ACR Annual Meeting 2020

Osteoporosis is frequently underdiagnosed and undertreated in men before and even after they have experienced a fracture, according to research presented at the virtual annual meeting of the American College of Rheumatology.

“This is an important public health concern,” as fractures contribute significantly to morbidity and mortality, said Jeffrey Curtis, MD, MS, MPH, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

Men are often overlooked, he said, “because it’s misconstrued as a disease that mainly, if not only, affects Caucasian women,” despite the fact that 20%-25% of fractures occur in men.

Emerging evidence suggests that men who have bone fractures have worse outcomes than women, Dr. Curtis said.
 

Guidelines lacking

Consistent guidelines for osteoporosis screening among men are also lacking, leading to ambiguity and increased disease burden.

Researchers studied records for a 5% random sample of male Medicare fee-for-service beneficiaries (n = 9,876) aged at least 65 years with a closed fragility fracture between January 2010 and September 2014. Average age for the men with fractures was 77.9 years, and the most common sites of the fracture were the spine, hip, and ankle.

They looked back to see whether these men had been effectively screened and treated.

Very few had.

“We found that 92.8% of them did not have any diagnosis or treatment of osteoporosis at baseline,” Curtis said. On top of that, less than 6% of men had undergone any dual-energy x-ray absorptiometry (DEXA) or bone mineral testing in the 2 years prior to their fracture.

Even men who had high-risk factors for falls, such as those using beta-blockers, mobility impairment, or a history of opioid use, were unlikely to be screened, he said.

Dr. Curtis’s data show there was actually a decline in DEXA scans from 2012 to 2014, and that decline was particularly high in men aged 75 years and older who are more likely to be at risk for fracture.

In addition to underscreening and undertreating before the fracture, Dr. Curtis said, “The treatment patterns after the fracture were not much better.” In the year after the fracture, “only about 10% of these men had BMD [bone mineral density] testing. Only 9% were treated with an osteoporosis medication.”

“Importantly, about 7% of the men in this large cohort went on to have one or more fractures in the next year,” he added.

Reasons for undertreatment

Reasons for the poor rates of diagnosis and treatment may begin with patients not having symptoms. Therefore, they aren’t coming into doctors’ offices asking to be screened. “Even if they break bones, they may not know enough to ask how to prevent the next fracture,” Dr. Curtis said.

There’s a financial obstacle as well, Dr. Curtis explained. “U.S. legislation that provides population screening for Medicare patients really, for men, is quite dissimilar to the near-universal coverage for women. So many clinicians worry they won’t get reimbursed if they order DEXA in men for screening.”

Additionally, postfracture quality-of-care guidelines that are reimbursed as part of the Medicare Access and CHIP Reauthorization Act of 2015 and the Merit-based Incentive Payment System program specifically exclude men, he noted.

Better management of male osteoporosis, including early identification of at-risk individuals is clearly warranted, he said, so they can be screened and put on effective therapy.

Sonali Khandelwal, MD, a rheumatologist with Rush University Medical Center, Chicago, who was not part of the research, agreed.

She said in an interview that part of the problem is that diagnosis and treatment could come from a variety of specialists – endocrinologists, rheumatologists, orthopedists, and primary care physicians – and each may think it falls in another’s realm.

At Rush and some other sites nationally, she said, an alert is registered in electronic medical records flagging any patient who may need bone density screening based on age, medications, or history.

Rush University also has a fracture liaison service under which everyone hospitalized there who may have had a history of a fracture or is admitted with a fracture gets followed up with screening and treatment, “to capture those patients who may not have come through the system otherwise.”

She said guidelines have called for DEXA screening for men at age 70, but she said clinical screening should start younger – as young as 50 – for patients with conditions such as lupus, rheumatoid arthritis, hypogonadism, or those on chronic steroids.

Dr. Khandelwal said that, even when an insurance company doesn›t typically cover bone density screening for men, physicians can often make a case for reimbursement if the patient has a history of falls or fractures.

“In the long run, preventing a fracture is saving so much more money than when you get a fracture and end up in a hospital and have to go to a nursing home,” she said.

Dr. Curtis reported relationships with AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Gilead Sciences, and Sanofi. Dr. Khandelwal reported no relevant financial relationships.

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

Osteoporosis is frequently underdiagnosed and undertreated in men before and even after they have experienced a fracture, according to research presented at the virtual annual meeting of the American College of Rheumatology.

“This is an important public health concern,” as fractures contribute significantly to morbidity and mortality, said Jeffrey Curtis, MD, MS, MPH, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

Men are often overlooked, he said, “because it’s misconstrued as a disease that mainly, if not only, affects Caucasian women,” despite the fact that 20%-25% of fractures occur in men.

Emerging evidence suggests that men who have bone fractures have worse outcomes than women, Dr. Curtis said.
 

Guidelines lacking

Consistent guidelines for osteoporosis screening among men are also lacking, leading to ambiguity and increased disease burden.

Researchers studied records for a 5% random sample of male Medicare fee-for-service beneficiaries (n = 9,876) aged at least 65 years with a closed fragility fracture between January 2010 and September 2014. Average age for the men with fractures was 77.9 years, and the most common sites of the fracture were the spine, hip, and ankle.

They looked back to see whether these men had been effectively screened and treated.

Very few had.

“We found that 92.8% of them did not have any diagnosis or treatment of osteoporosis at baseline,” Curtis said. On top of that, less than 6% of men had undergone any dual-energy x-ray absorptiometry (DEXA) or bone mineral testing in the 2 years prior to their fracture.

Even men who had high-risk factors for falls, such as those using beta-blockers, mobility impairment, or a history of opioid use, were unlikely to be screened, he said.

Dr. Curtis’s data show there was actually a decline in DEXA scans from 2012 to 2014, and that decline was particularly high in men aged 75 years and older who are more likely to be at risk for fracture.

In addition to underscreening and undertreating before the fracture, Dr. Curtis said, “The treatment patterns after the fracture were not much better.” In the year after the fracture, “only about 10% of these men had BMD [bone mineral density] testing. Only 9% were treated with an osteoporosis medication.”

“Importantly, about 7% of the men in this large cohort went on to have one or more fractures in the next year,” he added.

Reasons for undertreatment

Reasons for the poor rates of diagnosis and treatment may begin with patients not having symptoms. Therefore, they aren’t coming into doctors’ offices asking to be screened. “Even if they break bones, they may not know enough to ask how to prevent the next fracture,” Dr. Curtis said.

There’s a financial obstacle as well, Dr. Curtis explained. “U.S. legislation that provides population screening for Medicare patients really, for men, is quite dissimilar to the near-universal coverage for women. So many clinicians worry they won’t get reimbursed if they order DEXA in men for screening.”

Additionally, postfracture quality-of-care guidelines that are reimbursed as part of the Medicare Access and CHIP Reauthorization Act of 2015 and the Merit-based Incentive Payment System program specifically exclude men, he noted.

Better management of male osteoporosis, including early identification of at-risk individuals is clearly warranted, he said, so they can be screened and put on effective therapy.

Sonali Khandelwal, MD, a rheumatologist with Rush University Medical Center, Chicago, who was not part of the research, agreed.

She said in an interview that part of the problem is that diagnosis and treatment could come from a variety of specialists – endocrinologists, rheumatologists, orthopedists, and primary care physicians – and each may think it falls in another’s realm.

At Rush and some other sites nationally, she said, an alert is registered in electronic medical records flagging any patient who may need bone density screening based on age, medications, or history.

Rush University also has a fracture liaison service under which everyone hospitalized there who may have had a history of a fracture or is admitted with a fracture gets followed up with screening and treatment, “to capture those patients who may not have come through the system otherwise.”

She said guidelines have called for DEXA screening for men at age 70, but she said clinical screening should start younger – as young as 50 – for patients with conditions such as lupus, rheumatoid arthritis, hypogonadism, or those on chronic steroids.

Dr. Khandelwal said that, even when an insurance company doesn›t typically cover bone density screening for men, physicians can often make a case for reimbursement if the patient has a history of falls or fractures.

“In the long run, preventing a fracture is saving so much more money than when you get a fracture and end up in a hospital and have to go to a nursing home,” she said.

Dr. Curtis reported relationships with AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Gilead Sciences, and Sanofi. Dr. Khandelwal reported no relevant financial relationships.

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

Osteoporosis is frequently underdiagnosed and undertreated in men before and even after they have experienced a fracture, according to research presented at the virtual annual meeting of the American College of Rheumatology.

“This is an important public health concern,” as fractures contribute significantly to morbidity and mortality, said Jeffrey Curtis, MD, MS, MPH, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

Men are often overlooked, he said, “because it’s misconstrued as a disease that mainly, if not only, affects Caucasian women,” despite the fact that 20%-25% of fractures occur in men.

Emerging evidence suggests that men who have bone fractures have worse outcomes than women, Dr. Curtis said.
 

Guidelines lacking

Consistent guidelines for osteoporosis screening among men are also lacking, leading to ambiguity and increased disease burden.

Researchers studied records for a 5% random sample of male Medicare fee-for-service beneficiaries (n = 9,876) aged at least 65 years with a closed fragility fracture between January 2010 and September 2014. Average age for the men with fractures was 77.9 years, and the most common sites of the fracture were the spine, hip, and ankle.

They looked back to see whether these men had been effectively screened and treated.

Very few had.

“We found that 92.8% of them did not have any diagnosis or treatment of osteoporosis at baseline,” Curtis said. On top of that, less than 6% of men had undergone any dual-energy x-ray absorptiometry (DEXA) or bone mineral testing in the 2 years prior to their fracture.

Even men who had high-risk factors for falls, such as those using beta-blockers, mobility impairment, or a history of opioid use, were unlikely to be screened, he said.

Dr. Curtis’s data show there was actually a decline in DEXA scans from 2012 to 2014, and that decline was particularly high in men aged 75 years and older who are more likely to be at risk for fracture.

In addition to underscreening and undertreating before the fracture, Dr. Curtis said, “The treatment patterns after the fracture were not much better.” In the year after the fracture, “only about 10% of these men had BMD [bone mineral density] testing. Only 9% were treated with an osteoporosis medication.”

“Importantly, about 7% of the men in this large cohort went on to have one or more fractures in the next year,” he added.

Reasons for undertreatment

Reasons for the poor rates of diagnosis and treatment may begin with patients not having symptoms. Therefore, they aren’t coming into doctors’ offices asking to be screened. “Even if they break bones, they may not know enough to ask how to prevent the next fracture,” Dr. Curtis said.

There’s a financial obstacle as well, Dr. Curtis explained. “U.S. legislation that provides population screening for Medicare patients really, for men, is quite dissimilar to the near-universal coverage for women. So many clinicians worry they won’t get reimbursed if they order DEXA in men for screening.”

Additionally, postfracture quality-of-care guidelines that are reimbursed as part of the Medicare Access and CHIP Reauthorization Act of 2015 and the Merit-based Incentive Payment System program specifically exclude men, he noted.

Better management of male osteoporosis, including early identification of at-risk individuals is clearly warranted, he said, so they can be screened and put on effective therapy.

Sonali Khandelwal, MD, a rheumatologist with Rush University Medical Center, Chicago, who was not part of the research, agreed.

She said in an interview that part of the problem is that diagnosis and treatment could come from a variety of specialists – endocrinologists, rheumatologists, orthopedists, and primary care physicians – and each may think it falls in another’s realm.

At Rush and some other sites nationally, she said, an alert is registered in electronic medical records flagging any patient who may need bone density screening based on age, medications, or history.

Rush University also has a fracture liaison service under which everyone hospitalized there who may have had a history of a fracture or is admitted with a fracture gets followed up with screening and treatment, “to capture those patients who may not have come through the system otherwise.”

She said guidelines have called for DEXA screening for men at age 70, but she said clinical screening should start younger – as young as 50 – for patients with conditions such as lupus, rheumatoid arthritis, hypogonadism, or those on chronic steroids.

Dr. Khandelwal said that, even when an insurance company doesn›t typically cover bone density screening for men, physicians can often make a case for reimbursement if the patient has a history of falls or fractures.

“In the long run, preventing a fracture is saving so much more money than when you get a fracture and end up in a hospital and have to go to a nursing home,” she said.

Dr. Curtis reported relationships with AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Gilead Sciences, and Sanofi. Dr. Khandelwal reported no relevant financial relationships.

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

Timing is everything when it comes to the use of the anabolic agent romosozumab (Evenity) for the treatment of advanced osteoporosis, a review of clinical trials suggests.

In four studies with treatment sequences in which romosozumab was administered either before or following the use of an antiresorptive agent, initial treatment with 1 year of romosozumab produced substantial bone mineral density (BMD) gains in the total hip and lumbar spine.

Transition from romosozumab to a potent resorptive agent, either alendronate or denosumab (Prolia) augmented the initial gains, reported Felicia Cosman, MD, professor of clinical medicine at Columbia University, New York.

Romosozumab was the third approved agent in its class, following teriparatide in 2002, and abaloparatide (Tymlos) in 2017, both of which have been shown to produce rapid reductions in fracture risk and large improvements in BMD when they were administered up front, followed by an antiresorptive agent.

“But since romosozumab has a very different mechanism of action compared to both teriparatide and abaloparatide, we didn’t know if treatment sequence would be as important for this agent as it was for teriparatide,” she said during a press briefing prior to her presentation of the data in an oral abstract session at the virtual annual meeting of the American College of Rheumatology.

Two-for-one

Romosozumab is unique in that it both increases bone formation and decreases bone resorption, and has been shown in treatment-naive postmenopausal women with osteoporosis to significantly improve BMD and reduce fracture risk, compared with either placebo or alendronate. Romosozumab has also been studied as sequential therapy in patients treated initially with either alendronate or denosumab.

To see whether treatment sequence could have differential effects on clinical outcomes for patients with osteoporosis, Dr. Cosman and colleagues looked at results from four clinical trials, using levels of bone turnover markers (procollagen type I N-terminal propeptide [PINP] and beta-isomer of the C-terminal telopeptide of type I collagen [beta-CTX]) and BMD gains in the total hip and spine as outcomes.

The two trials of romosozumab in treatment-naive women were the ARCH trial comparing romosozumab with alendronate in a double-blind phase for 1 year, followed by 1 year of open-label alendronate, and the FRAME trial, in which romosozumab was compared with placebo in a 1-year double-blind phase, followed by 1-year of open-label denosumab.

The two trials of romosozumab in women treated initially with antiresorptive agents were the STRUCTURE trial in which patients on oral bisphosphonates for at least 3 years or alendronate 70 mg weekly for 1 year were randomized to receive either romosozumab or teriparatide, and a phase 2 trial (NCT00896532) that included a 24-month romosozumab or placebo treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.

Total hip BMD gains

In the ARCH trial, total hip BMD increased 6.2% with 1 year of romosozumab, and a cumulative total of 7.1% with the 2-year romosozumab/alendronate sequence. In the FRAME trial, patients gained 6.8% in total hip BMD after 1 year of romosozumab and a total of 8.8% after 2 years of romosozumab followed by denosumab.

In contrast, in the STRUCTURE trial, patients treated for 1 year or longer with alendronate and then with 1 year of romosozumab had a 2.9% BMD gain in the total hip. In the phase 2 trial, 1 year of romosozumab following 1 year of denosumab yielded a 0.9% BMD gain, for a total gain of 3.8% with the denosumab sequence.
 

Lumbar spine BMD gains

In ARCH, lumbar spine BMD increased 13.7% with 1 year of romosozumab, and a total of 15.2% with the 2-year sequence of romosozumab followed by alendronate. Similarly, in FRAME, patients gained 13.3% in BMD after a year of romosozumab, and total of 17.6% by the end of the 2-year romosozumab/denosumab sequence.

In contrast, in STRUCTURE, patients who had previously been on alendronate for at least 1 year had a gain of 9.8% after 1 year of romosozumab, and in the phase 2 study, patients who had been on denosumab for 1 year had an increase in lumbar spine BMD of 5.3% after 1 year on romosozumab, and a total gain of 11.5% at the end of the 2-year sequence.
 

Serum PINP and beta-CTX

Looking at the markers of bone turnover, the investigators saw that, in both ARCH and FRAME, PINP peaked at over 80% of baseline at 1 month, and then continued to steadily decline past 1 year. The beta-CTX nadir was 40%-50% below baseline at 1 year.

At the end of year 2, the PINP nadir was –67% with follow-on alendronate, and –69% with denosumab, and the beta-CTX nadir was –72% and –92%, respectively.

In the two trials where romosozumab was the follow-on therapy, however, the trends were distinctly different. In STRUCTURE, for example, PINP peaked at 141% of baseline at 1 month, and then returned toward baseline, whereas beta-CTX remained largely unchanged.

In the phase 2 trial, PINP peaked at 28% above baseline at 9 months, and then only slightly declined, and beta-CTX peaked at 211% at the end of 1 year of romosozumab.

Best used up front

“This study is important, because it suggests that for the three bone-building drugs that the best effects will really be attained on bone strength if the agents are used as initial therapy in very-high-risk patients. Those are people who have sustained fractures within the preceding 2 years, who had multiple fractures at any point in their adulthood, and who present with very low BMD, particularly if they have any associated clinical risk factors such as family history or other underlying diseases or medications that have detrimental effects on bone,” Dr. Cosman said at the briefing.

Marcy Bolster, MD, from the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston, and associate professor of medicine at Harvard Medical School in Boston, who was not involved in the study, commented that the study provides important information for clinicians who treat patients with osteoporosis.

“We have an increasing number of medications available for use in the treatment of patients with osteoporosis, and as we consider the importance of reducing fracture risk, the duration of therapy, the timing of a bisphosphonate holiday, it is essential that we consider any advantages to the order or sequence of our medications,” she said when asked for comment.

“This study provides evidence supporting the concept of the ‘anabolic window’ in which there is a demonstrated advantage in treating patients with an anabolic agent prior to treatment with an antiresorptive agent, and while gains in bone mineral density were achieved with either order of medication use, the gains were more dramatic with treatment with romosozumab as the first agent,” she added.

Dr. Bolster also noted it will be important to demonstrate reduction in fracture risk as well as gain in BMD.

The study was sponsored by Amgen, Astellas, and UCB. Dr. Cosman disclosed grants/research support from Amgen, and consulting fees and speaker activities for Amgen and Radius Health. Dr. Bolster disclosed relationships with AbbVie, Corbus, Cumberland, Gilead, Johnson & Johnson, and Pfizer.

SOURCE: Cosman F et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1973.

Timing is everything when it comes to the use of the anabolic agent romosozumab (Evenity) for the treatment of advanced osteoporosis, a review of clinical trials suggests.

In four studies with treatment sequences in which romosozumab was administered either before or following the use of an antiresorptive agent, initial treatment with 1 year of romosozumab produced substantial bone mineral density (BMD) gains in the total hip and lumbar spine.

Transition from romosozumab to a potent resorptive agent, either alendronate or denosumab (Prolia) augmented the initial gains, reported Felicia Cosman, MD, professor of clinical medicine at Columbia University, New York.

Romosozumab was the third approved agent in its class, following teriparatide in 2002, and abaloparatide (Tymlos) in 2017, both of which have been shown to produce rapid reductions in fracture risk and large improvements in BMD when they were administered up front, followed by an antiresorptive agent.

“But since romosozumab has a very different mechanism of action compared to both teriparatide and abaloparatide, we didn’t know if treatment sequence would be as important for this agent as it was for teriparatide,” she said during a press briefing prior to her presentation of the data in an oral abstract session at the virtual annual meeting of the American College of Rheumatology.

Two-for-one

Romosozumab is unique in that it both increases bone formation and decreases bone resorption, and has been shown in treatment-naive postmenopausal women with osteoporosis to significantly improve BMD and reduce fracture risk, compared with either placebo or alendronate. Romosozumab has also been studied as sequential therapy in patients treated initially with either alendronate or denosumab.

To see whether treatment sequence could have differential effects on clinical outcomes for patients with osteoporosis, Dr. Cosman and colleagues looked at results from four clinical trials, using levels of bone turnover markers (procollagen type I N-terminal propeptide [PINP] and beta-isomer of the C-terminal telopeptide of type I collagen [beta-CTX]) and BMD gains in the total hip and spine as outcomes.

The two trials of romosozumab in treatment-naive women were the ARCH trial comparing romosozumab with alendronate in a double-blind phase for 1 year, followed by 1 year of open-label alendronate, and the FRAME trial, in which romosozumab was compared with placebo in a 1-year double-blind phase, followed by 1-year of open-label denosumab.

The two trials of romosozumab in women treated initially with antiresorptive agents were the STRUCTURE trial in which patients on oral bisphosphonates for at least 3 years or alendronate 70 mg weekly for 1 year were randomized to receive either romosozumab or teriparatide, and a phase 2 trial (NCT00896532) that included a 24-month romosozumab or placebo treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.

Total hip BMD gains

In the ARCH trial, total hip BMD increased 6.2% with 1 year of romosozumab, and a cumulative total of 7.1% with the 2-year romosozumab/alendronate sequence. In the FRAME trial, patients gained 6.8% in total hip BMD after 1 year of romosozumab and a total of 8.8% after 2 years of romosozumab followed by denosumab.

In contrast, in the STRUCTURE trial, patients treated for 1 year or longer with alendronate and then with 1 year of romosozumab had a 2.9% BMD gain in the total hip. In the phase 2 trial, 1 year of romosozumab following 1 year of denosumab yielded a 0.9% BMD gain, for a total gain of 3.8% with the denosumab sequence.
 

Lumbar spine BMD gains

In ARCH, lumbar spine BMD increased 13.7% with 1 year of romosozumab, and a total of 15.2% with the 2-year sequence of romosozumab followed by alendronate. Similarly, in FRAME, patients gained 13.3% in BMD after a year of romosozumab, and total of 17.6% by the end of the 2-year romosozumab/denosumab sequence.

In contrast, in STRUCTURE, patients who had previously been on alendronate for at least 1 year had a gain of 9.8% after 1 year of romosozumab, and in the phase 2 study, patients who had been on denosumab for 1 year had an increase in lumbar spine BMD of 5.3% after 1 year on romosozumab, and a total gain of 11.5% at the end of the 2-year sequence.
 

Serum PINP and beta-CTX

Looking at the markers of bone turnover, the investigators saw that, in both ARCH and FRAME, PINP peaked at over 80% of baseline at 1 month, and then continued to steadily decline past 1 year. The beta-CTX nadir was 40%-50% below baseline at 1 year.

At the end of year 2, the PINP nadir was –67% with follow-on alendronate, and –69% with denosumab, and the beta-CTX nadir was –72% and –92%, respectively.

In the two trials where romosozumab was the follow-on therapy, however, the trends were distinctly different. In STRUCTURE, for example, PINP peaked at 141% of baseline at 1 month, and then returned toward baseline, whereas beta-CTX remained largely unchanged.

In the phase 2 trial, PINP peaked at 28% above baseline at 9 months, and then only slightly declined, and beta-CTX peaked at 211% at the end of 1 year of romosozumab.

Best used up front

“This study is important, because it suggests that for the three bone-building drugs that the best effects will really be attained on bone strength if the agents are used as initial therapy in very-high-risk patients. Those are people who have sustained fractures within the preceding 2 years, who had multiple fractures at any point in their adulthood, and who present with very low BMD, particularly if they have any associated clinical risk factors such as family history or other underlying diseases or medications that have detrimental effects on bone,” Dr. Cosman said at the briefing.

Marcy Bolster, MD, from the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston, and associate professor of medicine at Harvard Medical School in Boston, who was not involved in the study, commented that the study provides important information for clinicians who treat patients with osteoporosis.

“We have an increasing number of medications available for use in the treatment of patients with osteoporosis, and as we consider the importance of reducing fracture risk, the duration of therapy, the timing of a bisphosphonate holiday, it is essential that we consider any advantages to the order or sequence of our medications,” she said when asked for comment.

“This study provides evidence supporting the concept of the ‘anabolic window’ in which there is a demonstrated advantage in treating patients with an anabolic agent prior to treatment with an antiresorptive agent, and while gains in bone mineral density were achieved with either order of medication use, the gains were more dramatic with treatment with romosozumab as the first agent,” she added.

Dr. Bolster also noted it will be important to demonstrate reduction in fracture risk as well as gain in BMD.

The study was sponsored by Amgen, Astellas, and UCB. Dr. Cosman disclosed grants/research support from Amgen, and consulting fees and speaker activities for Amgen and Radius Health. Dr. Bolster disclosed relationships with AbbVie, Corbus, Cumberland, Gilead, Johnson & Johnson, and Pfizer.

SOURCE: Cosman F et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1973.

Timing is everything when it comes to the use of the anabolic agent romosozumab (Evenity) for the treatment of advanced osteoporosis, a review of clinical trials suggests.

In four studies with treatment sequences in which romosozumab was administered either before or following the use of an antiresorptive agent, initial treatment with 1 year of romosozumab produced substantial bone mineral density (BMD) gains in the total hip and lumbar spine.

Transition from romosozumab to a potent resorptive agent, either alendronate or denosumab (Prolia) augmented the initial gains, reported Felicia Cosman, MD, professor of clinical medicine at Columbia University, New York.

Romosozumab was the third approved agent in its class, following teriparatide in 2002, and abaloparatide (Tymlos) in 2017, both of which have been shown to produce rapid reductions in fracture risk and large improvements in BMD when they were administered up front, followed by an antiresorptive agent.

“But since romosozumab has a very different mechanism of action compared to both teriparatide and abaloparatide, we didn’t know if treatment sequence would be as important for this agent as it was for teriparatide,” she said during a press briefing prior to her presentation of the data in an oral abstract session at the virtual annual meeting of the American College of Rheumatology.

Two-for-one

Romosozumab is unique in that it both increases bone formation and decreases bone resorption, and has been shown in treatment-naive postmenopausal women with osteoporosis to significantly improve BMD and reduce fracture risk, compared with either placebo or alendronate. Romosozumab has also been studied as sequential therapy in patients treated initially with either alendronate or denosumab.

To see whether treatment sequence could have differential effects on clinical outcomes for patients with osteoporosis, Dr. Cosman and colleagues looked at results from four clinical trials, using levels of bone turnover markers (procollagen type I N-terminal propeptide [PINP] and beta-isomer of the C-terminal telopeptide of type I collagen [beta-CTX]) and BMD gains in the total hip and spine as outcomes.

The two trials of romosozumab in treatment-naive women were the ARCH trial comparing romosozumab with alendronate in a double-blind phase for 1 year, followed by 1 year of open-label alendronate, and the FRAME trial, in which romosozumab was compared with placebo in a 1-year double-blind phase, followed by 1-year of open-label denosumab.

The two trials of romosozumab in women treated initially with antiresorptive agents were the STRUCTURE trial in which patients on oral bisphosphonates for at least 3 years or alendronate 70 mg weekly for 1 year were randomized to receive either romosozumab or teriparatide, and a phase 2 trial (NCT00896532) that included a 24-month romosozumab or placebo treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.

Total hip BMD gains

In the ARCH trial, total hip BMD increased 6.2% with 1 year of romosozumab, and a cumulative total of 7.1% with the 2-year romosozumab/alendronate sequence. In the FRAME trial, patients gained 6.8% in total hip BMD after 1 year of romosozumab and a total of 8.8% after 2 years of romosozumab followed by denosumab.

In contrast, in the STRUCTURE trial, patients treated for 1 year or longer with alendronate and then with 1 year of romosozumab had a 2.9% BMD gain in the total hip. In the phase 2 trial, 1 year of romosozumab following 1 year of denosumab yielded a 0.9% BMD gain, for a total gain of 3.8% with the denosumab sequence.
 

Lumbar spine BMD gains

In ARCH, lumbar spine BMD increased 13.7% with 1 year of romosozumab, and a total of 15.2% with the 2-year sequence of romosozumab followed by alendronate. Similarly, in FRAME, patients gained 13.3% in BMD after a year of romosozumab, and total of 17.6% by the end of the 2-year romosozumab/denosumab sequence.

In contrast, in STRUCTURE, patients who had previously been on alendronate for at least 1 year had a gain of 9.8% after 1 year of romosozumab, and in the phase 2 study, patients who had been on denosumab for 1 year had an increase in lumbar spine BMD of 5.3% after 1 year on romosozumab, and a total gain of 11.5% at the end of the 2-year sequence.
 

Serum PINP and beta-CTX

Looking at the markers of bone turnover, the investigators saw that, in both ARCH and FRAME, PINP peaked at over 80% of baseline at 1 month, and then continued to steadily decline past 1 year. The beta-CTX nadir was 40%-50% below baseline at 1 year.

At the end of year 2, the PINP nadir was –67% with follow-on alendronate, and –69% with denosumab, and the beta-CTX nadir was –72% and –92%, respectively.

In the two trials where romosozumab was the follow-on therapy, however, the trends were distinctly different. In STRUCTURE, for example, PINP peaked at 141% of baseline at 1 month, and then returned toward baseline, whereas beta-CTX remained largely unchanged.

In the phase 2 trial, PINP peaked at 28% above baseline at 9 months, and then only slightly declined, and beta-CTX peaked at 211% at the end of 1 year of romosozumab.

Best used up front

“This study is important, because it suggests that for the three bone-building drugs that the best effects will really be attained on bone strength if the agents are used as initial therapy in very-high-risk patients. Those are people who have sustained fractures within the preceding 2 years, who had multiple fractures at any point in their adulthood, and who present with very low BMD, particularly if they have any associated clinical risk factors such as family history or other underlying diseases or medications that have detrimental effects on bone,” Dr. Cosman said at the briefing.

Marcy Bolster, MD, from the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston, and associate professor of medicine at Harvard Medical School in Boston, who was not involved in the study, commented that the study provides important information for clinicians who treat patients with osteoporosis.

“We have an increasing number of medications available for use in the treatment of patients with osteoporosis, and as we consider the importance of reducing fracture risk, the duration of therapy, the timing of a bisphosphonate holiday, it is essential that we consider any advantages to the order or sequence of our medications,” she said when asked for comment.

“This study provides evidence supporting the concept of the ‘anabolic window’ in which there is a demonstrated advantage in treating patients with an anabolic agent prior to treatment with an antiresorptive agent, and while gains in bone mineral density were achieved with either order of medication use, the gains were more dramatic with treatment with romosozumab as the first agent,” she added.

Dr. Bolster also noted it will be important to demonstrate reduction in fracture risk as well as gain in BMD.

The study was sponsored by Amgen, Astellas, and UCB. Dr. Cosman disclosed grants/research support from Amgen, and consulting fees and speaker activities for Amgen and Radius Health. Dr. Bolster disclosed relationships with AbbVie, Corbus, Cumberland, Gilead, Johnson & Johnson, and Pfizer.

SOURCE: Cosman F et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1973.

Survivors of Kawasaki disease remain at a higher long-term risk for cardiovascular events into young adulthood, including myocardial infarction, compared to people without the disease, new evidence reveals. The elevated risks emerged in survivors both with and without cardiovascular involvement at the time of initial diagnosis.

Overall risk of cardiovascular events was highest in the first year following Kawasaki disease diagnosis, and about 10 times greater than in healthy children, Cal Robinson, MD, said during a press conference at the virtual annual meeting of the American College of Rheumatology.

“The risk gradually decreased over time. However, even 10 years after diagnosis of their illness, they still had a 39% higher risk,” said study author Dr. Robinson, a PGY4 pediatric nephrology fellow at The Hospital for Sick Children in Toronto.

Dr. Robinson also put the numbers in perspective. “We fully acknowledged these are very rare events in children, especially healthy children, which is why we needed such a large cohort to study this. Interpret the numbers cautiously.”

In terms of patient and family counseling, “I would say children with Kawasaki disease have a higher risk of myocardial infarction, but the absolute risk is still low,” he added. For example, 16 Kawasaki disease survivors experienced a heart attack during follow-up, or 0.4% of the affected study population, compared to a rate of 0.1% among matched controls.

“These families are often very frightened after the initial Kawasaki disease diagnosis,” Dr. Robinson said. “We have to balance some discussion with what we know about Kawasaki disease without overly scaring or terrifying these families, who are already anxious.”

To quantify the incidence and timing of cardiovascular events and cardiac disease following diagnosis, Dr. Robinson and colleagues assessed large databases representing approximately 3 million children. They focused on children hospitalized with a Kawasaki disease diagnosis between 1995 and 2018. These children had a median length of stay of 3 days and 2.5% were admitted to critical care. The investigators matched his population 1:100 to unaffected children in Ontario.

Follow-up was up to 24 years (median, 11 years) in this retrospective, population-based cohort study.

Risks raised over a decade and beyond

Compared to matched controls, Kawasaki disease survivors had a higher risk for a cardiac event in the first year following diagnosis (adjusted hazard ratio, 11.65; 95% confidence interval, 10.34-13.13). The 1- to 5-year risk was lower (aHR, 3.35), a trend that continued between 5 and 10 years (aHR, 1.87) and as well as after more than 10 years (aHR, 1.39).

The risk of major adverse cardiac events (MACE, a composite of myocardial infarction, stroke, or cardiovascular death) was likewise highest in the first year after diagnosis (aHR, 3.27), followed by a 51% greater risk at 1-5 years, a 113% increased risk at 5-10 years, and a 17% elevated risk after 10 years.

The investigators compared the 144 Kawasaki disease survivors who experienced a coronary artery aneurysm (CAA) within 90 days of hospital admission to the 4,453 others who did not have a CAA. The risk for a composite cardiovascular event was elevated at each time point among those with a history of CAA, especially in the first year. The adjusted HR was 33.12 in the CAA group versus 10.44 in the non-CAA group.

“The most interesting finding of this study was that children with Kawasaki syndrome are at higher risk for composite cardiovascular events and major adverse cardiac events even if they were not diagnosed with coronary artery aneurysm,” session comoderator Shervin Assassi, MD, professor of medicine and director of division of rheumatology at the University of Texas Health Science Center at Houston, said when asked to comment.

Dr. Robinson and colleagues also looked at outcomes based on presence or absence of coronary involvement at the time of Kawasaki disease diagnosis. For example, among those with initial coronary involvement, 15% later experienced a cardiovascular event and 10% experienced a major cardiovascular event.

“However, we were specifically interested in looking at children without initial coronary involvement. In this group, we also found these children were at increased risk for cardiovascular events compared to children without Kawasaki disease,” Dr. Robinson said. He said the distinction is important because approximately 95% of children diagnosed with Kawasaki disease do not feature initial coronary involvement.

In terms of clinical care, “our data provides an early signal that Kawasaki disease survivors – including those without initial coronary involvement – may be at higher risk of cardiovascular events into early adulthood.”
 

A call for closer monitoring

“Based on our results, we find that Kawasaki disease survivors may benefit from additional follow-up and surveillance for cardiovascular disease risk factors, such as obesity, high blood pressure, and high cholesterol,” Dr. Robinson said. Early identification of heightened risk could allow physicians to more closely monitor this subgroup and emphasize potentially beneficial lifestyle modifications, including increasing physical activity, implementing a heart healthy diet, and avoiding smoking.

Mortality was not significantly different between groups. “Despite the risk of cardiac events we found, death was uncommon,” Dr. Robinson said. Among children with Kawasaki disease, 1 in 500 died during follow-up, so “the risk of death was actually lower than for children without Kawasaki disease.”

Similar findings of lower mortality have been reported in research out of Japan, he added during a plenary presentation at ACR 2020. Future research is warranted to evaluate this finding further, Dr. Robinson said.
 

Future plans

Going forward, the investigators plan to evaluate noncardiovascular outcomes in this patient population. They would also like to examine health care utilization following a diagnosis of Kawasaki disease “to better understand what kind of follow-up is happening now in Ontario,” Dr. Robinson said.

Another unanswered question is whether the cardiovascular events observed in the study stem from atherosclerotic disease or a different mechanism among survivors of Kawasaki disease.

The research was supported by a McMaster University Resident Research Grant, a Hamilton Health Sciences New Investigator Award, and Ontario’s Institute for Clinical Evaluative Sciences. Dr. Robinson had no relevant financial disclosures.

SOURCE: Robinson C et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 0937.

Survivors of Kawasaki disease remain at a higher long-term risk for cardiovascular events into young adulthood, including myocardial infarction, compared to people without the disease, new evidence reveals. The elevated risks emerged in survivors both with and without cardiovascular involvement at the time of initial diagnosis.

Overall risk of cardiovascular events was highest in the first year following Kawasaki disease diagnosis, and about 10 times greater than in healthy children, Cal Robinson, MD, said during a press conference at the virtual annual meeting of the American College of Rheumatology.

“The risk gradually decreased over time. However, even 10 years after diagnosis of their illness, they still had a 39% higher risk,” said study author Dr. Robinson, a PGY4 pediatric nephrology fellow at The Hospital for Sick Children in Toronto.

Dr. Robinson also put the numbers in perspective. “We fully acknowledged these are very rare events in children, especially healthy children, which is why we needed such a large cohort to study this. Interpret the numbers cautiously.”

In terms of patient and family counseling, “I would say children with Kawasaki disease have a higher risk of myocardial infarction, but the absolute risk is still low,” he added. For example, 16 Kawasaki disease survivors experienced a heart attack during follow-up, or 0.4% of the affected study population, compared to a rate of 0.1% among matched controls.

“These families are often very frightened after the initial Kawasaki disease diagnosis,” Dr. Robinson said. “We have to balance some discussion with what we know about Kawasaki disease without overly scaring or terrifying these families, who are already anxious.”

To quantify the incidence and timing of cardiovascular events and cardiac disease following diagnosis, Dr. Robinson and colleagues assessed large databases representing approximately 3 million children. They focused on children hospitalized with a Kawasaki disease diagnosis between 1995 and 2018. These children had a median length of stay of 3 days and 2.5% were admitted to critical care. The investigators matched his population 1:100 to unaffected children in Ontario.

Follow-up was up to 24 years (median, 11 years) in this retrospective, population-based cohort study.

Risks raised over a decade and beyond

Compared to matched controls, Kawasaki disease survivors had a higher risk for a cardiac event in the first year following diagnosis (adjusted hazard ratio, 11.65; 95% confidence interval, 10.34-13.13). The 1- to 5-year risk was lower (aHR, 3.35), a trend that continued between 5 and 10 years (aHR, 1.87) and as well as after more than 10 years (aHR, 1.39).

The risk of major adverse cardiac events (MACE, a composite of myocardial infarction, stroke, or cardiovascular death) was likewise highest in the first year after diagnosis (aHR, 3.27), followed by a 51% greater risk at 1-5 years, a 113% increased risk at 5-10 years, and a 17% elevated risk after 10 years.

The investigators compared the 144 Kawasaki disease survivors who experienced a coronary artery aneurysm (CAA) within 90 days of hospital admission to the 4,453 others who did not have a CAA. The risk for a composite cardiovascular event was elevated at each time point among those with a history of CAA, especially in the first year. The adjusted HR was 33.12 in the CAA group versus 10.44 in the non-CAA group.

“The most interesting finding of this study was that children with Kawasaki syndrome are at higher risk for composite cardiovascular events and major adverse cardiac events even if they were not diagnosed with coronary artery aneurysm,” session comoderator Shervin Assassi, MD, professor of medicine and director of division of rheumatology at the University of Texas Health Science Center at Houston, said when asked to comment.

Dr. Robinson and colleagues also looked at outcomes based on presence or absence of coronary involvement at the time of Kawasaki disease diagnosis. For example, among those with initial coronary involvement, 15% later experienced a cardiovascular event and 10% experienced a major cardiovascular event.

“However, we were specifically interested in looking at children without initial coronary involvement. In this group, we also found these children were at increased risk for cardiovascular events compared to children without Kawasaki disease,” Dr. Robinson said. He said the distinction is important because approximately 95% of children diagnosed with Kawasaki disease do not feature initial coronary involvement.

In terms of clinical care, “our data provides an early signal that Kawasaki disease survivors – including those without initial coronary involvement – may be at higher risk of cardiovascular events into early adulthood.”
 

A call for closer monitoring

“Based on our results, we find that Kawasaki disease survivors may benefit from additional follow-up and surveillance for cardiovascular disease risk factors, such as obesity, high blood pressure, and high cholesterol,” Dr. Robinson said. Early identification of heightened risk could allow physicians to more closely monitor this subgroup and emphasize potentially beneficial lifestyle modifications, including increasing physical activity, implementing a heart healthy diet, and avoiding smoking.

Mortality was not significantly different between groups. “Despite the risk of cardiac events we found, death was uncommon,” Dr. Robinson said. Among children with Kawasaki disease, 1 in 500 died during follow-up, so “the risk of death was actually lower than for children without Kawasaki disease.”

Similar findings of lower mortality have been reported in research out of Japan, he added during a plenary presentation at ACR 2020. Future research is warranted to evaluate this finding further, Dr. Robinson said.
 

Future plans

Going forward, the investigators plan to evaluate noncardiovascular outcomes in this patient population. They would also like to examine health care utilization following a diagnosis of Kawasaki disease “to better understand what kind of follow-up is happening now in Ontario,” Dr. Robinson said.

Another unanswered question is whether the cardiovascular events observed in the study stem from atherosclerotic disease or a different mechanism among survivors of Kawasaki disease.

The research was supported by a McMaster University Resident Research Grant, a Hamilton Health Sciences New Investigator Award, and Ontario’s Institute for Clinical Evaluative Sciences. Dr. Robinson had no relevant financial disclosures.

SOURCE: Robinson C et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 0937.

Survivors of Kawasaki disease remain at a higher long-term risk for cardiovascular events into young adulthood, including myocardial infarction, compared to people without the disease, new evidence reveals. The elevated risks emerged in survivors both with and without cardiovascular involvement at the time of initial diagnosis.

Overall risk of cardiovascular events was highest in the first year following Kawasaki disease diagnosis, and about 10 times greater than in healthy children, Cal Robinson, MD, said during a press conference at the virtual annual meeting of the American College of Rheumatology.

“The risk gradually decreased over time. However, even 10 years after diagnosis of their illness, they still had a 39% higher risk,” said study author Dr. Robinson, a PGY4 pediatric nephrology fellow at The Hospital for Sick Children in Toronto.

Dr. Robinson also put the numbers in perspective. “We fully acknowledged these are very rare events in children, especially healthy children, which is why we needed such a large cohort to study this. Interpret the numbers cautiously.”

In terms of patient and family counseling, “I would say children with Kawasaki disease have a higher risk of myocardial infarction, but the absolute risk is still low,” he added. For example, 16 Kawasaki disease survivors experienced a heart attack during follow-up, or 0.4% of the affected study population, compared to a rate of 0.1% among matched controls.

“These families are often very frightened after the initial Kawasaki disease diagnosis,” Dr. Robinson said. “We have to balance some discussion with what we know about Kawasaki disease without overly scaring or terrifying these families, who are already anxious.”

To quantify the incidence and timing of cardiovascular events and cardiac disease following diagnosis, Dr. Robinson and colleagues assessed large databases representing approximately 3 million children. They focused on children hospitalized with a Kawasaki disease diagnosis between 1995 and 2018. These children had a median length of stay of 3 days and 2.5% were admitted to critical care. The investigators matched his population 1:100 to unaffected children in Ontario.

Follow-up was up to 24 years (median, 11 years) in this retrospective, population-based cohort study.

Risks raised over a decade and beyond

Compared to matched controls, Kawasaki disease survivors had a higher risk for a cardiac event in the first year following diagnosis (adjusted hazard ratio, 11.65; 95% confidence interval, 10.34-13.13). The 1- to 5-year risk was lower (aHR, 3.35), a trend that continued between 5 and 10 years (aHR, 1.87) and as well as after more than 10 years (aHR, 1.39).

The risk of major adverse cardiac events (MACE, a composite of myocardial infarction, stroke, or cardiovascular death) was likewise highest in the first year after diagnosis (aHR, 3.27), followed by a 51% greater risk at 1-5 years, a 113% increased risk at 5-10 years, and a 17% elevated risk after 10 years.

The investigators compared the 144 Kawasaki disease survivors who experienced a coronary artery aneurysm (CAA) within 90 days of hospital admission to the 4,453 others who did not have a CAA. The risk for a composite cardiovascular event was elevated at each time point among those with a history of CAA, especially in the first year. The adjusted HR was 33.12 in the CAA group versus 10.44 in the non-CAA group.

“The most interesting finding of this study was that children with Kawasaki syndrome are at higher risk for composite cardiovascular events and major adverse cardiac events even if they were not diagnosed with coronary artery aneurysm,” session comoderator Shervin Assassi, MD, professor of medicine and director of division of rheumatology at the University of Texas Health Science Center at Houston, said when asked to comment.

Dr. Robinson and colleagues also looked at outcomes based on presence or absence of coronary involvement at the time of Kawasaki disease diagnosis. For example, among those with initial coronary involvement, 15% later experienced a cardiovascular event and 10% experienced a major cardiovascular event.

“However, we were specifically interested in looking at children without initial coronary involvement. In this group, we also found these children were at increased risk for cardiovascular events compared to children without Kawasaki disease,” Dr. Robinson said. He said the distinction is important because approximately 95% of children diagnosed with Kawasaki disease do not feature initial coronary involvement.

In terms of clinical care, “our data provides an early signal that Kawasaki disease survivors – including those without initial coronary involvement – may be at higher risk of cardiovascular events into early adulthood.”
 

A call for closer monitoring

“Based on our results, we find that Kawasaki disease survivors may benefit from additional follow-up and surveillance for cardiovascular disease risk factors, such as obesity, high blood pressure, and high cholesterol,” Dr. Robinson said. Early identification of heightened risk could allow physicians to more closely monitor this subgroup and emphasize potentially beneficial lifestyle modifications, including increasing physical activity, implementing a heart healthy diet, and avoiding smoking.

Mortality was not significantly different between groups. “Despite the risk of cardiac events we found, death was uncommon,” Dr. Robinson said. Among children with Kawasaki disease, 1 in 500 died during follow-up, so “the risk of death was actually lower than for children without Kawasaki disease.”

Similar findings of lower mortality have been reported in research out of Japan, he added during a plenary presentation at ACR 2020. Future research is warranted to evaluate this finding further, Dr. Robinson said.
 

Future plans

Going forward, the investigators plan to evaluate noncardiovascular outcomes in this patient population. They would also like to examine health care utilization following a diagnosis of Kawasaki disease “to better understand what kind of follow-up is happening now in Ontario,” Dr. Robinson said.

Another unanswered question is whether the cardiovascular events observed in the study stem from atherosclerotic disease or a different mechanism among survivors of Kawasaki disease.

The research was supported by a McMaster University Resident Research Grant, a Hamilton Health Sciences New Investigator Award, and Ontario’s Institute for Clinical Evaluative Sciences. Dr. Robinson had no relevant financial disclosures.

SOURCE: Robinson C et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 0937.

People taking even low-dose methotrexate need tuberculosis screening and ongoing clinical care if they live in areas where TB is common, results of a study presented at the virtual annual meeting of the American College of Rheumatology suggest.

Coauthor Carol Hitchon, MD, MSc, a rheumatologist with the University of Manitoba in Winnipeg, who presented the findings, warned that methotrexate (MTX) users who also take corticosteroids or other immunosuppressants are at particular risk and need TB screening.

Current management guidelines for rheumatic disease address TB in relation to biologics, but not in relation to methotrexate, Dr. Hitchon said.

“We know that methotrexate is the foundational DMARD [disease-modifying antirheumatic drug] for many rheumatic diseases, especially rheumatoid arthritis,” Dr. Hitchon noted at a press conference. “It’s safe and effective when dosed properly. However, methotrexate does have the potential for significant liver toxicity as well as infection, particularly for infectious organisms that are targeted by cell-mediated immunity, and TB is one of those agents.”

Using multiple databases, researchers conducted a systematic review of the literature published from 1990 to 2018 on TB rates among people who take less than 30 mg of methotrexate a week. Of the 4,700 studies they examined, 31 fit the criteria for this analysis.

They collected data on tuberculosis incidence or new TB diagnoses vs. reactivation of latent TB infection as well as TB outcomes, such as pulmonary symptoms, dissemination, and mortality.

They found a modest increase in the risk of TB infections in the setting of low-dose methotrexate. In addition, rates of TB in people with rheumatic disease who are treated with either methotrexate or biologics are generally higher than in the general population.

They also found that methotrexate users had higher rates of the type of TB that spreads beyond a patient’s lungs, compared with the general population.

Safety of INH with methotrexate

Researchers also looked at the safety of isoniazid (INH), the antibiotic used to treat TB, and found that isoniazid-related liver toxicity and neutropenia were more common when people took the antibiotic along with methotrexate, but those effects were usually reversible.

TB is endemic in various regions around the world. Historically there hasn’t been much rheumatology capacity in many of these areas, but as that capacity increases more people who are at high risk for developing or reactivating TB will be receiving methotrexate for rheumatic diseases, Dr. Hitchon said.

“It’s prudent for people managing patients who may be at higher risk for TB either from where they live or from where they travel that we should have a high suspicion for TB and consider screening as part of our workup in the course of initiating treatment like methotrexate,” she said.

Narender Annapureddy, MD, a rheumatologist at Vanderbilt University, Nashville, Tenn., who was not involved in the research, pointed out that a limitation of the work is that only 27% of the studies are from developing countries, which are more likely to have endemic TB, and those studies had very few cases.

“This finding needs to be studied in larger populations in TB-endemic areas and in high-risk populations,” he said in an interview.

As for practice implications in the United States, Dr. Annapureddy noted that TB is rare in the United States and most of the cases occur in people born in other countries.

“This population may be at risk for TB and should probably be screened for TB before initiating methotrexate,” he said. “Since biologics are usually the next step, especially in RA after patients fail methotrexate, having information on TB status may also help guide management options after MTX failure.

“Since high-dose steroids are another important risk factor for TB activation,” Dr. Annapureddy continued, “rheumatologists should likely consider screening patients who are going to be on moderate to high doses of steroids with MTX.”

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

People taking even low-dose methotrexate need tuberculosis screening and ongoing clinical care if they live in areas where TB is common, results of a study presented at the virtual annual meeting of the American College of Rheumatology suggest.

Coauthor Carol Hitchon, MD, MSc, a rheumatologist with the University of Manitoba in Winnipeg, who presented the findings, warned that methotrexate (MTX) users who also take corticosteroids or other immunosuppressants are at particular risk and need TB screening.

Current management guidelines for rheumatic disease address TB in relation to biologics, but not in relation to methotrexate, Dr. Hitchon said.

“We know that methotrexate is the foundational DMARD [disease-modifying antirheumatic drug] for many rheumatic diseases, especially rheumatoid arthritis,” Dr. Hitchon noted at a press conference. “It’s safe and effective when dosed properly. However, methotrexate does have the potential for significant liver toxicity as well as infection, particularly for infectious organisms that are targeted by cell-mediated immunity, and TB is one of those agents.”

Using multiple databases, researchers conducted a systematic review of the literature published from 1990 to 2018 on TB rates among people who take less than 30 mg of methotrexate a week. Of the 4,700 studies they examined, 31 fit the criteria for this analysis.

They collected data on tuberculosis incidence or new TB diagnoses vs. reactivation of latent TB infection as well as TB outcomes, such as pulmonary symptoms, dissemination, and mortality.

They found a modest increase in the risk of TB infections in the setting of low-dose methotrexate. In addition, rates of TB in people with rheumatic disease who are treated with either methotrexate or biologics are generally higher than in the general population.

They also found that methotrexate users had higher rates of the type of TB that spreads beyond a patient’s lungs, compared with the general population.

Safety of INH with methotrexate

Researchers also looked at the safety of isoniazid (INH), the antibiotic used to treat TB, and found that isoniazid-related liver toxicity and neutropenia were more common when people took the antibiotic along with methotrexate, but those effects were usually reversible.

TB is endemic in various regions around the world. Historically there hasn’t been much rheumatology capacity in many of these areas, but as that capacity increases more people who are at high risk for developing or reactivating TB will be receiving methotrexate for rheumatic diseases, Dr. Hitchon said.

“It’s prudent for people managing patients who may be at higher risk for TB either from where they live or from where they travel that we should have a high suspicion for TB and consider screening as part of our workup in the course of initiating treatment like methotrexate,” she said.

Narender Annapureddy, MD, a rheumatologist at Vanderbilt University, Nashville, Tenn., who was not involved in the research, pointed out that a limitation of the work is that only 27% of the studies are from developing countries, which are more likely to have endemic TB, and those studies had very few cases.

“This finding needs to be studied in larger populations in TB-endemic areas and in high-risk populations,” he said in an interview.

As for practice implications in the United States, Dr. Annapureddy noted that TB is rare in the United States and most of the cases occur in people born in other countries.

“This population may be at risk for TB and should probably be screened for TB before initiating methotrexate,” he said. “Since biologics are usually the next step, especially in RA after patients fail methotrexate, having information on TB status may also help guide management options after MTX failure.

“Since high-dose steroids are another important risk factor for TB activation,” Dr. Annapureddy continued, “rheumatologists should likely consider screening patients who are going to be on moderate to high doses of steroids with MTX.”

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

People taking even low-dose methotrexate need tuberculosis screening and ongoing clinical care if they live in areas where TB is common, results of a study presented at the virtual annual meeting of the American College of Rheumatology suggest.

Coauthor Carol Hitchon, MD, MSc, a rheumatologist with the University of Manitoba in Winnipeg, who presented the findings, warned that methotrexate (MTX) users who also take corticosteroids or other immunosuppressants are at particular risk and need TB screening.

Current management guidelines for rheumatic disease address TB in relation to biologics, but not in relation to methotrexate, Dr. Hitchon said.

“We know that methotrexate is the foundational DMARD [disease-modifying antirheumatic drug] for many rheumatic diseases, especially rheumatoid arthritis,” Dr. Hitchon noted at a press conference. “It’s safe and effective when dosed properly. However, methotrexate does have the potential for significant liver toxicity as well as infection, particularly for infectious organisms that are targeted by cell-mediated immunity, and TB is one of those agents.”

Using multiple databases, researchers conducted a systematic review of the literature published from 1990 to 2018 on TB rates among people who take less than 30 mg of methotrexate a week. Of the 4,700 studies they examined, 31 fit the criteria for this analysis.

They collected data on tuberculosis incidence or new TB diagnoses vs. reactivation of latent TB infection as well as TB outcomes, such as pulmonary symptoms, dissemination, and mortality.

They found a modest increase in the risk of TB infections in the setting of low-dose methotrexate. In addition, rates of TB in people with rheumatic disease who are treated with either methotrexate or biologics are generally higher than in the general population.

They also found that methotrexate users had higher rates of the type of TB that spreads beyond a patient’s lungs, compared with the general population.

Safety of INH with methotrexate

Researchers also looked at the safety of isoniazid (INH), the antibiotic used to treat TB, and found that isoniazid-related liver toxicity and neutropenia were more common when people took the antibiotic along with methotrexate, but those effects were usually reversible.

TB is endemic in various regions around the world. Historically there hasn’t been much rheumatology capacity in many of these areas, but as that capacity increases more people who are at high risk for developing or reactivating TB will be receiving methotrexate for rheumatic diseases, Dr. Hitchon said.

“It’s prudent for people managing patients who may be at higher risk for TB either from where they live or from where they travel that we should have a high suspicion for TB and consider screening as part of our workup in the course of initiating treatment like methotrexate,” she said.

Narender Annapureddy, MD, a rheumatologist at Vanderbilt University, Nashville, Tenn., who was not involved in the research, pointed out that a limitation of the work is that only 27% of the studies are from developing countries, which are more likely to have endemic TB, and those studies had very few cases.

“This finding needs to be studied in larger populations in TB-endemic areas and in high-risk populations,” he said in an interview.

As for practice implications in the United States, Dr. Annapureddy noted that TB is rare in the United States and most of the cases occur in people born in other countries.

“This population may be at risk for TB and should probably be screened for TB before initiating methotrexate,” he said. “Since biologics are usually the next step, especially in RA after patients fail methotrexate, having information on TB status may also help guide management options after MTX failure.

“Since high-dose steroids are another important risk factor for TB activation,” Dr. Annapureddy continued, “rheumatologists should likely consider screening patients who are going to be on moderate to high doses of steroids with MTX.”

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

Pregnant women with interstitial lung disease (ILD) related to autoimmune disease may not need to terminate their pregnancies if they have close monitoring before, during, and after pregnancy with a multidisciplinary team of physicians, new research suggests.

Senior author Megan Clowse, MD, MPH, associate professor of medicine in the division of rheumatology at Duke University, Durham, N.C., explained during a press conference at the virtual annual meeting of the American College of Rheumatology that women with ILD are often advised by obstetricians or rheumatologists to avoid conception or terminate their pregnancies, though evidence for that has been based on small studies of 9-15 patients that have had mixed results.

“Many of these pregnancies were delivered 20-30 years ago, definitely with different rheumatic and obstetric care than we can provide now,” she said. “It’s really time to rethink our approach to interstitial lung disease and pregnancy.”

This study showed that while adverse pregnancy outcomes are common in these women, overall maternal morbidity and mortality are low.

ILD may be a secondary disease in people who have scleroderma, lupus, and sarcoidosis.

Largest study to date

This Pfizer-sponsored retrospective study of 67 pregnant women is the largest to date, and it analyzed 94 pregnancies (including five sets of twins).

Sarah Rae Easter, MD, maternal-fetal medicine doctor in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston, called the work “exciting” as the researchers were able to look back at a large number of cases for a rare condition for more than 20 years.

“Their data provides much-needed evidence to provide some reassurance for women affected by this type of pulmonary disease regarding the relative safety of pregnancy,” she said in an interview.
 

Study spanned 23 years

The researchers reviewed pregnancy records in patients diagnosed with ILD secondary to autoimmune disease at Duke University Health System from January 1996 to July 2019.

They classified the severity of ILD based on two standard breathing tests – forced vital capacity and diffusion capacity for carbon monoxide.

Overall, 69% of the women were diagnosed with sarcoidosis and the remaining 31% had a connective tissue disease associated with ILD (CTD-ILD). Of those measured for ILD severity, 11% were severe, 25% were moderate, 50% were mild, and 14% were normal. Their average maternal age was 32.1 and 83% were Black.

While 70% of the pregnancies resulted in live births, 9% were terminated. The remainder resulted in miscarriage or stillbirth.

Researchers reported a 15% rate of preeclampsia, a 34% rate of the composite measure PROMISSE-Adverse Pregnancy Outcome (APO), and a 15% rate of PROMISSE-APO SEVERE. Patients with severe disease had the highest rates of PROMISSE-APO (P = .03 across groups).

(PROMISSE stands for the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus study.)

None of the women died

Dr. Clowse said it was a pleasant surprise to find that none of the women died, though patients with severe ILD had more adverse outcomes. Only 2.1% were treated in an intensive care unit during or soon after delivery. In 4.2%, ILD patients had significant shortness of breath due to fluid volume overload around the time of delivery.

For the women who had normal-to-moderate lung disease, Dr. Clowse said, “they really had remarkably good outcomes, really pretty comparable to the general population. About 15% delivered preterm and about 20% suffered a pregnancy loss.”

Dr. Easter, who was not involved with the study, noted the large number of Black women in the cohort.

“Focusing in on improving outcomes for Black and Brown women related to pregnancy in our country is a much-needed undertaking,” Dr. Easter said.

Being able to quote percentages from this research, based on a good-sized study “at least gives people a benchmark about what kind of risk they are willing to assume for themselves,” she said.

For providers, being able to place this rare disease within the spectrum of other diseases where there is more data is also very helpful, she said.

Dr. Clowse said in an interview that the preponderance of Black women in the study was a surprise but may be explained by two factors: Sarcoidosis is seen more frequently in Black women and in the study area in North Carolina there is a large population of Black women.

“Also, our patients with more severe lupus, the ones who are more likely to have interstitial lung disease, are often Black and that’s likely contributing as well,” she said.
 

Multidisciplinary teams advised

Dr. Clowse emphasized that women with ILD need multidisciplinary teams in pregnancy and should be managed at tertiary care centers where there is a full complement of obstetric and internal medicine experts.

“We do recommend evaluating the severity of their lungs and their heart disease around the time of pregnancy and during pregnancy if they have shortness of breath,” she said.

“We currently recommend that these patients with moderate or severe disease stay in the hospital for up to a week, just for monitoring,” she said.

Dr. Easter said having that kind of access to a large academic healthcare center should be an important part of the decision-making.

Patients need to think about whether they would have access to care similar to what the researchers are describing when they are making the decision to pursue or continue pregnancy, she said.

The study was sponsored by Pfizer Inc. Dr. Clowse reported relationships with UCB, GlaxoSmithKline, AstraZeneca, and Pfizer. Dr. Easter has disclosed no relevant financial relationships.

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

Pregnant women with interstitial lung disease (ILD) related to autoimmune disease may not need to terminate their pregnancies if they have close monitoring before, during, and after pregnancy with a multidisciplinary team of physicians, new research suggests.

Senior author Megan Clowse, MD, MPH, associate professor of medicine in the division of rheumatology at Duke University, Durham, N.C., explained during a press conference at the virtual annual meeting of the American College of Rheumatology that women with ILD are often advised by obstetricians or rheumatologists to avoid conception or terminate their pregnancies, though evidence for that has been based on small studies of 9-15 patients that have had mixed results.

“Many of these pregnancies were delivered 20-30 years ago, definitely with different rheumatic and obstetric care than we can provide now,” she said. “It’s really time to rethink our approach to interstitial lung disease and pregnancy.”

This study showed that while adverse pregnancy outcomes are common in these women, overall maternal morbidity and mortality are low.

ILD may be a secondary disease in people who have scleroderma, lupus, and sarcoidosis.

Largest study to date

This Pfizer-sponsored retrospective study of 67 pregnant women is the largest to date, and it analyzed 94 pregnancies (including five sets of twins).

Sarah Rae Easter, MD, maternal-fetal medicine doctor in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston, called the work “exciting” as the researchers were able to look back at a large number of cases for a rare condition for more than 20 years.

“Their data provides much-needed evidence to provide some reassurance for women affected by this type of pulmonary disease regarding the relative safety of pregnancy,” she said in an interview.
 

Study spanned 23 years

The researchers reviewed pregnancy records in patients diagnosed with ILD secondary to autoimmune disease at Duke University Health System from January 1996 to July 2019.

They classified the severity of ILD based on two standard breathing tests – forced vital capacity and diffusion capacity for carbon monoxide.

Overall, 69% of the women were diagnosed with sarcoidosis and the remaining 31% had a connective tissue disease associated with ILD (CTD-ILD). Of those measured for ILD severity, 11% were severe, 25% were moderate, 50% were mild, and 14% were normal. Their average maternal age was 32.1 and 83% were Black.

While 70% of the pregnancies resulted in live births, 9% were terminated. The remainder resulted in miscarriage or stillbirth.

Researchers reported a 15% rate of preeclampsia, a 34% rate of the composite measure PROMISSE-Adverse Pregnancy Outcome (APO), and a 15% rate of PROMISSE-APO SEVERE. Patients with severe disease had the highest rates of PROMISSE-APO (P = .03 across groups).

(PROMISSE stands for the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus study.)

None of the women died

Dr. Clowse said it was a pleasant surprise to find that none of the women died, though patients with severe ILD had more adverse outcomes. Only 2.1% were treated in an intensive care unit during or soon after delivery. In 4.2%, ILD patients had significant shortness of breath due to fluid volume overload around the time of delivery.

For the women who had normal-to-moderate lung disease, Dr. Clowse said, “they really had remarkably good outcomes, really pretty comparable to the general population. About 15% delivered preterm and about 20% suffered a pregnancy loss.”

Dr. Easter, who was not involved with the study, noted the large number of Black women in the cohort.

“Focusing in on improving outcomes for Black and Brown women related to pregnancy in our country is a much-needed undertaking,” Dr. Easter said.

Being able to quote percentages from this research, based on a good-sized study “at least gives people a benchmark about what kind of risk they are willing to assume for themselves,” she said.

For providers, being able to place this rare disease within the spectrum of other diseases where there is more data is also very helpful, she said.

Dr. Clowse said in an interview that the preponderance of Black women in the study was a surprise but may be explained by two factors: Sarcoidosis is seen more frequently in Black women and in the study area in North Carolina there is a large population of Black women.

“Also, our patients with more severe lupus, the ones who are more likely to have interstitial lung disease, are often Black and that’s likely contributing as well,” she said.
 

Multidisciplinary teams advised

Dr. Clowse emphasized that women with ILD need multidisciplinary teams in pregnancy and should be managed at tertiary care centers where there is a full complement of obstetric and internal medicine experts.

“We do recommend evaluating the severity of their lungs and their heart disease around the time of pregnancy and during pregnancy if they have shortness of breath,” she said.

“We currently recommend that these patients with moderate or severe disease stay in the hospital for up to a week, just for monitoring,” she said.

Dr. Easter said having that kind of access to a large academic healthcare center should be an important part of the decision-making.

Patients need to think about whether they would have access to care similar to what the researchers are describing when they are making the decision to pursue or continue pregnancy, she said.

The study was sponsored by Pfizer Inc. Dr. Clowse reported relationships with UCB, GlaxoSmithKline, AstraZeneca, and Pfizer. Dr. Easter has disclosed no relevant financial relationships.

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

Pregnant women with interstitial lung disease (ILD) related to autoimmune disease may not need to terminate their pregnancies if they have close monitoring before, during, and after pregnancy with a multidisciplinary team of physicians, new research suggests.

Senior author Megan Clowse, MD, MPH, associate professor of medicine in the division of rheumatology at Duke University, Durham, N.C., explained during a press conference at the virtual annual meeting of the American College of Rheumatology that women with ILD are often advised by obstetricians or rheumatologists to avoid conception or terminate their pregnancies, though evidence for that has been based on small studies of 9-15 patients that have had mixed results.

“Many of these pregnancies were delivered 20-30 years ago, definitely with different rheumatic and obstetric care than we can provide now,” she said. “It’s really time to rethink our approach to interstitial lung disease and pregnancy.”

This study showed that while adverse pregnancy outcomes are common in these women, overall maternal morbidity and mortality are low.

ILD may be a secondary disease in people who have scleroderma, lupus, and sarcoidosis.

Largest study to date

This Pfizer-sponsored retrospective study of 67 pregnant women is the largest to date, and it analyzed 94 pregnancies (including five sets of twins).

Sarah Rae Easter, MD, maternal-fetal medicine doctor in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston, called the work “exciting” as the researchers were able to look back at a large number of cases for a rare condition for more than 20 years.

“Their data provides much-needed evidence to provide some reassurance for women affected by this type of pulmonary disease regarding the relative safety of pregnancy,” she said in an interview.
 

Study spanned 23 years

The researchers reviewed pregnancy records in patients diagnosed with ILD secondary to autoimmune disease at Duke University Health System from January 1996 to July 2019.

They classified the severity of ILD based on two standard breathing tests – forced vital capacity and diffusion capacity for carbon monoxide.

Overall, 69% of the women were diagnosed with sarcoidosis and the remaining 31% had a connective tissue disease associated with ILD (CTD-ILD). Of those measured for ILD severity, 11% were severe, 25% were moderate, 50% were mild, and 14% were normal. Their average maternal age was 32.1 and 83% were Black.

While 70% of the pregnancies resulted in live births, 9% were terminated. The remainder resulted in miscarriage or stillbirth.

Researchers reported a 15% rate of preeclampsia, a 34% rate of the composite measure PROMISSE-Adverse Pregnancy Outcome (APO), and a 15% rate of PROMISSE-APO SEVERE. Patients with severe disease had the highest rates of PROMISSE-APO (P = .03 across groups).

(PROMISSE stands for the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus study.)

None of the women died

Dr. Clowse said it was a pleasant surprise to find that none of the women died, though patients with severe ILD had more adverse outcomes. Only 2.1% were treated in an intensive care unit during or soon after delivery. In 4.2%, ILD patients had significant shortness of breath due to fluid volume overload around the time of delivery.

For the women who had normal-to-moderate lung disease, Dr. Clowse said, “they really had remarkably good outcomes, really pretty comparable to the general population. About 15% delivered preterm and about 20% suffered a pregnancy loss.”

Dr. Easter, who was not involved with the study, noted the large number of Black women in the cohort.

“Focusing in on improving outcomes for Black and Brown women related to pregnancy in our country is a much-needed undertaking,” Dr. Easter said.

Being able to quote percentages from this research, based on a good-sized study “at least gives people a benchmark about what kind of risk they are willing to assume for themselves,” she said.

For providers, being able to place this rare disease within the spectrum of other diseases where there is more data is also very helpful, she said.

Dr. Clowse said in an interview that the preponderance of Black women in the study was a surprise but may be explained by two factors: Sarcoidosis is seen more frequently in Black women and in the study area in North Carolina there is a large population of Black women.

“Also, our patients with more severe lupus, the ones who are more likely to have interstitial lung disease, are often Black and that’s likely contributing as well,” she said.
 

Multidisciplinary teams advised

Dr. Clowse emphasized that women with ILD need multidisciplinary teams in pregnancy and should be managed at tertiary care centers where there is a full complement of obstetric and internal medicine experts.

“We do recommend evaluating the severity of their lungs and their heart disease around the time of pregnancy and during pregnancy if they have shortness of breath,” she said.

“We currently recommend that these patients with moderate or severe disease stay in the hospital for up to a week, just for monitoring,” she said.

Dr. Easter said having that kind of access to a large academic healthcare center should be an important part of the decision-making.

Patients need to think about whether they would have access to care similar to what the researchers are describing when they are making the decision to pursue or continue pregnancy, she said.

The study was sponsored by Pfizer Inc. Dr. Clowse reported relationships with UCB, GlaxoSmithKline, AstraZeneca, and Pfizer. Dr. Easter has disclosed no relevant financial relationships.

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

Patients who take the vitamin K antagonist warfarin to prevent thromboembolic events are significantly more likely to require knee or hip replacement surgery – a surrogate endpoint for end-stage osteoarthritis – than are patients who take direct oral anticoagulants (DOACs), results of a U.K.-based study showed.

In a nested case-control study, warfarin use was associated with a 1.5-fold risk for knee and hip replacement, compared with use of DOACs.

The findings provide additional evidence for the role of vitamin K and vitamin K–dependent proteins for limiting osteoarthritis progression, said lead author Priyanka Ballal, MD, a rheumatology fellow at Boston University.

“Given the prevalence and impact of osteoarthritis, our data, along with the existing literature, support the need for a well-powered, randomized, controlled trial for evaluating vitamin K supplementation in osteoarthritis. Our study also raises the consideration of using DOACs over warfarin when indicated in people with or at risk of osteoarthritis,“ she said in a plenary session at the virtual annual meeting of the American College of Rheumatology.

Warfarin targets vitamin K for its role in coagulation, but vitamin K is also an essential co-factor for vitamin K-dependent proteins in bone and cartilage, Dr. Ballal said,

Inadequate vitamin K levels are associated with abnormal joint tissue mineralization, and with increased incidence and prevalence of osteoarthritis. In a randomized, controlled trial, vitamin K supplementation was associated with trends toward less osteoarthritis progression among patients with vitamin K deficiency, she said.

To see whether warfarin therapy has biologic effects similar to that seen in patients with vitamin K deficiency, Dr. Ballal and colleagues conducted a nested, case-control study using data from The Health Improvement Network (THIN), an electronic medical record database of patients enrolled with general practitioners in the United Kingdom.

The sample included adults aged 40-80 years with atrial fibrillation who had received one or more prescriptions for warfarin or a DOAC beginning in 2009, a year after DOACs were first marketed in the United Kingdom, and within 1 year of the index date (date of joint replacement surgery). The researchers excluded patients with knee or hip replacements before 2014, severe comorbidities that would limit joint replacement, or who had used either warfarin or a DOAC prior to study entry. Each case was matched by age, gender, and index date with up to four control patients (those who did not have surgery).

A total of 913 cases and 3,652 controls were included. The groups had similar characteristics (sex, age, cancer, renal disease, chronic lung disease, hypertension, and incidence of venous thromboembolism [VTE]), except for somewhat higher rates of diabetes and heart failure among controls, and a higher rate of obesity among cases.

The investigators first looked at warfarin use among all knee and/or hip replacement cases and controls and calculated an odds ratio of 1.57 (95% confidence interval [CI], 1.30-1.89) for knee and hip replacement with warfarin after adjustment for body mass index, factors influencing choice of anticoagulant, comorbidities, other medications, general practitioner visits, and hospitalizations.

The association between warfarin and joint replacement held up in an analysis restricted to knee replacement only, with an adjusted OR of 1.48 (95% CI, 1.16-1.89).

There was also a clear association between duration of warfarin use and risk of knee and hip replacement.

“This abstract suggests the role of adequate vitamin K may be important in decreasing progression of osteoarthritis, which would then favor patients with OA who are on warfarin to consider changing to a DOAC; however, further studies are needed to confirm this finding and consider its impact on VTE and wound healing postop,” said Minna Kohler, MD, director of the rheumatology musculoskeletal ultrasound program at Massachusetts General Hospital in Boston. Dr. Kohler, who was not involved in the study, replied to an email request for comment.

The study was supported by grants from the National Institutes of Health. Dr. Ballal and Dr. Kohler reported having no conflicts of interest to disclose.

SOURCE: Ballal P et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 0934.

Patients who take the vitamin K antagonist warfarin to prevent thromboembolic events are significantly more likely to require knee or hip replacement surgery – a surrogate endpoint for end-stage osteoarthritis – than are patients who take direct oral anticoagulants (DOACs), results of a U.K.-based study showed.

In a nested case-control study, warfarin use was associated with a 1.5-fold risk for knee and hip replacement, compared with use of DOACs.

The findings provide additional evidence for the role of vitamin K and vitamin K–dependent proteins for limiting osteoarthritis progression, said lead author Priyanka Ballal, MD, a rheumatology fellow at Boston University.

“Given the prevalence and impact of osteoarthritis, our data, along with the existing literature, support the need for a well-powered, randomized, controlled trial for evaluating vitamin K supplementation in osteoarthritis. Our study also raises the consideration of using DOACs over warfarin when indicated in people with or at risk of osteoarthritis,“ she said in a plenary session at the virtual annual meeting of the American College of Rheumatology.

Warfarin targets vitamin K for its role in coagulation, but vitamin K is also an essential co-factor for vitamin K-dependent proteins in bone and cartilage, Dr. Ballal said,

Inadequate vitamin K levels are associated with abnormal joint tissue mineralization, and with increased incidence and prevalence of osteoarthritis. In a randomized, controlled trial, vitamin K supplementation was associated with trends toward less osteoarthritis progression among patients with vitamin K deficiency, she said.

To see whether warfarin therapy has biologic effects similar to that seen in patients with vitamin K deficiency, Dr. Ballal and colleagues conducted a nested, case-control study using data from The Health Improvement Network (THIN), an electronic medical record database of patients enrolled with general practitioners in the United Kingdom.

The sample included adults aged 40-80 years with atrial fibrillation who had received one or more prescriptions for warfarin or a DOAC beginning in 2009, a year after DOACs were first marketed in the United Kingdom, and within 1 year of the index date (date of joint replacement surgery). The researchers excluded patients with knee or hip replacements before 2014, severe comorbidities that would limit joint replacement, or who had used either warfarin or a DOAC prior to study entry. Each case was matched by age, gender, and index date with up to four control patients (those who did not have surgery).

A total of 913 cases and 3,652 controls were included. The groups had similar characteristics (sex, age, cancer, renal disease, chronic lung disease, hypertension, and incidence of venous thromboembolism [VTE]), except for somewhat higher rates of diabetes and heart failure among controls, and a higher rate of obesity among cases.

The investigators first looked at warfarin use among all knee and/or hip replacement cases and controls and calculated an odds ratio of 1.57 (95% confidence interval [CI], 1.30-1.89) for knee and hip replacement with warfarin after adjustment for body mass index, factors influencing choice of anticoagulant, comorbidities, other medications, general practitioner visits, and hospitalizations.

The association between warfarin and joint replacement held up in an analysis restricted to knee replacement only, with an adjusted OR of 1.48 (95% CI, 1.16-1.89).

There was also a clear association between duration of warfarin use and risk of knee and hip replacement.

“This abstract suggests the role of adequate vitamin K may be important in decreasing progression of osteoarthritis, which would then favor patients with OA who are on warfarin to consider changing to a DOAC; however, further studies are needed to confirm this finding and consider its impact on VTE and wound healing postop,” said Minna Kohler, MD, director of the rheumatology musculoskeletal ultrasound program at Massachusetts General Hospital in Boston. Dr. Kohler, who was not involved in the study, replied to an email request for comment.

The study was supported by grants from the National Institutes of Health. Dr. Ballal and Dr. Kohler reported having no conflicts of interest to disclose.

SOURCE: Ballal P et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 0934.

Patients who take the vitamin K antagonist warfarin to prevent thromboembolic events are significantly more likely to require knee or hip replacement surgery – a surrogate endpoint for end-stage osteoarthritis – than are patients who take direct oral anticoagulants (DOACs), results of a U.K.-based study showed.

In a nested case-control study, warfarin use was associated with a 1.5-fold risk for knee and hip replacement, compared with use of DOACs.

The findings provide additional evidence for the role of vitamin K and vitamin K–dependent proteins for limiting osteoarthritis progression, said lead author Priyanka Ballal, MD, a rheumatology fellow at Boston University.

“Given the prevalence and impact of osteoarthritis, our data, along with the existing literature, support the need for a well-powered, randomized, controlled trial for evaluating vitamin K supplementation in osteoarthritis. Our study also raises the consideration of using DOACs over warfarin when indicated in people with or at risk of osteoarthritis,“ she said in a plenary session at the virtual annual meeting of the American College of Rheumatology.

Warfarin targets vitamin K for its role in coagulation, but vitamin K is also an essential co-factor for vitamin K-dependent proteins in bone and cartilage, Dr. Ballal said,

Inadequate vitamin K levels are associated with abnormal joint tissue mineralization, and with increased incidence and prevalence of osteoarthritis. In a randomized, controlled trial, vitamin K supplementation was associated with trends toward less osteoarthritis progression among patients with vitamin K deficiency, she said.

To see whether warfarin therapy has biologic effects similar to that seen in patients with vitamin K deficiency, Dr. Ballal and colleagues conducted a nested, case-control study using data from The Health Improvement Network (THIN), an electronic medical record database of patients enrolled with general practitioners in the United Kingdom.

The sample included adults aged 40-80 years with atrial fibrillation who had received one or more prescriptions for warfarin or a DOAC beginning in 2009, a year after DOACs were first marketed in the United Kingdom, and within 1 year of the index date (date of joint replacement surgery). The researchers excluded patients with knee or hip replacements before 2014, severe comorbidities that would limit joint replacement, or who had used either warfarin or a DOAC prior to study entry. Each case was matched by age, gender, and index date with up to four control patients (those who did not have surgery).

A total of 913 cases and 3,652 controls were included. The groups had similar characteristics (sex, age, cancer, renal disease, chronic lung disease, hypertension, and incidence of venous thromboembolism [VTE]), except for somewhat higher rates of diabetes and heart failure among controls, and a higher rate of obesity among cases.

The investigators first looked at warfarin use among all knee and/or hip replacement cases and controls and calculated an odds ratio of 1.57 (95% confidence interval [CI], 1.30-1.89) for knee and hip replacement with warfarin after adjustment for body mass index, factors influencing choice of anticoagulant, comorbidities, other medications, general practitioner visits, and hospitalizations.

The association between warfarin and joint replacement held up in an analysis restricted to knee replacement only, with an adjusted OR of 1.48 (95% CI, 1.16-1.89).

There was also a clear association between duration of warfarin use and risk of knee and hip replacement.

“This abstract suggests the role of adequate vitamin K may be important in decreasing progression of osteoarthritis, which would then favor patients with OA who are on warfarin to consider changing to a DOAC; however, further studies are needed to confirm this finding and consider its impact on VTE and wound healing postop,” said Minna Kohler, MD, director of the rheumatology musculoskeletal ultrasound program at Massachusetts General Hospital in Boston. Dr. Kohler, who was not involved in the study, replied to an email request for comment.

The study was supported by grants from the National Institutes of Health. Dr. Ballal and Dr. Kohler reported having no conflicts of interest to disclose.

SOURCE: Ballal P et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 0934.

Among people with COVID-19, those with systemic autoimmune rheumatic diseases had an elevated 30-day risk of hospitalization, ICU admission, need for mechanical ventilation, and acute kidney injury, compared to a group without rheumatic diseases at 4 months in a match-controlled study.

When investigators expanded the study to 6 months, the difference in need for mechanical ventilation disappeared. However, relative risk for venous thromboembolism (VTE) emerged as 74% higher among people with COVID-19 and with rheumatic disease, said Kristin D’Silva, MD, who presented the findings during a plenary session at the virtual annual meeting of the American College of Rheumatology. She noted that rheumatic disease itself could contribute to VTE risk.

Comorbidities including hypertension, diabetes, and asthma were more common among people with systemic autoimmune rheumatic diseases (SARDs). After adjustment for comorbidities, “the risks of hospitalization and ICU admission were attenuated, suggesting comorbidities are likely key mediators of the increased risk of severe COVID-19 outcomes observed in SARDs patients versus comparators,” Dr. D’Silva, a rheumatology fellow at Massachusetts General Hospital in Boston, said in an interview.

“The risk of venous thromboembolism persisted even after adjusting for comorbidities,” Dr. D’Silva said. Patients with SARDs should be closely monitored for VTE during COVID-19 infection, she added. “Patients with significant cardiovascular, pulmonary, and metabolic comorbidities should be closely monitored for severe COVID-19.”

At the same time, a systematic review of 15 published studies revealed a low incidence of COVID-19 infection among people with rheumatic disease. Furthermore, most experienced a mild clinical course and low mortality, Akhil Sood, MD, said when presenting results of his poster at the meeting.

Underlying immunosuppression, chronic inflammation, comorbidities, and disparities based on racial, ethnic, and socioeconomic status could predispose people with rheumatic disease to poorer COVID-19 outcomes. However, the risks and outcomes of COVID-19 infection among this population “are not well understood,” said Dr. Sood, a second-year resident in internal medicine at the University of Texas Medical Branch in Galveston.

Elevated risks in match-controlled study

Dr. D’Silva and colleagues examined a COVID-19 population and compared 716 people with SARDs and another 716 people from the general public at 4 months, as well as 2,379 people each in similar groups at 6 months. They used real-time electronic medical record data from the TriNetX research network to identify ICD-10 codes for inflammatory arthritis, connective tissue diseases, and systemic vasculitis. They also used ICD-10 codes and positive PCR tests to identify people with COVID-19.

Mean age was 57 years and women accounted for 79% of both groups evaluated at 4 months. Those with SARDs were 23% more likely to be hospitalized (relative risk, 1.23; 95% confidence interval, 1.01-1.50). This group was 75% more likely to be admitted to the ICU (RR, 1.75; 95% CI, 1.11-2.75), 77% more likely to require mechanical ventilation (RR, 1.77; 95% CI, 1.06-2.96), and 83% more likely to experience acute kidney injury (RR, 1.83; 95% CI, 1.11-3.00).

Risk of death was not significantly higher in the SARDs group (RR, 1.16; 95% CI, 0.73-1.86).

When Dr. D’Silva expanded the study to more people at 6 months, they added additional 30-day outcomes of interest: renal replacement therapy, VTE, and ischemic stroke. Risk of need for renal replacement therapy, for example, was 81% higher in the SARDs group (RR, 1.81; 95% CI, 1.07-3.07). Risk of stroke was not significantly different between groups.The improvement in mechanical ventilation risk between 4 and 6 months was not completely unexpected, Dr. D’Silva said. The relative risk dropped from 1.77 to 1.05. “This is not particularly surprising given national trends in the general population reporting decreased severe outcomes of COVID-19 including mortality as the pandemic progresses. This is likely multifactorial including changes in COVID-19 management (such as increasing use of nonintubated prone positioning rather than early intubation and treatments such as dexamethasone and remdesivir), decreased strain on hospitals and staffing compared to the early crisis phase of the pandemic, and higher testing capacity leading to detection of milder cases.”

When the 6-month analysis was further adjusted for comorbidities and a history of prior hospitalization within 1 year, only risk for acute kidney injury and VTE remained significant with relative risks of 1.33 and 1.60, respectively, likely because comorbidities are causal intermediates of COVID-19 30-day outcomes rather than confounders.

When asked to comment on the results, session comoderator Victoria K. Shanmugam, MD, said in an interview that the study “is of great interest both to rheumatologists and to patients with rheumatic disease.”

The higher risk of hospitalization, ICU admission, mechanical ventilation, acute kidney injury, and heart failure “is an important finding with implications for how our patients navigate risk during this pandemic,” said Dr. Shanmugam, director of the division of rheumatology at George Washington University in Washington.
 

Lower risks emerge in systematic review

The 15 observational studies in the systematic review included 11,815 participants. A total of 179, or 1.5%, tested positive for COVID-19.

“The incidence of COVID-19 infection among patients with rheumatic disease was low,” Dr. Sood said.

Within the COVID-19-positive group, almost 50% required hospitalization, 10% required ICU admission, and 8% died. The pooled event rate for hospitalization was 0.440 (95% CI, 0.296-0.596), while for ICU admission it was 0.132 (95% CI, 0.087-0.194) and for death it was 0.125 (95% CI, 0.082-0.182).
 

Different calculations of risk

The two studies seem to offer contradictory findings, but the disparities could be explained by study design differences. For example, Dr. D’Silva’s study evaluated a population with COVID-19 and compared those with SARDs versus a matched group from the general public. Dr. Sood and colleagues assessed study populations with rheumatic disease and assessed incidence of SARS-CoV-2 infection and difference in outcomes.

“We are asking very different questions,” Dr. D’Silva said.

“The study by D’Silva et al. was able to account for different factors to reduce confounding,” Dr. Sood said, adding that Dr. D’Silva and colleagues included a high proportion of minorities, compared with a less diverse population in the systematic review, which featured a large number of studies from Italy.

The authors of the two studies had no relevant financial disclosures to report.

SOURCES: D’Silva K et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 0430, and Sood A et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 0008.

Among people with COVID-19, those with systemic autoimmune rheumatic diseases had an elevated 30-day risk of hospitalization, ICU admission, need for mechanical ventilation, and acute kidney injury, compared to a group without rheumatic diseases at 4 months in a match-controlled study.

When investigators expanded the study to 6 months, the difference in need for mechanical ventilation disappeared. However, relative risk for venous thromboembolism (VTE) emerged as 74% higher among people with COVID-19 and with rheumatic disease, said Kristin D’Silva, MD, who presented the findings during a plenary session at the virtual annual meeting of the American College of Rheumatology. She noted that rheumatic disease itself could contribute to VTE risk.

Comorbidities including hypertension, diabetes, and asthma were more common among people with systemic autoimmune rheumatic diseases (SARDs). After adjustment for comorbidities, “the risks of hospitalization and ICU admission were attenuated, suggesting comorbidities are likely key mediators of the increased risk of severe COVID-19 outcomes observed in SARDs patients versus comparators,” Dr. D’Silva, a rheumatology fellow at Massachusetts General Hospital in Boston, said in an interview.

“The risk of venous thromboembolism persisted even after adjusting for comorbidities,” Dr. D’Silva said. Patients with SARDs should be closely monitored for VTE during COVID-19 infection, she added. “Patients with significant cardiovascular, pulmonary, and metabolic comorbidities should be closely monitored for severe COVID-19.”

At the same time, a systematic review of 15 published studies revealed a low incidence of COVID-19 infection among people with rheumatic disease. Furthermore, most experienced a mild clinical course and low mortality, Akhil Sood, MD, said when presenting results of his poster at the meeting.

Underlying immunosuppression, chronic inflammation, comorbidities, and disparities based on racial, ethnic, and socioeconomic status could predispose people with rheumatic disease to poorer COVID-19 outcomes. However, the risks and outcomes of COVID-19 infection among this population “are not well understood,” said Dr. Sood, a second-year resident in internal medicine at the University of Texas Medical Branch in Galveston.

Elevated risks in match-controlled study

Dr. D’Silva and colleagues examined a COVID-19 population and compared 716 people with SARDs and another 716 people from the general public at 4 months, as well as 2,379 people each in similar groups at 6 months. They used real-time electronic medical record data from the TriNetX research network to identify ICD-10 codes for inflammatory arthritis, connective tissue diseases, and systemic vasculitis. They also used ICD-10 codes and positive PCR tests to identify people with COVID-19.

Mean age was 57 years and women accounted for 79% of both groups evaluated at 4 months. Those with SARDs were 23% more likely to be hospitalized (relative risk, 1.23; 95% confidence interval, 1.01-1.50). This group was 75% more likely to be admitted to the ICU (RR, 1.75; 95% CI, 1.11-2.75), 77% more likely to require mechanical ventilation (RR, 1.77; 95% CI, 1.06-2.96), and 83% more likely to experience acute kidney injury (RR, 1.83; 95% CI, 1.11-3.00).

Risk of death was not significantly higher in the SARDs group (RR, 1.16; 95% CI, 0.73-1.86).

When Dr. D’Silva expanded the study to more people at 6 months, they added additional 30-day outcomes of interest: renal replacement therapy, VTE, and ischemic stroke. Risk of need for renal replacement therapy, for example, was 81% higher in the SARDs group (RR, 1.81; 95% CI, 1.07-3.07). Risk of stroke was not significantly different between groups.The improvement in mechanical ventilation risk between 4 and 6 months was not completely unexpected, Dr. D’Silva said. The relative risk dropped from 1.77 to 1.05. “This is not particularly surprising given national trends in the general population reporting decreased severe outcomes of COVID-19 including mortality as the pandemic progresses. This is likely multifactorial including changes in COVID-19 management (such as increasing use of nonintubated prone positioning rather than early intubation and treatments such as dexamethasone and remdesivir), decreased strain on hospitals and staffing compared to the early crisis phase of the pandemic, and higher testing capacity leading to detection of milder cases.”

When the 6-month analysis was further adjusted for comorbidities and a history of prior hospitalization within 1 year, only risk for acute kidney injury and VTE remained significant with relative risks of 1.33 and 1.60, respectively, likely because comorbidities are causal intermediates of COVID-19 30-day outcomes rather than confounders.

When asked to comment on the results, session comoderator Victoria K. Shanmugam, MD, said in an interview that the study “is of great interest both to rheumatologists and to patients with rheumatic disease.”

The higher risk of hospitalization, ICU admission, mechanical ventilation, acute kidney injury, and heart failure “is an important finding with implications for how our patients navigate risk during this pandemic,” said Dr. Shanmugam, director of the division of rheumatology at George Washington University in Washington.
 

Lower risks emerge in systematic review

The 15 observational studies in the systematic review included 11,815 participants. A total of 179, or 1.5%, tested positive for COVID-19.

“The incidence of COVID-19 infection among patients with rheumatic disease was low,” Dr. Sood said.

Within the COVID-19-positive group, almost 50% required hospitalization, 10% required ICU admission, and 8% died. The pooled event rate for hospitalization was 0.440 (95% CI, 0.296-0.596), while for ICU admission it was 0.132 (95% CI, 0.087-0.194) and for death it was 0.125 (95% CI, 0.082-0.182).
 

Different calculations of risk

The two studies seem to offer contradictory findings, but the disparities could be explained by study design differences. For example, Dr. D’Silva’s study evaluated a population with COVID-19 and compared those with SARDs versus a matched group from the general public. Dr. Sood and colleagues assessed study populations with rheumatic disease and assessed incidence of SARS-CoV-2 infection and difference in outcomes.

“We are asking very different questions,” Dr. D’Silva said.

“The study by D’Silva et al. was able to account for different factors to reduce confounding,” Dr. Sood said, adding that Dr. D’Silva and colleagues included a high proportion of minorities, compared with a less diverse population in the systematic review, which featured a large number of studies from Italy.

The authors of the two studies had no relevant financial disclosures to report.

SOURCES: D’Silva K et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 0430, and Sood A et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 0008.

Among people with COVID-19, those with systemic autoimmune rheumatic diseases had an elevated 30-day risk of hospitalization, ICU admission, need for mechanical ventilation, and acute kidney injury, compared to a group without rheumatic diseases at 4 months in a match-controlled study.

When investigators expanded the study to 6 months, the difference in need for mechanical ventilation disappeared. However, relative risk for venous thromboembolism (VTE) emerged as 74% higher among people with COVID-19 and with rheumatic disease, said Kristin D’Silva, MD, who presented the findings during a plenary session at the virtual annual meeting of the American College of Rheumatology. She noted that rheumatic disease itself could contribute to VTE risk.

Comorbidities including hypertension, diabetes, and asthma were more common among people with systemic autoimmune rheumatic diseases (SARDs). After adjustment for comorbidities, “the risks of hospitalization and ICU admission were attenuated, suggesting comorbidities are likely key mediators of the increased risk of severe COVID-19 outcomes observed in SARDs patients versus comparators,” Dr. D’Silva, a rheumatology fellow at Massachusetts General Hospital in Boston, said in an interview.

“The risk of venous thromboembolism persisted even after adjusting for comorbidities,” Dr. D’Silva said. Patients with SARDs should be closely monitored for VTE during COVID-19 infection, she added. “Patients with significant cardiovascular, pulmonary, and metabolic comorbidities should be closely monitored for severe COVID-19.”

At the same time, a systematic review of 15 published studies revealed a low incidence of COVID-19 infection among people with rheumatic disease. Furthermore, most experienced a mild clinical course and low mortality, Akhil Sood, MD, said when presenting results of his poster at the meeting.

Underlying immunosuppression, chronic inflammation, comorbidities, and disparities based on racial, ethnic, and socioeconomic status could predispose people with rheumatic disease to poorer COVID-19 outcomes. However, the risks and outcomes of COVID-19 infection among this population “are not well understood,” said Dr. Sood, a second-year resident in internal medicine at the University of Texas Medical Branch in Galveston.

Elevated risks in match-controlled study

Dr. D’Silva and colleagues examined a COVID-19 population and compared 716 people with SARDs and another 716 people from the general public at 4 months, as well as 2,379 people each in similar groups at 6 months. They used real-time electronic medical record data from the TriNetX research network to identify ICD-10 codes for inflammatory arthritis, connective tissue diseases, and systemic vasculitis. They also used ICD-10 codes and positive PCR tests to identify people with COVID-19.

Mean age was 57 years and women accounted for 79% of both groups evaluated at 4 months. Those with SARDs were 23% more likely to be hospitalized (relative risk, 1.23; 95% confidence interval, 1.01-1.50). This group was 75% more likely to be admitted to the ICU (RR, 1.75; 95% CI, 1.11-2.75), 77% more likely to require mechanical ventilation (RR, 1.77; 95% CI, 1.06-2.96), and 83% more likely to experience acute kidney injury (RR, 1.83; 95% CI, 1.11-3.00).

Risk of death was not significantly higher in the SARDs group (RR, 1.16; 95% CI, 0.73-1.86).

When Dr. D’Silva expanded the study to more people at 6 months, they added additional 30-day outcomes of interest: renal replacement therapy, VTE, and ischemic stroke. Risk of need for renal replacement therapy, for example, was 81% higher in the SARDs group (RR, 1.81; 95% CI, 1.07-3.07). Risk of stroke was not significantly different between groups.The improvement in mechanical ventilation risk between 4 and 6 months was not completely unexpected, Dr. D’Silva said. The relative risk dropped from 1.77 to 1.05. “This is not particularly surprising given national trends in the general population reporting decreased severe outcomes of COVID-19 including mortality as the pandemic progresses. This is likely multifactorial including changes in COVID-19 management (such as increasing use of nonintubated prone positioning rather than early intubation and treatments such as dexamethasone and remdesivir), decreased strain on hospitals and staffing compared to the early crisis phase of the pandemic, and higher testing capacity leading to detection of milder cases.”

When the 6-month analysis was further adjusted for comorbidities and a history of prior hospitalization within 1 year, only risk for acute kidney injury and VTE remained significant with relative risks of 1.33 and 1.60, respectively, likely because comorbidities are causal intermediates of COVID-19 30-day outcomes rather than confounders.

When asked to comment on the results, session comoderator Victoria K. Shanmugam, MD, said in an interview that the study “is of great interest both to rheumatologists and to patients with rheumatic disease.”

The higher risk of hospitalization, ICU admission, mechanical ventilation, acute kidney injury, and heart failure “is an important finding with implications for how our patients navigate risk during this pandemic,” said Dr. Shanmugam, director of the division of rheumatology at George Washington University in Washington.
 

Lower risks emerge in systematic review

The 15 observational studies in the systematic review included 11,815 participants. A total of 179, or 1.5%, tested positive for COVID-19.

“The incidence of COVID-19 infection among patients with rheumatic disease was low,” Dr. Sood said.

Within the COVID-19-positive group, almost 50% required hospitalization, 10% required ICU admission, and 8% died. The pooled event rate for hospitalization was 0.440 (95% CI, 0.296-0.596), while for ICU admission it was 0.132 (95% CI, 0.087-0.194) and for death it was 0.125 (95% CI, 0.082-0.182).
 

Different calculations of risk

The two studies seem to offer contradictory findings, but the disparities could be explained by study design differences. For example, Dr. D’Silva’s study evaluated a population with COVID-19 and compared those with SARDs versus a matched group from the general public. Dr. Sood and colleagues assessed study populations with rheumatic disease and assessed incidence of SARS-CoV-2 infection and difference in outcomes.

“We are asking very different questions,” Dr. D’Silva said.

“The study by D’Silva et al. was able to account for different factors to reduce confounding,” Dr. Sood said, adding that Dr. D’Silva and colleagues included a high proportion of minorities, compared with a less diverse population in the systematic review, which featured a large number of studies from Italy.

The authors of the two studies had no relevant financial disclosures to report.

SOURCES: D’Silva K et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 0430, and Sood A et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 0008.

Black patients with systemic lupus erythematosus (SLE) are known to have significantly elevated risk for stroke and ischemic heart disease (IHD), compared with non-Black patients with SLE.

Now a team of investigators has identified SLE-specific predictors for major cardiovascular complications in Black patients, pointing to potential prevention strategies in this high-risk population.

Among Black patients in a study of 336 patients with incident SLE, discoid rash at the time of SLE diagnosis predicted a fivefold higher risk for stroke, and renal disorder at the time of diagnosis was associated with a twofold higher risk, compared with non-Black patients, but neither of these symptoms predicted elevated risk of IHD.

In contrast, neurologic disorders, including prior psychosis or seizure, were associated with a fourfold higher risk for IHD, and immunologic disorders including anti-DNA, anti-Smith, or antiphospholipid antibodies were associated with a nearly fivefold greater risk for IHD in Black patients, but neither of these comorbidities predicted strokes, reported Shivani Garg, MD, assistant professor of medicine at the University of Wisconsin in Madison.

“Our study was one of the first to highlight racial disparities in CVD subtypes, with a threefold higher stroke risk and 24-fold higher ischemic heart disease risk in Black patients with lupus. Compared to previous studies in Black populations, our study highlights different peak timing of early stroke and ischemic heart disease in our cohort,“ she said at a plenary session during the virtual annual meeting of the American College of Rheumatology.

The study is one of the first to identify specific and unique SLE disease-related predictors of stroke and ischemic heart disease, she said.

Georgia Lupus Registry data

Dr. Garg and colleagues at the University of Wisconsin and Emory University in Atlanta drew on data from the Georgia Lupus Registry, a population-based registry of SLE patients from the Atlanta area. They identified patients diagnosed from 2002 through 2004 who had four or more ACR criteria for SLE, or three or more criteria plus a final diagnosis of SLE made by their board-certified rheumatologists.

The patients were matched to the Georgia Hospital Discharge Database and National Death Index from 2000 through 2013, with stroke- and IHD-related hospitalizations and deaths classified by the first three admission codes or cause-of-death codes.

Patients with transient ischemic attacks were included in the stroke category, and those with myocardial infarction and angina were included in the IHD category.

They identified 336 patients, 87% of whom were female, and 75% of whom were Black. The mean age at SLE diagnosis was 40 years. Among this cohort, there were 38 stroke-related events or deaths and 25 IHD-related events or deaths recorded from the period 2 years before through 14 years after an SLE diagnosis.
 

Early stroke, late IHD

The investigators first looked at the timing of stroke vs. IHD and found that a disproportionately high percentage of stroke events occurred in the second year after SLE diagnosis, whereas the peak of IHD-related events occurred in the 14^th year after diagnosis.

They then performed a race-stratified Cox proportional hazard analysis, and found a threefold higher risk for stroke in Black patients versus non-Black patients (P = .007) and a 24-fold higher risk for IHD (P < .0001).

In multivariate analysis, significant predictors of stroke were Black race with a hazard ratio (HR) of 3.4 (P = .028), discoid rash (HR, 4.6; P = .0028), and renal disorder (HR, 2.4; P = .04). However, stroke was not predicted by age, sex, immunologic disorder, serositis, hematologic disorder, or ACR criteria total greater than four.

Significant predictors of IHD included age 65 and older (HR, 61; P = .0007), Black race (HR, 24; P = .004), neurologic disorder (HR, 4.0; P = .018), and immunologic disorder (HR, 4.7; P = .02). But IHD could not be predicted by oral ulcers, discoid rash, or ACR criteria more than four.

“In future studies, we will examine mechanisms that drive the different timing and predictors of CVD subtypes and disparities. We will also examine the impact of timely prevention in high-risk SLE subsets,” Dr. Garg said.
 

Managing CVD risk

Angus Worthing, MD, from Arthritis & Rheumatism Associates in Chevy Chase, Md., and Washington, D.C., who moderated a press briefing where Dr. Garg discussed her data, routinely treats patients of different racial backgrounds with lupus. When asked how he manages patients with SLE and suspected cardiovascular complications, Dr. Worthing said, “I tend to, in my practice – and these kinds of studies may change what I do – watch for symptoms that might reflect coronary artery disease or cerebrovascular disease, potentially looking at the smaller arteries in the hands and feet as clues, and I will refer promptly to a vascular surgery expert or cardiologist for screening,” he said.

Dr. Garg added that in her practice, she and colleagues treat high-risk subsets of patients, such as those with lupus nephritis or multiple comorbidities, with aggressive blood pressure control and monitoring, as well as smoking cessation recommendations and lipid monitoring. They also try to limit or, if possible, decrease steroid doses to reduce risk for cardiovascular side effects.

Support for the study came in part from the U.S. Centers for Disease Control and Prevention. Dr. Garg and Dr. Worthing reported having no relevant disclosures.

SOURCE: Garg S et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 433 .

Black patients with systemic lupus erythematosus (SLE) are known to have significantly elevated risk for stroke and ischemic heart disease (IHD), compared with non-Black patients with SLE.

Now a team of investigators has identified SLE-specific predictors for major cardiovascular complications in Black patients, pointing to potential prevention strategies in this high-risk population.

Among Black patients in a study of 336 patients with incident SLE, discoid rash at the time of SLE diagnosis predicted a fivefold higher risk for stroke, and renal disorder at the time of diagnosis was associated with a twofold higher risk, compared with non-Black patients, but neither of these symptoms predicted elevated risk of IHD.

In contrast, neurologic disorders, including prior psychosis or seizure, were associated with a fourfold higher risk for IHD, and immunologic disorders including anti-DNA, anti-Smith, or antiphospholipid antibodies were associated with a nearly fivefold greater risk for IHD in Black patients, but neither of these comorbidities predicted strokes, reported Shivani Garg, MD, assistant professor of medicine at the University of Wisconsin in Madison.

“Our study was one of the first to highlight racial disparities in CVD subtypes, with a threefold higher stroke risk and 24-fold higher ischemic heart disease risk in Black patients with lupus. Compared to previous studies in Black populations, our study highlights different peak timing of early stroke and ischemic heart disease in our cohort,“ she said at a plenary session during the virtual annual meeting of the American College of Rheumatology.

The study is one of the first to identify specific and unique SLE disease-related predictors of stroke and ischemic heart disease, she said.

Georgia Lupus Registry data

Dr. Garg and colleagues at the University of Wisconsin and Emory University in Atlanta drew on data from the Georgia Lupus Registry, a population-based registry of SLE patients from the Atlanta area. They identified patients diagnosed from 2002 through 2004 who had four or more ACR criteria for SLE, or three or more criteria plus a final diagnosis of SLE made by their board-certified rheumatologists.

The patients were matched to the Georgia Hospital Discharge Database and National Death Index from 2000 through 2013, with stroke- and IHD-related hospitalizations and deaths classified by the first three admission codes or cause-of-death codes.

Patients with transient ischemic attacks were included in the stroke category, and those with myocardial infarction and angina were included in the IHD category.

They identified 336 patients, 87% of whom were female, and 75% of whom were Black. The mean age at SLE diagnosis was 40 years. Among this cohort, there were 38 stroke-related events or deaths and 25 IHD-related events or deaths recorded from the period 2 years before through 14 years after an SLE diagnosis.
 

Early stroke, late IHD

The investigators first looked at the timing of stroke vs. IHD and found that a disproportionately high percentage of stroke events occurred in the second year after SLE diagnosis, whereas the peak of IHD-related events occurred in the 14^th year after diagnosis.

They then performed a race-stratified Cox proportional hazard analysis, and found a threefold higher risk for stroke in Black patients versus non-Black patients (P = .007) and a 24-fold higher risk for IHD (P < .0001).

In multivariate analysis, significant predictors of stroke were Black race with a hazard ratio (HR) of 3.4 (P = .028), discoid rash (HR, 4.6; P = .0028), and renal disorder (HR, 2.4; P = .04). However, stroke was not predicted by age, sex, immunologic disorder, serositis, hematologic disorder, or ACR criteria total greater than four.

Significant predictors of IHD included age 65 and older (HR, 61; P = .0007), Black race (HR, 24; P = .004), neurologic disorder (HR, 4.0; P = .018), and immunologic disorder (HR, 4.7; P = .02). But IHD could not be predicted by oral ulcers, discoid rash, or ACR criteria more than four.

“In future studies, we will examine mechanisms that drive the different timing and predictors of CVD subtypes and disparities. We will also examine the impact of timely prevention in high-risk SLE subsets,” Dr. Garg said.
 

Managing CVD risk

Angus Worthing, MD, from Arthritis & Rheumatism Associates in Chevy Chase, Md., and Washington, D.C., who moderated a press briefing where Dr. Garg discussed her data, routinely treats patients of different racial backgrounds with lupus. When asked how he manages patients with SLE and suspected cardiovascular complications, Dr. Worthing said, “I tend to, in my practice – and these kinds of studies may change what I do – watch for symptoms that might reflect coronary artery disease or cerebrovascular disease, potentially looking at the smaller arteries in the hands and feet as clues, and I will refer promptly to a vascular surgery expert or cardiologist for screening,” he said.

Dr. Garg added that in her practice, she and colleagues treat high-risk subsets of patients, such as those with lupus nephritis or multiple comorbidities, with aggressive blood pressure control and monitoring, as well as smoking cessation recommendations and lipid monitoring. They also try to limit or, if possible, decrease steroid doses to reduce risk for cardiovascular side effects.

Support for the study came in part from the U.S. Centers for Disease Control and Prevention. Dr. Garg and Dr. Worthing reported having no relevant disclosures.

SOURCE: Garg S et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 433 .

Black patients with systemic lupus erythematosus (SLE) are known to have significantly elevated risk for stroke and ischemic heart disease (IHD), compared with non-Black patients with SLE.

Now a team of investigators has identified SLE-specific predictors for major cardiovascular complications in Black patients, pointing to potential prevention strategies in this high-risk population.

Among Black patients in a study of 336 patients with incident SLE, discoid rash at the time of SLE diagnosis predicted a fivefold higher risk for stroke, and renal disorder at the time of diagnosis was associated with a twofold higher risk, compared with non-Black patients, but neither of these symptoms predicted elevated risk of IHD.

In contrast, neurologic disorders, including prior psychosis or seizure, were associated with a fourfold higher risk for IHD, and immunologic disorders including anti-DNA, anti-Smith, or antiphospholipid antibodies were associated with a nearly fivefold greater risk for IHD in Black patients, but neither of these comorbidities predicted strokes, reported Shivani Garg, MD, assistant professor of medicine at the University of Wisconsin in Madison.

“Our study was one of the first to highlight racial disparities in CVD subtypes, with a threefold higher stroke risk and 24-fold higher ischemic heart disease risk in Black patients with lupus. Compared to previous studies in Black populations, our study highlights different peak timing of early stroke and ischemic heart disease in our cohort,“ she said at a plenary session during the virtual annual meeting of the American College of Rheumatology.

The study is one of the first to identify specific and unique SLE disease-related predictors of stroke and ischemic heart disease, she said.

Georgia Lupus Registry data

Dr. Garg and colleagues at the University of Wisconsin and Emory University in Atlanta drew on data from the Georgia Lupus Registry, a population-based registry of SLE patients from the Atlanta area. They identified patients diagnosed from 2002 through 2004 who had four or more ACR criteria for SLE, or three or more criteria plus a final diagnosis of SLE made by their board-certified rheumatologists.

The patients were matched to the Georgia Hospital Discharge Database and National Death Index from 2000 through 2013, with stroke- and IHD-related hospitalizations and deaths classified by the first three admission codes or cause-of-death codes.

Patients with transient ischemic attacks were included in the stroke category, and those with myocardial infarction and angina were included in the IHD category.

They identified 336 patients, 87% of whom were female, and 75% of whom were Black. The mean age at SLE diagnosis was 40 years. Among this cohort, there were 38 stroke-related events or deaths and 25 IHD-related events or deaths recorded from the period 2 years before through 14 years after an SLE diagnosis.
 

Early stroke, late IHD

The investigators first looked at the timing of stroke vs. IHD and found that a disproportionately high percentage of stroke events occurred in the second year after SLE diagnosis, whereas the peak of IHD-related events occurred in the 14^th year after diagnosis.

They then performed a race-stratified Cox proportional hazard analysis, and found a threefold higher risk for stroke in Black patients versus non-Black patients (P = .007) and a 24-fold higher risk for IHD (P < .0001).

In multivariate analysis, significant predictors of stroke were Black race with a hazard ratio (HR) of 3.4 (P = .028), discoid rash (HR, 4.6; P = .0028), and renal disorder (HR, 2.4; P = .04). However, stroke was not predicted by age, sex, immunologic disorder, serositis, hematologic disorder, or ACR criteria total greater than four.

Significant predictors of IHD included age 65 and older (HR, 61; P = .0007), Black race (HR, 24; P = .004), neurologic disorder (HR, 4.0; P = .018), and immunologic disorder (HR, 4.7; P = .02). But IHD could not be predicted by oral ulcers, discoid rash, or ACR criteria more than four.

“In future studies, we will examine mechanisms that drive the different timing and predictors of CVD subtypes and disparities. We will also examine the impact of timely prevention in high-risk SLE subsets,” Dr. Garg said.
 

Managing CVD risk

Angus Worthing, MD, from Arthritis & Rheumatism Associates in Chevy Chase, Md., and Washington, D.C., who moderated a press briefing where Dr. Garg discussed her data, routinely treats patients of different racial backgrounds with lupus. When asked how he manages patients with SLE and suspected cardiovascular complications, Dr. Worthing said, “I tend to, in my practice – and these kinds of studies may change what I do – watch for symptoms that might reflect coronary artery disease or cerebrovascular disease, potentially looking at the smaller arteries in the hands and feet as clues, and I will refer promptly to a vascular surgery expert or cardiologist for screening,” he said.

Dr. Garg added that in her practice, she and colleagues treat high-risk subsets of patients, such as those with lupus nephritis or multiple comorbidities, with aggressive blood pressure control and monitoring, as well as smoking cessation recommendations and lipid monitoring. They also try to limit or, if possible, decrease steroid doses to reduce risk for cardiovascular side effects.

Support for the study came in part from the U.S. Centers for Disease Control and Prevention. Dr. Garg and Dr. Worthing reported having no relevant disclosures.

SOURCE: Garg S et al. Arthritis Rheumatol. 2020;72(suppl 10): Abstract 433 .

New data document the global fallout for rheumatology patients when hydroxychloroquine (HCQ) supplies were being diverted to hospitals for COVID-19 patients.

Demand for HCQ soared on evidence-lacking claims that the drug was effective in treating and preventing SARS-CoV-2 infection. Further research has since shown HCQ to be ineffective for COVID-19 and potentially harmful to patients.

But during the height of the COVID-19-related hype, patients worldwide with autoimmune diseases, particularly lupus and rheumatoid arthritis, had trouble getting the pills at all or couldn’t get as many as they needed for their chronic conditions.

Emily Sirotich, MSc, a PhD student at McMaster University in Hamilton, Ont., presented data at the virtual annual meeting of the American College of Rheumatology demonstrating that the severity of shortages differed widely.

Whereas 26.7% of rheumatology patients in Africa and 21.4% in southeast Asia said their pharmacy ran short of HCQ – which was originally developed as an antimalarial drug but has been found effective in treating some rheumatic diseases – only 6.8% of patients in the Americas and 2.1% in European regions reported the shortages.

“There are large regional disparities in access to antimalarials whether they were caused by the COVID-19 pandemic or already existed,” she said in an interview.

Global survey polled patient experience

Ms. Sirotich’s team analyzed data from the Global Rheumatology Alliance Patient Experience Survey.

They found that from 9,393 respondents (average age 46.1 years and 90% female), 3,872 (41.2%) were taking antimalarials. Of these, 230 (6.2% globally) were unable to keep taking the drugs because their pharmacy ran out.

Researchers evaluated the effect of drug shortages on disease activity, mental health, and physical health by comparing mean values with two-sided independent t-tests to identify significant differences.

They found that patients who were unable to obtain antimalarials had significantly higher levels of rheumatic disease activity as well as poorer mental and physical health (all P < .001).

The survey was distributed online through patient support groups and on social media. Patients with rheumatic diseases or their parents anonymously entered data including their rheumatic disease diagnosis, medications, COVID-19 status, and disease outcomes.

Ms. Sirotich said they are currently gathering new data to see if the gaps in access to HCQ persist and whether the physical and mental consequences of not having the medications continue.

Hospitals stockpiled HCQ in the U.S.

Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists (ASHP), said in an interview that hospitals in the United States received large amounts of HCQ in late spring and early summer, donated by pharmaceutical companies for COVID-19 before the lack of evidence for efficacy became clear.

Hospitals found themselves sitting on large quantities of HCQ they couldn’t use while prescriptions for rheumatology outpatients were going unfilled.

It is only in recent months that the U.S. Department of Health and Human Services has given clear direction to hospitals on how to redistribute those supplies, Dr. Ganio said.

“There’s no good real good way to move a product from a hospital to a [drug store] down the street,” he said.

The Food and Drug Administration now lists the HCQ shortages as resolved.
 

Declined prescriptions have frustrated physicians

Brett Smith, DO, a pediatric and adult rheumatologist in Alcoa, Tenn., said he was frustrated by pharmacies declining his prescriptions for HCQ for patients with rheumatoid arthritis.

“I got notes from pharmacies that I should consider alternative agents,” he said in an interview. But the safety profiles of the alternatives were not as good, he said.

“Hydroxychloroquine has no risk of infection and no risk of malignancy, and they were proposing alternative agents that carry those risks,” he said.

“I had some people with RA who couldn’t get [HCQ] who had a substantial increase in swollen joints and pain without it,” he said.

Dr. Smith said some patients who use HCQ for off-label uses such as certain skin disorders still aren’t getting the drug, as off-label use has been discouraged to make sure those with lupus and RA have enough, he said.

Saira Sheikh, MD, director of the University of North Carolina Rheumatology Lupus Clinic in Chapel Hill, said in an interview that during the summer months pharmacists required additional documentation of the diagnosis of autoimmune disease, resulting in unnecessary delays even when patients had been on the medication for many years.

She said emerging research has found patient-reported barriers to filling prescriptions, interruptions in HCQ treatment, and reported emotional stress and anxiety related to medication access during the COVID-19 pandemic.

“This experience with HCQ during the COVID-19 pandemic teaches us that while swift action and progress to address the immediate threats of the pandemic should be commended, it is important that we move forward in a conscious manner, guided by an evidence base that comes from high-quality research, not from rushed judgments based on preliminary studies, or pressure from political leaders,” Dr. Sheikh said.

Ms. Sirotich, Dr. Smith, Dr. Sheikh, and Dr. Ganio have disclosed no relevant financial relationships.

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

New data document the global fallout for rheumatology patients when hydroxychloroquine (HCQ) supplies were being diverted to hospitals for COVID-19 patients.

Demand for HCQ soared on evidence-lacking claims that the drug was effective in treating and preventing SARS-CoV-2 infection. Further research has since shown HCQ to be ineffective for COVID-19 and potentially harmful to patients.

But during the height of the COVID-19-related hype, patients worldwide with autoimmune diseases, particularly lupus and rheumatoid arthritis, had trouble getting the pills at all or couldn’t get as many as they needed for their chronic conditions.

Emily Sirotich, MSc, a PhD student at McMaster University in Hamilton, Ont., presented data at the virtual annual meeting of the American College of Rheumatology demonstrating that the severity of shortages differed widely.

Whereas 26.7% of rheumatology patients in Africa and 21.4% in southeast Asia said their pharmacy ran short of HCQ – which was originally developed as an antimalarial drug but has been found effective in treating some rheumatic diseases – only 6.8% of patients in the Americas and 2.1% in European regions reported the shortages.

“There are large regional disparities in access to antimalarials whether they were caused by the COVID-19 pandemic or already existed,” she said in an interview.

Global survey polled patient experience

Ms. Sirotich’s team analyzed data from the Global Rheumatology Alliance Patient Experience Survey.

They found that from 9,393 respondents (average age 46.1 years and 90% female), 3,872 (41.2%) were taking antimalarials. Of these, 230 (6.2% globally) were unable to keep taking the drugs because their pharmacy ran out.

Researchers evaluated the effect of drug shortages on disease activity, mental health, and physical health by comparing mean values with two-sided independent t-tests to identify significant differences.

They found that patients who were unable to obtain antimalarials had significantly higher levels of rheumatic disease activity as well as poorer mental and physical health (all P < .001).

The survey was distributed online through patient support groups and on social media. Patients with rheumatic diseases or their parents anonymously entered data including their rheumatic disease diagnosis, medications, COVID-19 status, and disease outcomes.

Ms. Sirotich said they are currently gathering new data to see if the gaps in access to HCQ persist and whether the physical and mental consequences of not having the medications continue.

Hospitals stockpiled HCQ in the U.S.

Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists (ASHP), said in an interview that hospitals in the United States received large amounts of HCQ in late spring and early summer, donated by pharmaceutical companies for COVID-19 before the lack of evidence for efficacy became clear.

Hospitals found themselves sitting on large quantities of HCQ they couldn’t use while prescriptions for rheumatology outpatients were going unfilled.

It is only in recent months that the U.S. Department of Health and Human Services has given clear direction to hospitals on how to redistribute those supplies, Dr. Ganio said.

“There’s no good real good way to move a product from a hospital to a [drug store] down the street,” he said.

The Food and Drug Administration now lists the HCQ shortages as resolved.
 

Declined prescriptions have frustrated physicians

Brett Smith, DO, a pediatric and adult rheumatologist in Alcoa, Tenn., said he was frustrated by pharmacies declining his prescriptions for HCQ for patients with rheumatoid arthritis.

“I got notes from pharmacies that I should consider alternative agents,” he said in an interview. But the safety profiles of the alternatives were not as good, he said.

“Hydroxychloroquine has no risk of infection and no risk of malignancy, and they were proposing alternative agents that carry those risks,” he said.

“I had some people with RA who couldn’t get [HCQ] who had a substantial increase in swollen joints and pain without it,” he said.

Dr. Smith said some patients who use HCQ for off-label uses such as certain skin disorders still aren’t getting the drug, as off-label use has been discouraged to make sure those with lupus and RA have enough, he said.

Saira Sheikh, MD, director of the University of North Carolina Rheumatology Lupus Clinic in Chapel Hill, said in an interview that during the summer months pharmacists required additional documentation of the diagnosis of autoimmune disease, resulting in unnecessary delays even when patients had been on the medication for many years.

She said emerging research has found patient-reported barriers to filling prescriptions, interruptions in HCQ treatment, and reported emotional stress and anxiety related to medication access during the COVID-19 pandemic.

“This experience with HCQ during the COVID-19 pandemic teaches us that while swift action and progress to address the immediate threats of the pandemic should be commended, it is important that we move forward in a conscious manner, guided by an evidence base that comes from high-quality research, not from rushed judgments based on preliminary studies, or pressure from political leaders,” Dr. Sheikh said.

Ms. Sirotich, Dr. Smith, Dr. Sheikh, and Dr. Ganio have disclosed no relevant financial relationships.

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

New data document the global fallout for rheumatology patients when hydroxychloroquine (HCQ) supplies were being diverted to hospitals for COVID-19 patients.

Demand for HCQ soared on evidence-lacking claims that the drug was effective in treating and preventing SARS-CoV-2 infection. Further research has since shown HCQ to be ineffective for COVID-19 and potentially harmful to patients.

But during the height of the COVID-19-related hype, patients worldwide with autoimmune diseases, particularly lupus and rheumatoid arthritis, had trouble getting the pills at all or couldn’t get as many as they needed for their chronic conditions.

Emily Sirotich, MSc, a PhD student at McMaster University in Hamilton, Ont., presented data at the virtual annual meeting of the American College of Rheumatology demonstrating that the severity of shortages differed widely.

Whereas 26.7% of rheumatology patients in Africa and 21.4% in southeast Asia said their pharmacy ran short of HCQ – which was originally developed as an antimalarial drug but has been found effective in treating some rheumatic diseases – only 6.8% of patients in the Americas and 2.1% in European regions reported the shortages.

“There are large regional disparities in access to antimalarials whether they were caused by the COVID-19 pandemic or already existed,” she said in an interview.

Global survey polled patient experience

Ms. Sirotich’s team analyzed data from the Global Rheumatology Alliance Patient Experience Survey.

They found that from 9,393 respondents (average age 46.1 years and 90% female), 3,872 (41.2%) were taking antimalarials. Of these, 230 (6.2% globally) were unable to keep taking the drugs because their pharmacy ran out.

Researchers evaluated the effect of drug shortages on disease activity, mental health, and physical health by comparing mean values with two-sided independent t-tests to identify significant differences.

They found that patients who were unable to obtain antimalarials had significantly higher levels of rheumatic disease activity as well as poorer mental and physical health (all P < .001).

The survey was distributed online through patient support groups and on social media. Patients with rheumatic diseases or their parents anonymously entered data including their rheumatic disease diagnosis, medications, COVID-19 status, and disease outcomes.

Ms. Sirotich said they are currently gathering new data to see if the gaps in access to HCQ persist and whether the physical and mental consequences of not having the medications continue.

Hospitals stockpiled HCQ in the U.S.

Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists (ASHP), said in an interview that hospitals in the United States received large amounts of HCQ in late spring and early summer, donated by pharmaceutical companies for COVID-19 before the lack of evidence for efficacy became clear.

Hospitals found themselves sitting on large quantities of HCQ they couldn’t use while prescriptions for rheumatology outpatients were going unfilled.

It is only in recent months that the U.S. Department of Health and Human Services has given clear direction to hospitals on how to redistribute those supplies, Dr. Ganio said.

“There’s no good real good way to move a product from a hospital to a [drug store] down the street,” he said.

The Food and Drug Administration now lists the HCQ shortages as resolved.
 

Declined prescriptions have frustrated physicians

Brett Smith, DO, a pediatric and adult rheumatologist in Alcoa, Tenn., said he was frustrated by pharmacies declining his prescriptions for HCQ for patients with rheumatoid arthritis.

“I got notes from pharmacies that I should consider alternative agents,” he said in an interview. But the safety profiles of the alternatives were not as good, he said.

“Hydroxychloroquine has no risk of infection and no risk of malignancy, and they were proposing alternative agents that carry those risks,” he said.

“I had some people with RA who couldn’t get [HCQ] who had a substantial increase in swollen joints and pain without it,” he said.

Dr. Smith said some patients who use HCQ for off-label uses such as certain skin disorders still aren’t getting the drug, as off-label use has been discouraged to make sure those with lupus and RA have enough, he said.

Saira Sheikh, MD, director of the University of North Carolina Rheumatology Lupus Clinic in Chapel Hill, said in an interview that during the summer months pharmacists required additional documentation of the diagnosis of autoimmune disease, resulting in unnecessary delays even when patients had been on the medication for many years.

She said emerging research has found patient-reported barriers to filling prescriptions, interruptions in HCQ treatment, and reported emotional stress and anxiety related to medication access during the COVID-19 pandemic.

“This experience with HCQ during the COVID-19 pandemic teaches us that while swift action and progress to address the immediate threats of the pandemic should be commended, it is important that we move forward in a conscious manner, guided by an evidence base that comes from high-quality research, not from rushed judgments based on preliminary studies, or pressure from political leaders,” Dr. Sheikh said.

Ms. Sirotich, Dr. Smith, Dr. Sheikh, and Dr. Ganio have disclosed no relevant financial relationships.

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

The American College of Rheumatology will hold its annual meeting as a completely online event during Nov. 5-9, 2020, rather than in Washington, Nov. 6-11, as originally planned “due to public health/safety concerns related to the COVID-19 pandemic,” according to an announcement from the organization.

“We’ve given our annual meeting a new name, ACR Convergence 2020, and a fresh look, and we have reimagined #ACR20 without losing the elements you care about most: stellar rheumatology education, cutting-edge advances in science, and outstanding networking opportunities,” according to the announcement.

A frequently asked questions page for the meeting says that “ACR Convergence will include oral and poster discussion presentations, track-based clinical and basic science symposia, opportunities to engage with speakers and participants, as well as an exhibition and several special events.”

The ACR said that the meeting will be held on a new online platform, with more details to come in August, when registration will open. The final program for the virtual meeting will be available on the ACR website in July.

[email protected]

The American College of Rheumatology will hold its annual meeting as a completely online event during Nov. 5-9, 2020, rather than in Washington, Nov. 6-11, as originally planned “due to public health/safety concerns related to the COVID-19 pandemic,” according to an announcement from the organization.

“We’ve given our annual meeting a new name, ACR Convergence 2020, and a fresh look, and we have reimagined #ACR20 without losing the elements you care about most: stellar rheumatology education, cutting-edge advances in science, and outstanding networking opportunities,” according to the announcement.

A frequently asked questions page for the meeting says that “ACR Convergence will include oral and poster discussion presentations, track-based clinical and basic science symposia, opportunities to engage with speakers and participants, as well as an exhibition and several special events.”

The ACR said that the meeting will be held on a new online platform, with more details to come in August, when registration will open. The final program for the virtual meeting will be available on the ACR website in July.

[email protected]

The American College of Rheumatology will hold its annual meeting as a completely online event during Nov. 5-9, 2020, rather than in Washington, Nov. 6-11, as originally planned “due to public health/safety concerns related to the COVID-19 pandemic,” according to an announcement from the organization.

“We’ve given our annual meeting a new name, ACR Convergence 2020, and a fresh look, and we have reimagined #ACR20 without losing the elements you care about most: stellar rheumatology education, cutting-edge advances in science, and outstanding networking opportunities,” according to the announcement.

A frequently asked questions page for the meeting says that “ACR Convergence will include oral and poster discussion presentations, track-based clinical and basic science symposia, opportunities to engage with speakers and participants, as well as an exhibition and several special events.”

The ACR said that the meeting will be held on a new online platform, with more details to come in August, when registration will open. The final program for the virtual meeting will be available on the ACR website in July.

[email protected]