Developments in early breast cancer reported at the European Society for Medical Oncology (ESMO) 2023 Congress are discussed by Dr Lisa Carey of University of North Carolina, Chapel Hill. 

Dr Carey begins with 5-year results from the KEYNOTE-522 study in patients with early triple-negative breast cancer in which the immune checkpoint inhibitor pembrolizumab was incorporated into combination therapy both pre- and postoperatively. The new findings were consistent with earlier results, showing that pembrolizumab improved pathologic complete response (pCR) and event-free survival. 

Turning to human epidermal growth factor receptor 2–positive (HER2+) disease, Dr Carey discusses the PHERGain trial's use of a genomic assay to define risk and predict pCR. She suggests that such assays could lead to tailored therapy for HER2+ patients. 

On estrogen receptor–positive (ER+)/HER2- disease, Dr Carey reports first on KEYNOTE-756, which examined the addition of pembrolizumab to combination therapy for high-risk patients in both the neoadjuvant and adjuvant settings. Pembrolizumab improved pCR compared with placebo. 

Dr Carey closes by discussing another study in high-risk ER+/HER2- disease. Similar in design to KEYNOTE-756, CheckMate 7FL found that nivolumab added to combination therapy again augmented pCR results. 

--

Lisa A. Carey, MD, Distinguished Professor or Breast Cancer Research, University of North Carolina Lineberger Comprehensive Cancer Center; Professor, Division of Medical Oncology, Bassnight North Carolina Cancer Hospital, Chapel Hill, North Carolina  

Lisa A. Carey, MD, has disclosed no relevant financial relationships.

Developments in early breast cancer reported at the European Society for Medical Oncology (ESMO) 2023 Congress are discussed by Dr Lisa Carey of University of North Carolina, Chapel Hill. 

Dr Carey begins with 5-year results from the KEYNOTE-522 study in patients with early triple-negative breast cancer in which the immune checkpoint inhibitor pembrolizumab was incorporated into combination therapy both pre- and postoperatively. The new findings were consistent with earlier results, showing that pembrolizumab improved pathologic complete response (pCR) and event-free survival. 

Turning to human epidermal growth factor receptor 2–positive (HER2+) disease, Dr Carey discusses the PHERGain trial's use of a genomic assay to define risk and predict pCR. She suggests that such assays could lead to tailored therapy for HER2+ patients. 

On estrogen receptor–positive (ER+)/HER2- disease, Dr Carey reports first on KEYNOTE-756, which examined the addition of pembrolizumab to combination therapy for high-risk patients in both the neoadjuvant and adjuvant settings. Pembrolizumab improved pCR compared with placebo. 

Dr Carey closes by discussing another study in high-risk ER+/HER2- disease. Similar in design to KEYNOTE-756, CheckMate 7FL found that nivolumab added to combination therapy again augmented pCR results. 

--

Lisa A. Carey, MD, Distinguished Professor or Breast Cancer Research, University of North Carolina Lineberger Comprehensive Cancer Center; Professor, Division of Medical Oncology, Bassnight North Carolina Cancer Hospital, Chapel Hill, North Carolina  

Lisa A. Carey, MD, has disclosed no relevant financial relationships.

Developments in early breast cancer reported at the European Society for Medical Oncology (ESMO) 2023 Congress are discussed by Dr Lisa Carey of University of North Carolina, Chapel Hill. 

Dr Carey begins with 5-year results from the KEYNOTE-522 study in patients with early triple-negative breast cancer in which the immune checkpoint inhibitor pembrolizumab was incorporated into combination therapy both pre- and postoperatively. The new findings were consistent with earlier results, showing that pembrolizumab improved pathologic complete response (pCR) and event-free survival. 

Turning to human epidermal growth factor receptor 2–positive (HER2+) disease, Dr Carey discusses the PHERGain trial's use of a genomic assay to define risk and predict pCR. She suggests that such assays could lead to tailored therapy for HER2+ patients. 

On estrogen receptor–positive (ER+)/HER2- disease, Dr Carey reports first on KEYNOTE-756, which examined the addition of pembrolizumab to combination therapy for high-risk patients in both the neoadjuvant and adjuvant settings. Pembrolizumab improved pCR compared with placebo. 

Dr Carey closes by discussing another study in high-risk ER+/HER2- disease. Similar in design to KEYNOTE-756, CheckMate 7FL found that nivolumab added to combination therapy again augmented pCR results. 

--

Lisa A. Carey, MD, Distinguished Professor or Breast Cancer Research, University of North Carolina Lineberger Comprehensive Cancer Center; Professor, Division of Medical Oncology, Bassnight North Carolina Cancer Hospital, Chapel Hill, North Carolina  

Lisa A. Carey, MD, has disclosed no relevant financial relationships.

I am not a marketing person. I never will be. I don’t think like one.

A current article on FiercePharma talked about Boehringer Ingelheim’s recent “rebranding,” which involved (among other things) changing the blues in its logo and ads to greens.

Maybe someone else out there would notice that change, but I wouldn’t have if I hadn’t read about it. Nor am I sure what affect it would have on me, if any. But I’m sure they paid psychologists and marketing teams quite a bit to make sure it was a good idea.

Likewise, when AbbVie repackaged Ubrelvy from 10 to a package to 16, the company felt the need to change the design of the sample boxes (which are also now green). I’m pretty sure none of my patients noticed. The only reason I did is because I’m the one who stocks my sample shelf here.

Abbvie and Boehringer aren’t alone in this, of course. Pharmaceutical marketing is big business. I understand the companies want doctors and patients to know about their products. In that respect they’re no different from General Motors or Kellogg’s.

But pharmaceuticals fall into a different area. Kellogg’s products don’t require a middleman handing you a script allowing you to buy corn flakes, so although the products are sold to the public, they also have to be sold to a person who isn’t buying them – the prescriber.

Not all these ads are bad, of course. At best they raise public awareness of different health conditions and the options to treat them. At worst ... well, currently there are several movies out there about the results of marketing done by the Sackler family and Purdue.

To me, most pharmaceutical ads look the same. They show happy people going about their lives, with the impression being that they couldn’t have done this without the benefit of the drug being marketed.

To a large extent I can’t knock that. Pharmaceuticals are amazing things. They’ve contributed dramatically to human health, life quality, and longevity.

But would I, or most people, notice if the lettering in the ads were blue, green, or yellow? Probably not. Someone with a background in the psychology of marketing would be able to show me data on how different colors affect our perceptions, but I still look at this and wonder if the money could have been better spent.

Maybe that’s why I’m not in marketing. I tend to be on the practical side. The idea of hiring a celebrity to endorse a migraine (or pretty much any) medication would never have occurred to me. I have no idea how much Pfizer paid Lady Gaga to sell Nurtec, but I’m pretty sure it’s a lot more than I’ll earn this year. Probably ever.

Like most neurologists I’m hopelessly left-brained. But I still wonder how much things like this really make a difference.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I am not a marketing person. I never will be. I don’t think like one.

A current article on FiercePharma talked about Boehringer Ingelheim’s recent “rebranding,” which involved (among other things) changing the blues in its logo and ads to greens.

Maybe someone else out there would notice that change, but I wouldn’t have if I hadn’t read about it. Nor am I sure what affect it would have on me, if any. But I’m sure they paid psychologists and marketing teams quite a bit to make sure it was a good idea.

Likewise, when AbbVie repackaged Ubrelvy from 10 to a package to 16, the company felt the need to change the design of the sample boxes (which are also now green). I’m pretty sure none of my patients noticed. The only reason I did is because I’m the one who stocks my sample shelf here.

Abbvie and Boehringer aren’t alone in this, of course. Pharmaceutical marketing is big business. I understand the companies want doctors and patients to know about their products. In that respect they’re no different from General Motors or Kellogg’s.

But pharmaceuticals fall into a different area. Kellogg’s products don’t require a middleman handing you a script allowing you to buy corn flakes, so although the products are sold to the public, they also have to be sold to a person who isn’t buying them – the prescriber.

Not all these ads are bad, of course. At best they raise public awareness of different health conditions and the options to treat them. At worst ... well, currently there are several movies out there about the results of marketing done by the Sackler family and Purdue.

To me, most pharmaceutical ads look the same. They show happy people going about their lives, with the impression being that they couldn’t have done this without the benefit of the drug being marketed.

To a large extent I can’t knock that. Pharmaceuticals are amazing things. They’ve contributed dramatically to human health, life quality, and longevity.

But would I, or most people, notice if the lettering in the ads were blue, green, or yellow? Probably not. Someone with a background in the psychology of marketing would be able to show me data on how different colors affect our perceptions, but I still look at this and wonder if the money could have been better spent.

Maybe that’s why I’m not in marketing. I tend to be on the practical side. The idea of hiring a celebrity to endorse a migraine (or pretty much any) medication would never have occurred to me. I have no idea how much Pfizer paid Lady Gaga to sell Nurtec, but I’m pretty sure it’s a lot more than I’ll earn this year. Probably ever.

Like most neurologists I’m hopelessly left-brained. But I still wonder how much things like this really make a difference.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I am not a marketing person. I never will be. I don’t think like one.

A current article on FiercePharma talked about Boehringer Ingelheim’s recent “rebranding,” which involved (among other things) changing the blues in its logo and ads to greens.

Maybe someone else out there would notice that change, but I wouldn’t have if I hadn’t read about it. Nor am I sure what affect it would have on me, if any. But I’m sure they paid psychologists and marketing teams quite a bit to make sure it was a good idea.

Likewise, when AbbVie repackaged Ubrelvy from 10 to a package to 16, the company felt the need to change the design of the sample boxes (which are also now green). I’m pretty sure none of my patients noticed. The only reason I did is because I’m the one who stocks my sample shelf here.

Abbvie and Boehringer aren’t alone in this, of course. Pharmaceutical marketing is big business. I understand the companies want doctors and patients to know about their products. In that respect they’re no different from General Motors or Kellogg’s.

But pharmaceuticals fall into a different area. Kellogg’s products don’t require a middleman handing you a script allowing you to buy corn flakes, so although the products are sold to the public, they also have to be sold to a person who isn’t buying them – the prescriber.

Not all these ads are bad, of course. At best they raise public awareness of different health conditions and the options to treat them. At worst ... well, currently there are several movies out there about the results of marketing done by the Sackler family and Purdue.

To me, most pharmaceutical ads look the same. They show happy people going about their lives, with the impression being that they couldn’t have done this without the benefit of the drug being marketed.

To a large extent I can’t knock that. Pharmaceuticals are amazing things. They’ve contributed dramatically to human health, life quality, and longevity.

But would I, or most people, notice if the lettering in the ads were blue, green, or yellow? Probably not. Someone with a background in the psychology of marketing would be able to show me data on how different colors affect our perceptions, but I still look at this and wonder if the money could have been better spent.

Maybe that’s why I’m not in marketing. I tend to be on the practical side. The idea of hiring a celebrity to endorse a migraine (or pretty much any) medication would never have occurred to me. I have no idea how much Pfizer paid Lady Gaga to sell Nurtec, but I’m pretty sure it’s a lot more than I’ll earn this year. Probably ever.

Like most neurologists I’m hopelessly left-brained. But I still wonder how much things like this really make a difference.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

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

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

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

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

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

Developments in metastatic breast cancer (MBC) were reported at the European Society for Medical Oncology (ESMO) 2023 Congress and are discussed by Dr Ann Partridge of Dana-Farber Cancer Institute. 

To begin, Dr Partridge highlights a late-breaking abstract showing that use of the antibody-drug conjugate (ADC) datopotamab deruxtecan in hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) MBC results in improved progression-free survival (PFS) compared with chemotherapy. 

Next, Dr Partridge turns to two studies on another ADC, trastuzumab deruxtecan (T-DXd), in MBC. The first study showed positive PFS and overall survival results among patients with either estrogen receptor–positive (ER+)/HER2-low or triple-negative/HER2-low breast cancer. The second T-DXd study examined the ADC's impact on brain metastases in patients with HER2+ disease and reported favorable results. 

She then highlights promising phase 2 results for a novel agent called OP-1250, or palazestrant, studied in patients with ER+/HER2- MBC. 

Finally, Dr Partridge points to a study of a supportive-care program called MOATT, designed for patients on oral MBC therapy, which aims to improve home management. Compared with local standard of care, patients in the program show higher rates of persistence in therapy management and, importantly, concomitant improvements in PFS. 

--

Ann H. Partridge, MD, Professor of Medicine, Harvard Medical School; Vice Chair of Clinical Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 

Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships. 

Developments in metastatic breast cancer (MBC) were reported at the European Society for Medical Oncology (ESMO) 2023 Congress and are discussed by Dr Ann Partridge of Dana-Farber Cancer Institute. 

To begin, Dr Partridge highlights a late-breaking abstract showing that use of the antibody-drug conjugate (ADC) datopotamab deruxtecan in hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) MBC results in improved progression-free survival (PFS) compared with chemotherapy. 

Next, Dr Partridge turns to two studies on another ADC, trastuzumab deruxtecan (T-DXd), in MBC. The first study showed positive PFS and overall survival results among patients with either estrogen receptor–positive (ER+)/HER2-low or triple-negative/HER2-low breast cancer. The second T-DXd study examined the ADC's impact on brain metastases in patients with HER2+ disease and reported favorable results. 

She then highlights promising phase 2 results for a novel agent called OP-1250, or palazestrant, studied in patients with ER+/HER2- MBC. 

Finally, Dr Partridge points to a study of a supportive-care program called MOATT, designed for patients on oral MBC therapy, which aims to improve home management. Compared with local standard of care, patients in the program show higher rates of persistence in therapy management and, importantly, concomitant improvements in PFS. 

--

Ann H. Partridge, MD, Professor of Medicine, Harvard Medical School; Vice Chair of Clinical Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 

Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships. 

Developments in metastatic breast cancer (MBC) were reported at the European Society for Medical Oncology (ESMO) 2023 Congress and are discussed by Dr Ann Partridge of Dana-Farber Cancer Institute. 

To begin, Dr Partridge highlights a late-breaking abstract showing that use of the antibody-drug conjugate (ADC) datopotamab deruxtecan in hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) MBC results in improved progression-free survival (PFS) compared with chemotherapy. 

Next, Dr Partridge turns to two studies on another ADC, trastuzumab deruxtecan (T-DXd), in MBC. The first study showed positive PFS and overall survival results among patients with either estrogen receptor–positive (ER+)/HER2-low or triple-negative/HER2-low breast cancer. The second T-DXd study examined the ADC's impact on brain metastases in patients with HER2+ disease and reported favorable results. 

She then highlights promising phase 2 results for a novel agent called OP-1250, or palazestrant, studied in patients with ER+/HER2- MBC. 

Finally, Dr Partridge points to a study of a supportive-care program called MOATT, designed for patients on oral MBC therapy, which aims to improve home management. Compared with local standard of care, patients in the program show higher rates of persistence in therapy management and, importantly, concomitant improvements in PFS. 

--

Ann H. Partridge, MD, Professor of Medicine, Harvard Medical School; Vice Chair of Clinical Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 

Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships. 

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.

A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radio­iodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).

Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A).­ The spaces contained basophilic strands ­(FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.

The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid¹ and obstructing lymphatic microcirculation, resulting in nonpitting edema.²

There are 5 distinct clinical variants of pretibial myxedema^1,3:

• The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
• The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
• The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
• The mixed form manifests as 2 or more of the other variants.
• The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.

A rare, late manifestation

Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.⁴ The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.⁴

While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.⁵

Continue to: More serious conditions must be ruled out

The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.

Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma ­(PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type ­(PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,⁶ differing from our case.

Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.

Treatment is simple and noninvasive

Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intra­lesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.²

This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.

A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radio­iodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).

Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A).­ The spaces contained basophilic strands ­(FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.

The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid¹ and obstructing lymphatic microcirculation, resulting in nonpitting edema.²

There are 5 distinct clinical variants of pretibial myxedema^1,3:

• The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
• The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
• The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
• The mixed form manifests as 2 or more of the other variants.
• The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.

A rare, late manifestation

Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.⁴ The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.⁴

While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.⁵

Continue to: More serious conditions must be ruled out

The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.

Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma ­(PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type ­(PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,⁶ differing from our case.

Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.

Treatment is simple and noninvasive

Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intra­lesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.²

This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.

A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radio­iodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).

Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A).­ The spaces contained basophilic strands ­(FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.

The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid¹ and obstructing lymphatic microcirculation, resulting in nonpitting edema.²

There are 5 distinct clinical variants of pretibial myxedema^1,3:

• The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
• The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
• The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
• The mixed form manifests as 2 or more of the other variants.
• The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.

A rare, late manifestation

Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.⁴ The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.⁴

While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.⁵

Continue to: More serious conditions must be ruled out

The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.

Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma ­(PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type ­(PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,⁶ differing from our case.

Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.

Treatment is simple and noninvasive

Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intra­lesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.²

This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.

ANAHEIM, CALIF. – Alpha-gal syndrome (AGS) is commonly described as an allergy to red meat, but that is “just the beginning,” allergist and immunologist Scott P. Commins, MD, PhD, told attendees at the annual meeting of the American College of Allergy, Asthma, and Immunology (ACAAI) annual meeting.

Dr. Commins, associate chief for allergy and immunology at the University of North Carolina at Chapel Hill, has made alpha-gal, a potentially fatal allergy, which, in the United States is tied to the bite of the Lone Star tick, his primary research focus.

Beyond red meat, “there are some people who are allergic to all things mammal,” he explained. Dairy products from mammals, medical devices made from mammalian products, vaccines and medicines that contain gelatin, and even commercial products such as perfumes and cosmetics may be behind an AGS reaction.

“The derived products from pigs and cows really find their way into a lot of our day-to-day products,” he said. “I try to keep an open mind about these exposures.”

Physicians should also be aware that “this can happen to kids,” said Dr. Commins. “It looks very similar to adults’ [AGS]. They can end up in the emergency department.”

He also had clinical advice about food challenges for AGS. He explained that there’s more alpha-gal in beef than in other red meats (including pork, venison, and lamb) with the exception of pork kidney. Pork kidney, he said, “has the most alpha-gal that we can find in the lab.”

Dr. Commins said he has stopped using beef for AGS food challenges and has switched to pork sausage patties with a high fat content microwaved in the clinic because they have less alpha-gal in general and he views them as safer.

Long delay in symptom onset

AGS symptoms typically take 2-6 hours to appear after eating red meat or being exposed to mammalian products, but Dr. Commins related a story about a patient he sent home who had very mild symptoms (some lower back itching) after he had spent the day at the clinic after a pork sausage food challenge for AGS.

The patient had returned home. Eight hours after the food challenge, his wife sent Dr. Commins a picture of her husband’s back, which was riddled with welts and was itching badly.

“I learned that if you’re going to do these food challenges, if there is a hint of symptoms at the clinic at 6 hours, keep them in the clinic, because it may really take that long to evolve,” Dr. Commins said.

One of the early signs he’s discovered is palmar erythema (redness and swelling of the hands).

Research has shown that AGS has been heavily concentrated in the Southeast, where Lone Star tick populations are clustered, but research has shown that from 2017 to 2022, it moved up the East Coast to the central United States and Upper Midwest.

“We are seeing increasing diagnoses of AGS in places that are not, perhaps, where we first thought this allergy existed,” said Dr. Commins. “Stay aware,” he cautioned.

The allergy is not exclusive to the United States, he noted. In Europe and Australia, for example, AGS is not thought to be tied to the Lone Star tick, which doesn’t inhabit those regions.

“It is a global phenomenon,” Dr. Commins said.

In August, the CDC alerted physicians to emerging cases of alpha-gal allergy after an article in Morbidity and Mortality Weekly Report indicated that health care providers have little knowledge about the allergy. Of the 1,500 health care providers surveyed, 42% had never heard of the syndrome, and another 35% were not confident in diagnosing or managing affected patients.

Matthew Lau, MD, an allergist with Kaiser Permanente in Honolulu who listened to Dr. Commins’ talk, told this news organization, “It’s important to raise awareness in primary care particularly, he said, as “allergists see only a fraction of the [AGS] patients.”

Allergists can help raise awareness

“Allergists have a role to alert the general community” and to drive more referrals, he said. That includes emergency departments, where physicians commonly see anaphylaxis.

Dr. Lau said he expects the incidence of AGS to increase, because global warming will likely lengthen warmer seasons and cause the geographic distribution to change.

Jay Lieberman, MD, a pediatric allergist at Le Bonheur Children’s Hospital in Memphis, Tenn., told this news organization, “There’s still a lot of confusion, and hearing from an expert like Dr. Commins helps tease out the not-obvious things about patients who are having more mild symptoms,” such as from allergy to dairy or medicines or vaccines that contain gelatin.

As a pediatric allergist, Dr. Lieberman said he sees less alpha-gal than his colleagues, but, he said, “On the adult side in Tennessee, it’s rampant.”

Dr. Commins, Dr. Lieberman, and Dr. Lau report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

ANAHEIM, CALIF. – Alpha-gal syndrome (AGS) is commonly described as an allergy to red meat, but that is “just the beginning,” allergist and immunologist Scott P. Commins, MD, PhD, told attendees at the annual meeting of the American College of Allergy, Asthma, and Immunology (ACAAI) annual meeting.

Dr. Commins, associate chief for allergy and immunology at the University of North Carolina at Chapel Hill, has made alpha-gal, a potentially fatal allergy, which, in the United States is tied to the bite of the Lone Star tick, his primary research focus.

Beyond red meat, “there are some people who are allergic to all things mammal,” he explained. Dairy products from mammals, medical devices made from mammalian products, vaccines and medicines that contain gelatin, and even commercial products such as perfumes and cosmetics may be behind an AGS reaction.

“The derived products from pigs and cows really find their way into a lot of our day-to-day products,” he said. “I try to keep an open mind about these exposures.”

Physicians should also be aware that “this can happen to kids,” said Dr. Commins. “It looks very similar to adults’ [AGS]. They can end up in the emergency department.”

He also had clinical advice about food challenges for AGS. He explained that there’s more alpha-gal in beef than in other red meats (including pork, venison, and lamb) with the exception of pork kidney. Pork kidney, he said, “has the most alpha-gal that we can find in the lab.”

Dr. Commins said he has stopped using beef for AGS food challenges and has switched to pork sausage patties with a high fat content microwaved in the clinic because they have less alpha-gal in general and he views them as safer.

Long delay in symptom onset

AGS symptoms typically take 2-6 hours to appear after eating red meat or being exposed to mammalian products, but Dr. Commins related a story about a patient he sent home who had very mild symptoms (some lower back itching) after he had spent the day at the clinic after a pork sausage food challenge for AGS.

The patient had returned home. Eight hours after the food challenge, his wife sent Dr. Commins a picture of her husband’s back, which was riddled with welts and was itching badly.

“I learned that if you’re going to do these food challenges, if there is a hint of symptoms at the clinic at 6 hours, keep them in the clinic, because it may really take that long to evolve,” Dr. Commins said.

One of the early signs he’s discovered is palmar erythema (redness and swelling of the hands).

Research has shown that AGS has been heavily concentrated in the Southeast, where Lone Star tick populations are clustered, but research has shown that from 2017 to 2022, it moved up the East Coast to the central United States and Upper Midwest.

“We are seeing increasing diagnoses of AGS in places that are not, perhaps, where we first thought this allergy existed,” said Dr. Commins. “Stay aware,” he cautioned.

The allergy is not exclusive to the United States, he noted. In Europe and Australia, for example, AGS is not thought to be tied to the Lone Star tick, which doesn’t inhabit those regions.

“It is a global phenomenon,” Dr. Commins said.

In August, the CDC alerted physicians to emerging cases of alpha-gal allergy after an article in Morbidity and Mortality Weekly Report indicated that health care providers have little knowledge about the allergy. Of the 1,500 health care providers surveyed, 42% had never heard of the syndrome, and another 35% were not confident in diagnosing or managing affected patients.

Matthew Lau, MD, an allergist with Kaiser Permanente in Honolulu who listened to Dr. Commins’ talk, told this news organization, “It’s important to raise awareness in primary care particularly, he said, as “allergists see only a fraction of the [AGS] patients.”

Allergists can help raise awareness

“Allergists have a role to alert the general community” and to drive more referrals, he said. That includes emergency departments, where physicians commonly see anaphylaxis.

Dr. Lau said he expects the incidence of AGS to increase, because global warming will likely lengthen warmer seasons and cause the geographic distribution to change.

Jay Lieberman, MD, a pediatric allergist at Le Bonheur Children’s Hospital in Memphis, Tenn., told this news organization, “There’s still a lot of confusion, and hearing from an expert like Dr. Commins helps tease out the not-obvious things about patients who are having more mild symptoms,” such as from allergy to dairy or medicines or vaccines that contain gelatin.

As a pediatric allergist, Dr. Lieberman said he sees less alpha-gal than his colleagues, but, he said, “On the adult side in Tennessee, it’s rampant.”

Dr. Commins, Dr. Lieberman, and Dr. Lau report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

ANAHEIM, CALIF. – Alpha-gal syndrome (AGS) is commonly described as an allergy to red meat, but that is “just the beginning,” allergist and immunologist Scott P. Commins, MD, PhD, told attendees at the annual meeting of the American College of Allergy, Asthma, and Immunology (ACAAI) annual meeting.

Dr. Commins, associate chief for allergy and immunology at the University of North Carolina at Chapel Hill, has made alpha-gal, a potentially fatal allergy, which, in the United States is tied to the bite of the Lone Star tick, his primary research focus.

Beyond red meat, “there are some people who are allergic to all things mammal,” he explained. Dairy products from mammals, medical devices made from mammalian products, vaccines and medicines that contain gelatin, and even commercial products such as perfumes and cosmetics may be behind an AGS reaction.

“The derived products from pigs and cows really find their way into a lot of our day-to-day products,” he said. “I try to keep an open mind about these exposures.”

Physicians should also be aware that “this can happen to kids,” said Dr. Commins. “It looks very similar to adults’ [AGS]. They can end up in the emergency department.”

He also had clinical advice about food challenges for AGS. He explained that there’s more alpha-gal in beef than in other red meats (including pork, venison, and lamb) with the exception of pork kidney. Pork kidney, he said, “has the most alpha-gal that we can find in the lab.”

Dr. Commins said he has stopped using beef for AGS food challenges and has switched to pork sausage patties with a high fat content microwaved in the clinic because they have less alpha-gal in general and he views them as safer.

Long delay in symptom onset

AGS symptoms typically take 2-6 hours to appear after eating red meat or being exposed to mammalian products, but Dr. Commins related a story about a patient he sent home who had very mild symptoms (some lower back itching) after he had spent the day at the clinic after a pork sausage food challenge for AGS.

The patient had returned home. Eight hours after the food challenge, his wife sent Dr. Commins a picture of her husband’s back, which was riddled with welts and was itching badly.

“I learned that if you’re going to do these food challenges, if there is a hint of symptoms at the clinic at 6 hours, keep them in the clinic, because it may really take that long to evolve,” Dr. Commins said.

One of the early signs he’s discovered is palmar erythema (redness and swelling of the hands).

Research has shown that AGS has been heavily concentrated in the Southeast, where Lone Star tick populations are clustered, but research has shown that from 2017 to 2022, it moved up the East Coast to the central United States and Upper Midwest.

“We are seeing increasing diagnoses of AGS in places that are not, perhaps, where we first thought this allergy existed,” said Dr. Commins. “Stay aware,” he cautioned.

The allergy is not exclusive to the United States, he noted. In Europe and Australia, for example, AGS is not thought to be tied to the Lone Star tick, which doesn’t inhabit those regions.

“It is a global phenomenon,” Dr. Commins said.

In August, the CDC alerted physicians to emerging cases of alpha-gal allergy after an article in Morbidity and Mortality Weekly Report indicated that health care providers have little knowledge about the allergy. Of the 1,500 health care providers surveyed, 42% had never heard of the syndrome, and another 35% were not confident in diagnosing or managing affected patients.

Matthew Lau, MD, an allergist with Kaiser Permanente in Honolulu who listened to Dr. Commins’ talk, told this news organization, “It’s important to raise awareness in primary care particularly, he said, as “allergists see only a fraction of the [AGS] patients.”

Allergists can help raise awareness

“Allergists have a role to alert the general community” and to drive more referrals, he said. That includes emergency departments, where physicians commonly see anaphylaxis.

Dr. Lau said he expects the incidence of AGS to increase, because global warming will likely lengthen warmer seasons and cause the geographic distribution to change.

Jay Lieberman, MD, a pediatric allergist at Le Bonheur Children’s Hospital in Memphis, Tenn., told this news organization, “There’s still a lot of confusion, and hearing from an expert like Dr. Commins helps tease out the not-obvious things about patients who are having more mild symptoms,” such as from allergy to dairy or medicines or vaccines that contain gelatin.

As a pediatric allergist, Dr. Lieberman said he sees less alpha-gal than his colleagues, but, he said, “On the adult side in Tennessee, it’s rampant.”

Dr. Commins, Dr. Lieberman, and Dr. Lau report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Adults with lupus nephritis (LN) who received obinutuzumab (Gazyva) plus standard of care therapy experienced significantly improved kidney function and fewer flares compared with those given a placebo plus standard of care.

METHODOLOGY:

• Researchers conducted a post hoc analysis of the phase 2 NOBILITY study, a randomized trial in which 63 adults received 1,000 mg of obinutuzumab or placebo by infusion on day 1 and at weeks 2, 24, and 26.
• Outcomes were time to an unfavorable kidney outcome, defined by the first of any of the following events: treatment failure, doubling of serum creatinine, or death; researchers also measured LN flare outcomes including the first 30% and 40% declines in estimated glomerular filtration rate (eGFR) from baseline, chronic eGFR slope, and how many patients achieved complete renal response (CRR) on no more than 7.5 mg of prednisone.

TAKEAWAY:

• Adding obinutuzumab to the treatment of patients with LN reduced the risk of the composite outcome by 60% and reduced the risk for LN flare by 57%.
• The risk of first eGFR 30% and 40% decline was reduced by 80% and 91%, respectively, with obinutuzumab, and patients who took obinutuzumab had a significantly slower eGFR decline than with placebo (annualized eGFR slope advantage, 4.1 mL/min/1.73 m² /year).
• At 76 weeks (1.5 years), 38% of patients receiving obinutuzumab achieved CRR on 7.5 mg or less of daily prednisone, compared with 16% of placebo patients, but this difference was not statistically significant at 104 weeks (2 years).
• The total numbers of unfavorable kidney outcomes for obinutuzumab vs. placebo were 12 vs. 24 for treatment failure, 1 vs. 6 for creatinine doubling, and 1 vs. 4 for death, respectively.

IN PRACTICE:

“By reducing flare risk, obinutuzumab should decrease the accumulation of chronic parenchymal kidney damage,” the authors wrote.

SOURCE:

The study was presented at the American College of Rheumatology (ACR) 2023 annual meeting and was published online in Arthritis & Rheumatology. The lead author was Brad H. Rovin, MD, of The Ohio State University in Columbus.

LIMITATIONS:

The analyses were post hoc and not prespecified, and the number of events was small, which prevented statistical confirmation, but the analyses are being repeated in an ongoing phase 3 study.

DISCLOSURES:

The study was supported by F. Hoffman–La Roche. Dr. Rovin reported receiving personal fees from F. Hoffman–La Roche during the conduct of the original trial. Several coauthors are F. Hoffman–La Roche employees.

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

TOPLINE:

Adults with lupus nephritis (LN) who received obinutuzumab (Gazyva) plus standard of care therapy experienced significantly improved kidney function and fewer flares compared with those given a placebo plus standard of care.

METHODOLOGY:

• Researchers conducted a post hoc analysis of the phase 2 NOBILITY study, a randomized trial in which 63 adults received 1,000 mg of obinutuzumab or placebo by infusion on day 1 and at weeks 2, 24, and 26.
• Outcomes were time to an unfavorable kidney outcome, defined by the first of any of the following events: treatment failure, doubling of serum creatinine, or death; researchers also measured LN flare outcomes including the first 30% and 40% declines in estimated glomerular filtration rate (eGFR) from baseline, chronic eGFR slope, and how many patients achieved complete renal response (CRR) on no more than 7.5 mg of prednisone.

TAKEAWAY:

• Adding obinutuzumab to the treatment of patients with LN reduced the risk of the composite outcome by 60% and reduced the risk for LN flare by 57%.
• The risk of first eGFR 30% and 40% decline was reduced by 80% and 91%, respectively, with obinutuzumab, and patients who took obinutuzumab had a significantly slower eGFR decline than with placebo (annualized eGFR slope advantage, 4.1 mL/min/1.73 m² /year).
• At 76 weeks (1.5 years), 38% of patients receiving obinutuzumab achieved CRR on 7.5 mg or less of daily prednisone, compared with 16% of placebo patients, but this difference was not statistically significant at 104 weeks (2 years).
• The total numbers of unfavorable kidney outcomes for obinutuzumab vs. placebo were 12 vs. 24 for treatment failure, 1 vs. 6 for creatinine doubling, and 1 vs. 4 for death, respectively.

IN PRACTICE:

“By reducing flare risk, obinutuzumab should decrease the accumulation of chronic parenchymal kidney damage,” the authors wrote.

SOURCE:

The study was presented at the American College of Rheumatology (ACR) 2023 annual meeting and was published online in Arthritis & Rheumatology. The lead author was Brad H. Rovin, MD, of The Ohio State University in Columbus.

LIMITATIONS:

The analyses were post hoc and not prespecified, and the number of events was small, which prevented statistical confirmation, but the analyses are being repeated in an ongoing phase 3 study.

DISCLOSURES:

The study was supported by F. Hoffman–La Roche. Dr. Rovin reported receiving personal fees from F. Hoffman–La Roche during the conduct of the original trial. Several coauthors are F. Hoffman–La Roche employees.

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

TOPLINE:

Adults with lupus nephritis (LN) who received obinutuzumab (Gazyva) plus standard of care therapy experienced significantly improved kidney function and fewer flares compared with those given a placebo plus standard of care.

METHODOLOGY:

• Researchers conducted a post hoc analysis of the phase 2 NOBILITY study, a randomized trial in which 63 adults received 1,000 mg of obinutuzumab or placebo by infusion on day 1 and at weeks 2, 24, and 26.
• Outcomes were time to an unfavorable kidney outcome, defined by the first of any of the following events: treatment failure, doubling of serum creatinine, or death; researchers also measured LN flare outcomes including the first 30% and 40% declines in estimated glomerular filtration rate (eGFR) from baseline, chronic eGFR slope, and how many patients achieved complete renal response (CRR) on no more than 7.5 mg of prednisone.

TAKEAWAY:

• Adding obinutuzumab to the treatment of patients with LN reduced the risk of the composite outcome by 60% and reduced the risk for LN flare by 57%.
• The risk of first eGFR 30% and 40% decline was reduced by 80% and 91%, respectively, with obinutuzumab, and patients who took obinutuzumab had a significantly slower eGFR decline than with placebo (annualized eGFR slope advantage, 4.1 mL/min/1.73 m² /year).
• At 76 weeks (1.5 years), 38% of patients receiving obinutuzumab achieved CRR on 7.5 mg or less of daily prednisone, compared with 16% of placebo patients, but this difference was not statistically significant at 104 weeks (2 years).
• The total numbers of unfavorable kidney outcomes for obinutuzumab vs. placebo were 12 vs. 24 for treatment failure, 1 vs. 6 for creatinine doubling, and 1 vs. 4 for death, respectively.

IN PRACTICE:

“By reducing flare risk, obinutuzumab should decrease the accumulation of chronic parenchymal kidney damage,” the authors wrote.

SOURCE:

The study was presented at the American College of Rheumatology (ACR) 2023 annual meeting and was published online in Arthritis & Rheumatology. The lead author was Brad H. Rovin, MD, of The Ohio State University in Columbus.

LIMITATIONS:

The analyses were post hoc and not prespecified, and the number of events was small, which prevented statistical confirmation, but the analyses are being repeated in an ongoing phase 3 study.

DISCLOSURES:

The study was supported by F. Hoffman–La Roche. Dr. Rovin reported receiving personal fees from F. Hoffman–La Roche during the conduct of the original trial. Several coauthors are F. Hoffman–La Roche employees.

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

TOPLINE:

People who report frequently adding salt to their food are at significantly greater risk of developing type 2 diabetes (T2D), even after adjustment for confounding factors.

METHODOLOGY:

• Researchers identified 402,982 participants in the UK Biobank from March 2006 to October 2010 who had completed a questionnaire about the frequency with which they added salt to food and who did not have diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline.
• Urine samples were collected at baseline, sodium and potassium levels were measured, and 24-hour sodium excretion was estimated.
• Investigators followed participants from baseline to diagnosis of diabetes, death, or the censoring date (May 23, 2021), whichever occurred first. Information on T2D events were collected through medical history linkage to data on hospital admissions, questionnaire, and the death register.

TAKEAWAY:

• During a mean follow-up of 11.9 years, 13,120 incident cases of T2D were documented.
• Compared with people who reported “never/rarely” adding salt to food, the sex- and age-adjusted hazard ratios (HRs) for developing T2D were 1.20, 1.32, and 1.86 for those who reported “sometimes,” “usually,” and “always” adding salt, respectively (P-trend < .001).
• After further adjustment for the Townsend deprivation index, education level, income, smoking, drinking, physical activity, and high cholesterol, the association was attenuated but remained significant, with HRs of 1.11, 1.18, and 1.28 for “sometimes,” “usually,” and “always” responses, respectively (P-trend < .001).
• After full adjustment, there was also a dose-dependent relationship across quintiles of urinary sodium and higher T2D risk, with HRs of 1 (reference), 1.12, 1.17, 1.28, and 1.34 for quintiles 2-5, respectively (P-trend < .001).
• Body fat percentage and body fat mass significantly mediated the association of adding salt with T2D, by estimated effects of 37.9% and 39.9%, respectively (both P < .001).

IN PRACTICE:

“These findings provide support that reduction of adding salt to foods may act as a potential behavioral intervention approach for preventing T2D. Future clinical trials are needed to further validate our findings,” the authors wrote.

SOURCE:

The study by Xuan Wang, MD, PhD, department of epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, and colleagues was published in the November 2023 issue of Mayo Clinic Proceedings.

LIMITATIONS:

The researchers could not completely exclude the possibility that high frequency of adding salt to foods is a marker for an unhealthy lifestyle. Self-reported frequency of adding salt to food might be subject to information bias and did not provide quantitative information on total sodium intake. In addition, participants were mainly of European descent, making application of the findings to other ethnic groups unclear; the observational design meant researchers could not rule out residual confounding; and information on addition of salt to food was available only at baseline, so potential changes in salt consumption during follow-up could not be considered.

DISCLOSURES:

The study was supported by grants from the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the Fogarty International Center; and Tulane Research Centers of Excellence Awards. The authors reported no potential competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

People who report frequently adding salt to their food are at significantly greater risk of developing type 2 diabetes (T2D), even after adjustment for confounding factors.

METHODOLOGY:

• Researchers identified 402,982 participants in the UK Biobank from March 2006 to October 2010 who had completed a questionnaire about the frequency with which they added salt to food and who did not have diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline.
• Urine samples were collected at baseline, sodium and potassium levels were measured, and 24-hour sodium excretion was estimated.
• Investigators followed participants from baseline to diagnosis of diabetes, death, or the censoring date (May 23, 2021), whichever occurred first. Information on T2D events were collected through medical history linkage to data on hospital admissions, questionnaire, and the death register.

TAKEAWAY:

• During a mean follow-up of 11.9 years, 13,120 incident cases of T2D were documented.
• Compared with people who reported “never/rarely” adding salt to food, the sex- and age-adjusted hazard ratios (HRs) for developing T2D were 1.20, 1.32, and 1.86 for those who reported “sometimes,” “usually,” and “always” adding salt, respectively (P-trend < .001).
• After further adjustment for the Townsend deprivation index, education level, income, smoking, drinking, physical activity, and high cholesterol, the association was attenuated but remained significant, with HRs of 1.11, 1.18, and 1.28 for “sometimes,” “usually,” and “always” responses, respectively (P-trend < .001).
• After full adjustment, there was also a dose-dependent relationship across quintiles of urinary sodium and higher T2D risk, with HRs of 1 (reference), 1.12, 1.17, 1.28, and 1.34 for quintiles 2-5, respectively (P-trend < .001).
• Body fat percentage and body fat mass significantly mediated the association of adding salt with T2D, by estimated effects of 37.9% and 39.9%, respectively (both P < .001).

IN PRACTICE:

“These findings provide support that reduction of adding salt to foods may act as a potential behavioral intervention approach for preventing T2D. Future clinical trials are needed to further validate our findings,” the authors wrote.

SOURCE:

The study by Xuan Wang, MD, PhD, department of epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, and colleagues was published in the November 2023 issue of Mayo Clinic Proceedings.

LIMITATIONS:

The researchers could not completely exclude the possibility that high frequency of adding salt to foods is a marker for an unhealthy lifestyle. Self-reported frequency of adding salt to food might be subject to information bias and did not provide quantitative information on total sodium intake. In addition, participants were mainly of European descent, making application of the findings to other ethnic groups unclear; the observational design meant researchers could not rule out residual confounding; and information on addition of salt to food was available only at baseline, so potential changes in salt consumption during follow-up could not be considered.

DISCLOSURES:

The study was supported by grants from the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the Fogarty International Center; and Tulane Research Centers of Excellence Awards. The authors reported no potential competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

People who report frequently adding salt to their food are at significantly greater risk of developing type 2 diabetes (T2D), even after adjustment for confounding factors.

METHODOLOGY:

• Researchers identified 402,982 participants in the UK Biobank from March 2006 to October 2010 who had completed a questionnaire about the frequency with which they added salt to food and who did not have diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline.
• Urine samples were collected at baseline, sodium and potassium levels were measured, and 24-hour sodium excretion was estimated.
• Investigators followed participants from baseline to diagnosis of diabetes, death, or the censoring date (May 23, 2021), whichever occurred first. Information on T2D events were collected through medical history linkage to data on hospital admissions, questionnaire, and the death register.

TAKEAWAY:

• During a mean follow-up of 11.9 years, 13,120 incident cases of T2D were documented.
• Compared with people who reported “never/rarely” adding salt to food, the sex- and age-adjusted hazard ratios (HRs) for developing T2D were 1.20, 1.32, and 1.86 for those who reported “sometimes,” “usually,” and “always” adding salt, respectively (P-trend < .001).
• After further adjustment for the Townsend deprivation index, education level, income, smoking, drinking, physical activity, and high cholesterol, the association was attenuated but remained significant, with HRs of 1.11, 1.18, and 1.28 for “sometimes,” “usually,” and “always” responses, respectively (P-trend < .001).
• After full adjustment, there was also a dose-dependent relationship across quintiles of urinary sodium and higher T2D risk, with HRs of 1 (reference), 1.12, 1.17, 1.28, and 1.34 for quintiles 2-5, respectively (P-trend < .001).
• Body fat percentage and body fat mass significantly mediated the association of adding salt with T2D, by estimated effects of 37.9% and 39.9%, respectively (both P < .001).

IN PRACTICE:

“These findings provide support that reduction of adding salt to foods may act as a potential behavioral intervention approach for preventing T2D. Future clinical trials are needed to further validate our findings,” the authors wrote.

SOURCE:

The study by Xuan Wang, MD, PhD, department of epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, and colleagues was published in the November 2023 issue of Mayo Clinic Proceedings.

LIMITATIONS:

The researchers could not completely exclude the possibility that high frequency of adding salt to foods is a marker for an unhealthy lifestyle. Self-reported frequency of adding salt to food might be subject to information bias and did not provide quantitative information on total sodium intake. In addition, participants were mainly of European descent, making application of the findings to other ethnic groups unclear; the observational design meant researchers could not rule out residual confounding; and information on addition of salt to food was available only at baseline, so potential changes in salt consumption during follow-up could not be considered.

DISCLOSURES:

The study was supported by grants from the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the Fogarty International Center; and Tulane Research Centers of Excellence Awards. The authors reported no potential competing interests.

A version of this article appeared on Medscape.com.