median of 10 points from a baseline of 27 in the belimumab group, compared with just a 3-point reduction in controls on MMF plus placebo.

This small study raises several key points. It definitely warrants confirmation in a large phase 3 trial, 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 Care, both in London.

For one thing, the pilot study makes a good case for multidrug therapy in scleroderma. “In rheumatoid arthritis, if in general one drug is not as good as two, why would we ever think, in our most difficult-to-treat disease, one drug would be okay?” the rheumatologist observed.

The belimumab study also highlights the role of abnormalities in B-cell function in the pathogenesis of skin involvement in early diffuse cutaneous systemic sclerosis. Belimumab is a fully human monoclonal antibody which binds to soluble B-lymphocyte stimulator and inhibits autoantibody production.

Belimumab’s mechanism of benefit was as expected: The improvement in skin scores in the belimumab group was accompanied by decreased expression of profibrotic genes and B-cell signaling, changes that didn’t occur in the controls on MMF alone.

The belimumab study makes another important point: MMF, despite its growing popularity for treatment of skin manifestations of scleroderma, is actually a wimpy drug for that purpose, achieving a mere 3-point reduction in mRSS.

“To be quite honest, mycophenolate mofetil is not all that great on skin,” Dr. Pope said.

Nonetheless, when she and her coworkers recently polled 170 scleroderma experts as to their favored treatments directed at various target organs impaired by the disease, as she had previously done in 2012, a clear trend was evident. “There’s a shift in that mycophenolate mofetil is moving to first-line treatment across the board for skin,” Dr. Pope observed.

Indeed, in the more recent survey, 71% of the experts agreed upon a scleroderma skin involvement treatment algorithm in which the first-line treatment for severe skin disease as defined by an mRSS of 32 was MMF, with methotrexate as second line, intravenous cyclophosphamide third, and autologous stem cell transplantation as fourth line for the small number of patients who qualify for it.

For moderate skin involvement, with an mRSS of 24, methotrexate was endorsed as first line, although by the narrowest of margins, over MMF, with intravenous cyclophosphamide as third line. For mild disease, with an mRSS of 10, methotrexate again narrowly beat out MMF by expert consensus as the preferred first-line therapy.

When asked about concomitant use of corticosteroids for treatment of skin involvement, 35% of experts said they never prescribe them for that indication, 33% do so occasionally, 19% sometimes, and 13% routinely. There was an even split on dosing among those who prescribe steroids: 49% suggested using prednisone at less than 7.5 mg/day, and 51% recommended 7.5-20 mg/day.

The purpose in polling the experts, who were drawn from the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research Group, was to provide treatment guidance to general rheumatologists and dermatologists who may not see many patients with scleroderma. In contrast, the great majority of the polled experts see more than 50 scleroderma patients per year. And they had a high level of total agreement for treatment algorithms addressing not only skin disease, but also pulmonary arterial hypertension, interstitial lung disease, Raynaud’s phenomenon, renal crisis, digital ulcers, inflammatory arthritis, cardiac involvement, and gastrointestinal disease, Dr. Pope noted.

She attributed the experts’ rising enthusiasm for MMF for scleroderma skin involvement to the results of the Scleroderma Lung Study II, the first randomized, controlled trial to compare MMF and cyclophosphamide for the treatment of symptomatic scleroderma interstitial lung disease. Two years of MMF improved forced vital capacity as much as 1 year of oral cyclophosphamide. At 2 years of follow-up, the mRSS dropped modestly from baseline by an average of 6.1 points in the cyclophosphamide group and 2.9 points with MMF, a nonsignificant difference. But the incidence of serious adverse events was roughly three times higher and deaths were twice as frequent in the cyclophosphamide group.

“I think mycophenolate mofetil is surging for treatment of skin because of the lung protection and it was safer, but it’s hard for me to know if the deaths were more common in the cyclophosphamide group because of the cyclophosphamide or because of no treatment in year 2,” Dr. Pope commented.

She reported receiving research grants from Bristol-Myers Squibb, Merck, Roche, Seattle Genetics, and UCB, and serving as a consultant to more than a dozen pharmaceutical companies.

[email protected]

Patients being treated for RA or spondyloarthritis who develop symptoms of COVID-19 do not appear to be at higher risk of respiratory or life-threatening complications, results from a new study in Italy suggest.

Such patients, the study authors wrote, do not need to be taken off their immunosuppressive medications if they develop COVID-19 symptoms.

In a letter published in Annals of the Rheumatic Diseases, Sara Monti, MD, and colleagues in the rheumatology department of the Fondazione IRCCS Policlinico in San Matteo, Italy, described results from an observational cohort of 320 patients (68% women; mean age, 55 years) with RA or spondyloarthritis from a single outpatient clinic. The vast majority of subjects (92%) were taking biologic disease-modifying antirheumatic drugs (bDMARD), including tumor necrosis factor inhibitors, while the rest were taking targeted synthetic DMARDs (tsDMARD).

Four patients in the cohort developed laboratory-confirmed COVID-19; another four developed symptoms highly suggestive of the disease but did not receive confirmatory testing, and five had contact with a confirmed COVID-19 case but did not develop symptoms of COVID-19.

Among the eight confirmed and suspected COVID-19 patients, only one was hospitalized. All temporarily withdrew bDMARD or tsDMARD treatment at symptom onset.

“To date, there have been no significant relapses of the rheumatic disease,” Dr. Monti and colleagues reported. “None of the patients with a confirmed diagnosis of COVID-19 or with a highly suggestive clinical picture developed severe respiratory complications or died. Only one patient, aged 65, required admission to hospital and low-flow oxygen supplementation for a few days.”

The findings “do not allow any conclusions on the incidence rate of SARS-CoV-2 infection in patients with rheumatic diseases, nor on the overall outcome of immunocompromised patients affected by COVID-19,” the investigators cautioned, adding that such patients should receive careful attention and follow-up. “However, our preliminary experience shows that patients with chronic arthritis treated with bDMARDs or tsDMARDs do not seem to be at increased risk of respiratory or life-threatening complications from SARS-CoV-2, compared with the general population.”

Dr. Monti and colleagues noted that, during previous outbreaks of other coronaviruses, no increased mortality was reported for people taking immunosuppressive drugs for a range of conditions, including autoimmune diseases.

“These data can support rheumatologists [in] avoiding the unjustifiable preventive withdrawal of DMARDs, which could lead to an increased risk of relapses and morbidity from the chronic rheumatological condition,” the researchers concluded.

Dr. Monti and colleagues reported no outside funding or financial conflicts of interest.

SOURCE: Monti S et al. Ann Rheum Dis. 2020 April 2. doi: 10.1136/annrheumdis-2020-217424.

Patients being treated for RA or spondyloarthritis who develop symptoms of COVID-19 do not appear to be at higher risk of respiratory or life-threatening complications, results from a new study in Italy suggest.

Such patients, the study authors wrote, do not need to be taken off their immunosuppressive medications if they develop COVID-19 symptoms.

In a letter published in Annals of the Rheumatic Diseases, Sara Monti, MD, and colleagues in the rheumatology department of the Fondazione IRCCS Policlinico in San Matteo, Italy, described results from an observational cohort of 320 patients (68% women; mean age, 55 years) with RA or spondyloarthritis from a single outpatient clinic. The vast majority of subjects (92%) were taking biologic disease-modifying antirheumatic drugs (bDMARD), including tumor necrosis factor inhibitors, while the rest were taking targeted synthetic DMARDs (tsDMARD).

Four patients in the cohort developed laboratory-confirmed COVID-19; another four developed symptoms highly suggestive of the disease but did not receive confirmatory testing, and five had contact with a confirmed COVID-19 case but did not develop symptoms of COVID-19.

Among the eight confirmed and suspected COVID-19 patients, only one was hospitalized. All temporarily withdrew bDMARD or tsDMARD treatment at symptom onset.

“To date, there have been no significant relapses of the rheumatic disease,” Dr. Monti and colleagues reported. “None of the patients with a confirmed diagnosis of COVID-19 or with a highly suggestive clinical picture developed severe respiratory complications or died. Only one patient, aged 65, required admission to hospital and low-flow oxygen supplementation for a few days.”

The findings “do not allow any conclusions on the incidence rate of SARS-CoV-2 infection in patients with rheumatic diseases, nor on the overall outcome of immunocompromised patients affected by COVID-19,” the investigators cautioned, adding that such patients should receive careful attention and follow-up. “However, our preliminary experience shows that patients with chronic arthritis treated with bDMARDs or tsDMARDs do not seem to be at increased risk of respiratory or life-threatening complications from SARS-CoV-2, compared with the general population.”

Dr. Monti and colleagues noted that, during previous outbreaks of other coronaviruses, no increased mortality was reported for people taking immunosuppressive drugs for a range of conditions, including autoimmune diseases.

“These data can support rheumatologists [in] avoiding the unjustifiable preventive withdrawal of DMARDs, which could lead to an increased risk of relapses and morbidity from the chronic rheumatological condition,” the researchers concluded.

Dr. Monti and colleagues reported no outside funding or financial conflicts of interest.

SOURCE: Monti S et al. Ann Rheum Dis. 2020 April 2. doi: 10.1136/annrheumdis-2020-217424.

Patients being treated for RA or spondyloarthritis who develop symptoms of COVID-19 do not appear to be at higher risk of respiratory or life-threatening complications, results from a new study in Italy suggest.

Such patients, the study authors wrote, do not need to be taken off their immunosuppressive medications if they develop COVID-19 symptoms.

In a letter published in Annals of the Rheumatic Diseases, Sara Monti, MD, and colleagues in the rheumatology department of the Fondazione IRCCS Policlinico in San Matteo, Italy, described results from an observational cohort of 320 patients (68% women; mean age, 55 years) with RA or spondyloarthritis from a single outpatient clinic. The vast majority of subjects (92%) were taking biologic disease-modifying antirheumatic drugs (bDMARD), including tumor necrosis factor inhibitors, while the rest were taking targeted synthetic DMARDs (tsDMARD).

Four patients in the cohort developed laboratory-confirmed COVID-19; another four developed symptoms highly suggestive of the disease but did not receive confirmatory testing, and five had contact with a confirmed COVID-19 case but did not develop symptoms of COVID-19.

Among the eight confirmed and suspected COVID-19 patients, only one was hospitalized. All temporarily withdrew bDMARD or tsDMARD treatment at symptom onset.

“To date, there have been no significant relapses of the rheumatic disease,” Dr. Monti and colleagues reported. “None of the patients with a confirmed diagnosis of COVID-19 or with a highly suggestive clinical picture developed severe respiratory complications or died. Only one patient, aged 65, required admission to hospital and low-flow oxygen supplementation for a few days.”

The findings “do not allow any conclusions on the incidence rate of SARS-CoV-2 infection in patients with rheumatic diseases, nor on the overall outcome of immunocompromised patients affected by COVID-19,” the investigators cautioned, adding that such patients should receive careful attention and follow-up. “However, our preliminary experience shows that patients with chronic arthritis treated with bDMARDs or tsDMARDs do not seem to be at increased risk of respiratory or life-threatening complications from SARS-CoV-2, compared with the general population.”

Dr. Monti and colleagues noted that, during previous outbreaks of other coronaviruses, no increased mortality was reported for people taking immunosuppressive drugs for a range of conditions, including autoimmune diseases.

“These data can support rheumatologists [in] avoiding the unjustifiable preventive withdrawal of DMARDs, which could lead to an increased risk of relapses and morbidity from the chronic rheumatological condition,” the researchers concluded.

Dr. Monti and colleagues reported no outside funding or financial conflicts of interest.

SOURCE: Monti S et al. Ann Rheum Dis. 2020 April 2. doi: 10.1136/annrheumdis-2020-217424.

Average measures of bone mineral density were similar for individuals with high-trauma and low-trauma fractures, and both were significantly distinct from those with no fracture history, based on data from a cohort study of adults aged 40 years and older.

©eranicle/Thinkstock

In the past, low-trauma fractures have typically been associated with osteoporosis, wrote William D. Leslie, MD, of the University of Manitoba, Canada, and his colleagues. However, features distinguishing between low- and high-trauma fractures are often arbitrary and “empirical data have questioned whether distinguishing low-trauma from high-trauma fractures is clinically useful for purposes of risk assessment and treatment,” they wrote.

In a study published in Osteoporosis International, the researchers reviewed data from 64,626 individuals with no prior fracture, 858 with high-trauma fractures, and 14,758 with low-trauma fractures. Overall, the average BMD Z-scores for individuals with no previous fracture were slightly positive, while those with either a high-trauma or low-trauma fracture were negative. The scores for individuals with high-trauma fractures or major osteoporotic fractures were similar to those with low-trauma fractures, and significantly lower (P less than .001) than among individuals with no prior fractures.

The study population included adults aged 40 years and older with baseline DXA scans between Jan. 1, 1996, and Mar. 31, 2016. Those with high-trauma fractures were younger than those with low-trauma fractures (65 years vs. 67 years), and fewer individuals with high-trauma fractures were women (77% vs. 87%).

Both high-trauma and low-trauma fractures were similarly and significantly associated with increased risk for incident major osteoporotic fractures (adjusted hazard ratios 1.31 and 1.55, respectively).

The study findings were limited by several factors including incomplete data on external injury codes, the retrospective study design, and the lack of analysis of the time since prior fractures, the researchers noted. However, the results were strengthened by the large sample size, long-term follow-up, and large numbers of incident fractures, they wrote.

The results support data from previous studies and support “the inclusion of high-trauma clinical fractures in clinical assessment for underlying osteoporosis and in the evaluation for intervention to reduce future fracture risk,” they wrote.

In an accompanying editorial, Steven R. Cummings, MD, of California Pacific Medical Center Research Institute, San Francisco, and Richard Eastell, MD, of the University of Sheffield, England, wrote that the practice of rating fractures according to degree of trauma should be eliminated.

“The study adds evidence to the case that it is time to abandon the mistaken beliefs that fractures rated as high trauma are not associated with decreased BMD, indicate no higher risk of subsequent fracture, or are less likely to be prevented by treatments for osteoporosis,” they wrote.

Describing some fractures as due to trauma reinforces the mistaken belief that the fractures are simply due to the trauma, not decreased bone strength, they noted.

“Indeed, we recommend that people stop attempting to rate or record degree of trauma because such ratings are at best inaccurate and would promote the continued neglect of those patients who are misclassified as having fractures that do not warrant evaluation and treatment,” they concluded.

The study received no outside funding. Dr. Leslie, the study’s first author, reported having no financial conflicts to disclose.

Dr. Cummings disclosed consultancy and grant funding from Amgen and Radius. Dr. Eastell disclosed consultancy funding from IDS, Roche Diagnostics, GSK Nutrition, FNIH, Mereo, Lilly, Sandoz, Nittobo, Abbvie, Samsung, and Haoma Medica and grant funding from Nittobo, IDS, Roche, Amgen, and Alexion.

SOURCE: Leslie WD et al. Osteroporos Int. 2020 Mar 16. doi: 10.1007/s00198-019-05274-2.

Average measures of bone mineral density were similar for individuals with high-trauma and low-trauma fractures, and both were significantly distinct from those with no fracture history, based on data from a cohort study of adults aged 40 years and older.

©eranicle/Thinkstock

In the past, low-trauma fractures have typically been associated with osteoporosis, wrote William D. Leslie, MD, of the University of Manitoba, Canada, and his colleagues. However, features distinguishing between low- and high-trauma fractures are often arbitrary and “empirical data have questioned whether distinguishing low-trauma from high-trauma fractures is clinically useful for purposes of risk assessment and treatment,” they wrote.

In a study published in Osteoporosis International, the researchers reviewed data from 64,626 individuals with no prior fracture, 858 with high-trauma fractures, and 14,758 with low-trauma fractures. Overall, the average BMD Z-scores for individuals with no previous fracture were slightly positive, while those with either a high-trauma or low-trauma fracture were negative. The scores for individuals with high-trauma fractures or major osteoporotic fractures were similar to those with low-trauma fractures, and significantly lower (P less than .001) than among individuals with no prior fractures.

The study population included adults aged 40 years and older with baseline DXA scans between Jan. 1, 1996, and Mar. 31, 2016. Those with high-trauma fractures were younger than those with low-trauma fractures (65 years vs. 67 years), and fewer individuals with high-trauma fractures were women (77% vs. 87%).

Both high-trauma and low-trauma fractures were similarly and significantly associated with increased risk for incident major osteoporotic fractures (adjusted hazard ratios 1.31 and 1.55, respectively).

The study findings were limited by several factors including incomplete data on external injury codes, the retrospective study design, and the lack of analysis of the time since prior fractures, the researchers noted. However, the results were strengthened by the large sample size, long-term follow-up, and large numbers of incident fractures, they wrote.

The results support data from previous studies and support “the inclusion of high-trauma clinical fractures in clinical assessment for underlying osteoporosis and in the evaluation for intervention to reduce future fracture risk,” they wrote.

In an accompanying editorial, Steven R. Cummings, MD, of California Pacific Medical Center Research Institute, San Francisco, and Richard Eastell, MD, of the University of Sheffield, England, wrote that the practice of rating fractures according to degree of trauma should be eliminated.

“The study adds evidence to the case that it is time to abandon the mistaken beliefs that fractures rated as high trauma are not associated with decreased BMD, indicate no higher risk of subsequent fracture, or are less likely to be prevented by treatments for osteoporosis,” they wrote.

Describing some fractures as due to trauma reinforces the mistaken belief that the fractures are simply due to the trauma, not decreased bone strength, they noted.

“Indeed, we recommend that people stop attempting to rate or record degree of trauma because such ratings are at best inaccurate and would promote the continued neglect of those patients who are misclassified as having fractures that do not warrant evaluation and treatment,” they concluded.

The study received no outside funding. Dr. Leslie, the study’s first author, reported having no financial conflicts to disclose.

Dr. Cummings disclosed consultancy and grant funding from Amgen and Radius. Dr. Eastell disclosed consultancy funding from IDS, Roche Diagnostics, GSK Nutrition, FNIH, Mereo, Lilly, Sandoz, Nittobo, Abbvie, Samsung, and Haoma Medica and grant funding from Nittobo, IDS, Roche, Amgen, and Alexion.

SOURCE: Leslie WD et al. Osteroporos Int. 2020 Mar 16. doi: 10.1007/s00198-019-05274-2.

Average measures of bone mineral density were similar for individuals with high-trauma and low-trauma fractures, and both were significantly distinct from those with no fracture history, based on data from a cohort study of adults aged 40 years and older.

©eranicle/Thinkstock

In the past, low-trauma fractures have typically been associated with osteoporosis, wrote William D. Leslie, MD, of the University of Manitoba, Canada, and his colleagues. However, features distinguishing between low- and high-trauma fractures are often arbitrary and “empirical data have questioned whether distinguishing low-trauma from high-trauma fractures is clinically useful for purposes of risk assessment and treatment,” they wrote.

In a study published in Osteoporosis International, the researchers reviewed data from 64,626 individuals with no prior fracture, 858 with high-trauma fractures, and 14,758 with low-trauma fractures. Overall, the average BMD Z-scores for individuals with no previous fracture were slightly positive, while those with either a high-trauma or low-trauma fracture were negative. The scores for individuals with high-trauma fractures or major osteoporotic fractures were similar to those with low-trauma fractures, and significantly lower (P less than .001) than among individuals with no prior fractures.

The study population included adults aged 40 years and older with baseline DXA scans between Jan. 1, 1996, and Mar. 31, 2016. Those with high-trauma fractures were younger than those with low-trauma fractures (65 years vs. 67 years), and fewer individuals with high-trauma fractures were women (77% vs. 87%).

Both high-trauma and low-trauma fractures were similarly and significantly associated with increased risk for incident major osteoporotic fractures (adjusted hazard ratios 1.31 and 1.55, respectively).

The study findings were limited by several factors including incomplete data on external injury codes, the retrospective study design, and the lack of analysis of the time since prior fractures, the researchers noted. However, the results were strengthened by the large sample size, long-term follow-up, and large numbers of incident fractures, they wrote.

The results support data from previous studies and support “the inclusion of high-trauma clinical fractures in clinical assessment for underlying osteoporosis and in the evaluation for intervention to reduce future fracture risk,” they wrote.

In an accompanying editorial, Steven R. Cummings, MD, of California Pacific Medical Center Research Institute, San Francisco, and Richard Eastell, MD, of the University of Sheffield, England, wrote that the practice of rating fractures according to degree of trauma should be eliminated.

“The study adds evidence to the case that it is time to abandon the mistaken beliefs that fractures rated as high trauma are not associated with decreased BMD, indicate no higher risk of subsequent fracture, or are less likely to be prevented by treatments for osteoporosis,” they wrote.

Describing some fractures as due to trauma reinforces the mistaken belief that the fractures are simply due to the trauma, not decreased bone strength, they noted.

“Indeed, we recommend that people stop attempting to rate or record degree of trauma because such ratings are at best inaccurate and would promote the continued neglect of those patients who are misclassified as having fractures that do not warrant evaluation and treatment,” they concluded.

The study received no outside funding. Dr. Leslie, the study’s first author, reported having no financial conflicts to disclose.

Dr. Cummings disclosed consultancy and grant funding from Amgen and Radius. Dr. Eastell disclosed consultancy funding from IDS, Roche Diagnostics, GSK Nutrition, FNIH, Mereo, Lilly, Sandoz, Nittobo, Abbvie, Samsung, and Haoma Medica and grant funding from Nittobo, IDS, Roche, Amgen, and Alexion.

SOURCE: Leslie WD et al. Osteroporos Int. 2020 Mar 16. doi: 10.1007/s00198-019-05274-2.

Levels of three vascular biomarkers – hepatocyte growth factor, soluble Flt-1, and platelet-derived growth factor – were elevated a mean of 3 years before systemic sclerosis (SSc) patients developed pulmonary hypertension (PH) in a prospective cohort of 300 subjects.

However, the associations with PH were not very robust. For instance, above an optimal cut point of 9.89 pg/mL for platelet-derived growth factor (PlGF), the sensitivity for future PH was 82%, specificity 56%, and area under the curve (AUC) 0.69. An elevation above the optimal cut point for soluble Flt-1 (sFlt1) – 93.8 pg/mL – was 71% specific and 51% sensitive, with an AUC of 0.61.

Adding PlGF and sFlt1 elevations to carbon monoxide diffusing capacity, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) level, and percent forced vital capacity to predict PH increased the AUC modestly, from 0.72 to 0.77.

The data suggest, perhaps, an early warning system for PH. “Once vascular biomarkers are observed to be elevated, the frequency of other screening tests (e.g., NT-proBNP, DLCO) may be increased in a more cost-effective approach,” wrote investigators led by rheumatologist Christopher Mecoli, MD, an assistant professor at Johns Hopkins University, Baltimore, in Arthritis & Rheumatology.

“In the end, the authors did not overstate the case and cautiously recommended that using biomarkers might be useful in the future. The finding that when there are increased numbers of abnormalities of vascular markers, there would be an increased probability of pulmonary hypertension, makes sense.” However, “this was a major fishing expedition, and the data are certainly not sufficient to suggest anything clinical but are of some interest with respect to the general hypothesis,” said rheumatologist Daniel Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, when asked for comment.

The subjects were followed for at least 5 years and had no evidence of PH at study entry. Levels of P1GF, sFlt-1, hepatocyte growth factor (HGF), soluble endoglin, and endostatin were assessed at baseline and at regular intervals thereafter. A total of 46 patients (15%) developed PH after a mean of 3 years.

Risk of PH was associated with baseline elevations of HGF (hazard ratio, 1.99; 95% CI, 1.24-3.17; P = .004); sFlt1 (HR, 3.04; 95% CI, 1.29-7.14; P = .011); and PlGF (HR, 2.74; 95% CI, 1.32-5.69; P = .007).

Just 2 of 25 patients (8%) with no biomarkers elevated at baseline developed PH versus 12 of 29 (42%) with all five elevated. That translated to a dose-response relationship, with each additional elevated biomarker increasing the risk of PH by 78% (95% CI, 1.2-2.6; P = .004).

“There [was] no consistent trend of increasing biomarker levels over time as patients approach[ed] a diagnosis of [PH]. ... Serial testing may have value in patients with early disease to first detect elevations in biomarkers,” but “once elevated, the utility of serially monitoring appears low,” the investigators wrote.

It’s not surprising that “a higher number of elevated biomarkers relating to vascular dysfunction would correspond to a higher risk of PH,” the team wrote. However, “while these biomarkers hold promise in the risk stratification of SSc patients, many more vascular molecules exist which may have similar or greater value.”

There was no substantial correlation between any biomarker and disease duration, age at enrollment, or age at diagnosis, and no significant difference in biomarker level based on patient comorbidities. No biomarker was significantly associated with medication use at cohort entry, and none were significantly associated with the risk of ischemic digital lesions.

The majority of patients were white women. At enrollment, the average age was 52 years, and subjects had SSc for a mean of 10 years.

The work was funded by the National Institutes of Health, among others. Investigator disclosures were not reported.

[email protected]

SOURCE: Mecoli C et al. Arthritis Rheumatol. 2020 Mar 21. doi: 10.1002/art.41265.

Levels of three vascular biomarkers – hepatocyte growth factor, soluble Flt-1, and platelet-derived growth factor – were elevated a mean of 3 years before systemic sclerosis (SSc) patients developed pulmonary hypertension (PH) in a prospective cohort of 300 subjects.

However, the associations with PH were not very robust. For instance, above an optimal cut point of 9.89 pg/mL for platelet-derived growth factor (PlGF), the sensitivity for future PH was 82%, specificity 56%, and area under the curve (AUC) 0.69. An elevation above the optimal cut point for soluble Flt-1 (sFlt1) – 93.8 pg/mL – was 71% specific and 51% sensitive, with an AUC of 0.61.

Adding PlGF and sFlt1 elevations to carbon monoxide diffusing capacity, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) level, and percent forced vital capacity to predict PH increased the AUC modestly, from 0.72 to 0.77.

The data suggest, perhaps, an early warning system for PH. “Once vascular biomarkers are observed to be elevated, the frequency of other screening tests (e.g., NT-proBNP, DLCO) may be increased in a more cost-effective approach,” wrote investigators led by rheumatologist Christopher Mecoli, MD, an assistant professor at Johns Hopkins University, Baltimore, in Arthritis & Rheumatology.

“In the end, the authors did not overstate the case and cautiously recommended that using biomarkers might be useful in the future. The finding that when there are increased numbers of abnormalities of vascular markers, there would be an increased probability of pulmonary hypertension, makes sense.” However, “this was a major fishing expedition, and the data are certainly not sufficient to suggest anything clinical but are of some interest with respect to the general hypothesis,” said rheumatologist Daniel Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, when asked for comment.

The subjects were followed for at least 5 years and had no evidence of PH at study entry. Levels of P1GF, sFlt-1, hepatocyte growth factor (HGF), soluble endoglin, and endostatin were assessed at baseline and at regular intervals thereafter. A total of 46 patients (15%) developed PH after a mean of 3 years.

Risk of PH was associated with baseline elevations of HGF (hazard ratio, 1.99; 95% CI, 1.24-3.17; P = .004); sFlt1 (HR, 3.04; 95% CI, 1.29-7.14; P = .011); and PlGF (HR, 2.74; 95% CI, 1.32-5.69; P = .007).

Just 2 of 25 patients (8%) with no biomarkers elevated at baseline developed PH versus 12 of 29 (42%) with all five elevated. That translated to a dose-response relationship, with each additional elevated biomarker increasing the risk of PH by 78% (95% CI, 1.2-2.6; P = .004).

“There [was] no consistent trend of increasing biomarker levels over time as patients approach[ed] a diagnosis of [PH]. ... Serial testing may have value in patients with early disease to first detect elevations in biomarkers,” but “once elevated, the utility of serially monitoring appears low,” the investigators wrote.

It’s not surprising that “a higher number of elevated biomarkers relating to vascular dysfunction would correspond to a higher risk of PH,” the team wrote. However, “while these biomarkers hold promise in the risk stratification of SSc patients, many more vascular molecules exist which may have similar or greater value.”

There was no substantial correlation between any biomarker and disease duration, age at enrollment, or age at diagnosis, and no significant difference in biomarker level based on patient comorbidities. No biomarker was significantly associated with medication use at cohort entry, and none were significantly associated with the risk of ischemic digital lesions.

The majority of patients were white women. At enrollment, the average age was 52 years, and subjects had SSc for a mean of 10 years.

The work was funded by the National Institutes of Health, among others. Investigator disclosures were not reported.

[email protected]

SOURCE: Mecoli C et al. Arthritis Rheumatol. 2020 Mar 21. doi: 10.1002/art.41265.

Levels of three vascular biomarkers – hepatocyte growth factor, soluble Flt-1, and platelet-derived growth factor – were elevated a mean of 3 years before systemic sclerosis (SSc) patients developed pulmonary hypertension (PH) in a prospective cohort of 300 subjects.

However, the associations with PH were not very robust. For instance, above an optimal cut point of 9.89 pg/mL for platelet-derived growth factor (PlGF), the sensitivity for future PH was 82%, specificity 56%, and area under the curve (AUC) 0.69. An elevation above the optimal cut point for soluble Flt-1 (sFlt1) – 93.8 pg/mL – was 71% specific and 51% sensitive, with an AUC of 0.61.

Adding PlGF and sFlt1 elevations to carbon monoxide diffusing capacity, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) level, and percent forced vital capacity to predict PH increased the AUC modestly, from 0.72 to 0.77.

The data suggest, perhaps, an early warning system for PH. “Once vascular biomarkers are observed to be elevated, the frequency of other screening tests (e.g., NT-proBNP, DLCO) may be increased in a more cost-effective approach,” wrote investigators led by rheumatologist Christopher Mecoli, MD, an assistant professor at Johns Hopkins University, Baltimore, in Arthritis & Rheumatology.

“In the end, the authors did not overstate the case and cautiously recommended that using biomarkers might be useful in the future. The finding that when there are increased numbers of abnormalities of vascular markers, there would be an increased probability of pulmonary hypertension, makes sense.” However, “this was a major fishing expedition, and the data are certainly not sufficient to suggest anything clinical but are of some interest with respect to the general hypothesis,” said rheumatologist Daniel Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, when asked for comment.

The subjects were followed for at least 5 years and had no evidence of PH at study entry. Levels of P1GF, sFlt-1, hepatocyte growth factor (HGF), soluble endoglin, and endostatin were assessed at baseline and at regular intervals thereafter. A total of 46 patients (15%) developed PH after a mean of 3 years.

Risk of PH was associated with baseline elevations of HGF (hazard ratio, 1.99; 95% CI, 1.24-3.17; P = .004); sFlt1 (HR, 3.04; 95% CI, 1.29-7.14; P = .011); and PlGF (HR, 2.74; 95% CI, 1.32-5.69; P = .007).

Just 2 of 25 patients (8%) with no biomarkers elevated at baseline developed PH versus 12 of 29 (42%) with all five elevated. That translated to a dose-response relationship, with each additional elevated biomarker increasing the risk of PH by 78% (95% CI, 1.2-2.6; P = .004).

“There [was] no consistent trend of increasing biomarker levels over time as patients approach[ed] a diagnosis of [PH]. ... Serial testing may have value in patients with early disease to first detect elevations in biomarkers,” but “once elevated, the utility of serially monitoring appears low,” the investigators wrote.

It’s not surprising that “a higher number of elevated biomarkers relating to vascular dysfunction would correspond to a higher risk of PH,” the team wrote. However, “while these biomarkers hold promise in the risk stratification of SSc patients, many more vascular molecules exist which may have similar or greater value.”

There was no substantial correlation between any biomarker and disease duration, age at enrollment, or age at diagnosis, and no significant difference in biomarker level based on patient comorbidities. No biomarker was significantly associated with medication use at cohort entry, and none were significantly associated with the risk of ischemic digital lesions.

The majority of patients were white women. At enrollment, the average age was 52 years, and subjects had SSc for a mean of 10 years.

The work was funded by the National Institutes of Health, among others. Investigator disclosures were not reported.

[email protected]

SOURCE: Mecoli C et al. Arthritis Rheumatol. 2020 Mar 21. doi: 10.1002/art.41265.

Combination therapy with leflunomide and hydroxychloroquine is safe in patients with primary Sjögren’s syndrome and may elicit clinical improvement, according to results from a phase 2a, randomized clinical trial published in Lancet Rheumatology.

The combination’s statistically significant effect on the European League Against Rheumatism (EULAR) Sjögren’s syndrome disease activity index (ESSDAI) score at 24 weeks, the primary endpoint of the small, double-blind, placebo-controlled trial, suggests that the combination should be studied further in larger trials, according to first author Eefje Hanna Martine van der Heijden, MD, a rheumatologist at University Medical Center Utrecht (the Netherlands), and colleagues.

The investigators decided to study leflunomide and hydroxychloroquine, which target overlapping and distinct immunopathologic pathways, because data support the safety of each drug individually, and a previous in vitro study by the authors indicated that they have complementary effects when administered together.

“To our knowledge, this is the first randomized, placebo-controlled clinical trial in patients with primary Sjögren’s syndrome that shows significant clinical efficacy, as measured by ESSDAI, and is associated with significant improvements in other clinical parameters, including dryness and fatigue,” the investigators wrote.

Dr. van der Heijden and colleagues screened 37 patients from the outpatient clinic of their medical center and enrolled 29 (28 women) who met American-European Consensus Criteria into their study. They had moderate to active disease, defined as an ESSDAI score of 5 or higher, and a lymphocytic focus score of 1 or higher in labial salivary gland biopsy specimens that were obtained before inclusion. The population’s average age was approximately 54 years. They had an average disease duration of about 8 years, a mean ESSDAI score of about 9, and mean EULAR Sjögren’s syndrome patient reported index (ESSPRI) score of 6.7. A total of 21 patients were randomized to leflunomide 20 mg and hydroxychloroquine 400 mg daily, and 8 patients were randomized to placebos. Baseline characteristics were similar between groups, but mean serum IgG level was 19.4 g/L in the treatment group and 13.8 g/L in the placebo group. One patient in the placebo group developed polymyalgia rheumatica and required high-dose prednisone treatment. The investigators excluded this patient from the primary analysis.

At 24 weeks, the mean difference in ESSDAI score in the leflunomide-hydroxychloroquine group, compared with the placebo group, was –4.35 points after adjustment for baseline values. This difference was statistically significant.

Secondary endpoints in the study showed inconsistent statistically significant differences between the treatment groups at 8, 16, and 24 weeks. The total ESSPRI score at 16 weeks was 1.66 points lower in the treatment group than in the placebo group. Stimulated whole saliva production was increased in the leflunomide-hydroxychloroquine group at 16 weeks, compared with the placebo group. Unstimulated whole saliva production at 24 weeks was higher in the leflunomide-hydroxychloroquine group than in controls. The investigators found no differences between groups in visual analog scores for ocular or oral dryness.

No patient in the leflunomide-hydroxychloroquine group had a serious adverse event. Two serious adverse events (hospital admission for pancreatitis and hospital admission for nephrolithiasis) occurred in the placebo group. The most common adverse events in the leflunomide-hydroxychloroquine group were GI discomfort (52% vs. 25% in the placebo group), modest transient increases in ALT (48% vs. 13%), and short episodes of general malaise and shivering (43% vs. 13%).

In an accompanying editorial, Astrid Rasmussen, MD, PhD, of the Oklahoma Sjögren’s Syndrome Center of Research Translation at the Oklahoma Medical Research Foundation in Oklahoma City, wrote that the trial by Dr. van der Heijden and colleagues was limited by a small sample size and short duration. In addition, some of the findings were unexplained, such as modest changes in secondary endpoints and a concomitant decrease in ESSDAI scores at 8 weeks for both study groups.

Nevertheless, the study provides reason to think in new ways about old drugs, wrote Dr. Rasmussen. “Combination or sequential use of existing agents that target different aspects of immune dysregulation, while having acceptable safety profiles and cost-benefit ratios, should represent an avenue of further exploration. Just as importantly, subphenotyping patients on the basis of their underlying pathogenic processes and identifying sensitive outcome measures could transform the current enthusiasm for identifying effective treatments for Sjögren’s syndrome into a reality for the patients that need them the most.”

The study was funded by ZonMw. The authors of the study reported no conflicts of interest. Dr. Rasmussen reported having no conflicts of interest.

[email protected]

SOURCE: van der Heijden EHM et al. Lancet Rheumatol. 2020 Mar 26. doi: 10.1016/S2665-9913(20)30057-6.

Combination therapy with leflunomide and hydroxychloroquine is safe in patients with primary Sjögren’s syndrome and may elicit clinical improvement, according to results from a phase 2a, randomized clinical trial published in Lancet Rheumatology.

The combination’s statistically significant effect on the European League Against Rheumatism (EULAR) Sjögren’s syndrome disease activity index (ESSDAI) score at 24 weeks, the primary endpoint of the small, double-blind, placebo-controlled trial, suggests that the combination should be studied further in larger trials, according to first author Eefje Hanna Martine van der Heijden, MD, a rheumatologist at University Medical Center Utrecht (the Netherlands), and colleagues.

The investigators decided to study leflunomide and hydroxychloroquine, which target overlapping and distinct immunopathologic pathways, because data support the safety of each drug individually, and a previous in vitro study by the authors indicated that they have complementary effects when administered together.

“To our knowledge, this is the first randomized, placebo-controlled clinical trial in patients with primary Sjögren’s syndrome that shows significant clinical efficacy, as measured by ESSDAI, and is associated with significant improvements in other clinical parameters, including dryness and fatigue,” the investigators wrote.

Dr. van der Heijden and colleagues screened 37 patients from the outpatient clinic of their medical center and enrolled 29 (28 women) who met American-European Consensus Criteria into their study. They had moderate to active disease, defined as an ESSDAI score of 5 or higher, and a lymphocytic focus score of 1 or higher in labial salivary gland biopsy specimens that were obtained before inclusion. The population’s average age was approximately 54 years. They had an average disease duration of about 8 years, a mean ESSDAI score of about 9, and mean EULAR Sjögren’s syndrome patient reported index (ESSPRI) score of 6.7. A total of 21 patients were randomized to leflunomide 20 mg and hydroxychloroquine 400 mg daily, and 8 patients were randomized to placebos. Baseline characteristics were similar between groups, but mean serum IgG level was 19.4 g/L in the treatment group and 13.8 g/L in the placebo group. One patient in the placebo group developed polymyalgia rheumatica and required high-dose prednisone treatment. The investigators excluded this patient from the primary analysis.

At 24 weeks, the mean difference in ESSDAI score in the leflunomide-hydroxychloroquine group, compared with the placebo group, was –4.35 points after adjustment for baseline values. This difference was statistically significant.

Secondary endpoints in the study showed inconsistent statistically significant differences between the treatment groups at 8, 16, and 24 weeks. The total ESSPRI score at 16 weeks was 1.66 points lower in the treatment group than in the placebo group. Stimulated whole saliva production was increased in the leflunomide-hydroxychloroquine group at 16 weeks, compared with the placebo group. Unstimulated whole saliva production at 24 weeks was higher in the leflunomide-hydroxychloroquine group than in controls. The investigators found no differences between groups in visual analog scores for ocular or oral dryness.

No patient in the leflunomide-hydroxychloroquine group had a serious adverse event. Two serious adverse events (hospital admission for pancreatitis and hospital admission for nephrolithiasis) occurred in the placebo group. The most common adverse events in the leflunomide-hydroxychloroquine group were GI discomfort (52% vs. 25% in the placebo group), modest transient increases in ALT (48% vs. 13%), and short episodes of general malaise and shivering (43% vs. 13%).

In an accompanying editorial, Astrid Rasmussen, MD, PhD, of the Oklahoma Sjögren’s Syndrome Center of Research Translation at the Oklahoma Medical Research Foundation in Oklahoma City, wrote that the trial by Dr. van der Heijden and colleagues was limited by a small sample size and short duration. In addition, some of the findings were unexplained, such as modest changes in secondary endpoints and a concomitant decrease in ESSDAI scores at 8 weeks for both study groups.

Nevertheless, the study provides reason to think in new ways about old drugs, wrote Dr. Rasmussen. “Combination or sequential use of existing agents that target different aspects of immune dysregulation, while having acceptable safety profiles and cost-benefit ratios, should represent an avenue of further exploration. Just as importantly, subphenotyping patients on the basis of their underlying pathogenic processes and identifying sensitive outcome measures could transform the current enthusiasm for identifying effective treatments for Sjögren’s syndrome into a reality for the patients that need them the most.”

The study was funded by ZonMw. The authors of the study reported no conflicts of interest. Dr. Rasmussen reported having no conflicts of interest.

[email protected]

SOURCE: van der Heijden EHM et al. Lancet Rheumatol. 2020 Mar 26. doi: 10.1016/S2665-9913(20)30057-6.

Combination therapy with leflunomide and hydroxychloroquine is safe in patients with primary Sjögren’s syndrome and may elicit clinical improvement, according to results from a phase 2a, randomized clinical trial published in Lancet Rheumatology.

The combination’s statistically significant effect on the European League Against Rheumatism (EULAR) Sjögren’s syndrome disease activity index (ESSDAI) score at 24 weeks, the primary endpoint of the small, double-blind, placebo-controlled trial, suggests that the combination should be studied further in larger trials, according to first author Eefje Hanna Martine van der Heijden, MD, a rheumatologist at University Medical Center Utrecht (the Netherlands), and colleagues.

The investigators decided to study leflunomide and hydroxychloroquine, which target overlapping and distinct immunopathologic pathways, because data support the safety of each drug individually, and a previous in vitro study by the authors indicated that they have complementary effects when administered together.

“To our knowledge, this is the first randomized, placebo-controlled clinical trial in patients with primary Sjögren’s syndrome that shows significant clinical efficacy, as measured by ESSDAI, and is associated with significant improvements in other clinical parameters, including dryness and fatigue,” the investigators wrote.

Dr. van der Heijden and colleagues screened 37 patients from the outpatient clinic of their medical center and enrolled 29 (28 women) who met American-European Consensus Criteria into their study. They had moderate to active disease, defined as an ESSDAI score of 5 or higher, and a lymphocytic focus score of 1 or higher in labial salivary gland biopsy specimens that were obtained before inclusion. The population’s average age was approximately 54 years. They had an average disease duration of about 8 years, a mean ESSDAI score of about 9, and mean EULAR Sjögren’s syndrome patient reported index (ESSPRI) score of 6.7. A total of 21 patients were randomized to leflunomide 20 mg and hydroxychloroquine 400 mg daily, and 8 patients were randomized to placebos. Baseline characteristics were similar between groups, but mean serum IgG level was 19.4 g/L in the treatment group and 13.8 g/L in the placebo group. One patient in the placebo group developed polymyalgia rheumatica and required high-dose prednisone treatment. The investigators excluded this patient from the primary analysis.

At 24 weeks, the mean difference in ESSDAI score in the leflunomide-hydroxychloroquine group, compared with the placebo group, was –4.35 points after adjustment for baseline values. This difference was statistically significant.

Secondary endpoints in the study showed inconsistent statistically significant differences between the treatment groups at 8, 16, and 24 weeks. The total ESSPRI score at 16 weeks was 1.66 points lower in the treatment group than in the placebo group. Stimulated whole saliva production was increased in the leflunomide-hydroxychloroquine group at 16 weeks, compared with the placebo group. Unstimulated whole saliva production at 24 weeks was higher in the leflunomide-hydroxychloroquine group than in controls. The investigators found no differences between groups in visual analog scores for ocular or oral dryness.

No patient in the leflunomide-hydroxychloroquine group had a serious adverse event. Two serious adverse events (hospital admission for pancreatitis and hospital admission for nephrolithiasis) occurred in the placebo group. The most common adverse events in the leflunomide-hydroxychloroquine group were GI discomfort (52% vs. 25% in the placebo group), modest transient increases in ALT (48% vs. 13%), and short episodes of general malaise and shivering (43% vs. 13%).

In an accompanying editorial, Astrid Rasmussen, MD, PhD, of the Oklahoma Sjögren’s Syndrome Center of Research Translation at the Oklahoma Medical Research Foundation in Oklahoma City, wrote that the trial by Dr. van der Heijden and colleagues was limited by a small sample size and short duration. In addition, some of the findings were unexplained, such as modest changes in secondary endpoints and a concomitant decrease in ESSDAI scores at 8 weeks for both study groups.

Nevertheless, the study provides reason to think in new ways about old drugs, wrote Dr. Rasmussen. “Combination or sequential use of existing agents that target different aspects of immune dysregulation, while having acceptable safety profiles and cost-benefit ratios, should represent an avenue of further exploration. Just as importantly, subphenotyping patients on the basis of their underlying pathogenic processes and identifying sensitive outcome measures could transform the current enthusiasm for identifying effective treatments for Sjögren’s syndrome into a reality for the patients that need them the most.”

The study was funded by ZonMw. The authors of the study reported no conflicts of interest. Dr. Rasmussen reported having no conflicts of interest.

[email protected]

SOURCE: van der Heijden EHM et al. Lancet Rheumatol. 2020 Mar 26. doi: 10.1016/S2665-9913(20)30057-6.

Adalimumab biosimilars are years away from entering the marketplace in the United States because of patent disputes, but they already have led to substantial discounts in Denmark, researchers wrote in JAMA Internal Medicine.

The Danish health care system switched almost entirely to adalimumab biosimilars after the patent on the original adalimumab product, Humira, expired there in October 2018. The switch to biosimilars led to an 82% decrease in costs for the medication, wrote Thomas Bo Jensen, MD, and colleagues in a research letter.

Denmark did not automatically substitute biosimilars, but the Danish Medicines Council recommended adalimumab biosimilars for all indications following Humira’s patent expiration. The recommendations “included switching patients to a biosimilar who were already well treated with the originator,” the researchers wrote.

To study the shift to adalimumab biosimilars across all indications in Denmark and calculate cost reductions, Dr. Jensen, of the department of clinical pharmacology at Copenhagen University Hospital Bispebjerg, and coinvestigators examined monthly data on drug sales from Amgros, which purchases all hospital drugs in the country.

“The proportion of adalimumab biosimilars increased from 71.6% (7,040 of 9,829 pens) in November 2018 to 95.1% (8,974 of 9,438 pens) in December 2018,” the researchers wrote. “Costs of adalimumab decreased by 82.8% from September 2018 to December 2018 (September: 8,197 pens at $5.13 million; December: 9,438 pens at $1.01 million).” The results were similar in rheumatology, dermatology, and gastroenterology.

The Food and Drug Administration has approved five adalimumab biosimilars in the United States, but “they will not enter the market until 2023 owing to patent disputes with AbbVie, the manufacturer of Humira,” wrote Jennifer D. Claytor, MD, of the department of internal medicine at University of California, San Francisco, and Walid Gellad, MD, of the division of general internal medicine at University of Pittsburgh, in an accompanying editorial.

The annual postrebate price of Humira doubled between 2013 and 2018, from $19,000 to $38,000, and these price increases may influence the price of biosimilars, “which will be priced using Humira’s price as an anchor,” Dr. Claytor and Dr. Gellad wrote.

A rapid shift to adalimumab biosimilars across the United States when they become available is “unlikely,” they wrote. Nonetheless, “some health care systems of comparable size to Denmark (e.g., the Veterans Affairs system) and others that are larger (e.g., Kaiser Permanente) ... have the ability to switch products quickly through use of formularies and a prescriber workforce. For example, Kaiser Permanente has successfully replaced Remicade (infliximab) with biosimilars in 80% of patients.”

Given the many biologics in development and increasing health care spending, “we need to take seriously the substantial savings offered by biosimilars and the feasibility, as evidenced by Denmark, of switching to biosimilars quickly once they are available on the market,” Dr. Claytor and Dr. Gellad concluded.

The research was supported by an unrestricted grant from Helsefonden. One author disclosed receiving grants from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb outside the current study. The editorial authors had no disclosures.

[email protected]

SOURCE: Jensen TB et al. JAMA Intern Med. 2020 Mar 30. doi: 10.1001/jamainternmed.2020.0338.

Adalimumab biosimilars are years away from entering the marketplace in the United States because of patent disputes, but they already have led to substantial discounts in Denmark, researchers wrote in JAMA Internal Medicine.

The Danish health care system switched almost entirely to adalimumab biosimilars after the patent on the original adalimumab product, Humira, expired there in October 2018. The switch to biosimilars led to an 82% decrease in costs for the medication, wrote Thomas Bo Jensen, MD, and colleagues in a research letter.

Denmark did not automatically substitute biosimilars, but the Danish Medicines Council recommended adalimumab biosimilars for all indications following Humira’s patent expiration. The recommendations “included switching patients to a biosimilar who were already well treated with the originator,” the researchers wrote.

To study the shift to adalimumab biosimilars across all indications in Denmark and calculate cost reductions, Dr. Jensen, of the department of clinical pharmacology at Copenhagen University Hospital Bispebjerg, and coinvestigators examined monthly data on drug sales from Amgros, which purchases all hospital drugs in the country.

“The proportion of adalimumab biosimilars increased from 71.6% (7,040 of 9,829 pens) in November 2018 to 95.1% (8,974 of 9,438 pens) in December 2018,” the researchers wrote. “Costs of adalimumab decreased by 82.8% from September 2018 to December 2018 (September: 8,197 pens at $5.13 million; December: 9,438 pens at $1.01 million).” The results were similar in rheumatology, dermatology, and gastroenterology.

The Food and Drug Administration has approved five adalimumab biosimilars in the United States, but “they will not enter the market until 2023 owing to patent disputes with AbbVie, the manufacturer of Humira,” wrote Jennifer D. Claytor, MD, of the department of internal medicine at University of California, San Francisco, and Walid Gellad, MD, of the division of general internal medicine at University of Pittsburgh, in an accompanying editorial.

The annual postrebate price of Humira doubled between 2013 and 2018, from $19,000 to $38,000, and these price increases may influence the price of biosimilars, “which will be priced using Humira’s price as an anchor,” Dr. Claytor and Dr. Gellad wrote.

A rapid shift to adalimumab biosimilars across the United States when they become available is “unlikely,” they wrote. Nonetheless, “some health care systems of comparable size to Denmark (e.g., the Veterans Affairs system) and others that are larger (e.g., Kaiser Permanente) ... have the ability to switch products quickly through use of formularies and a prescriber workforce. For example, Kaiser Permanente has successfully replaced Remicade (infliximab) with biosimilars in 80% of patients.”

Given the many biologics in development and increasing health care spending, “we need to take seriously the substantial savings offered by biosimilars and the feasibility, as evidenced by Denmark, of switching to biosimilars quickly once they are available on the market,” Dr. Claytor and Dr. Gellad concluded.

The research was supported by an unrestricted grant from Helsefonden. One author disclosed receiving grants from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb outside the current study. The editorial authors had no disclosures.

[email protected]

SOURCE: Jensen TB et al. JAMA Intern Med. 2020 Mar 30. doi: 10.1001/jamainternmed.2020.0338.

Adalimumab biosimilars are years away from entering the marketplace in the United States because of patent disputes, but they already have led to substantial discounts in Denmark, researchers wrote in JAMA Internal Medicine.

The Danish health care system switched almost entirely to adalimumab biosimilars after the patent on the original adalimumab product, Humira, expired there in October 2018. The switch to biosimilars led to an 82% decrease in costs for the medication, wrote Thomas Bo Jensen, MD, and colleagues in a research letter.

Denmark did not automatically substitute biosimilars, but the Danish Medicines Council recommended adalimumab biosimilars for all indications following Humira’s patent expiration. The recommendations “included switching patients to a biosimilar who were already well treated with the originator,” the researchers wrote.

To study the shift to adalimumab biosimilars across all indications in Denmark and calculate cost reductions, Dr. Jensen, of the department of clinical pharmacology at Copenhagen University Hospital Bispebjerg, and coinvestigators examined monthly data on drug sales from Amgros, which purchases all hospital drugs in the country.

“The proportion of adalimumab biosimilars increased from 71.6% (7,040 of 9,829 pens) in November 2018 to 95.1% (8,974 of 9,438 pens) in December 2018,” the researchers wrote. “Costs of adalimumab decreased by 82.8% from September 2018 to December 2018 (September: 8,197 pens at $5.13 million; December: 9,438 pens at $1.01 million).” The results were similar in rheumatology, dermatology, and gastroenterology.

The Food and Drug Administration has approved five adalimumab biosimilars in the United States, but “they will not enter the market until 2023 owing to patent disputes with AbbVie, the manufacturer of Humira,” wrote Jennifer D. Claytor, MD, of the department of internal medicine at University of California, San Francisco, and Walid Gellad, MD, of the division of general internal medicine at University of Pittsburgh, in an accompanying editorial.

The annual postrebate price of Humira doubled between 2013 and 2018, from $19,000 to $38,000, and these price increases may influence the price of biosimilars, “which will be priced using Humira’s price as an anchor,” Dr. Claytor and Dr. Gellad wrote.

A rapid shift to adalimumab biosimilars across the United States when they become available is “unlikely,” they wrote. Nonetheless, “some health care systems of comparable size to Denmark (e.g., the Veterans Affairs system) and others that are larger (e.g., Kaiser Permanente) ... have the ability to switch products quickly through use of formularies and a prescriber workforce. For example, Kaiser Permanente has successfully replaced Remicade (infliximab) with biosimilars in 80% of patients.”

Given the many biologics in development and increasing health care spending, “we need to take seriously the substantial savings offered by biosimilars and the feasibility, as evidenced by Denmark, of switching to biosimilars quickly once they are available on the market,” Dr. Claytor and Dr. Gellad concluded.

The research was supported by an unrestricted grant from Helsefonden. One author disclosed receiving grants from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb outside the current study. The editorial authors had no disclosures.

[email protected]

SOURCE: Jensen TB et al. JAMA Intern Med. 2020 Mar 30. doi: 10.1001/jamainternmed.2020.0338.

For patients with lupus nephritis, kidney response improves when voclosporin (Aurinia Pharmaceuticals) is added to mycophenolate and low-dose corticosteroids, results from the phase 3 AURORA trial show.
 

The calcineurin inhibitor is the first novel agent to demonstrate effectiveness in the treatment of people with lupus nephritis, a disease that can lead to irreversible kidney damage, kidney failure, and even death.

“We believe that voclosporin – as an add-on therapy – will help more patients achieve remission,” said Keisha Gibson, MD, MPH, chief of pediatric nephrology at the UNC Kidney Center in Chapel Hill, North Carolina, who led the study and presented the findings during a virtual session at the National Kidney Foundation 2020 Spring Clinical Meetings.

The burden that lupus places on patients and the health system is high, she reported. Patients with lupus and uncontrolled kidney disease frequently have complications that require hospitalization, can suffer complete or partial loss of income, and can become temporarily disabled. And up to 50% of lupus patients will develop lupus nephritis.

“When we are lucky and see early treatment responses in our patients, we know that their long-term outcomes, measured by proteinuria reduction, are quite good,” said Gibson. “Unfortunately, in 10% to 30% of patients, despite standard-of-care therapies, we see progression to end-stage kidney disease within 15 years of diagnosis. This confers a huge cost to overall health and quality of life, and is an excess burden to the healthcare system.

“It is clear that one of the biggest risk factors for these patients who have kidney disease that is progressing to kidney failure is an inability to control the inflammation and chronic damage from uncontrolled disease,” she told Medscape Medical News.

“While there have certainly been a few advances in the care of patients with lupus disease, I believe that this therapy may help move the needle, specifically for patients with kidney involvement from their lupus disease,” she added.

Renal Response Much Higher With Voclosporin

The typical standard of care for patients with active lupus and kidney disease is either a combination of cyclophosphamide plus steroids or a combination of mycophenolate mofetil plus steroids.

The global, double-blind, randomized, placebo-controlled trial compared the effectiveness and safety of twice-daily oral voclosporin 23.7 mg with placebo. All 357 study participants also received mycophenolate 2 g daily and rapidly tapered low-dose oral corticosteroids.

At 1 year, the renal response rate was higher in the voclosporin group than in the placebo group (40.8% vs 22.5%; odds ratio, 2.65; P < .001).

“AURORA patients achieved low levels of protein twice as quickly as patients on standard of care,” the researchers write in their abstract. Median time to the achievement of a urine protein to creatinine ratio below 0.5 mg/mg was significantly and clinically better with voclosporin than with placebo (169 vs 372 days; log rank P < .001).

And voclosporin was well tolerated. The percentage of serious adverse events was similar in the voclosporin and placebo groups (20.8% vs 21.3%), with infection being the most common serious event (10.1% vs 11.2%).

In the voclosporin group, there were no significant differences between baseline and 1 year estimated glomerular filtration rates (eGFR), blood pressure, lipid levels, or sugar levels.

And there were fewer deaths in the voclosporin group than in the placebo group (1 vs 5).

Benefits were seen in all subgroups, including age, sex, race, biopsy class, geographic region of origin, and mycophenolate exposure at screening, Gibson reported.

Promise of a New Treatment

The promise of a new treatment is exciting for the field, said Joseph Vassalotti, MD, chief medical officer of the National Kidney Foundation.

However, it’s important to note that “this study is applicable only to patients with lupus nephritis with preserved kidney function,” he added.

An “eGFR less than 45 mL/min per 1.73 m² was implied as an exclusion criteria, so I would say it certainly doesn’t apply to patients with impaired kidney function,” he said, pointing out that this will be clearer when the final data are published.

The study cohort was heterogeneous; 86% of participants had class 3 or 4 biopsy findings and 14% had class 5, so the superiority of voclosporin is convincing, he said.

“We look forward to full publication and more details,” he told Medscape Medical News. “They do have an extension study, and it will be interesting to see how that plays out.”

Voclosporin was granted Fast Track designation by the US Food and Drug Administration in 2016, and these positive phase 3 results mean that a New Drug Application will likely be filed in the next few months. If approved, the drug could be on the market by 2021, according to a press release from Aurinia.

Nephrologists are familiar with calcineurin inhibitors, so it will be interesting to see, given the success of this trial, if voclosporin has a potential role in other kidney diseases, “such as minimal change disease,” said Vassalotti.

He added that there are concerns, unrelated to the AURORA trial, about the supply of hydroxychloroquine, which is also used for the treatment of lupus nephritis. “An overarching concern is that the supply will be limited now that the drug is being studied and used as prophylaxis after exposure to SARS-CoV-2 and as a treatment for COVID-19, creating challenges for patients with lupus nephritis trying to obtain their needed medication,” he said.

Gibson reports no relevant financial relationships. Two coauthors work for the drugmaker, Aurinia. Vassalotti reports no relevant financial relationships.
 

This article first appeared on Medscape.com.

For patients with lupus nephritis, kidney response improves when voclosporin (Aurinia Pharmaceuticals) is added to mycophenolate and low-dose corticosteroids, results from the phase 3 AURORA trial show.
 

The calcineurin inhibitor is the first novel agent to demonstrate effectiveness in the treatment of people with lupus nephritis, a disease that can lead to irreversible kidney damage, kidney failure, and even death.

“We believe that voclosporin – as an add-on therapy – will help more patients achieve remission,” said Keisha Gibson, MD, MPH, chief of pediatric nephrology at the UNC Kidney Center in Chapel Hill, North Carolina, who led the study and presented the findings during a virtual session at the National Kidney Foundation 2020 Spring Clinical Meetings.

The burden that lupus places on patients and the health system is high, she reported. Patients with lupus and uncontrolled kidney disease frequently have complications that require hospitalization, can suffer complete or partial loss of income, and can become temporarily disabled. And up to 50% of lupus patients will develop lupus nephritis.

“When we are lucky and see early treatment responses in our patients, we know that their long-term outcomes, measured by proteinuria reduction, are quite good,” said Gibson. “Unfortunately, in 10% to 30% of patients, despite standard-of-care therapies, we see progression to end-stage kidney disease within 15 years of diagnosis. This confers a huge cost to overall health and quality of life, and is an excess burden to the healthcare system.

“It is clear that one of the biggest risk factors for these patients who have kidney disease that is progressing to kidney failure is an inability to control the inflammation and chronic damage from uncontrolled disease,” she told Medscape Medical News.

“While there have certainly been a few advances in the care of patients with lupus disease, I believe that this therapy may help move the needle, specifically for patients with kidney involvement from their lupus disease,” she added.

Renal Response Much Higher With Voclosporin

The typical standard of care for patients with active lupus and kidney disease is either a combination of cyclophosphamide plus steroids or a combination of mycophenolate mofetil plus steroids.

The global, double-blind, randomized, placebo-controlled trial compared the effectiveness and safety of twice-daily oral voclosporin 23.7 mg with placebo. All 357 study participants also received mycophenolate 2 g daily and rapidly tapered low-dose oral corticosteroids.

At 1 year, the renal response rate was higher in the voclosporin group than in the placebo group (40.8% vs 22.5%; odds ratio, 2.65; P < .001).

“AURORA patients achieved low levels of protein twice as quickly as patients on standard of care,” the researchers write in their abstract. Median time to the achievement of a urine protein to creatinine ratio below 0.5 mg/mg was significantly and clinically better with voclosporin than with placebo (169 vs 372 days; log rank P < .001).

And voclosporin was well tolerated. The percentage of serious adverse events was similar in the voclosporin and placebo groups (20.8% vs 21.3%), with infection being the most common serious event (10.1% vs 11.2%).

In the voclosporin group, there were no significant differences between baseline and 1 year estimated glomerular filtration rates (eGFR), blood pressure, lipid levels, or sugar levels.

And there were fewer deaths in the voclosporin group than in the placebo group (1 vs 5).

Benefits were seen in all subgroups, including age, sex, race, biopsy class, geographic region of origin, and mycophenolate exposure at screening, Gibson reported.

Promise of a New Treatment

The promise of a new treatment is exciting for the field, said Joseph Vassalotti, MD, chief medical officer of the National Kidney Foundation.

However, it’s important to note that “this study is applicable only to patients with lupus nephritis with preserved kidney function,” he added.

An “eGFR less than 45 mL/min per 1.73 m² was implied as an exclusion criteria, so I would say it certainly doesn’t apply to patients with impaired kidney function,” he said, pointing out that this will be clearer when the final data are published.

The study cohort was heterogeneous; 86% of participants had class 3 or 4 biopsy findings and 14% had class 5, so the superiority of voclosporin is convincing, he said.

“We look forward to full publication and more details,” he told Medscape Medical News. “They do have an extension study, and it will be interesting to see how that plays out.”

Voclosporin was granted Fast Track designation by the US Food and Drug Administration in 2016, and these positive phase 3 results mean that a New Drug Application will likely be filed in the next few months. If approved, the drug could be on the market by 2021, according to a press release from Aurinia.

Nephrologists are familiar with calcineurin inhibitors, so it will be interesting to see, given the success of this trial, if voclosporin has a potential role in other kidney diseases, “such as minimal change disease,” said Vassalotti.

He added that there are concerns, unrelated to the AURORA trial, about the supply of hydroxychloroquine, which is also used for the treatment of lupus nephritis. “An overarching concern is that the supply will be limited now that the drug is being studied and used as prophylaxis after exposure to SARS-CoV-2 and as a treatment for COVID-19, creating challenges for patients with lupus nephritis trying to obtain their needed medication,” he said.

Gibson reports no relevant financial relationships. Two coauthors work for the drugmaker, Aurinia. Vassalotti reports no relevant financial relationships.
 

This article first appeared on Medscape.com.

For patients with lupus nephritis, kidney response improves when voclosporin (Aurinia Pharmaceuticals) is added to mycophenolate and low-dose corticosteroids, results from the phase 3 AURORA trial show.
 

The calcineurin inhibitor is the first novel agent to demonstrate effectiveness in the treatment of people with lupus nephritis, a disease that can lead to irreversible kidney damage, kidney failure, and even death.

“We believe that voclosporin – as an add-on therapy – will help more patients achieve remission,” said Keisha Gibson, MD, MPH, chief of pediatric nephrology at the UNC Kidney Center in Chapel Hill, North Carolina, who led the study and presented the findings during a virtual session at the National Kidney Foundation 2020 Spring Clinical Meetings.

The burden that lupus places on patients and the health system is high, she reported. Patients with lupus and uncontrolled kidney disease frequently have complications that require hospitalization, can suffer complete or partial loss of income, and can become temporarily disabled. And up to 50% of lupus patients will develop lupus nephritis.

“When we are lucky and see early treatment responses in our patients, we know that their long-term outcomes, measured by proteinuria reduction, are quite good,” said Gibson. “Unfortunately, in 10% to 30% of patients, despite standard-of-care therapies, we see progression to end-stage kidney disease within 15 years of diagnosis. This confers a huge cost to overall health and quality of life, and is an excess burden to the healthcare system.

“It is clear that one of the biggest risk factors for these patients who have kidney disease that is progressing to kidney failure is an inability to control the inflammation and chronic damage from uncontrolled disease,” she told Medscape Medical News.

“While there have certainly been a few advances in the care of patients with lupus disease, I believe that this therapy may help move the needle, specifically for patients with kidney involvement from their lupus disease,” she added.

Renal Response Much Higher With Voclosporin

The typical standard of care for patients with active lupus and kidney disease is either a combination of cyclophosphamide plus steroids or a combination of mycophenolate mofetil plus steroids.

The global, double-blind, randomized, placebo-controlled trial compared the effectiveness and safety of twice-daily oral voclosporin 23.7 mg with placebo. All 357 study participants also received mycophenolate 2 g daily and rapidly tapered low-dose oral corticosteroids.

At 1 year, the renal response rate was higher in the voclosporin group than in the placebo group (40.8% vs 22.5%; odds ratio, 2.65; P < .001).

“AURORA patients achieved low levels of protein twice as quickly as patients on standard of care,” the researchers write in their abstract. Median time to the achievement of a urine protein to creatinine ratio below 0.5 mg/mg was significantly and clinically better with voclosporin than with placebo (169 vs 372 days; log rank P < .001).

And voclosporin was well tolerated. The percentage of serious adverse events was similar in the voclosporin and placebo groups (20.8% vs 21.3%), with infection being the most common serious event (10.1% vs 11.2%).

In the voclosporin group, there were no significant differences between baseline and 1 year estimated glomerular filtration rates (eGFR), blood pressure, lipid levels, or sugar levels.

And there were fewer deaths in the voclosporin group than in the placebo group (1 vs 5).

Benefits were seen in all subgroups, including age, sex, race, biopsy class, geographic region of origin, and mycophenolate exposure at screening, Gibson reported.

Promise of a New Treatment

The promise of a new treatment is exciting for the field, said Joseph Vassalotti, MD, chief medical officer of the National Kidney Foundation.

However, it’s important to note that “this study is applicable only to patients with lupus nephritis with preserved kidney function,” he added.

An “eGFR less than 45 mL/min per 1.73 m² was implied as an exclusion criteria, so I would say it certainly doesn’t apply to patients with impaired kidney function,” he said, pointing out that this will be clearer when the final data are published.

The study cohort was heterogeneous; 86% of participants had class 3 or 4 biopsy findings and 14% had class 5, so the superiority of voclosporin is convincing, he said.

“We look forward to full publication and more details,” he told Medscape Medical News. “They do have an extension study, and it will be interesting to see how that plays out.”

Voclosporin was granted Fast Track designation by the US Food and Drug Administration in 2016, and these positive phase 3 results mean that a New Drug Application will likely be filed in the next few months. If approved, the drug could be on the market by 2021, according to a press release from Aurinia.

Nephrologists are familiar with calcineurin inhibitors, so it will be interesting to see, given the success of this trial, if voclosporin has a potential role in other kidney diseases, “such as minimal change disease,” said Vassalotti.

He added that there are concerns, unrelated to the AURORA trial, about the supply of hydroxychloroquine, which is also used for the treatment of lupus nephritis. “An overarching concern is that the supply will be limited now that the drug is being studied and used as prophylaxis after exposure to SARS-CoV-2 and as a treatment for COVID-19, creating challenges for patients with lupus nephritis trying to obtain their needed medication,” he said.

Gibson reports no relevant financial relationships. Two coauthors work for the drugmaker, Aurinia. Vassalotti reports no relevant financial relationships.
 

This article first appeared on Medscape.com.

MAUI, HAWAII – Viewing seronegative rheumatoid arthritis as something akin to RA-lite would be a big mistake, John J. Cush, MD, asserted at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“It’s not a benign subtype of RA. And then again, it may not be RA,” Dr. Cush observed,

“Seronegative RA means that either you need to get serious about what is probably badass disease or you need to reevaluate whether this really is RA and your need for DMARDs [disease-modifying antirheumatic drugs] in an ongoing fashion,” the rheumatologist said. “Always reconsider whether they need less therapy or maybe no therapy at all. Maybe they had inflammation at one point and now they’re left with degenerative and mechanical changes that don’t require a DMARD or biologic.”

He highlighted a Finnish 10-year, prospective, observational study that sheds light on the subject. The study demonstrated that seronegative RA is seldom what it at first seems. The Finnish rheumatologists followed 435 consecutive patients initially diagnosed as having seronegative early RA. The structured follow-up entailed four or five interdisciplinary clinic visits within the first 2 years after diagnosis and again at 5 and 10 years.

By the 10-year mark only 4 of the 435 initially seronegative RA patients had been reclassified as having seropositive RA, while another 9 were reclassified as having erosive RA based upon the development of pathognomonic joint lesions. That’s a paltry 3% reclassification rate to classic RA.

Nearly two-thirds of patients were ultimately reclassified within 10 years as they evolved into diagnoses other than their original seronegative RA. The most common included nonerosive polymyalgia rheumatica in 16% of participants, psoriatic arthritis in 11%, osteoarthritis in 10%, spondyloarthritis in 8.7%, gout in 2.3%, and pseudogout in 3.9%.

“I think that’s sobering for you if you’re taking care of these patients, that maybe you need to rethink the diagnosis at every visit or at periodic intervals, especially if you’re going to change therapy,” advised Dr. Cush, who is professor of medicine and rheumatology at Baylor University Medical Center, Dallas, and director of clinical rheumatology at the Baylor Research Institute.

The Finnish rheumatologists observed that their findings have important implications both for clinical practice and for research, since RA clinical trials typically include a substantial proportion of seronegative patients.

“If seronegative patients are treated according to the treatment guidelines for progressive RA, a substantial proportion of patients is exposed to unnecessary long-term medication,” the investigators wrote, adding that their “results suggest that it may not be reasonable to study seronegative arthritis patients as a homogeneous entity in RA studies.”

The best recent data suggests about 15% of RA patients are seronegative, Dr. Cush said.

Delay in diagnosis is common in seronegative RA, as highlighted in a recent population-based study by Mayo Clinic rheumatologists. They reported that the median time from first joint swelling to diagnosis of seronegative RA using the 2010 American College of Rheumatology/European League Against Rheumatism criteria was 187 days, compared with a mere 11 days for seropositive RA. The median time to DMARD initiation was longer, too. Half of seropositive RA patients achieved remission within 5 years, as did 28% of seronegative patients, prompting the investigators to conclude “the window of opportunity for intervention may be more frequently missed in this group.”
 

Choosing the best treatment

Several medications appear to have greater efficacy in seropositive than seronegative RA patients. For example, a meta-analysis of four randomized trials including a collective 2,177 RA patients assigned 2:1 to rituximab (Rituxan) or placebo concluded that 75% of seropositive RA patients had a EULAR moderate or good response at week 24 on the biologic, compared with 44% of seronegative patients.

“Would you not use rituximab in someone who’s seronegative? No, I actually would use it. I may not rush to use it as much, maybe give it earlier in someone who’s seropositive, but I’ve used rituximab in seronegative patients who’ve done just fine,” according to Dr. Cush.

The published experience with abatacept (Orencia) is mixed, most of it coming from European observational datasets. On balance though, 80% of the articles addressing the issue have concluded that response rates to the biologic are better in seropositive RA, he continued.

Australian investigators who pooled data from five phase 3 randomized clinical trials of tofacitinib (Xeljanz) in RA concluded that double-positive patients – that is, those who were seropositive for both rheumatoid factor and anti–citrullinated protein antibody (ACPA) – were roughly twice as likely to achieve ACR20 and ACR50 responses to the oral Janus kinase inhibitor at either 5 or 10 mg twice daily than patients who were double negative.

“Double positivity is very important in prognosis and severity, compared to single positivity,” the rheumatologist observed. “I think you should worry most about the patients who have the highest titers of rheumatoid factor and ACPA.”

Asked about the merits of supplemental laboratory testing for serum 14-3-3 eta, a proposed novel biomarker in RA, as well as for anti–carbamylated protein antibodies (anti-CarP), Dr. Cush replied that it’s unclear that the additional testing is really worthwhile.

“Ordering more tests doesn’t make us smarter,” he commented. “Quite simply, with rheumatoid factor and ACPA, adding one on top of the other, you just gain maybe 10% more certainty in the diagnosis. Adding anti-CarP antibodies or serum 14-3-3 eta doesn’t add more than a few percentage points, but now you’ve quadrupled the cost of testing.”

Dr. Cush reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.

[email protected]

MAUI, HAWAII – Viewing seronegative rheumatoid arthritis as something akin to RA-lite would be a big mistake, John J. Cush, MD, asserted at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“It’s not a benign subtype of RA. And then again, it may not be RA,” Dr. Cush observed,

“Seronegative RA means that either you need to get serious about what is probably badass disease or you need to reevaluate whether this really is RA and your need for DMARDs [disease-modifying antirheumatic drugs] in an ongoing fashion,” the rheumatologist said. “Always reconsider whether they need less therapy or maybe no therapy at all. Maybe they had inflammation at one point and now they’re left with degenerative and mechanical changes that don’t require a DMARD or biologic.”

He highlighted a Finnish 10-year, prospective, observational study that sheds light on the subject. The study demonstrated that seronegative RA is seldom what it at first seems. The Finnish rheumatologists followed 435 consecutive patients initially diagnosed as having seronegative early RA. The structured follow-up entailed four or five interdisciplinary clinic visits within the first 2 years after diagnosis and again at 5 and 10 years.

By the 10-year mark only 4 of the 435 initially seronegative RA patients had been reclassified as having seropositive RA, while another 9 were reclassified as having erosive RA based upon the development of pathognomonic joint lesions. That’s a paltry 3% reclassification rate to classic RA.

Nearly two-thirds of patients were ultimately reclassified within 10 years as they evolved into diagnoses other than their original seronegative RA. The most common included nonerosive polymyalgia rheumatica in 16% of participants, psoriatic arthritis in 11%, osteoarthritis in 10%, spondyloarthritis in 8.7%, gout in 2.3%, and pseudogout in 3.9%.

“I think that’s sobering for you if you’re taking care of these patients, that maybe you need to rethink the diagnosis at every visit or at periodic intervals, especially if you’re going to change therapy,” advised Dr. Cush, who is professor of medicine and rheumatology at Baylor University Medical Center, Dallas, and director of clinical rheumatology at the Baylor Research Institute.

The Finnish rheumatologists observed that their findings have important implications both for clinical practice and for research, since RA clinical trials typically include a substantial proportion of seronegative patients.

“If seronegative patients are treated according to the treatment guidelines for progressive RA, a substantial proportion of patients is exposed to unnecessary long-term medication,” the investigators wrote, adding that their “results suggest that it may not be reasonable to study seronegative arthritis patients as a homogeneous entity in RA studies.”

The best recent data suggests about 15% of RA patients are seronegative, Dr. Cush said.

Delay in diagnosis is common in seronegative RA, as highlighted in a recent population-based study by Mayo Clinic rheumatologists. They reported that the median time from first joint swelling to diagnosis of seronegative RA using the 2010 American College of Rheumatology/European League Against Rheumatism criteria was 187 days, compared with a mere 11 days for seropositive RA. The median time to DMARD initiation was longer, too. Half of seropositive RA patients achieved remission within 5 years, as did 28% of seronegative patients, prompting the investigators to conclude “the window of opportunity for intervention may be more frequently missed in this group.”
 

Choosing the best treatment

Several medications appear to have greater efficacy in seropositive than seronegative RA patients. For example, a meta-analysis of four randomized trials including a collective 2,177 RA patients assigned 2:1 to rituximab (Rituxan) or placebo concluded that 75% of seropositive RA patients had a EULAR moderate or good response at week 24 on the biologic, compared with 44% of seronegative patients.

“Would you not use rituximab in someone who’s seronegative? No, I actually would use it. I may not rush to use it as much, maybe give it earlier in someone who’s seropositive, but I’ve used rituximab in seronegative patients who’ve done just fine,” according to Dr. Cush.

The published experience with abatacept (Orencia) is mixed, most of it coming from European observational datasets. On balance though, 80% of the articles addressing the issue have concluded that response rates to the biologic are better in seropositive RA, he continued.

Australian investigators who pooled data from five phase 3 randomized clinical trials of tofacitinib (Xeljanz) in RA concluded that double-positive patients – that is, those who were seropositive for both rheumatoid factor and anti–citrullinated protein antibody (ACPA) – were roughly twice as likely to achieve ACR20 and ACR50 responses to the oral Janus kinase inhibitor at either 5 or 10 mg twice daily than patients who were double negative.

“Double positivity is very important in prognosis and severity, compared to single positivity,” the rheumatologist observed. “I think you should worry most about the patients who have the highest titers of rheumatoid factor and ACPA.”

Asked about the merits of supplemental laboratory testing for serum 14-3-3 eta, a proposed novel biomarker in RA, as well as for anti–carbamylated protein antibodies (anti-CarP), Dr. Cush replied that it’s unclear that the additional testing is really worthwhile.

“Ordering more tests doesn’t make us smarter,” he commented. “Quite simply, with rheumatoid factor and ACPA, adding one on top of the other, you just gain maybe 10% more certainty in the diagnosis. Adding anti-CarP antibodies or serum 14-3-3 eta doesn’t add more than a few percentage points, but now you’ve quadrupled the cost of testing.”

Dr. Cush reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.

[email protected]

MAUI, HAWAII – Viewing seronegative rheumatoid arthritis as something akin to RA-lite would be a big mistake, John J. Cush, MD, asserted at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“It’s not a benign subtype of RA. And then again, it may not be RA,” Dr. Cush observed,

“Seronegative RA means that either you need to get serious about what is probably badass disease or you need to reevaluate whether this really is RA and your need for DMARDs [disease-modifying antirheumatic drugs] in an ongoing fashion,” the rheumatologist said. “Always reconsider whether they need less therapy or maybe no therapy at all. Maybe they had inflammation at one point and now they’re left with degenerative and mechanical changes that don’t require a DMARD or biologic.”

He highlighted a Finnish 10-year, prospective, observational study that sheds light on the subject. The study demonstrated that seronegative RA is seldom what it at first seems. The Finnish rheumatologists followed 435 consecutive patients initially diagnosed as having seronegative early RA. The structured follow-up entailed four or five interdisciplinary clinic visits within the first 2 years after diagnosis and again at 5 and 10 years.

By the 10-year mark only 4 of the 435 initially seronegative RA patients had been reclassified as having seropositive RA, while another 9 were reclassified as having erosive RA based upon the development of pathognomonic joint lesions. That’s a paltry 3% reclassification rate to classic RA.

Nearly two-thirds of patients were ultimately reclassified within 10 years as they evolved into diagnoses other than their original seronegative RA. The most common included nonerosive polymyalgia rheumatica in 16% of participants, psoriatic arthritis in 11%, osteoarthritis in 10%, spondyloarthritis in 8.7%, gout in 2.3%, and pseudogout in 3.9%.

“I think that’s sobering for you if you’re taking care of these patients, that maybe you need to rethink the diagnosis at every visit or at periodic intervals, especially if you’re going to change therapy,” advised Dr. Cush, who is professor of medicine and rheumatology at Baylor University Medical Center, Dallas, and director of clinical rheumatology at the Baylor Research Institute.

The Finnish rheumatologists observed that their findings have important implications both for clinical practice and for research, since RA clinical trials typically include a substantial proportion of seronegative patients.

“If seronegative patients are treated according to the treatment guidelines for progressive RA, a substantial proportion of patients is exposed to unnecessary long-term medication,” the investigators wrote, adding that their “results suggest that it may not be reasonable to study seronegative arthritis patients as a homogeneous entity in RA studies.”

The best recent data suggests about 15% of RA patients are seronegative, Dr. Cush said.

Delay in diagnosis is common in seronegative RA, as highlighted in a recent population-based study by Mayo Clinic rheumatologists. They reported that the median time from first joint swelling to diagnosis of seronegative RA using the 2010 American College of Rheumatology/European League Against Rheumatism criteria was 187 days, compared with a mere 11 days for seropositive RA. The median time to DMARD initiation was longer, too. Half of seropositive RA patients achieved remission within 5 years, as did 28% of seronegative patients, prompting the investigators to conclude “the window of opportunity for intervention may be more frequently missed in this group.”
 

Choosing the best treatment

Several medications appear to have greater efficacy in seropositive than seronegative RA patients. For example, a meta-analysis of four randomized trials including a collective 2,177 RA patients assigned 2:1 to rituximab (Rituxan) or placebo concluded that 75% of seropositive RA patients had a EULAR moderate or good response at week 24 on the biologic, compared with 44% of seronegative patients.

“Would you not use rituximab in someone who’s seronegative? No, I actually would use it. I may not rush to use it as much, maybe give it earlier in someone who’s seropositive, but I’ve used rituximab in seronegative patients who’ve done just fine,” according to Dr. Cush.

The published experience with abatacept (Orencia) is mixed, most of it coming from European observational datasets. On balance though, 80% of the articles addressing the issue have concluded that response rates to the biologic are better in seropositive RA, he continued.

Australian investigators who pooled data from five phase 3 randomized clinical trials of tofacitinib (Xeljanz) in RA concluded that double-positive patients – that is, those who were seropositive for both rheumatoid factor and anti–citrullinated protein antibody (ACPA) – were roughly twice as likely to achieve ACR20 and ACR50 responses to the oral Janus kinase inhibitor at either 5 or 10 mg twice daily than patients who were double negative.

“Double positivity is very important in prognosis and severity, compared to single positivity,” the rheumatologist observed. “I think you should worry most about the patients who have the highest titers of rheumatoid factor and ACPA.”

Asked about the merits of supplemental laboratory testing for serum 14-3-3 eta, a proposed novel biomarker in RA, as well as for anti–carbamylated protein antibodies (anti-CarP), Dr. Cush replied that it’s unclear that the additional testing is really worthwhile.

“Ordering more tests doesn’t make us smarter,” he commented. “Quite simply, with rheumatoid factor and ACPA, adding one on top of the other, you just gain maybe 10% more certainty in the diagnosis. Adding anti-CarP antibodies or serum 14-3-3 eta doesn’t add more than a few percentage points, but now you’ve quadrupled the cost of testing.”

Dr. Cush reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.

[email protected]