Rheumatology News

Muscle relaxants and NSAIDs effectively improved symptoms of acute low back pain after 1 week of treatment, based on data from more than 3,000 individuals.

Acute low back pain (LBP) remains a common cause of disability worldwide, with a high socioeconomic burden, write Alice Baroncini, MD, of RWTH University Hospital, Aachen, Germany, and colleagues.

In an analysis published in the Journal of Orthopaedic Research, a team of investigators from Germany examined which nonopioid drugs are best for treating LBP.

The researchers identified 18 studies totaling 3,478 patients with acute low back pain of less than 12 weeks’ duration. They selected studies that only investigated the lumbar spine, and studies involving opioids were excluded. The mean age of the patients across all the studies was 42.5 years, and 54% were women. The mean duration of symptoms before treatment was 15.1 days.

Overall, muscle relaxants and NSAIDs demonstrated effectiveness in reducing pain and disability for acute LBP patients after about 1 week of use.

In addition, studies of a combination of NSAIDs and paracetamol (also known as acetaminophen) showed a greater improvement than NSAIDs alone, but paracetamol/acetaminophen alone had no significant impact on LBP.

Most patients with acute LBP experience spontaneous recovery and reduction of symptoms, thus the real impact of most medications is uncertain, the researchers write in their discussion. The lack of a placebo effect in the selected studies reinforces the hypothesis that nonopioid medications improve LBP symptoms, they say.

However, “while this work only focuses on the pharmacological management of acute LBP, it is fundamental to highlight that the use of drugs should always be a second-line strategy once other nonpharmacological, noninvasive therapies have proved to be insufficient,” the researchers write.

The study findings were limited by several factors, including the inability to distinguish among different NSAID classes, the inability to conduct a subanalysis of the best drug or treatment protocol for a given drug class, and the short follow-up period for the included studies, the researchers note.

More research is needed to address the effects of different drugs on LBP recurrence, they add.

However, the results support the current opinion that NSAIDs can be effectively used for LBP, strengthened by the large number of studies and relatively low risk of bias, the researchers conclude.

The current study addresses a common cause of morbidity among patients and highlights alternatives to opioid analgesics for its management, Suman Pal, MBBS, a specialist in hospital medicine at the University of New Mexico, Albuquerque, said in an interview.

Dr. Pal said he was not surprised by the results. “The findings of the study mirror prior studies,” he said. “However, the lack of benefit of paracetamol alone needs to be highlighted as important to clinical practice.”

A key message for clinicians is the role of NSAIDs in LBP, Dr. Pal said. “NSAIDs, either alone or in combination with paracetamol or myorelaxants, can be effective therapy for select patients with acute LBP.” However, “further research is needed to better identify which patients would derive most benefit from this approach,” he said.

Other research needs include more evidence to better understand the appropriate duration of therapy, given the potential for adverse effects with chronic NSAID use, Dr. Pal said.

The study received no outside funding. The researchers and Dr. Pal have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Muscle relaxants and NSAIDs effectively improved symptoms of acute low back pain after 1 week of treatment, based on data from more than 3,000 individuals.

Acute low back pain (LBP) remains a common cause of disability worldwide, with a high socioeconomic burden, write Alice Baroncini, MD, of RWTH University Hospital, Aachen, Germany, and colleagues.

In an analysis published in the Journal of Orthopaedic Research, a team of investigators from Germany examined which nonopioid drugs are best for treating LBP.

The researchers identified 18 studies totaling 3,478 patients with acute low back pain of less than 12 weeks’ duration. They selected studies that only investigated the lumbar spine, and studies involving opioids were excluded. The mean age of the patients across all the studies was 42.5 years, and 54% were women. The mean duration of symptoms before treatment was 15.1 days.

Overall, muscle relaxants and NSAIDs demonstrated effectiveness in reducing pain and disability for acute LBP patients after about 1 week of use.

In addition, studies of a combination of NSAIDs and paracetamol (also known as acetaminophen) showed a greater improvement than NSAIDs alone, but paracetamol/acetaminophen alone had no significant impact on LBP.

Most patients with acute LBP experience spontaneous recovery and reduction of symptoms, thus the real impact of most medications is uncertain, the researchers write in their discussion. The lack of a placebo effect in the selected studies reinforces the hypothesis that nonopioid medications improve LBP symptoms, they say.

However, “while this work only focuses on the pharmacological management of acute LBP, it is fundamental to highlight that the use of drugs should always be a second-line strategy once other nonpharmacological, noninvasive therapies have proved to be insufficient,” the researchers write.

The study findings were limited by several factors, including the inability to distinguish among different NSAID classes, the inability to conduct a subanalysis of the best drug or treatment protocol for a given drug class, and the short follow-up period for the included studies, the researchers note.

More research is needed to address the effects of different drugs on LBP recurrence, they add.

However, the results support the current opinion that NSAIDs can be effectively used for LBP, strengthened by the large number of studies and relatively low risk of bias, the researchers conclude.

The current study addresses a common cause of morbidity among patients and highlights alternatives to opioid analgesics for its management, Suman Pal, MBBS, a specialist in hospital medicine at the University of New Mexico, Albuquerque, said in an interview.

Dr. Pal said he was not surprised by the results. “The findings of the study mirror prior studies,” he said. “However, the lack of benefit of paracetamol alone needs to be highlighted as important to clinical practice.”

A key message for clinicians is the role of NSAIDs in LBP, Dr. Pal said. “NSAIDs, either alone or in combination with paracetamol or myorelaxants, can be effective therapy for select patients with acute LBP.” However, “further research is needed to better identify which patients would derive most benefit from this approach,” he said.

Other research needs include more evidence to better understand the appropriate duration of therapy, given the potential for adverse effects with chronic NSAID use, Dr. Pal said.

The study received no outside funding. The researchers and Dr. Pal have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Muscle relaxants and NSAIDs effectively improved symptoms of acute low back pain after 1 week of treatment, based on data from more than 3,000 individuals.

Acute low back pain (LBP) remains a common cause of disability worldwide, with a high socioeconomic burden, write Alice Baroncini, MD, of RWTH University Hospital, Aachen, Germany, and colleagues.

In an analysis published in the Journal of Orthopaedic Research, a team of investigators from Germany examined which nonopioid drugs are best for treating LBP.

The researchers identified 18 studies totaling 3,478 patients with acute low back pain of less than 12 weeks’ duration. They selected studies that only investigated the lumbar spine, and studies involving opioids were excluded. The mean age of the patients across all the studies was 42.5 years, and 54% were women. The mean duration of symptoms before treatment was 15.1 days.

Overall, muscle relaxants and NSAIDs demonstrated effectiveness in reducing pain and disability for acute LBP patients after about 1 week of use.

In addition, studies of a combination of NSAIDs and paracetamol (also known as acetaminophen) showed a greater improvement than NSAIDs alone, but paracetamol/acetaminophen alone had no significant impact on LBP.

Most patients with acute LBP experience spontaneous recovery and reduction of symptoms, thus the real impact of most medications is uncertain, the researchers write in their discussion. The lack of a placebo effect in the selected studies reinforces the hypothesis that nonopioid medications improve LBP symptoms, they say.

However, “while this work only focuses on the pharmacological management of acute LBP, it is fundamental to highlight that the use of drugs should always be a second-line strategy once other nonpharmacological, noninvasive therapies have proved to be insufficient,” the researchers write.

The study findings were limited by several factors, including the inability to distinguish among different NSAID classes, the inability to conduct a subanalysis of the best drug or treatment protocol for a given drug class, and the short follow-up period for the included studies, the researchers note.

More research is needed to address the effects of different drugs on LBP recurrence, they add.

However, the results support the current opinion that NSAIDs can be effectively used for LBP, strengthened by the large number of studies and relatively low risk of bias, the researchers conclude.

The current study addresses a common cause of morbidity among patients and highlights alternatives to opioid analgesics for its management, Suman Pal, MBBS, a specialist in hospital medicine at the University of New Mexico, Albuquerque, said in an interview.

Dr. Pal said he was not surprised by the results. “The findings of the study mirror prior studies,” he said. “However, the lack of benefit of paracetamol alone needs to be highlighted as important to clinical practice.”

A key message for clinicians is the role of NSAIDs in LBP, Dr. Pal said. “NSAIDs, either alone or in combination with paracetamol or myorelaxants, can be effective therapy for select patients with acute LBP.” However, “further research is needed to better identify which patients would derive most benefit from this approach,” he said.

Other research needs include more evidence to better understand the appropriate duration of therapy, given the potential for adverse effects with chronic NSAID use, Dr. Pal said.

The study received no outside funding. The researchers and Dr. Pal have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Surgeon goes the extra half mile for his patient

Sorry medical profession, but it’s Adam Bodzin’s world now. When a donor liver got stuck in the middle of the Philadelphia Half Marathon’s 30,000 participants, Dr. Bodzin, the transplant team’s lead surgeon, took matters into his own hands. And by hands, of course, we mean feet.

Pixnio

Still wearing his hospital scrubs, Dr. Bodzin ran more than half a mile to where the van carrying the liver was stranded, according to the Philadelphia Inquirer. Fortunately, he was able to hitch a ride in a police car for the return trip and didn’t have to run back through the crowd carrying his somewhat unusual package. By package, of course, we mean human liver.

It’s been 3 months since the surgery/marathon and it’s still not clear why the driver had such trouble getting through – he had been trying for more than an hour and half by the time Dr. Bodzin reached him – but the surgery half of the big event was deemed a success and the patient has recovered.

Rick Hasz, president and chief executive officer of the Gift of Life Donor Program, which coordinates organ donation for transplants in the Philadelphia region, told the newspaper that “Dr. Bodzin’s quick action demonstrated his commitment to honoring the selfless generosity of all donors and their families and gives hope to everyone waiting for a second chance at life.”

Should Dr. Bodzin consider a step up from the transplant team to another group that’s fighting for the common good? The recipient of the liver in question seems to think so. “I guess he has a cape on under that white jacket,” 66-year-old Charles Rowe told Fox29. You already know where we’re going with this, right?

Avengers … Assemble.
 

Your spleen’s due for its 5,000-mile oil change

The human body is an incredible biological machine, capable of performing a countless array of tasks automatically and essentially without flaw, but there’s always room for improvement. After all, there are animals that can regrow entire missing limbs or live for up to 500 years. It would be nice if we could get some of that going.

Sigmund/Unsplash

Rather than any of that cool stuff, a recent survey of 2,000 average Americans revealed that our ambitions for improving the human body are a bit more mundane. The big thing that would make our lives better and easier, according to three-fourths of Americans, would be a built-in “check engine” light in our bodies. Come on guys, starfish can literally be cut in half and not only survive, but become two starfish. Mantis shrimp can punch with a force thousands of times their own weight. If we could punch like they could, we could literally break steel with our fists. Wouldn’t we rather have that?

Apparently not. Fine, we’ll stick with the check engine light.

Maybe it isn’t a huge surprise that we’d like the extra help in figuring out what our body needs. According to the survey, more than 60% of Americans struggle to identify when their body is trying to tell them something important, and only one-third actively checked in with their health every day. Considering about 40% said they feel tired for much of the day and nearly half reported not having a meal with fruits or vegetables in the past 3 days, perhaps a gentle reminder wouldn’t be the worst thing in the world.

So, if we did have a built-in check engine light, what would we use it for? A majority said they’d like to be reminded to drink a glass of water, with 45% saying they wanted to know when to take a nap. Feeling thirsty or tired isn’t quite enough, it seems.

Of course, the technology certainly exists to make the human check engine light a reality. An implanted microchip could absolutely tell us to drink a glass of water, but that would put our health in the hands of tech companies, and you just know Meta and Elon Muskrat wouldn’t pass up the chance for monetization. “Oh, sorry, we could have notified the hospital that you were about to have a heart attack, but you didn’t pay your life subscription this month.”
 

Sext offenders show more than their, well, you know

As we have become more and more attached to our phones, especially post pandemic, it’s no surprise that sexting – sending sexually explicit images and messages with those phones – has become a fairly common way for people to sexually communicate. And with dating apps just another venture in the dating landscape, regardless of age, sexting is an easy avenue to incite a mood without being physically present.

©agmit/istockphoto.com

A recent study, though, has linked sexting with anxiety, sleep issues, depression, and compulsive sexual behaviors. Yikes.

Although the researchers noted that sexting was primarily reciprocal (sending and receiving), “over 50% of adults report sending a sext, while women are up to four times more likely than men to report having received nonconsensual sexts,” said Brenda K. Wiederhold, PhD, editor-in-chief of Cyberpsychology, Behavior, and Social Networking, which published the study, in which Dr. Wiederhold was not involved.

Among the 2,160 U.S. college students who were involved, participants who had only sent sexts reported more anxiety, depression, and sleep problems than other groups (no sexting, received only, reciprocal). There was also a possible connection between sexting, marijuana use, and compulsive sexual behavior, the investigators said in a written statement.

Considering the study population, these data are perhaps not that surprising. For young adults, to receive or send an elusive nude is as common as it once was to give someone flowers. Not that the two things elicit the same reactions. “Many individuals reveal they enjoy consensual sexting and feel it empowers them and builds self-confidence,” Dr. Wiederhold added.

Receiving a nonconsensual sext, though, is definitely going to result in feeling violated and super awkward. Senders beware: Don’t be surprised if you’re ghosted after that.

Surgeon goes the extra half mile for his patient

Sorry medical profession, but it’s Adam Bodzin’s world now. When a donor liver got stuck in the middle of the Philadelphia Half Marathon’s 30,000 participants, Dr. Bodzin, the transplant team’s lead surgeon, took matters into his own hands. And by hands, of course, we mean feet.

Pixnio

Still wearing his hospital scrubs, Dr. Bodzin ran more than half a mile to where the van carrying the liver was stranded, according to the Philadelphia Inquirer. Fortunately, he was able to hitch a ride in a police car for the return trip and didn’t have to run back through the crowd carrying his somewhat unusual package. By package, of course, we mean human liver.

It’s been 3 months since the surgery/marathon and it’s still not clear why the driver had such trouble getting through – he had been trying for more than an hour and half by the time Dr. Bodzin reached him – but the surgery half of the big event was deemed a success and the patient has recovered.

Rick Hasz, president and chief executive officer of the Gift of Life Donor Program, which coordinates organ donation for transplants in the Philadelphia region, told the newspaper that “Dr. Bodzin’s quick action demonstrated his commitment to honoring the selfless generosity of all donors and their families and gives hope to everyone waiting for a second chance at life.”

Should Dr. Bodzin consider a step up from the transplant team to another group that’s fighting for the common good? The recipient of the liver in question seems to think so. “I guess he has a cape on under that white jacket,” 66-year-old Charles Rowe told Fox29. You already know where we’re going with this, right?

Avengers … Assemble.
 

Your spleen’s due for its 5,000-mile oil change

The human body is an incredible biological machine, capable of performing a countless array of tasks automatically and essentially without flaw, but there’s always room for improvement. After all, there are animals that can regrow entire missing limbs or live for up to 500 years. It would be nice if we could get some of that going.

Sigmund/Unsplash

Rather than any of that cool stuff, a recent survey of 2,000 average Americans revealed that our ambitions for improving the human body are a bit more mundane. The big thing that would make our lives better and easier, according to three-fourths of Americans, would be a built-in “check engine” light in our bodies. Come on guys, starfish can literally be cut in half and not only survive, but become two starfish. Mantis shrimp can punch with a force thousands of times their own weight. If we could punch like they could, we could literally break steel with our fists. Wouldn’t we rather have that?

Apparently not. Fine, we’ll stick with the check engine light.

Maybe it isn’t a huge surprise that we’d like the extra help in figuring out what our body needs. According to the survey, more than 60% of Americans struggle to identify when their body is trying to tell them something important, and only one-third actively checked in with their health every day. Considering about 40% said they feel tired for much of the day and nearly half reported not having a meal with fruits or vegetables in the past 3 days, perhaps a gentle reminder wouldn’t be the worst thing in the world.

So, if we did have a built-in check engine light, what would we use it for? A majority said they’d like to be reminded to drink a glass of water, with 45% saying they wanted to know when to take a nap. Feeling thirsty or tired isn’t quite enough, it seems.

Of course, the technology certainly exists to make the human check engine light a reality. An implanted microchip could absolutely tell us to drink a glass of water, but that would put our health in the hands of tech companies, and you just know Meta and Elon Muskrat wouldn’t pass up the chance for monetization. “Oh, sorry, we could have notified the hospital that you were about to have a heart attack, but you didn’t pay your life subscription this month.”
 

Sext offenders show more than their, well, you know

As we have become more and more attached to our phones, especially post pandemic, it’s no surprise that sexting – sending sexually explicit images and messages with those phones – has become a fairly common way for people to sexually communicate. And with dating apps just another venture in the dating landscape, regardless of age, sexting is an easy avenue to incite a mood without being physically present.

©agmit/istockphoto.com

A recent study, though, has linked sexting with anxiety, sleep issues, depression, and compulsive sexual behaviors. Yikes.

Although the researchers noted that sexting was primarily reciprocal (sending and receiving), “over 50% of adults report sending a sext, while women are up to four times more likely than men to report having received nonconsensual sexts,” said Brenda K. Wiederhold, PhD, editor-in-chief of Cyberpsychology, Behavior, and Social Networking, which published the study, in which Dr. Wiederhold was not involved.

Among the 2,160 U.S. college students who were involved, participants who had only sent sexts reported more anxiety, depression, and sleep problems than other groups (no sexting, received only, reciprocal). There was also a possible connection between sexting, marijuana use, and compulsive sexual behavior, the investigators said in a written statement.

Considering the study population, these data are perhaps not that surprising. For young adults, to receive or send an elusive nude is as common as it once was to give someone flowers. Not that the two things elicit the same reactions. “Many individuals reveal they enjoy consensual sexting and feel it empowers them and builds self-confidence,” Dr. Wiederhold added.

Receiving a nonconsensual sext, though, is definitely going to result in feeling violated and super awkward. Senders beware: Don’t be surprised if you’re ghosted after that.

Surgeon goes the extra half mile for his patient

Sorry medical profession, but it’s Adam Bodzin’s world now. When a donor liver got stuck in the middle of the Philadelphia Half Marathon’s 30,000 participants, Dr. Bodzin, the transplant team’s lead surgeon, took matters into his own hands. And by hands, of course, we mean feet.

Pixnio

Still wearing his hospital scrubs, Dr. Bodzin ran more than half a mile to where the van carrying the liver was stranded, according to the Philadelphia Inquirer. Fortunately, he was able to hitch a ride in a police car for the return trip and didn’t have to run back through the crowd carrying his somewhat unusual package. By package, of course, we mean human liver.

It’s been 3 months since the surgery/marathon and it’s still not clear why the driver had such trouble getting through – he had been trying for more than an hour and half by the time Dr. Bodzin reached him – but the surgery half of the big event was deemed a success and the patient has recovered.

Rick Hasz, president and chief executive officer of the Gift of Life Donor Program, which coordinates organ donation for transplants in the Philadelphia region, told the newspaper that “Dr. Bodzin’s quick action demonstrated his commitment to honoring the selfless generosity of all donors and their families and gives hope to everyone waiting for a second chance at life.”

Should Dr. Bodzin consider a step up from the transplant team to another group that’s fighting for the common good? The recipient of the liver in question seems to think so. “I guess he has a cape on under that white jacket,” 66-year-old Charles Rowe told Fox29. You already know where we’re going with this, right?

Avengers … Assemble.
 

Your spleen’s due for its 5,000-mile oil change

The human body is an incredible biological machine, capable of performing a countless array of tasks automatically and essentially without flaw, but there’s always room for improvement. After all, there are animals that can regrow entire missing limbs or live for up to 500 years. It would be nice if we could get some of that going.

Sigmund/Unsplash

Rather than any of that cool stuff, a recent survey of 2,000 average Americans revealed that our ambitions for improving the human body are a bit more mundane. The big thing that would make our lives better and easier, according to three-fourths of Americans, would be a built-in “check engine” light in our bodies. Come on guys, starfish can literally be cut in half and not only survive, but become two starfish. Mantis shrimp can punch with a force thousands of times their own weight. If we could punch like they could, we could literally break steel with our fists. Wouldn’t we rather have that?

Apparently not. Fine, we’ll stick with the check engine light.

Maybe it isn’t a huge surprise that we’d like the extra help in figuring out what our body needs. According to the survey, more than 60% of Americans struggle to identify when their body is trying to tell them something important, and only one-third actively checked in with their health every day. Considering about 40% said they feel tired for much of the day and nearly half reported not having a meal with fruits or vegetables in the past 3 days, perhaps a gentle reminder wouldn’t be the worst thing in the world.

So, if we did have a built-in check engine light, what would we use it for? A majority said they’d like to be reminded to drink a glass of water, with 45% saying they wanted to know when to take a nap. Feeling thirsty or tired isn’t quite enough, it seems.

Of course, the technology certainly exists to make the human check engine light a reality. An implanted microchip could absolutely tell us to drink a glass of water, but that would put our health in the hands of tech companies, and you just know Meta and Elon Muskrat wouldn’t pass up the chance for monetization. “Oh, sorry, we could have notified the hospital that you were about to have a heart attack, but you didn’t pay your life subscription this month.”
 

Sext offenders show more than their, well, you know

As we have become more and more attached to our phones, especially post pandemic, it’s no surprise that sexting – sending sexually explicit images and messages with those phones – has become a fairly common way for people to sexually communicate. And with dating apps just another venture in the dating landscape, regardless of age, sexting is an easy avenue to incite a mood without being physically present.

©agmit/istockphoto.com

A recent study, though, has linked sexting with anxiety, sleep issues, depression, and compulsive sexual behaviors. Yikes.

Although the researchers noted that sexting was primarily reciprocal (sending and receiving), “over 50% of adults report sending a sext, while women are up to four times more likely than men to report having received nonconsensual sexts,” said Brenda K. Wiederhold, PhD, editor-in-chief of Cyberpsychology, Behavior, and Social Networking, which published the study, in which Dr. Wiederhold was not involved.

Among the 2,160 U.S. college students who were involved, participants who had only sent sexts reported more anxiety, depression, and sleep problems than other groups (no sexting, received only, reciprocal). There was also a possible connection between sexting, marijuana use, and compulsive sexual behavior, the investigators said in a written statement.

Considering the study population, these data are perhaps not that surprising. For young adults, to receive or send an elusive nude is as common as it once was to give someone flowers. Not that the two things elicit the same reactions. “Many individuals reveal they enjoy consensual sexting and feel it empowers them and builds self-confidence,” Dr. Wiederhold added.

Receiving a nonconsensual sext, though, is definitely going to result in feeling violated and super awkward. Senders beware: Don’t be surprised if you’re ghosted after that.

The Food and Drug Administration approved sarilumab (Kevzara) on March 1 for the treatment of polymyalgia rheumatica (PMR) in adults who have had an inadequate response to corticosteroids or could not tolerate a corticosteroid taper, joint developers Sanofi and Regeneron announced. The drug is the first and only FDA-approved biologic treatment for this inflammatory rheumatic disease. 

The FDA previously approved sarilumab, an interleukin-6 receptor antagonist, in May 2017 for the treatment of moderate to severe active rheumatoid arthritis in adults who do not respond well or have an intolerance to disease-modifying antirheumatic drugs (DMARDs), like methotrexate.

Olivier Le Moal/Getty Images

The FDA approval for this new indication was based on results from the multicenter, phase 3 SAPHYR trial in patients with corticosteroid-resistant, active PMR. In the randomized, double-blind, placebo-controlled study, 59 participants received 200 mg of sarilumab plus a 14-week taper of corticosteroid treatment and 58 participants received placebo every 2 weeks along with a 52-week taper of corticosteroid treatment.

After 1 year, 28% of sarilumab patients achieved sustained remission, compared with 10% of the placebo group (P = .0193). This news organization previously reported these trial results in November when they were presented at the 2022 annual meeting of the American College of Rheumatology.

The most common adverse events in the sarilumab group were neutropenia (15%), leukopenia (7%), constipation (7%), pruritic rash (5%), myalgia (7%), fatigue (5%), and injection-site pruritus (5%). Two patients had serious adverse reactions of neutropenia, which resolved after discontinuing treatment.

“Polymyalgia rheumatica can be an incapacitating disease, causing painful disease flares in multiple parts of the bodies that leave people fatigued and unable to fully perform everyday activities. Corticosteroids have been the primary treatment to date, but many patients do not adequately respond to steroids or cannot be tapered off steroids, which puts such patients at risk of complications from long-term steroid therapy,” George D. Yancopolous, MD, PhD, president and chief scientific officer at Regeneron, said in the announcement. “With the approval of Kevzara for polymyalgia rheumatica, patients now have an FDA-approved treatment to help offer relief from the disabling symptoms of this disease and long-term dependence on steroids.”

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration approved sarilumab (Kevzara) on March 1 for the treatment of polymyalgia rheumatica (PMR) in adults who have had an inadequate response to corticosteroids or could not tolerate a corticosteroid taper, joint developers Sanofi and Regeneron announced. The drug is the first and only FDA-approved biologic treatment for this inflammatory rheumatic disease. 

The FDA previously approved sarilumab, an interleukin-6 receptor antagonist, in May 2017 for the treatment of moderate to severe active rheumatoid arthritis in adults who do not respond well or have an intolerance to disease-modifying antirheumatic drugs (DMARDs), like methotrexate.

Olivier Le Moal/Getty Images

The FDA approval for this new indication was based on results from the multicenter, phase 3 SAPHYR trial in patients with corticosteroid-resistant, active PMR. In the randomized, double-blind, placebo-controlled study, 59 participants received 200 mg of sarilumab plus a 14-week taper of corticosteroid treatment and 58 participants received placebo every 2 weeks along with a 52-week taper of corticosteroid treatment.

After 1 year, 28% of sarilumab patients achieved sustained remission, compared with 10% of the placebo group (P = .0193). This news organization previously reported these trial results in November when they were presented at the 2022 annual meeting of the American College of Rheumatology.

The most common adverse events in the sarilumab group were neutropenia (15%), leukopenia (7%), constipation (7%), pruritic rash (5%), myalgia (7%), fatigue (5%), and injection-site pruritus (5%). Two patients had serious adverse reactions of neutropenia, which resolved after discontinuing treatment.

“Polymyalgia rheumatica can be an incapacitating disease, causing painful disease flares in multiple parts of the bodies that leave people fatigued and unable to fully perform everyday activities. Corticosteroids have been the primary treatment to date, but many patients do not adequately respond to steroids or cannot be tapered off steroids, which puts such patients at risk of complications from long-term steroid therapy,” George D. Yancopolous, MD, PhD, president and chief scientific officer at Regeneron, said in the announcement. “With the approval of Kevzara for polymyalgia rheumatica, patients now have an FDA-approved treatment to help offer relief from the disabling symptoms of this disease and long-term dependence on steroids.”

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration approved sarilumab (Kevzara) on March 1 for the treatment of polymyalgia rheumatica (PMR) in adults who have had an inadequate response to corticosteroids or could not tolerate a corticosteroid taper, joint developers Sanofi and Regeneron announced. The drug is the first and only FDA-approved biologic treatment for this inflammatory rheumatic disease. 

The FDA previously approved sarilumab, an interleukin-6 receptor antagonist, in May 2017 for the treatment of moderate to severe active rheumatoid arthritis in adults who do not respond well or have an intolerance to disease-modifying antirheumatic drugs (DMARDs), like methotrexate.

Olivier Le Moal/Getty Images

The FDA approval for this new indication was based on results from the multicenter, phase 3 SAPHYR trial in patients with corticosteroid-resistant, active PMR. In the randomized, double-blind, placebo-controlled study, 59 participants received 200 mg of sarilumab plus a 14-week taper of corticosteroid treatment and 58 participants received placebo every 2 weeks along with a 52-week taper of corticosteroid treatment.

After 1 year, 28% of sarilumab patients achieved sustained remission, compared with 10% of the placebo group (P = .0193). This news organization previously reported these trial results in November when they were presented at the 2022 annual meeting of the American College of Rheumatology.

The most common adverse events in the sarilumab group were neutropenia (15%), leukopenia (7%), constipation (7%), pruritic rash (5%), myalgia (7%), fatigue (5%), and injection-site pruritus (5%). Two patients had serious adverse reactions of neutropenia, which resolved after discontinuing treatment.

“Polymyalgia rheumatica can be an incapacitating disease, causing painful disease flares in multiple parts of the bodies that leave people fatigued and unable to fully perform everyday activities. Corticosteroids have been the primary treatment to date, but many patients do not adequately respond to steroids or cannot be tapered off steroids, which puts such patients at risk of complications from long-term steroid therapy,” George D. Yancopolous, MD, PhD, president and chief scientific officer at Regeneron, said in the announcement. “With the approval of Kevzara for polymyalgia rheumatica, patients now have an FDA-approved treatment to help offer relief from the disabling symptoms of this disease and long-term dependence on steroids.”

A version of this article originally appeared on Medscape.com.

Lille, France – The American College of Physicians has just updated its guidelines for osteoporosis treatment. Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.

Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?

Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.

Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.

Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.

In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].

Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.

Q. But it’s not really as simple as prescribing a bisphosphonate, is it?

A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.

These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.

Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?

A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.

Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?

A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.

The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.

The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.

But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.

Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).

Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.

Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.

In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.

Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.

Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?

A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.

Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.

Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.

A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.

Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.

In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.

In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.

For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.

Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?

A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.

In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.

But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.

In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.

This article was translated from Medscape’s French edition.

A version of this article first appeared on Medscape.com.

Lille, France – The American College of Physicians has just updated its guidelines for osteoporosis treatment. Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.

Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?

Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.

Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.

Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.

In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].

Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.

Q. But it’s not really as simple as prescribing a bisphosphonate, is it?

A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.

These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.

Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?

A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.

Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?

A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.

The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.

The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.

But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.

Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).

Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.

Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.

In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.

Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.

Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?

A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.

Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.

Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.

A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.

Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.

In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.

In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.

For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.

Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?

A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.

In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.

But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.

In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.

This article was translated from Medscape’s French edition.

A version of this article first appeared on Medscape.com.

Lille, France – The American College of Physicians has just updated its guidelines for osteoporosis treatment. Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.

Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?

Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.

Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.

Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.

In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].

Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.

Q. But it’s not really as simple as prescribing a bisphosphonate, is it?

A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.

These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.

Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?

A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.

Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?

A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.

The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.

The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.

But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.

Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).

Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.

Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.

In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.

Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.

Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?

A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.

Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.

Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.

A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.

Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.

In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.

In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.

For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.

Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?

A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.

In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.

But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.

In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.

This article was translated from Medscape’s French edition.

A version of this article first appeared on Medscape.com.

Proinflammatory elements mediated through metabolic pathways related to obesity and increased cellular senescence in CD57 expression in CD8+ T cells are associated with postacute sequelae of COVID-19 (PASC), according to a Mexican study. The researchers followed a Mexican cohort of 102 patients 3 months and 6 months after acute SARS-CoV-2 infection.

The study’s principal investigator was Diana Gómez-Martín, MD, PhD, of the department of immunology and rheumatology at the Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City. She told this news organization that follow-up of the patients began with the objective of understanding the determinative clinical, genetic, metabolic, and immunological factors in the progression of the acute disease. However, clinical aspects associated with PASC developed in the selected cohort. As a result, the study was extended, and the clinical, metabolic, and immunologic conditions in this single-center Mexican cohort were evaluated 3 months 6 months after the onset of infection.

Dr. Gómez-Martín explained that the immune senescence in CD57 of CD8+ T cells is one of the best-known findings of the present study. If it is confirmed in future studies, it could have important implications. “Its main implication is the possibility of better understanding the physiopathology of the clinical aspects associated with postacute sequelae of COVID-19, potentially being used for early detection and to provide follow-up aimed at patients, in addition to eventually developing targeted therapeutic strategies, such as immunometabolism regulation, in certain populations.”
 

Patients with PASC

The study was conducted from August 2020 to August 2021. Investigators recruited 102 patients (median age, 50.5 years; 55% were women) at the Mexico City Temporary Unit with a confirmed diagnosis of SARS-CoV-2. Of the patients, 44% had mild or moderate COVID-19, 30% had severe cases, and 26% of patients had critical cases. The most frequent comorbidities were obesity (44%), hypertension (24%), and type 2 diabetes (24%). The authors used a questionnaire to assess the presence of symptoms during follow-up. They analyzed immunologic variables at the time of recruitment, as well as levels of cytokines, immunoglobulin G against SARS-CoV-2, and neutrophil extracellular traps (NETs) at 1, 3, and 6 months. At 6 months’ follow-up, 12.7% of the cohort had symptoms compatible with PASC, which was defined for the study as the presence and report of three or more symptoms at 6 months’ follow-up.

As in similar studies, the authors found that female gender, remaining in intensive care, and having had more symptoms and greater titers of anti-SARS-CoV-2 antibodies during the acute infection were associated with the development of clinical aspects associated with PASC. Patients who had the disease at 6 months had increased serum levels of interleukin-1 alpha (6.21 pg/mL vs. 2.21 pg/mL), granulocyte colony-stimulating factor (55.08 pg/mL vs. 14.68 pg/mL), and interferon gamma-induced protein 10 (2,309.40 pg/mL vs. 780 pg/mL). Also, there was a trend toward an increase in serum concentration of interleukin-1 beta, interleukin-6, and interferon-gamma.

Patients whose condition met the definition of persistent PASC had increased expression of CD57 in CD8+ T cells (42,714 arbitrary units vs. 28,506) 6 months after the acute infection. The authors reported that there was no association between the persistence of PASC and the baseline amount of NETs, TRIM63, and anticellular antibodies. Nor was there an association between PASC and the titers of anti-SARS-CoV-2 antibodies at baseline and 1 month after COVID-19 diagnosis. Nonetheless, patients with persistent PASC had higher titers of anti-SARS-CoV-2 IgGs 3 months after the onset of COVID-19.

On the basis of previous data, the researchers aimed to construct a preliminary explanatory model to address the clinical and immunologic features associated with persistent PASC 6 months after SARS-CoV-2 infection. In the univariate analysis, the variables associated with the diagnosis of persistent PASC were the serum levels of granulocyte colony-stimulating factor (odds ratio, 1.01), macrophage inflammatory protein-1 alpha (OR, 1.13), interferon gamma-induced protein 10 (OR, 1.00), interleukin-6 (OR, 1.03), the expression of CD57 in CD8+ T cells (OR, 1.00), and the titers of anti-SARS-CoV-2 IgG at 1 month (OR, 1.45).

Patients with a diagnosis of clinical aspects associated with PASC at 6 months were characterized by certain predisposing factors, such as obesity, greater levels of macrophage inflammatory protein-1 alpha and interferon gamma-induced protein 10 in peripheral blood, greater expression of the senescence CD57 marker in CD8+ T lymphocytes, and persistent symptoms at 3 months.

Using these parameters to construct a predictive model after 3 months, the authors found a sensitivity of 97.7%, specificity of 53.8%, positive predictive value of 93.5%, and a negative predictive value of 77.7% for the diagnosis of clinical aspects associated with PASC at 6 months.
 

Interpreting CD57

One of the researchers who participated in the study was Luis Martínez-Juárez, MD, MPH, DrPH. He is on the operative solutions team at the Carlos Slim Foundation. Dr. Martínez-Juárez pointed out that one of the contributions of this study was that it specifically examined the Mexican population. He noted that “according to the findings, obesity is not only a comorbidity associated with more severe progressions during acute COVID-19 disease, but also, through inflammation parameters, such as interleukin-6, interferon gamma-induced protein 10, and macrophage inflammatory protein-1 alpha, it’s involved in the development of clinical aspects related to postacute sequelae of COVID-19.”

Dr. Gómez-Martín added that finding proinflammatory and obesity parameters in the patients could potentially support the hypothesis of the persistence of virus fragments in adipose tissue as possibly involved in clinical aspects associated with PASC, as some groups have reported in the medical literature.

Angélica Cuapio, MD, DrMed, an immunologist and senior investigator at the Karolinska Institute, Stockholm, who did not participate in the study, said in an interview that the authors’ findings on the sustained increase of the CD57 marker in CD8+ lymphocytes are of notable interest. They may be associated with senescence states or cellular aging or with a stage of chronic viral infections. Therefore, Dr. Cuapio argued, it would have been valuable to include cellular markers of the innate system, such as natural killer cells, since in various infections, an increase in CD57 in lymphocytes is accompanied by an almost proportional increase of this marker in natural killer cells.

“This information would help to determine more accurately if we are talking about a cellular senescence or more about a chronic infection in persistent COVID-19.” The finding is important, but future research is needed in this developing field.

Dr. Cuapio pointed out that the authors found an interesting elevation in interleukin-1 alpha in patients with clinical aspects associated with PASC in a clinically well-characterized population in Mexico. “It is possible that this is a specific marker either of a specific population or location, or this could be an association with a humoral response. Despite the fact that this finding is new and unclear, it is worth investigating. This study is of great value for the scientific community because it’s one more piece in the complex puzzle of clinical aspects associated with postacute sequelae of COVID-19.”

Dr. Gómez-Martín noted that the main limitations of the study consist of its single-center design and the small patient sample. Dr. Martínez-Juárez added that the study did not consider reinfections. In future studies, it would be ideal to integrate other molecular assessments associated with various hypotheses of the physiopathology of clinical aspects associated with PASC, such as microbiota alteration, coagulation anomalies, endothelial damage, and dysfunctional neurologic signaling.

The study was supported and funded by the Carlos Slim Foundation. Dr. Gómez-Martín, Dr. Martínez-Juárez, and Dr. Cuapio have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Proinflammatory elements mediated through metabolic pathways related to obesity and increased cellular senescence in CD57 expression in CD8+ T cells are associated with postacute sequelae of COVID-19 (PASC), according to a Mexican study. The researchers followed a Mexican cohort of 102 patients 3 months and 6 months after acute SARS-CoV-2 infection.

The study’s principal investigator was Diana Gómez-Martín, MD, PhD, of the department of immunology and rheumatology at the Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City. She told this news organization that follow-up of the patients began with the objective of understanding the determinative clinical, genetic, metabolic, and immunological factors in the progression of the acute disease. However, clinical aspects associated with PASC developed in the selected cohort. As a result, the study was extended, and the clinical, metabolic, and immunologic conditions in this single-center Mexican cohort were evaluated 3 months 6 months after the onset of infection.

Dr. Gómez-Martín explained that the immune senescence in CD57 of CD8+ T cells is one of the best-known findings of the present study. If it is confirmed in future studies, it could have important implications. “Its main implication is the possibility of better understanding the physiopathology of the clinical aspects associated with postacute sequelae of COVID-19, potentially being used for early detection and to provide follow-up aimed at patients, in addition to eventually developing targeted therapeutic strategies, such as immunometabolism regulation, in certain populations.”
 

Patients with PASC

The study was conducted from August 2020 to August 2021. Investigators recruited 102 patients (median age, 50.5 years; 55% were women) at the Mexico City Temporary Unit with a confirmed diagnosis of SARS-CoV-2. Of the patients, 44% had mild or moderate COVID-19, 30% had severe cases, and 26% of patients had critical cases. The most frequent comorbidities were obesity (44%), hypertension (24%), and type 2 diabetes (24%). The authors used a questionnaire to assess the presence of symptoms during follow-up. They analyzed immunologic variables at the time of recruitment, as well as levels of cytokines, immunoglobulin G against SARS-CoV-2, and neutrophil extracellular traps (NETs) at 1, 3, and 6 months. At 6 months’ follow-up, 12.7% of the cohort had symptoms compatible with PASC, which was defined for the study as the presence and report of three or more symptoms at 6 months’ follow-up.

As in similar studies, the authors found that female gender, remaining in intensive care, and having had more symptoms and greater titers of anti-SARS-CoV-2 antibodies during the acute infection were associated with the development of clinical aspects associated with PASC. Patients who had the disease at 6 months had increased serum levels of interleukin-1 alpha (6.21 pg/mL vs. 2.21 pg/mL), granulocyte colony-stimulating factor (55.08 pg/mL vs. 14.68 pg/mL), and interferon gamma-induced protein 10 (2,309.40 pg/mL vs. 780 pg/mL). Also, there was a trend toward an increase in serum concentration of interleukin-1 beta, interleukin-6, and interferon-gamma.

Patients whose condition met the definition of persistent PASC had increased expression of CD57 in CD8+ T cells (42,714 arbitrary units vs. 28,506) 6 months after the acute infection. The authors reported that there was no association between the persistence of PASC and the baseline amount of NETs, TRIM63, and anticellular antibodies. Nor was there an association between PASC and the titers of anti-SARS-CoV-2 antibodies at baseline and 1 month after COVID-19 diagnosis. Nonetheless, patients with persistent PASC had higher titers of anti-SARS-CoV-2 IgGs 3 months after the onset of COVID-19.

On the basis of previous data, the researchers aimed to construct a preliminary explanatory model to address the clinical and immunologic features associated with persistent PASC 6 months after SARS-CoV-2 infection. In the univariate analysis, the variables associated with the diagnosis of persistent PASC were the serum levels of granulocyte colony-stimulating factor (odds ratio, 1.01), macrophage inflammatory protein-1 alpha (OR, 1.13), interferon gamma-induced protein 10 (OR, 1.00), interleukin-6 (OR, 1.03), the expression of CD57 in CD8+ T cells (OR, 1.00), and the titers of anti-SARS-CoV-2 IgG at 1 month (OR, 1.45).

Patients with a diagnosis of clinical aspects associated with PASC at 6 months were characterized by certain predisposing factors, such as obesity, greater levels of macrophage inflammatory protein-1 alpha and interferon gamma-induced protein 10 in peripheral blood, greater expression of the senescence CD57 marker in CD8+ T lymphocytes, and persistent symptoms at 3 months.

Using these parameters to construct a predictive model after 3 months, the authors found a sensitivity of 97.7%, specificity of 53.8%, positive predictive value of 93.5%, and a negative predictive value of 77.7% for the diagnosis of clinical aspects associated with PASC at 6 months.
 

Interpreting CD57

One of the researchers who participated in the study was Luis Martínez-Juárez, MD, MPH, DrPH. He is on the operative solutions team at the Carlos Slim Foundation. Dr. Martínez-Juárez pointed out that one of the contributions of this study was that it specifically examined the Mexican population. He noted that “according to the findings, obesity is not only a comorbidity associated with more severe progressions during acute COVID-19 disease, but also, through inflammation parameters, such as interleukin-6, interferon gamma-induced protein 10, and macrophage inflammatory protein-1 alpha, it’s involved in the development of clinical aspects related to postacute sequelae of COVID-19.”

Dr. Gómez-Martín added that finding proinflammatory and obesity parameters in the patients could potentially support the hypothesis of the persistence of virus fragments in adipose tissue as possibly involved in clinical aspects associated with PASC, as some groups have reported in the medical literature.

Angélica Cuapio, MD, DrMed, an immunologist and senior investigator at the Karolinska Institute, Stockholm, who did not participate in the study, said in an interview that the authors’ findings on the sustained increase of the CD57 marker in CD8+ lymphocytes are of notable interest. They may be associated with senescence states or cellular aging or with a stage of chronic viral infections. Therefore, Dr. Cuapio argued, it would have been valuable to include cellular markers of the innate system, such as natural killer cells, since in various infections, an increase in CD57 in lymphocytes is accompanied by an almost proportional increase of this marker in natural killer cells.

“This information would help to determine more accurately if we are talking about a cellular senescence or more about a chronic infection in persistent COVID-19.” The finding is important, but future research is needed in this developing field.

Dr. Cuapio pointed out that the authors found an interesting elevation in interleukin-1 alpha in patients with clinical aspects associated with PASC in a clinically well-characterized population in Mexico. “It is possible that this is a specific marker either of a specific population or location, or this could be an association with a humoral response. Despite the fact that this finding is new and unclear, it is worth investigating. This study is of great value for the scientific community because it’s one more piece in the complex puzzle of clinical aspects associated with postacute sequelae of COVID-19.”

Dr. Gómez-Martín noted that the main limitations of the study consist of its single-center design and the small patient sample. Dr. Martínez-Juárez added that the study did not consider reinfections. In future studies, it would be ideal to integrate other molecular assessments associated with various hypotheses of the physiopathology of clinical aspects associated with PASC, such as microbiota alteration, coagulation anomalies, endothelial damage, and dysfunctional neurologic signaling.

The study was supported and funded by the Carlos Slim Foundation. Dr. Gómez-Martín, Dr. Martínez-Juárez, and Dr. Cuapio have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Proinflammatory elements mediated through metabolic pathways related to obesity and increased cellular senescence in CD57 expression in CD8+ T cells are associated with postacute sequelae of COVID-19 (PASC), according to a Mexican study. The researchers followed a Mexican cohort of 102 patients 3 months and 6 months after acute SARS-CoV-2 infection.

The study’s principal investigator was Diana Gómez-Martín, MD, PhD, of the department of immunology and rheumatology at the Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City. She told this news organization that follow-up of the patients began with the objective of understanding the determinative clinical, genetic, metabolic, and immunological factors in the progression of the acute disease. However, clinical aspects associated with PASC developed in the selected cohort. As a result, the study was extended, and the clinical, metabolic, and immunologic conditions in this single-center Mexican cohort were evaluated 3 months 6 months after the onset of infection.

Dr. Gómez-Martín explained that the immune senescence in CD57 of CD8+ T cells is one of the best-known findings of the present study. If it is confirmed in future studies, it could have important implications. “Its main implication is the possibility of better understanding the physiopathology of the clinical aspects associated with postacute sequelae of COVID-19, potentially being used for early detection and to provide follow-up aimed at patients, in addition to eventually developing targeted therapeutic strategies, such as immunometabolism regulation, in certain populations.”
 

Patients with PASC

The study was conducted from August 2020 to August 2021. Investigators recruited 102 patients (median age, 50.5 years; 55% were women) at the Mexico City Temporary Unit with a confirmed diagnosis of SARS-CoV-2. Of the patients, 44% had mild or moderate COVID-19, 30% had severe cases, and 26% of patients had critical cases. The most frequent comorbidities were obesity (44%), hypertension (24%), and type 2 diabetes (24%). The authors used a questionnaire to assess the presence of symptoms during follow-up. They analyzed immunologic variables at the time of recruitment, as well as levels of cytokines, immunoglobulin G against SARS-CoV-2, and neutrophil extracellular traps (NETs) at 1, 3, and 6 months. At 6 months’ follow-up, 12.7% of the cohort had symptoms compatible with PASC, which was defined for the study as the presence and report of three or more symptoms at 6 months’ follow-up.

As in similar studies, the authors found that female gender, remaining in intensive care, and having had more symptoms and greater titers of anti-SARS-CoV-2 antibodies during the acute infection were associated with the development of clinical aspects associated with PASC. Patients who had the disease at 6 months had increased serum levels of interleukin-1 alpha (6.21 pg/mL vs. 2.21 pg/mL), granulocyte colony-stimulating factor (55.08 pg/mL vs. 14.68 pg/mL), and interferon gamma-induced protein 10 (2,309.40 pg/mL vs. 780 pg/mL). Also, there was a trend toward an increase in serum concentration of interleukin-1 beta, interleukin-6, and interferon-gamma.

Patients whose condition met the definition of persistent PASC had increased expression of CD57 in CD8+ T cells (42,714 arbitrary units vs. 28,506) 6 months after the acute infection. The authors reported that there was no association between the persistence of PASC and the baseline amount of NETs, TRIM63, and anticellular antibodies. Nor was there an association between PASC and the titers of anti-SARS-CoV-2 antibodies at baseline and 1 month after COVID-19 diagnosis. Nonetheless, patients with persistent PASC had higher titers of anti-SARS-CoV-2 IgGs 3 months after the onset of COVID-19.

On the basis of previous data, the researchers aimed to construct a preliminary explanatory model to address the clinical and immunologic features associated with persistent PASC 6 months after SARS-CoV-2 infection. In the univariate analysis, the variables associated with the diagnosis of persistent PASC were the serum levels of granulocyte colony-stimulating factor (odds ratio, 1.01), macrophage inflammatory protein-1 alpha (OR, 1.13), interferon gamma-induced protein 10 (OR, 1.00), interleukin-6 (OR, 1.03), the expression of CD57 in CD8+ T cells (OR, 1.00), and the titers of anti-SARS-CoV-2 IgG at 1 month (OR, 1.45).

Patients with a diagnosis of clinical aspects associated with PASC at 6 months were characterized by certain predisposing factors, such as obesity, greater levels of macrophage inflammatory protein-1 alpha and interferon gamma-induced protein 10 in peripheral blood, greater expression of the senescence CD57 marker in CD8+ T lymphocytes, and persistent symptoms at 3 months.

Using these parameters to construct a predictive model after 3 months, the authors found a sensitivity of 97.7%, specificity of 53.8%, positive predictive value of 93.5%, and a negative predictive value of 77.7% for the diagnosis of clinical aspects associated with PASC at 6 months.
 

Interpreting CD57

One of the researchers who participated in the study was Luis Martínez-Juárez, MD, MPH, DrPH. He is on the operative solutions team at the Carlos Slim Foundation. Dr. Martínez-Juárez pointed out that one of the contributions of this study was that it specifically examined the Mexican population. He noted that “according to the findings, obesity is not only a comorbidity associated with more severe progressions during acute COVID-19 disease, but also, through inflammation parameters, such as interleukin-6, interferon gamma-induced protein 10, and macrophage inflammatory protein-1 alpha, it’s involved in the development of clinical aspects related to postacute sequelae of COVID-19.”

Dr. Gómez-Martín added that finding proinflammatory and obesity parameters in the patients could potentially support the hypothesis of the persistence of virus fragments in adipose tissue as possibly involved in clinical aspects associated with PASC, as some groups have reported in the medical literature.

Angélica Cuapio, MD, DrMed, an immunologist and senior investigator at the Karolinska Institute, Stockholm, who did not participate in the study, said in an interview that the authors’ findings on the sustained increase of the CD57 marker in CD8+ lymphocytes are of notable interest. They may be associated with senescence states or cellular aging or with a stage of chronic viral infections. Therefore, Dr. Cuapio argued, it would have been valuable to include cellular markers of the innate system, such as natural killer cells, since in various infections, an increase in CD57 in lymphocytes is accompanied by an almost proportional increase of this marker in natural killer cells.

“This information would help to determine more accurately if we are talking about a cellular senescence or more about a chronic infection in persistent COVID-19.” The finding is important, but future research is needed in this developing field.

Dr. Cuapio pointed out that the authors found an interesting elevation in interleukin-1 alpha in patients with clinical aspects associated with PASC in a clinically well-characterized population in Mexico. “It is possible that this is a specific marker either of a specific population or location, or this could be an association with a humoral response. Despite the fact that this finding is new and unclear, it is worth investigating. This study is of great value for the scientific community because it’s one more piece in the complex puzzle of clinical aspects associated with postacute sequelae of COVID-19.”

Dr. Gómez-Martín noted that the main limitations of the study consist of its single-center design and the small patient sample. Dr. Martínez-Juárez added that the study did not consider reinfections. In future studies, it would be ideal to integrate other molecular assessments associated with various hypotheses of the physiopathology of clinical aspects associated with PASC, such as microbiota alteration, coagulation anomalies, endothelial damage, and dysfunctional neurologic signaling.

The study was supported and funded by the Carlos Slim Foundation. Dr. Gómez-Martín, Dr. Martínez-Juárez, and Dr. Cuapio have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. On tonight’s episode, we are going to be talking about back pain. This is based on an interview, Back Pain Update with Dr. Austin Baraki. He gave us some great pearls about how to manage back pain, which we see so much of in primary care. I’ll use one of my famous teaching techniques: If the patient has any kind of back pain, they should just not move. Right?

Paul N. Williams, MD: That’s right, Matt – we should recommend bedrest until they get better for anyone who has any back pain? No. For back pain, early activity and exercise are great. Patients are often concerned that physical therapy will make their pain worse, so they don’t exercise. This misunderstanding is not surprising. They believe that if they are experiencing pain, it’s facilitating more damage, which is not necessarily the case. It will get better, and a little bit of anticipatory guidance goes a long way in terms of managing patient expectations related to early mobilization, early exercise, and physical therapy.

Dr. Watto: Absolutely. One of the goals of treatment is symptom relief to the extent that we’re able to achieve. We’re not expecting the pain to go to zero. That just doesn’t happen, especially if someone’s on a medication long term. Another goal is return to function. We want them sleeping. We want them to be able to tolerate movement.

We have medications – NSAIDs and muscle relaxants, which are actually tranquilizers. But most therapy for back pain doesn’t involve medications. It involves active movement, so we have to find movement that the patient enjoys doing. Passive treatments, things being done to patients, just don’t work as well.
 

Dr. Williams: We should be clear – we’re talking primarily about chronic back pain here. For acute back pain, we actually have some decent medications, but acute back pain tends to improve no matter what you do. We don’t have much to offer pharmacologically for chronic low back pain. The best modalities usually involve physical activity of some kind.

Dr. Watto: Let’s discuss the evaluation of back pain. Something that always comes up: Should we order imaging, and is there a right time to get it? Dr. Baraki was very clear about when to do imaging. Two big buckets of patients might need imaging.

First, a patient who has a serious underlying condition and you’re using imaging to try to diagnose it; or in a chronic setting, a patient who needs surgery, and imaging is part of the presurgical evaluation. We talked about red flags.

The red flags are major trauma, where we have reason to believe there might be something going on – if we strongly suspect infection, or the patient is injecting drugs. If the patient has a history of cancer, we would be worried that they might have a recurrence. Those are some of the main red flags. With a patient who has osteoporosis or is on chronic steroids, you might even be able to get by with plain films instead of an MRI to look for fracture.

The other thing I wanted to ask you about is, when should we get imaging? Are there any pitfalls we need to worry about?
 

Dr. Williams: I always like podcasts I’m not on because I enjoy listening to them much more. Dr. Baraki talked about the very specific language that is used in radiology reports, such as spondylitis, spondylolysis, and multilevel degenerative disease. They sound bad, but if they are just reframed as age-related degenerative changes, that sounds so much more benign. When discussing with patients, we should avoid medical jargon and say that we saw some changes that we would expect for someone of your age. That sounds so much better than saying we saw multilevel degenerative disease, which sounds like an alarming pathology if you’re not a physician. Without being inaccurate, we should frame the discussion such that we aren’t providing a very specific diagnosis, because that is rarely the case with chronic low back pain. Typically, many things are going on and you may never identify a single unifying diagnosis, which doesn’t tend to help anyway.

Dr. Watto: There’s evidence showing that if the radiology report uses clinical terminology that both clinician and patient think of as less serious, they are less likely to proceed to more invasive treatments. Calling an episode of back pain a “lumbar strain” helps the patient understand that this is a pretty common thing. Almost everyone is going to have an episode of back pain at some point in their life, and almost all of them will get better. Most of the time there’s no serious underlying condition.

This was a great discussion with Dr. Baraki. Click on Back Pain Update with Dr Austin Baraki to hear the full discussion. Until next time, I’ve been Dr. Matthew Frank Watto.
 

Dr. Williams: And I’m Dr. Paul Nelson Williams.

Dr. Watto is Clinical Assistant Professor, Department of Medicine, University of Pennsylvania, Philadelphia. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, Temple University, Philadelphia. Neither reported any conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. On tonight’s episode, we are going to be talking about back pain. This is based on an interview, Back Pain Update with Dr. Austin Baraki. He gave us some great pearls about how to manage back pain, which we see so much of in primary care. I’ll use one of my famous teaching techniques: If the patient has any kind of back pain, they should just not move. Right?

Paul N. Williams, MD: That’s right, Matt – we should recommend bedrest until they get better for anyone who has any back pain? No. For back pain, early activity and exercise are great. Patients are often concerned that physical therapy will make their pain worse, so they don’t exercise. This misunderstanding is not surprising. They believe that if they are experiencing pain, it’s facilitating more damage, which is not necessarily the case. It will get better, and a little bit of anticipatory guidance goes a long way in terms of managing patient expectations related to early mobilization, early exercise, and physical therapy.

Dr. Watto: Absolutely. One of the goals of treatment is symptom relief to the extent that we’re able to achieve. We’re not expecting the pain to go to zero. That just doesn’t happen, especially if someone’s on a medication long term. Another goal is return to function. We want them sleeping. We want them to be able to tolerate movement.

We have medications – NSAIDs and muscle relaxants, which are actually tranquilizers. But most therapy for back pain doesn’t involve medications. It involves active movement, so we have to find movement that the patient enjoys doing. Passive treatments, things being done to patients, just don’t work as well.
 

Dr. Williams: We should be clear – we’re talking primarily about chronic back pain here. For acute back pain, we actually have some decent medications, but acute back pain tends to improve no matter what you do. We don’t have much to offer pharmacologically for chronic low back pain. The best modalities usually involve physical activity of some kind.

Dr. Watto: Let’s discuss the evaluation of back pain. Something that always comes up: Should we order imaging, and is there a right time to get it? Dr. Baraki was very clear about when to do imaging. Two big buckets of patients might need imaging.

First, a patient who has a serious underlying condition and you’re using imaging to try to diagnose it; or in a chronic setting, a patient who needs surgery, and imaging is part of the presurgical evaluation. We talked about red flags.

The red flags are major trauma, where we have reason to believe there might be something going on – if we strongly suspect infection, or the patient is injecting drugs. If the patient has a history of cancer, we would be worried that they might have a recurrence. Those are some of the main red flags. With a patient who has osteoporosis or is on chronic steroids, you might even be able to get by with plain films instead of an MRI to look for fracture.

The other thing I wanted to ask you about is, when should we get imaging? Are there any pitfalls we need to worry about?
 

Dr. Williams: I always like podcasts I’m not on because I enjoy listening to them much more. Dr. Baraki talked about the very specific language that is used in radiology reports, such as spondylitis, spondylolysis, and multilevel degenerative disease. They sound bad, but if they are just reframed as age-related degenerative changes, that sounds so much more benign. When discussing with patients, we should avoid medical jargon and say that we saw some changes that we would expect for someone of your age. That sounds so much better than saying we saw multilevel degenerative disease, which sounds like an alarming pathology if you’re not a physician. Without being inaccurate, we should frame the discussion such that we aren’t providing a very specific diagnosis, because that is rarely the case with chronic low back pain. Typically, many things are going on and you may never identify a single unifying diagnosis, which doesn’t tend to help anyway.

Dr. Watto: There’s evidence showing that if the radiology report uses clinical terminology that both clinician and patient think of as less serious, they are less likely to proceed to more invasive treatments. Calling an episode of back pain a “lumbar strain” helps the patient understand that this is a pretty common thing. Almost everyone is going to have an episode of back pain at some point in their life, and almost all of them will get better. Most of the time there’s no serious underlying condition.

This was a great discussion with Dr. Baraki. Click on Back Pain Update with Dr Austin Baraki to hear the full discussion. Until next time, I’ve been Dr. Matthew Frank Watto.
 

Dr. Williams: And I’m Dr. Paul Nelson Williams.

Dr. Watto is Clinical Assistant Professor, Department of Medicine, University of Pennsylvania, Philadelphia. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, Temple University, Philadelphia. Neither reported any conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. On tonight’s episode, we are going to be talking about back pain. This is based on an interview, Back Pain Update with Dr. Austin Baraki. He gave us some great pearls about how to manage back pain, which we see so much of in primary care. I’ll use one of my famous teaching techniques: If the patient has any kind of back pain, they should just not move. Right?

Paul N. Williams, MD: That’s right, Matt – we should recommend bedrest until they get better for anyone who has any back pain? No. For back pain, early activity and exercise are great. Patients are often concerned that physical therapy will make their pain worse, so they don’t exercise. This misunderstanding is not surprising. They believe that if they are experiencing pain, it’s facilitating more damage, which is not necessarily the case. It will get better, and a little bit of anticipatory guidance goes a long way in terms of managing patient expectations related to early mobilization, early exercise, and physical therapy.

Dr. Watto: Absolutely. One of the goals of treatment is symptom relief to the extent that we’re able to achieve. We’re not expecting the pain to go to zero. That just doesn’t happen, especially if someone’s on a medication long term. Another goal is return to function. We want them sleeping. We want them to be able to tolerate movement.

We have medications – NSAIDs and muscle relaxants, which are actually tranquilizers. But most therapy for back pain doesn’t involve medications. It involves active movement, so we have to find movement that the patient enjoys doing. Passive treatments, things being done to patients, just don’t work as well.
 

Dr. Williams: We should be clear – we’re talking primarily about chronic back pain here. For acute back pain, we actually have some decent medications, but acute back pain tends to improve no matter what you do. We don’t have much to offer pharmacologically for chronic low back pain. The best modalities usually involve physical activity of some kind.

Dr. Watto: Let’s discuss the evaluation of back pain. Something that always comes up: Should we order imaging, and is there a right time to get it? Dr. Baraki was very clear about when to do imaging. Two big buckets of patients might need imaging.

First, a patient who has a serious underlying condition and you’re using imaging to try to diagnose it; or in a chronic setting, a patient who needs surgery, and imaging is part of the presurgical evaluation. We talked about red flags.

The red flags are major trauma, where we have reason to believe there might be something going on – if we strongly suspect infection, or the patient is injecting drugs. If the patient has a history of cancer, we would be worried that they might have a recurrence. Those are some of the main red flags. With a patient who has osteoporosis or is on chronic steroids, you might even be able to get by with plain films instead of an MRI to look for fracture.

The other thing I wanted to ask you about is, when should we get imaging? Are there any pitfalls we need to worry about?
 

Dr. Williams: I always like podcasts I’m not on because I enjoy listening to them much more. Dr. Baraki talked about the very specific language that is used in radiology reports, such as spondylitis, spondylolysis, and multilevel degenerative disease. They sound bad, but if they are just reframed as age-related degenerative changes, that sounds so much more benign. When discussing with patients, we should avoid medical jargon and say that we saw some changes that we would expect for someone of your age. That sounds so much better than saying we saw multilevel degenerative disease, which sounds like an alarming pathology if you’re not a physician. Without being inaccurate, we should frame the discussion such that we aren’t providing a very specific diagnosis, because that is rarely the case with chronic low back pain. Typically, many things are going on and you may never identify a single unifying diagnosis, which doesn’t tend to help anyway.

Dr. Watto: There’s evidence showing that if the radiology report uses clinical terminology that both clinician and patient think of as less serious, they are less likely to proceed to more invasive treatments. Calling an episode of back pain a “lumbar strain” helps the patient understand that this is a pretty common thing. Almost everyone is going to have an episode of back pain at some point in their life, and almost all of them will get better. Most of the time there’s no serious underlying condition.

This was a great discussion with Dr. Baraki. Click on Back Pain Update with Dr Austin Baraki to hear the full discussion. Until next time, I’ve been Dr. Matthew Frank Watto.
 

Dr. Williams: And I’m Dr. Paul Nelson Williams.

Dr. Watto is Clinical Assistant Professor, Department of Medicine, University of Pennsylvania, Philadelphia. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, Temple University, Philadelphia. Neither reported any conflicts of interest.

A version of this article first appeared on Medscape.com.

The often-delayed diagnosis of isolated nail psoriasis (NP), along with the possibility of a “reciprocal relationship” with psoriatic arthritis, “should serve as an impetus for dermatologists to improve their diagnostic accuracy,” investigators said in a research letter.

Diagnosis of isolated NP was delayed by almost 3 years among the 87 cases recorded and “arthritis was most often diagnosed concurrently with NP,” at a major nail referral center between Jan. 1, 2001, and Dec. 21, 2022, Michelle J. Chang of Drexel University, Philadelphia, and associates reported.

In what the authors say is, “the largest study documenting clinical and histologic features in patients with isolated NP,” the two most common clinical features were onycholysis and nail plate pitting, seen in 79% and 70% of cases, respectively. No other single feature had a prevalence higher than 28%.

The most frequent clinical dyad was onycholysis and pitting in 66% of patients, followed by onycholysis/nail thickening in 33% and onycholysis/splinter hemorrhage in 32%. The most common histologic features were parakeratosis in 79% and neutrophil infiltration in 48%, the investigators said.

Psoriatic arthritis (PsA), a focus of the study, occurred in 10 (11%) of the 87 individuals with isolated NP. Considering this finding, and “the close proximity between the nail apparatus and joint, we hypothesize a reciprocal relationship, with nail unit inflammation precipitating PsA,” Ms. Chang and associates wrote.

Senior author, Shari Lipner, MD, PhD, of the department of dermatology, Weill Cornell Medicine, New York, is a consultant for Ortho-Dermatologics, Hoth Therapeutics, and BelleTorus. Ms. Chang and the two other investigators had no conflicts of interest to declare.

 

The often-delayed diagnosis of isolated nail psoriasis (NP), along with the possibility of a “reciprocal relationship” with psoriatic arthritis, “should serve as an impetus for dermatologists to improve their diagnostic accuracy,” investigators said in a research letter.

Diagnosis of isolated NP was delayed by almost 3 years among the 87 cases recorded and “arthritis was most often diagnosed concurrently with NP,” at a major nail referral center between Jan. 1, 2001, and Dec. 21, 2022, Michelle J. Chang of Drexel University, Philadelphia, and associates reported.

In what the authors say is, “the largest study documenting clinical and histologic features in patients with isolated NP,” the two most common clinical features were onycholysis and nail plate pitting, seen in 79% and 70% of cases, respectively. No other single feature had a prevalence higher than 28%.

The most frequent clinical dyad was onycholysis and pitting in 66% of patients, followed by onycholysis/nail thickening in 33% and onycholysis/splinter hemorrhage in 32%. The most common histologic features were parakeratosis in 79% and neutrophil infiltration in 48%, the investigators said.

Psoriatic arthritis (PsA), a focus of the study, occurred in 10 (11%) of the 87 individuals with isolated NP. Considering this finding, and “the close proximity between the nail apparatus and joint, we hypothesize a reciprocal relationship, with nail unit inflammation precipitating PsA,” Ms. Chang and associates wrote.

Senior author, Shari Lipner, MD, PhD, of the department of dermatology, Weill Cornell Medicine, New York, is a consultant for Ortho-Dermatologics, Hoth Therapeutics, and BelleTorus. Ms. Chang and the two other investigators had no conflicts of interest to declare.

 

The often-delayed diagnosis of isolated nail psoriasis (NP), along with the possibility of a “reciprocal relationship” with psoriatic arthritis, “should serve as an impetus for dermatologists to improve their diagnostic accuracy,” investigators said in a research letter.

Diagnosis of isolated NP was delayed by almost 3 years among the 87 cases recorded and “arthritis was most often diagnosed concurrently with NP,” at a major nail referral center between Jan. 1, 2001, and Dec. 21, 2022, Michelle J. Chang of Drexel University, Philadelphia, and associates reported.

In what the authors say is, “the largest study documenting clinical and histologic features in patients with isolated NP,” the two most common clinical features were onycholysis and nail plate pitting, seen in 79% and 70% of cases, respectively. No other single feature had a prevalence higher than 28%.

The most frequent clinical dyad was onycholysis and pitting in 66% of patients, followed by onycholysis/nail thickening in 33% and onycholysis/splinter hemorrhage in 32%. The most common histologic features were parakeratosis in 79% and neutrophil infiltration in 48%, the investigators said.

Psoriatic arthritis (PsA), a focus of the study, occurred in 10 (11%) of the 87 individuals with isolated NP. Considering this finding, and “the close proximity between the nail apparatus and joint, we hypothesize a reciprocal relationship, with nail unit inflammation precipitating PsA,” Ms. Chang and associates wrote.

Senior author, Shari Lipner, MD, PhD, of the department of dermatology, Weill Cornell Medicine, New York, is a consultant for Ortho-Dermatologics, Hoth Therapeutics, and BelleTorus. Ms. Chang and the two other investigators had no conflicts of interest to declare.

 

Bacterial proteins in the bleeding gums of patients with periodontal disease (PD) and rheumatoid arthritis (RA) enter the bloodstream and trigger immune responses that may contribute to RA pathogenesis and disease flares, a new longitudinal study suggests.

The results suggest that PD involves repeated oral mucosa breakdowns with the release of citrullinated oral bacteria into the bloodstream and that these bacteria activate inflammatory monocytes in the inflamed RA synovium and in the blood of patients with RA. The bacteria also activate anti-citrullinated protein antibody (ACPA)–positive B cells, promoting affinity maturation and epitope spreading to citrullinated human antigens, the authors wrote.

“Our study discovered frequent and repeated episodes of oral bacteria in the blood of patients with periodontal disease and rheumatoid arthritis,” senior study author Dana E. Orange, MD, associate professor of clinical investigation at Rockefeller University, New York, said in an interview. “We saw that these bacteria were triggering an inflammatory [monocyte] response that is similar to what we see in the inflamed joints of patients with RA.

“RA patients are less likely to benefit from RA treatment if they have concurrent periodontal disease,” she said.

“RA patients tend to harbor cyclic citrullinated peptide [CCP] autoantibodies. Many groups have noted that CCP antibodies are very highly mutated, a signature of a B-cell/antibody response that has been stimulated over and over again,” Dr. Orange explained. “We found that CCP antibodies also bind the same oral bacteria we detected in the bloodstream. That patients with PD experience frequent, repeated episodes of oral bacteria in the blood is consistent with the very high level of mutation burden of CCP antibodies.”
 

Periodontal disease is a large problem among older adults

Periodontal disease ranges from gingivitis with swollen, red gums that may bleed, to periodontitis with gums pulling away from teeth, bone loss, and loose or lost teeth. PD is very prevalent in the United States, with some form of it occurring in 47% of people 30 years of age and older and in 70% of those 65 years and older, according to the Centers for Disease Control and Prevention.

PD is more common in people with RA who have detectable ACPAs, and that link implicates oral mucosal inflammation in RA pathogenesis.
 

Investigating whether PD leads to RA

At Rockefeller University, Dr. Orange and her colleagues followed five female patients with RA who were seropositive for CCP over the course of 1-4 years. Two had severe PD, and three showed no signs of PD. Each week, participants provided finger-stick blood samples for RNA sequencing and B-cell repertoire sequencing, reported changes in their medication and dental work, and completed questionnaires. They also underwent monthly physical exams that evaluated tenderness and swelling in 28 joints, and they provided additional samples during self-reported flares.

At Stanford (Calif.) University, researchers isolated plasmablasts from blood samples collected from 12 donors with anti-CPP+ RA and healthy donors. They also analyzed synovial fluid samples from 65 RA and OA patients.

In addition, University of Colorado researchers collected plasma samples from patients with RA and healthy donors, and they classified the gingival health of participants.

The researchers found that the patients with PD also had repeated flare-ups of oral bacteria in the blood, mainly from the Streptococcaceae family, suggesting that the oral mucosa repeatedly broke down and introduced bacteria into the bloodstream. In the blood, inflammatory immune cells targeted the bacteria and released ACPAs, which have been linked with RA.

“Even without dental procedures, patients with RA and periodontal disease experience repeated episodes of bacteremia,” Dr. Orange said. “While dental procedures are known to be associated with dissemination of oral bacteria into the bloodstream, we didn’t expect to see this happening so frequently and independent of dental procedures. We also had thought that people with oral bacteria in their blood would have symptoms such as fever or malaise, but they were asymptomatic.”
 

Experts welcome the results

“It is well established that oral health impacts overall health. In particular, the link between periodontal disease and chronic systemic diseases has been explored in many robust studies,” Chi T. Viet, MD, DDS, PhD, oral and maxillofacial surgeon and associate professor at the Loma Linda (Calif.) University School of Dentistry, told this news organization.

“The study ... highlights the importance of early treatment and prevention of oral health issues, as they can have devastating systemic sequelae,” added Dr. Viet, who was not involved in the study.

Devon Charlton, MD, MPH, director of rheumatology at the University of Pittsburgh Medical Center Regional Orthopedics in New Castle, Pa., advised patients and providers to team up to manage RA and PD.

“If the patient and provider aggressively treat periodontal disease and dental health in general, the patient decreases their risk of infection and inflammation, decreases the potential development of RA, and increases their future quality of life,” said Dr. Charlton, also not involved in the study.

However, findings from the study population may be difficult to generalize to other populations, he added.

Dr. Orange and her colleagues suggest further related research, including studies on whether treating PD makes RA easier to treat and whether the treatment of PD in patients whose RA is in clinical remission raises the likelihood of being able to discontinue therapy safely.

The study was supported through grant funding from the National Institutes of Health, the National Science Foundation, the Robertson Foundation, Rockefeller University, the Bernard and Irene Schwartz Foundation, the Iris and Junming Le Foundation, and the Rheumatology Research Foundation. Dr. Orange reports no relevant financial relationships. Several coauthors report financial relationships with the pharmaceutical industry. Dr. Viet and Dr. Charlton report no relevant financial relationships. All experts commented by email.

A version of this article first appeared on Medscape.com.

Bacterial proteins in the bleeding gums of patients with periodontal disease (PD) and rheumatoid arthritis (RA) enter the bloodstream and trigger immune responses that may contribute to RA pathogenesis and disease flares, a new longitudinal study suggests.

The results suggest that PD involves repeated oral mucosa breakdowns with the release of citrullinated oral bacteria into the bloodstream and that these bacteria activate inflammatory monocytes in the inflamed RA synovium and in the blood of patients with RA. The bacteria also activate anti-citrullinated protein antibody (ACPA)–positive B cells, promoting affinity maturation and epitope spreading to citrullinated human antigens, the authors wrote.

“Our study discovered frequent and repeated episodes of oral bacteria in the blood of patients with periodontal disease and rheumatoid arthritis,” senior study author Dana E. Orange, MD, associate professor of clinical investigation at Rockefeller University, New York, said in an interview. “We saw that these bacteria were triggering an inflammatory [monocyte] response that is similar to what we see in the inflamed joints of patients with RA.

“RA patients are less likely to benefit from RA treatment if they have concurrent periodontal disease,” she said.

“RA patients tend to harbor cyclic citrullinated peptide [CCP] autoantibodies. Many groups have noted that CCP antibodies are very highly mutated, a signature of a B-cell/antibody response that has been stimulated over and over again,” Dr. Orange explained. “We found that CCP antibodies also bind the same oral bacteria we detected in the bloodstream. That patients with PD experience frequent, repeated episodes of oral bacteria in the blood is consistent with the very high level of mutation burden of CCP antibodies.”
 

Periodontal disease is a large problem among older adults

Periodontal disease ranges from gingivitis with swollen, red gums that may bleed, to periodontitis with gums pulling away from teeth, bone loss, and loose or lost teeth. PD is very prevalent in the United States, with some form of it occurring in 47% of people 30 years of age and older and in 70% of those 65 years and older, according to the Centers for Disease Control and Prevention.

PD is more common in people with RA who have detectable ACPAs, and that link implicates oral mucosal inflammation in RA pathogenesis.
 

Investigating whether PD leads to RA

At Rockefeller University, Dr. Orange and her colleagues followed five female patients with RA who were seropositive for CCP over the course of 1-4 years. Two had severe PD, and three showed no signs of PD. Each week, participants provided finger-stick blood samples for RNA sequencing and B-cell repertoire sequencing, reported changes in their medication and dental work, and completed questionnaires. They also underwent monthly physical exams that evaluated tenderness and swelling in 28 joints, and they provided additional samples during self-reported flares.

At Stanford (Calif.) University, researchers isolated plasmablasts from blood samples collected from 12 donors with anti-CPP+ RA and healthy donors. They also analyzed synovial fluid samples from 65 RA and OA patients.

In addition, University of Colorado researchers collected plasma samples from patients with RA and healthy donors, and they classified the gingival health of participants.

The researchers found that the patients with PD also had repeated flare-ups of oral bacteria in the blood, mainly from the Streptococcaceae family, suggesting that the oral mucosa repeatedly broke down and introduced bacteria into the bloodstream. In the blood, inflammatory immune cells targeted the bacteria and released ACPAs, which have been linked with RA.

“Even without dental procedures, patients with RA and periodontal disease experience repeated episodes of bacteremia,” Dr. Orange said. “While dental procedures are known to be associated with dissemination of oral bacteria into the bloodstream, we didn’t expect to see this happening so frequently and independent of dental procedures. We also had thought that people with oral bacteria in their blood would have symptoms such as fever or malaise, but they were asymptomatic.”
 

Experts welcome the results

“It is well established that oral health impacts overall health. In particular, the link between periodontal disease and chronic systemic diseases has been explored in many robust studies,” Chi T. Viet, MD, DDS, PhD, oral and maxillofacial surgeon and associate professor at the Loma Linda (Calif.) University School of Dentistry, told this news organization.

“The study ... highlights the importance of early treatment and prevention of oral health issues, as they can have devastating systemic sequelae,” added Dr. Viet, who was not involved in the study.

Devon Charlton, MD, MPH, director of rheumatology at the University of Pittsburgh Medical Center Regional Orthopedics in New Castle, Pa., advised patients and providers to team up to manage RA and PD.

“If the patient and provider aggressively treat periodontal disease and dental health in general, the patient decreases their risk of infection and inflammation, decreases the potential development of RA, and increases their future quality of life,” said Dr. Charlton, also not involved in the study.

However, findings from the study population may be difficult to generalize to other populations, he added.

Dr. Orange and her colleagues suggest further related research, including studies on whether treating PD makes RA easier to treat and whether the treatment of PD in patients whose RA is in clinical remission raises the likelihood of being able to discontinue therapy safely.

The study was supported through grant funding from the National Institutes of Health, the National Science Foundation, the Robertson Foundation, Rockefeller University, the Bernard and Irene Schwartz Foundation, the Iris and Junming Le Foundation, and the Rheumatology Research Foundation. Dr. Orange reports no relevant financial relationships. Several coauthors report financial relationships with the pharmaceutical industry. Dr. Viet and Dr. Charlton report no relevant financial relationships. All experts commented by email.

A version of this article first appeared on Medscape.com.

Bacterial proteins in the bleeding gums of patients with periodontal disease (PD) and rheumatoid arthritis (RA) enter the bloodstream and trigger immune responses that may contribute to RA pathogenesis and disease flares, a new longitudinal study suggests.

The results suggest that PD involves repeated oral mucosa breakdowns with the release of citrullinated oral bacteria into the bloodstream and that these bacteria activate inflammatory monocytes in the inflamed RA synovium and in the blood of patients with RA. The bacteria also activate anti-citrullinated protein antibody (ACPA)–positive B cells, promoting affinity maturation and epitope spreading to citrullinated human antigens, the authors wrote.

“Our study discovered frequent and repeated episodes of oral bacteria in the blood of patients with periodontal disease and rheumatoid arthritis,” senior study author Dana E. Orange, MD, associate professor of clinical investigation at Rockefeller University, New York, said in an interview. “We saw that these bacteria were triggering an inflammatory [monocyte] response that is similar to what we see in the inflamed joints of patients with RA.

“RA patients are less likely to benefit from RA treatment if they have concurrent periodontal disease,” she said.

“RA patients tend to harbor cyclic citrullinated peptide [CCP] autoantibodies. Many groups have noted that CCP antibodies are very highly mutated, a signature of a B-cell/antibody response that has been stimulated over and over again,” Dr. Orange explained. “We found that CCP antibodies also bind the same oral bacteria we detected in the bloodstream. That patients with PD experience frequent, repeated episodes of oral bacteria in the blood is consistent with the very high level of mutation burden of CCP antibodies.”
 

Periodontal disease is a large problem among older adults

Periodontal disease ranges from gingivitis with swollen, red gums that may bleed, to periodontitis with gums pulling away from teeth, bone loss, and loose or lost teeth. PD is very prevalent in the United States, with some form of it occurring in 47% of people 30 years of age and older and in 70% of those 65 years and older, according to the Centers for Disease Control and Prevention.

PD is more common in people with RA who have detectable ACPAs, and that link implicates oral mucosal inflammation in RA pathogenesis.
 

Investigating whether PD leads to RA

At Rockefeller University, Dr. Orange and her colleagues followed five female patients with RA who were seropositive for CCP over the course of 1-4 years. Two had severe PD, and three showed no signs of PD. Each week, participants provided finger-stick blood samples for RNA sequencing and B-cell repertoire sequencing, reported changes in their medication and dental work, and completed questionnaires. They also underwent monthly physical exams that evaluated tenderness and swelling in 28 joints, and they provided additional samples during self-reported flares.

At Stanford (Calif.) University, researchers isolated plasmablasts from blood samples collected from 12 donors with anti-CPP+ RA and healthy donors. They also analyzed synovial fluid samples from 65 RA and OA patients.

In addition, University of Colorado researchers collected plasma samples from patients with RA and healthy donors, and they classified the gingival health of participants.

The researchers found that the patients with PD also had repeated flare-ups of oral bacteria in the blood, mainly from the Streptococcaceae family, suggesting that the oral mucosa repeatedly broke down and introduced bacteria into the bloodstream. In the blood, inflammatory immune cells targeted the bacteria and released ACPAs, which have been linked with RA.

“Even without dental procedures, patients with RA and periodontal disease experience repeated episodes of bacteremia,” Dr. Orange said. “While dental procedures are known to be associated with dissemination of oral bacteria into the bloodstream, we didn’t expect to see this happening so frequently and independent of dental procedures. We also had thought that people with oral bacteria in their blood would have symptoms such as fever or malaise, but they were asymptomatic.”
 

Experts welcome the results

“It is well established that oral health impacts overall health. In particular, the link between periodontal disease and chronic systemic diseases has been explored in many robust studies,” Chi T. Viet, MD, DDS, PhD, oral and maxillofacial surgeon and associate professor at the Loma Linda (Calif.) University School of Dentistry, told this news organization.

“The study ... highlights the importance of early treatment and prevention of oral health issues, as they can have devastating systemic sequelae,” added Dr. Viet, who was not involved in the study.

Devon Charlton, MD, MPH, director of rheumatology at the University of Pittsburgh Medical Center Regional Orthopedics in New Castle, Pa., advised patients and providers to team up to manage RA and PD.

“If the patient and provider aggressively treat periodontal disease and dental health in general, the patient decreases their risk of infection and inflammation, decreases the potential development of RA, and increases their future quality of life,” said Dr. Charlton, also not involved in the study.

However, findings from the study population may be difficult to generalize to other populations, he added.

Dr. Orange and her colleagues suggest further related research, including studies on whether treating PD makes RA easier to treat and whether the treatment of PD in patients whose RA is in clinical remission raises the likelihood of being able to discontinue therapy safely.

The study was supported through grant funding from the National Institutes of Health, the National Science Foundation, the Robertson Foundation, Rockefeller University, the Bernard and Irene Schwartz Foundation, the Iris and Junming Le Foundation, and the Rheumatology Research Foundation. Dr. Orange reports no relevant financial relationships. Several coauthors report financial relationships with the pharmaceutical industry. Dr. Viet and Dr. Charlton report no relevant financial relationships. All experts commented by email.

A version of this article first appeared on Medscape.com.

An Ohio physician pled guilty to charges that he prescribed opioids for nonmedical purposes and continued to prescribe to patients he knew had psychiatric and substance use disorders, admitting that he also engaged in sex with at least three patients in exchange for opioids.

Jeffrey B. Sutton, DO, a neuromuscular medicine specialist, pled guilty on January 30 in federal court to 31 counts of illegally prescribing opioids and other controlled substances, 1 count of illegally distributing controlled substances, and 20 counts of health care fraud.

Prosecutors said Dr. Sutton admitted that he ignored warnings from prescription drug management organizations, insurers, and state authorities that he was prescribing excessively high dosages of opioids.

Dr. Sutton also admitted to ignoring patient requests to lower dosages and that he also ignored signs that patients were selling prescribed medications or otherwise engaging in illicit activity, including violations of a “pain management agreement” that he required them to sign.

The fraud counts pertained to Dr. Sutton billing Medicare, Medicaid, and other insurers for medically unnecessary visits that he required of patients so that he could prescribe inappropriate or unnecessary opioids.

In the charging document shared with this news organization, prosecutors said Dr. Sutton had sex with at least three patients, including during office visits and outside of the office. Occasionally, the physician would give opioids or other controlled substances – often benzodiazepines – to these patients, without a prescription or valid medical need.

Dr. Sutton escalated the dosage for one of those patients, even as the subjective pain score did not improve and when the patient’s urine tests showed the presence of THC and buprenorphine, but not any of the prescribed medications.

Another patient came to Dr. Sutton in 2007 with a warning that she had a history of “narcotic-seeking” behavior and diagnoses of depression, anxiety, paranoid schizophrenia, and obsessive-compulsive disorder.

The patient was hospitalized in 2018 for complications from benzodiazepine use (prescribed by Dr. Sutton). She weighed 80 pounds at the time. Dr. Sutton continued to prescribe benzodiazepines and extreme doses of opioids – in excess of 2,000 morphine equivalent dose – “despite recognizing and documenting repeated instances of noncompliance with treatment for psychiatric conditions, and despite the known contraindications of long-term opioid use for patients with these mental illnesses,” according to the charging document.

Dr. Sutton continued to prescribe opioids despite two hospitalizations for overdoses, more than 20 failed urine drug screens that showed presence of illicit drugs such as cocaine, and documented excessive use of alprazolam (Xanax) and methadone.

The physician surrendered his Drug Enforcement Administration Certificate of Registration of Controlled Substances Privileges in February 2022 “as an indication of your good faith in desiring to remedy any incorrect or unlawful practices on your part,” according to a letter to Dr. Sutton from the State Medical Board of Ohio. In that September 2022 letter, the Board notified Dr. Sutton of its intention to possibly suspend or revoke his license.

Dr. Sutton did not request a hearing, and the Board permanently revoked his medical license on January 16.

The court will sentence Dr. Sutton on May 23, according to a report by WFMJ.

A version of this article originally appeared on Medscape.com.

An Ohio physician pled guilty to charges that he prescribed opioids for nonmedical purposes and continued to prescribe to patients he knew had psychiatric and substance use disorders, admitting that he also engaged in sex with at least three patients in exchange for opioids.

Jeffrey B. Sutton, DO, a neuromuscular medicine specialist, pled guilty on January 30 in federal court to 31 counts of illegally prescribing opioids and other controlled substances, 1 count of illegally distributing controlled substances, and 20 counts of health care fraud.

Prosecutors said Dr. Sutton admitted that he ignored warnings from prescription drug management organizations, insurers, and state authorities that he was prescribing excessively high dosages of opioids.

Dr. Sutton also admitted to ignoring patient requests to lower dosages and that he also ignored signs that patients were selling prescribed medications or otherwise engaging in illicit activity, including violations of a “pain management agreement” that he required them to sign.

The fraud counts pertained to Dr. Sutton billing Medicare, Medicaid, and other insurers for medically unnecessary visits that he required of patients so that he could prescribe inappropriate or unnecessary opioids.

In the charging document shared with this news organization, prosecutors said Dr. Sutton had sex with at least three patients, including during office visits and outside of the office. Occasionally, the physician would give opioids or other controlled substances – often benzodiazepines – to these patients, without a prescription or valid medical need.

Dr. Sutton escalated the dosage for one of those patients, even as the subjective pain score did not improve and when the patient’s urine tests showed the presence of THC and buprenorphine, but not any of the prescribed medications.

Another patient came to Dr. Sutton in 2007 with a warning that she had a history of “narcotic-seeking” behavior and diagnoses of depression, anxiety, paranoid schizophrenia, and obsessive-compulsive disorder.

The patient was hospitalized in 2018 for complications from benzodiazepine use (prescribed by Dr. Sutton). She weighed 80 pounds at the time. Dr. Sutton continued to prescribe benzodiazepines and extreme doses of opioids – in excess of 2,000 morphine equivalent dose – “despite recognizing and documenting repeated instances of noncompliance with treatment for psychiatric conditions, and despite the known contraindications of long-term opioid use for patients with these mental illnesses,” according to the charging document.

Dr. Sutton continued to prescribe opioids despite two hospitalizations for overdoses, more than 20 failed urine drug screens that showed presence of illicit drugs such as cocaine, and documented excessive use of alprazolam (Xanax) and methadone.

The physician surrendered his Drug Enforcement Administration Certificate of Registration of Controlled Substances Privileges in February 2022 “as an indication of your good faith in desiring to remedy any incorrect or unlawful practices on your part,” according to a letter to Dr. Sutton from the State Medical Board of Ohio. In that September 2022 letter, the Board notified Dr. Sutton of its intention to possibly suspend or revoke his license.

Dr. Sutton did not request a hearing, and the Board permanently revoked his medical license on January 16.

The court will sentence Dr. Sutton on May 23, according to a report by WFMJ.

A version of this article originally appeared on Medscape.com.

An Ohio physician pled guilty to charges that he prescribed opioids for nonmedical purposes and continued to prescribe to patients he knew had psychiatric and substance use disorders, admitting that he also engaged in sex with at least three patients in exchange for opioids.

Jeffrey B. Sutton, DO, a neuromuscular medicine specialist, pled guilty on January 30 in federal court to 31 counts of illegally prescribing opioids and other controlled substances, 1 count of illegally distributing controlled substances, and 20 counts of health care fraud.

Prosecutors said Dr. Sutton admitted that he ignored warnings from prescription drug management organizations, insurers, and state authorities that he was prescribing excessively high dosages of opioids.

Dr. Sutton also admitted to ignoring patient requests to lower dosages and that he also ignored signs that patients were selling prescribed medications or otherwise engaging in illicit activity, including violations of a “pain management agreement” that he required them to sign.

The fraud counts pertained to Dr. Sutton billing Medicare, Medicaid, and other insurers for medically unnecessary visits that he required of patients so that he could prescribe inappropriate or unnecessary opioids.

In the charging document shared with this news organization, prosecutors said Dr. Sutton had sex with at least three patients, including during office visits and outside of the office. Occasionally, the physician would give opioids or other controlled substances – often benzodiazepines – to these patients, without a prescription or valid medical need.

Dr. Sutton escalated the dosage for one of those patients, even as the subjective pain score did not improve and when the patient’s urine tests showed the presence of THC and buprenorphine, but not any of the prescribed medications.

Another patient came to Dr. Sutton in 2007 with a warning that she had a history of “narcotic-seeking” behavior and diagnoses of depression, anxiety, paranoid schizophrenia, and obsessive-compulsive disorder.

The patient was hospitalized in 2018 for complications from benzodiazepine use (prescribed by Dr. Sutton). She weighed 80 pounds at the time. Dr. Sutton continued to prescribe benzodiazepines and extreme doses of opioids – in excess of 2,000 morphine equivalent dose – “despite recognizing and documenting repeated instances of noncompliance with treatment for psychiatric conditions, and despite the known contraindications of long-term opioid use for patients with these mental illnesses,” according to the charging document.

Dr. Sutton continued to prescribe opioids despite two hospitalizations for overdoses, more than 20 failed urine drug screens that showed presence of illicit drugs such as cocaine, and documented excessive use of alprazolam (Xanax) and methadone.

The physician surrendered his Drug Enforcement Administration Certificate of Registration of Controlled Substances Privileges in February 2022 “as an indication of your good faith in desiring to remedy any incorrect or unlawful practices on your part,” according to a letter to Dr. Sutton from the State Medical Board of Ohio. In that September 2022 letter, the Board notified Dr. Sutton of its intention to possibly suspend or revoke his license.

Dr. Sutton did not request a hearing, and the Board permanently revoked his medical license on January 16.

The court will sentence Dr. Sutton on May 23, according to a report by WFMJ.

A version of this article originally appeared on Medscape.com.