Lupus & Connective Tissue Diseases

The U.S. Food and Drug Administration has expanded the indication for belimumab (Benlysta) to adults with active lupus nephritis who are receiving standard therapy.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Roughly 40% of patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), which causes inflammation in the kidneys and can lead to end-stage kidney disease.

“Benlysta is the first medicine approved to treat systemic lupus and adults with active lupus nephritis, an important treatment advance for patients with this incurable autoimmune disease,” Hal Barron, MD, GlaxoSmithKline’s chief scientific officer and president of research and development, said in a company news release.

Belimumab IV infusion was first approved in the United States in March 2011 for adults with SLE. The FDA approved belimumab IV infusion for use in children as young as age 5 years with SLE in 2019.

Both the IV and subcutaneous formulations are now indicated in the United States for adults with SLE and LN.

Belimumab is a B-lymphocyte stimulator protein inhibitor that is thought to decrease the amount of abnormal B cells; the latter are thought to play a role in lupus.

The expanded indication for belimumab for patients with LN is based on findings from the BLISS-LN phase 3 trial, published in The New England Journal of Medicine in September.

“Neutralizing B-cell activating factor and down-regulating autoreactive B-cell function in kidneys” represents a “compelling therapeutic approach to lupus nephritis,” the lead investigator of BLISS-LN, Richard Furie, MD, told the online annual Perspectives in Rheumatic Diseases meeting recently.

“In the 4 decades I have been caring for people with lupus, we have not been able to achieve remission in more than just one-third of patients with lupus nephritis, and despite all of our efforts, 10%-30% of patients with lupus kidney disease still progress to end-stage kidney disease,” Dr. Furie, who is chief of the division of rheumatology at Northwell Health, notes in the GSK statement.

“The data from the BLISS-LN study show that Benlysta added to standard therapy not only increased response rates over 2 years, but it also prevented worsening of kidney disease in patients with active lupus nephritis, compared to standard therapy alone,” he added.

BLISS-LN study: Belimumab effect seen mostly in those on MMF

BLISS-LN enrolled 448 adults with biopsy-confirmed active LN. Half were randomly allocated to receive IV belimumab (10 mg/kg) plus standard therapy (mycophenolate mofetil for induction and maintenance or cyclophosphamide for induction followed by azathioprine for maintenance, with steroids) and half to receive placebo plus standard therapy.

At 2 years, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval, 1.0- 2.3; P = .03).

This primary endpoint was defined as a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate that was no worse than 20% below the value before the renal flare or ≥60 mL per minute per 1.73 m² of body surface area, without use of rescue therapy.

The risk for a renal-related event or death was also significantly lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; P = .001). The safety profile of belimumab was consistent with that observed in prior studies.

But in a commentary that accompanied the publication of BLISS-LN, editorialists noted that “most of the treatment effect was seen in patients who had received mycophenolate mofetil. No benefit was present in the subgroup of patients who received cyclophosphamide-azathioprine.”

In addition, induction treatment was not randomly assigned, editorialists Michael Ward, MD, MPH, and Maria Tektonidou, MD, PhD, noted.

“If patients with more severe nephritis were preferentially treated with cyclophosphamide, a likely inclination among most physicians, the trial may be telling us that belimumab enhances responses only among less severely affected patients,” observed Dr. Ward, who is with the National Institutes of Health, and Dr. Tektonidou, of the National and Kopodistrian University, in Athens.

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

The U.S. Food and Drug Administration has expanded the indication for belimumab (Benlysta) to adults with active lupus nephritis who are receiving standard therapy.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Roughly 40% of patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), which causes inflammation in the kidneys and can lead to end-stage kidney disease.

“Benlysta is the first medicine approved to treat systemic lupus and adults with active lupus nephritis, an important treatment advance for patients with this incurable autoimmune disease,” Hal Barron, MD, GlaxoSmithKline’s chief scientific officer and president of research and development, said in a company news release.

Belimumab IV infusion was first approved in the United States in March 2011 for adults with SLE. The FDA approved belimumab IV infusion for use in children as young as age 5 years with SLE in 2019.

Both the IV and subcutaneous formulations are now indicated in the United States for adults with SLE and LN.

Belimumab is a B-lymphocyte stimulator protein inhibitor that is thought to decrease the amount of abnormal B cells; the latter are thought to play a role in lupus.

The expanded indication for belimumab for patients with LN is based on findings from the BLISS-LN phase 3 trial, published in The New England Journal of Medicine in September.

“Neutralizing B-cell activating factor and down-regulating autoreactive B-cell function in kidneys” represents a “compelling therapeutic approach to lupus nephritis,” the lead investigator of BLISS-LN, Richard Furie, MD, told the online annual Perspectives in Rheumatic Diseases meeting recently.

“In the 4 decades I have been caring for people with lupus, we have not been able to achieve remission in more than just one-third of patients with lupus nephritis, and despite all of our efforts, 10%-30% of patients with lupus kidney disease still progress to end-stage kidney disease,” Dr. Furie, who is chief of the division of rheumatology at Northwell Health, notes in the GSK statement.

“The data from the BLISS-LN study show that Benlysta added to standard therapy not only increased response rates over 2 years, but it also prevented worsening of kidney disease in patients with active lupus nephritis, compared to standard therapy alone,” he added.

BLISS-LN study: Belimumab effect seen mostly in those on MMF

BLISS-LN enrolled 448 adults with biopsy-confirmed active LN. Half were randomly allocated to receive IV belimumab (10 mg/kg) plus standard therapy (mycophenolate mofetil for induction and maintenance or cyclophosphamide for induction followed by azathioprine for maintenance, with steroids) and half to receive placebo plus standard therapy.

At 2 years, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval, 1.0- 2.3; P = .03).

This primary endpoint was defined as a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate that was no worse than 20% below the value before the renal flare or ≥60 mL per minute per 1.73 m² of body surface area, without use of rescue therapy.

The risk for a renal-related event or death was also significantly lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; P = .001). The safety profile of belimumab was consistent with that observed in prior studies.

But in a commentary that accompanied the publication of BLISS-LN, editorialists noted that “most of the treatment effect was seen in patients who had received mycophenolate mofetil. No benefit was present in the subgroup of patients who received cyclophosphamide-azathioprine.”

In addition, induction treatment was not randomly assigned, editorialists Michael Ward, MD, MPH, and Maria Tektonidou, MD, PhD, noted.

“If patients with more severe nephritis were preferentially treated with cyclophosphamide, a likely inclination among most physicians, the trial may be telling us that belimumab enhances responses only among less severely affected patients,” observed Dr. Ward, who is with the National Institutes of Health, and Dr. Tektonidou, of the National and Kopodistrian University, in Athens.

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

The U.S. Food and Drug Administration has expanded the indication for belimumab (Benlysta) to adults with active lupus nephritis who are receiving standard therapy.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Roughly 40% of patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), which causes inflammation in the kidneys and can lead to end-stage kidney disease.

“Benlysta is the first medicine approved to treat systemic lupus and adults with active lupus nephritis, an important treatment advance for patients with this incurable autoimmune disease,” Hal Barron, MD, GlaxoSmithKline’s chief scientific officer and president of research and development, said in a company news release.

Belimumab IV infusion was first approved in the United States in March 2011 for adults with SLE. The FDA approved belimumab IV infusion for use in children as young as age 5 years with SLE in 2019.

Both the IV and subcutaneous formulations are now indicated in the United States for adults with SLE and LN.

Belimumab is a B-lymphocyte stimulator protein inhibitor that is thought to decrease the amount of abnormal B cells; the latter are thought to play a role in lupus.

The expanded indication for belimumab for patients with LN is based on findings from the BLISS-LN phase 3 trial, published in The New England Journal of Medicine in September.

“Neutralizing B-cell activating factor and down-regulating autoreactive B-cell function in kidneys” represents a “compelling therapeutic approach to lupus nephritis,” the lead investigator of BLISS-LN, Richard Furie, MD, told the online annual Perspectives in Rheumatic Diseases meeting recently.

“In the 4 decades I have been caring for people with lupus, we have not been able to achieve remission in more than just one-third of patients with lupus nephritis, and despite all of our efforts, 10%-30% of patients with lupus kidney disease still progress to end-stage kidney disease,” Dr. Furie, who is chief of the division of rheumatology at Northwell Health, notes in the GSK statement.

“The data from the BLISS-LN study show that Benlysta added to standard therapy not only increased response rates over 2 years, but it also prevented worsening of kidney disease in patients with active lupus nephritis, compared to standard therapy alone,” he added.

BLISS-LN study: Belimumab effect seen mostly in those on MMF

BLISS-LN enrolled 448 adults with biopsy-confirmed active LN. Half were randomly allocated to receive IV belimumab (10 mg/kg) plus standard therapy (mycophenolate mofetil for induction and maintenance or cyclophosphamide for induction followed by azathioprine for maintenance, with steroids) and half to receive placebo plus standard therapy.

At 2 years, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval, 1.0- 2.3; P = .03).

This primary endpoint was defined as a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate that was no worse than 20% below the value before the renal flare or ≥60 mL per minute per 1.73 m² of body surface area, without use of rescue therapy.

The risk for a renal-related event or death was also significantly lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; P = .001). The safety profile of belimumab was consistent with that observed in prior studies.

But in a commentary that accompanied the publication of BLISS-LN, editorialists noted that “most of the treatment effect was seen in patients who had received mycophenolate mofetil. No benefit was present in the subgroup of patients who received cyclophosphamide-azathioprine.”

In addition, induction treatment was not randomly assigned, editorialists Michael Ward, MD, MPH, and Maria Tektonidou, MD, PhD, noted.

“If patients with more severe nephritis were preferentially treated with cyclophosphamide, a likely inclination among most physicians, the trial may be telling us that belimumab enhances responses only among less severely affected patients,” observed Dr. Ward, who is with the National Institutes of Health, and Dr. Tektonidou, of the National and Kopodistrian University, in Athens.

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

A small group of patients with systemic lupus erythematosus (SLE) who have high costs and needs and frequent hospitalizations can be identified through a shared set of sociodemographic characteristics and risk factors that distinguish them from other patients, according to a retrospective analysis of hospitalization data from a tertiary care center.

“The identification of the HNHC [high-need, high-cost] cohort and the risk factors for hospitalizations for this cohort will help pave the way to develop programs that improve the quality of care for high-risk lupus patients and [at the same time] lower the cost of care for all lupus patients,” first author Allen Anandarajah, MBBS, and colleagues at the University of Rochester (N.Y.) wrote in Arthritis Care & Research.

Hospitalizations and readmissions are known to be common in patients with SLE, the authors said, and they “account for a large proportion of the direct costs associated with the care of this disease.”

“While HNHC cohorts have been described with other chronic diseases, this report is the first to describe the existence of such a cohort in the SLE population,” the researchers said.

To see if a small group of SLE patients would constitute the majority of hospitalizations and consequently the costs of such care, Dr. Anandarajah and associates analyzed data from 202 SLE patients and their 467 hospitalizations at the University of Rochester–affiliated Strong Memorial Hospital during July 1, 2013, to June 30, 2016. The patients had a mean age of 46 years and included 183 females. A total of 46.5% were White, 43.1% were African American, 6.9% were Hispanic, and 3.5% were of Asian descent. These patients had median lengths of stay of 7 days per SLE patient and 4 days per admission, with median costs of $19,271 per patient and $14,375 per admission.

The researchers identified 44 patients (22%) who accounted for 275 admissions (59%) during the 3-year period. This group’s median of 4 admissions per patient was significantly higher than the median of 1 recorded in all the other hospitalized SLE patients, as was its number of readmissions within 30 days (105 total and median of 1 vs. 11 total and median of 0). The high-risk SLE patients spent a significantly greater amount of time in the hospital than did other patients (median of 30 days vs. 5 days), and their median cost was more than six times as great ($95,262 vs. $14,360). High-risk patients’ median cost per admission also was significantly greater ($19,376 vs. $12,833).

Infections were the most common cause of hospitalization among both high-risk patients and others (28% vs. 23%, respectively) and the rate of involvement of different organ systems as a cause for hospitalization were similar between the groups, except that patients at lower risk significantly more often had gynecologic/obstetric concerns (10% vs. 2%) or nervous system involvement (16% vs. 5%), and high-risk patients were significantly more likely to have gastrointestinal complaints (20% vs. 8%).

Clinically, high-risk patients had significantly higher median scores on the Systemic Lupus International Collaborating Clinics Damage Index and the Comorbidity Index, as well as a significantly higher median level of double-stranded DNA. However, they had no differences in complement factor levels or body mass index.

The high-risk patients also were younger (mean of 42 vs. 46 years) and were diagnosed at a younger mean age (26 vs. 31 years). More high-risk patients were African American (55% vs. 40%) and were more likely to live in areas identified with poverty (50% vs. 29%).

A multivariate analysis that controlled for relevant confounders showed that high-risk patients had a 10 percentage point lower medication possession ratio, which is an indicator of whether a patient had adequate medication supply in a given time frame. High-risk patients overall had a higher average number of medications to treat lupus.

“Our findings underscore the importance of identifying HNHC SLE patients when designing and implementing interventions to lower hospitalizations and improve the quality of care for lupus patients. Furthermore, it is imperative that we develop programs to address the modifiable social and behavioral factors in addition to providing high-quality clinical care targeted for this group,” the researchers wrote.

Some of the limitations in the generalizability of the results include the use of data from a large tertiary medical center serving a large catchment area, with a consequently sicker group of patients, and the potential to miss readmissions to other nearby hospitals. However, “as one of the few centers [in the region] that provides in-patient rheumatology care ... it is less likely that patients would have sought care elsewhere,” they noted.

The study involved no outside source of funding, and the authors had no relevant conflicts of interest.

[email protected]

SOURCE: Anandarajah A et al. Arthritis Care Res. 2020 Nov 17. doi: 10.1002/acr.24510.

A small group of patients with systemic lupus erythematosus (SLE) who have high costs and needs and frequent hospitalizations can be identified through a shared set of sociodemographic characteristics and risk factors that distinguish them from other patients, according to a retrospective analysis of hospitalization data from a tertiary care center.

“The identification of the HNHC [high-need, high-cost] cohort and the risk factors for hospitalizations for this cohort will help pave the way to develop programs that improve the quality of care for high-risk lupus patients and [at the same time] lower the cost of care for all lupus patients,” first author Allen Anandarajah, MBBS, and colleagues at the University of Rochester (N.Y.) wrote in Arthritis Care & Research.

Hospitalizations and readmissions are known to be common in patients with SLE, the authors said, and they “account for a large proportion of the direct costs associated with the care of this disease.”

“While HNHC cohorts have been described with other chronic diseases, this report is the first to describe the existence of such a cohort in the SLE population,” the researchers said.

To see if a small group of SLE patients would constitute the majority of hospitalizations and consequently the costs of such care, Dr. Anandarajah and associates analyzed data from 202 SLE patients and their 467 hospitalizations at the University of Rochester–affiliated Strong Memorial Hospital during July 1, 2013, to June 30, 2016. The patients had a mean age of 46 years and included 183 females. A total of 46.5% were White, 43.1% were African American, 6.9% were Hispanic, and 3.5% were of Asian descent. These patients had median lengths of stay of 7 days per SLE patient and 4 days per admission, with median costs of $19,271 per patient and $14,375 per admission.

The researchers identified 44 patients (22%) who accounted for 275 admissions (59%) during the 3-year period. This group’s median of 4 admissions per patient was significantly higher than the median of 1 recorded in all the other hospitalized SLE patients, as was its number of readmissions within 30 days (105 total and median of 1 vs. 11 total and median of 0). The high-risk SLE patients spent a significantly greater amount of time in the hospital than did other patients (median of 30 days vs. 5 days), and their median cost was more than six times as great ($95,262 vs. $14,360). High-risk patients’ median cost per admission also was significantly greater ($19,376 vs. $12,833).

Infections were the most common cause of hospitalization among both high-risk patients and others (28% vs. 23%, respectively) and the rate of involvement of different organ systems as a cause for hospitalization were similar between the groups, except that patients at lower risk significantly more often had gynecologic/obstetric concerns (10% vs. 2%) or nervous system involvement (16% vs. 5%), and high-risk patients were significantly more likely to have gastrointestinal complaints (20% vs. 8%).

Clinically, high-risk patients had significantly higher median scores on the Systemic Lupus International Collaborating Clinics Damage Index and the Comorbidity Index, as well as a significantly higher median level of double-stranded DNA. However, they had no differences in complement factor levels or body mass index.

The high-risk patients also were younger (mean of 42 vs. 46 years) and were diagnosed at a younger mean age (26 vs. 31 years). More high-risk patients were African American (55% vs. 40%) and were more likely to live in areas identified with poverty (50% vs. 29%).

A multivariate analysis that controlled for relevant confounders showed that high-risk patients had a 10 percentage point lower medication possession ratio, which is an indicator of whether a patient had adequate medication supply in a given time frame. High-risk patients overall had a higher average number of medications to treat lupus.

“Our findings underscore the importance of identifying HNHC SLE patients when designing and implementing interventions to lower hospitalizations and improve the quality of care for lupus patients. Furthermore, it is imperative that we develop programs to address the modifiable social and behavioral factors in addition to providing high-quality clinical care targeted for this group,” the researchers wrote.

Some of the limitations in the generalizability of the results include the use of data from a large tertiary medical center serving a large catchment area, with a consequently sicker group of patients, and the potential to miss readmissions to other nearby hospitals. However, “as one of the few centers [in the region] that provides in-patient rheumatology care ... it is less likely that patients would have sought care elsewhere,” they noted.

The study involved no outside source of funding, and the authors had no relevant conflicts of interest.

[email protected]

SOURCE: Anandarajah A et al. Arthritis Care Res. 2020 Nov 17. doi: 10.1002/acr.24510.

A small group of patients with systemic lupus erythematosus (SLE) who have high costs and needs and frequent hospitalizations can be identified through a shared set of sociodemographic characteristics and risk factors that distinguish them from other patients, according to a retrospective analysis of hospitalization data from a tertiary care center.

“The identification of the HNHC [high-need, high-cost] cohort and the risk factors for hospitalizations for this cohort will help pave the way to develop programs that improve the quality of care for high-risk lupus patients and [at the same time] lower the cost of care for all lupus patients,” first author Allen Anandarajah, MBBS, and colleagues at the University of Rochester (N.Y.) wrote in Arthritis Care & Research.

Hospitalizations and readmissions are known to be common in patients with SLE, the authors said, and they “account for a large proportion of the direct costs associated with the care of this disease.”

“While HNHC cohorts have been described with other chronic diseases, this report is the first to describe the existence of such a cohort in the SLE population,” the researchers said.

To see if a small group of SLE patients would constitute the majority of hospitalizations and consequently the costs of such care, Dr. Anandarajah and associates analyzed data from 202 SLE patients and their 467 hospitalizations at the University of Rochester–affiliated Strong Memorial Hospital during July 1, 2013, to June 30, 2016. The patients had a mean age of 46 years and included 183 females. A total of 46.5% were White, 43.1% were African American, 6.9% were Hispanic, and 3.5% were of Asian descent. These patients had median lengths of stay of 7 days per SLE patient and 4 days per admission, with median costs of $19,271 per patient and $14,375 per admission.

The researchers identified 44 patients (22%) who accounted for 275 admissions (59%) during the 3-year period. This group’s median of 4 admissions per patient was significantly higher than the median of 1 recorded in all the other hospitalized SLE patients, as was its number of readmissions within 30 days (105 total and median of 1 vs. 11 total and median of 0). The high-risk SLE patients spent a significantly greater amount of time in the hospital than did other patients (median of 30 days vs. 5 days), and their median cost was more than six times as great ($95,262 vs. $14,360). High-risk patients’ median cost per admission also was significantly greater ($19,376 vs. $12,833).

Infections were the most common cause of hospitalization among both high-risk patients and others (28% vs. 23%, respectively) and the rate of involvement of different organ systems as a cause for hospitalization were similar between the groups, except that patients at lower risk significantly more often had gynecologic/obstetric concerns (10% vs. 2%) or nervous system involvement (16% vs. 5%), and high-risk patients were significantly more likely to have gastrointestinal complaints (20% vs. 8%).

Clinically, high-risk patients had significantly higher median scores on the Systemic Lupus International Collaborating Clinics Damage Index and the Comorbidity Index, as well as a significantly higher median level of double-stranded DNA. However, they had no differences in complement factor levels or body mass index.

The high-risk patients also were younger (mean of 42 vs. 46 years) and were diagnosed at a younger mean age (26 vs. 31 years). More high-risk patients were African American (55% vs. 40%) and were more likely to live in areas identified with poverty (50% vs. 29%).

A multivariate analysis that controlled for relevant confounders showed that high-risk patients had a 10 percentage point lower medication possession ratio, which is an indicator of whether a patient had adequate medication supply in a given time frame. High-risk patients overall had a higher average number of medications to treat lupus.

“Our findings underscore the importance of identifying HNHC SLE patients when designing and implementing interventions to lower hospitalizations and improve the quality of care for lupus patients. Furthermore, it is imperative that we develop programs to address the modifiable social and behavioral factors in addition to providing high-quality clinical care targeted for this group,” the researchers wrote.

Some of the limitations in the generalizability of the results include the use of data from a large tertiary medical center serving a large catchment area, with a consequently sicker group of patients, and the potential to miss readmissions to other nearby hospitals. However, “as one of the few centers [in the region] that provides in-patient rheumatology care ... it is less likely that patients would have sought care elsewhere,” they noted.

The study involved no outside source of funding, and the authors had no relevant conflicts of interest.

[email protected]

SOURCE: Anandarajah A et al. Arthritis Care Res. 2020 Nov 17. doi: 10.1002/acr.24510.

The American College of Rheumatology hosted its first-ever all-virtual annual meeting this year. Convergence 2020 highlighted several important treatment abstracts related to systemic lupus erythematosus. 

Dr Michelle Petri, of Johns Hopkins University, reports on the use of hydroxychloroquine, which was not found to be associated with QTc length in a large cohort of patients with lupus and rheumatoid arthritis. This is notable because hydroxychloroquine was implicated in ventricular arrhythmias in patients with COVID-19 who were also given azithromycin.

Dr Petri also looks at the results of two trials focusing on the effects of belimumab and obinutuzumab on renal outcomes.

In the belimumab trial, the primary outcome was a 700-mg reduction in the urine protein to creatinine ratio, and it met that outcome with a 10.8% delta that was statistically significant. It also met the complete renal response outcome of less than 500 mg with a 10% delta, which is statistically significant.

In the other study, obinutuzumab showed a marked improvement over rituximab as a B-cell depleter.

The completion of the phase 2 trial means that there are now 2 years of data showing a 19% delta between obinutuzumab and standard-of-care treatment.  

Finally, Dr Petri highlights two studies focusing on nonrenal lupus and the use of both BIIB059 and iberdomide.

--

Michelle Petri, MD, MPH, Professor, Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Director, Johns Hopkins Lupus Center, Johns Hopkins Hospital, Baltimore, Maryland.

Michelle Petri, MD, MPH, has disclosed the following relevant financial relationships:
Received research grant from: GlaxoSmithKline; Eli Lilly and Company; Thermo Fisher; Hexagen; AstraZeneca
Received income in an amount equal to or greater than $250 from: AbbVie; Amgen; AstraZeneca; Blackrock; Bristol-Myers Squibb; Hexagen; Glenmark; GlaxoSmithKline; IQVIA; Janssen; Eli Lilly and Company; Merck; EMD Serono; Novartis; Sanofi; Thermo Fisher; UCB

The American College of Rheumatology hosted its first-ever all-virtual annual meeting this year. Convergence 2020 highlighted several important treatment abstracts related to systemic lupus erythematosus. 

Dr Michelle Petri, of Johns Hopkins University, reports on the use of hydroxychloroquine, which was not found to be associated with QTc length in a large cohort of patients with lupus and rheumatoid arthritis. This is notable because hydroxychloroquine was implicated in ventricular arrhythmias in patients with COVID-19 who were also given azithromycin.

Dr Petri also looks at the results of two trials focusing on the effects of belimumab and obinutuzumab on renal outcomes.

In the belimumab trial, the primary outcome was a 700-mg reduction in the urine protein to creatinine ratio, and it met that outcome with a 10.8% delta that was statistically significant. It also met the complete renal response outcome of less than 500 mg with a 10% delta, which is statistically significant.

In the other study, obinutuzumab showed a marked improvement over rituximab as a B-cell depleter.

The completion of the phase 2 trial means that there are now 2 years of data showing a 19% delta between obinutuzumab and standard-of-care treatment.  

Finally, Dr Petri highlights two studies focusing on nonrenal lupus and the use of both BIIB059 and iberdomide.

--

Michelle Petri, MD, MPH, Professor, Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Director, Johns Hopkins Lupus Center, Johns Hopkins Hospital, Baltimore, Maryland.

Michelle Petri, MD, MPH, has disclosed the following relevant financial relationships:
Received research grant from: GlaxoSmithKline; Eli Lilly and Company; Thermo Fisher; Hexagen; AstraZeneca
Received income in an amount equal to or greater than $250 from: AbbVie; Amgen; AstraZeneca; Blackrock; Bristol-Myers Squibb; Hexagen; Glenmark; GlaxoSmithKline; IQVIA; Janssen; Eli Lilly and Company; Merck; EMD Serono; Novartis; Sanofi; Thermo Fisher; UCB

The American College of Rheumatology hosted its first-ever all-virtual annual meeting this year. Convergence 2020 highlighted several important treatment abstracts related to systemic lupus erythematosus. 

Dr Michelle Petri, of Johns Hopkins University, reports on the use of hydroxychloroquine, which was not found to be associated with QTc length in a large cohort of patients with lupus and rheumatoid arthritis. This is notable because hydroxychloroquine was implicated in ventricular arrhythmias in patients with COVID-19 who were also given azithromycin.

Dr Petri also looks at the results of two trials focusing on the effects of belimumab and obinutuzumab on renal outcomes.

In the belimumab trial, the primary outcome was a 700-mg reduction in the urine protein to creatinine ratio, and it met that outcome with a 10.8% delta that was statistically significant. It also met the complete renal response outcome of less than 500 mg with a 10% delta, which is statistically significant.

In the other study, obinutuzumab showed a marked improvement over rituximab as a B-cell depleter.

The completion of the phase 2 trial means that there are now 2 years of data showing a 19% delta between obinutuzumab and standard-of-care treatment.  

Finally, Dr Petri highlights two studies focusing on nonrenal lupus and the use of both BIIB059 and iberdomide.

--

Michelle Petri, MD, MPH, Professor, Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Director, Johns Hopkins Lupus Center, Johns Hopkins Hospital, Baltimore, Maryland.

Michelle Petri, MD, MPH, has disclosed the following relevant financial relationships:
Received research grant from: GlaxoSmithKline; Eli Lilly and Company; Thermo Fisher; Hexagen; AstraZeneca
Received income in an amount equal to or greater than $250 from: AbbVie; Amgen; AstraZeneca; Blackrock; Bristol-Myers Squibb; Hexagen; Glenmark; GlaxoSmithKline; IQVIA; Janssen; Eli Lilly and Company; Merck; EMD Serono; Novartis; Sanofi; Thermo Fisher; UCB

Slowly tapering off – or remaining on – antimalarial medications can help prevent disease flare in patients with systemic lupus erythematosus (SLE) who’ve achieved clinical remission for at least a year, according to a new study that was presented at the virtual annual meeting of the American College of Rheumatology.

“Except in the setting of toxicity, cessation of antimalarial medication in patients with disease quiescence is feasible using a slow taper,” lead author Danaë Papachristos, MBBS, said during an oral abstract presentation at the online meeting. Dr. Papachristos conducted the research while a clinical and research fellow at the University of Toronto’s lupus clinic, but is now a consultant rheumatologist at the Wesley Hospital in Brisbane, Queensland, Australia.

To investigate flare in patients with SLE who were on or recently off antimalarial medications (AMs), the researchers identified 1,573 potential participants from a long-term observational cohort study at the university’s lupus clinic. From that larger group, 88 cases – patients who achieved clinical remission for at least a year and stopped taking AMs – were matched to at least one control – patients who also achieved remission and continued on medication. Most cases were also matched to a second control, bringing the total number to 173. All patients had at least 2 years of follow-up.

Flare was defined as any increase in the SLEDAI-2K score, with major flare defined as an increase of 4 or more. Patients in the case group were roughly 44 years old, compared with an average age of 46 in the control group. Both groups were almost entirely female and largely white. Reasons for withdrawal in the case group included self-cessation, disease quiescence, and retinal, mucocutaneous, or cardiac toxicities. Twenty participants in the case group reported AM toxicity, compared with four controls.

Dr. Papachristos noted in her presentation that the toxicity disparity was expected, “because controls are those who continue their medication, and most patients who have toxicity will stop their medication.”

Disease flare occurred in 61.4% of cases, compared with 45.1% of controls (P = .002), with the most common types being cutaneous and musculoskeletal flares. After multivariate analysis, the risk of flare more than doubled for those who ceased AMs (odds ratio, 2.26; 95% confidence interval, 1.24-4.11; P = .008). More than half of the cases (n = 46) restarted AMs after withdrawal, which was largely due to disease flare. Of the patients who restarted due to flare, 88% either recaptured control or improved, and the remaining 12% had further flares.

Of the 88 patients in the case group, 51 abruptly withdrew AMs while 37 tapered off. Patients who tapered had fewer flares (45.9%), compared with patients who withdrew abruptly (72.6%). After multivariate analysis, the risk of flare more than tripled for the abrupt withdrawal group (OR, 3.42; 95% CI, 1.26-9.26; P = .016). Fewer patients who tapered later restarted AMs, compared with the abrupt withdrawal group (37.8% vs. 62.7%; P = .02).

When asked about other differences in medications between the two groups, Dr. Papachristos answered: “We didn’t look into that specifically. We did look at those patients who were on prednisone and on any immunosuppression, although we didn’t look at specific therapies. Those variables were adjusted for in the analysis, and it didn’t make any difference if patients were on immunosuppression or prednisone at the point of index date.

“But we would like to look into the different forms of immunosuppression,” she added, “just to see if that made any difference.”

Withdrawing hydroxychloroquine in older patients

Older patients with SLE who discontinue their use of hydroxychloroquine (HCQ) are also not at increased risk of disease flare, according to a retrospective chart review from rheumatologists Ruth Fernandez-Ruiz, MD, and Peter M. Izmirly, MD, of New York University (Arthritis Res Ther. 2020;22:191. doi: 10.1186/s13075-020-02282-0).

“We wanted to focus on older patients who may have a lower risk of flaring and a higher risk of side effects from the drug,” Dr. Fernandez-Ruiz said in an interview.

The doctors embarked on the study after noticing eye and heart toxicities in certain older patients. They matched 26 lupus patients who had been on HCQ for at least 5 years before discontinuing the drug with 32 control patients who remained on HCQ, ultimately finding that withdrawal had no effect on their risk of lupus flares within a year.

“After starting a drug, the second question most people ask, after ‘What are the side effects?’ is ‘How long do I have to be on this?’ ” Dr. Izmirly said in an interview. “These patients are having side effects associated with long-term HCQ use. And we were noticing that, after you stop the drug, despite what you’re taught, they weren’t flaring.”

Only five patients from each group – 19.2% of the withdrawal group and 15.6% of the continuation group – experienced a flare (OR, 1.28; 95% CI, 0.31-5.30; P = .73). Most of the flares were cutaneous and musculoskeletal in nature, and no severe flares occurred in either group.

“On each side, the overall flare rate was not that high, and they were all relatively mild,” Dr. Izmirly said.

The two doctors acknowledged their study’s smaller sample size, compared with the study by Papachristos and colleagues, along with the advanced age of their patient population, which limits the generalizability of their findings. “We selected patients who had a very low disease activity to begin with, and who were older,” Dr. Fernandez-Ruiz noted.

That said, they reinforced the scarcity of existing research on this subset of lupus patients, one that will only continue to grow.

“Older [patients with] lupus,” Dr. Izmirly said, are “an understudied demographic.”

One of the authors of the study presented at ACR 2020 acknowledged receiving research support and consulting fees from various pharmaceutical companies. The HCQ study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases; its authors declared no conflicts of interest.

SOURCE: Papachristos D et al. Arthritis Rheumatol. 2020;72(suppl 10). Abstract 0983.

Slowly tapering off – or remaining on – antimalarial medications can help prevent disease flare in patients with systemic lupus erythematosus (SLE) who’ve achieved clinical remission for at least a year, according to a new study that was presented at the virtual annual meeting of the American College of Rheumatology.

“Except in the setting of toxicity, cessation of antimalarial medication in patients with disease quiescence is feasible using a slow taper,” lead author Danaë Papachristos, MBBS, said during an oral abstract presentation at the online meeting. Dr. Papachristos conducted the research while a clinical and research fellow at the University of Toronto’s lupus clinic, but is now a consultant rheumatologist at the Wesley Hospital in Brisbane, Queensland, Australia.

To investigate flare in patients with SLE who were on or recently off antimalarial medications (AMs), the researchers identified 1,573 potential participants from a long-term observational cohort study at the university’s lupus clinic. From that larger group, 88 cases – patients who achieved clinical remission for at least a year and stopped taking AMs – were matched to at least one control – patients who also achieved remission and continued on medication. Most cases were also matched to a second control, bringing the total number to 173. All patients had at least 2 years of follow-up.

Flare was defined as any increase in the SLEDAI-2K score, with major flare defined as an increase of 4 or more. Patients in the case group were roughly 44 years old, compared with an average age of 46 in the control group. Both groups were almost entirely female and largely white. Reasons for withdrawal in the case group included self-cessation, disease quiescence, and retinal, mucocutaneous, or cardiac toxicities. Twenty participants in the case group reported AM toxicity, compared with four controls.

Dr. Papachristos noted in her presentation that the toxicity disparity was expected, “because controls are those who continue their medication, and most patients who have toxicity will stop their medication.”

Disease flare occurred in 61.4% of cases, compared with 45.1% of controls (P = .002), with the most common types being cutaneous and musculoskeletal flares. After multivariate analysis, the risk of flare more than doubled for those who ceased AMs (odds ratio, 2.26; 95% confidence interval, 1.24-4.11; P = .008). More than half of the cases (n = 46) restarted AMs after withdrawal, which was largely due to disease flare. Of the patients who restarted due to flare, 88% either recaptured control or improved, and the remaining 12% had further flares.

Of the 88 patients in the case group, 51 abruptly withdrew AMs while 37 tapered off. Patients who tapered had fewer flares (45.9%), compared with patients who withdrew abruptly (72.6%). After multivariate analysis, the risk of flare more than tripled for the abrupt withdrawal group (OR, 3.42; 95% CI, 1.26-9.26; P = .016). Fewer patients who tapered later restarted AMs, compared with the abrupt withdrawal group (37.8% vs. 62.7%; P = .02).

When asked about other differences in medications between the two groups, Dr. Papachristos answered: “We didn’t look into that specifically. We did look at those patients who were on prednisone and on any immunosuppression, although we didn’t look at specific therapies. Those variables were adjusted for in the analysis, and it didn’t make any difference if patients were on immunosuppression or prednisone at the point of index date.

“But we would like to look into the different forms of immunosuppression,” she added, “just to see if that made any difference.”

Withdrawing hydroxychloroquine in older patients

Older patients with SLE who discontinue their use of hydroxychloroquine (HCQ) are also not at increased risk of disease flare, according to a retrospective chart review from rheumatologists Ruth Fernandez-Ruiz, MD, and Peter M. Izmirly, MD, of New York University (Arthritis Res Ther. 2020;22:191. doi: 10.1186/s13075-020-02282-0).

“We wanted to focus on older patients who may have a lower risk of flaring and a higher risk of side effects from the drug,” Dr. Fernandez-Ruiz said in an interview.

The doctors embarked on the study after noticing eye and heart toxicities in certain older patients. They matched 26 lupus patients who had been on HCQ for at least 5 years before discontinuing the drug with 32 control patients who remained on HCQ, ultimately finding that withdrawal had no effect on their risk of lupus flares within a year.

“After starting a drug, the second question most people ask, after ‘What are the side effects?’ is ‘How long do I have to be on this?’ ” Dr. Izmirly said in an interview. “These patients are having side effects associated with long-term HCQ use. And we were noticing that, after you stop the drug, despite what you’re taught, they weren’t flaring.”

Only five patients from each group – 19.2% of the withdrawal group and 15.6% of the continuation group – experienced a flare (OR, 1.28; 95% CI, 0.31-5.30; P = .73). Most of the flares were cutaneous and musculoskeletal in nature, and no severe flares occurred in either group.

“On each side, the overall flare rate was not that high, and they were all relatively mild,” Dr. Izmirly said.

The two doctors acknowledged their study’s smaller sample size, compared with the study by Papachristos and colleagues, along with the advanced age of their patient population, which limits the generalizability of their findings. “We selected patients who had a very low disease activity to begin with, and who were older,” Dr. Fernandez-Ruiz noted.

That said, they reinforced the scarcity of existing research on this subset of lupus patients, one that will only continue to grow.

“Older [patients with] lupus,” Dr. Izmirly said, are “an understudied demographic.”

One of the authors of the study presented at ACR 2020 acknowledged receiving research support and consulting fees from various pharmaceutical companies. The HCQ study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases; its authors declared no conflicts of interest.

SOURCE: Papachristos D et al. Arthritis Rheumatol. 2020;72(suppl 10). Abstract 0983.

Slowly tapering off – or remaining on – antimalarial medications can help prevent disease flare in patients with systemic lupus erythematosus (SLE) who’ve achieved clinical remission for at least a year, according to a new study that was presented at the virtual annual meeting of the American College of Rheumatology.

“Except in the setting of toxicity, cessation of antimalarial medication in patients with disease quiescence is feasible using a slow taper,” lead author Danaë Papachristos, MBBS, said during an oral abstract presentation at the online meeting. Dr. Papachristos conducted the research while a clinical and research fellow at the University of Toronto’s lupus clinic, but is now a consultant rheumatologist at the Wesley Hospital in Brisbane, Queensland, Australia.

To investigate flare in patients with SLE who were on or recently off antimalarial medications (AMs), the researchers identified 1,573 potential participants from a long-term observational cohort study at the university’s lupus clinic. From that larger group, 88 cases – patients who achieved clinical remission for at least a year and stopped taking AMs – were matched to at least one control – patients who also achieved remission and continued on medication. Most cases were also matched to a second control, bringing the total number to 173. All patients had at least 2 years of follow-up.

Flare was defined as any increase in the SLEDAI-2K score, with major flare defined as an increase of 4 or more. Patients in the case group were roughly 44 years old, compared with an average age of 46 in the control group. Both groups were almost entirely female and largely white. Reasons for withdrawal in the case group included self-cessation, disease quiescence, and retinal, mucocutaneous, or cardiac toxicities. Twenty participants in the case group reported AM toxicity, compared with four controls.

Dr. Papachristos noted in her presentation that the toxicity disparity was expected, “because controls are those who continue their medication, and most patients who have toxicity will stop their medication.”

Disease flare occurred in 61.4% of cases, compared with 45.1% of controls (P = .002), with the most common types being cutaneous and musculoskeletal flares. After multivariate analysis, the risk of flare more than doubled for those who ceased AMs (odds ratio, 2.26; 95% confidence interval, 1.24-4.11; P = .008). More than half of the cases (n = 46) restarted AMs after withdrawal, which was largely due to disease flare. Of the patients who restarted due to flare, 88% either recaptured control or improved, and the remaining 12% had further flares.

Of the 88 patients in the case group, 51 abruptly withdrew AMs while 37 tapered off. Patients who tapered had fewer flares (45.9%), compared with patients who withdrew abruptly (72.6%). After multivariate analysis, the risk of flare more than tripled for the abrupt withdrawal group (OR, 3.42; 95% CI, 1.26-9.26; P = .016). Fewer patients who tapered later restarted AMs, compared with the abrupt withdrawal group (37.8% vs. 62.7%; P = .02).

When asked about other differences in medications between the two groups, Dr. Papachristos answered: “We didn’t look into that specifically. We did look at those patients who were on prednisone and on any immunosuppression, although we didn’t look at specific therapies. Those variables were adjusted for in the analysis, and it didn’t make any difference if patients were on immunosuppression or prednisone at the point of index date.

“But we would like to look into the different forms of immunosuppression,” she added, “just to see if that made any difference.”

Withdrawing hydroxychloroquine in older patients

Older patients with SLE who discontinue their use of hydroxychloroquine (HCQ) are also not at increased risk of disease flare, according to a retrospective chart review from rheumatologists Ruth Fernandez-Ruiz, MD, and Peter M. Izmirly, MD, of New York University (Arthritis Res Ther. 2020;22:191. doi: 10.1186/s13075-020-02282-0).

“We wanted to focus on older patients who may have a lower risk of flaring and a higher risk of side effects from the drug,” Dr. Fernandez-Ruiz said in an interview.

The doctors embarked on the study after noticing eye and heart toxicities in certain older patients. They matched 26 lupus patients who had been on HCQ for at least 5 years before discontinuing the drug with 32 control patients who remained on HCQ, ultimately finding that withdrawal had no effect on their risk of lupus flares within a year.

“After starting a drug, the second question most people ask, after ‘What are the side effects?’ is ‘How long do I have to be on this?’ ” Dr. Izmirly said in an interview. “These patients are having side effects associated with long-term HCQ use. And we were noticing that, after you stop the drug, despite what you’re taught, they weren’t flaring.”

Only five patients from each group – 19.2% of the withdrawal group and 15.6% of the continuation group – experienced a flare (OR, 1.28; 95% CI, 0.31-5.30; P = .73). Most of the flares were cutaneous and musculoskeletal in nature, and no severe flares occurred in either group.

“On each side, the overall flare rate was not that high, and they were all relatively mild,” Dr. Izmirly said.

The two doctors acknowledged their study’s smaller sample size, compared with the study by Papachristos and colleagues, along with the advanced age of their patient population, which limits the generalizability of their findings. “We selected patients who had a very low disease activity to begin with, and who were older,” Dr. Fernandez-Ruiz noted.

That said, they reinforced the scarcity of existing research on this subset of lupus patients, one that will only continue to grow.

“Older [patients with] lupus,” Dr. Izmirly said, are “an understudied demographic.”

One of the authors of the study presented at ACR 2020 acknowledged receiving research support and consulting fees from various pharmaceutical companies. The HCQ study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases; its authors declared no conflicts of interest.

SOURCE: Papachristos D et al. Arthritis Rheumatol. 2020;72(suppl 10). Abstract 0983.

Not all chronic systemic inflammatory diseases are equal enhancers of atherosclerotic cardiovascular disease risk, according to a large case-control study.  

Current AHA/American College of Cardiology guidelines cite three chronic inflammatory diseases as atherosclerotic cardiovascular disease risk enhancers: rheumatoid arthritis, psoriasis, and HIV infection. But this study of those three diseases, along with three others marked by elevated high sensitivity C-reactive protein (systemic sclerosis, inflammatory bowel disease, and systemic lupus erythematosus [SLE]), showed that chronic inflammatory diseases are not monolithic in terms of their associated risk of incident coronary heart disease (CHD).

Indeed, two of the six inflammatory diseases – psoriasis and inflammatory bowel disease – turned out to be not at all associated with increased cardiovascular risk in the 37,117-patient study. The highest-risk disease was SLE, not specifically mentioned in the guidelines, Arjun Sinha, MD, a cardiology fellow at Northwestern University, Chicago, noted in his presentation at the virtual American Heart Association scientific sessions. 

The study included 18,129 patients with one of the six chronic inflammatory diseases and 18,988 matched controls, none with CHD at baseline. All regularly received outpatient care at Northwestern during 2000-2019. There were 1,011 incident CHD events during a median of 3.5 years of follow-up. 

In a Cox proportional hazards analysis adjusted for demographics, insurance status, hypertension, diabetes, current smoking, total cholesterol, and estimated glomerular filtration rate, here’s how the chronic inflammatory diseases stacked up in terms of incident CHD and MI risks: 

• SLE: hazard ratio for CHD, 2.85; for MI, 4.76.
• Systemic sclerosis: HR for CHD, 2.14; for MI, 3.19.
• HIV: HR for CHD, 1.38; for MI, 1.69.
• Rheumatoid arthritis: HR for CHD, 1.22; for MI, 1.45.
• Psoriasis: no significant increase.
• Inflammatory bowel disease: no significant increase.

In an exploratory analysis, Dr. Sinha and coinvestigators evaluated the risk of incident CHD stratified by disease severity. For lack of standardized disease severity scales, the investigators relied upon tertiles of CD4 T cell count in the HIV group and CRP in the others. The HR for new-onset CHD in the more than 5,000 patients with psoriasis didn’t vary by CRP tertile. However, there was a nonsignificant trend for greater disease severity, as reflected by CRP tertile, to be associated with increased incident CHD risk in the HIV and inflammatory bowel disease groups. 

In contrast, patients with rheumatoid arthritis or systemic sclerosis who were in the top CRP tertile had a significantly greater risk of developing CHD than that of controls, with HRs of 2.11 in the rheumatoid arthritis group and 4.59 with systemic sclerosis, although patients in the other two tertiles weren’t at significantly increased risk. But all three tertiles of CRP in patients with SLE were associated with significantly increased CHD risk: 3.17-fold in the lowest tertile of lupus severity, 5.38-fold in the middle tertile, and 4.04-fold in the top tertile for inflammation. 

These findings could be used in clinical practice to fine-tune atherosclerotic cardiovascular disease risk assessment based upon chronic inflammatory disease type and severity. That’s information which in turn can help guide the timing and intensity of preventive therapy for patients with each disease type. 

But studying the association between chronic systemic inflammatory diseases and CHD risk can be useful in additional ways, according to Dr. Sinha. These inflammatory diseases can serve as models of atherosclerosis that shed light on the non–lipid-related mechanisms involved in cardiovascular disease. 

“The gradient in risk may be hypothesis-generating with respect to which specific inflammatory pathways may contribute to CHD,” he explained. 

Each of these six chronic inflammatory diseases is characterized by a different form of major immune dysfunction, Dr. Sinha continued. A case in point is SLE, the inflammatory disease associated with the highest risk of CHD and MI. Lupus is characterized by a form of neutrophil dysfunction marked by increased formation and reduced degradation of neutrophil extracellular traps, or NETs, as well as by an increase in autoreactive B cells and dysfunctional CD4+ T helper cells. The increase in NETs of of particular interest because NETs have also been shown to contribute to the development of atherosclerosis, endothelial dysfunction, plaque erosion, and thrombosis. 

In another exploratory analysis, Dr. Sinha and coworkers found that SLE patients with a neutrophil count above the median level were twice as likely to develop CHD than were those with a neutrophil count below the median. 

A better understanding of the upstream pathways linking NET formation in SLE and atherosclerosis could lead to development of new or repurposed medications that target immune dysfunction in order to curb atherosclerosis, said Dr. Sinha, whose study won the AHA’s Samuel A. Levine Early Career Clinical Investigator Award. 

He reported having no financial conflicts regarding his study. 

[email protected] 

Not all chronic systemic inflammatory diseases are equal enhancers of atherosclerotic cardiovascular disease risk, according to a large case-control study.  

Current AHA/American College of Cardiology guidelines cite three chronic inflammatory diseases as atherosclerotic cardiovascular disease risk enhancers: rheumatoid arthritis, psoriasis, and HIV infection. But this study of those three diseases, along with three others marked by elevated high sensitivity C-reactive protein (systemic sclerosis, inflammatory bowel disease, and systemic lupus erythematosus [SLE]), showed that chronic inflammatory diseases are not monolithic in terms of their associated risk of incident coronary heart disease (CHD).

Indeed, two of the six inflammatory diseases – psoriasis and inflammatory bowel disease – turned out to be not at all associated with increased cardiovascular risk in the 37,117-patient study. The highest-risk disease was SLE, not specifically mentioned in the guidelines, Arjun Sinha, MD, a cardiology fellow at Northwestern University, Chicago, noted in his presentation at the virtual American Heart Association scientific sessions. 

The study included 18,129 patients with one of the six chronic inflammatory diseases and 18,988 matched controls, none with CHD at baseline. All regularly received outpatient care at Northwestern during 2000-2019. There were 1,011 incident CHD events during a median of 3.5 years of follow-up. 

In a Cox proportional hazards analysis adjusted for demographics, insurance status, hypertension, diabetes, current smoking, total cholesterol, and estimated glomerular filtration rate, here’s how the chronic inflammatory diseases stacked up in terms of incident CHD and MI risks: 

• SLE: hazard ratio for CHD, 2.85; for MI, 4.76.
• Systemic sclerosis: HR for CHD, 2.14; for MI, 3.19.
• HIV: HR for CHD, 1.38; for MI, 1.69.
• Rheumatoid arthritis: HR for CHD, 1.22; for MI, 1.45.
• Psoriasis: no significant increase.
• Inflammatory bowel disease: no significant increase.

In an exploratory analysis, Dr. Sinha and coinvestigators evaluated the risk of incident CHD stratified by disease severity. For lack of standardized disease severity scales, the investigators relied upon tertiles of CD4 T cell count in the HIV group and CRP in the others. The HR for new-onset CHD in the more than 5,000 patients with psoriasis didn’t vary by CRP tertile. However, there was a nonsignificant trend for greater disease severity, as reflected by CRP tertile, to be associated with increased incident CHD risk in the HIV and inflammatory bowel disease groups. 

In contrast, patients with rheumatoid arthritis or systemic sclerosis who were in the top CRP tertile had a significantly greater risk of developing CHD than that of controls, with HRs of 2.11 in the rheumatoid arthritis group and 4.59 with systemic sclerosis, although patients in the other two tertiles weren’t at significantly increased risk. But all three tertiles of CRP in patients with SLE were associated with significantly increased CHD risk: 3.17-fold in the lowest tertile of lupus severity, 5.38-fold in the middle tertile, and 4.04-fold in the top tertile for inflammation. 

These findings could be used in clinical practice to fine-tune atherosclerotic cardiovascular disease risk assessment based upon chronic inflammatory disease type and severity. That’s information which in turn can help guide the timing and intensity of preventive therapy for patients with each disease type. 

But studying the association between chronic systemic inflammatory diseases and CHD risk can be useful in additional ways, according to Dr. Sinha. These inflammatory diseases can serve as models of atherosclerosis that shed light on the non–lipid-related mechanisms involved in cardiovascular disease. 

“The gradient in risk may be hypothesis-generating with respect to which specific inflammatory pathways may contribute to CHD,” he explained. 

Each of these six chronic inflammatory diseases is characterized by a different form of major immune dysfunction, Dr. Sinha continued. A case in point is SLE, the inflammatory disease associated with the highest risk of CHD and MI. Lupus is characterized by a form of neutrophil dysfunction marked by increased formation and reduced degradation of neutrophil extracellular traps, or NETs, as well as by an increase in autoreactive B cells and dysfunctional CD4+ T helper cells. The increase in NETs of of particular interest because NETs have also been shown to contribute to the development of atherosclerosis, endothelial dysfunction, plaque erosion, and thrombosis. 

In another exploratory analysis, Dr. Sinha and coworkers found that SLE patients with a neutrophil count above the median level were twice as likely to develop CHD than were those with a neutrophil count below the median. 

A better understanding of the upstream pathways linking NET formation in SLE and atherosclerosis could lead to development of new or repurposed medications that target immune dysfunction in order to curb atherosclerosis, said Dr. Sinha, whose study won the AHA’s Samuel A. Levine Early Career Clinical Investigator Award. 

He reported having no financial conflicts regarding his study. 

[email protected] 

Not all chronic systemic inflammatory diseases are equal enhancers of atherosclerotic cardiovascular disease risk, according to a large case-control study.  

Current AHA/American College of Cardiology guidelines cite three chronic inflammatory diseases as atherosclerotic cardiovascular disease risk enhancers: rheumatoid arthritis, psoriasis, and HIV infection. But this study of those three diseases, along with three others marked by elevated high sensitivity C-reactive protein (systemic sclerosis, inflammatory bowel disease, and systemic lupus erythematosus [SLE]), showed that chronic inflammatory diseases are not monolithic in terms of their associated risk of incident coronary heart disease (CHD).

Indeed, two of the six inflammatory diseases – psoriasis and inflammatory bowel disease – turned out to be not at all associated with increased cardiovascular risk in the 37,117-patient study. The highest-risk disease was SLE, not specifically mentioned in the guidelines, Arjun Sinha, MD, a cardiology fellow at Northwestern University, Chicago, noted in his presentation at the virtual American Heart Association scientific sessions. 

The study included 18,129 patients with one of the six chronic inflammatory diseases and 18,988 matched controls, none with CHD at baseline. All regularly received outpatient care at Northwestern during 2000-2019. There were 1,011 incident CHD events during a median of 3.5 years of follow-up. 

In a Cox proportional hazards analysis adjusted for demographics, insurance status, hypertension, diabetes, current smoking, total cholesterol, and estimated glomerular filtration rate, here’s how the chronic inflammatory diseases stacked up in terms of incident CHD and MI risks: 

• SLE: hazard ratio for CHD, 2.85; for MI, 4.76.
• Systemic sclerosis: HR for CHD, 2.14; for MI, 3.19.
• HIV: HR for CHD, 1.38; for MI, 1.69.
• Rheumatoid arthritis: HR for CHD, 1.22; for MI, 1.45.
• Psoriasis: no significant increase.
• Inflammatory bowel disease: no significant increase.

In an exploratory analysis, Dr. Sinha and coinvestigators evaluated the risk of incident CHD stratified by disease severity. For lack of standardized disease severity scales, the investigators relied upon tertiles of CD4 T cell count in the HIV group and CRP in the others. The HR for new-onset CHD in the more than 5,000 patients with psoriasis didn’t vary by CRP tertile. However, there was a nonsignificant trend for greater disease severity, as reflected by CRP tertile, to be associated with increased incident CHD risk in the HIV and inflammatory bowel disease groups. 

In contrast, patients with rheumatoid arthritis or systemic sclerosis who were in the top CRP tertile had a significantly greater risk of developing CHD than that of controls, with HRs of 2.11 in the rheumatoid arthritis group and 4.59 with systemic sclerosis, although patients in the other two tertiles weren’t at significantly increased risk. But all three tertiles of CRP in patients with SLE were associated with significantly increased CHD risk: 3.17-fold in the lowest tertile of lupus severity, 5.38-fold in the middle tertile, and 4.04-fold in the top tertile for inflammation. 

These findings could be used in clinical practice to fine-tune atherosclerotic cardiovascular disease risk assessment based upon chronic inflammatory disease type and severity. That’s information which in turn can help guide the timing and intensity of preventive therapy for patients with each disease type. 

But studying the association between chronic systemic inflammatory diseases and CHD risk can be useful in additional ways, according to Dr. Sinha. These inflammatory diseases can serve as models of atherosclerosis that shed light on the non–lipid-related mechanisms involved in cardiovascular disease. 

“The gradient in risk may be hypothesis-generating with respect to which specific inflammatory pathways may contribute to CHD,” he explained. 

Each of these six chronic inflammatory diseases is characterized by a different form of major immune dysfunction, Dr. Sinha continued. A case in point is SLE, the inflammatory disease associated with the highest risk of CHD and MI. Lupus is characterized by a form of neutrophil dysfunction marked by increased formation and reduced degradation of neutrophil extracellular traps, or NETs, as well as by an increase in autoreactive B cells and dysfunctional CD4+ T helper cells. The increase in NETs of of particular interest because NETs have also been shown to contribute to the development of atherosclerosis, endothelial dysfunction, plaque erosion, and thrombosis. 

In another exploratory analysis, Dr. Sinha and coworkers found that SLE patients with a neutrophil count above the median level were twice as likely to develop CHD than were those with a neutrophil count below the median. 

A better understanding of the upstream pathways linking NET formation in SLE and atherosclerosis could lead to development of new or repurposed medications that target immune dysfunction in order to curb atherosclerosis, said Dr. Sinha, whose study won the AHA’s Samuel A. Levine Early Career Clinical Investigator Award. 

He reported having no financial conflicts regarding his study. 

[email protected] 

Patients with Sjögren’s syndrome can be categorized into four distinct symptom clusters – independent of age, sex, and some disease manifestations – that may both improve symptom relief and aid in the development of targeted therapies, investigators reported.

Analysis of data from a survey conducted by the Sjögren’s Foundation identified four symptom clusters based on the grouping of five common characteristics: anxiety, depression, pain, fatigue, and dryness, Sara S. McCoy, MD, of the University of Wisconsin–Madison, and colleagues reported.

“Verification of features unique to each Sjögren’s cluster might provide guidance for future cluster-targeted therapy,” Dr. McCoy said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.

The dearth of Food and Drug Administration–approved disease-modifying therapies for Sjögren’s syndrome can be attributed in part to the small number of patients with extraglandular disease manifestations, the heterogeneity of disease, and the failure of available therapy to improve common symptoms such as fatigue, dryness, quality-of-life decrements, anxiety and depression, she said.
 

Symptom clusters verify smaller study’s findings

Dr. McCoy and colleagues explored whether symptom clusters identified in a 2019 study from the United Kingdom would apply to a larger U.S. population.

In the U.K. study, Jessica R. Tarn, PhD, and colleagues performed a hierarchical cluster analysis to identify subgroups among 608 patients in the U.K. Primary Sjögren’s Syndrome Registry and in 396 patients in two independent validation cohorts from Norway and France.

They identified four subgroups they categorized as low symptom burden, high symptom burden, dryness dominant with fatigue, and pain dominant with fatigue, and reported that the groups showed significant difference in serum and transcriptomic markers.

In the U.S. study, McCoy et al. sought to verify the symptom-based cluster and report on differences in key measures between the groups. They used data from a survey by the Sjögren’s Foundation of 2,961 adults with self-reported Sjögren’s syndrome. The investigators then used an unsupervised hierarchical clustering method to identify the optimal phenotypically similar clusters based on patient-reported severity of anxiety (from never to daily), depression (never to daily), pain on a visual analog scale (0 to 10), fatigue on a VAS, and dryness on a VAS. They collected data on demographics, medications, quality of life, and Sjögren’s-specific symptom frequency and systemic manifestations within each cluster, and identified cluster differences controlled for age, sex, race, and Social Security disability.

They identified four symptom-based clusters from 2,806 participants for whom complete data on the five key symptoms were available:

• Cluster 1 patients (prevalence, 30%) had high symptom burden in all categories.
• Cluster 2 patients (22%) had high anxiety and depression (22%), with some fatigue.
• Cluster 3 patients (34%) had predominant high dryness and fatigue.
• Cluster 4 patients (14%) had low symptom burden.

“We found that clusters differed in Sjögren’s-specific symptoms,” Dr. McCoy said.

For example, patients in the high-symptom-burden cluster had, as the name implies, an overall higher burden of symptoms among all major ocular, oral, and other dryness symptoms, as well as systemic organ system symptoms, whereas patients in the low-symptom-burden group consistently had the lowest levels of symptoms across the spectrum.

“We also noticed significant differences in systemic medication use. High symptom burden and high dryness and fatigue had higher use of systemic therapies targeting dryness, as might be expected,” she said.

The highest corticosteroid use was in the high-symptom-burden group, while hydroxychloroquine use was highest in the high-anxiety/depression group. Antidepressant use was also high in these two groups.

In addition, 35% of patients in the high-symptom-burden group used prescription opioid analgesics, compared with just 7% in the low-symptom-burden group.

The categories from low to high symptom burden also significantly correlated with quality-of-life measures, including Social Security Disability enrollment, emotional burden of disease, effects of disease on independence, and effects of Sjögren’s on relationships with family and friends (P < .001 for all).

Systemic manifestations of disease differed significantly among the groups for inflammatory arthritis, interstitial lung disease, and neuropathy, but there were no significant differences in the incidence of leukopenia or lymphoma.

The investigators plan to perform symptom-based cluster analysis with validated Sjögren’s syndrome populations, and propose studies to define phenotypic features of distinct clusters “to better define subsets of this heterogeneous disease, and ultimately inform targeted therapy,” Dr. McCoy concluded.
 

Opportunity to tailor practice and research

During the question-and-answer period following the presentation, Gabriela Hernandez-Molina, MD, of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, commented that “fatigue and pain might be also attributed to other comorbidities in these patients such as fibromyalgia,” and asked Dr. McCoy to comment on that.

“That’s exactly what we’re driving at,” Dr. McCoy replied. “Fatigue and pain frequently affect how patients experience their disease, and it would be beneficial to take this into account when we evaluate patients, and also for the studies that we’re performing, as well as future ‘-omic’ studies – transcriptomics and what-not – there’s potential here to take that type of patient we frequently see and try to tailor our clinical practice and our research to clearly what we’re seeing in practice, which is these other comorbidities.”

Dana DiRenzo, MD, from Johns Hopkins University, Baltimore, who moderated the session, asked how the information is changing the management of patients with Sjögren’s syndrome in clinic.

Dr. McCoy said that the study was based on self-reported data that can introduce bias, and that she and colleagues plan to validate the results before applying them to clinical care.

The study was supported by grants from the National Institutes of Health and the University of Wisconsin. Dr. McCoy disclosed consulting fees from Novartis and Bristol-Myers Squibb. Dr. Hernandez-Molina and Dr. DiRenzo reported no relevant disclosures.

SOURCE: McCoy SS et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1504.

Patients with Sjögren’s syndrome can be categorized into four distinct symptom clusters – independent of age, sex, and some disease manifestations – that may both improve symptom relief and aid in the development of targeted therapies, investigators reported.

Analysis of data from a survey conducted by the Sjögren’s Foundation identified four symptom clusters based on the grouping of five common characteristics: anxiety, depression, pain, fatigue, and dryness, Sara S. McCoy, MD, of the University of Wisconsin–Madison, and colleagues reported.

“Verification of features unique to each Sjögren’s cluster might provide guidance for future cluster-targeted therapy,” Dr. McCoy said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.

The dearth of Food and Drug Administration–approved disease-modifying therapies for Sjögren’s syndrome can be attributed in part to the small number of patients with extraglandular disease manifestations, the heterogeneity of disease, and the failure of available therapy to improve common symptoms such as fatigue, dryness, quality-of-life decrements, anxiety and depression, she said.
 

Symptom clusters verify smaller study’s findings

Dr. McCoy and colleagues explored whether symptom clusters identified in a 2019 study from the United Kingdom would apply to a larger U.S. population.

In the U.K. study, Jessica R. Tarn, PhD, and colleagues performed a hierarchical cluster analysis to identify subgroups among 608 patients in the U.K. Primary Sjögren’s Syndrome Registry and in 396 patients in two independent validation cohorts from Norway and France.

They identified four subgroups they categorized as low symptom burden, high symptom burden, dryness dominant with fatigue, and pain dominant with fatigue, and reported that the groups showed significant difference in serum and transcriptomic markers.

In the U.S. study, McCoy et al. sought to verify the symptom-based cluster and report on differences in key measures between the groups. They used data from a survey by the Sjögren’s Foundation of 2,961 adults with self-reported Sjögren’s syndrome. The investigators then used an unsupervised hierarchical clustering method to identify the optimal phenotypically similar clusters based on patient-reported severity of anxiety (from never to daily), depression (never to daily), pain on a visual analog scale (0 to 10), fatigue on a VAS, and dryness on a VAS. They collected data on demographics, medications, quality of life, and Sjögren’s-specific symptom frequency and systemic manifestations within each cluster, and identified cluster differences controlled for age, sex, race, and Social Security disability.

They identified four symptom-based clusters from 2,806 participants for whom complete data on the five key symptoms were available:

• Cluster 1 patients (prevalence, 30%) had high symptom burden in all categories.
• Cluster 2 patients (22%) had high anxiety and depression (22%), with some fatigue.
• Cluster 3 patients (34%) had predominant high dryness and fatigue.
• Cluster 4 patients (14%) had low symptom burden.

“We found that clusters differed in Sjögren’s-specific symptoms,” Dr. McCoy said.

For example, patients in the high-symptom-burden cluster had, as the name implies, an overall higher burden of symptoms among all major ocular, oral, and other dryness symptoms, as well as systemic organ system symptoms, whereas patients in the low-symptom-burden group consistently had the lowest levels of symptoms across the spectrum.

“We also noticed significant differences in systemic medication use. High symptom burden and high dryness and fatigue had higher use of systemic therapies targeting dryness, as might be expected,” she said.

The highest corticosteroid use was in the high-symptom-burden group, while hydroxychloroquine use was highest in the high-anxiety/depression group. Antidepressant use was also high in these two groups.

In addition, 35% of patients in the high-symptom-burden group used prescription opioid analgesics, compared with just 7% in the low-symptom-burden group.

The categories from low to high symptom burden also significantly correlated with quality-of-life measures, including Social Security Disability enrollment, emotional burden of disease, effects of disease on independence, and effects of Sjögren’s on relationships with family and friends (P < .001 for all).

Systemic manifestations of disease differed significantly among the groups for inflammatory arthritis, interstitial lung disease, and neuropathy, but there were no significant differences in the incidence of leukopenia or lymphoma.

The investigators plan to perform symptom-based cluster analysis with validated Sjögren’s syndrome populations, and propose studies to define phenotypic features of distinct clusters “to better define subsets of this heterogeneous disease, and ultimately inform targeted therapy,” Dr. McCoy concluded.
 

Opportunity to tailor practice and research

During the question-and-answer period following the presentation, Gabriela Hernandez-Molina, MD, of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, commented that “fatigue and pain might be also attributed to other comorbidities in these patients such as fibromyalgia,” and asked Dr. McCoy to comment on that.

“That’s exactly what we’re driving at,” Dr. McCoy replied. “Fatigue and pain frequently affect how patients experience their disease, and it would be beneficial to take this into account when we evaluate patients, and also for the studies that we’re performing, as well as future ‘-omic’ studies – transcriptomics and what-not – there’s potential here to take that type of patient we frequently see and try to tailor our clinical practice and our research to clearly what we’re seeing in practice, which is these other comorbidities.”

Dana DiRenzo, MD, from Johns Hopkins University, Baltimore, who moderated the session, asked how the information is changing the management of patients with Sjögren’s syndrome in clinic.

Dr. McCoy said that the study was based on self-reported data that can introduce bias, and that she and colleagues plan to validate the results before applying them to clinical care.

The study was supported by grants from the National Institutes of Health and the University of Wisconsin. Dr. McCoy disclosed consulting fees from Novartis and Bristol-Myers Squibb. Dr. Hernandez-Molina and Dr. DiRenzo reported no relevant disclosures.

SOURCE: McCoy SS et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1504.

Patients with Sjögren’s syndrome can be categorized into four distinct symptom clusters – independent of age, sex, and some disease manifestations – that may both improve symptom relief and aid in the development of targeted therapies, investigators reported.

Analysis of data from a survey conducted by the Sjögren’s Foundation identified four symptom clusters based on the grouping of five common characteristics: anxiety, depression, pain, fatigue, and dryness, Sara S. McCoy, MD, of the University of Wisconsin–Madison, and colleagues reported.

“Verification of features unique to each Sjögren’s cluster might provide guidance for future cluster-targeted therapy,” Dr. McCoy said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.

The dearth of Food and Drug Administration–approved disease-modifying therapies for Sjögren’s syndrome can be attributed in part to the small number of patients with extraglandular disease manifestations, the heterogeneity of disease, and the failure of available therapy to improve common symptoms such as fatigue, dryness, quality-of-life decrements, anxiety and depression, she said.
 

Symptom clusters verify smaller study’s findings

Dr. McCoy and colleagues explored whether symptom clusters identified in a 2019 study from the United Kingdom would apply to a larger U.S. population.

In the U.K. study, Jessica R. Tarn, PhD, and colleagues performed a hierarchical cluster analysis to identify subgroups among 608 patients in the U.K. Primary Sjögren’s Syndrome Registry and in 396 patients in two independent validation cohorts from Norway and France.

They identified four subgroups they categorized as low symptom burden, high symptom burden, dryness dominant with fatigue, and pain dominant with fatigue, and reported that the groups showed significant difference in serum and transcriptomic markers.

In the U.S. study, McCoy et al. sought to verify the symptom-based cluster and report on differences in key measures between the groups. They used data from a survey by the Sjögren’s Foundation of 2,961 adults with self-reported Sjögren’s syndrome. The investigators then used an unsupervised hierarchical clustering method to identify the optimal phenotypically similar clusters based on patient-reported severity of anxiety (from never to daily), depression (never to daily), pain on a visual analog scale (0 to 10), fatigue on a VAS, and dryness on a VAS. They collected data on demographics, medications, quality of life, and Sjögren’s-specific symptom frequency and systemic manifestations within each cluster, and identified cluster differences controlled for age, sex, race, and Social Security disability.

They identified four symptom-based clusters from 2,806 participants for whom complete data on the five key symptoms were available:

• Cluster 1 patients (prevalence, 30%) had high symptom burden in all categories.
• Cluster 2 patients (22%) had high anxiety and depression (22%), with some fatigue.
• Cluster 3 patients (34%) had predominant high dryness and fatigue.
• Cluster 4 patients (14%) had low symptom burden.

“We found that clusters differed in Sjögren’s-specific symptoms,” Dr. McCoy said.

For example, patients in the high-symptom-burden cluster had, as the name implies, an overall higher burden of symptoms among all major ocular, oral, and other dryness symptoms, as well as systemic organ system symptoms, whereas patients in the low-symptom-burden group consistently had the lowest levels of symptoms across the spectrum.

“We also noticed significant differences in systemic medication use. High symptom burden and high dryness and fatigue had higher use of systemic therapies targeting dryness, as might be expected,” she said.

The highest corticosteroid use was in the high-symptom-burden group, while hydroxychloroquine use was highest in the high-anxiety/depression group. Antidepressant use was also high in these two groups.

In addition, 35% of patients in the high-symptom-burden group used prescription opioid analgesics, compared with just 7% in the low-symptom-burden group.

The categories from low to high symptom burden also significantly correlated with quality-of-life measures, including Social Security Disability enrollment, emotional burden of disease, effects of disease on independence, and effects of Sjögren’s on relationships with family and friends (P < .001 for all).

Systemic manifestations of disease differed significantly among the groups for inflammatory arthritis, interstitial lung disease, and neuropathy, but there were no significant differences in the incidence of leukopenia or lymphoma.

The investigators plan to perform symptom-based cluster analysis with validated Sjögren’s syndrome populations, and propose studies to define phenotypic features of distinct clusters “to better define subsets of this heterogeneous disease, and ultimately inform targeted therapy,” Dr. McCoy concluded.
 

Opportunity to tailor practice and research

During the question-and-answer period following the presentation, Gabriela Hernandez-Molina, MD, of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, commented that “fatigue and pain might be also attributed to other comorbidities in these patients such as fibromyalgia,” and asked Dr. McCoy to comment on that.

“That’s exactly what we’re driving at,” Dr. McCoy replied. “Fatigue and pain frequently affect how patients experience their disease, and it would be beneficial to take this into account when we evaluate patients, and also for the studies that we’re performing, as well as future ‘-omic’ studies – transcriptomics and what-not – there’s potential here to take that type of patient we frequently see and try to tailor our clinical practice and our research to clearly what we’re seeing in practice, which is these other comorbidities.”

Dana DiRenzo, MD, from Johns Hopkins University, Baltimore, who moderated the session, asked how the information is changing the management of patients with Sjögren’s syndrome in clinic.

Dr. McCoy said that the study was based on self-reported data that can introduce bias, and that she and colleagues plan to validate the results before applying them to clinical care.

The study was supported by grants from the National Institutes of Health and the University of Wisconsin. Dr. McCoy disclosed consulting fees from Novartis and Bristol-Myers Squibb. Dr. Hernandez-Molina and Dr. DiRenzo reported no relevant disclosures.

SOURCE: McCoy SS et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1504.

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.

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 .