User login
Around 5% of US Population Diagnosed With Autoimmune Disease
TOPLINE:
In 2022, autoimmune diseases affected over 15 million individuals in the United States, with women nearly twice as likely to be affected as men and more than one third of affected individuals having more than one autoimmune condition.
METHODOLOGY:
- Researchers used electronic health record (EHR) data from six healthcare systems in the United States between 2011 and 2022 to estimate the prevalence of autoimmune diseases according to sex and age.
- They selected 105 autoimmune diseases from the textbook The Autoimmune Diseases and estimated their prevalence in more than 10 million individuals from these healthcare systems; these statistics were subsequently extrapolated to an estimated US population of 333.3 million.
- An individual was considered to have a diagnosis of an autoimmune disease if they had at least two diagnosis codes for the condition, with the codes being at least 30 days apart.
- A software program was developed to compute the prevalence of autoimmune diseases alone and in aggregate, enabling other researchers to replicate or modify the analysis over time.
TAKEAWAY:
- More than 15 million people, accounting for 4.6% of the US population, were diagnosed with at least one autoimmune disease from January 2011 to June 2022; 34% were diagnosed with more than one autoimmune disease.
- Sex-stratified analysis revealed that 63% of patients diagnosed with autoimmune disease were women, and only 37% were men, establishing a female-to-male ratio of 1.7:1; age-stratified analysis revealed increasing prevalence of autoimmune conditions with age, peaking in individuals aged ≥ 65 years.
- Among individuals with autoimmune diseases, 65% of patients had one condition, whereas 24% had two, 8% had three, and 2% had four or more autoimmune diseases (does not add to 100% due to rounding).
- Rheumatoid arthritis emerged as the most prevalent autoimmune disease, followed by psoriasis, type 1 diabetes, Grave’s disease, and autoimmune thyroiditis; 19 of the top 20 most prevalent autoimmune diseases occurred more frequently in women.
IN PRACTICE:
“Accurate data on the prevalence of autoimmune diseases as a category of disease and for individual autoimmune diseases are needed to further clinical and basic research to improve diagnosis, biomarkers, and therapies for these diseases, which significantly impact the US population,” the authors wrote.
SOURCE:
The study was led by Aaron H. Abend, Autoimmune Registry, Guilford, Connecticut, and was published online in The Journal of Clinical Investigation.
LIMITATIONS:
The use of EHR data presented several challenges, including potential inaccuracies in diagnosis codes and the possibility of missing patients with single diagnosis codes because of the two-code requirement. Certain autoimmune diseases evolve over time and involve nonspecific clinical signs and symptoms that can mimic other diseases, potentially resulting in underdiagnosis. Moreover, rare diseases lacking specific diagnosis codes may have been underrepresented.
DISCLOSURES:
The study received support from Autoimmune Registry; the National Institutes of Health National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and other sources. Information on potential conflicts of interest was not disclosed.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
In 2022, autoimmune diseases affected over 15 million individuals in the United States, with women nearly twice as likely to be affected as men and more than one third of affected individuals having more than one autoimmune condition.
METHODOLOGY:
- Researchers used electronic health record (EHR) data from six healthcare systems in the United States between 2011 and 2022 to estimate the prevalence of autoimmune diseases according to sex and age.
- They selected 105 autoimmune diseases from the textbook The Autoimmune Diseases and estimated their prevalence in more than 10 million individuals from these healthcare systems; these statistics were subsequently extrapolated to an estimated US population of 333.3 million.
- An individual was considered to have a diagnosis of an autoimmune disease if they had at least two diagnosis codes for the condition, with the codes being at least 30 days apart.
- A software program was developed to compute the prevalence of autoimmune diseases alone and in aggregate, enabling other researchers to replicate or modify the analysis over time.
TAKEAWAY:
- More than 15 million people, accounting for 4.6% of the US population, were diagnosed with at least one autoimmune disease from January 2011 to June 2022; 34% were diagnosed with more than one autoimmune disease.
- Sex-stratified analysis revealed that 63% of patients diagnosed with autoimmune disease were women, and only 37% were men, establishing a female-to-male ratio of 1.7:1; age-stratified analysis revealed increasing prevalence of autoimmune conditions with age, peaking in individuals aged ≥ 65 years.
- Among individuals with autoimmune diseases, 65% of patients had one condition, whereas 24% had two, 8% had three, and 2% had four or more autoimmune diseases (does not add to 100% due to rounding).
- Rheumatoid arthritis emerged as the most prevalent autoimmune disease, followed by psoriasis, type 1 diabetes, Grave’s disease, and autoimmune thyroiditis; 19 of the top 20 most prevalent autoimmune diseases occurred more frequently in women.
IN PRACTICE:
“Accurate data on the prevalence of autoimmune diseases as a category of disease and for individual autoimmune diseases are needed to further clinical and basic research to improve diagnosis, biomarkers, and therapies for these diseases, which significantly impact the US population,” the authors wrote.
SOURCE:
The study was led by Aaron H. Abend, Autoimmune Registry, Guilford, Connecticut, and was published online in The Journal of Clinical Investigation.
LIMITATIONS:
The use of EHR data presented several challenges, including potential inaccuracies in diagnosis codes and the possibility of missing patients with single diagnosis codes because of the two-code requirement. Certain autoimmune diseases evolve over time and involve nonspecific clinical signs and symptoms that can mimic other diseases, potentially resulting in underdiagnosis. Moreover, rare diseases lacking specific diagnosis codes may have been underrepresented.
DISCLOSURES:
The study received support from Autoimmune Registry; the National Institutes of Health National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and other sources. Information on potential conflicts of interest was not disclosed.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
In 2022, autoimmune diseases affected over 15 million individuals in the United States, with women nearly twice as likely to be affected as men and more than one third of affected individuals having more than one autoimmune condition.
METHODOLOGY:
- Researchers used electronic health record (EHR) data from six healthcare systems in the United States between 2011 and 2022 to estimate the prevalence of autoimmune diseases according to sex and age.
- They selected 105 autoimmune diseases from the textbook The Autoimmune Diseases and estimated their prevalence in more than 10 million individuals from these healthcare systems; these statistics were subsequently extrapolated to an estimated US population of 333.3 million.
- An individual was considered to have a diagnosis of an autoimmune disease if they had at least two diagnosis codes for the condition, with the codes being at least 30 days apart.
- A software program was developed to compute the prevalence of autoimmune diseases alone and in aggregate, enabling other researchers to replicate or modify the analysis over time.
TAKEAWAY:
- More than 15 million people, accounting for 4.6% of the US population, were diagnosed with at least one autoimmune disease from January 2011 to June 2022; 34% were diagnosed with more than one autoimmune disease.
- Sex-stratified analysis revealed that 63% of patients diagnosed with autoimmune disease were women, and only 37% were men, establishing a female-to-male ratio of 1.7:1; age-stratified analysis revealed increasing prevalence of autoimmune conditions with age, peaking in individuals aged ≥ 65 years.
- Among individuals with autoimmune diseases, 65% of patients had one condition, whereas 24% had two, 8% had three, and 2% had four or more autoimmune diseases (does not add to 100% due to rounding).
- Rheumatoid arthritis emerged as the most prevalent autoimmune disease, followed by psoriasis, type 1 diabetes, Grave’s disease, and autoimmune thyroiditis; 19 of the top 20 most prevalent autoimmune diseases occurred more frequently in women.
IN PRACTICE:
“Accurate data on the prevalence of autoimmune diseases as a category of disease and for individual autoimmune diseases are needed to further clinical and basic research to improve diagnosis, biomarkers, and therapies for these diseases, which significantly impact the US population,” the authors wrote.
SOURCE:
The study was led by Aaron H. Abend, Autoimmune Registry, Guilford, Connecticut, and was published online in The Journal of Clinical Investigation.
LIMITATIONS:
The use of EHR data presented several challenges, including potential inaccuracies in diagnosis codes and the possibility of missing patients with single diagnosis codes because of the two-code requirement. Certain autoimmune diseases evolve over time and involve nonspecific clinical signs and symptoms that can mimic other diseases, potentially resulting in underdiagnosis. Moreover, rare diseases lacking specific diagnosis codes may have been underrepresented.
DISCLOSURES:
The study received support from Autoimmune Registry; the National Institutes of Health National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and other sources. Information on potential conflicts of interest was not disclosed.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
How Does End of Life Impact Diabetes Care?
TOPLINE:
Among older adults with type 2 diabetes (T2D), the use of antidiabetes medications declined in the last year before death, with notable shifts from metformin and sulfonylureas toward insulin therapy.
METHODOLOGY:
Current recommendations emphasize a more liberal approach to glycemic control in people with a high burden of comorbidities and shorter life expectancy, but little is known about the changes and discontinuation patterns of diabetes medications among older adults near the end of life.
.
All medication classes available during the study period were considered, including short-acting and long-acting insulins, metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and other medications.
Analysis included temporal trends in prescribing antidiabetes medications, stratified by frailty using a validated claims-based frailty index, with scores ≥ 0.30 indicating higher frailty.
Antidiabetes medication fills were assessed within 1 year before death, examining changes across three time periods: 12 to 8 months, 8 to 4 months, and 4 to 0 months before death.
TAKEAWAY:
The proportion of older patients receiving antidiabetes medications increased slightly from 71.4% in 2015 to 72.9% in 2019, with metformin showing the largest increase from 40.7% to 46.5% (standardized mean difference [SMD], −0.12) and sulfonylureas showing the largest decrease from 37.0% to 31.8% (SMD, 0.11).
The use of newer diabetes medications with cardiovascular benefits, such as GLP-1 receptor agonists and SGLT2 inhibitors, remained less common but showed increasing trends over time.
The use of any antidiabetes medication decreased from 66.1% in the 9 to 12 months before death to 60.8% in the last 4 months of life (P < .01), primarily due to the reduced use of metformin and sulfonylureas.
The use of both short-acting and long-acting insulin agents increased toward the end of life (from 28.0% to 32.9% and from 41.2% to 43.9%, respectively; both P < .001) , particularly among frailer individuals.
IN PRACTICE:
“[The study] findings underscore important implications for diabetes management in patients nearing the end of life. With ~70% of patients with T2D using at least one antidiabetes medication, there is a need to consider further de-escalation or deprescribing in this vulnerable population,” the authors wrote.
SOURCE:
The study was led by Alexander Kutz, MD, MPH, MSc, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, and was published online in Diabetes Care.
LIMITATIONS:
The study lacked details on the reasons for changes in medication patterns, making it unclear whether these changes were due to clinical guidelines or to reduce adverse events. Moreover, the study could not capture transitions or substitutions between medications, information on the dosage data, and causes of death.
DISCLOSURES:
This study was supported by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School. Some authors reported receiving personal fees or research grants from the National Institutes of Health and other institutions and a few pharmaceutical companies. One author reported acting as a principal investigator and receiving a research grant from Boehringer-Ingelheim, unrelated to the work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Among older adults with type 2 diabetes (T2D), the use of antidiabetes medications declined in the last year before death, with notable shifts from metformin and sulfonylureas toward insulin therapy.
METHODOLOGY:
Current recommendations emphasize a more liberal approach to glycemic control in people with a high burden of comorbidities and shorter life expectancy, but little is known about the changes and discontinuation patterns of diabetes medications among older adults near the end of life.
.
All medication classes available during the study period were considered, including short-acting and long-acting insulins, metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and other medications.
Analysis included temporal trends in prescribing antidiabetes medications, stratified by frailty using a validated claims-based frailty index, with scores ≥ 0.30 indicating higher frailty.
Antidiabetes medication fills were assessed within 1 year before death, examining changes across three time periods: 12 to 8 months, 8 to 4 months, and 4 to 0 months before death.
TAKEAWAY:
The proportion of older patients receiving antidiabetes medications increased slightly from 71.4% in 2015 to 72.9% in 2019, with metformin showing the largest increase from 40.7% to 46.5% (standardized mean difference [SMD], −0.12) and sulfonylureas showing the largest decrease from 37.0% to 31.8% (SMD, 0.11).
The use of newer diabetes medications with cardiovascular benefits, such as GLP-1 receptor agonists and SGLT2 inhibitors, remained less common but showed increasing trends over time.
The use of any antidiabetes medication decreased from 66.1% in the 9 to 12 months before death to 60.8% in the last 4 months of life (P < .01), primarily due to the reduced use of metformin and sulfonylureas.
The use of both short-acting and long-acting insulin agents increased toward the end of life (from 28.0% to 32.9% and from 41.2% to 43.9%, respectively; both P < .001) , particularly among frailer individuals.
IN PRACTICE:
“[The study] findings underscore important implications for diabetes management in patients nearing the end of life. With ~70% of patients with T2D using at least one antidiabetes medication, there is a need to consider further de-escalation or deprescribing in this vulnerable population,” the authors wrote.
SOURCE:
The study was led by Alexander Kutz, MD, MPH, MSc, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, and was published online in Diabetes Care.
LIMITATIONS:
The study lacked details on the reasons for changes in medication patterns, making it unclear whether these changes were due to clinical guidelines or to reduce adverse events. Moreover, the study could not capture transitions or substitutions between medications, information on the dosage data, and causes of death.
DISCLOSURES:
This study was supported by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School. Some authors reported receiving personal fees or research grants from the National Institutes of Health and other institutions and a few pharmaceutical companies. One author reported acting as a principal investigator and receiving a research grant from Boehringer-Ingelheim, unrelated to the work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Among older adults with type 2 diabetes (T2D), the use of antidiabetes medications declined in the last year before death, with notable shifts from metformin and sulfonylureas toward insulin therapy.
METHODOLOGY:
Current recommendations emphasize a more liberal approach to glycemic control in people with a high burden of comorbidities and shorter life expectancy, but little is known about the changes and discontinuation patterns of diabetes medications among older adults near the end of life.
.
All medication classes available during the study period were considered, including short-acting and long-acting insulins, metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and other medications.
Analysis included temporal trends in prescribing antidiabetes medications, stratified by frailty using a validated claims-based frailty index, with scores ≥ 0.30 indicating higher frailty.
Antidiabetes medication fills were assessed within 1 year before death, examining changes across three time periods: 12 to 8 months, 8 to 4 months, and 4 to 0 months before death.
TAKEAWAY:
The proportion of older patients receiving antidiabetes medications increased slightly from 71.4% in 2015 to 72.9% in 2019, with metformin showing the largest increase from 40.7% to 46.5% (standardized mean difference [SMD], −0.12) and sulfonylureas showing the largest decrease from 37.0% to 31.8% (SMD, 0.11).
The use of newer diabetes medications with cardiovascular benefits, such as GLP-1 receptor agonists and SGLT2 inhibitors, remained less common but showed increasing trends over time.
The use of any antidiabetes medication decreased from 66.1% in the 9 to 12 months before death to 60.8% in the last 4 months of life (P < .01), primarily due to the reduced use of metformin and sulfonylureas.
The use of both short-acting and long-acting insulin agents increased toward the end of life (from 28.0% to 32.9% and from 41.2% to 43.9%, respectively; both P < .001) , particularly among frailer individuals.
IN PRACTICE:
“[The study] findings underscore important implications for diabetes management in patients nearing the end of life. With ~70% of patients with T2D using at least one antidiabetes medication, there is a need to consider further de-escalation or deprescribing in this vulnerable population,” the authors wrote.
SOURCE:
The study was led by Alexander Kutz, MD, MPH, MSc, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, and was published online in Diabetes Care.
LIMITATIONS:
The study lacked details on the reasons for changes in medication patterns, making it unclear whether these changes were due to clinical guidelines or to reduce adverse events. Moreover, the study could not capture transitions or substitutions between medications, information on the dosage data, and causes of death.
DISCLOSURES:
This study was supported by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School. Some authors reported receiving personal fees or research grants from the National Institutes of Health and other institutions and a few pharmaceutical companies. One author reported acting as a principal investigator and receiving a research grant from Boehringer-Ingelheim, unrelated to the work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Choline Alfoscerate Has Modest Benefits on Cognition in Type 2 Diabetes
TOPLINE:
METHODOLOGY:
- Prior studies have demonstrated the efficacy of choline alfoscerate, a phospholipid metabolite naturally found in the brain, in improving cognitive function in patients with neurodegenerative conditions, but its use in patients with T2D remains unexplored.
- Researchers at a hospital in Korea enrolled patients aged over 60 years with T2D and mild cognitive impairment (assessed by Mini-Mental State Examination [MMSE] scores of 25-28), who were randomly assigned to receive either 1200 mg/d choline alfoscerate or placebo for 12 months.
- The primary efficacy endpoint was the change in the total MMSE score from baseline to month 6; secondary efficacy endpoints included changes in cognitive performance and quality of life, measured by the 36-Item Short Form Health Survey, at 6 and 12 months.
TAKEAWAY:
- Thirty-six patients (average age, 71.8 years; 25% men) with an average diabetes duration of 12.1 years were randomized to receive choline alfoscerate (n = 18) or placebo (n = 18).
- At 6 months, there was modest but nonsignificant improvement in MMSE score with choline alfoscerate vs placebo (P = .059).
- After 12 months, the choline alfoscerate group showed an increase in the MMSE score from 26.2 to 27.1, whereas the placebo group showed a slight decline from 26.6 to 25.8, which represented a significant improvement for the treatment arm (P < .001).
- Physical health scores were significantly superior in the choline alfoscerate group vs the placebo group at 6 months (P = .014), with similar observations at 12 months (P = .039).
- No serious adverse events were reported in either group.
IN PRACTICE:
“Choline alfoscerate could be considered an anticipated therapeutic option to preserve cognitive function and subsequently physical health in elderly patients with diabetes and mild cognitive impairment,” the authors wrote.
SOURCE:
The study was led by Minji Sohn, PhD, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea, and published online in Diabetes, Obesity and Metabolism.
LIMITATIONS:
The study population primarily comprised non–insulin-dependent patients with controlled glycemia and minimal comorbidities, which may have limited the applicability of the results to a broader population. The small sample size may have contributed to the lack of statistical significance in some outcomes. Moreover, the 12-month study duration may have not been sufficient to investigate the long-term effects of choline alfoscerate.
DISCLOSURES:
This study was funded by Daewoong Pharmaceutical through subcontracting with Seoul National University Bundang Hospital. The authors declared no competing interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Prior studies have demonstrated the efficacy of choline alfoscerate, a phospholipid metabolite naturally found in the brain, in improving cognitive function in patients with neurodegenerative conditions, but its use in patients with T2D remains unexplored.
- Researchers at a hospital in Korea enrolled patients aged over 60 years with T2D and mild cognitive impairment (assessed by Mini-Mental State Examination [MMSE] scores of 25-28), who were randomly assigned to receive either 1200 mg/d choline alfoscerate or placebo for 12 months.
- The primary efficacy endpoint was the change in the total MMSE score from baseline to month 6; secondary efficacy endpoints included changes in cognitive performance and quality of life, measured by the 36-Item Short Form Health Survey, at 6 and 12 months.
TAKEAWAY:
- Thirty-six patients (average age, 71.8 years; 25% men) with an average diabetes duration of 12.1 years were randomized to receive choline alfoscerate (n = 18) or placebo (n = 18).
- At 6 months, there was modest but nonsignificant improvement in MMSE score with choline alfoscerate vs placebo (P = .059).
- After 12 months, the choline alfoscerate group showed an increase in the MMSE score from 26.2 to 27.1, whereas the placebo group showed a slight decline from 26.6 to 25.8, which represented a significant improvement for the treatment arm (P < .001).
- Physical health scores were significantly superior in the choline alfoscerate group vs the placebo group at 6 months (P = .014), with similar observations at 12 months (P = .039).
- No serious adverse events were reported in either group.
IN PRACTICE:
“Choline alfoscerate could be considered an anticipated therapeutic option to preserve cognitive function and subsequently physical health in elderly patients with diabetes and mild cognitive impairment,” the authors wrote.
SOURCE:
The study was led by Minji Sohn, PhD, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea, and published online in Diabetes, Obesity and Metabolism.
LIMITATIONS:
The study population primarily comprised non–insulin-dependent patients with controlled glycemia and minimal comorbidities, which may have limited the applicability of the results to a broader population. The small sample size may have contributed to the lack of statistical significance in some outcomes. Moreover, the 12-month study duration may have not been sufficient to investigate the long-term effects of choline alfoscerate.
DISCLOSURES:
This study was funded by Daewoong Pharmaceutical through subcontracting with Seoul National University Bundang Hospital. The authors declared no competing interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Prior studies have demonstrated the efficacy of choline alfoscerate, a phospholipid metabolite naturally found in the brain, in improving cognitive function in patients with neurodegenerative conditions, but its use in patients with T2D remains unexplored.
- Researchers at a hospital in Korea enrolled patients aged over 60 years with T2D and mild cognitive impairment (assessed by Mini-Mental State Examination [MMSE] scores of 25-28), who were randomly assigned to receive either 1200 mg/d choline alfoscerate or placebo for 12 months.
- The primary efficacy endpoint was the change in the total MMSE score from baseline to month 6; secondary efficacy endpoints included changes in cognitive performance and quality of life, measured by the 36-Item Short Form Health Survey, at 6 and 12 months.
TAKEAWAY:
- Thirty-six patients (average age, 71.8 years; 25% men) with an average diabetes duration of 12.1 years were randomized to receive choline alfoscerate (n = 18) or placebo (n = 18).
- At 6 months, there was modest but nonsignificant improvement in MMSE score with choline alfoscerate vs placebo (P = .059).
- After 12 months, the choline alfoscerate group showed an increase in the MMSE score from 26.2 to 27.1, whereas the placebo group showed a slight decline from 26.6 to 25.8, which represented a significant improvement for the treatment arm (P < .001).
- Physical health scores were significantly superior in the choline alfoscerate group vs the placebo group at 6 months (P = .014), with similar observations at 12 months (P = .039).
- No serious adverse events were reported in either group.
IN PRACTICE:
“Choline alfoscerate could be considered an anticipated therapeutic option to preserve cognitive function and subsequently physical health in elderly patients with diabetes and mild cognitive impairment,” the authors wrote.
SOURCE:
The study was led by Minji Sohn, PhD, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea, and published online in Diabetes, Obesity and Metabolism.
LIMITATIONS:
The study population primarily comprised non–insulin-dependent patients with controlled glycemia and minimal comorbidities, which may have limited the applicability of the results to a broader population. The small sample size may have contributed to the lack of statistical significance in some outcomes. Moreover, the 12-month study duration may have not been sufficient to investigate the long-term effects of choline alfoscerate.
DISCLOSURES:
This study was funded by Daewoong Pharmaceutical through subcontracting with Seoul National University Bundang Hospital. The authors declared no competing interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Sjögren Subtypes Have Distinct Pathophysiologic Profiles
TOPLINE:
Sjögren disease (SjD) presents three distinct phenotypes ― B-cell active with low symptom burden, high systemic activity with high symptom burden, and low systemic activity with high symptom burden; each phenotype has unique cytokine profiles and interferon (IFN) signatures, with elevated cytokine levels for T and B lymphocyte activation in the first two groups and a prominent IFN signature in the B-cell active group.
METHODOLOGY:
- Researchers conducted this study to assess whether three distinct phenotypes of patients with SjD were associated with distinct pathophysiological pathways and IFN signatures.
- They included 395 patients (median age, 53 years; 94% women) from the Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome (ASSESS) cohort who met the 2002 American-European Consensus Group criteria for SjD.
- A panel of biomarkers including IFN alpha-2, IFN gamma, CXCL10, CXCL13, B-cell activating factor, interleukin (IL) 7, FLT3, CCL19, and tumor necrosis factor receptor II (TNF-RII) was compared between the three phenotypes.
- The IFN signature was assessed using whole blood transcriptomic analysis.
- Analysis compared systemic and symptomatic evolution and assessed the risk for new immunosuppressant prescription and lymphoma development across three clusters on the basis of the IFN signature.
TAKEAWAY:
- Higher levels of CXCL13, IL-7, and TNF-RII cytokines were found in both the B-cell active and high systemic activity groups than in the low systemic activity group (P < .05 for all).
- The low systemic activity cluster with reduced cytokine levels showed less disease progression, with no instances of lymphoma reported in this group.
- A high IFN signature was found in a higher percentage of patients in the B-cell active group (57%) than in the high systemic activity (48%) and low systemic activity (38%) groups.
- In the B-cell active cluster, this high IFN signature was associated with an increased risk for new immunosuppressant prescription, indicating greater disease progression (hazard ratio, 9.38; P = .0032); also, all cases of lymphoma within this group were found in individuals exhibiting a high IFN signature.
IN PRACTICE:
“Our study demonstrated that our stratification, defined by symptoms, systemic clinical signs, and routine biological data, is based on different pathophysiological pathways, particularly B and T lymphocyte activation and the interferon alpha pathway. The latter could help predict the evolution of the BALS cluster, a biological but minimally symptomatic cluster, to consider closer monitoring and/or early treatments to prevent complications,” the authors wrote.
SOURCE:
The study was led by Yann Nguyen, MD, PhD, Department of Rheumatology, Hôpital Bicêtre, Assistance Publique — Hôpitaux de Paris, Université Paris-Saclay, Paris, France, and was published online on December 25, 2024, in Arthritis & Rheumatology.
LIMITATIONS:
The study evaluated only a few cytokines at the time of inclusion in the ASSESS cohort, which may not have captured the full range of biologic markers relevant to SjD. The evolution of systemic activity defined using the European Alliance of Associations for Rheumatology Sjogren’s Syndrome Disease Activity Index showed no difference according to the IFN signature in the B-cell active with low symptom burden cluster, possibly due to treatments received between annual evaluations.
DISCLOSURES:
The ASSESS cohort is supported by research grants from the French Society of Rheumatology. Some authors reported receiving grants, payments, honoraria, consulting fees, and support for attending meetings and having contracts or other ties with pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Sjögren disease (SjD) presents three distinct phenotypes ― B-cell active with low symptom burden, high systemic activity with high symptom burden, and low systemic activity with high symptom burden; each phenotype has unique cytokine profiles and interferon (IFN) signatures, with elevated cytokine levels for T and B lymphocyte activation in the first two groups and a prominent IFN signature in the B-cell active group.
METHODOLOGY:
- Researchers conducted this study to assess whether three distinct phenotypes of patients with SjD were associated with distinct pathophysiological pathways and IFN signatures.
- They included 395 patients (median age, 53 years; 94% women) from the Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome (ASSESS) cohort who met the 2002 American-European Consensus Group criteria for SjD.
- A panel of biomarkers including IFN alpha-2, IFN gamma, CXCL10, CXCL13, B-cell activating factor, interleukin (IL) 7, FLT3, CCL19, and tumor necrosis factor receptor II (TNF-RII) was compared between the three phenotypes.
- The IFN signature was assessed using whole blood transcriptomic analysis.
- Analysis compared systemic and symptomatic evolution and assessed the risk for new immunosuppressant prescription and lymphoma development across three clusters on the basis of the IFN signature.
TAKEAWAY:
- Higher levels of CXCL13, IL-7, and TNF-RII cytokines were found in both the B-cell active and high systemic activity groups than in the low systemic activity group (P < .05 for all).
- The low systemic activity cluster with reduced cytokine levels showed less disease progression, with no instances of lymphoma reported in this group.
- A high IFN signature was found in a higher percentage of patients in the B-cell active group (57%) than in the high systemic activity (48%) and low systemic activity (38%) groups.
- In the B-cell active cluster, this high IFN signature was associated with an increased risk for new immunosuppressant prescription, indicating greater disease progression (hazard ratio, 9.38; P = .0032); also, all cases of lymphoma within this group were found in individuals exhibiting a high IFN signature.
IN PRACTICE:
“Our study demonstrated that our stratification, defined by symptoms, systemic clinical signs, and routine biological data, is based on different pathophysiological pathways, particularly B and T lymphocyte activation and the interferon alpha pathway. The latter could help predict the evolution of the BALS cluster, a biological but minimally symptomatic cluster, to consider closer monitoring and/or early treatments to prevent complications,” the authors wrote.
SOURCE:
The study was led by Yann Nguyen, MD, PhD, Department of Rheumatology, Hôpital Bicêtre, Assistance Publique — Hôpitaux de Paris, Université Paris-Saclay, Paris, France, and was published online on December 25, 2024, in Arthritis & Rheumatology.
LIMITATIONS:
The study evaluated only a few cytokines at the time of inclusion in the ASSESS cohort, which may not have captured the full range of biologic markers relevant to SjD. The evolution of systemic activity defined using the European Alliance of Associations for Rheumatology Sjogren’s Syndrome Disease Activity Index showed no difference according to the IFN signature in the B-cell active with low symptom burden cluster, possibly due to treatments received between annual evaluations.
DISCLOSURES:
The ASSESS cohort is supported by research grants from the French Society of Rheumatology. Some authors reported receiving grants, payments, honoraria, consulting fees, and support for attending meetings and having contracts or other ties with pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Sjögren disease (SjD) presents three distinct phenotypes ― B-cell active with low symptom burden, high systemic activity with high symptom burden, and low systemic activity with high symptom burden; each phenotype has unique cytokine profiles and interferon (IFN) signatures, with elevated cytokine levels for T and B lymphocyte activation in the first two groups and a prominent IFN signature in the B-cell active group.
METHODOLOGY:
- Researchers conducted this study to assess whether three distinct phenotypes of patients with SjD were associated with distinct pathophysiological pathways and IFN signatures.
- They included 395 patients (median age, 53 years; 94% women) from the Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome (ASSESS) cohort who met the 2002 American-European Consensus Group criteria for SjD.
- A panel of biomarkers including IFN alpha-2, IFN gamma, CXCL10, CXCL13, B-cell activating factor, interleukin (IL) 7, FLT3, CCL19, and tumor necrosis factor receptor II (TNF-RII) was compared between the three phenotypes.
- The IFN signature was assessed using whole blood transcriptomic analysis.
- Analysis compared systemic and symptomatic evolution and assessed the risk for new immunosuppressant prescription and lymphoma development across three clusters on the basis of the IFN signature.
TAKEAWAY:
- Higher levels of CXCL13, IL-7, and TNF-RII cytokines were found in both the B-cell active and high systemic activity groups than in the low systemic activity group (P < .05 for all).
- The low systemic activity cluster with reduced cytokine levels showed less disease progression, with no instances of lymphoma reported in this group.
- A high IFN signature was found in a higher percentage of patients in the B-cell active group (57%) than in the high systemic activity (48%) and low systemic activity (38%) groups.
- In the B-cell active cluster, this high IFN signature was associated with an increased risk for new immunosuppressant prescription, indicating greater disease progression (hazard ratio, 9.38; P = .0032); also, all cases of lymphoma within this group were found in individuals exhibiting a high IFN signature.
IN PRACTICE:
“Our study demonstrated that our stratification, defined by symptoms, systemic clinical signs, and routine biological data, is based on different pathophysiological pathways, particularly B and T lymphocyte activation and the interferon alpha pathway. The latter could help predict the evolution of the BALS cluster, a biological but minimally symptomatic cluster, to consider closer monitoring and/or early treatments to prevent complications,” the authors wrote.
SOURCE:
The study was led by Yann Nguyen, MD, PhD, Department of Rheumatology, Hôpital Bicêtre, Assistance Publique — Hôpitaux de Paris, Université Paris-Saclay, Paris, France, and was published online on December 25, 2024, in Arthritis & Rheumatology.
LIMITATIONS:
The study evaluated only a few cytokines at the time of inclusion in the ASSESS cohort, which may not have captured the full range of biologic markers relevant to SjD. The evolution of systemic activity defined using the European Alliance of Associations for Rheumatology Sjogren’s Syndrome Disease Activity Index showed no difference according to the IFN signature in the B-cell active with low symptom burden cluster, possibly due to treatments received between annual evaluations.
DISCLOSURES:
The ASSESS cohort is supported by research grants from the French Society of Rheumatology. Some authors reported receiving grants, payments, honoraria, consulting fees, and support for attending meetings and having contracts or other ties with pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Patients With Rheumatoid Arthritis Show Higher Risk for Heart Failure With Preserved Ejection Fraction
TOPLINE:
Patients with rheumatoid arthritis (RA) face a higher risk for heart failure (HF) than those without the condition, with the elevated risk primarily driven by HF with preserved ejection fraction (HFpEF).
METHODOLOGY:
- The researchers conducted a retrospective cohort study using data from the Mass General Brigham Biobank to investigate the risk for overall HF and its subtypes, particularly HF with reduced EF (HFrEF) and HFpEF, in patients with RA.
- They included 1445 patients newly diagnosed with RA (mean age, 51.4 years; 78.7% women) and 4335 matched comparators without RA.
- Patients with RA were identified using diagnosis codes and RA-related natural language processing concepts.
- HFpEF and HFrEF were defined as HF with an EF ≥ 50% and ≤ 40%, respectively; incidences for overall HF, HFpEF, and HFrEF were calculated per 1000 person-years.
TAKEAWAY:
- The study identified 92 incident HF cases in the RA cohort and 157 in the non-RA cohort over a median follow-up of 10.3 years per patient.
- HFpEF was the predominant HF subtype in both cohorts, with a higher incidence in patients with RA than in those without the condition (4.33 vs 2.11 per 1000 person-years).
- Patients with RA showed a 79% higher risk for HF than those without the condition (adjusted hazard ratio [aHR], 1.79; 95% CI, 1.38-2.32).
- Among the HF subtypes, patients with RA had a significantly increased risk for HFpEF (aHR, 1.99; 95% CI, 1.43-2.77) but not for HFrEF.
IN PRACTICE:
“RA can be considered a human model for inflammation, and findings from this study support the notion that chronic inflammation increases risk for HFpEF,” the authors wrote.
SOURCE:
This study was led by Yumeko Kawano, MD, Brigham and Women’s Hospital, Boston, Massachusetts, and was published online in Arthritis Care & Research.
LIMITATIONS:
This study was conducted within an academic tertiary hospital system and involved participants from a biobank, which may have introduced selection bias and limited generalizability. The study did not account for post-baseline variables that could mediate the observed associations, such as the chronic use of nonsteroidal anti-inflammatory drugs, steroids, or specific disease-modifying antirheumatic drugs. The study relied on the availability of clinically performed cardiology studies for HF subtyping, possibly introducing misclassification of HF.
DISCLOSURES:
This study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author received support from the Ruth L. Kirschstein Institutional National Research Service Award, National Institutes of Health.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Patients with rheumatoid arthritis (RA) face a higher risk for heart failure (HF) than those without the condition, with the elevated risk primarily driven by HF with preserved ejection fraction (HFpEF).
METHODOLOGY:
- The researchers conducted a retrospective cohort study using data from the Mass General Brigham Biobank to investigate the risk for overall HF and its subtypes, particularly HF with reduced EF (HFrEF) and HFpEF, in patients with RA.
- They included 1445 patients newly diagnosed with RA (mean age, 51.4 years; 78.7% women) and 4335 matched comparators without RA.
- Patients with RA were identified using diagnosis codes and RA-related natural language processing concepts.
- HFpEF and HFrEF were defined as HF with an EF ≥ 50% and ≤ 40%, respectively; incidences for overall HF, HFpEF, and HFrEF were calculated per 1000 person-years.
TAKEAWAY:
- The study identified 92 incident HF cases in the RA cohort and 157 in the non-RA cohort over a median follow-up of 10.3 years per patient.
- HFpEF was the predominant HF subtype in both cohorts, with a higher incidence in patients with RA than in those without the condition (4.33 vs 2.11 per 1000 person-years).
- Patients with RA showed a 79% higher risk for HF than those without the condition (adjusted hazard ratio [aHR], 1.79; 95% CI, 1.38-2.32).
- Among the HF subtypes, patients with RA had a significantly increased risk for HFpEF (aHR, 1.99; 95% CI, 1.43-2.77) but not for HFrEF.
IN PRACTICE:
“RA can be considered a human model for inflammation, and findings from this study support the notion that chronic inflammation increases risk for HFpEF,” the authors wrote.
SOURCE:
This study was led by Yumeko Kawano, MD, Brigham and Women’s Hospital, Boston, Massachusetts, and was published online in Arthritis Care & Research.
LIMITATIONS:
This study was conducted within an academic tertiary hospital system and involved participants from a biobank, which may have introduced selection bias and limited generalizability. The study did not account for post-baseline variables that could mediate the observed associations, such as the chronic use of nonsteroidal anti-inflammatory drugs, steroids, or specific disease-modifying antirheumatic drugs. The study relied on the availability of clinically performed cardiology studies for HF subtyping, possibly introducing misclassification of HF.
DISCLOSURES:
This study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author received support from the Ruth L. Kirschstein Institutional National Research Service Award, National Institutes of Health.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Patients with rheumatoid arthritis (RA) face a higher risk for heart failure (HF) than those without the condition, with the elevated risk primarily driven by HF with preserved ejection fraction (HFpEF).
METHODOLOGY:
- The researchers conducted a retrospective cohort study using data from the Mass General Brigham Biobank to investigate the risk for overall HF and its subtypes, particularly HF with reduced EF (HFrEF) and HFpEF, in patients with RA.
- They included 1445 patients newly diagnosed with RA (mean age, 51.4 years; 78.7% women) and 4335 matched comparators without RA.
- Patients with RA were identified using diagnosis codes and RA-related natural language processing concepts.
- HFpEF and HFrEF were defined as HF with an EF ≥ 50% and ≤ 40%, respectively; incidences for overall HF, HFpEF, and HFrEF were calculated per 1000 person-years.
TAKEAWAY:
- The study identified 92 incident HF cases in the RA cohort and 157 in the non-RA cohort over a median follow-up of 10.3 years per patient.
- HFpEF was the predominant HF subtype in both cohorts, with a higher incidence in patients with RA than in those without the condition (4.33 vs 2.11 per 1000 person-years).
- Patients with RA showed a 79% higher risk for HF than those without the condition (adjusted hazard ratio [aHR], 1.79; 95% CI, 1.38-2.32).
- Among the HF subtypes, patients with RA had a significantly increased risk for HFpEF (aHR, 1.99; 95% CI, 1.43-2.77) but not for HFrEF.
IN PRACTICE:
“RA can be considered a human model for inflammation, and findings from this study support the notion that chronic inflammation increases risk for HFpEF,” the authors wrote.
SOURCE:
This study was led by Yumeko Kawano, MD, Brigham and Women’s Hospital, Boston, Massachusetts, and was published online in Arthritis Care & Research.
LIMITATIONS:
This study was conducted within an academic tertiary hospital system and involved participants from a biobank, which may have introduced selection bias and limited generalizability. The study did not account for post-baseline variables that could mediate the observed associations, such as the chronic use of nonsteroidal anti-inflammatory drugs, steroids, or specific disease-modifying antirheumatic drugs. The study relied on the availability of clinically performed cardiology studies for HF subtyping, possibly introducing misclassification of HF.
DISCLOSURES:
This study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author received support from the Ruth L. Kirschstein Institutional National Research Service Award, National Institutes of Health.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Need for Biologic in Early RA Signals Lower Likelihood of Achieving Drug-Free Remission
TOPLINE:
Patients who require biologic disease-modifying antirheumatic drugs (DMARDs) for severe RA are less likely to achieve sustained DMARD-free remission than those not needing the medication.
METHODOLOGY:
- Patients with early RA from the Leiden Early Arthritis Clinic (EAC; n = 627) and the Rotterdam Early Arthritis Cohort (tREACH) trial (n = 425) were followed for 5 years and 3 years, respectively.
- Most patients in both the EAC (86%) and tREACH (64%) cohorts had never used a biologic DMARD during the follow-up period.
- The primary outcome measure was sustained DMARD-free remission, defined as the absence of clinical synovitis after discontinuation of DMARDs for at least 1 year.
TAKEAWAY:
- None of the EAC patients using a biologic DMARD achieved sustained DMARD-free remission, but 37% of those who never used the drug reached remission at 5 years (hazard ratio [HR], 0.02; P < .0001).
- No tREACH patients using a biologic DMARD reached sustained DMARD-free remission, but 15% of those who never used the drug achieved remission at 3 years (HR, 0.03; P < .0001).
- Sustained DMARD-free remission was higher in EAC patients who were negative for anti-citrullinated protein antibody (ACPA) than in those who were ACPA-positive at 5 years (56% vs 14%; P < .0001).
- During follow-up, some patients in both the EAC (9%) and tREACH (14%) cohorts experienced late flares after more than 1 year of discontinuing DMARDs.
IN PRACTICE:
“Sustained DMARD-free remission is unlikely in patients needing a biologic DMARD,” the authors said.
SOURCE:
Judith W. Heutz, MD, Erasmus Medical Center, Rotterdam, the Netherlands, led the study, published online on December 20, 2024, in The Lancet Rheumatology.
LIMITATIONS:
Because both cohorts were defined during follow-up rather than at baseline, outcomes related to the use of DMARDs and remission status could have been misinterpreted. Although the study adjusted for ACPA status, other factors such as disease activity were not corrected, which could have potentially led to residual confounding. Sparse data bias was present, especially in the biologic DMARD user group, in which none of the patients reached sustained DMARD-free remission.
DISCLOSURES:
The EAC received funding from the Dutch Arthritis Foundation and the European Research Council under the European Union’s Horizon 2020 research and innovation program. The tREACH trial was supported by an unrestricted grant from Pfizer. The authors declared no competing interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Patients who require biologic disease-modifying antirheumatic drugs (DMARDs) for severe RA are less likely to achieve sustained DMARD-free remission than those not needing the medication.
METHODOLOGY:
- Patients with early RA from the Leiden Early Arthritis Clinic (EAC; n = 627) and the Rotterdam Early Arthritis Cohort (tREACH) trial (n = 425) were followed for 5 years and 3 years, respectively.
- Most patients in both the EAC (86%) and tREACH (64%) cohorts had never used a biologic DMARD during the follow-up period.
- The primary outcome measure was sustained DMARD-free remission, defined as the absence of clinical synovitis after discontinuation of DMARDs for at least 1 year.
TAKEAWAY:
- None of the EAC patients using a biologic DMARD achieved sustained DMARD-free remission, but 37% of those who never used the drug reached remission at 5 years (hazard ratio [HR], 0.02; P < .0001).
- No tREACH patients using a biologic DMARD reached sustained DMARD-free remission, but 15% of those who never used the drug achieved remission at 3 years (HR, 0.03; P < .0001).
- Sustained DMARD-free remission was higher in EAC patients who were negative for anti-citrullinated protein antibody (ACPA) than in those who were ACPA-positive at 5 years (56% vs 14%; P < .0001).
- During follow-up, some patients in both the EAC (9%) and tREACH (14%) cohorts experienced late flares after more than 1 year of discontinuing DMARDs.
IN PRACTICE:
“Sustained DMARD-free remission is unlikely in patients needing a biologic DMARD,” the authors said.
SOURCE:
Judith W. Heutz, MD, Erasmus Medical Center, Rotterdam, the Netherlands, led the study, published online on December 20, 2024, in The Lancet Rheumatology.
LIMITATIONS:
Because both cohorts were defined during follow-up rather than at baseline, outcomes related to the use of DMARDs and remission status could have been misinterpreted. Although the study adjusted for ACPA status, other factors such as disease activity were not corrected, which could have potentially led to residual confounding. Sparse data bias was present, especially in the biologic DMARD user group, in which none of the patients reached sustained DMARD-free remission.
DISCLOSURES:
The EAC received funding from the Dutch Arthritis Foundation and the European Research Council under the European Union’s Horizon 2020 research and innovation program. The tREACH trial was supported by an unrestricted grant from Pfizer. The authors declared no competing interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Patients who require biologic disease-modifying antirheumatic drugs (DMARDs) for severe RA are less likely to achieve sustained DMARD-free remission than those not needing the medication.
METHODOLOGY:
- Patients with early RA from the Leiden Early Arthritis Clinic (EAC; n = 627) and the Rotterdam Early Arthritis Cohort (tREACH) trial (n = 425) were followed for 5 years and 3 years, respectively.
- Most patients in both the EAC (86%) and tREACH (64%) cohorts had never used a biologic DMARD during the follow-up period.
- The primary outcome measure was sustained DMARD-free remission, defined as the absence of clinical synovitis after discontinuation of DMARDs for at least 1 year.
TAKEAWAY:
- None of the EAC patients using a biologic DMARD achieved sustained DMARD-free remission, but 37% of those who never used the drug reached remission at 5 years (hazard ratio [HR], 0.02; P < .0001).
- No tREACH patients using a biologic DMARD reached sustained DMARD-free remission, but 15% of those who never used the drug achieved remission at 3 years (HR, 0.03; P < .0001).
- Sustained DMARD-free remission was higher in EAC patients who were negative for anti-citrullinated protein antibody (ACPA) than in those who were ACPA-positive at 5 years (56% vs 14%; P < .0001).
- During follow-up, some patients in both the EAC (9%) and tREACH (14%) cohorts experienced late flares after more than 1 year of discontinuing DMARDs.
IN PRACTICE:
“Sustained DMARD-free remission is unlikely in patients needing a biologic DMARD,” the authors said.
SOURCE:
Judith W. Heutz, MD, Erasmus Medical Center, Rotterdam, the Netherlands, led the study, published online on December 20, 2024, in The Lancet Rheumatology.
LIMITATIONS:
Because both cohorts were defined during follow-up rather than at baseline, outcomes related to the use of DMARDs and remission status could have been misinterpreted. Although the study adjusted for ACPA status, other factors such as disease activity were not corrected, which could have potentially led to residual confounding. Sparse data bias was present, especially in the biologic DMARD user group, in which none of the patients reached sustained DMARD-free remission.
DISCLOSURES:
The EAC received funding from the Dutch Arthritis Foundation and the European Research Council under the European Union’s Horizon 2020 research and innovation program. The tREACH trial was supported by an unrestricted grant from Pfizer. The authors declared no competing interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Vitamin D3 Does Not Reduce T2D Risk in Healthy Seniors
TOPLINE:
Long-term daily supplementation with moderate (1600 international units [IU]) or high (3200 IU) doses of vitamin D3 doesn’t reduce the risk for type 2 diabetes (T2D) among generally healthy older adults who have serum vitamin D levels sufficient for bone health.
METHODOLOGY:
- Observational studies have consistently linked low vitamin D levels with an increased risk for T2D, and short-term randomized trials have shown a protective effect of vitamin D supplementation for those with impaired glucose metabolism but not in populations of average risk-taking low doses.
- The Finnish Vitamin D Trial, conducted from 2012 to 2018 in generally healthy men (≥ 60 years) and women (≥ 65 years) without a history of cardiovascular disease or cancer, assessed the effects of 5 years of moderate and high vitamin D3 supplementation on the incidence of major chronic diseases.
- This analysis of T2D incidence included 2271 older participants (mean age, 68.2 years; 43.9% women) without self-reported use of diabetes medications at baseline.
- Participants were randomly assigned to receive placebo (n = 760), 1600 IU/d of vitamin D3 (n = 744), or 3200 IU/d of vitamin D3 (n = 767) and followed for a mean duration of 4.2 years, with T2D incidence assessed by diagnostic code from health registries.
- A representative subcohort of 505 participants underwent detailed investigations including blood sampling at months 0, 6, 12, and 24 for serum 25-hydroxyvitamin D3 [25(OH)D3], plasma glucose, and insulin concentrations.
TAKEAWAY:
- No significant difference in T2D incidence was observed between groups: Placebo (5.0%; 38 people), 1600 IU/d (4.2%; 31 people), and 3200 IU/d (4.7%; 36 people; P = .731 for trend), with no appreciable sex differences.
- When stratified by body mass index (BMI), a lower incidence of T2D with vitamin D supplementation was observed among those with a BMI < 25 (with wide CIs), but not among those with a higher BMI.
- In the subcohort, no significant differences in changes in plasma glucose, insulin concentrations, BMI, or waist circumference with vitamin D3 were observed between the three treatment groups during the 24-month follow-up (P ≥ .19).
- In an analysis excluding T2D from the first 2 years, researchers observed a potentially increased risk for T2D with increasing vitamin D dose (with wide CIs).
IN PRACTICE:
“Our findings do not suggest benefits of long-term moderate- or high-dose vitamin D3 supplementation for incidence of type 2 diabetes or glucose metabolism or body size among generally healthy older vitamin D–sufficient men and women who were not at high risk for type 2 diabetes,” the authors wrote.
SOURCE:
The study was led by Jyrki K. Virtanen, University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, and was published online in Diabetologia.
LIMITATIONS:
The study relied on national health registries to collect data on incident T2D events, which may have led to some T2D cases being missed. Data on serum 25(OH)D3 concentrations were available for the subcohort only, which prevented the investigation of whether vitamin D–deficient participants would have benefited from supplementation. The study was not specifically designed or powered for diabetes prevention, and information on participants’ diabetes history at baseline was not available. Wide CIs suggest uncertainty around some of the findings. Study participants were White and older, so caution is needed in generalizing results to groups of other ages, races and ethnicities, and different vitamin D levels.
DISCLOSURES:
The study received funding from the Academy of Finland, University of Eastern Finland, Juho Vainio Foundation, and other sources. Some authors reported receiving grants or travel support from pharmaceutical companies and certain institutions.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Long-term daily supplementation with moderate (1600 international units [IU]) or high (3200 IU) doses of vitamin D3 doesn’t reduce the risk for type 2 diabetes (T2D) among generally healthy older adults who have serum vitamin D levels sufficient for bone health.
METHODOLOGY:
- Observational studies have consistently linked low vitamin D levels with an increased risk for T2D, and short-term randomized trials have shown a protective effect of vitamin D supplementation for those with impaired glucose metabolism but not in populations of average risk-taking low doses.
- The Finnish Vitamin D Trial, conducted from 2012 to 2018 in generally healthy men (≥ 60 years) and women (≥ 65 years) without a history of cardiovascular disease or cancer, assessed the effects of 5 years of moderate and high vitamin D3 supplementation on the incidence of major chronic diseases.
- This analysis of T2D incidence included 2271 older participants (mean age, 68.2 years; 43.9% women) without self-reported use of diabetes medications at baseline.
- Participants were randomly assigned to receive placebo (n = 760), 1600 IU/d of vitamin D3 (n = 744), or 3200 IU/d of vitamin D3 (n = 767) and followed for a mean duration of 4.2 years, with T2D incidence assessed by diagnostic code from health registries.
- A representative subcohort of 505 participants underwent detailed investigations including blood sampling at months 0, 6, 12, and 24 for serum 25-hydroxyvitamin D3 [25(OH)D3], plasma glucose, and insulin concentrations.
TAKEAWAY:
- No significant difference in T2D incidence was observed between groups: Placebo (5.0%; 38 people), 1600 IU/d (4.2%; 31 people), and 3200 IU/d (4.7%; 36 people; P = .731 for trend), with no appreciable sex differences.
- When stratified by body mass index (BMI), a lower incidence of T2D with vitamin D supplementation was observed among those with a BMI < 25 (with wide CIs), but not among those with a higher BMI.
- In the subcohort, no significant differences in changes in plasma glucose, insulin concentrations, BMI, or waist circumference with vitamin D3 were observed between the three treatment groups during the 24-month follow-up (P ≥ .19).
- In an analysis excluding T2D from the first 2 years, researchers observed a potentially increased risk for T2D with increasing vitamin D dose (with wide CIs).
IN PRACTICE:
“Our findings do not suggest benefits of long-term moderate- or high-dose vitamin D3 supplementation for incidence of type 2 diabetes or glucose metabolism or body size among generally healthy older vitamin D–sufficient men and women who were not at high risk for type 2 diabetes,” the authors wrote.
SOURCE:
The study was led by Jyrki K. Virtanen, University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, and was published online in Diabetologia.
LIMITATIONS:
The study relied on national health registries to collect data on incident T2D events, which may have led to some T2D cases being missed. Data on serum 25(OH)D3 concentrations were available for the subcohort only, which prevented the investigation of whether vitamin D–deficient participants would have benefited from supplementation. The study was not specifically designed or powered for diabetes prevention, and information on participants’ diabetes history at baseline was not available. Wide CIs suggest uncertainty around some of the findings. Study participants were White and older, so caution is needed in generalizing results to groups of other ages, races and ethnicities, and different vitamin D levels.
DISCLOSURES:
The study received funding from the Academy of Finland, University of Eastern Finland, Juho Vainio Foundation, and other sources. Some authors reported receiving grants or travel support from pharmaceutical companies and certain institutions.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Long-term daily supplementation with moderate (1600 international units [IU]) or high (3200 IU) doses of vitamin D3 doesn’t reduce the risk for type 2 diabetes (T2D) among generally healthy older adults who have serum vitamin D levels sufficient for bone health.
METHODOLOGY:
- Observational studies have consistently linked low vitamin D levels with an increased risk for T2D, and short-term randomized trials have shown a protective effect of vitamin D supplementation for those with impaired glucose metabolism but not in populations of average risk-taking low doses.
- The Finnish Vitamin D Trial, conducted from 2012 to 2018 in generally healthy men (≥ 60 years) and women (≥ 65 years) without a history of cardiovascular disease or cancer, assessed the effects of 5 years of moderate and high vitamin D3 supplementation on the incidence of major chronic diseases.
- This analysis of T2D incidence included 2271 older participants (mean age, 68.2 years; 43.9% women) without self-reported use of diabetes medications at baseline.
- Participants were randomly assigned to receive placebo (n = 760), 1600 IU/d of vitamin D3 (n = 744), or 3200 IU/d of vitamin D3 (n = 767) and followed for a mean duration of 4.2 years, with T2D incidence assessed by diagnostic code from health registries.
- A representative subcohort of 505 participants underwent detailed investigations including blood sampling at months 0, 6, 12, and 24 for serum 25-hydroxyvitamin D3 [25(OH)D3], plasma glucose, and insulin concentrations.
TAKEAWAY:
- No significant difference in T2D incidence was observed between groups: Placebo (5.0%; 38 people), 1600 IU/d (4.2%; 31 people), and 3200 IU/d (4.7%; 36 people; P = .731 for trend), with no appreciable sex differences.
- When stratified by body mass index (BMI), a lower incidence of T2D with vitamin D supplementation was observed among those with a BMI < 25 (with wide CIs), but not among those with a higher BMI.
- In the subcohort, no significant differences in changes in plasma glucose, insulin concentrations, BMI, or waist circumference with vitamin D3 were observed between the three treatment groups during the 24-month follow-up (P ≥ .19).
- In an analysis excluding T2D from the first 2 years, researchers observed a potentially increased risk for T2D with increasing vitamin D dose (with wide CIs).
IN PRACTICE:
“Our findings do not suggest benefits of long-term moderate- or high-dose vitamin D3 supplementation for incidence of type 2 diabetes or glucose metabolism or body size among generally healthy older vitamin D–sufficient men and women who were not at high risk for type 2 diabetes,” the authors wrote.
SOURCE:
The study was led by Jyrki K. Virtanen, University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, and was published online in Diabetologia.
LIMITATIONS:
The study relied on national health registries to collect data on incident T2D events, which may have led to some T2D cases being missed. Data on serum 25(OH)D3 concentrations were available for the subcohort only, which prevented the investigation of whether vitamin D–deficient participants would have benefited from supplementation. The study was not specifically designed or powered for diabetes prevention, and information on participants’ diabetes history at baseline was not available. Wide CIs suggest uncertainty around some of the findings. Study participants were White and older, so caution is needed in generalizing results to groups of other ages, races and ethnicities, and different vitamin D levels.
DISCLOSURES:
The study received funding from the Academy of Finland, University of Eastern Finland, Juho Vainio Foundation, and other sources. Some authors reported receiving grants or travel support from pharmaceutical companies and certain institutions.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Popular Diabetes Drug May Raise Vascular Surgery Risk
TOPLINE:
Among older veterans with type 2 diabetes (T2D), the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors as an add-on therapy is associated with a higher risk for peripheral artery disease (PAD)-related surgical events than the use of dipeptidyl peptidase 4 (DPP-4) inhibitors.
METHODOLOGY:
- Some placebo-controlled randomized trials have reported an increased risk for amputation with the use of SGLT2 inhibitors in patients with underlying cardiovascular diseases; however, the evidence remains unconfirmed by other subsequent trials.
- Researchers conducted a retrospective study of US veterans with T2D initiating SGLT2 inhibitors or DPP-4 inhibitors (a reference drug) as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination.
- The primary outcome was the time to the first surgical event for PAD (amputation, peripheral revascularization and bypass, or peripheral vascular stent).
- A Cox proportional hazards model was used to compare PAD event risk between the SGLT2 inhibitor and DPP-4 inhibitor groups, allowing events up to 90 days or 360 days after stopping SGLT2 inhibitors.
TAKEAWAY:
- After propensity score weighting, 76,072 episodes of SGLT2 inhibitor use (94% empagliflozin, 4% canagliflozin, and 2% dapagliflozin) and 75,833 episodes of DPP-4 inhibitor use (45% saxagliptin, 34% alogliptin, 15% sitagliptin, and 6% linagliptin) were included.
- Participants had a median age of 69 years and a median duration of diabetes of 10.1 years.
- SGLT2 inhibitor users had higher PAD-related surgical events than DPP-4 inhibitor users (874 vs 780), with event rates of 11.2 vs 10.0 per 1000 person-years (adjusted hazard ratio [aHR], 1.18).
- The results remained consistent after 90 and 360 days of stopping SGLT2 inhibitors.
- SGLT2 inhibitor use was also associated with a higher risk for amputation (aHR, 1.15) and revascularization (aHR, 1.25) events than DPP-4 inhibitor use.
IN PRACTICE:
“These results underscore the need to determine the safety of [SGLT2 inhibitor] use among patients with diabetes who remain at very high risk for PAD,” the authors wrote.
SOURCE:
This study was led by Katherine E. Griffin, Geriatric Research Education and Clinical Center, Tennessee Valley Healthcare System, Nashville, and published online in Diabetes Care.
LIMITATIONS:
The study excluded patients whose initial diabetes treatment was not metformin, insulin, or sulfonylurea, which might have influenced the interpretation of the results. The median follow-up period of approximately 0.7 years for both groups may have affected the number of amputations and revascularization events observed. The study population primarily comprised White men, limiting generalizability to women and other demographic groups.
DISCLOSURES:
The study received funding through an investigator-initiated grant from the Veterans Affairs Clinical Science Research and Development. Two authors received partial research support through a grant from the Center for Diabetes Translation Research. All authors received partial support from the VETWISE-LHS Center of Innovation. No potential conflicts of interest relevant to the article were reported.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Among older veterans with type 2 diabetes (T2D), the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors as an add-on therapy is associated with a higher risk for peripheral artery disease (PAD)-related surgical events than the use of dipeptidyl peptidase 4 (DPP-4) inhibitors.
METHODOLOGY:
- Some placebo-controlled randomized trials have reported an increased risk for amputation with the use of SGLT2 inhibitors in patients with underlying cardiovascular diseases; however, the evidence remains unconfirmed by other subsequent trials.
- Researchers conducted a retrospective study of US veterans with T2D initiating SGLT2 inhibitors or DPP-4 inhibitors (a reference drug) as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination.
- The primary outcome was the time to the first surgical event for PAD (amputation, peripheral revascularization and bypass, or peripheral vascular stent).
- A Cox proportional hazards model was used to compare PAD event risk between the SGLT2 inhibitor and DPP-4 inhibitor groups, allowing events up to 90 days or 360 days after stopping SGLT2 inhibitors.
TAKEAWAY:
- After propensity score weighting, 76,072 episodes of SGLT2 inhibitor use (94% empagliflozin, 4% canagliflozin, and 2% dapagliflozin) and 75,833 episodes of DPP-4 inhibitor use (45% saxagliptin, 34% alogliptin, 15% sitagliptin, and 6% linagliptin) were included.
- Participants had a median age of 69 years and a median duration of diabetes of 10.1 years.
- SGLT2 inhibitor users had higher PAD-related surgical events than DPP-4 inhibitor users (874 vs 780), with event rates of 11.2 vs 10.0 per 1000 person-years (adjusted hazard ratio [aHR], 1.18).
- The results remained consistent after 90 and 360 days of stopping SGLT2 inhibitors.
- SGLT2 inhibitor use was also associated with a higher risk for amputation (aHR, 1.15) and revascularization (aHR, 1.25) events than DPP-4 inhibitor use.
IN PRACTICE:
“These results underscore the need to determine the safety of [SGLT2 inhibitor] use among patients with diabetes who remain at very high risk for PAD,” the authors wrote.
SOURCE:
This study was led by Katherine E. Griffin, Geriatric Research Education and Clinical Center, Tennessee Valley Healthcare System, Nashville, and published online in Diabetes Care.
LIMITATIONS:
The study excluded patients whose initial diabetes treatment was not metformin, insulin, or sulfonylurea, which might have influenced the interpretation of the results. The median follow-up period of approximately 0.7 years for both groups may have affected the number of amputations and revascularization events observed. The study population primarily comprised White men, limiting generalizability to women and other demographic groups.
DISCLOSURES:
The study received funding through an investigator-initiated grant from the Veterans Affairs Clinical Science Research and Development. Two authors received partial research support through a grant from the Center for Diabetes Translation Research. All authors received partial support from the VETWISE-LHS Center of Innovation. No potential conflicts of interest relevant to the article were reported.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Among older veterans with type 2 diabetes (T2D), the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors as an add-on therapy is associated with a higher risk for peripheral artery disease (PAD)-related surgical events than the use of dipeptidyl peptidase 4 (DPP-4) inhibitors.
METHODOLOGY:
- Some placebo-controlled randomized trials have reported an increased risk for amputation with the use of SGLT2 inhibitors in patients with underlying cardiovascular diseases; however, the evidence remains unconfirmed by other subsequent trials.
- Researchers conducted a retrospective study of US veterans with T2D initiating SGLT2 inhibitors or DPP-4 inhibitors (a reference drug) as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination.
- The primary outcome was the time to the first surgical event for PAD (amputation, peripheral revascularization and bypass, or peripheral vascular stent).
- A Cox proportional hazards model was used to compare PAD event risk between the SGLT2 inhibitor and DPP-4 inhibitor groups, allowing events up to 90 days or 360 days after stopping SGLT2 inhibitors.
TAKEAWAY:
- After propensity score weighting, 76,072 episodes of SGLT2 inhibitor use (94% empagliflozin, 4% canagliflozin, and 2% dapagliflozin) and 75,833 episodes of DPP-4 inhibitor use (45% saxagliptin, 34% alogliptin, 15% sitagliptin, and 6% linagliptin) were included.
- Participants had a median age of 69 years and a median duration of diabetes of 10.1 years.
- SGLT2 inhibitor users had higher PAD-related surgical events than DPP-4 inhibitor users (874 vs 780), with event rates of 11.2 vs 10.0 per 1000 person-years (adjusted hazard ratio [aHR], 1.18).
- The results remained consistent after 90 and 360 days of stopping SGLT2 inhibitors.
- SGLT2 inhibitor use was also associated with a higher risk for amputation (aHR, 1.15) and revascularization (aHR, 1.25) events than DPP-4 inhibitor use.
IN PRACTICE:
“These results underscore the need to determine the safety of [SGLT2 inhibitor] use among patients with diabetes who remain at very high risk for PAD,” the authors wrote.
SOURCE:
This study was led by Katherine E. Griffin, Geriatric Research Education and Clinical Center, Tennessee Valley Healthcare System, Nashville, and published online in Diabetes Care.
LIMITATIONS:
The study excluded patients whose initial diabetes treatment was not metformin, insulin, or sulfonylurea, which might have influenced the interpretation of the results. The median follow-up period of approximately 0.7 years for both groups may have affected the number of amputations and revascularization events observed. The study population primarily comprised White men, limiting generalizability to women and other demographic groups.
DISCLOSURES:
The study received funding through an investigator-initiated grant from the Veterans Affairs Clinical Science Research and Development. Two authors received partial research support through a grant from the Center for Diabetes Translation Research. All authors received partial support from the VETWISE-LHS Center of Innovation. No potential conflicts of interest relevant to the article were reported.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Patients With Refractory Systemic Sclerosis Have Early Success With CAR T-Cell Therapy
TOPLINE:
CD19-targeting chimeric antigen receptor (CAR) T-cell therapy shows potential to intercept fibrotic organ manifestations and improve disease measures in patients with diffuse cutaneous systemic sclerosis (SSc) who had disease progression despite multiple previous treatments.
METHODOLOGY:
- Researchers conducted a case series to examine the effect of CD19-targeting CAR T-cell therapy on fibrotic and vascular organ manifestations in six patients with diffuse cutaneous SSc (median age, 42 years; four men and two women) who had an insufficient response to at least two previous treatments.
- Participants received CD19-targeting CAR T-cell treatment at a dose of 1 × 106 CAR T cells per kilogram of body weight after lymphodepletion with fludarabine and cyclophosphamide.
- The primary outcome was event-free time or treatment intensification after study entry, with events defined as the progression of interstitial lung disease, onset of congestive heart or renal failure or arterial hypertension, or initiation of new therapy.
- The secondary outcomes included changes in the modified Rodnan skin score (mRSS), imaging and laboratory assessments, patient-reported outcomes, and the modified American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS), assessed at baseline and 3, 6, 9, and 12 months after treatment.
TAKEAWAY:
- No progression of organ manifestations or new lung, cardiac, or renal events occurred within the median follow-up period of 487 days.
- The probability of improvement in the ACR-CRISS score increased to a median value of 100% within 6 and 12 months of CAR T-cell treatment compared with baseline.
- Skin involvement improved in all the patients after CAR T-cell treatment, with a median mRSS decrease of 8 points within 100 days; the improvements were maintained throughout the 1-year follow-up period.
- This treatment also led to a depletion of antinuclear antibodies and SSc-specific autoantibodies.
IN PRACTICE:
“This case series highlights the potential of CAR T-cell therapy to address a crucial unmet need in refractory systemic sclerosis treatment. The study’s most significant contribution is the demonstration that CD19-targeting CAR T-cell therapy can halt or reverse aspects of fibrosis in systemic sclerosis,” Jérôme Avouac, Service de Rhumatologie, Hôpital Cochin, AP-HP Centre-Université Paris Cité, Paris, France, wrote in an accompanying editorial.
SOURCE:
The study was led by Janina Auth, MD, Deutsches Zentrum Immuntherapie, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen in Germany, and was published online on November 11, 2024, in The Lancet Rheumatology.
LIMITATIONS:
The study lacked a control group, which limited the ability to draw definitive conclusions about the efficacy of CD19-targeting CAR T-cell therapy compared with standard treatments. The unpredictable nature of SSc, in which periods of stability can occur spontaneously, makes it difficult to attribute the improvements merely to the intervention. Moreover, the effect of CAR T-cell therapy on other disease manifestations, such as pulmonary hypertension, myocardial involvement, and scleroderma renal crisis, remains unclear.
DISCLOSURES:
The study was funded by Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, ELAN Foundation Erlangen, Interdisziplinäres Zentrum für Klinische Forschung Erlangen, Bundesministerium für Bildung und Forschung, and the European Union. Some authors reported receiving research grants, consulting fees, speaker fees, honoraria, or travel grants from Boehringer Ingelheim, Novartis, Almirall, and other pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
CD19-targeting chimeric antigen receptor (CAR) T-cell therapy shows potential to intercept fibrotic organ manifestations and improve disease measures in patients with diffuse cutaneous systemic sclerosis (SSc) who had disease progression despite multiple previous treatments.
METHODOLOGY:
- Researchers conducted a case series to examine the effect of CD19-targeting CAR T-cell therapy on fibrotic and vascular organ manifestations in six patients with diffuse cutaneous SSc (median age, 42 years; four men and two women) who had an insufficient response to at least two previous treatments.
- Participants received CD19-targeting CAR T-cell treatment at a dose of 1 × 106 CAR T cells per kilogram of body weight after lymphodepletion with fludarabine and cyclophosphamide.
- The primary outcome was event-free time or treatment intensification after study entry, with events defined as the progression of interstitial lung disease, onset of congestive heart or renal failure or arterial hypertension, or initiation of new therapy.
- The secondary outcomes included changes in the modified Rodnan skin score (mRSS), imaging and laboratory assessments, patient-reported outcomes, and the modified American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS), assessed at baseline and 3, 6, 9, and 12 months after treatment.
TAKEAWAY:
- No progression of organ manifestations or new lung, cardiac, or renal events occurred within the median follow-up period of 487 days.
- The probability of improvement in the ACR-CRISS score increased to a median value of 100% within 6 and 12 months of CAR T-cell treatment compared with baseline.
- Skin involvement improved in all the patients after CAR T-cell treatment, with a median mRSS decrease of 8 points within 100 days; the improvements were maintained throughout the 1-year follow-up period.
- This treatment also led to a depletion of antinuclear antibodies and SSc-specific autoantibodies.
IN PRACTICE:
“This case series highlights the potential of CAR T-cell therapy to address a crucial unmet need in refractory systemic sclerosis treatment. The study’s most significant contribution is the demonstration that CD19-targeting CAR T-cell therapy can halt or reverse aspects of fibrosis in systemic sclerosis,” Jérôme Avouac, Service de Rhumatologie, Hôpital Cochin, AP-HP Centre-Université Paris Cité, Paris, France, wrote in an accompanying editorial.
SOURCE:
The study was led by Janina Auth, MD, Deutsches Zentrum Immuntherapie, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen in Germany, and was published online on November 11, 2024, in The Lancet Rheumatology.
LIMITATIONS:
The study lacked a control group, which limited the ability to draw definitive conclusions about the efficacy of CD19-targeting CAR T-cell therapy compared with standard treatments. The unpredictable nature of SSc, in which periods of stability can occur spontaneously, makes it difficult to attribute the improvements merely to the intervention. Moreover, the effect of CAR T-cell therapy on other disease manifestations, such as pulmonary hypertension, myocardial involvement, and scleroderma renal crisis, remains unclear.
DISCLOSURES:
The study was funded by Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, ELAN Foundation Erlangen, Interdisziplinäres Zentrum für Klinische Forschung Erlangen, Bundesministerium für Bildung und Forschung, and the European Union. Some authors reported receiving research grants, consulting fees, speaker fees, honoraria, or travel grants from Boehringer Ingelheim, Novartis, Almirall, and other pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
CD19-targeting chimeric antigen receptor (CAR) T-cell therapy shows potential to intercept fibrotic organ manifestations and improve disease measures in patients with diffuse cutaneous systemic sclerosis (SSc) who had disease progression despite multiple previous treatments.
METHODOLOGY:
- Researchers conducted a case series to examine the effect of CD19-targeting CAR T-cell therapy on fibrotic and vascular organ manifestations in six patients with diffuse cutaneous SSc (median age, 42 years; four men and two women) who had an insufficient response to at least two previous treatments.
- Participants received CD19-targeting CAR T-cell treatment at a dose of 1 × 106 CAR T cells per kilogram of body weight after lymphodepletion with fludarabine and cyclophosphamide.
- The primary outcome was event-free time or treatment intensification after study entry, with events defined as the progression of interstitial lung disease, onset of congestive heart or renal failure or arterial hypertension, or initiation of new therapy.
- The secondary outcomes included changes in the modified Rodnan skin score (mRSS), imaging and laboratory assessments, patient-reported outcomes, and the modified American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS), assessed at baseline and 3, 6, 9, and 12 months after treatment.
TAKEAWAY:
- No progression of organ manifestations or new lung, cardiac, or renal events occurred within the median follow-up period of 487 days.
- The probability of improvement in the ACR-CRISS score increased to a median value of 100% within 6 and 12 months of CAR T-cell treatment compared with baseline.
- Skin involvement improved in all the patients after CAR T-cell treatment, with a median mRSS decrease of 8 points within 100 days; the improvements were maintained throughout the 1-year follow-up period.
- This treatment also led to a depletion of antinuclear antibodies and SSc-specific autoantibodies.
IN PRACTICE:
“This case series highlights the potential of CAR T-cell therapy to address a crucial unmet need in refractory systemic sclerosis treatment. The study’s most significant contribution is the demonstration that CD19-targeting CAR T-cell therapy can halt or reverse aspects of fibrosis in systemic sclerosis,” Jérôme Avouac, Service de Rhumatologie, Hôpital Cochin, AP-HP Centre-Université Paris Cité, Paris, France, wrote in an accompanying editorial.
SOURCE:
The study was led by Janina Auth, MD, Deutsches Zentrum Immuntherapie, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen in Germany, and was published online on November 11, 2024, in The Lancet Rheumatology.
LIMITATIONS:
The study lacked a control group, which limited the ability to draw definitive conclusions about the efficacy of CD19-targeting CAR T-cell therapy compared with standard treatments. The unpredictable nature of SSc, in which periods of stability can occur spontaneously, makes it difficult to attribute the improvements merely to the intervention. Moreover, the effect of CAR T-cell therapy on other disease manifestations, such as pulmonary hypertension, myocardial involvement, and scleroderma renal crisis, remains unclear.
DISCLOSURES:
The study was funded by Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, ELAN Foundation Erlangen, Interdisziplinäres Zentrum für Klinische Forschung Erlangen, Bundesministerium für Bildung und Forschung, and the European Union. Some authors reported receiving research grants, consulting fees, speaker fees, honoraria, or travel grants from Boehringer Ingelheim, Novartis, Almirall, and other pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
NT-proBNP May Predict Atrial Fibrillation Risk Early
TOPLINE:
Elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP), a key biomarker for diagnosing heart failure, show a nearly fourfold increased risk for atrial fibrillation (AF) in at-risk individuals. The utility of this biomarker was particularly evident in older adults and when serum-based measurements were used.
METHODOLOGY:
- Researchers conducted a meta-analysis of prospective cohort, case-cohort, or nested case-control studies to examine the association between NT-proBNP and the incidence of AF.
- They also explored the potential of NT-proBNP in improving risk prediction models for AF.
- Overall, 136,089 adults were included from 16 cohorts, and 8017 cases of incident AF were reported over a median follow-up of 4-20 years.
- Most of the included cohorts were from Europe (n = 12), followed by America (n = 3) and Asia (n = 1).
- The accuracy of the risk prediction models was evaluated using C-indexes, with values in the range of 0.50-0.70, low accuracy; 0.70-0.90, moderate accuracy; and > 0.90, high accuracy.
TAKEAWAY:
- Elevated NT-proBNP levels showed a strong association with the risk for AF, with individuals in the highest quintile of NT-proBNP facing a 3.84-fold higher risk for incident AF (pooled relative risk [RR], 3.84; 95% CI, 3.03-4.87) than those in the lowest quintile.
- The risk increased by 9% for each 10 pg/mL increase in NT-proBNP (RR, 1.09; 95% CI, 1.04-1.14), with a significant nonlinear dose-response association found between NT-proBNP and the risk for AF (P for nonlinearity < .001).
- The association was stronger in the subgroups of older adults and when the biomarker was measured in serum samples.
- The addition of NT-proBNP to traditional risk prediction models for AF may improve predictive accuracy, with the ΔC-indexes ranging from 0.010 to 0.060.
IN PRACTICE:
“The significance of NT-proBNP in enhancing AF risk stratification deserves greater attention, with potential expansion to routine health screening,” the authors wrote.
SOURCE:
The study was led by Wanyue Wang, Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and was published online on December 06, 2024, in Heart.
LIMITATIONS:
Significant heterogeneity was observed in this meta-analysis, with the subgroup articles only providing exploratory and indicative findings. Due to the observational nature of this study, residual confounding could not be excluded. None of the prospective studies included differentiated subtypes of AF, such as paroxysmal and asymptomatic forms, which might have influenced the observed outcomes.
DISCLOSURES:
This study was supported by grants from the National Key Research and Development Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and National High Level Hospital Clinical Research Funding. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP), a key biomarker for diagnosing heart failure, show a nearly fourfold increased risk for atrial fibrillation (AF) in at-risk individuals. The utility of this biomarker was particularly evident in older adults and when serum-based measurements were used.
METHODOLOGY:
- Researchers conducted a meta-analysis of prospective cohort, case-cohort, or nested case-control studies to examine the association between NT-proBNP and the incidence of AF.
- They also explored the potential of NT-proBNP in improving risk prediction models for AF.
- Overall, 136,089 adults were included from 16 cohorts, and 8017 cases of incident AF were reported over a median follow-up of 4-20 years.
- Most of the included cohorts were from Europe (n = 12), followed by America (n = 3) and Asia (n = 1).
- The accuracy of the risk prediction models was evaluated using C-indexes, with values in the range of 0.50-0.70, low accuracy; 0.70-0.90, moderate accuracy; and > 0.90, high accuracy.
TAKEAWAY:
- Elevated NT-proBNP levels showed a strong association with the risk for AF, with individuals in the highest quintile of NT-proBNP facing a 3.84-fold higher risk for incident AF (pooled relative risk [RR], 3.84; 95% CI, 3.03-4.87) than those in the lowest quintile.
- The risk increased by 9% for each 10 pg/mL increase in NT-proBNP (RR, 1.09; 95% CI, 1.04-1.14), with a significant nonlinear dose-response association found between NT-proBNP and the risk for AF (P for nonlinearity < .001).
- The association was stronger in the subgroups of older adults and when the biomarker was measured in serum samples.
- The addition of NT-proBNP to traditional risk prediction models for AF may improve predictive accuracy, with the ΔC-indexes ranging from 0.010 to 0.060.
IN PRACTICE:
“The significance of NT-proBNP in enhancing AF risk stratification deserves greater attention, with potential expansion to routine health screening,” the authors wrote.
SOURCE:
The study was led by Wanyue Wang, Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and was published online on December 06, 2024, in Heart.
LIMITATIONS:
Significant heterogeneity was observed in this meta-analysis, with the subgroup articles only providing exploratory and indicative findings. Due to the observational nature of this study, residual confounding could not be excluded. None of the prospective studies included differentiated subtypes of AF, such as paroxysmal and asymptomatic forms, which might have influenced the observed outcomes.
DISCLOSURES:
This study was supported by grants from the National Key Research and Development Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and National High Level Hospital Clinical Research Funding. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP), a key biomarker for diagnosing heart failure, show a nearly fourfold increased risk for atrial fibrillation (AF) in at-risk individuals. The utility of this biomarker was particularly evident in older adults and when serum-based measurements were used.
METHODOLOGY:
- Researchers conducted a meta-analysis of prospective cohort, case-cohort, or nested case-control studies to examine the association between NT-proBNP and the incidence of AF.
- They also explored the potential of NT-proBNP in improving risk prediction models for AF.
- Overall, 136,089 adults were included from 16 cohorts, and 8017 cases of incident AF were reported over a median follow-up of 4-20 years.
- Most of the included cohorts were from Europe (n = 12), followed by America (n = 3) and Asia (n = 1).
- The accuracy of the risk prediction models was evaluated using C-indexes, with values in the range of 0.50-0.70, low accuracy; 0.70-0.90, moderate accuracy; and > 0.90, high accuracy.
TAKEAWAY:
- Elevated NT-proBNP levels showed a strong association with the risk for AF, with individuals in the highest quintile of NT-proBNP facing a 3.84-fold higher risk for incident AF (pooled relative risk [RR], 3.84; 95% CI, 3.03-4.87) than those in the lowest quintile.
- The risk increased by 9% for each 10 pg/mL increase in NT-proBNP (RR, 1.09; 95% CI, 1.04-1.14), with a significant nonlinear dose-response association found between NT-proBNP and the risk for AF (P for nonlinearity < .001).
- The association was stronger in the subgroups of older adults and when the biomarker was measured in serum samples.
- The addition of NT-proBNP to traditional risk prediction models for AF may improve predictive accuracy, with the ΔC-indexes ranging from 0.010 to 0.060.
IN PRACTICE:
“The significance of NT-proBNP in enhancing AF risk stratification deserves greater attention, with potential expansion to routine health screening,” the authors wrote.
SOURCE:
The study was led by Wanyue Wang, Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and was published online on December 06, 2024, in Heart.
LIMITATIONS:
Significant heterogeneity was observed in this meta-analysis, with the subgroup articles only providing exploratory and indicative findings. Due to the observational nature of this study, residual confounding could not be excluded. None of the prospective studies included differentiated subtypes of AF, such as paroxysmal and asymptomatic forms, which might have influenced the observed outcomes.
DISCLOSURES:
This study was supported by grants from the National Key Research and Development Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and National High Level Hospital Clinical Research Funding. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.