Lupus & Connective Tissue Diseases

TOPLINE:

In individuals with low B-cell counts, T cells have enhanced responses to COVID-19 vaccination and may help prevent severe disease after infection.

METHODOLOGY:

• How the immune systems of B cell–deficient patients respond to SARS-CoV-2 infection and vaccination is not fully understood.
• Researchers evaluated anti–SARS-CoV-2 T-cell responses in 33 patients treated with rituximab (RTX), 12 patients with common variable immune deficiency, and 44 controls.
• The study analyzed effector and memory CD4+ and CD8+ T-cell responses to SARS-CoV-2 after infection and vaccination.

TAKEAWAY: 

• All B cell–deficient individuals (those treated with RTX or those with a diagnosis of common variable immune deficiency) had increased effector and memory T-cell responses after SARS-CoV-2 vaccination, compared with controls.
• Patients treated with RTX who were vaccinated against COVID-19 had 4.8-fold reduced odds of moderate or severe disease. (These data were not available for patients with common variable immune deficiency.)
• RTX treatment was associated with a decrease in preexisting T-cell immunity in unvaccinated patients, regardless of prior infection with SARS-CoV-2.
• This association was not found in vaccinated patients treated with RTX.

IN PRACTICE:

“[These findings] provide support for vaccination in this vulnerable population and demonstrate the potential benefit of vaccine-induced CD8+ T-cell responses on reducing disease severity from SARS-CoV-2 infection in the absence of spike protein–specific antibodies,” the authors wrote.

SOURCE:

The study was published online on November 29 in Science Translational Medicine. The first author is Reza Zonozi, MD, who conducted the research while at Massachusetts General Hospital, Boston, and is now in private practice in northern Virginia. 

LIMITATIONS:

Researchers did not obtain specimens from patients with common variable immune deficiency after SARS-CoV-2 infection. Only a small subset of immunophenotyped participants had subsequent SARS-CoV-2 infection.

DISCLOSURES:

The research was supported by grants from the National Institutes of Health, the Centers for Disease Control and Prevention, the Howard Hughes Medical Institute, the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, the Mark and Lisa Schwartz Foundation and E. Schwartz; the Lambertus Family Foundation; and S. Edgerly and P. Edgerly. Four authors reported relationships with pharmaceutical companies including AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Merck, and Pfizer.

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

TOPLINE:

In individuals with low B-cell counts, T cells have enhanced responses to COVID-19 vaccination and may help prevent severe disease after infection.

METHODOLOGY:

• How the immune systems of B cell–deficient patients respond to SARS-CoV-2 infection and vaccination is not fully understood.
• Researchers evaluated anti–SARS-CoV-2 T-cell responses in 33 patients treated with rituximab (RTX), 12 patients with common variable immune deficiency, and 44 controls.
• The study analyzed effector and memory CD4+ and CD8+ T-cell responses to SARS-CoV-2 after infection and vaccination.

TAKEAWAY: 

• All B cell–deficient individuals (those treated with RTX or those with a diagnosis of common variable immune deficiency) had increased effector and memory T-cell responses after SARS-CoV-2 vaccination, compared with controls.
• Patients treated with RTX who were vaccinated against COVID-19 had 4.8-fold reduced odds of moderate or severe disease. (These data were not available for patients with common variable immune deficiency.)
• RTX treatment was associated with a decrease in preexisting T-cell immunity in unvaccinated patients, regardless of prior infection with SARS-CoV-2.
• This association was not found in vaccinated patients treated with RTX.

IN PRACTICE:

“[These findings] provide support for vaccination in this vulnerable population and demonstrate the potential benefit of vaccine-induced CD8+ T-cell responses on reducing disease severity from SARS-CoV-2 infection in the absence of spike protein–specific antibodies,” the authors wrote.

SOURCE:

The study was published online on November 29 in Science Translational Medicine. The first author is Reza Zonozi, MD, who conducted the research while at Massachusetts General Hospital, Boston, and is now in private practice in northern Virginia. 

LIMITATIONS:

Researchers did not obtain specimens from patients with common variable immune deficiency after SARS-CoV-2 infection. Only a small subset of immunophenotyped participants had subsequent SARS-CoV-2 infection.

DISCLOSURES:

The research was supported by grants from the National Institutes of Health, the Centers for Disease Control and Prevention, the Howard Hughes Medical Institute, the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, the Mark and Lisa Schwartz Foundation and E. Schwartz; the Lambertus Family Foundation; and S. Edgerly and P. Edgerly. Four authors reported relationships with pharmaceutical companies including AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Merck, and Pfizer.

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

TOPLINE:

In individuals with low B-cell counts, T cells have enhanced responses to COVID-19 vaccination and may help prevent severe disease after infection.

METHODOLOGY:

• How the immune systems of B cell–deficient patients respond to SARS-CoV-2 infection and vaccination is not fully understood.
• Researchers evaluated anti–SARS-CoV-2 T-cell responses in 33 patients treated with rituximab (RTX), 12 patients with common variable immune deficiency, and 44 controls.
• The study analyzed effector and memory CD4+ and CD8+ T-cell responses to SARS-CoV-2 after infection and vaccination.

TAKEAWAY: 

• All B cell–deficient individuals (those treated with RTX or those with a diagnosis of common variable immune deficiency) had increased effector and memory T-cell responses after SARS-CoV-2 vaccination, compared with controls.
• Patients treated with RTX who were vaccinated against COVID-19 had 4.8-fold reduced odds of moderate or severe disease. (These data were not available for patients with common variable immune deficiency.)
• RTX treatment was associated with a decrease in preexisting T-cell immunity in unvaccinated patients, regardless of prior infection with SARS-CoV-2.
• This association was not found in vaccinated patients treated with RTX.

IN PRACTICE:

“[These findings] provide support for vaccination in this vulnerable population and demonstrate the potential benefit of vaccine-induced CD8+ T-cell responses on reducing disease severity from SARS-CoV-2 infection in the absence of spike protein–specific antibodies,” the authors wrote.

SOURCE:

The study was published online on November 29 in Science Translational Medicine. The first author is Reza Zonozi, MD, who conducted the research while at Massachusetts General Hospital, Boston, and is now in private practice in northern Virginia. 

LIMITATIONS:

Researchers did not obtain specimens from patients with common variable immune deficiency after SARS-CoV-2 infection. Only a small subset of immunophenotyped participants had subsequent SARS-CoV-2 infection.

DISCLOSURES:

The research was supported by grants from the National Institutes of Health, the Centers for Disease Control and Prevention, the Howard Hughes Medical Institute, the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, the Mark and Lisa Schwartz Foundation and E. Schwartz; the Lambertus Family Foundation; and S. Edgerly and P. Edgerly. Four authors reported relationships with pharmaceutical companies including AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Merck, and Pfizer.

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

TOPLINE:

The use of low-dose methotrexate among older adults with chronic kidney disease (CKD) was associated with a significantly increased risk at 90 days for serious adverse events requiring a hospital visit, compared with starting treatment with hydroxychloroquine.

METHODOLOGY:

• In a retrospective, population-based cohort study conducted in Ontario, researchers used linked administrative healthcare data to identify adults aged 66 years and older with CKD who were not undergoing dialysis and were new to medication; CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m².
• The study population included 2,309 individuals who began treatment with low-dose methotrexate (5-35 mg/week); they were matched with 2,309 individuals who began treatment with hydroxychloroquine (200-400 mg/day). The median age was 76 years, 69% were women, and rheumatoid arthritis was the most common diagnosis (56%).
• The primary outcome was the risk of a hospital visit at 90 days for a composite of serious adverse events that included myelosuppression, sepsis, pneumotoxic effects, or hepatoxic effects.

TAKEAWAY:

• Overall, 3.55% of methotrexate patients and 1.73% of hydroxychloroquine patients met the primary outcome (risk ratio, 2.05); these events occurred at a median of 49 days and 43 days after starting the medications for the two groups, respectively.
• In an analysis by eGFR category, the risk of serious adverse events at 90 days increased among patients with eGFR levels less than 45 mL/min per 1.73 m² (RR, 2.79).
• In a secondary comparison, the 90-day risk of serious adverse events was higher among methotrexate patients who began treatment with doses of 15-35 mg/week in comparison with those whose initial doses were 5 to less than 15 mg/week.

IN PRACTICE:

“Patients with CKD starting low-dose methotrexate should have active surveillance, including blood tests and chest radiographs performed regularly to monitor for signs of myelosuppression, infection, hepatotoxic effects, and pneumotoxic effects,” the researchers wrote.

SOURCE:

The lead author on the study was Flory T. Muanda, MD, of Western University, London, Ont. The study was published online in JAMA Network Open.

LIMITATIONS:

The observational design and lack of data on patients’ adherence to medications were among the limiting factors, as were the focus on older adults with CKD and the lack of assessment of the risk-benefit ratio of low-dose methotrexate.

DISCLOSURES:

The study was supported by the Institute for Clinical Evaluative Sciences. Dr. Muanda had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of low-dose methotrexate among older adults with chronic kidney disease (CKD) was associated with a significantly increased risk at 90 days for serious adverse events requiring a hospital visit, compared with starting treatment with hydroxychloroquine.

METHODOLOGY:

• In a retrospective, population-based cohort study conducted in Ontario, researchers used linked administrative healthcare data to identify adults aged 66 years and older with CKD who were not undergoing dialysis and were new to medication; CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m².
• The study population included 2,309 individuals who began treatment with low-dose methotrexate (5-35 mg/week); they were matched with 2,309 individuals who began treatment with hydroxychloroquine (200-400 mg/day). The median age was 76 years, 69% were women, and rheumatoid arthritis was the most common diagnosis (56%).
• The primary outcome was the risk of a hospital visit at 90 days for a composite of serious adverse events that included myelosuppression, sepsis, pneumotoxic effects, or hepatoxic effects.

TAKEAWAY:

• Overall, 3.55% of methotrexate patients and 1.73% of hydroxychloroquine patients met the primary outcome (risk ratio, 2.05); these events occurred at a median of 49 days and 43 days after starting the medications for the two groups, respectively.
• In an analysis by eGFR category, the risk of serious adverse events at 90 days increased among patients with eGFR levels less than 45 mL/min per 1.73 m² (RR, 2.79).
• In a secondary comparison, the 90-day risk of serious adverse events was higher among methotrexate patients who began treatment with doses of 15-35 mg/week in comparison with those whose initial doses were 5 to less than 15 mg/week.

IN PRACTICE:

“Patients with CKD starting low-dose methotrexate should have active surveillance, including blood tests and chest radiographs performed regularly to monitor for signs of myelosuppression, infection, hepatotoxic effects, and pneumotoxic effects,” the researchers wrote.

SOURCE:

The lead author on the study was Flory T. Muanda, MD, of Western University, London, Ont. The study was published online in JAMA Network Open.

LIMITATIONS:

The observational design and lack of data on patients’ adherence to medications were among the limiting factors, as were the focus on older adults with CKD and the lack of assessment of the risk-benefit ratio of low-dose methotrexate.

DISCLOSURES:

The study was supported by the Institute for Clinical Evaluative Sciences. Dr. Muanda had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of low-dose methotrexate among older adults with chronic kidney disease (CKD) was associated with a significantly increased risk at 90 days for serious adverse events requiring a hospital visit, compared with starting treatment with hydroxychloroquine.

METHODOLOGY:

• In a retrospective, population-based cohort study conducted in Ontario, researchers used linked administrative healthcare data to identify adults aged 66 years and older with CKD who were not undergoing dialysis and were new to medication; CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m².
• The study population included 2,309 individuals who began treatment with low-dose methotrexate (5-35 mg/week); they were matched with 2,309 individuals who began treatment with hydroxychloroquine (200-400 mg/day). The median age was 76 years, 69% were women, and rheumatoid arthritis was the most common diagnosis (56%).
• The primary outcome was the risk of a hospital visit at 90 days for a composite of serious adverse events that included myelosuppression, sepsis, pneumotoxic effects, or hepatoxic effects.

TAKEAWAY:

• Overall, 3.55% of methotrexate patients and 1.73% of hydroxychloroquine patients met the primary outcome (risk ratio, 2.05); these events occurred at a median of 49 days and 43 days after starting the medications for the two groups, respectively.
• In an analysis by eGFR category, the risk of serious adverse events at 90 days increased among patients with eGFR levels less than 45 mL/min per 1.73 m² (RR, 2.79).
• In a secondary comparison, the 90-day risk of serious adverse events was higher among methotrexate patients who began treatment with doses of 15-35 mg/week in comparison with those whose initial doses were 5 to less than 15 mg/week.

IN PRACTICE:

“Patients with CKD starting low-dose methotrexate should have active surveillance, including blood tests and chest radiographs performed regularly to monitor for signs of myelosuppression, infection, hepatotoxic effects, and pneumotoxic effects,” the researchers wrote.

SOURCE:

The lead author on the study was Flory T. Muanda, MD, of Western University, London, Ont. The study was published online in JAMA Network Open.

LIMITATIONS:

The observational design and lack of data on patients’ adherence to medications were among the limiting factors, as were the focus on older adults with CKD and the lack of assessment of the risk-benefit ratio of low-dose methotrexate.

DISCLOSURES:

The study was supported by the Institute for Clinical Evaluative Sciences. Dr. Muanda had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).

The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:

• For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
• For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
• For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.

Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.

Pediatric patients with SARDs excluded

The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.

In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”

Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”

The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”

Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
 

Preferred treatment options described

First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”

The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”

The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.

University of Toronto

A patient panel provided input

For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.

The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.

Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.

SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).

The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:

• For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
• For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
• For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.

Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.

Pediatric patients with SARDs excluded

The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.

In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”

Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”

The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”

Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
 

Preferred treatment options described

First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”

The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”

The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.

University of Toronto

A patient panel provided input

For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.

The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.

Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.

SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).

The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:

• For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
• For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
• For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.

Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.

Pediatric patients with SARDs excluded

The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.

In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”

Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”

The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”

Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
 

Preferred treatment options described

First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”

The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”

The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.

University of Toronto

A patient panel provided input

For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.

The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.

Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.

SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.

Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.

Lucy Hicks/Medscape Medical News

While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.

Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”

Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.

Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.

Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.

“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.

In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.

Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.

These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.

The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”

Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.

“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”

A version of this article appeared on Medscape.com.

SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.

Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.

Lucy Hicks/Medscape Medical News

While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.

Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”

Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.

Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.

Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.

“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.

In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.

Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.

These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.

The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”

Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.

“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”

A version of this article appeared on Medscape.com.

SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.

Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.

Lucy Hicks/Medscape Medical News

While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.

Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”

Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.

Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.

Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.

“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.

In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.

Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.

These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.

The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”

Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.

“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”

A version of this article appeared on Medscape.com.

SAN DIEGO – Treatment with benralizumab (Fasenra) achieved remission at 36 and 48 weeks at rates similar to those of mepolizumab (Nucala) in a head-to-head phase 3 trial of the two drugs for patients with a relapsing or refractory case of the rare vasculitis eosinophilic granulomatosis with polyangiitis (EGPA).

Benralizumab, a monoclonal antibody from AstraZeneca that binds to the alpha chain of the interleukin (IL)-5 receptor, is indicated as an add-on maintenance treatment for patients 12 years and older with severe eosinophilic asthma but is not currently approved for EGPA. Mepolizumab is a humanized monoclonal antibody targeting IL-5 and the only approved drug for EGPA.

Peter A. Merkel, MD, presented the trial, known as MANDARA, during a late-breaking poster session at the annual meeting of the American College of Rheumatology. A total of 140 patients with EGPA received either subcutaneous benralizumab 30 mg or mepolizumab 300 mg every 4 weeks for 52 weeks. The trial, which began recruitment in late 2019, was limited to patients at least 18 years of age with relapsing/refractory EGPA that required stable use of oral glucocorticoids (OGCs) and immunosuppressive therapy for at least 4 weeks prior to randomization, and the primary endpoint was the proportion of patients who achieved remission at weeks 36 and 48. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 plus an OGC dose of no more than 4 mg/day. Secondary endpoints included rates of accrued and maintained remission, OGC use, clinical benefit and complete response, blood eosinophil counts, total BVAS, and Vascular Damage Index scores. The mean age of the 140 patients was 52 years, and 60% were women.

Dr. Merkel and colleagues reported that the adjusted remission rate at both weeks 36 and 48 was 59.2% for those in the benralizumab arm and 56.5% for those in the mepolizumab arm (P = .7278). The percentage of patients who achieved a BVAS of 0 was similar between the two arms (83% in the benralizumab arm vs. 84.2% for those in the mepolizumab arm; P = .8502), as was the percentage of patients on an OGC dose of up to 4 mg/day (62.1% vs. 57.9%; P = .5942). At 48-52 weeks, 86.1% of patients in the benralizumab arm achieved up to a 50% reduction in OGC use, compared with 73.9% of those in the mepolizumab arm (P = .0611), and 41.4% of patients in the benralizumab arm achieved a 100% reduction in OGC use, compared with 25.8% of those in the mepolizumab arm (P = .0406).

In findings related to safety, the top three adverse events were COVID-19 (21.4% in the benralizumab arm vs. 27.1% in the mepolizumab arm, respectively), headache (17.1% vs. 15.7%), and arthralgia (17.1% vs. 11.4%).

“We were pleased with the findings because they met our expectations,” Dr. Merkel, chief of rheumatology and professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, said in an interview. “The hypothesis was that these two drugs would be equivalent and safe. The implication for patients is that they’ll have another treatment option for EGPA, which is an underrecognized disease with need for more effective treatments. I anticipate that the drug will be approved for use in EGPA, providing another option for treating this complicated multisystem eosinophilic-associated disease. Having more options for our biologic therapies is good.”

He characterized the retention of patients in MANDARA as “remarkable, despite the COVID-19 pandemic. Patients with rare diseases are quite dedicated to helping conduct research. They know that their disease is not common and that they could help others.”

The study was sponsored and funded by AstraZeneca. Dr. Merkel disclosed that he has received consulting fees and research support from many pharmaceutical companies, including AstraZeneca.

SAN DIEGO – Treatment with benralizumab (Fasenra) achieved remission at 36 and 48 weeks at rates similar to those of mepolizumab (Nucala) in a head-to-head phase 3 trial of the two drugs for patients with a relapsing or refractory case of the rare vasculitis eosinophilic granulomatosis with polyangiitis (EGPA).

Benralizumab, a monoclonal antibody from AstraZeneca that binds to the alpha chain of the interleukin (IL)-5 receptor, is indicated as an add-on maintenance treatment for patients 12 years and older with severe eosinophilic asthma but is not currently approved for EGPA. Mepolizumab is a humanized monoclonal antibody targeting IL-5 and the only approved drug for EGPA.

Peter A. Merkel, MD, presented the trial, known as MANDARA, during a late-breaking poster session at the annual meeting of the American College of Rheumatology. A total of 140 patients with EGPA received either subcutaneous benralizumab 30 mg or mepolizumab 300 mg every 4 weeks for 52 weeks. The trial, which began recruitment in late 2019, was limited to patients at least 18 years of age with relapsing/refractory EGPA that required stable use of oral glucocorticoids (OGCs) and immunosuppressive therapy for at least 4 weeks prior to randomization, and the primary endpoint was the proportion of patients who achieved remission at weeks 36 and 48. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 plus an OGC dose of no more than 4 mg/day. Secondary endpoints included rates of accrued and maintained remission, OGC use, clinical benefit and complete response, blood eosinophil counts, total BVAS, and Vascular Damage Index scores. The mean age of the 140 patients was 52 years, and 60% were women.

Dr. Merkel and colleagues reported that the adjusted remission rate at both weeks 36 and 48 was 59.2% for those in the benralizumab arm and 56.5% for those in the mepolizumab arm (P = .7278). The percentage of patients who achieved a BVAS of 0 was similar between the two arms (83% in the benralizumab arm vs. 84.2% for those in the mepolizumab arm; P = .8502), as was the percentage of patients on an OGC dose of up to 4 mg/day (62.1% vs. 57.9%; P = .5942). At 48-52 weeks, 86.1% of patients in the benralizumab arm achieved up to a 50% reduction in OGC use, compared with 73.9% of those in the mepolizumab arm (P = .0611), and 41.4% of patients in the benralizumab arm achieved a 100% reduction in OGC use, compared with 25.8% of those in the mepolizumab arm (P = .0406).

In findings related to safety, the top three adverse events were COVID-19 (21.4% in the benralizumab arm vs. 27.1% in the mepolizumab arm, respectively), headache (17.1% vs. 15.7%), and arthralgia (17.1% vs. 11.4%).

“We were pleased with the findings because they met our expectations,” Dr. Merkel, chief of rheumatology and professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, said in an interview. “The hypothesis was that these two drugs would be equivalent and safe. The implication for patients is that they’ll have another treatment option for EGPA, which is an underrecognized disease with need for more effective treatments. I anticipate that the drug will be approved for use in EGPA, providing another option for treating this complicated multisystem eosinophilic-associated disease. Having more options for our biologic therapies is good.”

He characterized the retention of patients in MANDARA as “remarkable, despite the COVID-19 pandemic. Patients with rare diseases are quite dedicated to helping conduct research. They know that their disease is not common and that they could help others.”

The study was sponsored and funded by AstraZeneca. Dr. Merkel disclosed that he has received consulting fees and research support from many pharmaceutical companies, including AstraZeneca.

SAN DIEGO – Treatment with benralizumab (Fasenra) achieved remission at 36 and 48 weeks at rates similar to those of mepolizumab (Nucala) in a head-to-head phase 3 trial of the two drugs for patients with a relapsing or refractory case of the rare vasculitis eosinophilic granulomatosis with polyangiitis (EGPA).

Benralizumab, a monoclonal antibody from AstraZeneca that binds to the alpha chain of the interleukin (IL)-5 receptor, is indicated as an add-on maintenance treatment for patients 12 years and older with severe eosinophilic asthma but is not currently approved for EGPA. Mepolizumab is a humanized monoclonal antibody targeting IL-5 and the only approved drug for EGPA.

Peter A. Merkel, MD, presented the trial, known as MANDARA, during a late-breaking poster session at the annual meeting of the American College of Rheumatology. A total of 140 patients with EGPA received either subcutaneous benralizumab 30 mg or mepolizumab 300 mg every 4 weeks for 52 weeks. The trial, which began recruitment in late 2019, was limited to patients at least 18 years of age with relapsing/refractory EGPA that required stable use of oral glucocorticoids (OGCs) and immunosuppressive therapy for at least 4 weeks prior to randomization, and the primary endpoint was the proportion of patients who achieved remission at weeks 36 and 48. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 plus an OGC dose of no more than 4 mg/day. Secondary endpoints included rates of accrued and maintained remission, OGC use, clinical benefit and complete response, blood eosinophil counts, total BVAS, and Vascular Damage Index scores. The mean age of the 140 patients was 52 years, and 60% were women.

Dr. Merkel and colleagues reported that the adjusted remission rate at both weeks 36 and 48 was 59.2% for those in the benralizumab arm and 56.5% for those in the mepolizumab arm (P = .7278). The percentage of patients who achieved a BVAS of 0 was similar between the two arms (83% in the benralizumab arm vs. 84.2% for those in the mepolizumab arm; P = .8502), as was the percentage of patients on an OGC dose of up to 4 mg/day (62.1% vs. 57.9%; P = .5942). At 48-52 weeks, 86.1% of patients in the benralizumab arm achieved up to a 50% reduction in OGC use, compared with 73.9% of those in the mepolizumab arm (P = .0611), and 41.4% of patients in the benralizumab arm achieved a 100% reduction in OGC use, compared with 25.8% of those in the mepolizumab arm (P = .0406).

In findings related to safety, the top three adverse events were COVID-19 (21.4% in the benralizumab arm vs. 27.1% in the mepolizumab arm, respectively), headache (17.1% vs. 15.7%), and arthralgia (17.1% vs. 11.4%).

“We were pleased with the findings because they met our expectations,” Dr. Merkel, chief of rheumatology and professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, said in an interview. “The hypothesis was that these two drugs would be equivalent and safe. The implication for patients is that they’ll have another treatment option for EGPA, which is an underrecognized disease with need for more effective treatments. I anticipate that the drug will be approved for use in EGPA, providing another option for treating this complicated multisystem eosinophilic-associated disease. Having more options for our biologic therapies is good.”

He characterized the retention of patients in MANDARA as “remarkable, despite the COVID-19 pandemic. Patients with rare diseases are quite dedicated to helping conduct research. They know that their disease is not common and that they could help others.”

The study was sponsored and funded by AstraZeneca. Dr. Merkel disclosed that he has received consulting fees and research support from many pharmaceutical companies, including AstraZeneca.

A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?

A. Erythrocyte sedimentation rate

B. C-reactive protein

C. Lymphocyte count

D. Antinuclear antibodies

The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.¹ Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.

Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.² Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).

Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.³ The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).

Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)₂ vitamin D, which is the active form of vitamin D.

Several studies have looked at the diagnostic utility of 1,25(OH)₂ vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)₂ vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.⁴ They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)₂ vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)₂D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).

Kavathia et al. looked at whether elevated 1,25(OH)₂ vitamin D levels predicted chronicity of sarcoidosis.⁵ A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)₂ vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)₂ vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).

Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.⁶ Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)₂ vitamin D level checked.


Pearl: Lymphocyte count and 1,25(OH)₂ vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)₂ vitamin D levels monitored.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.

2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.

3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.

4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.

5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.

6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.

A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?

A. Erythrocyte sedimentation rate

B. C-reactive protein

C. Lymphocyte count

D. Antinuclear antibodies

The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.¹ Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.

Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.² Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).

Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.³ The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).

Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)₂ vitamin D, which is the active form of vitamin D.

Several studies have looked at the diagnostic utility of 1,25(OH)₂ vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)₂ vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.⁴ They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)₂ vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)₂D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).

Kavathia et al. looked at whether elevated 1,25(OH)₂ vitamin D levels predicted chronicity of sarcoidosis.⁵ A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)₂ vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)₂ vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).

Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.⁶ Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)₂ vitamin D level checked.


Pearl: Lymphocyte count and 1,25(OH)₂ vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)₂ vitamin D levels monitored.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.

2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.

3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.

4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.

5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.

6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.

A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?

A. Erythrocyte sedimentation rate

B. C-reactive protein

C. Lymphocyte count

D. Antinuclear antibodies

The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.¹ Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.

Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.² Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).

Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.³ The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).

Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)₂ vitamin D, which is the active form of vitamin D.

Several studies have looked at the diagnostic utility of 1,25(OH)₂ vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)₂ vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.⁴ They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)₂ vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)₂D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).

Kavathia et al. looked at whether elevated 1,25(OH)₂ vitamin D levels predicted chronicity of sarcoidosis.⁵ A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)₂ vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)₂ vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).

Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.⁶ Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)₂ vitamin D level checked.


Pearl: Lymphocyte count and 1,25(OH)₂ vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)₂ vitamin D levels monitored.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.

2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.

3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.

4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.

5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.

6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.

SAN DIEGO – Pregnancy in patients with vasculitis had a higher risk for preterm delivery and preeclampsia/eclampsia – especially those with small-vessel vasculitis – compared with the general obstetric population, in a large analysis of administrative claims data presented at the American College of Rheumatology annual meeting.

“We suspect that there is a relationship between the increased risk of these serious hypertensive disorders and preterm delivery, given the higher risk of medically indicated preterm delivery,” one the of the study authors, Audra Horomanski, MD, said in an interview prior to her presentation in a plenary session at the meeting.

Limited data exist on the risks of pregnancy in patients with systemic vasculitis, according to Dr. Horomanski, a rheumatologist who directs the Stanford Vasculitis Clinic at Stanford (Calif.) University. “The majority of what we do know comes from relatively small cohort studies,” she said. “This is the first U.S., nationwide database study looking at the risk of preterm delivery and other adverse pregnancy outcomes.”

Steve Fisch Photography

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

SAN DIEGO – Pregnancy in patients with vasculitis had a higher risk for preterm delivery and preeclampsia/eclampsia – especially those with small-vessel vasculitis – compared with the general obstetric population, in a large analysis of administrative claims data presented at the American College of Rheumatology annual meeting.

“We suspect that there is a relationship between the increased risk of these serious hypertensive disorders and preterm delivery, given the higher risk of medically indicated preterm delivery,” one the of the study authors, Audra Horomanski, MD, said in an interview prior to her presentation in a plenary session at the meeting.

Limited data exist on the risks of pregnancy in patients with systemic vasculitis, according to Dr. Horomanski, a rheumatologist who directs the Stanford Vasculitis Clinic at Stanford (Calif.) University. “The majority of what we do know comes from relatively small cohort studies,” she said. “This is the first U.S., nationwide database study looking at the risk of preterm delivery and other adverse pregnancy outcomes.”

Steve Fisch Photography

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

SAN DIEGO – Pregnancy in patients with vasculitis had a higher risk for preterm delivery and preeclampsia/eclampsia – especially those with small-vessel vasculitis – compared with the general obstetric population, in a large analysis of administrative claims data presented at the American College of Rheumatology annual meeting.

“We suspect that there is a relationship between the increased risk of these serious hypertensive disorders and preterm delivery, given the higher risk of medically indicated preterm delivery,” one the of the study authors, Audra Horomanski, MD, said in an interview prior to her presentation in a plenary session at the meeting.

Limited data exist on the risks of pregnancy in patients with systemic vasculitis, according to Dr. Horomanski, a rheumatologist who directs the Stanford Vasculitis Clinic at Stanford (Calif.) University. “The majority of what we do know comes from relatively small cohort studies,” she said. “This is the first U.S., nationwide database study looking at the risk of preterm delivery and other adverse pregnancy outcomes.”

Steve Fisch Photography

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

SAN DIEGO – A real-world analysis linked the PEXIVAS reduced-dose glucocorticoid (GC) regimen to a higher likelihood of a group of poor outcomes such as death in patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).

The retrospective observational study, presented at the annual meeting of the American College of Rheumatology, aimed to see whether results from the landmark PEXIVAS trial would hold up in a real-world analysis given some important limitations of the PEXIVAS’s primary outcome and its relative lack of balance in choice of induction agents.

First author of the new study, Sophie Nagle, MD, of Cochin Hospital in Paris, and colleagues in the French Vasculitis Study Group noted that PEXIVAS “demonstrated noninferiority of reduced-dose GC regimen compared to standard dose for the incidence of death or end-stage kidney disease (ESKD), with a significant reduction in serious infections at 1 year. However, the primary endpoint did not include disease progression or relapse, the majority of patients received cyclophosphamide as induction therapy, and subgroup analysis showed a trend towards an increased risk of death or ESKD in [rituximab]-treated patients.”

The new findings “give us pause about using low-dose glucocorticoid regimens” and suggest that rheumatologists might be a little more conservative about their use than randomized controlled trials such as PEXIVAS might suggest, said Vanderbilt University vasculitis specialist Kevin W. Byram, MD, who’s familiar with the findings but did not take part in the study.

Dr. Nagle reported that among 234 patients with either GPA or MPA, 33.3% of 126 who received a reduced-dose GC regimen experienced one of the 12-month composite primary outcome’s events of death, disease relapse, ESKD, or disease progression before remission that required treatment modification, compared with 18.5% of 108 who received the standard GC regimen (P = .016).

In a propensity score analysis, the higher risk of poor outcomes in the reduced-dose group remained (hazard ratio, 1.57; 95% confidence interval, 0.93-2.64). A multivariate analysis also identified a higher risk for the composite primary outcome in the reduced-dose group (HR, 1.72; 95% CI, 1.08-2.74), although there was no association with an increased risk of death or ESKD.

The PEXIVAS study, published in 2020, supported lower GC doses in antineutrophil cytoplasmic antibody–associated vasculitis, potentially revolutionizing treatment. “Historically, we have used high doses of glucocorticoids on slower tapers to treat this disease, which itself is a strategy that leads to potential complications,” Dr. Byram said. “PEXIVAS suggested we could potentially use less glucocorticoids in these patients.”

For the retrospective, multicenter study, researchers tracked patients from 2018 to 2022, all aged 15 and above. They included 93 with MPA and 141 with GPA. Nearly half were female, and they had a mean age of 61 years. The patients had severe flare-ups treated with rituximab or cyclophosphamide induction and reduced-dose or standard GC regimen.

The standard care and reduced-dose groups were similar, Dr. Nagle said, although the standard group had significantly more patients with GPA (71% vs. 29% with MPA) than did the low-dose group (51% with GPA, 49% with MPA).

The researchers reported that in a reduced-dose subgroup, patients with creatinine levels above 300 micromol/L were more likely to meet the primary endpoint (relative risk, 2.14; 95% CI, 1.14-4.03). Those treated with the reduced-dose GC regimen were also more likely to reach the primary endpoint (HR, 1.61; 95% CI, 0.94-2.77) and die or develop ESKD (HR, 2.42; 95% CI, 1.04-5.66).

However, adverse events at 12 months were similar in both groups: The authors noted that those who received the reduced-dose GC regimen didn’t have higher risk of death, ESKD, or severe infections.

The authors highlighted that “increased vigilance is required when using the reduced-dose GC regimen especially in two subgroups of patients due to the risk of failure: Patients receiving rituximab as induction therapy [and] patients with severe initial kidney disease (serum creatinine > 300 micromol/L).”

The study authors note several limitations: The study is retrospective, and the standard dose group is heterogeneous.

“This study raises the idea that we need to be careful in using low-dose glucocorticoid regimens, but not avoid them all together,” Dr. Byram said. “The finding that those with worse kidney function fared worse lines up with my clinical experiences. There are clearly populations with this disease that could benefit from more steroid, and it tends to be the ones that are sicker at presentation, particularly those requiring ICU-level care.”

He advised colleagues to “not be dogmatic and use strict low-dose regimens ‘just because.’ ”

No study funding was reported. Dr. Nagle reported having no relevant financial relationships, and disclosures for other authors were not reported. Dr. Byram reports serving on the Vasculitis Foundation board of directors.

SAN DIEGO – A real-world analysis linked the PEXIVAS reduced-dose glucocorticoid (GC) regimen to a higher likelihood of a group of poor outcomes such as death in patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).

The retrospective observational study, presented at the annual meeting of the American College of Rheumatology, aimed to see whether results from the landmark PEXIVAS trial would hold up in a real-world analysis given some important limitations of the PEXIVAS’s primary outcome and its relative lack of balance in choice of induction agents.

First author of the new study, Sophie Nagle, MD, of Cochin Hospital in Paris, and colleagues in the French Vasculitis Study Group noted that PEXIVAS “demonstrated noninferiority of reduced-dose GC regimen compared to standard dose for the incidence of death or end-stage kidney disease (ESKD), with a significant reduction in serious infections at 1 year. However, the primary endpoint did not include disease progression or relapse, the majority of patients received cyclophosphamide as induction therapy, and subgroup analysis showed a trend towards an increased risk of death or ESKD in [rituximab]-treated patients.”

The new findings “give us pause about using low-dose glucocorticoid regimens” and suggest that rheumatologists might be a little more conservative about their use than randomized controlled trials such as PEXIVAS might suggest, said Vanderbilt University vasculitis specialist Kevin W. Byram, MD, who’s familiar with the findings but did not take part in the study.

Dr. Nagle reported that among 234 patients with either GPA or MPA, 33.3% of 126 who received a reduced-dose GC regimen experienced one of the 12-month composite primary outcome’s events of death, disease relapse, ESKD, or disease progression before remission that required treatment modification, compared with 18.5% of 108 who received the standard GC regimen (P = .016).

In a propensity score analysis, the higher risk of poor outcomes in the reduced-dose group remained (hazard ratio, 1.57; 95% confidence interval, 0.93-2.64). A multivariate analysis also identified a higher risk for the composite primary outcome in the reduced-dose group (HR, 1.72; 95% CI, 1.08-2.74), although there was no association with an increased risk of death or ESKD.

The PEXIVAS study, published in 2020, supported lower GC doses in antineutrophil cytoplasmic antibody–associated vasculitis, potentially revolutionizing treatment. “Historically, we have used high doses of glucocorticoids on slower tapers to treat this disease, which itself is a strategy that leads to potential complications,” Dr. Byram said. “PEXIVAS suggested we could potentially use less glucocorticoids in these patients.”

For the retrospective, multicenter study, researchers tracked patients from 2018 to 2022, all aged 15 and above. They included 93 with MPA and 141 with GPA. Nearly half were female, and they had a mean age of 61 years. The patients had severe flare-ups treated with rituximab or cyclophosphamide induction and reduced-dose or standard GC regimen.

The standard care and reduced-dose groups were similar, Dr. Nagle said, although the standard group had significantly more patients with GPA (71% vs. 29% with MPA) than did the low-dose group (51% with GPA, 49% with MPA).

The researchers reported that in a reduced-dose subgroup, patients with creatinine levels above 300 micromol/L were more likely to meet the primary endpoint (relative risk, 2.14; 95% CI, 1.14-4.03). Those treated with the reduced-dose GC regimen were also more likely to reach the primary endpoint (HR, 1.61; 95% CI, 0.94-2.77) and die or develop ESKD (HR, 2.42; 95% CI, 1.04-5.66).

However, adverse events at 12 months were similar in both groups: The authors noted that those who received the reduced-dose GC regimen didn’t have higher risk of death, ESKD, or severe infections.

The authors highlighted that “increased vigilance is required when using the reduced-dose GC regimen especially in two subgroups of patients due to the risk of failure: Patients receiving rituximab as induction therapy [and] patients with severe initial kidney disease (serum creatinine > 300 micromol/L).”

The study authors note several limitations: The study is retrospective, and the standard dose group is heterogeneous.

“This study raises the idea that we need to be careful in using low-dose glucocorticoid regimens, but not avoid them all together,” Dr. Byram said. “The finding that those with worse kidney function fared worse lines up with my clinical experiences. There are clearly populations with this disease that could benefit from more steroid, and it tends to be the ones that are sicker at presentation, particularly those requiring ICU-level care.”

He advised colleagues to “not be dogmatic and use strict low-dose regimens ‘just because.’ ”

No study funding was reported. Dr. Nagle reported having no relevant financial relationships, and disclosures for other authors were not reported. Dr. Byram reports serving on the Vasculitis Foundation board of directors.

SAN DIEGO – A real-world analysis linked the PEXIVAS reduced-dose glucocorticoid (GC) regimen to a higher likelihood of a group of poor outcomes such as death in patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).

The retrospective observational study, presented at the annual meeting of the American College of Rheumatology, aimed to see whether results from the landmark PEXIVAS trial would hold up in a real-world analysis given some important limitations of the PEXIVAS’s primary outcome and its relative lack of balance in choice of induction agents.

First author of the new study, Sophie Nagle, MD, of Cochin Hospital in Paris, and colleagues in the French Vasculitis Study Group noted that PEXIVAS “demonstrated noninferiority of reduced-dose GC regimen compared to standard dose for the incidence of death or end-stage kidney disease (ESKD), with a significant reduction in serious infections at 1 year. However, the primary endpoint did not include disease progression or relapse, the majority of patients received cyclophosphamide as induction therapy, and subgroup analysis showed a trend towards an increased risk of death or ESKD in [rituximab]-treated patients.”

The new findings “give us pause about using low-dose glucocorticoid regimens” and suggest that rheumatologists might be a little more conservative about their use than randomized controlled trials such as PEXIVAS might suggest, said Vanderbilt University vasculitis specialist Kevin W. Byram, MD, who’s familiar with the findings but did not take part in the study.

Dr. Nagle reported that among 234 patients with either GPA or MPA, 33.3% of 126 who received a reduced-dose GC regimen experienced one of the 12-month composite primary outcome’s events of death, disease relapse, ESKD, or disease progression before remission that required treatment modification, compared with 18.5% of 108 who received the standard GC regimen (P = .016).

In a propensity score analysis, the higher risk of poor outcomes in the reduced-dose group remained (hazard ratio, 1.57; 95% confidence interval, 0.93-2.64). A multivariate analysis also identified a higher risk for the composite primary outcome in the reduced-dose group (HR, 1.72; 95% CI, 1.08-2.74), although there was no association with an increased risk of death or ESKD.

The PEXIVAS study, published in 2020, supported lower GC doses in antineutrophil cytoplasmic antibody–associated vasculitis, potentially revolutionizing treatment. “Historically, we have used high doses of glucocorticoids on slower tapers to treat this disease, which itself is a strategy that leads to potential complications,” Dr. Byram said. “PEXIVAS suggested we could potentially use less glucocorticoids in these patients.”

For the retrospective, multicenter study, researchers tracked patients from 2018 to 2022, all aged 15 and above. They included 93 with MPA and 141 with GPA. Nearly half were female, and they had a mean age of 61 years. The patients had severe flare-ups treated with rituximab or cyclophosphamide induction and reduced-dose or standard GC regimen.

The standard care and reduced-dose groups were similar, Dr. Nagle said, although the standard group had significantly more patients with GPA (71% vs. 29% with MPA) than did the low-dose group (51% with GPA, 49% with MPA).

The researchers reported that in a reduced-dose subgroup, patients with creatinine levels above 300 micromol/L were more likely to meet the primary endpoint (relative risk, 2.14; 95% CI, 1.14-4.03). Those treated with the reduced-dose GC regimen were also more likely to reach the primary endpoint (HR, 1.61; 95% CI, 0.94-2.77) and die or develop ESKD (HR, 2.42; 95% CI, 1.04-5.66).

However, adverse events at 12 months were similar in both groups: The authors noted that those who received the reduced-dose GC regimen didn’t have higher risk of death, ESKD, or severe infections.

The authors highlighted that “increased vigilance is required when using the reduced-dose GC regimen especially in two subgroups of patients due to the risk of failure: Patients receiving rituximab as induction therapy [and] patients with severe initial kidney disease (serum creatinine > 300 micromol/L).”

The study authors note several limitations: The study is retrospective, and the standard dose group is heterogeneous.

“This study raises the idea that we need to be careful in using low-dose glucocorticoid regimens, but not avoid them all together,” Dr. Byram said. “The finding that those with worse kidney function fared worse lines up with my clinical experiences. There are clearly populations with this disease that could benefit from more steroid, and it tends to be the ones that are sicker at presentation, particularly those requiring ICU-level care.”

He advised colleagues to “not be dogmatic and use strict low-dose regimens ‘just because.’ ”

No study funding was reported. Dr. Nagle reported having no relevant financial relationships, and disclosures for other authors were not reported. Dr. Byram reports serving on the Vasculitis Foundation board of directors.

SAN DIEGO – Pregnant individuals with autoimmune rheumatic diseases (ARDs) are at least four times more likely to experience an acute cardiovascular event (CVE) than are pregnant individuals without these conditions, according to new research presented at the annual meeting of the American College of Rheumatology. Pregnant individuals with primary antiphospholipid syndrome (APS) had a 15-fold increase in CVE risk.

Patients who experienced CVEs were also more likely to experience preterm birth and other adverse pregnancy outcomes (APOs).

zoranm/Getty Images

Rashmi Dhital, MD, a rheumatology fellow at the University of California, San Diego, and colleagues examined the medical records of pregnant individuals in California who had delivered singleton live-born infants from 2005 to 2020. Using data from the Study of Outcomes in Mothers and Infants (SOMI) database, an administrative population-based birth cohort in California, they identified more than 7 million individuals, 19,340 with ARDs and 7,758 with APS.

They then analyzed how many patients experienced an acute CVE during pregnancy and up to 6 weeks after giving birth.

CVEs occurred in 2.0% of patients with ARDs, 6.9% of individuals with APS, and 0.4% of women without these conditions. CVE risk was four times higher in the ARDs group (adjusted relative risk, 4.1; 95% confidence interval, 3.7-4.5) and nearly 15 times higher in the APS group (aRR, 14.7; 95% CI, 13.5-16.0) than in the comparison group. Patients with systemic lupus erythematosus (SLE) had a sixfold higher risk of CVE, which was further exacerbated by concomitant APS (18-fold higher risk) or lupus nephritis (15-fold higher risk).

Dr. Dhital also classified CVEs as either venous thromboembolism and non-VTE events. Pregnant patients with APS had a high risk for VTE-only CVE (40-fold greater) and a 3.7-fold higher risk of non-VTE events, compared with pregnant patients without these conditions. Patients with SLE along with lupus nephritis had a 20-fold increased risk of VTE-only CVE and an 11-fold higher risk of non-VTE CVE.

Although the study grouped rheumatic diseases together, “lupus is generally driving these results,” Sharon Kolasinski, MD, of the University of Pennsylvania, Philadelphia, noted in an interview. She moderated the plenary session where the research was presented. “If you take out lupus, then what is the risk? That would be an interesting question.”

Between 25% and 30% of all CVEs occurred in the postpartum period, highlighting the importance of close monitoring of cardiovascular risks and events in women with ARDs or APS both during pregnancy and postpartum, Dr. Dhital noted.

Recognizing these risks “can sometimes be challenging due to a lower suspicion of CVE in younger patients, and also symptoms overlap with normal pregnancy,” Dr. Dhital said during her plenary presentation. Working with other clinical teams could help physicians detect these risks in patients.

“It’s important for us to remember that there’s increased risk of cardiovascular events in pregnancy in our patients. It’s uncommon, but it’s not zero,” added Dr. Kolasinski, and this study highlighted when physicians should be more focused about that risk.

Dr. Dhital noted there were some limitations to the study that are inherent in using administrative databases for research that relies on ICD codes, including “the availability of information on disease activity, medications, and labs, which may restrict clinical interpretation.”
 

SOMI data reinforced by National Inpatient Sample study

The findings were complemented by a study using the National Inpatient Sample database to explore CVE risk in pregnant individuals with various rheumatic diseases. Lead author Karun Shrestha, MD, a resident physician at St. Barnabas Hospital in New York, and colleagues identified delivery hospitalizations from 2016 to 2019 for individuals with SLE, RA, and systemic vasculitis and looked for CVEs including preeclampsia, peripartum cardiomyopathy (PPCM), heart failure, stroke, cardiac arrhythmias, and VTE.

Lucy Hicks/Medscape Medical News

Out of over 3.4 million delivery hospitalizations, researchers identified 5,900 individuals with SLE, 4,895 with RA, and 325 with vasculitis. After adjusting for confounding factors such as race, age, insurance, and other comorbidities, SLE was identified as an independent risk factor for preeclampsia (odds ratio, 1.5; 95% CI, 1.1-2.1), arrhythmia (OR, 3.17; 95% CI, 1.73-5.79), and venous thrombosis (OR, 8.4; 95% CI, 2.9-22.1). Vasculitis was tied to increased risk for preeclampsia (OR, 4.7; 95% CI, 2-11.3), stroke (OR, 513.3; 95% CI, 114-2,284), heart failure (OR, 24.17; 95% CI, 4.68-124.6), and PPCM (OR, 66.7; 95% CI, 8.7-509.4). RA was tied to an increased risk for preeclampsia (OR, 1.5; 95% CI, 1.05-2.1).

Patients with SLE or vasculitis had longer, more costly hospital stays, compared with those without these conditions, and they experienced higher rates of in-hospital mortality. While previous research has demonstrated that patients with SLE have higher risk of cardiac events, there is less literature on CVE risk in pregnancies for vasculitis, Dr. Shrestha said in an interview.

“It’s something to work on,” he said.
 

Adverse pregnancy outcomes higher with ARDs, APS

In a second abstract also led by Dr. Dhital using SOMI data, researchers found that pregnant individuals with ARDs or APS had a higher risk of experiencing an APO – preterm birth or small-for-gestational age – than individuals without these conditions. CVEs exacerbated that risk, regardless of underlying chronic health conditions.

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

SAN DIEGO – Pregnant individuals with autoimmune rheumatic diseases (ARDs) are at least four times more likely to experience an acute cardiovascular event (CVE) than are pregnant individuals without these conditions, according to new research presented at the annual meeting of the American College of Rheumatology. Pregnant individuals with primary antiphospholipid syndrome (APS) had a 15-fold increase in CVE risk.

Patients who experienced CVEs were also more likely to experience preterm birth and other adverse pregnancy outcomes (APOs).

zoranm/Getty Images

Rashmi Dhital, MD, a rheumatology fellow at the University of California, San Diego, and colleagues examined the medical records of pregnant individuals in California who had delivered singleton live-born infants from 2005 to 2020. Using data from the Study of Outcomes in Mothers and Infants (SOMI) database, an administrative population-based birth cohort in California, they identified more than 7 million individuals, 19,340 with ARDs and 7,758 with APS.

They then analyzed how many patients experienced an acute CVE during pregnancy and up to 6 weeks after giving birth.

CVEs occurred in 2.0% of patients with ARDs, 6.9% of individuals with APS, and 0.4% of women without these conditions. CVE risk was four times higher in the ARDs group (adjusted relative risk, 4.1; 95% confidence interval, 3.7-4.5) and nearly 15 times higher in the APS group (aRR, 14.7; 95% CI, 13.5-16.0) than in the comparison group. Patients with systemic lupus erythematosus (SLE) had a sixfold higher risk of CVE, which was further exacerbated by concomitant APS (18-fold higher risk) or lupus nephritis (15-fold higher risk).

Dr. Dhital also classified CVEs as either venous thromboembolism and non-VTE events. Pregnant patients with APS had a high risk for VTE-only CVE (40-fold greater) and a 3.7-fold higher risk of non-VTE events, compared with pregnant patients without these conditions. Patients with SLE along with lupus nephritis had a 20-fold increased risk of VTE-only CVE and an 11-fold higher risk of non-VTE CVE.

Although the study grouped rheumatic diseases together, “lupus is generally driving these results,” Sharon Kolasinski, MD, of the University of Pennsylvania, Philadelphia, noted in an interview. She moderated the plenary session where the research was presented. “If you take out lupus, then what is the risk? That would be an interesting question.”

Between 25% and 30% of all CVEs occurred in the postpartum period, highlighting the importance of close monitoring of cardiovascular risks and events in women with ARDs or APS both during pregnancy and postpartum, Dr. Dhital noted.

Recognizing these risks “can sometimes be challenging due to a lower suspicion of CVE in younger patients, and also symptoms overlap with normal pregnancy,” Dr. Dhital said during her plenary presentation. Working with other clinical teams could help physicians detect these risks in patients.

“It’s important for us to remember that there’s increased risk of cardiovascular events in pregnancy in our patients. It’s uncommon, but it’s not zero,” added Dr. Kolasinski, and this study highlighted when physicians should be more focused about that risk.

Dr. Dhital noted there were some limitations to the study that are inherent in using administrative databases for research that relies on ICD codes, including “the availability of information on disease activity, medications, and labs, which may restrict clinical interpretation.”
 

SOMI data reinforced by National Inpatient Sample study

The findings were complemented by a study using the National Inpatient Sample database to explore CVE risk in pregnant individuals with various rheumatic diseases. Lead author Karun Shrestha, MD, a resident physician at St. Barnabas Hospital in New York, and colleagues identified delivery hospitalizations from 2016 to 2019 for individuals with SLE, RA, and systemic vasculitis and looked for CVEs including preeclampsia, peripartum cardiomyopathy (PPCM), heart failure, stroke, cardiac arrhythmias, and VTE.

Lucy Hicks/Medscape Medical News

Out of over 3.4 million delivery hospitalizations, researchers identified 5,900 individuals with SLE, 4,895 with RA, and 325 with vasculitis. After adjusting for confounding factors such as race, age, insurance, and other comorbidities, SLE was identified as an independent risk factor for preeclampsia (odds ratio, 1.5; 95% CI, 1.1-2.1), arrhythmia (OR, 3.17; 95% CI, 1.73-5.79), and venous thrombosis (OR, 8.4; 95% CI, 2.9-22.1). Vasculitis was tied to increased risk for preeclampsia (OR, 4.7; 95% CI, 2-11.3), stroke (OR, 513.3; 95% CI, 114-2,284), heart failure (OR, 24.17; 95% CI, 4.68-124.6), and PPCM (OR, 66.7; 95% CI, 8.7-509.4). RA was tied to an increased risk for preeclampsia (OR, 1.5; 95% CI, 1.05-2.1).

Patients with SLE or vasculitis had longer, more costly hospital stays, compared with those without these conditions, and they experienced higher rates of in-hospital mortality. While previous research has demonstrated that patients with SLE have higher risk of cardiac events, there is less literature on CVE risk in pregnancies for vasculitis, Dr. Shrestha said in an interview.

“It’s something to work on,” he said.
 

Adverse pregnancy outcomes higher with ARDs, APS

In a second abstract also led by Dr. Dhital using SOMI data, researchers found that pregnant individuals with ARDs or APS had a higher risk of experiencing an APO – preterm birth or small-for-gestational age – than individuals without these conditions. CVEs exacerbated that risk, regardless of underlying chronic health conditions.

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

SAN DIEGO – Pregnant individuals with autoimmune rheumatic diseases (ARDs) are at least four times more likely to experience an acute cardiovascular event (CVE) than are pregnant individuals without these conditions, according to new research presented at the annual meeting of the American College of Rheumatology. Pregnant individuals with primary antiphospholipid syndrome (APS) had a 15-fold increase in CVE risk.

Patients who experienced CVEs were also more likely to experience preterm birth and other adverse pregnancy outcomes (APOs).

zoranm/Getty Images

Rashmi Dhital, MD, a rheumatology fellow at the University of California, San Diego, and colleagues examined the medical records of pregnant individuals in California who had delivered singleton live-born infants from 2005 to 2020. Using data from the Study of Outcomes in Mothers and Infants (SOMI) database, an administrative population-based birth cohort in California, they identified more than 7 million individuals, 19,340 with ARDs and 7,758 with APS.

They then analyzed how many patients experienced an acute CVE during pregnancy and up to 6 weeks after giving birth.

CVEs occurred in 2.0% of patients with ARDs, 6.9% of individuals with APS, and 0.4% of women without these conditions. CVE risk was four times higher in the ARDs group (adjusted relative risk, 4.1; 95% confidence interval, 3.7-4.5) and nearly 15 times higher in the APS group (aRR, 14.7; 95% CI, 13.5-16.0) than in the comparison group. Patients with systemic lupus erythematosus (SLE) had a sixfold higher risk of CVE, which was further exacerbated by concomitant APS (18-fold higher risk) or lupus nephritis (15-fold higher risk).

Dr. Dhital also classified CVEs as either venous thromboembolism and non-VTE events. Pregnant patients with APS had a high risk for VTE-only CVE (40-fold greater) and a 3.7-fold higher risk of non-VTE events, compared with pregnant patients without these conditions. Patients with SLE along with lupus nephritis had a 20-fold increased risk of VTE-only CVE and an 11-fold higher risk of non-VTE CVE.

Although the study grouped rheumatic diseases together, “lupus is generally driving these results,” Sharon Kolasinski, MD, of the University of Pennsylvania, Philadelphia, noted in an interview. She moderated the plenary session where the research was presented. “If you take out lupus, then what is the risk? That would be an interesting question.”

Between 25% and 30% of all CVEs occurred in the postpartum period, highlighting the importance of close monitoring of cardiovascular risks and events in women with ARDs or APS both during pregnancy and postpartum, Dr. Dhital noted.

Recognizing these risks “can sometimes be challenging due to a lower suspicion of CVE in younger patients, and also symptoms overlap with normal pregnancy,” Dr. Dhital said during her plenary presentation. Working with other clinical teams could help physicians detect these risks in patients.

“It’s important for us to remember that there’s increased risk of cardiovascular events in pregnancy in our patients. It’s uncommon, but it’s not zero,” added Dr. Kolasinski, and this study highlighted when physicians should be more focused about that risk.

Dr. Dhital noted there were some limitations to the study that are inherent in using administrative databases for research that relies on ICD codes, including “the availability of information on disease activity, medications, and labs, which may restrict clinical interpretation.”
 

SOMI data reinforced by National Inpatient Sample study

The findings were complemented by a study using the National Inpatient Sample database to explore CVE risk in pregnant individuals with various rheumatic diseases. Lead author Karun Shrestha, MD, a resident physician at St. Barnabas Hospital in New York, and colleagues identified delivery hospitalizations from 2016 to 2019 for individuals with SLE, RA, and systemic vasculitis and looked for CVEs including preeclampsia, peripartum cardiomyopathy (PPCM), heart failure, stroke, cardiac arrhythmias, and VTE.

Lucy Hicks/Medscape Medical News

Out of over 3.4 million delivery hospitalizations, researchers identified 5,900 individuals with SLE, 4,895 with RA, and 325 with vasculitis. After adjusting for confounding factors such as race, age, insurance, and other comorbidities, SLE was identified as an independent risk factor for preeclampsia (odds ratio, 1.5; 95% CI, 1.1-2.1), arrhythmia (OR, 3.17; 95% CI, 1.73-5.79), and venous thrombosis (OR, 8.4; 95% CI, 2.9-22.1). Vasculitis was tied to increased risk for preeclampsia (OR, 4.7; 95% CI, 2-11.3), stroke (OR, 513.3; 95% CI, 114-2,284), heart failure (OR, 24.17; 95% CI, 4.68-124.6), and PPCM (OR, 66.7; 95% CI, 8.7-509.4). RA was tied to an increased risk for preeclampsia (OR, 1.5; 95% CI, 1.05-2.1).

Patients with SLE or vasculitis had longer, more costly hospital stays, compared with those without these conditions, and they experienced higher rates of in-hospital mortality. While previous research has demonstrated that patients with SLE have higher risk of cardiac events, there is less literature on CVE risk in pregnancies for vasculitis, Dr. Shrestha said in an interview.

“It’s something to work on,” he said.
 

Adverse pregnancy outcomes higher with ARDs, APS

In a second abstract also led by Dr. Dhital using SOMI data, researchers found that pregnant individuals with ARDs or APS had a higher risk of experiencing an APO – preterm birth or small-for-gestational age – than individuals without these conditions. CVEs exacerbated that risk, regardless of underlying chronic health conditions.

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

SAN DIEGO – Pregnant women with anti-SSA/Ro autoantibodies at titer levels of less than 1,000 ELISA units per mL are at minimal to no risk for fetal atrioventricular (AV) block and may be able to forgo traditional echocardiographic heart rhythm monitoring, results from an ongoing, prospective, multicenter trial demonstrated.

However, pregnant patients with higher titer antibodies seem to be at greatest risk for fetal AV block and may benefit from ambulatory fetal heart rhythm monitoring (FHRM), which can detect emergent AV block, according to the study findings. The findings were published online in Arthritis & Rheumatology and will be presented Nov. 13 at the American College of Rheumatology (ACR) 2023 Annual Meeting by Jill P. Buyon, MD, a rheumatologist who directs the division of rheumatology and the Lupus Center at NYU Langone Health in New York.

“While anti-Ro antibodies have been known to be associated with AV block for decades, it has become increasingly clear that antibody titers matter,” Dr. Buyon said in an interview.

For the investigation, which is the largest of its kind, researchers at 22 sites drew from the large multiracial national study of pregnant women, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), to address the impact of anti-Ro titers and use of frequent ambulatory FHRM on outcomes in women with no previously affected children and those at risk for recurrence. Monitoring occurred during the second trimester of pregnancy (from 17 weeks through 26 weeks) and consisted of daily fetal home testing by mothers using handheld, commercially available Doppler devices.

These were followed up by weekly or biweekly echocardiograms, and ultrasound tests to evaluate fetal heart rhythm and function, as well as to show any structural problems. Three times per day, the pregnant women texted the Doppler sound recordings in real time to a pediatric cardiologist, who immediately ordered an additional echocardiogram in cases of irregular or slowing fetal heart rates. If second-degree heart block was detected, drug therapy was initiated.
 

No AV block seen with low anti-Ro titers

Dr. Buyon, who led the study with Bettina Cuneo, MD, clinical scholar and professor of surgery and pediatrics at the University of Arizona in Tucson, presented findings from 413 pregnant subjects with a mean age of 33 years who finished monitoring surveillance: 152 women had low titers of both anti-Ro60 and –Ro52 (defined as < 1,000 ELISA units per mL), and 261 women with titers above the threshold for either antibody (defined as ≥ 1,000 ELISA units per mL). Of the 152 women with low titers of both anti-Ro60 and –Ro52, none of the pregnancies past 26 weeks resulted in AV block. Of the 261 women with titers above the threshold for either antibody, 10 of the pregnancies resulted in AV block (3.8%). The incidence of AV block increased with higher antibody titer levels, reaching 7.7% for those in the top quartile for anti–60-kD SSA/Ro; this increased to 27.3% in study participants with a previous child who had AV block, although numbers in this category were small.

Analysis of cumulative FHRM recordings between surveillance echocardiograms revealed that no case of second-degree or third-degree AV block was missed. In addition, 70% of AV blocks detected by FHRM were second-degree and all occurred less than 12 hours from normal FHRM and within another 45 minutes to 4.5 hours to echocardiogram. The one case of second/third-degree and two cases of third-degree AV block were diagnosed by urgent echocardiogram more than 17 to 72 hours from a previously normal FHRM episode.
 

Other factors besides high anti-Ro titer likely play a role

“STOP BLOQ nicely demonstrates that low titer is associated with a very low risk AV block, and intense monitoring may not be needed,” Dr. Buyon told this news organization. “However, high titer is not the whole answer since even women with the very highest titers can have healthy babies. This report also shows that titers stay constant through pregnancies in the same mother, whether there is the complication of AV block or not. This suggests other factors contribute to AV block.”

She added that FHRM can be easily performed by the mother, but at this time is still best interpreted by a cardiologist. “FHRM detected all cases of AV block, which can happen in hours,” she said. “FHRM should decrease the need for frequent echocardiograms. Some mothers do have more difficulty in deciding whether the baby’s heart is beating irregularly. We need [to improve our teaching] and for how best to have a cardiologist or trained listener interpret. FHRM can be done by the mother but needs interpretation by a cardiologist until we develop a device which can identify abnormalities.”

She acknowledged certain limitations of the study, including the fact that a commercial test for anti-SSA/Ro antibody levels is not available to all clinicians. “Try to find a lab that measures high titer anti-Ro antibodies, but if not, then use one of the common commercial tests such as the BioPlex 2000 autoimmune panels and consider decreased surveillance if titer is < 8,” Dr. Buyon advised.

Vaneet K. Sandhu, MD, a rheumatologist with Loma Linda (Calif.) Medical Center, who was asked to comment on the work, said that the study not only justifies the limited use of FHRM in those with high titer antibodies (followed by urgent fetal echocardiography where indicated), but also risk stratification for fetal AV block.

Loma Linda University Health

“For years, we have recommended frequent fetal echocardiography testing in pregnant women with positive anti-SSA/Ro,” Dr. Sandhu said. “This study tells us we need to look deeper. On one hand, recognizing that low titer anti-Ro antibodies do not confer a risk of AV block is cost effective. On the other hand, while the titer of the antibody appears to contribute to fetal AV block, we need to delve deeper into additional factors contributing to fetal AV block risk in order to better navigate our surveillance methods.”

The study was supported by NIH grants from the National Institute of Child Health and Human Development and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Sandhu has disclosed no relevant financial relationships.
 

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

SAN DIEGO – Pregnant women with anti-SSA/Ro autoantibodies at titer levels of less than 1,000 ELISA units per mL are at minimal to no risk for fetal atrioventricular (AV) block and may be able to forgo traditional echocardiographic heart rhythm monitoring, results from an ongoing, prospective, multicenter trial demonstrated.

However, pregnant patients with higher titer antibodies seem to be at greatest risk for fetal AV block and may benefit from ambulatory fetal heart rhythm monitoring (FHRM), which can detect emergent AV block, according to the study findings. The findings were published online in Arthritis & Rheumatology and will be presented Nov. 13 at the American College of Rheumatology (ACR) 2023 Annual Meeting by Jill P. Buyon, MD, a rheumatologist who directs the division of rheumatology and the Lupus Center at NYU Langone Health in New York.

“While anti-Ro antibodies have been known to be associated with AV block for decades, it has become increasingly clear that antibody titers matter,” Dr. Buyon said in an interview.

For the investigation, which is the largest of its kind, researchers at 22 sites drew from the large multiracial national study of pregnant women, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), to address the impact of anti-Ro titers and use of frequent ambulatory FHRM on outcomes in women with no previously affected children and those at risk for recurrence. Monitoring occurred during the second trimester of pregnancy (from 17 weeks through 26 weeks) and consisted of daily fetal home testing by mothers using handheld, commercially available Doppler devices.

These were followed up by weekly or biweekly echocardiograms, and ultrasound tests to evaluate fetal heart rhythm and function, as well as to show any structural problems. Three times per day, the pregnant women texted the Doppler sound recordings in real time to a pediatric cardiologist, who immediately ordered an additional echocardiogram in cases of irregular or slowing fetal heart rates. If second-degree heart block was detected, drug therapy was initiated.
 

No AV block seen with low anti-Ro titers

Dr. Buyon, who led the study with Bettina Cuneo, MD, clinical scholar and professor of surgery and pediatrics at the University of Arizona in Tucson, presented findings from 413 pregnant subjects with a mean age of 33 years who finished monitoring surveillance: 152 women had low titers of both anti-Ro60 and –Ro52 (defined as < 1,000 ELISA units per mL), and 261 women with titers above the threshold for either antibody (defined as ≥ 1,000 ELISA units per mL). Of the 152 women with low titers of both anti-Ro60 and –Ro52, none of the pregnancies past 26 weeks resulted in AV block. Of the 261 women with titers above the threshold for either antibody, 10 of the pregnancies resulted in AV block (3.8%). The incidence of AV block increased with higher antibody titer levels, reaching 7.7% for those in the top quartile for anti–60-kD SSA/Ro; this increased to 27.3% in study participants with a previous child who had AV block, although numbers in this category were small.

Analysis of cumulative FHRM recordings between surveillance echocardiograms revealed that no case of second-degree or third-degree AV block was missed. In addition, 70% of AV blocks detected by FHRM were second-degree and all occurred less than 12 hours from normal FHRM and within another 45 minutes to 4.5 hours to echocardiogram. The one case of second/third-degree and two cases of third-degree AV block were diagnosed by urgent echocardiogram more than 17 to 72 hours from a previously normal FHRM episode.
 

Other factors besides high anti-Ro titer likely play a role

“STOP BLOQ nicely demonstrates that low titer is associated with a very low risk AV block, and intense monitoring may not be needed,” Dr. Buyon told this news organization. “However, high titer is not the whole answer since even women with the very highest titers can have healthy babies. This report also shows that titers stay constant through pregnancies in the same mother, whether there is the complication of AV block or not. This suggests other factors contribute to AV block.”

She added that FHRM can be easily performed by the mother, but at this time is still best interpreted by a cardiologist. “FHRM detected all cases of AV block, which can happen in hours,” she said. “FHRM should decrease the need for frequent echocardiograms. Some mothers do have more difficulty in deciding whether the baby’s heart is beating irregularly. We need [to improve our teaching] and for how best to have a cardiologist or trained listener interpret. FHRM can be done by the mother but needs interpretation by a cardiologist until we develop a device which can identify abnormalities.”

She acknowledged certain limitations of the study, including the fact that a commercial test for anti-SSA/Ro antibody levels is not available to all clinicians. “Try to find a lab that measures high titer anti-Ro antibodies, but if not, then use one of the common commercial tests such as the BioPlex 2000 autoimmune panels and consider decreased surveillance if titer is < 8,” Dr. Buyon advised.

Vaneet K. Sandhu, MD, a rheumatologist with Loma Linda (Calif.) Medical Center, who was asked to comment on the work, said that the study not only justifies the limited use of FHRM in those with high titer antibodies (followed by urgent fetal echocardiography where indicated), but also risk stratification for fetal AV block.

Loma Linda University Health

“For years, we have recommended frequent fetal echocardiography testing in pregnant women with positive anti-SSA/Ro,” Dr. Sandhu said. “This study tells us we need to look deeper. On one hand, recognizing that low titer anti-Ro antibodies do not confer a risk of AV block is cost effective. On the other hand, while the titer of the antibody appears to contribute to fetal AV block, we need to delve deeper into additional factors contributing to fetal AV block risk in order to better navigate our surveillance methods.”

The study was supported by NIH grants from the National Institute of Child Health and Human Development and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Sandhu has disclosed no relevant financial relationships.
 

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

SAN DIEGO – Pregnant women with anti-SSA/Ro autoantibodies at titer levels of less than 1,000 ELISA units per mL are at minimal to no risk for fetal atrioventricular (AV) block and may be able to forgo traditional echocardiographic heart rhythm monitoring, results from an ongoing, prospective, multicenter trial demonstrated.

However, pregnant patients with higher titer antibodies seem to be at greatest risk for fetal AV block and may benefit from ambulatory fetal heart rhythm monitoring (FHRM), which can detect emergent AV block, according to the study findings. The findings were published online in Arthritis & Rheumatology and will be presented Nov. 13 at the American College of Rheumatology (ACR) 2023 Annual Meeting by Jill P. Buyon, MD, a rheumatologist who directs the division of rheumatology and the Lupus Center at NYU Langone Health in New York.

“While anti-Ro antibodies have been known to be associated with AV block for decades, it has become increasingly clear that antibody titers matter,” Dr. Buyon said in an interview.

For the investigation, which is the largest of its kind, researchers at 22 sites drew from the large multiracial national study of pregnant women, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), to address the impact of anti-Ro titers and use of frequent ambulatory FHRM on outcomes in women with no previously affected children and those at risk for recurrence. Monitoring occurred during the second trimester of pregnancy (from 17 weeks through 26 weeks) and consisted of daily fetal home testing by mothers using handheld, commercially available Doppler devices.

These were followed up by weekly or biweekly echocardiograms, and ultrasound tests to evaluate fetal heart rhythm and function, as well as to show any structural problems. Three times per day, the pregnant women texted the Doppler sound recordings in real time to a pediatric cardiologist, who immediately ordered an additional echocardiogram in cases of irregular or slowing fetal heart rates. If second-degree heart block was detected, drug therapy was initiated.
 

No AV block seen with low anti-Ro titers

Dr. Buyon, who led the study with Bettina Cuneo, MD, clinical scholar and professor of surgery and pediatrics at the University of Arizona in Tucson, presented findings from 413 pregnant subjects with a mean age of 33 years who finished monitoring surveillance: 152 women had low titers of both anti-Ro60 and –Ro52 (defined as < 1,000 ELISA units per mL), and 261 women with titers above the threshold for either antibody (defined as ≥ 1,000 ELISA units per mL). Of the 152 women with low titers of both anti-Ro60 and –Ro52, none of the pregnancies past 26 weeks resulted in AV block. Of the 261 women with titers above the threshold for either antibody, 10 of the pregnancies resulted in AV block (3.8%). The incidence of AV block increased with higher antibody titer levels, reaching 7.7% for those in the top quartile for anti–60-kD SSA/Ro; this increased to 27.3% in study participants with a previous child who had AV block, although numbers in this category were small.

Analysis of cumulative FHRM recordings between surveillance echocardiograms revealed that no case of second-degree or third-degree AV block was missed. In addition, 70% of AV blocks detected by FHRM were second-degree and all occurred less than 12 hours from normal FHRM and within another 45 minutes to 4.5 hours to echocardiogram. The one case of second/third-degree and two cases of third-degree AV block were diagnosed by urgent echocardiogram more than 17 to 72 hours from a previously normal FHRM episode.
 

Other factors besides high anti-Ro titer likely play a role

“STOP BLOQ nicely demonstrates that low titer is associated with a very low risk AV block, and intense monitoring may not be needed,” Dr. Buyon told this news organization. “However, high titer is not the whole answer since even women with the very highest titers can have healthy babies. This report also shows that titers stay constant through pregnancies in the same mother, whether there is the complication of AV block or not. This suggests other factors contribute to AV block.”

She added that FHRM can be easily performed by the mother, but at this time is still best interpreted by a cardiologist. “FHRM detected all cases of AV block, which can happen in hours,” she said. “FHRM should decrease the need for frequent echocardiograms. Some mothers do have more difficulty in deciding whether the baby’s heart is beating irregularly. We need [to improve our teaching] and for how best to have a cardiologist or trained listener interpret. FHRM can be done by the mother but needs interpretation by a cardiologist until we develop a device which can identify abnormalities.”

She acknowledged certain limitations of the study, including the fact that a commercial test for anti-SSA/Ro antibody levels is not available to all clinicians. “Try to find a lab that measures high titer anti-Ro antibodies, but if not, then use one of the common commercial tests such as the BioPlex 2000 autoimmune panels and consider decreased surveillance if titer is < 8,” Dr. Buyon advised.

Vaneet K. Sandhu, MD, a rheumatologist with Loma Linda (Calif.) Medical Center, who was asked to comment on the work, said that the study not only justifies the limited use of FHRM in those with high titer antibodies (followed by urgent fetal echocardiography where indicated), but also risk stratification for fetal AV block.

Loma Linda University Health

“For years, we have recommended frequent fetal echocardiography testing in pregnant women with positive anti-SSA/Ro,” Dr. Sandhu said. “This study tells us we need to look deeper. On one hand, recognizing that low titer anti-Ro antibodies do not confer a risk of AV block is cost effective. On the other hand, while the titer of the antibody appears to contribute to fetal AV block, we need to delve deeper into additional factors contributing to fetal AV block risk in order to better navigate our surveillance methods.”

The study was supported by NIH grants from the National Institute of Child Health and Human Development and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Sandhu has disclosed no relevant financial relationships.
 

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