Rheumatology News

SAN DIEGO – Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) who start a tumor necrosis factor inhibitor (TNFi) appear to have rates of survival and respiratory-related hospitalization similar to those initiating a non-TNFi biologic disease-modifying antirheumatic drug (bDMARD) or Janus kinase inhibitor (JAKi), results from a large pharmacoepidemiologic study show.

“These results challenge some of the findings in prior literature that perhaps TNFi should be avoided in RA-ILD,” lead study investigator Bryant R. England, MD, PhD,  said in an interview. The findings were presented during a plenary session at the American College of Rheumatology annual meeting.

Dr. England, associate professor of rheumatology and immunology at the University of Nebraska Medical Center, Omaha, said that while RA-ILD carries a poor prognosis, a paucity of evidence exists on the effectiveness and safety of disease-modifying therapies in this population.

It’s a pleasant surprise “to see that the investigators were unable to demonstrate a significant difference in the risk of respiratory hospitalization or death between people with RA-ILD initiating non-TNFi/JAKi versus TNFi. Here is a unique situation where a so called ‘negative’ study contributes important information. This study provides needed safety data, as they were unable to show that TNFi results in worsening of severe RA-ILD outcomes,” Sindhu R. Johnson, MD, PhD, professor of medicine at the University of Toronto, said when asked for comment on the study.

University of Toronto

“While this study does not address the use of these medications for the treatment of RA-ILD, these data suggest that TNFi may remain a treatment option for articular disease in people with RA-ILD,” said Dr. Johnson, who was not involved with the study.

For the study, Dr. England and colleagues drew from Veterans Health Administration data between 2006 and 2018 to identify patients with RA-ILD initiating TNFi or non-TNFi biologic/JAKi for the first time. Those who received ILD-focused therapies such as mycophenolate and antifibrotics were excluded from the analysis.

The researchers used validated administrative algorithms requiring multiple RA and ILD diagnostic codes to identify RA-ILD and used 1:1 propensity score matching to compare TNFi and non-TNFi biologic/JAKi factors such as health care use, comorbidities, and several RA-ILD factors, such as pretreatment forced vital capacity, obtained from electronic health records and administrative data. The primary outcome was a composite of time to respiratory-related hospitalization or death using Cox regression models.

Dr. England reported findings from 237 TNFi initiators and 237 non-TNFi/JAKi initiators. Their mean age was 68 years and 92% were male. After matching, the mean standardized differences of variables in the propensity score model improved, but a few variables remained slightly imbalanced, such as two markers of inflammation, inhaled corticosteroid use, and body mass index. The most frequently prescribed TNFi drugs were adalimumab (51%) and etanercept (37%), and the most frequently prescribed non-TNFi/JAKi drugs were rituximab (53%) and abatacept (28%).

The researchers observed no significant difference in the primary outcome between non-TNFi/JAKi and TNFi initiators (adjusted hazard ratio [aHR], 1.22; 95% confidence interval [CI], 0.92-1.60). They also observed no significant differences in respiratory hospitalization, all-cause mortality, or respiratory-related death at 1 and 3 years. In sensitivity analyses with modified cohort eligibility requirements, no significant differences in outcomes were observed between non-TNFi/JAKi and TNFi initiators.

During his presentation at the meeting, Dr. England posed the question: Are TNFi drugs safe to be used in RA-ILD?

“The answer is: It’s complex,” he said. “Our findings don’t suggest that we should be systematically avoiding TNFis with every single person with RA-ILD. But that’s different than whether there are specific subpopulations of RA-ILD for which the choice of these therapies may differ. Unfortunately, we could not address that in this study. We also could not address whether TNFis have efficacy at stopping, slowing, or reversing progression of the ILD itself. This calls for us as a field to gather together and pursue clinical trials to try to generate robust evidence that can guide these important clinical decisions that we’re making with our patients.”

He acknowledged certain limitations of the analysis, including its observational design. “So, despite best efforts to minimize bias with pharmacoepidemiologic designs and approaches, there could still be confounding and selection,” he said. “Additionally, RA-ILD is a heterogeneous disease characterized by different patterns and trajectories. While we did account for several RA- and ILD-related factors, we could not account for all heterogeneity in RA-ILD.”

When asked for comment on the study, session moderator Janet Pope, MD, MPH, professor of medicine in the division of rheumatology at the University of Western Ontario, London, said that the study findings surprised her.

“Sometimes RA patients on TNFis were thought to have more new or worsening ILD vs. [those on] non-TNFi bDMARDs, but most [data were] from older studies where TNFis were used as initial bDMARD in sicker patients,” she told this news organization. “So, data were confounded previously. Even in this study, there may have been channeling bias as it was not a randomized controlled trial. We need a definitive randomized controlled trial to answer this question of what the most optimal therapy for RA-ILD is.”

Dr. England reports receiving consulting fees and research support from Boehringer Ingelheim, and several coauthors reported financial relationships from various pharmaceutical companies and medical publishers. Dr. Johnson reports no relevant financial relationships. Dr. Pope reports being a consultant for several pharmaceutical companies. She has received grant/research support from AbbVie/Abbott and Eli Lilly and is an adviser for Boehringer Ingelheim.

A version of this article appeared on Medscape.com.

SAN DIEGO – Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) who start a tumor necrosis factor inhibitor (TNFi) appear to have rates of survival and respiratory-related hospitalization similar to those initiating a non-TNFi biologic disease-modifying antirheumatic drug (bDMARD) or Janus kinase inhibitor (JAKi), results from a large pharmacoepidemiologic study show.

“These results challenge some of the findings in prior literature that perhaps TNFi should be avoided in RA-ILD,” lead study investigator Bryant R. England, MD, PhD,  said in an interview. The findings were presented during a plenary session at the American College of Rheumatology annual meeting.

Dr. England, associate professor of rheumatology and immunology at the University of Nebraska Medical Center, Omaha, said that while RA-ILD carries a poor prognosis, a paucity of evidence exists on the effectiveness and safety of disease-modifying therapies in this population.

It’s a pleasant surprise “to see that the investigators were unable to demonstrate a significant difference in the risk of respiratory hospitalization or death between people with RA-ILD initiating non-TNFi/JAKi versus TNFi. Here is a unique situation where a so called ‘negative’ study contributes important information. This study provides needed safety data, as they were unable to show that TNFi results in worsening of severe RA-ILD outcomes,” Sindhu R. Johnson, MD, PhD, professor of medicine at the University of Toronto, said when asked for comment on the study.

University of Toronto

“While this study does not address the use of these medications for the treatment of RA-ILD, these data suggest that TNFi may remain a treatment option for articular disease in people with RA-ILD,” said Dr. Johnson, who was not involved with the study.

For the study, Dr. England and colleagues drew from Veterans Health Administration data between 2006 and 2018 to identify patients with RA-ILD initiating TNFi or non-TNFi biologic/JAKi for the first time. Those who received ILD-focused therapies such as mycophenolate and antifibrotics were excluded from the analysis.

The researchers used validated administrative algorithms requiring multiple RA and ILD diagnostic codes to identify RA-ILD and used 1:1 propensity score matching to compare TNFi and non-TNFi biologic/JAKi factors such as health care use, comorbidities, and several RA-ILD factors, such as pretreatment forced vital capacity, obtained from electronic health records and administrative data. The primary outcome was a composite of time to respiratory-related hospitalization or death using Cox regression models.

Dr. England reported findings from 237 TNFi initiators and 237 non-TNFi/JAKi initiators. Their mean age was 68 years and 92% were male. After matching, the mean standardized differences of variables in the propensity score model improved, but a few variables remained slightly imbalanced, such as two markers of inflammation, inhaled corticosteroid use, and body mass index. The most frequently prescribed TNFi drugs were adalimumab (51%) and etanercept (37%), and the most frequently prescribed non-TNFi/JAKi drugs were rituximab (53%) and abatacept (28%).

The researchers observed no significant difference in the primary outcome between non-TNFi/JAKi and TNFi initiators (adjusted hazard ratio [aHR], 1.22; 95% confidence interval [CI], 0.92-1.60). They also observed no significant differences in respiratory hospitalization, all-cause mortality, or respiratory-related death at 1 and 3 years. In sensitivity analyses with modified cohort eligibility requirements, no significant differences in outcomes were observed between non-TNFi/JAKi and TNFi initiators.

During his presentation at the meeting, Dr. England posed the question: Are TNFi drugs safe to be used in RA-ILD?

“The answer is: It’s complex,” he said. “Our findings don’t suggest that we should be systematically avoiding TNFis with every single person with RA-ILD. But that’s different than whether there are specific subpopulations of RA-ILD for which the choice of these therapies may differ. Unfortunately, we could not address that in this study. We also could not address whether TNFis have efficacy at stopping, slowing, or reversing progression of the ILD itself. This calls for us as a field to gather together and pursue clinical trials to try to generate robust evidence that can guide these important clinical decisions that we’re making with our patients.”

He acknowledged certain limitations of the analysis, including its observational design. “So, despite best efforts to minimize bias with pharmacoepidemiologic designs and approaches, there could still be confounding and selection,” he said. “Additionally, RA-ILD is a heterogeneous disease characterized by different patterns and trajectories. While we did account for several RA- and ILD-related factors, we could not account for all heterogeneity in RA-ILD.”

When asked for comment on the study, session moderator Janet Pope, MD, MPH, professor of medicine in the division of rheumatology at the University of Western Ontario, London, said that the study findings surprised her.

“Sometimes RA patients on TNFis were thought to have more new or worsening ILD vs. [those on] non-TNFi bDMARDs, but most [data were] from older studies where TNFis were used as initial bDMARD in sicker patients,” she told this news organization. “So, data were confounded previously. Even in this study, there may have been channeling bias as it was not a randomized controlled trial. We need a definitive randomized controlled trial to answer this question of what the most optimal therapy for RA-ILD is.”

Dr. England reports receiving consulting fees and research support from Boehringer Ingelheim, and several coauthors reported financial relationships from various pharmaceutical companies and medical publishers. Dr. Johnson reports no relevant financial relationships. Dr. Pope reports being a consultant for several pharmaceutical companies. She has received grant/research support from AbbVie/Abbott and Eli Lilly and is an adviser for Boehringer Ingelheim.

A version of this article appeared on Medscape.com.

SAN DIEGO – Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) who start a tumor necrosis factor inhibitor (TNFi) appear to have rates of survival and respiratory-related hospitalization similar to those initiating a non-TNFi biologic disease-modifying antirheumatic drug (bDMARD) or Janus kinase inhibitor (JAKi), results from a large pharmacoepidemiologic study show.

“These results challenge some of the findings in prior literature that perhaps TNFi should be avoided in RA-ILD,” lead study investigator Bryant R. England, MD, PhD,  said in an interview. The findings were presented during a plenary session at the American College of Rheumatology annual meeting.

Dr. England, associate professor of rheumatology and immunology at the University of Nebraska Medical Center, Omaha, said that while RA-ILD carries a poor prognosis, a paucity of evidence exists on the effectiveness and safety of disease-modifying therapies in this population.

It’s a pleasant surprise “to see that the investigators were unable to demonstrate a significant difference in the risk of respiratory hospitalization or death between people with RA-ILD initiating non-TNFi/JAKi versus TNFi. Here is a unique situation where a so called ‘negative’ study contributes important information. This study provides needed safety data, as they were unable to show that TNFi results in worsening of severe RA-ILD outcomes,” Sindhu R. Johnson, MD, PhD, professor of medicine at the University of Toronto, said when asked for comment on the study.

University of Toronto

“While this study does not address the use of these medications for the treatment of RA-ILD, these data suggest that TNFi may remain a treatment option for articular disease in people with RA-ILD,” said Dr. Johnson, who was not involved with the study.

For the study, Dr. England and colleagues drew from Veterans Health Administration data between 2006 and 2018 to identify patients with RA-ILD initiating TNFi or non-TNFi biologic/JAKi for the first time. Those who received ILD-focused therapies such as mycophenolate and antifibrotics were excluded from the analysis.

The researchers used validated administrative algorithms requiring multiple RA and ILD diagnostic codes to identify RA-ILD and used 1:1 propensity score matching to compare TNFi and non-TNFi biologic/JAKi factors such as health care use, comorbidities, and several RA-ILD factors, such as pretreatment forced vital capacity, obtained from electronic health records and administrative data. The primary outcome was a composite of time to respiratory-related hospitalization or death using Cox regression models.

Dr. England reported findings from 237 TNFi initiators and 237 non-TNFi/JAKi initiators. Their mean age was 68 years and 92% were male. After matching, the mean standardized differences of variables in the propensity score model improved, but a few variables remained slightly imbalanced, such as two markers of inflammation, inhaled corticosteroid use, and body mass index. The most frequently prescribed TNFi drugs were adalimumab (51%) and etanercept (37%), and the most frequently prescribed non-TNFi/JAKi drugs were rituximab (53%) and abatacept (28%).

The researchers observed no significant difference in the primary outcome between non-TNFi/JAKi and TNFi initiators (adjusted hazard ratio [aHR], 1.22; 95% confidence interval [CI], 0.92-1.60). They also observed no significant differences in respiratory hospitalization, all-cause mortality, or respiratory-related death at 1 and 3 years. In sensitivity analyses with modified cohort eligibility requirements, no significant differences in outcomes were observed between non-TNFi/JAKi and TNFi initiators.

During his presentation at the meeting, Dr. England posed the question: Are TNFi drugs safe to be used in RA-ILD?

“The answer is: It’s complex,” he said. “Our findings don’t suggest that we should be systematically avoiding TNFis with every single person with RA-ILD. But that’s different than whether there are specific subpopulations of RA-ILD for which the choice of these therapies may differ. Unfortunately, we could not address that in this study. We also could not address whether TNFis have efficacy at stopping, slowing, or reversing progression of the ILD itself. This calls for us as a field to gather together and pursue clinical trials to try to generate robust evidence that can guide these important clinical decisions that we’re making with our patients.”

He acknowledged certain limitations of the analysis, including its observational design. “So, despite best efforts to minimize bias with pharmacoepidemiologic designs and approaches, there could still be confounding and selection,” he said. “Additionally, RA-ILD is a heterogeneous disease characterized by different patterns and trajectories. While we did account for several RA- and ILD-related factors, we could not account for all heterogeneity in RA-ILD.”

When asked for comment on the study, session moderator Janet Pope, MD, MPH, professor of medicine in the division of rheumatology at the University of Western Ontario, London, said that the study findings surprised her.

“Sometimes RA patients on TNFis were thought to have more new or worsening ILD vs. [those on] non-TNFi bDMARDs, but most [data were] from older studies where TNFis were used as initial bDMARD in sicker patients,” she told this news organization. “So, data were confounded previously. Even in this study, there may have been channeling bias as it was not a randomized controlled trial. We need a definitive randomized controlled trial to answer this question of what the most optimal therapy for RA-ILD is.”

Dr. England reports receiving consulting fees and research support from Boehringer Ingelheim, and several coauthors reported financial relationships from various pharmaceutical companies and medical publishers. Dr. Johnson reports no relevant financial relationships. Dr. Pope reports being a consultant for several pharmaceutical companies. She has received grant/research support from AbbVie/Abbott and Eli Lilly and is an adviser for Boehringer Ingelheim.

A version of this article appeared on Medscape.com.

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

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

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

Steve Fisch Photography

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

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

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

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

Steve Fisch Photography

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

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

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

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

Steve Fisch Photography

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

SAN DIEGO – Patients with early oligoarticular psoriatic arthritis (PsA) who took apremilast (Otezla) had more than double the response rate of placebo-treated patients by 16 weeks in a double-blind and randomized phase 4 study.

Oligoarticular PsA can significantly affect quality of life even though few joints are affected, and there’s a lack of relevant clinical data to guide treatment, said rheumatologist Philip J. Mease, MD, of the University of Washington and Swedish Medical Center, Seattle, who reported the results in a presentation at the annual meeting of the American College of Rheumatology.

The findings of the study, called FOREMOST, support the use of the drug in mild PsA, Alexis Ogdie, MD, director of the Penn Psoriatic Arthritis Clinic and the Penn Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, Philadelphia, said in an interview. Dr. Ogdie, who was not involved with the research, noted that rheumatologists commonly prescribe apremilast for mild PsA, although previous research has focused on severe PsA cases.

By 16 weeks, 33.9% of 203 who received apremilast and 16% of 105 who received placebo (difference, 18.5%; 95% confidence interval, 8.9-28.1; P = .0008) met the trial’s primary outcome, a modified version of minimal disease activity score (MDA-Joints), which required attainment of 1 or fewer swollen and/or tender joints plus three of five additional criteria (psoriasis body surface area of 3% or less, a patient pain visual analog scale assessment of 15 mm or less out of 0-100 mm, a patient global assessment of 20 mm or less out of 0-100 mm, a Health Assessment Questionnaire-Disability Index score of 0.5 or less, and a Leeds Enthesitis Index score of 1 or less). The primary analysis was conducted only in joints affected at baseline.

The researchers recruited patients with 2-4 swollen and/or tender joints out of a total of 66-68 joints assessed; most patients (87%) randomized in the study had 4 or fewer active joints at baseline. The patients had a mean age of 50.9. The mean duration of PsA was 9.9 months, and 39.9% of patients were taking a conventional disease-modifying antirheumatic drug.

In a clinically important outcome, the percentage who had a patient-reported pain response improvement defined as “significant” reached 31.4% with placebo, compared with 48.8% for apremilast (difference, 17.7%; 95% CI, 6.0-29.4; P = .0044), and the percentage who reached a patient-reported pain response defined as “major” totaled 19.1% for placebo vs. 41.3% for apremilast (difference, 22.3%; 95% CI, 11.7-32.9; P = .002).

In an exploratory analysis of all joints, the percentages meeting MDA-Joints criteria for response were 7.9% with placebo and 21.3% with apremilast (difference, 13.6%; 95% CI, 5.9-21.4; P = .0028. Focusing on this exploratory analysis, Dr. Ogdie noted that examination of all joints is “more consistent” with the understanding of disease activity than only looking at the initial joints that had disease activity.

A post-hoc analysis among subjects with 2-4 affected joints found rates similar to the primary endpoint analysis: MDA-Joints response rates were reached by 34.4% of those who took apremilast and by 17.2% of those who took placebo.

When asked about the relatively low response rate for apremilast, Dr. Ogdie said the drug is “a really mild medication, which is why it belongs in the mild disease population. That’s balanced by the fact that it has a pretty good safety profile,” especially compared with the alternative of methotrexate, she said.

Almost all patients can tolerate apremilast, she said, although they may experience nausea or diarrhea. (The study found that adverse events were as expected for apremilast, and the drug was well tolerated.) Blood labs aren’t necessary, she added, as they are in patients taking methotrexate.

As for cost, apremilast is a highly expensive drug, especially when compared to methotrexate, which costs pennies per tablet at some pharmacies. Amgen, the manufacturer of apremilast, lists the price as $4,600 a month. Still, insurers generally cover apremilast, Dr. Ogdie said.

The study was sponsored by Amgen. Dr. Mease reported financial relationships with many pharmaceutical companies, including Amgen. Many other coauthors reported financial relationships with Amgen and other pharmaceutical companies or were employees of Amgen. Dr. Ogdie reported having multiple consulting relationships with pharmaceutical companies, including Amgen, and receiving grant funding from multiple companies as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Psoriasis Foundation, Rheumatology Research Foundation, and Forward Databank.

SAN DIEGO – Patients with early oligoarticular psoriatic arthritis (PsA) who took apremilast (Otezla) had more than double the response rate of placebo-treated patients by 16 weeks in a double-blind and randomized phase 4 study.

Oligoarticular PsA can significantly affect quality of life even though few joints are affected, and there’s a lack of relevant clinical data to guide treatment, said rheumatologist Philip J. Mease, MD, of the University of Washington and Swedish Medical Center, Seattle, who reported the results in a presentation at the annual meeting of the American College of Rheumatology.

The findings of the study, called FOREMOST, support the use of the drug in mild PsA, Alexis Ogdie, MD, director of the Penn Psoriatic Arthritis Clinic and the Penn Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, Philadelphia, said in an interview. Dr. Ogdie, who was not involved with the research, noted that rheumatologists commonly prescribe apremilast for mild PsA, although previous research has focused on severe PsA cases.

By 16 weeks, 33.9% of 203 who received apremilast and 16% of 105 who received placebo (difference, 18.5%; 95% confidence interval, 8.9-28.1; P = .0008) met the trial’s primary outcome, a modified version of minimal disease activity score (MDA-Joints), which required attainment of 1 or fewer swollen and/or tender joints plus three of five additional criteria (psoriasis body surface area of 3% or less, a patient pain visual analog scale assessment of 15 mm or less out of 0-100 mm, a patient global assessment of 20 mm or less out of 0-100 mm, a Health Assessment Questionnaire-Disability Index score of 0.5 or less, and a Leeds Enthesitis Index score of 1 or less). The primary analysis was conducted only in joints affected at baseline.

The researchers recruited patients with 2-4 swollen and/or tender joints out of a total of 66-68 joints assessed; most patients (87%) randomized in the study had 4 or fewer active joints at baseline. The patients had a mean age of 50.9. The mean duration of PsA was 9.9 months, and 39.9% of patients were taking a conventional disease-modifying antirheumatic drug.

In a clinically important outcome, the percentage who had a patient-reported pain response improvement defined as “significant” reached 31.4% with placebo, compared with 48.8% for apremilast (difference, 17.7%; 95% CI, 6.0-29.4; P = .0044), and the percentage who reached a patient-reported pain response defined as “major” totaled 19.1% for placebo vs. 41.3% for apremilast (difference, 22.3%; 95% CI, 11.7-32.9; P = .002).

In an exploratory analysis of all joints, the percentages meeting MDA-Joints criteria for response were 7.9% with placebo and 21.3% with apremilast (difference, 13.6%; 95% CI, 5.9-21.4; P = .0028. Focusing on this exploratory analysis, Dr. Ogdie noted that examination of all joints is “more consistent” with the understanding of disease activity than only looking at the initial joints that had disease activity.

A post-hoc analysis among subjects with 2-4 affected joints found rates similar to the primary endpoint analysis: MDA-Joints response rates were reached by 34.4% of those who took apremilast and by 17.2% of those who took placebo.

When asked about the relatively low response rate for apremilast, Dr. Ogdie said the drug is “a really mild medication, which is why it belongs in the mild disease population. That’s balanced by the fact that it has a pretty good safety profile,” especially compared with the alternative of methotrexate, she said.

Almost all patients can tolerate apremilast, she said, although they may experience nausea or diarrhea. (The study found that adverse events were as expected for apremilast, and the drug was well tolerated.) Blood labs aren’t necessary, she added, as they are in patients taking methotrexate.

As for cost, apremilast is a highly expensive drug, especially when compared to methotrexate, which costs pennies per tablet at some pharmacies. Amgen, the manufacturer of apremilast, lists the price as $4,600 a month. Still, insurers generally cover apremilast, Dr. Ogdie said.

The study was sponsored by Amgen. Dr. Mease reported financial relationships with many pharmaceutical companies, including Amgen. Many other coauthors reported financial relationships with Amgen and other pharmaceutical companies or were employees of Amgen. Dr. Ogdie reported having multiple consulting relationships with pharmaceutical companies, including Amgen, and receiving grant funding from multiple companies as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Psoriasis Foundation, Rheumatology Research Foundation, and Forward Databank.

SAN DIEGO – Patients with early oligoarticular psoriatic arthritis (PsA) who took apremilast (Otezla) had more than double the response rate of placebo-treated patients by 16 weeks in a double-blind and randomized phase 4 study.

Oligoarticular PsA can significantly affect quality of life even though few joints are affected, and there’s a lack of relevant clinical data to guide treatment, said rheumatologist Philip J. Mease, MD, of the University of Washington and Swedish Medical Center, Seattle, who reported the results in a presentation at the annual meeting of the American College of Rheumatology.

The findings of the study, called FOREMOST, support the use of the drug in mild PsA, Alexis Ogdie, MD, director of the Penn Psoriatic Arthritis Clinic and the Penn Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, Philadelphia, said in an interview. Dr. Ogdie, who was not involved with the research, noted that rheumatologists commonly prescribe apremilast for mild PsA, although previous research has focused on severe PsA cases.

By 16 weeks, 33.9% of 203 who received apremilast and 16% of 105 who received placebo (difference, 18.5%; 95% confidence interval, 8.9-28.1; P = .0008) met the trial’s primary outcome, a modified version of minimal disease activity score (MDA-Joints), which required attainment of 1 or fewer swollen and/or tender joints plus three of five additional criteria (psoriasis body surface area of 3% or less, a patient pain visual analog scale assessment of 15 mm or less out of 0-100 mm, a patient global assessment of 20 mm or less out of 0-100 mm, a Health Assessment Questionnaire-Disability Index score of 0.5 or less, and a Leeds Enthesitis Index score of 1 or less). The primary analysis was conducted only in joints affected at baseline.

The researchers recruited patients with 2-4 swollen and/or tender joints out of a total of 66-68 joints assessed; most patients (87%) randomized in the study had 4 or fewer active joints at baseline. The patients had a mean age of 50.9. The mean duration of PsA was 9.9 months, and 39.9% of patients were taking a conventional disease-modifying antirheumatic drug.

In a clinically important outcome, the percentage who had a patient-reported pain response improvement defined as “significant” reached 31.4% with placebo, compared with 48.8% for apremilast (difference, 17.7%; 95% CI, 6.0-29.4; P = .0044), and the percentage who reached a patient-reported pain response defined as “major” totaled 19.1% for placebo vs. 41.3% for apremilast (difference, 22.3%; 95% CI, 11.7-32.9; P = .002).

In an exploratory analysis of all joints, the percentages meeting MDA-Joints criteria for response were 7.9% with placebo and 21.3% with apremilast (difference, 13.6%; 95% CI, 5.9-21.4; P = .0028. Focusing on this exploratory analysis, Dr. Ogdie noted that examination of all joints is “more consistent” with the understanding of disease activity than only looking at the initial joints that had disease activity.

A post-hoc analysis among subjects with 2-4 affected joints found rates similar to the primary endpoint analysis: MDA-Joints response rates were reached by 34.4% of those who took apremilast and by 17.2% of those who took placebo.

When asked about the relatively low response rate for apremilast, Dr. Ogdie said the drug is “a really mild medication, which is why it belongs in the mild disease population. That’s balanced by the fact that it has a pretty good safety profile,” especially compared with the alternative of methotrexate, she said.

Almost all patients can tolerate apremilast, she said, although they may experience nausea or diarrhea. (The study found that adverse events were as expected for apremilast, and the drug was well tolerated.) Blood labs aren’t necessary, she added, as they are in patients taking methotrexate.

As for cost, apremilast is a highly expensive drug, especially when compared to methotrexate, which costs pennies per tablet at some pharmacies. Amgen, the manufacturer of apremilast, lists the price as $4,600 a month. Still, insurers generally cover apremilast, Dr. Ogdie said.

The study was sponsored by Amgen. Dr. Mease reported financial relationships with many pharmaceutical companies, including Amgen. Many other coauthors reported financial relationships with Amgen and other pharmaceutical companies or were employees of Amgen. Dr. Ogdie reported having multiple consulting relationships with pharmaceutical companies, including Amgen, and receiving grant funding from multiple companies as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Psoriasis Foundation, Rheumatology Research Foundation, and Forward Databank.

SAN DIEGO – Continuing a tumor necrosis factor inhibitor (TNFi) during pregnancy does not increase risk of worse fetal or obstetric outcomes, according to new research presented at the annual meeting of the American College of Rheumatology.

Patients who continued a TNFi also had fewer severe infections requiring hospitalization, compared with those who stopped taking the medication during their pregnancy.

Lucy Hicks/Medscape Medical News

“The main message is that patients continuing were not doing worse than the patients stopping. It’s an important clinical message for rheumatologists who are not really confident in dealing with these drugs during pregnancy,” said Anna Moltó, MD, PhD, a rheumatologist at Cochin Hospital, Paris, who led the research. “It adds to the data that it seems to be safe,” she added in an interview.

Previous research, largely from pregnant patients with inflammatory bowel disease, suggests that taking a TNFi during pregnancy is safe, and 2020 ACR guidelines conditionally recommend continuing therapy prior to and during pregnancy; however, many people still stop taking the drugs during pregnancy for fear of potentially harming the fetus.

To better understand how TNFi use affected pregnancy outcomes, Dr. Moltó and colleagues analyzed data from a French nationwide health insurance database to identify adult women with chronic rheumatic inflammatory disease. All women included in the cohort had a singleton pregnancy between 2008 and 2017 and were taking a TNFi upon pregnancy diagnosis.

Patients who restarted TNFi after initially pausing because of pregnancy were included in the continuation group.

Researchers identified more than 2,000 pregnancies, including 1,503 in individuals with spondyloarthritis and 579 individuals with rheumatoid arthritis. Patients were, on average, 31 years old and were diagnosed with a rheumatic disease 4 years prior to their pregnancy.

About 72% (n = 1,497) discontinued TNFi after learning they were pregnant, and 584 individuals continued treatment. Dr. Moltó noted that data from more recent years might have captured lower discontinuation rates among pregnant individuals, but those data were not available for the study.

There was no difference in unfavorable obstetrical or infant outcomes, including spontaneous abortion, preeclampsia, gestational diabetes, major congenital malformation, and severe infection of the infant requiring hospitalization. Somewhat surprisingly, the data showed that women who discontinued a TNFi were more likely to be hospitalized for infection either during their pregnancy or up to 6 weeks after delivery, compared with those who continued therapy (1.3% vs. 0.2%, respectively).

Dr. Moltó is currently looking into what could be behind this counterintuitive result, but she hypothesizes that patients who had stopped TNFi may have been taking more glucocorticoids.

“At our institution, there is generally a comfort level with continuing TNF inhibitors during pregnancy, at least until about 36 weeks,” said Sara K. Tedeschi, MD, MPH, a rheumatologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. Sometimes, there is concern for risk of infection to the infant, depending on the type of TNFi being used, she added during a press conference.

“I think that these are really informative and supportive data to let women know that they probably have a really good chance of doing very well during the pregnancy if they continue” their TNFi, said Dr. Tedeschi, who was not involved with the study.
 

TNF discontinuation on the decline

In a related study, researchers at McGill University, Montreal, found that TNFi discontinuation prior to pregnancy had decreased over time in individuals with chronic inflammatory diseases.

Using a database of U.S. insurance claims, they identified 3,372 women with RA, ankylosing spondylitis (AS), psoriasis/psoriatic arthritis (PsA), and/or inflammatory bowel disease (IBD) who previously used a TNFi and gave birth between 2011 and 2019. A patient was considered to have used a TNFi if she had filled a prescription or had an infusion procedure insurance claim within 12 weeks before the gestational period or anytime during pregnancy. Researchers did not have time-specific data to account for women who stopped treatment at pregnancy diagnosis.

Nearly half (47%) of all identified pregnancies were in individuals with IBD, and the rest included patients with RA (24%), psoriasis or PsA (16%), AS (3%), or more than one diagnosis (10%).

In total, 14% of women discontinued TNFi use in the 12 weeks before becoming pregnant and did not restart. From 2011 to 2013, 19% of patients stopped their TNFi, but this proportion decreased overtime, with 10% of patients stopping therapy from 2017 to 2019 (P < .0001).

Lucy Hicks/Medscape Medical News

This decline “possibly reflects the increase in real-world evidence about the safety of TNFi in pregnancy. That research, in turn, led to new guidelines recommending the continuation of TNFi during pregnancy,” first author Leah Flatman, a PhD candidate in epidemiology at McGill, said in an interview. “I think we can see this potentially as good news.”

More patients with RA, psoriasis/PsA, and AS discontinued TNFi therapy prior to conception (23%-25%), compared with those with IBD (5%).

Ms. Flatman noted that her study and Moltó’s study complement each other by providing data on individuals stopping TNFi prior to conception versus those stopping treatment after pregnancy diagnosis.

“These findings demonstrate that continuing TNFi during pregnancy appears not to be associated with an increase in adverse obstetrical or infant outcomes,” Ms. Flatman said of Dr. Moltó’s study. “As guidelines currently recommend continuing TNFi, studies like this help demonstrate that the guideline changes do not appear to be associated with an increase in adverse events.”

Dr. Moltó and Ms. Flatman disclosed no relevant financial relationships. Dr. Tedeschi has worked as a consultant for Novartis.

A version of this article appeared on Medscape.com.

SAN DIEGO – Continuing a tumor necrosis factor inhibitor (TNFi) during pregnancy does not increase risk of worse fetal or obstetric outcomes, according to new research presented at the annual meeting of the American College of Rheumatology.

Patients who continued a TNFi also had fewer severe infections requiring hospitalization, compared with those who stopped taking the medication during their pregnancy.

Lucy Hicks/Medscape Medical News

“The main message is that patients continuing were not doing worse than the patients stopping. It’s an important clinical message for rheumatologists who are not really confident in dealing with these drugs during pregnancy,” said Anna Moltó, MD, PhD, a rheumatologist at Cochin Hospital, Paris, who led the research. “It adds to the data that it seems to be safe,” she added in an interview.

Previous research, largely from pregnant patients with inflammatory bowel disease, suggests that taking a TNFi during pregnancy is safe, and 2020 ACR guidelines conditionally recommend continuing therapy prior to and during pregnancy; however, many people still stop taking the drugs during pregnancy for fear of potentially harming the fetus.

To better understand how TNFi use affected pregnancy outcomes, Dr. Moltó and colleagues analyzed data from a French nationwide health insurance database to identify adult women with chronic rheumatic inflammatory disease. All women included in the cohort had a singleton pregnancy between 2008 and 2017 and were taking a TNFi upon pregnancy diagnosis.

Patients who restarted TNFi after initially pausing because of pregnancy were included in the continuation group.

Researchers identified more than 2,000 pregnancies, including 1,503 in individuals with spondyloarthritis and 579 individuals with rheumatoid arthritis. Patients were, on average, 31 years old and were diagnosed with a rheumatic disease 4 years prior to their pregnancy.

About 72% (n = 1,497) discontinued TNFi after learning they were pregnant, and 584 individuals continued treatment. Dr. Moltó noted that data from more recent years might have captured lower discontinuation rates among pregnant individuals, but those data were not available for the study.

There was no difference in unfavorable obstetrical or infant outcomes, including spontaneous abortion, preeclampsia, gestational diabetes, major congenital malformation, and severe infection of the infant requiring hospitalization. Somewhat surprisingly, the data showed that women who discontinued a TNFi were more likely to be hospitalized for infection either during their pregnancy or up to 6 weeks after delivery, compared with those who continued therapy (1.3% vs. 0.2%, respectively).

Dr. Moltó is currently looking into what could be behind this counterintuitive result, but she hypothesizes that patients who had stopped TNFi may have been taking more glucocorticoids.

“At our institution, there is generally a comfort level with continuing TNF inhibitors during pregnancy, at least until about 36 weeks,” said Sara K. Tedeschi, MD, MPH, a rheumatologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. Sometimes, there is concern for risk of infection to the infant, depending on the type of TNFi being used, she added during a press conference.

“I think that these are really informative and supportive data to let women know that they probably have a really good chance of doing very well during the pregnancy if they continue” their TNFi, said Dr. Tedeschi, who was not involved with the study.
 

TNF discontinuation on the decline

In a related study, researchers at McGill University, Montreal, found that TNFi discontinuation prior to pregnancy had decreased over time in individuals with chronic inflammatory diseases.

Using a database of U.S. insurance claims, they identified 3,372 women with RA, ankylosing spondylitis (AS), psoriasis/psoriatic arthritis (PsA), and/or inflammatory bowel disease (IBD) who previously used a TNFi and gave birth between 2011 and 2019. A patient was considered to have used a TNFi if she had filled a prescription or had an infusion procedure insurance claim within 12 weeks before the gestational period or anytime during pregnancy. Researchers did not have time-specific data to account for women who stopped treatment at pregnancy diagnosis.

Nearly half (47%) of all identified pregnancies were in individuals with IBD, and the rest included patients with RA (24%), psoriasis or PsA (16%), AS (3%), or more than one diagnosis (10%).

In total, 14% of women discontinued TNFi use in the 12 weeks before becoming pregnant and did not restart. From 2011 to 2013, 19% of patients stopped their TNFi, but this proportion decreased overtime, with 10% of patients stopping therapy from 2017 to 2019 (P < .0001).

Lucy Hicks/Medscape Medical News

This decline “possibly reflects the increase in real-world evidence about the safety of TNFi in pregnancy. That research, in turn, led to new guidelines recommending the continuation of TNFi during pregnancy,” first author Leah Flatman, a PhD candidate in epidemiology at McGill, said in an interview. “I think we can see this potentially as good news.”

More patients with RA, psoriasis/PsA, and AS discontinued TNFi therapy prior to conception (23%-25%), compared with those with IBD (5%).

Ms. Flatman noted that her study and Moltó’s study complement each other by providing data on individuals stopping TNFi prior to conception versus those stopping treatment after pregnancy diagnosis.

“These findings demonstrate that continuing TNFi during pregnancy appears not to be associated with an increase in adverse obstetrical or infant outcomes,” Ms. Flatman said of Dr. Moltó’s study. “As guidelines currently recommend continuing TNFi, studies like this help demonstrate that the guideline changes do not appear to be associated with an increase in adverse events.”

Dr. Moltó and Ms. Flatman disclosed no relevant financial relationships. Dr. Tedeschi has worked as a consultant for Novartis.

A version of this article appeared on Medscape.com.

SAN DIEGO – Continuing a tumor necrosis factor inhibitor (TNFi) during pregnancy does not increase risk of worse fetal or obstetric outcomes, according to new research presented at the annual meeting of the American College of Rheumatology.

Patients who continued a TNFi also had fewer severe infections requiring hospitalization, compared with those who stopped taking the medication during their pregnancy.

Lucy Hicks/Medscape Medical News

“The main message is that patients continuing were not doing worse than the patients stopping. It’s an important clinical message for rheumatologists who are not really confident in dealing with these drugs during pregnancy,” said Anna Moltó, MD, PhD, a rheumatologist at Cochin Hospital, Paris, who led the research. “It adds to the data that it seems to be safe,” she added in an interview.

Previous research, largely from pregnant patients with inflammatory bowel disease, suggests that taking a TNFi during pregnancy is safe, and 2020 ACR guidelines conditionally recommend continuing therapy prior to and during pregnancy; however, many people still stop taking the drugs during pregnancy for fear of potentially harming the fetus.

To better understand how TNFi use affected pregnancy outcomes, Dr. Moltó and colleagues analyzed data from a French nationwide health insurance database to identify adult women with chronic rheumatic inflammatory disease. All women included in the cohort had a singleton pregnancy between 2008 and 2017 and were taking a TNFi upon pregnancy diagnosis.

Patients who restarted TNFi after initially pausing because of pregnancy were included in the continuation group.

Researchers identified more than 2,000 pregnancies, including 1,503 in individuals with spondyloarthritis and 579 individuals with rheumatoid arthritis. Patients were, on average, 31 years old and were diagnosed with a rheumatic disease 4 years prior to their pregnancy.

About 72% (n = 1,497) discontinued TNFi after learning they were pregnant, and 584 individuals continued treatment. Dr. Moltó noted that data from more recent years might have captured lower discontinuation rates among pregnant individuals, but those data were not available for the study.

There was no difference in unfavorable obstetrical or infant outcomes, including spontaneous abortion, preeclampsia, gestational diabetes, major congenital malformation, and severe infection of the infant requiring hospitalization. Somewhat surprisingly, the data showed that women who discontinued a TNFi were more likely to be hospitalized for infection either during their pregnancy or up to 6 weeks after delivery, compared with those who continued therapy (1.3% vs. 0.2%, respectively).

Dr. Moltó is currently looking into what could be behind this counterintuitive result, but she hypothesizes that patients who had stopped TNFi may have been taking more glucocorticoids.

“At our institution, there is generally a comfort level with continuing TNF inhibitors during pregnancy, at least until about 36 weeks,” said Sara K. Tedeschi, MD, MPH, a rheumatologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. Sometimes, there is concern for risk of infection to the infant, depending on the type of TNFi being used, she added during a press conference.

“I think that these are really informative and supportive data to let women know that they probably have a really good chance of doing very well during the pregnancy if they continue” their TNFi, said Dr. Tedeschi, who was not involved with the study.
 

TNF discontinuation on the decline

In a related study, researchers at McGill University, Montreal, found that TNFi discontinuation prior to pregnancy had decreased over time in individuals with chronic inflammatory diseases.

Using a database of U.S. insurance claims, they identified 3,372 women with RA, ankylosing spondylitis (AS), psoriasis/psoriatic arthritis (PsA), and/or inflammatory bowel disease (IBD) who previously used a TNFi and gave birth between 2011 and 2019. A patient was considered to have used a TNFi if she had filled a prescription or had an infusion procedure insurance claim within 12 weeks before the gestational period or anytime during pregnancy. Researchers did not have time-specific data to account for women who stopped treatment at pregnancy diagnosis.

Nearly half (47%) of all identified pregnancies were in individuals with IBD, and the rest included patients with RA (24%), psoriasis or PsA (16%), AS (3%), or more than one diagnosis (10%).

In total, 14% of women discontinued TNFi use in the 12 weeks before becoming pregnant and did not restart. From 2011 to 2013, 19% of patients stopped their TNFi, but this proportion decreased overtime, with 10% of patients stopping therapy from 2017 to 2019 (P < .0001).

Lucy Hicks/Medscape Medical News

This decline “possibly reflects the increase in real-world evidence about the safety of TNFi in pregnancy. That research, in turn, led to new guidelines recommending the continuation of TNFi during pregnancy,” first author Leah Flatman, a PhD candidate in epidemiology at McGill, said in an interview. “I think we can see this potentially as good news.”

More patients with RA, psoriasis/PsA, and AS discontinued TNFi therapy prior to conception (23%-25%), compared with those with IBD (5%).

Ms. Flatman noted that her study and Moltó’s study complement each other by providing data on individuals stopping TNFi prior to conception versus those stopping treatment after pregnancy diagnosis.

“These findings demonstrate that continuing TNFi during pregnancy appears not to be associated with an increase in adverse obstetrical or infant outcomes,” Ms. Flatman said of Dr. Moltó’s study. “As guidelines currently recommend continuing TNFi, studies like this help demonstrate that the guideline changes do not appear to be associated with an increase in adverse events.”

Dr. Moltó and Ms. Flatman disclosed no relevant financial relationships. Dr. Tedeschi has worked as a consultant for Novartis.

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

zoranm/Getty Images

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

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

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

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

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

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

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

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

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

SOMI data reinforced by National Inpatient Sample study

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

Lucy Hicks/Medscape Medical News

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

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

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

Adverse pregnancy outcomes higher with ARDs, APS

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

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

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

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

zoranm/Getty Images

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

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

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

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

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

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

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

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

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

SOMI data reinforced by National Inpatient Sample study

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

Lucy Hicks/Medscape Medical News

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

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

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

Adverse pregnancy outcomes higher with ARDs, APS

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

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

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

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

zoranm/Getty Images

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

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

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

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

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

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

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

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

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

SOMI data reinforced by National Inpatient Sample study

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

Lucy Hicks/Medscape Medical News

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

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

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

Adverse pregnancy outcomes higher with ARDs, APS

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

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

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

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

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

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

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

No AV block seen with low anti-Ro titers

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

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

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

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

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

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

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

Loma Linda University Health

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

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

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

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

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

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

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

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

No AV block seen with low anti-Ro titers

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

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

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

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

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

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

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

Loma Linda University Health

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

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

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

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

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

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

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

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

No AV block seen with low anti-Ro titers

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

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

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

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

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

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

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

Loma Linda University Health

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

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

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

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.