Rheumatology News

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.

TOPLINE:

Tumor necrosis factor (TNF) inhibitors protect patients with axial spondyloarthritis (axSpA) from hip and spine fractures better than other drugs.

METHODOLOGY:

• Large US insurance claims database study comparing protective effects of TNF inhibitors vs other drugs on fractures in patients with axSpA.
• The study included 13,519 patients with axSpA aged 18-65 years, of whom 1229 had hip or spine fractures (mean age, 53 years; 38% women) and 12,290 were control participants without fractures.
• Effects of TNF inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), or no medication before the fracture were compared.
• The primary outcome was a composite hip and/or spine fracture, and the secondary outcome was a spine fracture.

TAKEAWAY:

• TNF inhibitor users had a lower risk for hip and spine fractures (adjusted odds ratio [aOR], 0.75; 95% CI, 0.62-0.91) than NSAID users, but this protective association was not seen in csDMARD users.
• Sex-stratified analysis showed similar protective effects of TNF inhibitors in both women and men.
• TNF inhibitor users showed a significantly lower risk for spine fractures than NSAID users (aOR, 0.81; 95% CI, 0.66-0.99).
• The protective effect of TNF inhibitors on hip and spine fractures was also seen in patients with a history of prior fractures; however, the effect was not statistically significant.

IN PRACTICE:

“Our findings underscore the multifaceted benefits of TNF inhibitors in axSpA,” the authors wrote.

SOURCE:

Devin Driscoll, MD, Section of Rheumatology, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, led the study, published online in Arthritis & Rheumatology.

LIMITATIONS:

Identification of the axSpA cohort and fracture outcomes was based solely on diagnostic and procedure codes, which may have led to misclassification. The administrative database lacked detailed information on disease activity levels, and the high proportion of missing data for body mass index, a known strong confounder for fracture risk, may have introduced bias. There were insufficient numbers of hip fractures to conduct analyses limited solely to hip fractures.

DISCLOSURES:

The study was supported by R03 AR076495 and NIH P30 AR072571. Two authors declared receiving grants, contracts, payments, honoraria, and other affiliations with various institutions and 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:

Tumor necrosis factor (TNF) inhibitors protect patients with axial spondyloarthritis (axSpA) from hip and spine fractures better than other drugs.

METHODOLOGY:

• Large US insurance claims database study comparing protective effects of TNF inhibitors vs other drugs on fractures in patients with axSpA.
• The study included 13,519 patients with axSpA aged 18-65 years, of whom 1229 had hip or spine fractures (mean age, 53 years; 38% women) and 12,290 were control participants without fractures.
• Effects of TNF inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), or no medication before the fracture were compared.
• The primary outcome was a composite hip and/or spine fracture, and the secondary outcome was a spine fracture.

TAKEAWAY:

• TNF inhibitor users had a lower risk for hip and spine fractures (adjusted odds ratio [aOR], 0.75; 95% CI, 0.62-0.91) than NSAID users, but this protective association was not seen in csDMARD users.
• Sex-stratified analysis showed similar protective effects of TNF inhibitors in both women and men.
• TNF inhibitor users showed a significantly lower risk for spine fractures than NSAID users (aOR, 0.81; 95% CI, 0.66-0.99).
• The protective effect of TNF inhibitors on hip and spine fractures was also seen in patients with a history of prior fractures; however, the effect was not statistically significant.

IN PRACTICE:

“Our findings underscore the multifaceted benefits of TNF inhibitors in axSpA,” the authors wrote.

SOURCE:

Devin Driscoll, MD, Section of Rheumatology, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, led the study, published online in Arthritis & Rheumatology.

LIMITATIONS:

Identification of the axSpA cohort and fracture outcomes was based solely on diagnostic and procedure codes, which may have led to misclassification. The administrative database lacked detailed information on disease activity levels, and the high proportion of missing data for body mass index, a known strong confounder for fracture risk, may have introduced bias. There were insufficient numbers of hip fractures to conduct analyses limited solely to hip fractures.

DISCLOSURES:

The study was supported by R03 AR076495 and NIH P30 AR072571. Two authors declared receiving grants, contracts, payments, honoraria, and other affiliations with various institutions and 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:

Tumor necrosis factor (TNF) inhibitors protect patients with axial spondyloarthritis (axSpA) from hip and spine fractures better than other drugs.

METHODOLOGY:

• Large US insurance claims database study comparing protective effects of TNF inhibitors vs other drugs on fractures in patients with axSpA.
• The study included 13,519 patients with axSpA aged 18-65 years, of whom 1229 had hip or spine fractures (mean age, 53 years; 38% women) and 12,290 were control participants without fractures.
• Effects of TNF inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), or no medication before the fracture were compared.
• The primary outcome was a composite hip and/or spine fracture, and the secondary outcome was a spine fracture.

TAKEAWAY:

• TNF inhibitor users had a lower risk for hip and spine fractures (adjusted odds ratio [aOR], 0.75; 95% CI, 0.62-0.91) than NSAID users, but this protective association was not seen in csDMARD users.
• Sex-stratified analysis showed similar protective effects of TNF inhibitors in both women and men.
• TNF inhibitor users showed a significantly lower risk for spine fractures than NSAID users (aOR, 0.81; 95% CI, 0.66-0.99).
• The protective effect of TNF inhibitors on hip and spine fractures was also seen in patients with a history of prior fractures; however, the effect was not statistically significant.

IN PRACTICE:

“Our findings underscore the multifaceted benefits of TNF inhibitors in axSpA,” the authors wrote.

SOURCE:

Devin Driscoll, MD, Section of Rheumatology, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, led the study, published online in Arthritis & Rheumatology.

LIMITATIONS:

Identification of the axSpA cohort and fracture outcomes was based solely on diagnostic and procedure codes, which may have led to misclassification. The administrative database lacked detailed information on disease activity levels, and the high proportion of missing data for body mass index, a known strong confounder for fracture risk, may have introduced bias. There were insufficient numbers of hip fractures to conduct analyses limited solely to hip fractures.

DISCLOSURES:

The study was supported by R03 AR076495 and NIH P30 AR072571. Two authors declared receiving grants, contracts, payments, honoraria, and other affiliations with various institutions and 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:

Stem cell transplantation tames some refractory systemic juvenile idiopathic arthritis–related lung disease that does not respond to other treatment.

METHODOLOGY:

• Retrospective cohort study of 13 children with refractory systemic juvenile idiopathic arthritis–related lung disease (sJIA-LD) who had allogeneic hematopoietic stem cell transplantation (HSCT).
• Children whose median age was 9 years at transplantation underwent HSCT at nine hospitals in the United States and Europe between January 2018 and October 2022, with a median follow-up of 16 months.
• Outcomes included transplant-related complications, pulmonary outcomes (eg, oxygen dependence and chest CT findings), and overall outcomes (eg, complete response, partial response, and death).

TAKEAWAY:

• Five patients developed acute graft vs host disease of varying grades, but none experienced chronic disease.
• All nine surviving patients achieved a complete response at the last follow-up, with no sJIA characteristics or need for immunosuppressive therapy or supplemental oxygen.
• Four patients died from complications including cytomegalovirus pneumonitis (n = 2), intracranial hemorrhage (n = 1), and progressive sJIA-LD (n = 1).
• Of six patients who underwent posttransplant chest CT, three had improved lung health, two had stable lung disease, and one experienced worsening lung disease, ultimately resulting in death.

IN PRACTICE:

“Allogeneic HSCT should be considered for treatment-refractory sJIA-LD,” the authors wrote.

“Efforts are being pursued for earlier recognition of patients with sJIA-LD at risk of adverse reactions to biologics. Early detection should help to avoid repeated treatments that are less effective and possibly deleterious and consider therapeutic approaches (eg, anti–[interleukin]-18 or [interferon]-delta–targeted treatments) that might act as a bridge therapy to control disease activity before HSCT,” wrote the author of an accompanying editorial.

SOURCE:

Michael G. Matt, MD, and Daniel Drozdov, MD, led the study, which was published online on December 20, 2024, in The Lancet Rheumatology.

LIMITATIONS:

Limitations included sampling bias and heterogeneity in clinical follow-up. The small sample size made it difficult to identify variables affecting survival and the achievement of a complete response. Additionally, many patients had relatively short follow-up periods.

DISCLOSURES:

This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. Several authors reported receiving advisory board fees, consulting fees, honoraria, grant funds, and stocks and shares from various research institutes and pharmaceutical organizations.

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:

Stem cell transplantation tames some refractory systemic juvenile idiopathic arthritis–related lung disease that does not respond to other treatment.

METHODOLOGY:

• Retrospective cohort study of 13 children with refractory systemic juvenile idiopathic arthritis–related lung disease (sJIA-LD) who had allogeneic hematopoietic stem cell transplantation (HSCT).
• Children whose median age was 9 years at transplantation underwent HSCT at nine hospitals in the United States and Europe between January 2018 and October 2022, with a median follow-up of 16 months.
• Outcomes included transplant-related complications, pulmonary outcomes (eg, oxygen dependence and chest CT findings), and overall outcomes (eg, complete response, partial response, and death).

TAKEAWAY:

• Five patients developed acute graft vs host disease of varying grades, but none experienced chronic disease.
• All nine surviving patients achieved a complete response at the last follow-up, with no sJIA characteristics or need for immunosuppressive therapy or supplemental oxygen.
• Four patients died from complications including cytomegalovirus pneumonitis (n = 2), intracranial hemorrhage (n = 1), and progressive sJIA-LD (n = 1).
• Of six patients who underwent posttransplant chest CT, three had improved lung health, two had stable lung disease, and one experienced worsening lung disease, ultimately resulting in death.

IN PRACTICE:

“Allogeneic HSCT should be considered for treatment-refractory sJIA-LD,” the authors wrote.

“Efforts are being pursued for earlier recognition of patients with sJIA-LD at risk of adverse reactions to biologics. Early detection should help to avoid repeated treatments that are less effective and possibly deleterious and consider therapeutic approaches (eg, anti–[interleukin]-18 or [interferon]-delta–targeted treatments) that might act as a bridge therapy to control disease activity before HSCT,” wrote the author of an accompanying editorial.

SOURCE:

Michael G. Matt, MD, and Daniel Drozdov, MD, led the study, which was published online on December 20, 2024, in The Lancet Rheumatology.

LIMITATIONS:

Limitations included sampling bias and heterogeneity in clinical follow-up. The small sample size made it difficult to identify variables affecting survival and the achievement of a complete response. Additionally, many patients had relatively short follow-up periods.

DISCLOSURES:

This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. Several authors reported receiving advisory board fees, consulting fees, honoraria, grant funds, and stocks and shares from various research institutes and pharmaceutical organizations.

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:

Stem cell transplantation tames some refractory systemic juvenile idiopathic arthritis–related lung disease that does not respond to other treatment.

METHODOLOGY:

• Retrospective cohort study of 13 children with refractory systemic juvenile idiopathic arthritis–related lung disease (sJIA-LD) who had allogeneic hematopoietic stem cell transplantation (HSCT).
• Children whose median age was 9 years at transplantation underwent HSCT at nine hospitals in the United States and Europe between January 2018 and October 2022, with a median follow-up of 16 months.
• Outcomes included transplant-related complications, pulmonary outcomes (eg, oxygen dependence and chest CT findings), and overall outcomes (eg, complete response, partial response, and death).

TAKEAWAY:

• Five patients developed acute graft vs host disease of varying grades, but none experienced chronic disease.
• All nine surviving patients achieved a complete response at the last follow-up, with no sJIA characteristics or need for immunosuppressive therapy or supplemental oxygen.
• Four patients died from complications including cytomegalovirus pneumonitis (n = 2), intracranial hemorrhage (n = 1), and progressive sJIA-LD (n = 1).
• Of six patients who underwent posttransplant chest CT, three had improved lung health, two had stable lung disease, and one experienced worsening lung disease, ultimately resulting in death.

IN PRACTICE:

“Allogeneic HSCT should be considered for treatment-refractory sJIA-LD,” the authors wrote.

“Efforts are being pursued for earlier recognition of patients with sJIA-LD at risk of adverse reactions to biologics. Early detection should help to avoid repeated treatments that are less effective and possibly deleterious and consider therapeutic approaches (eg, anti–[interleukin]-18 or [interferon]-delta–targeted treatments) that might act as a bridge therapy to control disease activity before HSCT,” wrote the author of an accompanying editorial.

SOURCE:

Michael G. Matt, MD, and Daniel Drozdov, MD, led the study, which was published online on December 20, 2024, in The Lancet Rheumatology.

LIMITATIONS:

Limitations included sampling bias and heterogeneity in clinical follow-up. The small sample size made it difficult to identify variables affecting survival and the achievement of a complete response. Additionally, many patients had relatively short follow-up periods.

DISCLOSURES:

This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. Several authors reported receiving advisory board fees, consulting fees, honoraria, grant funds, and stocks and shares from various research institutes and pharmaceutical organizations.

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:

Gout patients who take colchicine at the start of urate-lowering therapy have a lower risk for cardiovascular events than those who do not receive prophylaxis.

METHODOLOGY:

• Retrospective cohort study of 99,800 patients (mean age, 62.8 years; 74.4% men; 85.1% White) newly diagnosed with gout between January 1997 and March 2021 who initiated urate-lowering therapy.
• Gout flare prophylaxis, defined as a colchicine prescription for 21 days or more, was prescribed to 16,028 patients for a mean duration of 47.3 days at a mean daily dose of 0.97 mg.
• Patients who received colchicine prophylaxis and 83,772 patients who did not receive prophylaxis were followed for a mean of 175.5 and 176.9 days, respectively, in the intention-to-treat analysis.
• The primary outcome was the occurrence of the first cardiovascular event (fatal or nonfatal myocardial infarction or stroke) within 180 days of initiation of urate-lowering therapy.

TAKEAWAY:

• The risk for cardiovascular events was significantly lower with colchicine prophylaxis than without it (weighted hazard ratio [HR], 0.82; 95% CI, 0.69-0.94).
• The risk for a first-ever cardiovascular event was significantly lower with colchicine prophylaxis than without it (adjusted HR, 0.80; 95% CI, 0.62-0.97).
• The findings were similar regardless of analytical approach, and the intention-to-treat analysis did not show an increased risk for diarrhea with colchicine.

IN PRACTICE:

“The findings support consideration for the use of colchicine in people with gout and cardiovascular diseases,” the authors wrote. 

“The observed beneficial effect of colchicine concerns a huge group of patients worldwide. In addition, it is conceivable that, if a cardiovascular risk reduction is indeed confirmed, a strong argument arises to recommend the prescription of a course of colchicine to all [flaring] patients with gout, independently of their preference for urate-lowering therapy in general or urate-lowering therapy with or without colchicine prophylaxis more specifically,” experts wrote in a linked commentary.

SOURCE:

Edoardo Cipolletta, MD, Academic Rheumatology, School of Medicine, Nottingham City Hospital, University of Nottingham, England, led the study, which was published online in The Lancet Rheumatology.

LIMITATIONS: 

Because of the retrospective nature of the data extraction from a prospective database, the study had variations in follow-up and data completeness. Potential surveillance bias could have been introduced because patients with prior cardiovascular events were included in the study, and patients’ adherence to prescribed medications could not be verified.

DISCLOSURES:

This study was funded by the Foundation for Research in Rheumatology. Some authors reported receiving consulting fees, lecturing fees, and travel grants from various pharmaceutical companies and other additional sources.

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:

Gout patients who take colchicine at the start of urate-lowering therapy have a lower risk for cardiovascular events than those who do not receive prophylaxis.

METHODOLOGY:

• Retrospective cohort study of 99,800 patients (mean age, 62.8 years; 74.4% men; 85.1% White) newly diagnosed with gout between January 1997 and March 2021 who initiated urate-lowering therapy.
• Gout flare prophylaxis, defined as a colchicine prescription for 21 days or more, was prescribed to 16,028 patients for a mean duration of 47.3 days at a mean daily dose of 0.97 mg.
• Patients who received colchicine prophylaxis and 83,772 patients who did not receive prophylaxis were followed for a mean of 175.5 and 176.9 days, respectively, in the intention-to-treat analysis.
• The primary outcome was the occurrence of the first cardiovascular event (fatal or nonfatal myocardial infarction or stroke) within 180 days of initiation of urate-lowering therapy.

TAKEAWAY:

• The risk for cardiovascular events was significantly lower with colchicine prophylaxis than without it (weighted hazard ratio [HR], 0.82; 95% CI, 0.69-0.94).
• The risk for a first-ever cardiovascular event was significantly lower with colchicine prophylaxis than without it (adjusted HR, 0.80; 95% CI, 0.62-0.97).
• The findings were similar regardless of analytical approach, and the intention-to-treat analysis did not show an increased risk for diarrhea with colchicine.

IN PRACTICE:

“The findings support consideration for the use of colchicine in people with gout and cardiovascular diseases,” the authors wrote. 

“The observed beneficial effect of colchicine concerns a huge group of patients worldwide. In addition, it is conceivable that, if a cardiovascular risk reduction is indeed confirmed, a strong argument arises to recommend the prescription of a course of colchicine to all [flaring] patients with gout, independently of their preference for urate-lowering therapy in general or urate-lowering therapy with or without colchicine prophylaxis more specifically,” experts wrote in a linked commentary.

SOURCE:

Edoardo Cipolletta, MD, Academic Rheumatology, School of Medicine, Nottingham City Hospital, University of Nottingham, England, led the study, which was published online in The Lancet Rheumatology.

LIMITATIONS: 

Because of the retrospective nature of the data extraction from a prospective database, the study had variations in follow-up and data completeness. Potential surveillance bias could have been introduced because patients with prior cardiovascular events were included in the study, and patients’ adherence to prescribed medications could not be verified.

DISCLOSURES:

This study was funded by the Foundation for Research in Rheumatology. Some authors reported receiving consulting fees, lecturing fees, and travel grants from various pharmaceutical companies and other additional sources.

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:

Gout patients who take colchicine at the start of urate-lowering therapy have a lower risk for cardiovascular events than those who do not receive prophylaxis.

METHODOLOGY:

• Retrospective cohort study of 99,800 patients (mean age, 62.8 years; 74.4% men; 85.1% White) newly diagnosed with gout between January 1997 and March 2021 who initiated urate-lowering therapy.
• Gout flare prophylaxis, defined as a colchicine prescription for 21 days or more, was prescribed to 16,028 patients for a mean duration of 47.3 days at a mean daily dose of 0.97 mg.
• Patients who received colchicine prophylaxis and 83,772 patients who did not receive prophylaxis were followed for a mean of 175.5 and 176.9 days, respectively, in the intention-to-treat analysis.
• The primary outcome was the occurrence of the first cardiovascular event (fatal or nonfatal myocardial infarction or stroke) within 180 days of initiation of urate-lowering therapy.

TAKEAWAY:

• The risk for cardiovascular events was significantly lower with colchicine prophylaxis than without it (weighted hazard ratio [HR], 0.82; 95% CI, 0.69-0.94).
• The risk for a first-ever cardiovascular event was significantly lower with colchicine prophylaxis than without it (adjusted HR, 0.80; 95% CI, 0.62-0.97).
• The findings were similar regardless of analytical approach, and the intention-to-treat analysis did not show an increased risk for diarrhea with colchicine.

IN PRACTICE:

“The findings support consideration for the use of colchicine in people with gout and cardiovascular diseases,” the authors wrote. 

“The observed beneficial effect of colchicine concerns a huge group of patients worldwide. In addition, it is conceivable that, if a cardiovascular risk reduction is indeed confirmed, a strong argument arises to recommend the prescription of a course of colchicine to all [flaring] patients with gout, independently of their preference for urate-lowering therapy in general or urate-lowering therapy with or without colchicine prophylaxis more specifically,” experts wrote in a linked commentary.

SOURCE:

Edoardo Cipolletta, MD, Academic Rheumatology, School of Medicine, Nottingham City Hospital, University of Nottingham, England, led the study, which was published online in The Lancet Rheumatology.

LIMITATIONS: 

Because of the retrospective nature of the data extraction from a prospective database, the study had variations in follow-up and data completeness. Potential surveillance bias could have been introduced because patients with prior cardiovascular events were included in the study, and patients’ adherence to prescribed medications could not be verified.

DISCLOSURES:

This study was funded by the Foundation for Research in Rheumatology. Some authors reported receiving consulting fees, lecturing fees, and travel grants from various pharmaceutical companies and other additional sources.

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.

Laura Vater remembers sneaking into her home after 12-hour night shifts during medical training while her husband distracted their toddler. The stealthy tag-teaming effort helped her get enough undisturbed sleep before returning to an Indiana University hospital the following night to repeat the pattern.

“He would pretend to take out the trash when I pulled in,” said Vater, MD, now a gastrointestinal oncologist and assistant professor of medicine at IU Health Simon Cancer Center in Indianapolis. “I would sneak in so she [their daughter] wouldn’t see me, and then he would go back in.”

For Vater, prioritizing sleep during the day to combat sleep deprivation common among doctors-in-training on night shifts required enlisting a supportive spouse. It’s just one of the tips she and a few chief residents shared with this news organization for staying sharp and healthy during overnight rotations.

While the pace of patient rounds may slow from the frenetic daytime rush, training as a doctor after the sun goes down can be quite challenging for residents, they told this news organization. From sleep deprivation working while the rest of us slumbers to the after-effects of late-night caffeine, learning to manage night rotations requires a balance of preparation and attention to personal health while caring for others, the residents and adviser said.

Compromised sleep is one of the biggest hurdles residents have to overcome. Sleep loss comes with risks to cardiovascular disease and type 2 diabetes, among other heath conditions, according to Medscape Medical News reports. And night shift workers  who sleep 6 or fewer hours a night have at least one sleep disorder.

Sleep deprivation associated with overnight call schedules also can worsen a resident’s mood and motivation while impairing their judgment, leading to medical errors, according to a new study published in JAMA Open Network. The study proposed shorter consecutive night shifts and naps as ways to offset the results of sleep loss, especially for interns or first-year residents. 

Residency programs recently have been experimenting with shorter call schedules.

 

Catching Zzs

Working the night shift demands a disciplined sleep schedule, said Nat deQuillfeldt, MD, a Denver Health chief resident in the University of Colorado’s internal medicine residency program.

“When I was on night admissions, I was very strict about going to sleep at 8 AM and waking at 3 PM every single day. It can be very tempting to try to stay up and spend time with loved ones, but my husband and I both prioritized my physical well-being for those weeks,” said deQuillfeldt, a PGY-4 resident. “It was especially challenging for me because I had to commute about 50 minutes each way and without such a rigid schedule I would have struggled to be on time.”

deQuillfeldt doesn’t have young children at home, a noisy community, or other distractions to interrupt sleep during the day. But it was still difficult for her to sleep while the sun was out. “I used an eye mask and ear plugs but definitely woke up more often than I would at night.”

Blackout curtains may have helped, she added.

“Without adequate sleep, your clinical thinking is not as sharp. When emergencies happen overnight, you’re often the first person to arrive and need to be able to make rapid, accurate assessments and decisions.”

As a chief resident, she chooses never to sleep during night shifts.

“I personally didn’t want to leave my interns alone or make them feel like they were waking me up or bothering me if they needed help, and I also didn’t want to be groggy in case of a rapid response or code blue.”

But napping on night shift is definitely possible, deQuillfeldt said. Between following up on overnight lab results, answering nurses’ questions, and responding to emergencies, she found downtime on night shift to eat and hydrate. She believes others can catch an hour or 2 of shut eye, even if they work in the intensive care unit, or 3-4 hours on rare quiet nights.

Vater suggests residents transitioning from daytime work to night shift prepare by trying to catch an afternoon nap, staying up later the night before the change, and banking sleep hours in advance.

When he knows he’s starting night shifts, Apurva Popat, MD, said he tries to go to sleep an hour or so later nights before to avoid becoming sleep deprived. The chief resident of internal medicine at Marshfield Clinic Health System in Marshfield, Wisconsin, doesn’t recommend sleeping during the night shift.

“I typically try not to sleep, even if I have time, so I can go home and sleep later in the morning,” said Popat, a PGY-3 resident.

To help him snooze, he uses blackout curtains and a fan to block out noise. His wife, a first-year internal medicine intern, often works a different shift, so she helps set up his sleeping environment and he reciprocates when it’s her turn for night shifts.

Some interns may need to catch a 20- to 30-minute nap on the first night shift, he said.

Popat also seeks out brighter areas of the hospital, such as the emergency department, where there are more people and colleagues to keep him alert.

 

Bypass Vending Machines

Lack of sleep makes it even more difficult to eat healthy on night shift, said Vater, who advises residents about wellness issues at IU and on social media.

“When you are sleep deprived, when you do not get enough sleep, you eat but you don’t feel full,” she said. “It’s hard to eat well on night shift. It’s harder if you go to the break room and there’s candy and junk food.”

Vater said that, as a resident, she brought a lunch bag to the hospital during night shifts. “I never had time to prep food, so I’d bring a whole apple, a whole orange, a whole avocado or nuts. It allowed me to eat more fruits and vegetables than I normally would.”

She advises caution when considering coffee to stay awake, especially after about 9 PM, which could interfere with sleep residents need later when they finish their shifts. Caffeine may help in the moment, but it prevents deep sleep, Vater said. So when residents finally get sleep after their shifts, they may wake up feeling tired, she said.

To avoid sleepiness, Popat brings protein shakes with him to night shifts. They stave off sugar spikes and keep his energy level high, he said. He might have a protein shake and fruit before he leaves home and carry his vegetarian dinner with him to eat in the early morning hours when the hospital is calm.

Eating small and frequent meals also helps ward off sleepiness, deQuillfeldt said.

 

Take the Stairs

Trying to stay healthy on night shifts, Vater also checked on patients by taking the stairs. “I’d set the timer on my phone for 30 minutes and if I got paged at 15, I’d pause the timer and reset it if I had a moment later. I’d get at least 30 minutes in, although not always continuous. I think some activity is better than none.”

Vater said her hospital had a gym, but it wasn’t practical for her because it was further away from where she worked. “Sometimes my coresidents would be more creative, and we would do squats.”

Popat tries to lift weights 2 hours before his night shift, but he also takes short walks between patients’ rooms in the early morning hours when it’s quietest. He also promotes deep breathing to stay alert.

 

Ask for a Ride

Vater urges those coming off night shifts, especially those transitioning for the first time from daytime rotations, not to drive if they’re exhausted. “Get an Uber. ... Make sure you get a ride home.”

The CU residency program covers the cost of a ridesharing service when doctors-in-training are too tired to drive home, deQuillfeldt said. “We really try to encourage people to use this to reduce the risk of car accidents.”

 

Promoting Mental Health

The residency program also links residents with primary care and mental health services. People who really struggle with shift work sleep disorder may qualify for medications to help them stay awake overnight, in addition to sleep hygiene apps and sleep aides.

“Night shifts can put a strain on mental health, especially when you’re only working, eating, and sleeping and not spending any time with family and friends,” deQuillfeldt said. “My husband works late afternoons, so we often would go weeks seeing each other for 15-20 minutes a day.”

“Sleeping when the sun is out often leads to a lack of light exposure which can compound the problem. Seeking mental health support early is really important to avoiding burnout,” she said.

She also recommended planning a fun weekend activity, trip, or celebration with friends or family after night shifts end “so you have something to look forward to…It’s so important to have a light at the end of the tunnel, which will allow you to enjoy the sense of accomplishment even more.”

For more advice on the subject, consider the American Medical Association guide to managing sleep deprivation in residency or Laura Vater’s tips for night shifts.

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

Laura Vater remembers sneaking into her home after 12-hour night shifts during medical training while her husband distracted their toddler. The stealthy tag-teaming effort helped her get enough undisturbed sleep before returning to an Indiana University hospital the following night to repeat the pattern.

“He would pretend to take out the trash when I pulled in,” said Vater, MD, now a gastrointestinal oncologist and assistant professor of medicine at IU Health Simon Cancer Center in Indianapolis. “I would sneak in so she [their daughter] wouldn’t see me, and then he would go back in.”

For Vater, prioritizing sleep during the day to combat sleep deprivation common among doctors-in-training on night shifts required enlisting a supportive spouse. It’s just one of the tips she and a few chief residents shared with this news organization for staying sharp and healthy during overnight rotations.

While the pace of patient rounds may slow from the frenetic daytime rush, training as a doctor after the sun goes down can be quite challenging for residents, they told this news organization. From sleep deprivation working while the rest of us slumbers to the after-effects of late-night caffeine, learning to manage night rotations requires a balance of preparation and attention to personal health while caring for others, the residents and adviser said.

Compromised sleep is one of the biggest hurdles residents have to overcome. Sleep loss comes with risks to cardiovascular disease and type 2 diabetes, among other heath conditions, according to Medscape Medical News reports. And night shift workers  who sleep 6 or fewer hours a night have at least one sleep disorder.

Sleep deprivation associated with overnight call schedules also can worsen a resident’s mood and motivation while impairing their judgment, leading to medical errors, according to a new study published in JAMA Open Network. The study proposed shorter consecutive night shifts and naps as ways to offset the results of sleep loss, especially for interns or first-year residents. 

Residency programs recently have been experimenting with shorter call schedules.

 

Catching Zzs

Working the night shift demands a disciplined sleep schedule, said Nat deQuillfeldt, MD, a Denver Health chief resident in the University of Colorado’s internal medicine residency program.

“When I was on night admissions, I was very strict about going to sleep at 8 AM and waking at 3 PM every single day. It can be very tempting to try to stay up and spend time with loved ones, but my husband and I both prioritized my physical well-being for those weeks,” said deQuillfeldt, a PGY-4 resident. “It was especially challenging for me because I had to commute about 50 minutes each way and without such a rigid schedule I would have struggled to be on time.”

deQuillfeldt doesn’t have young children at home, a noisy community, or other distractions to interrupt sleep during the day. But it was still difficult for her to sleep while the sun was out. “I used an eye mask and ear plugs but definitely woke up more often than I would at night.”

Blackout curtains may have helped, she added.

“Without adequate sleep, your clinical thinking is not as sharp. When emergencies happen overnight, you’re often the first person to arrive and need to be able to make rapid, accurate assessments and decisions.”

As a chief resident, she chooses never to sleep during night shifts.

“I personally didn’t want to leave my interns alone or make them feel like they were waking me up or bothering me if they needed help, and I also didn’t want to be groggy in case of a rapid response or code blue.”

But napping on night shift is definitely possible, deQuillfeldt said. Between following up on overnight lab results, answering nurses’ questions, and responding to emergencies, she found downtime on night shift to eat and hydrate. She believes others can catch an hour or 2 of shut eye, even if they work in the intensive care unit, or 3-4 hours on rare quiet nights.

Vater suggests residents transitioning from daytime work to night shift prepare by trying to catch an afternoon nap, staying up later the night before the change, and banking sleep hours in advance.

When he knows he’s starting night shifts, Apurva Popat, MD, said he tries to go to sleep an hour or so later nights before to avoid becoming sleep deprived. The chief resident of internal medicine at Marshfield Clinic Health System in Marshfield, Wisconsin, doesn’t recommend sleeping during the night shift.

“I typically try not to sleep, even if I have time, so I can go home and sleep later in the morning,” said Popat, a PGY-3 resident.

To help him snooze, he uses blackout curtains and a fan to block out noise. His wife, a first-year internal medicine intern, often works a different shift, so she helps set up his sleeping environment and he reciprocates when it’s her turn for night shifts.

Some interns may need to catch a 20- to 30-minute nap on the first night shift, he said.

Popat also seeks out brighter areas of the hospital, such as the emergency department, where there are more people and colleagues to keep him alert.

 

Bypass Vending Machines

Lack of sleep makes it even more difficult to eat healthy on night shift, said Vater, who advises residents about wellness issues at IU and on social media.

“When you are sleep deprived, when you do not get enough sleep, you eat but you don’t feel full,” she said. “It’s hard to eat well on night shift. It’s harder if you go to the break room and there’s candy and junk food.”

Vater said that, as a resident, she brought a lunch bag to the hospital during night shifts. “I never had time to prep food, so I’d bring a whole apple, a whole orange, a whole avocado or nuts. It allowed me to eat more fruits and vegetables than I normally would.”

She advises caution when considering coffee to stay awake, especially after about 9 PM, which could interfere with sleep residents need later when they finish their shifts. Caffeine may help in the moment, but it prevents deep sleep, Vater said. So when residents finally get sleep after their shifts, they may wake up feeling tired, she said.

To avoid sleepiness, Popat brings protein shakes with him to night shifts. They stave off sugar spikes and keep his energy level high, he said. He might have a protein shake and fruit before he leaves home and carry his vegetarian dinner with him to eat in the early morning hours when the hospital is calm.

Eating small and frequent meals also helps ward off sleepiness, deQuillfeldt said.

 

Take the Stairs

Trying to stay healthy on night shifts, Vater also checked on patients by taking the stairs. “I’d set the timer on my phone for 30 minutes and if I got paged at 15, I’d pause the timer and reset it if I had a moment later. I’d get at least 30 minutes in, although not always continuous. I think some activity is better than none.”

Vater said her hospital had a gym, but it wasn’t practical for her because it was further away from where she worked. “Sometimes my coresidents would be more creative, and we would do squats.”

Popat tries to lift weights 2 hours before his night shift, but he also takes short walks between patients’ rooms in the early morning hours when it’s quietest. He also promotes deep breathing to stay alert.

 

Ask for a Ride

Vater urges those coming off night shifts, especially those transitioning for the first time from daytime rotations, not to drive if they’re exhausted. “Get an Uber. ... Make sure you get a ride home.”

The CU residency program covers the cost of a ridesharing service when doctors-in-training are too tired to drive home, deQuillfeldt said. “We really try to encourage people to use this to reduce the risk of car accidents.”

 

Promoting Mental Health

The residency program also links residents with primary care and mental health services. People who really struggle with shift work sleep disorder may qualify for medications to help them stay awake overnight, in addition to sleep hygiene apps and sleep aides.

“Night shifts can put a strain on mental health, especially when you’re only working, eating, and sleeping and not spending any time with family and friends,” deQuillfeldt said. “My husband works late afternoons, so we often would go weeks seeing each other for 15-20 minutes a day.”

“Sleeping when the sun is out often leads to a lack of light exposure which can compound the problem. Seeking mental health support early is really important to avoiding burnout,” she said.

She also recommended planning a fun weekend activity, trip, or celebration with friends or family after night shifts end “so you have something to look forward to…It’s so important to have a light at the end of the tunnel, which will allow you to enjoy the sense of accomplishment even more.”

For more advice on the subject, consider the American Medical Association guide to managing sleep deprivation in residency or Laura Vater’s tips for night shifts.

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

Laura Vater remembers sneaking into her home after 12-hour night shifts during medical training while her husband distracted their toddler. The stealthy tag-teaming effort helped her get enough undisturbed sleep before returning to an Indiana University hospital the following night to repeat the pattern.

“He would pretend to take out the trash when I pulled in,” said Vater, MD, now a gastrointestinal oncologist and assistant professor of medicine at IU Health Simon Cancer Center in Indianapolis. “I would sneak in so she [their daughter] wouldn’t see me, and then he would go back in.”

For Vater, prioritizing sleep during the day to combat sleep deprivation common among doctors-in-training on night shifts required enlisting a supportive spouse. It’s just one of the tips she and a few chief residents shared with this news organization for staying sharp and healthy during overnight rotations.

While the pace of patient rounds may slow from the frenetic daytime rush, training as a doctor after the sun goes down can be quite challenging for residents, they told this news organization. From sleep deprivation working while the rest of us slumbers to the after-effects of late-night caffeine, learning to manage night rotations requires a balance of preparation and attention to personal health while caring for others, the residents and adviser said.

Compromised sleep is one of the biggest hurdles residents have to overcome. Sleep loss comes with risks to cardiovascular disease and type 2 diabetes, among other heath conditions, according to Medscape Medical News reports. And night shift workers  who sleep 6 or fewer hours a night have at least one sleep disorder.

Sleep deprivation associated with overnight call schedules also can worsen a resident’s mood and motivation while impairing their judgment, leading to medical errors, according to a new study published in JAMA Open Network. The study proposed shorter consecutive night shifts and naps as ways to offset the results of sleep loss, especially for interns or first-year residents. 

Residency programs recently have been experimenting with shorter call schedules.

 

Catching Zzs

Working the night shift demands a disciplined sleep schedule, said Nat deQuillfeldt, MD, a Denver Health chief resident in the University of Colorado’s internal medicine residency program.

“When I was on night admissions, I was very strict about going to sleep at 8 AM and waking at 3 PM every single day. It can be very tempting to try to stay up and spend time with loved ones, but my husband and I both prioritized my physical well-being for those weeks,” said deQuillfeldt, a PGY-4 resident. “It was especially challenging for me because I had to commute about 50 minutes each way and without such a rigid schedule I would have struggled to be on time.”

deQuillfeldt doesn’t have young children at home, a noisy community, or other distractions to interrupt sleep during the day. But it was still difficult for her to sleep while the sun was out. “I used an eye mask and ear plugs but definitely woke up more often than I would at night.”

Blackout curtains may have helped, she added.

“Without adequate sleep, your clinical thinking is not as sharp. When emergencies happen overnight, you’re often the first person to arrive and need to be able to make rapid, accurate assessments and decisions.”

As a chief resident, she chooses never to sleep during night shifts.

“I personally didn’t want to leave my interns alone or make them feel like they were waking me up or bothering me if they needed help, and I also didn’t want to be groggy in case of a rapid response or code blue.”

But napping on night shift is definitely possible, deQuillfeldt said. Between following up on overnight lab results, answering nurses’ questions, and responding to emergencies, she found downtime on night shift to eat and hydrate. She believes others can catch an hour or 2 of shut eye, even if they work in the intensive care unit, or 3-4 hours on rare quiet nights.

Vater suggests residents transitioning from daytime work to night shift prepare by trying to catch an afternoon nap, staying up later the night before the change, and banking sleep hours in advance.

When he knows he’s starting night shifts, Apurva Popat, MD, said he tries to go to sleep an hour or so later nights before to avoid becoming sleep deprived. The chief resident of internal medicine at Marshfield Clinic Health System in Marshfield, Wisconsin, doesn’t recommend sleeping during the night shift.

“I typically try not to sleep, even if I have time, so I can go home and sleep later in the morning,” said Popat, a PGY-3 resident.

To help him snooze, he uses blackout curtains and a fan to block out noise. His wife, a first-year internal medicine intern, often works a different shift, so she helps set up his sleeping environment and he reciprocates when it’s her turn for night shifts.

Some interns may need to catch a 20- to 30-minute nap on the first night shift, he said.

Popat also seeks out brighter areas of the hospital, such as the emergency department, where there are more people and colleagues to keep him alert.

 

Bypass Vending Machines

Lack of sleep makes it even more difficult to eat healthy on night shift, said Vater, who advises residents about wellness issues at IU and on social media.

“When you are sleep deprived, when you do not get enough sleep, you eat but you don’t feel full,” she said. “It’s hard to eat well on night shift. It’s harder if you go to the break room and there’s candy and junk food.”

Vater said that, as a resident, she brought a lunch bag to the hospital during night shifts. “I never had time to prep food, so I’d bring a whole apple, a whole orange, a whole avocado or nuts. It allowed me to eat more fruits and vegetables than I normally would.”

She advises caution when considering coffee to stay awake, especially after about 9 PM, which could interfere with sleep residents need later when they finish their shifts. Caffeine may help in the moment, but it prevents deep sleep, Vater said. So when residents finally get sleep after their shifts, they may wake up feeling tired, she said.

To avoid sleepiness, Popat brings protein shakes with him to night shifts. They stave off sugar spikes and keep his energy level high, he said. He might have a protein shake and fruit before he leaves home and carry his vegetarian dinner with him to eat in the early morning hours when the hospital is calm.

Eating small and frequent meals also helps ward off sleepiness, deQuillfeldt said.

 

Take the Stairs

Trying to stay healthy on night shifts, Vater also checked on patients by taking the stairs. “I’d set the timer on my phone for 30 minutes and if I got paged at 15, I’d pause the timer and reset it if I had a moment later. I’d get at least 30 minutes in, although not always continuous. I think some activity is better than none.”

Vater said her hospital had a gym, but it wasn’t practical for her because it was further away from where she worked. “Sometimes my coresidents would be more creative, and we would do squats.”

Popat tries to lift weights 2 hours before his night shift, but he also takes short walks between patients’ rooms in the early morning hours when it’s quietest. He also promotes deep breathing to stay alert.

 

Ask for a Ride

Vater urges those coming off night shifts, especially those transitioning for the first time from daytime rotations, not to drive if they’re exhausted. “Get an Uber. ... Make sure you get a ride home.”

The CU residency program covers the cost of a ridesharing service when doctors-in-training are too tired to drive home, deQuillfeldt said. “We really try to encourage people to use this to reduce the risk of car accidents.”

 

Promoting Mental Health

The residency program also links residents with primary care and mental health services. People who really struggle with shift work sleep disorder may qualify for medications to help them stay awake overnight, in addition to sleep hygiene apps and sleep aides.

“Night shifts can put a strain on mental health, especially when you’re only working, eating, and sleeping and not spending any time with family and friends,” deQuillfeldt said. “My husband works late afternoons, so we often would go weeks seeing each other for 15-20 minutes a day.”

“Sleeping when the sun is out often leads to a lack of light exposure which can compound the problem. Seeking mental health support early is really important to avoiding burnout,” she said.

She also recommended planning a fun weekend activity, trip, or celebration with friends or family after night shifts end “so you have something to look forward to…It’s so important to have a light at the end of the tunnel, which will allow you to enjoy the sense of accomplishment even more.”

For more advice on the subject, consider the American Medical Association guide to managing sleep deprivation in residency or Laura Vater’s tips for night shifts.

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

TOPLINE:

Ivarmacitinib, a novel Janus kinase 1 inhibitor, alleviates symptoms, reduces disease activity, and improves physical function and quality of life in patients with moderate to severe rheumatoid arthritis (RA) who have an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

METHODOLOGY:

• This phase 3 trial, conducted across 59 sites in China, evaluated the efficacy and safety of ivarmacitinib in patients with moderate to severe active RA despite treatment with one or more csDMARDs.
• The patients were randomly assigned to receive either placebo (n = 188; mean age, 50.9 years; 85.6% women) or 4 mg ivarmacitinib (n = 189; mean age, 49.7 years; 91% women) or 8 mg ivarmacitinib (n = 189; mean age, 49.8 years; 83.6% women) once daily for 24 weeks, alongside background csDMARDs.
• After 24 weeks, the patients receiving placebo were switched to receive 4 mg ivarmacitinib for the additional 28-week extension period, whereas those receiving ivarmacitinib continued their initial dosage.
• Secondary endpoints included the proportion of patients achieving American College of Rheumatology (ACR) 50/70 responses and, Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP)) score < 2.6 or ≤ 3.2, as well as measures of other patient-reported outcomes such as pain, physical function, and quality of life at 24 and 52 weeks.

TAKEAWAY:

• At 24 weeks, the proportion of patients achieving a 20% improvement in the ACR20 response — the primary endpoint — was higher among those receiving 4 mg ivarmacitinib (70.4%) or 8 mg ivarmacitinib (75.1%) than among those receiving placebo (40.4%; P < .0001 for both comparisons), with the efficacy either maintained or improved through 52 weeks.
• The proportion of patients achieving ACR50/70 responses or a DAS28(CRP) score < 2.6 or ≤ 3.2 was higher in the ivarmacitinib groups than in the placebo group (P < .0001 for all comparisons).
• Compared with the placebo group, both the ivarmacitinib groups showed improvements in patient-reported outcomes such as pain, physical function, quality of life, and duration and severity of morning stiffness.
• The overall rates of treatment discontinuation caused by adverse events were low across all the groups, with no deaths, tuberculosis or gastrointestinal perforations reported throughout the 52 weeks.
•  

IN PRACTICE:

“Based on these findings, ivarmacitinib with background csDMARDs allowed, could be considered a treatment option in patients with moderate to severe active RA who have an inadequate response to csDMARDs,” the authors wrote.

SOURCE:

This study was led by Jinjing Liu and Xiaofeng Zeng, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China. It was published online on November 27, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

As the study was conducted in a Chinese population, the findings may have limited applicability across diverse global populations. Additionally, as the placebo-controlled period was limited to 24 weeks because of ethical concerns, comparisons between placebo and ivarmacitinib beyond that period were restricted. Lastly, this study was not powered to compare efficacy and safety between the two active dose regimens.

DISCLOSURES:

This study was funded by Jiangsu Hengrui Pharmaceuticals. Two authors declared being employees of the company. The other authors reported no competing interests.

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:

Ivarmacitinib, a novel Janus kinase 1 inhibitor, alleviates symptoms, reduces disease activity, and improves physical function and quality of life in patients with moderate to severe rheumatoid arthritis (RA) who have an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

METHODOLOGY:

• This phase 3 trial, conducted across 59 sites in China, evaluated the efficacy and safety of ivarmacitinib in patients with moderate to severe active RA despite treatment with one or more csDMARDs.
• The patients were randomly assigned to receive either placebo (n = 188; mean age, 50.9 years; 85.6% women) or 4 mg ivarmacitinib (n = 189; mean age, 49.7 years; 91% women) or 8 mg ivarmacitinib (n = 189; mean age, 49.8 years; 83.6% women) once daily for 24 weeks, alongside background csDMARDs.
• After 24 weeks, the patients receiving placebo were switched to receive 4 mg ivarmacitinib for the additional 28-week extension period, whereas those receiving ivarmacitinib continued their initial dosage.
• Secondary endpoints included the proportion of patients achieving American College of Rheumatology (ACR) 50/70 responses and, Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP)) score < 2.6 or ≤ 3.2, as well as measures of other patient-reported outcomes such as pain, physical function, and quality of life at 24 and 52 weeks.

TAKEAWAY:

• At 24 weeks, the proportion of patients achieving a 20% improvement in the ACR20 response — the primary endpoint — was higher among those receiving 4 mg ivarmacitinib (70.4%) or 8 mg ivarmacitinib (75.1%) than among those receiving placebo (40.4%; P < .0001 for both comparisons), with the efficacy either maintained or improved through 52 weeks.
• The proportion of patients achieving ACR50/70 responses or a DAS28(CRP) score < 2.6 or ≤ 3.2 was higher in the ivarmacitinib groups than in the placebo group (P < .0001 for all comparisons).
• Compared with the placebo group, both the ivarmacitinib groups showed improvements in patient-reported outcomes such as pain, physical function, quality of life, and duration and severity of morning stiffness.
• The overall rates of treatment discontinuation caused by adverse events were low across all the groups, with no deaths, tuberculosis or gastrointestinal perforations reported throughout the 52 weeks.
•  

IN PRACTICE:

“Based on these findings, ivarmacitinib with background csDMARDs allowed, could be considered a treatment option in patients with moderate to severe active RA who have an inadequate response to csDMARDs,” the authors wrote.

SOURCE:

This study was led by Jinjing Liu and Xiaofeng Zeng, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China. It was published online on November 27, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

As the study was conducted in a Chinese population, the findings may have limited applicability across diverse global populations. Additionally, as the placebo-controlled period was limited to 24 weeks because of ethical concerns, comparisons between placebo and ivarmacitinib beyond that period were restricted. Lastly, this study was not powered to compare efficacy and safety between the two active dose regimens.

DISCLOSURES:

This study was funded by Jiangsu Hengrui Pharmaceuticals. Two authors declared being employees of the company. The other authors reported no competing interests.

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:

Ivarmacitinib, a novel Janus kinase 1 inhibitor, alleviates symptoms, reduces disease activity, and improves physical function and quality of life in patients with moderate to severe rheumatoid arthritis (RA) who have an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

METHODOLOGY:

• This phase 3 trial, conducted across 59 sites in China, evaluated the efficacy and safety of ivarmacitinib in patients with moderate to severe active RA despite treatment with one or more csDMARDs.
• The patients were randomly assigned to receive either placebo (n = 188; mean age, 50.9 years; 85.6% women) or 4 mg ivarmacitinib (n = 189; mean age, 49.7 years; 91% women) or 8 mg ivarmacitinib (n = 189; mean age, 49.8 years; 83.6% women) once daily for 24 weeks, alongside background csDMARDs.
• After 24 weeks, the patients receiving placebo were switched to receive 4 mg ivarmacitinib for the additional 28-week extension period, whereas those receiving ivarmacitinib continued their initial dosage.
• Secondary endpoints included the proportion of patients achieving American College of Rheumatology (ACR) 50/70 responses and, Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP)) score < 2.6 or ≤ 3.2, as well as measures of other patient-reported outcomes such as pain, physical function, and quality of life at 24 and 52 weeks.

TAKEAWAY:

• At 24 weeks, the proportion of patients achieving a 20% improvement in the ACR20 response — the primary endpoint — was higher among those receiving 4 mg ivarmacitinib (70.4%) or 8 mg ivarmacitinib (75.1%) than among those receiving placebo (40.4%; P < .0001 for both comparisons), with the efficacy either maintained or improved through 52 weeks.
• The proportion of patients achieving ACR50/70 responses or a DAS28(CRP) score < 2.6 or ≤ 3.2 was higher in the ivarmacitinib groups than in the placebo group (P < .0001 for all comparisons).
• Compared with the placebo group, both the ivarmacitinib groups showed improvements in patient-reported outcomes such as pain, physical function, quality of life, and duration and severity of morning stiffness.
• The overall rates of treatment discontinuation caused by adverse events were low across all the groups, with no deaths, tuberculosis or gastrointestinal perforations reported throughout the 52 weeks.
•  

IN PRACTICE:

“Based on these findings, ivarmacitinib with background csDMARDs allowed, could be considered a treatment option in patients with moderate to severe active RA who have an inadequate response to csDMARDs,” the authors wrote.

SOURCE:

This study was led by Jinjing Liu and Xiaofeng Zeng, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China. It was published online on November 27, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

As the study was conducted in a Chinese population, the findings may have limited applicability across diverse global populations. Additionally, as the placebo-controlled period was limited to 24 weeks because of ethical concerns, comparisons between placebo and ivarmacitinib beyond that period were restricted. Lastly, this study was not powered to compare efficacy and safety between the two active dose regimens.

DISCLOSURES:

This study was funded by Jiangsu Hengrui Pharmaceuticals. Two authors declared being employees of the company. The other authors reported no competing interests.

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.

Identifying the phenomenon of post-exertional malaise (PEM) in patients with fatiguing conditions is critical because it necessitates a far more cautious approach to exercise, experts said.

PEM is a defining feature of the condition myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and it is present in many people with long COVID. It is characterized by a worsening of fatigue and of other symptoms after previously tolerated physical or mental exertion, typically emerging 24-72 hours after the exertion and lasting days or weeks thereafter. The experience is often called a “crash.”

In a study presented at the American College of Rheumatology (ACR) 2024 Annual Meeting, PEM was also identified in people with various rheumatologic conditions, ranging from 4% in those with osteoarthritis to 20% in those with fibromyalgia. The presence of PEM was also associated with worse pain, sleep, cognition, and other symptoms that are also characteristic of ME/CFS and many cases of long COVID.

“PEM assessment is becoming more important in those with long COVID, as we are assisting more of those with long durations of this condition. ... This is the first study we know of presenting PEM rates in a rheumatologic disease population,” Kaleb Michaud, PhD, director of FORWARD — The National Databank for Rheumatic Diseases and professor of rheumatology and immunology, University of Nebraska Medical Center, Omaha, said at the meeting.

During the discussion period, study investigator Leonard H. Calabrese, DO, head of the Section of Clinical Immunology, Cleveland Clinic, Ohio, commented, “PEM is seen with numerous post-acute infectious sequelae. It segregates with that population of patients who meet the diagnostic criteria for ME/CFS, of which 50%-70% of people will also meet criteria for fibromyalgia…This is a first step, but it has big ramifications regarding exercise.”

In an interview with this news organization, Calabrese said, “We recommend exercise to virtually everyone with fibromyalgia who doesn’t have ME/CFS,” but that the assessment tool used in the study, the 5-item DePaul Symptoms Questionnaire, isn’t adequate for assessing true PEM that would preclude exercise, despite being validated. “That instrument is inexact and lacks specificity. ... It just shows where the field is. We need better biomarkers.”

 

In Those With PEM, Exercise May Harm

Asked to comment, Brayden P. Yellman, MD, a rheumatologist at the Bateman Horne Center, Salt Lake City, Utah, told this news organization, “if there is an infection-associated chronic condition that meets criteria for what we would call ME/CFS or long COVID, and if there’s true post-exertional malaise, any graded exercise that ultimately leads to post-exertional malaise is harmful. ... There is a subset of people who have milder disease, who can sometimes do very mild exercise that does not trigger PEM, and they do see benefits over time very slowly with really carefully curated, carefully monitored exercise. But we have to be really careful.”

For the majority, however, the approach is to teach patients to pace their activities in order to avoid PEM, also referred to as staying within their “energy envelope.” Clinician resources are available on the Bateman Horne Center’s website.

This isn’t typically included in rheumatology training, Yellman noted. “Having completed an entire rheumatology fellowship and working in rheumatology, I was not taught at all about [then-termed] chronic fatigue syndrome. It was lumped under fibromyalgia. And of course, they teach about fibromyalgia because it’s a great mimic of a lot of inflammatory, rheumatologic conditions, but the idea of [PEM], that pathognomonic feature that we see in infection-associated chronic conditions, was not once mentioned when I trained, in 2014 to 2016.”

Nonetheless, he added, “rheumatologists are definitely seeing this in their fibromyalgia patients and some of their other patients at a high rate, and I’m sure that they’re missing it, along with other comorbidities like orthostatic hypotension.”

Another expert asked to weigh in, Todd Davenport, PT, DPT, PhD, professor and chair of the Department of Physical Therapy at the University of the Pacific, Stockton, California, told this news organization: “Our experience is that the body’s responses to short bouts of exercise are abnormal, and graded exercise is unsuccessful and makes people worse. ... Clinicians should be particularly on the lookout for PEM in patients who are already reporting fatigue, such as with fibromyalgia and rheumatologic conditions that can have some diagnostic overlaps with ME/CFS, because you can get fooled into thinking that your well-meaning exercise program intended to help give them a little more juice during their daily activities actually might be harmful.”

There are several lines of evidence for abnormal responses to exercise in people with PEM, Davenport said. These include muscle worsening, cardiac preload failure and impaired systemic oxygen extraction, metabolic dysregulation, and abnormal immunologic and neurologic changes.

Several studies show impaired recovery after 2-day cardiopulmonary exercise testing, with the largest to date published in July 2024. Patients with PEM have also reported harm from prescribed exercise.

Yellman commented: “We think of PEM like an injury, where you need to recover. If you keep stacking injuries on top of it, that injury is never going to heal the same way again…We are still trying to understand the pathophysiology of ME/CFS in general, and of PEM. But if you think of it as a neuroinflammatory injury, and there’s some evidence suggesting neuroinflammation, you can kind of understand the approach of needing to heal and to recover.”

 

How Prevalent Is PEM in Rheumatologic Conditions?

For the study presented at the ACR meeting, data of people with confirmed rheumatic diseases were taken from the ongoing longitudinal US-based research database FORWARD. Participants completed biannual self-reported questionnaires during January–June 2024 that included the 5-item PEM subscale from the validated DePaul Symptoms Questionnaire.

Questions relate to frequency and severity of each of the five items: “Dead, heavy feeling after starting to exercise,” “next-day soreness or fatigue after nonstrenuous, everyday activities,” “mentally tired after the slightest effort,” “minimum exercise makes you physically tired,” and “physically drained or sick after mild activity.” Participants are asked to rate each item on a scale from 0 if not present to 1 (mild/a little of the time) up to 4 (very severe/all of the time).

A positive PEM result was defined as a frequency of at least two and simultaneous severity of at least two on any survey item. Additional questions asked about recent and previous SARS-CoV-2 infections, long COVID diagnoses, and comorbidities.

Of 1158 individuals who completed the PEM questionnaire, 7.5% overall met PEM criteria. By individual condition, the proportions were 4.4% with osteoarthritis, 7.4% with rheumatoid arthritis, 12.2% with systemic lupus erythematosus, 13.8% with fibromyalgia diagnosed by rheumatologists, and 20.3% with fibromyalgia based on the 2016 revised ACR criteria.

The overall PEM prevalence was 8.3% among those reporting ever having COVID-19 and 9.5% among those who had COVID-19 during July–December 2023. The PEM prevalence increased more dramatically with more severe COVID-19 — 17.2% among those who had been hospitalized for COVID-19, 22.0% of those ever diagnosed with long COVID, and 28.1% with a long COVID diagnosis in January 2024.

By diagnosis, 50% of individuals who met the ACR’s 2016 fibromyalgia criteria and currently had long COVID scored positively for PEM.

Measures of pain, fatigue, sleep, patient global assessment, activity score, polysymptomatic distress, disability, depression, anxiety, and other functional scores were all significantly worse among those scoring positive for PEM (P < .001), Michaud reported.

 

Better Tools Are Available

The developer of the DePaul questionnaire, Leonard Jason, PhD, director of the Center for Community Research and professor of psychology at DePaul College of Science and Health, Chicago, Illinois, told this news organization that an updated 10-item screening tool specifically designed to screen for PEM adds some important elements missing from the 5-item version.

Here, patients are initially asked two questions: “Do you experience a worsening of your fatigue/energy related illness after engaging in minimal physical effort?” and “Do you experience a worsening of your fatigue/energy related illness after engaging in mental effort?” If they answer “yes” to either, the next question is “If you feel worse after activities, how long does this last?” Answers are coded from 0 to 6 (24 hours or more).

The fourth additional question then asks how quickly patients recover, while a fifth question asks whether the person is avoiding activity because it makes them feel worse (thereby potentially creating a false negative).

For those scoring positive on the 10-item screen, a more comprehensive measure could be used, such as this online screening tool, Jason said.

Yellman said that the Bateman Horne Center uses a “good day, bad day” questionnaire to tease out some of the same information. In addition, he noted that it’s important to capture the timeframe between the exertion and the onset of symptoms because PEM doesn’t start during or immediately after activity. “If somebody is mowing the lawn and they start feeling symptoms immediately, they’re probably, at least in ME/CFS, experiencing orthostatic intolerance. Post-exertional malaise occurs 12-72 hours later, when their function is severely reduced as compared to baseline.” 

And of course, Davenport noted, listening to patients is key. “Patients will tell you wildly unusual responses to activity before you even do the work of trying to figure out what the activity was. They’ll tell you things like they can’t think as well, that they have to be in bed for 3 days to a week to 2 weeks, depending on the level of exertion.”

Yellman, Davenport, and several other colleagues are currently working on a paper that will explain the differences between pacing and graded exercise, define PEM, and provide guidelines. They aim to submit it in time for publication early in 2025. In the meantime, the Bateman Horne Center’s website provides numerous resources for healthcare professionals and patients.

Yellman is also working to define minimum quality of care standards for infection-associated chronic conditions for state medical boards and to provide continuing medical education for clinicians on those standards. These would include recognizing and evaluating patients for PEM, as well as orthostatic intolerance, cognitive impairment, and other associated comorbidities.

Importantly, he said, the standards will include the principles of teaching people with PEM how to pace and will emphasize not prescribing them graded exercise as first- or even second-line therapy. “We need people to do some basic things. And the first thing is do no harm.”

None of the individuals quoted for this article had relevant financial disclosures.

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

Identifying the phenomenon of post-exertional malaise (PEM) in patients with fatiguing conditions is critical because it necessitates a far more cautious approach to exercise, experts said.

PEM is a defining feature of the condition myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and it is present in many people with long COVID. It is characterized by a worsening of fatigue and of other symptoms after previously tolerated physical or mental exertion, typically emerging 24-72 hours after the exertion and lasting days or weeks thereafter. The experience is often called a “crash.”

In a study presented at the American College of Rheumatology (ACR) 2024 Annual Meeting, PEM was also identified in people with various rheumatologic conditions, ranging from 4% in those with osteoarthritis to 20% in those with fibromyalgia. The presence of PEM was also associated with worse pain, sleep, cognition, and other symptoms that are also characteristic of ME/CFS and many cases of long COVID.

“PEM assessment is becoming more important in those with long COVID, as we are assisting more of those with long durations of this condition. ... This is the first study we know of presenting PEM rates in a rheumatologic disease population,” Kaleb Michaud, PhD, director of FORWARD — The National Databank for Rheumatic Diseases and professor of rheumatology and immunology, University of Nebraska Medical Center, Omaha, said at the meeting.

During the discussion period, study investigator Leonard H. Calabrese, DO, head of the Section of Clinical Immunology, Cleveland Clinic, Ohio, commented, “PEM is seen with numerous post-acute infectious sequelae. It segregates with that population of patients who meet the diagnostic criteria for ME/CFS, of which 50%-70% of people will also meet criteria for fibromyalgia…This is a first step, but it has big ramifications regarding exercise.”

In an interview with this news organization, Calabrese said, “We recommend exercise to virtually everyone with fibromyalgia who doesn’t have ME/CFS,” but that the assessment tool used in the study, the 5-item DePaul Symptoms Questionnaire, isn’t adequate for assessing true PEM that would preclude exercise, despite being validated. “That instrument is inexact and lacks specificity. ... It just shows where the field is. We need better biomarkers.”

 

In Those With PEM, Exercise May Harm

Asked to comment, Brayden P. Yellman, MD, a rheumatologist at the Bateman Horne Center, Salt Lake City, Utah, told this news organization, “if there is an infection-associated chronic condition that meets criteria for what we would call ME/CFS or long COVID, and if there’s true post-exertional malaise, any graded exercise that ultimately leads to post-exertional malaise is harmful. ... There is a subset of people who have milder disease, who can sometimes do very mild exercise that does not trigger PEM, and they do see benefits over time very slowly with really carefully curated, carefully monitored exercise. But we have to be really careful.”

For the majority, however, the approach is to teach patients to pace their activities in order to avoid PEM, also referred to as staying within their “energy envelope.” Clinician resources are available on the Bateman Horne Center’s website.

This isn’t typically included in rheumatology training, Yellman noted. “Having completed an entire rheumatology fellowship and working in rheumatology, I was not taught at all about [then-termed] chronic fatigue syndrome. It was lumped under fibromyalgia. And of course, they teach about fibromyalgia because it’s a great mimic of a lot of inflammatory, rheumatologic conditions, but the idea of [PEM], that pathognomonic feature that we see in infection-associated chronic conditions, was not once mentioned when I trained, in 2014 to 2016.”

Nonetheless, he added, “rheumatologists are definitely seeing this in their fibromyalgia patients and some of their other patients at a high rate, and I’m sure that they’re missing it, along with other comorbidities like orthostatic hypotension.”

Another expert asked to weigh in, Todd Davenport, PT, DPT, PhD, professor and chair of the Department of Physical Therapy at the University of the Pacific, Stockton, California, told this news organization: “Our experience is that the body’s responses to short bouts of exercise are abnormal, and graded exercise is unsuccessful and makes people worse. ... Clinicians should be particularly on the lookout for PEM in patients who are already reporting fatigue, such as with fibromyalgia and rheumatologic conditions that can have some diagnostic overlaps with ME/CFS, because you can get fooled into thinking that your well-meaning exercise program intended to help give them a little more juice during their daily activities actually might be harmful.”

There are several lines of evidence for abnormal responses to exercise in people with PEM, Davenport said. These include muscle worsening, cardiac preload failure and impaired systemic oxygen extraction, metabolic dysregulation, and abnormal immunologic and neurologic changes.

Several studies show impaired recovery after 2-day cardiopulmonary exercise testing, with the largest to date published in July 2024. Patients with PEM have also reported harm from prescribed exercise.

Yellman commented: “We think of PEM like an injury, where you need to recover. If you keep stacking injuries on top of it, that injury is never going to heal the same way again…We are still trying to understand the pathophysiology of ME/CFS in general, and of PEM. But if you think of it as a neuroinflammatory injury, and there’s some evidence suggesting neuroinflammation, you can kind of understand the approach of needing to heal and to recover.”

 

How Prevalent Is PEM in Rheumatologic Conditions?

For the study presented at the ACR meeting, data of people with confirmed rheumatic diseases were taken from the ongoing longitudinal US-based research database FORWARD. Participants completed biannual self-reported questionnaires during January–June 2024 that included the 5-item PEM subscale from the validated DePaul Symptoms Questionnaire.

Questions relate to frequency and severity of each of the five items: “Dead, heavy feeling after starting to exercise,” “next-day soreness or fatigue after nonstrenuous, everyday activities,” “mentally tired after the slightest effort,” “minimum exercise makes you physically tired,” and “physically drained or sick after mild activity.” Participants are asked to rate each item on a scale from 0 if not present to 1 (mild/a little of the time) up to 4 (very severe/all of the time).

A positive PEM result was defined as a frequency of at least two and simultaneous severity of at least two on any survey item. Additional questions asked about recent and previous SARS-CoV-2 infections, long COVID diagnoses, and comorbidities.

Of 1158 individuals who completed the PEM questionnaire, 7.5% overall met PEM criteria. By individual condition, the proportions were 4.4% with osteoarthritis, 7.4% with rheumatoid arthritis, 12.2% with systemic lupus erythematosus, 13.8% with fibromyalgia diagnosed by rheumatologists, and 20.3% with fibromyalgia based on the 2016 revised ACR criteria.

The overall PEM prevalence was 8.3% among those reporting ever having COVID-19 and 9.5% among those who had COVID-19 during July–December 2023. The PEM prevalence increased more dramatically with more severe COVID-19 — 17.2% among those who had been hospitalized for COVID-19, 22.0% of those ever diagnosed with long COVID, and 28.1% with a long COVID diagnosis in January 2024.

By diagnosis, 50% of individuals who met the ACR’s 2016 fibromyalgia criteria and currently had long COVID scored positively for PEM.

Measures of pain, fatigue, sleep, patient global assessment, activity score, polysymptomatic distress, disability, depression, anxiety, and other functional scores were all significantly worse among those scoring positive for PEM (P < .001), Michaud reported.

 

Better Tools Are Available

The developer of the DePaul questionnaire, Leonard Jason, PhD, director of the Center for Community Research and professor of psychology at DePaul College of Science and Health, Chicago, Illinois, told this news organization that an updated 10-item screening tool specifically designed to screen for PEM adds some important elements missing from the 5-item version.

Here, patients are initially asked two questions: “Do you experience a worsening of your fatigue/energy related illness after engaging in minimal physical effort?” and “Do you experience a worsening of your fatigue/energy related illness after engaging in mental effort?” If they answer “yes” to either, the next question is “If you feel worse after activities, how long does this last?” Answers are coded from 0 to 6 (24 hours or more).

The fourth additional question then asks how quickly patients recover, while a fifth question asks whether the person is avoiding activity because it makes them feel worse (thereby potentially creating a false negative).

For those scoring positive on the 10-item screen, a more comprehensive measure could be used, such as this online screening tool, Jason said.

Yellman said that the Bateman Horne Center uses a “good day, bad day” questionnaire to tease out some of the same information. In addition, he noted that it’s important to capture the timeframe between the exertion and the onset of symptoms because PEM doesn’t start during or immediately after activity. “If somebody is mowing the lawn and they start feeling symptoms immediately, they’re probably, at least in ME/CFS, experiencing orthostatic intolerance. Post-exertional malaise occurs 12-72 hours later, when their function is severely reduced as compared to baseline.” 

And of course, Davenport noted, listening to patients is key. “Patients will tell you wildly unusual responses to activity before you even do the work of trying to figure out what the activity was. They’ll tell you things like they can’t think as well, that they have to be in bed for 3 days to a week to 2 weeks, depending on the level of exertion.”

Yellman, Davenport, and several other colleagues are currently working on a paper that will explain the differences between pacing and graded exercise, define PEM, and provide guidelines. They aim to submit it in time for publication early in 2025. In the meantime, the Bateman Horne Center’s website provides numerous resources for healthcare professionals and patients.

Yellman is also working to define minimum quality of care standards for infection-associated chronic conditions for state medical boards and to provide continuing medical education for clinicians on those standards. These would include recognizing and evaluating patients for PEM, as well as orthostatic intolerance, cognitive impairment, and other associated comorbidities.

Importantly, he said, the standards will include the principles of teaching people with PEM how to pace and will emphasize not prescribing them graded exercise as first- or even second-line therapy. “We need people to do some basic things. And the first thing is do no harm.”

None of the individuals quoted for this article had relevant financial disclosures.

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

Identifying the phenomenon of post-exertional malaise (PEM) in patients with fatiguing conditions is critical because it necessitates a far more cautious approach to exercise, experts said.

PEM is a defining feature of the condition myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and it is present in many people with long COVID. It is characterized by a worsening of fatigue and of other symptoms after previously tolerated physical or mental exertion, typically emerging 24-72 hours after the exertion and lasting days or weeks thereafter. The experience is often called a “crash.”

In a study presented at the American College of Rheumatology (ACR) 2024 Annual Meeting, PEM was also identified in people with various rheumatologic conditions, ranging from 4% in those with osteoarthritis to 20% in those with fibromyalgia. The presence of PEM was also associated with worse pain, sleep, cognition, and other symptoms that are also characteristic of ME/CFS and many cases of long COVID.

“PEM assessment is becoming more important in those with long COVID, as we are assisting more of those with long durations of this condition. ... This is the first study we know of presenting PEM rates in a rheumatologic disease population,” Kaleb Michaud, PhD, director of FORWARD — The National Databank for Rheumatic Diseases and professor of rheumatology and immunology, University of Nebraska Medical Center, Omaha, said at the meeting.

During the discussion period, study investigator Leonard H. Calabrese, DO, head of the Section of Clinical Immunology, Cleveland Clinic, Ohio, commented, “PEM is seen with numerous post-acute infectious sequelae. It segregates with that population of patients who meet the diagnostic criteria for ME/CFS, of which 50%-70% of people will also meet criteria for fibromyalgia…This is a first step, but it has big ramifications regarding exercise.”

In an interview with this news organization, Calabrese said, “We recommend exercise to virtually everyone with fibromyalgia who doesn’t have ME/CFS,” but that the assessment tool used in the study, the 5-item DePaul Symptoms Questionnaire, isn’t adequate for assessing true PEM that would preclude exercise, despite being validated. “That instrument is inexact and lacks specificity. ... It just shows where the field is. We need better biomarkers.”

 

In Those With PEM, Exercise May Harm

Asked to comment, Brayden P. Yellman, MD, a rheumatologist at the Bateman Horne Center, Salt Lake City, Utah, told this news organization, “if there is an infection-associated chronic condition that meets criteria for what we would call ME/CFS or long COVID, and if there’s true post-exertional malaise, any graded exercise that ultimately leads to post-exertional malaise is harmful. ... There is a subset of people who have milder disease, who can sometimes do very mild exercise that does not trigger PEM, and they do see benefits over time very slowly with really carefully curated, carefully monitored exercise. But we have to be really careful.”

For the majority, however, the approach is to teach patients to pace their activities in order to avoid PEM, also referred to as staying within their “energy envelope.” Clinician resources are available on the Bateman Horne Center’s website.

This isn’t typically included in rheumatology training, Yellman noted. “Having completed an entire rheumatology fellowship and working in rheumatology, I was not taught at all about [then-termed] chronic fatigue syndrome. It was lumped under fibromyalgia. And of course, they teach about fibromyalgia because it’s a great mimic of a lot of inflammatory, rheumatologic conditions, but the idea of [PEM], that pathognomonic feature that we see in infection-associated chronic conditions, was not once mentioned when I trained, in 2014 to 2016.”

Nonetheless, he added, “rheumatologists are definitely seeing this in their fibromyalgia patients and some of their other patients at a high rate, and I’m sure that they’re missing it, along with other comorbidities like orthostatic hypotension.”

Another expert asked to weigh in, Todd Davenport, PT, DPT, PhD, professor and chair of the Department of Physical Therapy at the University of the Pacific, Stockton, California, told this news organization: “Our experience is that the body’s responses to short bouts of exercise are abnormal, and graded exercise is unsuccessful and makes people worse. ... Clinicians should be particularly on the lookout for PEM in patients who are already reporting fatigue, such as with fibromyalgia and rheumatologic conditions that can have some diagnostic overlaps with ME/CFS, because you can get fooled into thinking that your well-meaning exercise program intended to help give them a little more juice during their daily activities actually might be harmful.”

There are several lines of evidence for abnormal responses to exercise in people with PEM, Davenport said. These include muscle worsening, cardiac preload failure and impaired systemic oxygen extraction, metabolic dysregulation, and abnormal immunologic and neurologic changes.

Several studies show impaired recovery after 2-day cardiopulmonary exercise testing, with the largest to date published in July 2024. Patients with PEM have also reported harm from prescribed exercise.

Yellman commented: “We think of PEM like an injury, where you need to recover. If you keep stacking injuries on top of it, that injury is never going to heal the same way again…We are still trying to understand the pathophysiology of ME/CFS in general, and of PEM. But if you think of it as a neuroinflammatory injury, and there’s some evidence suggesting neuroinflammation, you can kind of understand the approach of needing to heal and to recover.”

 

How Prevalent Is PEM in Rheumatologic Conditions?

For the study presented at the ACR meeting, data of people with confirmed rheumatic diseases were taken from the ongoing longitudinal US-based research database FORWARD. Participants completed biannual self-reported questionnaires during January–June 2024 that included the 5-item PEM subscale from the validated DePaul Symptoms Questionnaire.

Questions relate to frequency and severity of each of the five items: “Dead, heavy feeling after starting to exercise,” “next-day soreness or fatigue after nonstrenuous, everyday activities,” “mentally tired after the slightest effort,” “minimum exercise makes you physically tired,” and “physically drained or sick after mild activity.” Participants are asked to rate each item on a scale from 0 if not present to 1 (mild/a little of the time) up to 4 (very severe/all of the time).

A positive PEM result was defined as a frequency of at least two and simultaneous severity of at least two on any survey item. Additional questions asked about recent and previous SARS-CoV-2 infections, long COVID diagnoses, and comorbidities.

Of 1158 individuals who completed the PEM questionnaire, 7.5% overall met PEM criteria. By individual condition, the proportions were 4.4% with osteoarthritis, 7.4% with rheumatoid arthritis, 12.2% with systemic lupus erythematosus, 13.8% with fibromyalgia diagnosed by rheumatologists, and 20.3% with fibromyalgia based on the 2016 revised ACR criteria.

The overall PEM prevalence was 8.3% among those reporting ever having COVID-19 and 9.5% among those who had COVID-19 during July–December 2023. The PEM prevalence increased more dramatically with more severe COVID-19 — 17.2% among those who had been hospitalized for COVID-19, 22.0% of those ever diagnosed with long COVID, and 28.1% with a long COVID diagnosis in January 2024.

By diagnosis, 50% of individuals who met the ACR’s 2016 fibromyalgia criteria and currently had long COVID scored positively for PEM.

Measures of pain, fatigue, sleep, patient global assessment, activity score, polysymptomatic distress, disability, depression, anxiety, and other functional scores were all significantly worse among those scoring positive for PEM (P < .001), Michaud reported.

 

Better Tools Are Available

The developer of the DePaul questionnaire, Leonard Jason, PhD, director of the Center for Community Research and professor of psychology at DePaul College of Science and Health, Chicago, Illinois, told this news organization that an updated 10-item screening tool specifically designed to screen for PEM adds some important elements missing from the 5-item version.

Here, patients are initially asked two questions: “Do you experience a worsening of your fatigue/energy related illness after engaging in minimal physical effort?” and “Do you experience a worsening of your fatigue/energy related illness after engaging in mental effort?” If they answer “yes” to either, the next question is “If you feel worse after activities, how long does this last?” Answers are coded from 0 to 6 (24 hours or more).

The fourth additional question then asks how quickly patients recover, while a fifth question asks whether the person is avoiding activity because it makes them feel worse (thereby potentially creating a false negative).

For those scoring positive on the 10-item screen, a more comprehensive measure could be used, such as this online screening tool, Jason said.

Yellman said that the Bateman Horne Center uses a “good day, bad day” questionnaire to tease out some of the same information. In addition, he noted that it’s important to capture the timeframe between the exertion and the onset of symptoms because PEM doesn’t start during or immediately after activity. “If somebody is mowing the lawn and they start feeling symptoms immediately, they’re probably, at least in ME/CFS, experiencing orthostatic intolerance. Post-exertional malaise occurs 12-72 hours later, when their function is severely reduced as compared to baseline.” 

And of course, Davenport noted, listening to patients is key. “Patients will tell you wildly unusual responses to activity before you even do the work of trying to figure out what the activity was. They’ll tell you things like they can’t think as well, that they have to be in bed for 3 days to a week to 2 weeks, depending on the level of exertion.”

Yellman, Davenport, and several other colleagues are currently working on a paper that will explain the differences between pacing and graded exercise, define PEM, and provide guidelines. They aim to submit it in time for publication early in 2025. In the meantime, the Bateman Horne Center’s website provides numerous resources for healthcare professionals and patients.

Yellman is also working to define minimum quality of care standards for infection-associated chronic conditions for state medical boards and to provide continuing medical education for clinicians on those standards. These would include recognizing and evaluating patients for PEM, as well as orthostatic intolerance, cognitive impairment, and other associated comorbidities.

Importantly, he said, the standards will include the principles of teaching people with PEM how to pace and will emphasize not prescribing them graded exercise as first- or even second-line therapy. “We need people to do some basic things. And the first thing is do no harm.”

None of the individuals quoted for this article had relevant financial disclosures.

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

While fewer than 10% of US physicians are unionized, the number of official union drives among private-sector doctors have skyrocketed in the last 2 years, compared with 2 decades prior, according to a new study. 

Researchers counted 21 union drives in 2023 and 12 in the first 5 months of 2024, compared with 0-6 drives each year between 2000 and 2022. 

If the 2023 and 2024 drives succeed, unions will represent 3523 new physicians — nearly equal to the 3541 doctors who sought unionization between 2000 and 2022.

“We were able to document a significant uptick in union petitions and success in certification drives,” said corresponding author Hayden Rooke-Ley, JD, of the Center for Advancing Health Policy Through Research, Brown University School of Public Health, Providence, Rhode Island. “We were surprised to see such a marked shift in 2023.”

About 72,000 physicians, an estimated 8% of all US doctors, are covered by unions, including some in the public sector. Physicians who are self-employed, now comprising less than a fifth of all doctors, are not eligible to join labor unions.

The study authors launched their research to better understand trends in physician unionization in light of high-profile union drives, especially among residents. Rooke-Ley said: “We suspected that declining morale and increased corporate employment for physicians were leading them to consider unionization.”

The researchers gathered data from the National Labor Relations Board about union drives by potential bargaining units that included physicians. From 2000 to 2022, 44 union petitions were filed. The number jumped to 33 from 2023-2024. 

 

“Tip of the Iceberg”

“This is the tip of the iceberg,” said ethicist Joseph F. Kras, MD, DDS, MA, an associate professor of anesthesiology at Washington University in St. Louis, Missouri, and corresponding author of a recent Anesthesia & Analgesia report about physician unionization.

“We are independent by nature,” Kras said. “But when you put us in an employed environment and start treating us as widgets, then we will act like employees of Amazon, Starbucks, and other companies and join together to push back against the increasing emphasis on profit over all at the expense of our independent judgment on what’s best for the patient.”

Of the 66 unionization efforts between 2000 and 2024 that were decided, 62% were certified, according to the JAMA study. The drives targeted hospitals (49%), community health centers (38%), and nonhospital corporate owners (13%).

The researchers only analyzed private-sector unionization and did not include physicians who are unionized at public institutions. 

 

What’s Behind Union Drives?

Alyssa Burgart, MD, MA, an ethicist and clinical associate professor of anesthesiology and pediatrics at Stanford University in California, told this news organization that physician unionization “is a big topic with a lot of really strong opinions.” 

Many doctors wrongly assume they can’t unionize because they’re physicians, said Burgart, a coauthor of the Anesthesia & Analgesia report.

Supporters of unionization believe it’s a strategy to be “recognized not as simply as a single physician with a concern,” she said. “When you’re among clinicians who can speak as a more unified group, organizations are more likely to take that seriously.”

A union may also be able to hold employers to account in areas such as the gender wage gap, sexual harassment, and bias in hiring and firing, Burgart said. And union supporters believe they’ll make more money if they collectively bargain. 

Other factors driving interest in unions include “increasing physician burnout, increasing physician exhaustion, and immense frustration with the ways that private equity is influencing how physicians need to work in order to practice,” she said. 

Earlier in 2024, physicians in Delaware’s ChristianaCare health system voted 288-130 to be represented by Doctors Council/Service Employees International, according to the union. 

“We have still not been able to staff up enough to where us physicians can get back to just focusing on taking care of patients,” a unionization leader told WHYY. 

The JAMA study examined news reports regarding most of the 2023-2024 union drives and found that supporters claimed they were motivated by working conditions (85%), lack of voice in management (81%), patient care concerns (54%), and pay (4%).

 

Critics Worry They’ll Lose Pay Because of Unions

Skeptics of unionization worry about whether “I’m going to be required to stand by some union stance that is actually out of alignment with my values as a physician,” Burgart said. And, she said, critics such as highly paid surgeons fear that adjustments to salaries because of union contracts could cause them to lose income.

In regard to compensation, a 2024 study surveyed unionized residents — along with faculty and staff — at general surgery programs and found evidence that unionization didn’t improve resident well-being or benefits, although it “provided a mechanism for resident voice and agency.”

“It is critical to study the outcomes of those who unionized to ensure that the reasons for unionizing were realized over time,” said that study’s coauthor Karl Bilimoria, MD, MS, chair of surgery at Indiana University School of Medicine, Indianapolis. “The unintended consequences of unionization must be examined along with the potential improvements.”

Rooke-Ley discloses consulting fees from the American Economic Liberties Project, National Academy of State Health Policy, and 32BJ Funds. Kras and Burgart disclose previous union membership. Bilimoria has no disclosures.

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

While fewer than 10% of US physicians are unionized, the number of official union drives among private-sector doctors have skyrocketed in the last 2 years, compared with 2 decades prior, according to a new study. 

Researchers counted 21 union drives in 2023 and 12 in the first 5 months of 2024, compared with 0-6 drives each year between 2000 and 2022. 

If the 2023 and 2024 drives succeed, unions will represent 3523 new physicians — nearly equal to the 3541 doctors who sought unionization between 2000 and 2022.

“We were able to document a significant uptick in union petitions and success in certification drives,” said corresponding author Hayden Rooke-Ley, JD, of the Center for Advancing Health Policy Through Research, Brown University School of Public Health, Providence, Rhode Island. “We were surprised to see such a marked shift in 2023.”

About 72,000 physicians, an estimated 8% of all US doctors, are covered by unions, including some in the public sector. Physicians who are self-employed, now comprising less than a fifth of all doctors, are not eligible to join labor unions.

The study authors launched their research to better understand trends in physician unionization in light of high-profile union drives, especially among residents. Rooke-Ley said: “We suspected that declining morale and increased corporate employment for physicians were leading them to consider unionization.”

The researchers gathered data from the National Labor Relations Board about union drives by potential bargaining units that included physicians. From 2000 to 2022, 44 union petitions were filed. The number jumped to 33 from 2023-2024. 

 

“Tip of the Iceberg”

“This is the tip of the iceberg,” said ethicist Joseph F. Kras, MD, DDS, MA, an associate professor of anesthesiology at Washington University in St. Louis, Missouri, and corresponding author of a recent Anesthesia & Analgesia report about physician unionization.

“We are independent by nature,” Kras said. “But when you put us in an employed environment and start treating us as widgets, then we will act like employees of Amazon, Starbucks, and other companies and join together to push back against the increasing emphasis on profit over all at the expense of our independent judgment on what’s best for the patient.”

Of the 66 unionization efforts between 2000 and 2024 that were decided, 62% were certified, according to the JAMA study. The drives targeted hospitals (49%), community health centers (38%), and nonhospital corporate owners (13%).

The researchers only analyzed private-sector unionization and did not include physicians who are unionized at public institutions. 

 

What’s Behind Union Drives?

Alyssa Burgart, MD, MA, an ethicist and clinical associate professor of anesthesiology and pediatrics at Stanford University in California, told this news organization that physician unionization “is a big topic with a lot of really strong opinions.” 

Many doctors wrongly assume they can’t unionize because they’re physicians, said Burgart, a coauthor of the Anesthesia & Analgesia report.

Supporters of unionization believe it’s a strategy to be “recognized not as simply as a single physician with a concern,” she said. “When you’re among clinicians who can speak as a more unified group, organizations are more likely to take that seriously.”

A union may also be able to hold employers to account in areas such as the gender wage gap, sexual harassment, and bias in hiring and firing, Burgart said. And union supporters believe they’ll make more money if they collectively bargain. 

Other factors driving interest in unions include “increasing physician burnout, increasing physician exhaustion, and immense frustration with the ways that private equity is influencing how physicians need to work in order to practice,” she said. 

Earlier in 2024, physicians in Delaware’s ChristianaCare health system voted 288-130 to be represented by Doctors Council/Service Employees International, according to the union. 

“We have still not been able to staff up enough to where us physicians can get back to just focusing on taking care of patients,” a unionization leader told WHYY. 

The JAMA study examined news reports regarding most of the 2023-2024 union drives and found that supporters claimed they were motivated by working conditions (85%), lack of voice in management (81%), patient care concerns (54%), and pay (4%).

 

Critics Worry They’ll Lose Pay Because of Unions

Skeptics of unionization worry about whether “I’m going to be required to stand by some union stance that is actually out of alignment with my values as a physician,” Burgart said. And, she said, critics such as highly paid surgeons fear that adjustments to salaries because of union contracts could cause them to lose income.

In regard to compensation, a 2024 study surveyed unionized residents — along with faculty and staff — at general surgery programs and found evidence that unionization didn’t improve resident well-being or benefits, although it “provided a mechanism for resident voice and agency.”

“It is critical to study the outcomes of those who unionized to ensure that the reasons for unionizing were realized over time,” said that study’s coauthor Karl Bilimoria, MD, MS, chair of surgery at Indiana University School of Medicine, Indianapolis. “The unintended consequences of unionization must be examined along with the potential improvements.”

Rooke-Ley discloses consulting fees from the American Economic Liberties Project, National Academy of State Health Policy, and 32BJ Funds. Kras and Burgart disclose previous union membership. Bilimoria has no disclosures.

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

While fewer than 10% of US physicians are unionized, the number of official union drives among private-sector doctors have skyrocketed in the last 2 years, compared with 2 decades prior, according to a new study. 

Researchers counted 21 union drives in 2023 and 12 in the first 5 months of 2024, compared with 0-6 drives each year between 2000 and 2022. 

If the 2023 and 2024 drives succeed, unions will represent 3523 new physicians — nearly equal to the 3541 doctors who sought unionization between 2000 and 2022.

“We were able to document a significant uptick in union petitions and success in certification drives,” said corresponding author Hayden Rooke-Ley, JD, of the Center for Advancing Health Policy Through Research, Brown University School of Public Health, Providence, Rhode Island. “We were surprised to see such a marked shift in 2023.”

About 72,000 physicians, an estimated 8% of all US doctors, are covered by unions, including some in the public sector. Physicians who are self-employed, now comprising less than a fifth of all doctors, are not eligible to join labor unions.

The study authors launched their research to better understand trends in physician unionization in light of high-profile union drives, especially among residents. Rooke-Ley said: “We suspected that declining morale and increased corporate employment for physicians were leading them to consider unionization.”

The researchers gathered data from the National Labor Relations Board about union drives by potential bargaining units that included physicians. From 2000 to 2022, 44 union petitions were filed. The number jumped to 33 from 2023-2024. 

 

“Tip of the Iceberg”

“This is the tip of the iceberg,” said ethicist Joseph F. Kras, MD, DDS, MA, an associate professor of anesthesiology at Washington University in St. Louis, Missouri, and corresponding author of a recent Anesthesia & Analgesia report about physician unionization.

“We are independent by nature,” Kras said. “But when you put us in an employed environment and start treating us as widgets, then we will act like employees of Amazon, Starbucks, and other companies and join together to push back against the increasing emphasis on profit over all at the expense of our independent judgment on what’s best for the patient.”

Of the 66 unionization efforts between 2000 and 2024 that were decided, 62% were certified, according to the JAMA study. The drives targeted hospitals (49%), community health centers (38%), and nonhospital corporate owners (13%).

The researchers only analyzed private-sector unionization and did not include physicians who are unionized at public institutions. 

 

What’s Behind Union Drives?

Alyssa Burgart, MD, MA, an ethicist and clinical associate professor of anesthesiology and pediatrics at Stanford University in California, told this news organization that physician unionization “is a big topic with a lot of really strong opinions.” 

Many doctors wrongly assume they can’t unionize because they’re physicians, said Burgart, a coauthor of the Anesthesia & Analgesia report.

Supporters of unionization believe it’s a strategy to be “recognized not as simply as a single physician with a concern,” she said. “When you’re among clinicians who can speak as a more unified group, organizations are more likely to take that seriously.”

A union may also be able to hold employers to account in areas such as the gender wage gap, sexual harassment, and bias in hiring and firing, Burgart said. And union supporters believe they’ll make more money if they collectively bargain. 

Other factors driving interest in unions include “increasing physician burnout, increasing physician exhaustion, and immense frustration with the ways that private equity is influencing how physicians need to work in order to practice,” she said. 

Earlier in 2024, physicians in Delaware’s ChristianaCare health system voted 288-130 to be represented by Doctors Council/Service Employees International, according to the union. 

“We have still not been able to staff up enough to where us physicians can get back to just focusing on taking care of patients,” a unionization leader told WHYY. 

The JAMA study examined news reports regarding most of the 2023-2024 union drives and found that supporters claimed they were motivated by working conditions (85%), lack of voice in management (81%), patient care concerns (54%), and pay (4%).

 

Critics Worry They’ll Lose Pay Because of Unions

Skeptics of unionization worry about whether “I’m going to be required to stand by some union stance that is actually out of alignment with my values as a physician,” Burgart said. And, she said, critics such as highly paid surgeons fear that adjustments to salaries because of union contracts could cause them to lose income.

In regard to compensation, a 2024 study surveyed unionized residents — along with faculty and staff — at general surgery programs and found evidence that unionization didn’t improve resident well-being or benefits, although it “provided a mechanism for resident voice and agency.”

“It is critical to study the outcomes of those who unionized to ensure that the reasons for unionizing were realized over time,” said that study’s coauthor Karl Bilimoria, MD, MS, chair of surgery at Indiana University School of Medicine, Indianapolis. “The unintended consequences of unionization must be examined along with the potential improvements.”

Rooke-Ley discloses consulting fees from the American Economic Liberties Project, National Academy of State Health Policy, and 32BJ Funds. Kras and Burgart disclose previous union membership. Bilimoria has no disclosures.

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

Interleukin-6 receptor (IL-6r) inhibition is a promising approach for the treatment of calcium pyrophosphate deposition disease (CPPD), although no prospective studies have been conducted to date. Nevertheless, a retrospective analysis of patients treated with the IL-6r inhibitor tocilizumab, presented at American College of Rheumatology (ACR) 2024 Annual Meeting, showed improved CPPD control in more than two thirds of patients who had failed or could not tolerate usual therapies.

Both the monosodium urate (MSU) crystals associated with gout and CPP crystals induce inflammation dependent on IL-1 beta, but IL-1 beta inhibitors have been investigated more as treatments for gout than for CPPD, and they are recommended by both ACR and European Alliance of Associations for Rheumatology (EULAR) guidelines for patients with gout who have flares despite efforts to treat with colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids. However, IL-1 beta inhibitors are sometimes used off label in CPPD.

There are similarities among the various crystal types that induce arthritis, typically producing similar clinical features of acute arthritis and severe pain and local inflammation and tending to self-resolve within days to weeks. Those shared clinical features suggest common inflammatory mechanisms, likely stemming from the innate immune system, said Augustin Latourte, MD, PhD, of Lariboisière Hospital, Paris, France, during a talk on the topic at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network (G-CAN).

CPPD management is generally derived from strategies developed for gout, but there is little evidence supporting IL-1 beta inhibitors outside of case reports, he said. One clinical trial published in 2020 showed efficacy of the IL-1 inhibitor anakinra, but the study was halted due to low patient recruitment, resulting in a small study population. In that study, “anakinra seems to have a faster onset of action than prednisone and could be useful in specific situations regarding acute CPPD arthritis. But it’s not relevant for chronic CPPD arthritis when you have persistent polyarthritis requiring chronic treatment. Anakinra requires daily injections and may not be appropriate in this situation,” he said.

IL-6r inhibition has been studied since IL-6 was first discovered in 1989 as a mediator of inflammatory responses in gout and CPPD, when it was shown that both CPP and MSU crystals can stimulate its production. In monocytes, IL-6 is expressed at higher levels than IL-1 beta in response to both CPP and MSU crystals. IL-6 production in monocytes in response to crystals is dependent on IL-1, and IL-1 inhibition reduces IL-6 production. “So the hypothesis is that IL-1 beta is the first event, and the production of IL-6 and the amplification of crystal inflammation occurs downstream before the self-limitation of the crystal-induced arthritis. IL-6 may be a very important event in the onset of crystal-induced inflammation,” Latourte said.

 

Building on Mechanistic Insights to Test Off-Label Use of Tocilizumab

Inspired by this insight, Latourte’s group tested tocilizumab in a 28-year-old man with a familial ANKH mutation who had not responded to anakinra and other conventional treatments. The patient experienced a reduction in flare intensity in the first month after the initial treatment and no flares after the second tocilizumab infusion. The group went on to test tocilizumab in 10 additional patients with CPPD (median age, 62.5 years), including 6 with idiopathic CPPD, 3 with Gitelman syndrome, and 1 with ANKH mutation. The clinical presentation included four with recurrent acute arthritis and six with chronic polyarthritis, and all had x-ray–proven disease, with a median visual analog scale (VAS) of 60 mm out of 100 mm. Tocilizumab was administered intravenously or subcutaneously. At 3 months, there was a median improvement of 30 mm in the VAS. Treatment efficacy continued for a median follow-up of 5.5 months at the time of publication, and the researchers have noted ongoing efficacy out to 50 months for some patients.

Tocilizumab has gone on to more frequent use in Europe as a second- or third-line therapy for CPPD, which led Latourte and his colleagues to perform the retrospective analysis that they presented at the ACR meeting. It included 55 patients who received tocilizumab for chronic inflammatory CPPD at two university hospitals. Participants had a median age of 72 years, and 67.3% were women. The patient group included 39 with chronic CPPD, 14 with recurrent acute CPPD (who experienced 0-4 attacks per month), and two patients with mixed CPPD. All participants had been treated with colchicine, and 20 had been treated also with prednisone and 24 with anakinra. Patients had stopped anakinra because it was either ineffective (n = 13) or poorly tolerated (n = 11).

Tocilizumab was administered intravenously in 46 patients and subcutaneously in nine patients for a median duration of 16.5 months (range, 0.8-76.4 months). The median VAS for pain (0- to 100-mm scale) dropped from 60 mm at baseline to 40 mm at 3 months and 30 mm at 6 months. There were 21 adverse events, including 8 cytopenias, 6 transaminase elevations, 4 infections (two severe), and 3 injection-site reactions. After a median of 7.8 months, 26 patients discontinued tocilizumab because of lack of efficacy in 15 patients and intolerance in 11. Among those who continued on tocilizumab, the median length of treatment was 26.0 months (range, 3-76.5 months).

 

Comments on the Study

The study population had some unusual characteristics, according to G-CAN President Robert Terkeltaub, MD, who was asked to comment on the study. “Almost half the patients had received anakinra and then, basically, they failed. In about half of the people who got anakinra, it didn’t work, and in the other half, it wasn’t well tolerated. It’s just rather odd. I find anakinra reasonably well tolerated by people, but we’re dealing with an older population of patients, and the subcutaneous administration of anakinra sometimes can give you injection site reactions, but people started off with a pain level that was close to what we register as severe pain, and the pain level decreased,” he said.

Treatment decisions can be difficult in patients with chronic or acute recurrent CPPD, said Terkeltaub, professor of medicine at the University of California, San Diego. “What’s the lesser evil? Putting people on chronic prednisone is really hard on patients or using a biologic that’s more of an immunologic scalpel here, and more selective, and trying to get people through a long course of therapy. If you have chronic arthritis, it took a while for it to get chronic, and it generally doesn’t go away overnight.”

Terkeltaub also pointed out the gastrointestinal side effects of IL-6r inhibitors, which can include diverticulitis, but there are also concerns over infections and lipid and liver abnormalities. Subcutaneously injected tocilizumab also has a longer half-life than something like anakinra.

Beyond the retrospective nature of the study and the limits it imposes on conclusions that can be drawn, Terkeltaub noted a lack of data on the number of “inflamed joints [in each patient] and what the functioning of the patients was.”

Still, the findings are encouraging. “What I can glean from this study is that the first biologic drug might be an IL-6 inhibitor, but you really need prospective, controlled, blinded clinical trials to know, and it’s hard. It’s just hard to do those trials” because patients tend to be of advanced age, Terkeltaub said.

Latourte said a randomized controlled trial of tocilizumab vs placebo, called TociCCAre, is planned to begin in France in 2025.

Latourte has financial relationships with Fresenius Kabi, Roche Chugai, AbbVie, Arsylab, Celltrion, Janssen, Nordic, Pfizer, UCB, Amgen, Biogen, Galapagos, and Eli Lilly. Terkeltaub had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

Interleukin-6 receptor (IL-6r) inhibition is a promising approach for the treatment of calcium pyrophosphate deposition disease (CPPD), although no prospective studies have been conducted to date. Nevertheless, a retrospective analysis of patients treated with the IL-6r inhibitor tocilizumab, presented at American College of Rheumatology (ACR) 2024 Annual Meeting, showed improved CPPD control in more than two thirds of patients who had failed or could not tolerate usual therapies.

Both the monosodium urate (MSU) crystals associated with gout and CPP crystals induce inflammation dependent on IL-1 beta, but IL-1 beta inhibitors have been investigated more as treatments for gout than for CPPD, and they are recommended by both ACR and European Alliance of Associations for Rheumatology (EULAR) guidelines for patients with gout who have flares despite efforts to treat with colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids. However, IL-1 beta inhibitors are sometimes used off label in CPPD.

There are similarities among the various crystal types that induce arthritis, typically producing similar clinical features of acute arthritis and severe pain and local inflammation and tending to self-resolve within days to weeks. Those shared clinical features suggest common inflammatory mechanisms, likely stemming from the innate immune system, said Augustin Latourte, MD, PhD, of Lariboisière Hospital, Paris, France, during a talk on the topic at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network (G-CAN).

CPPD management is generally derived from strategies developed for gout, but there is little evidence supporting IL-1 beta inhibitors outside of case reports, he said. One clinical trial published in 2020 showed efficacy of the IL-1 inhibitor anakinra, but the study was halted due to low patient recruitment, resulting in a small study population. In that study, “anakinra seems to have a faster onset of action than prednisone and could be useful in specific situations regarding acute CPPD arthritis. But it’s not relevant for chronic CPPD arthritis when you have persistent polyarthritis requiring chronic treatment. Anakinra requires daily injections and may not be appropriate in this situation,” he said.

IL-6r inhibition has been studied since IL-6 was first discovered in 1989 as a mediator of inflammatory responses in gout and CPPD, when it was shown that both CPP and MSU crystals can stimulate its production. In monocytes, IL-6 is expressed at higher levels than IL-1 beta in response to both CPP and MSU crystals. IL-6 production in monocytes in response to crystals is dependent on IL-1, and IL-1 inhibition reduces IL-6 production. “So the hypothesis is that IL-1 beta is the first event, and the production of IL-6 and the amplification of crystal inflammation occurs downstream before the self-limitation of the crystal-induced arthritis. IL-6 may be a very important event in the onset of crystal-induced inflammation,” Latourte said.

 

Building on Mechanistic Insights to Test Off-Label Use of Tocilizumab

Inspired by this insight, Latourte’s group tested tocilizumab in a 28-year-old man with a familial ANKH mutation who had not responded to anakinra and other conventional treatments. The patient experienced a reduction in flare intensity in the first month after the initial treatment and no flares after the second tocilizumab infusion. The group went on to test tocilizumab in 10 additional patients with CPPD (median age, 62.5 years), including 6 with idiopathic CPPD, 3 with Gitelman syndrome, and 1 with ANKH mutation. The clinical presentation included four with recurrent acute arthritis and six with chronic polyarthritis, and all had x-ray–proven disease, with a median visual analog scale (VAS) of 60 mm out of 100 mm. Tocilizumab was administered intravenously or subcutaneously. At 3 months, there was a median improvement of 30 mm in the VAS. Treatment efficacy continued for a median follow-up of 5.5 months at the time of publication, and the researchers have noted ongoing efficacy out to 50 months for some patients.

Tocilizumab has gone on to more frequent use in Europe as a second- or third-line therapy for CPPD, which led Latourte and his colleagues to perform the retrospective analysis that they presented at the ACR meeting. It included 55 patients who received tocilizumab for chronic inflammatory CPPD at two university hospitals. Participants had a median age of 72 years, and 67.3% were women. The patient group included 39 with chronic CPPD, 14 with recurrent acute CPPD (who experienced 0-4 attacks per month), and two patients with mixed CPPD. All participants had been treated with colchicine, and 20 had been treated also with prednisone and 24 with anakinra. Patients had stopped anakinra because it was either ineffective (n = 13) or poorly tolerated (n = 11).

Tocilizumab was administered intravenously in 46 patients and subcutaneously in nine patients for a median duration of 16.5 months (range, 0.8-76.4 months). The median VAS for pain (0- to 100-mm scale) dropped from 60 mm at baseline to 40 mm at 3 months and 30 mm at 6 months. There were 21 adverse events, including 8 cytopenias, 6 transaminase elevations, 4 infections (two severe), and 3 injection-site reactions. After a median of 7.8 months, 26 patients discontinued tocilizumab because of lack of efficacy in 15 patients and intolerance in 11. Among those who continued on tocilizumab, the median length of treatment was 26.0 months (range, 3-76.5 months).

 

Comments on the Study

The study population had some unusual characteristics, according to G-CAN President Robert Terkeltaub, MD, who was asked to comment on the study. “Almost half the patients had received anakinra and then, basically, they failed. In about half of the people who got anakinra, it didn’t work, and in the other half, it wasn’t well tolerated. It’s just rather odd. I find anakinra reasonably well tolerated by people, but we’re dealing with an older population of patients, and the subcutaneous administration of anakinra sometimes can give you injection site reactions, but people started off with a pain level that was close to what we register as severe pain, and the pain level decreased,” he said.

Treatment decisions can be difficult in patients with chronic or acute recurrent CPPD, said Terkeltaub, professor of medicine at the University of California, San Diego. “What’s the lesser evil? Putting people on chronic prednisone is really hard on patients or using a biologic that’s more of an immunologic scalpel here, and more selective, and trying to get people through a long course of therapy. If you have chronic arthritis, it took a while for it to get chronic, and it generally doesn’t go away overnight.”

Terkeltaub also pointed out the gastrointestinal side effects of IL-6r inhibitors, which can include diverticulitis, but there are also concerns over infections and lipid and liver abnormalities. Subcutaneously injected tocilizumab also has a longer half-life than something like anakinra.

Beyond the retrospective nature of the study and the limits it imposes on conclusions that can be drawn, Terkeltaub noted a lack of data on the number of “inflamed joints [in each patient] and what the functioning of the patients was.”

Still, the findings are encouraging. “What I can glean from this study is that the first biologic drug might be an IL-6 inhibitor, but you really need prospective, controlled, blinded clinical trials to know, and it’s hard. It’s just hard to do those trials” because patients tend to be of advanced age, Terkeltaub said.

Latourte said a randomized controlled trial of tocilizumab vs placebo, called TociCCAre, is planned to begin in France in 2025.

Latourte has financial relationships with Fresenius Kabi, Roche Chugai, AbbVie, Arsylab, Celltrion, Janssen, Nordic, Pfizer, UCB, Amgen, Biogen, Galapagos, and Eli Lilly. Terkeltaub had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

Interleukin-6 receptor (IL-6r) inhibition is a promising approach for the treatment of calcium pyrophosphate deposition disease (CPPD), although no prospective studies have been conducted to date. Nevertheless, a retrospective analysis of patients treated with the IL-6r inhibitor tocilizumab, presented at American College of Rheumatology (ACR) 2024 Annual Meeting, showed improved CPPD control in more than two thirds of patients who had failed or could not tolerate usual therapies.

Both the monosodium urate (MSU) crystals associated with gout and CPP crystals induce inflammation dependent on IL-1 beta, but IL-1 beta inhibitors have been investigated more as treatments for gout than for CPPD, and they are recommended by both ACR and European Alliance of Associations for Rheumatology (EULAR) guidelines for patients with gout who have flares despite efforts to treat with colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids. However, IL-1 beta inhibitors are sometimes used off label in CPPD.

There are similarities among the various crystal types that induce arthritis, typically producing similar clinical features of acute arthritis and severe pain and local inflammation and tending to self-resolve within days to weeks. Those shared clinical features suggest common inflammatory mechanisms, likely stemming from the innate immune system, said Augustin Latourte, MD, PhD, of Lariboisière Hospital, Paris, France, during a talk on the topic at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network (G-CAN).

CPPD management is generally derived from strategies developed for gout, but there is little evidence supporting IL-1 beta inhibitors outside of case reports, he said. One clinical trial published in 2020 showed efficacy of the IL-1 inhibitor anakinra, but the study was halted due to low patient recruitment, resulting in a small study population. In that study, “anakinra seems to have a faster onset of action than prednisone and could be useful in specific situations regarding acute CPPD arthritis. But it’s not relevant for chronic CPPD arthritis when you have persistent polyarthritis requiring chronic treatment. Anakinra requires daily injections and may not be appropriate in this situation,” he said.

IL-6r inhibition has been studied since IL-6 was first discovered in 1989 as a mediator of inflammatory responses in gout and CPPD, when it was shown that both CPP and MSU crystals can stimulate its production. In monocytes, IL-6 is expressed at higher levels than IL-1 beta in response to both CPP and MSU crystals. IL-6 production in monocytes in response to crystals is dependent on IL-1, and IL-1 inhibition reduces IL-6 production. “So the hypothesis is that IL-1 beta is the first event, and the production of IL-6 and the amplification of crystal inflammation occurs downstream before the self-limitation of the crystal-induced arthritis. IL-6 may be a very important event in the onset of crystal-induced inflammation,” Latourte said.

 

Building on Mechanistic Insights to Test Off-Label Use of Tocilizumab

Inspired by this insight, Latourte’s group tested tocilizumab in a 28-year-old man with a familial ANKH mutation who had not responded to anakinra and other conventional treatments. The patient experienced a reduction in flare intensity in the first month after the initial treatment and no flares after the second tocilizumab infusion. The group went on to test tocilizumab in 10 additional patients with CPPD (median age, 62.5 years), including 6 with idiopathic CPPD, 3 with Gitelman syndrome, and 1 with ANKH mutation. The clinical presentation included four with recurrent acute arthritis and six with chronic polyarthritis, and all had x-ray–proven disease, with a median visual analog scale (VAS) of 60 mm out of 100 mm. Tocilizumab was administered intravenously or subcutaneously. At 3 months, there was a median improvement of 30 mm in the VAS. Treatment efficacy continued for a median follow-up of 5.5 months at the time of publication, and the researchers have noted ongoing efficacy out to 50 months for some patients.

Tocilizumab has gone on to more frequent use in Europe as a second- or third-line therapy for CPPD, which led Latourte and his colleagues to perform the retrospective analysis that they presented at the ACR meeting. It included 55 patients who received tocilizumab for chronic inflammatory CPPD at two university hospitals. Participants had a median age of 72 years, and 67.3% were women. The patient group included 39 with chronic CPPD, 14 with recurrent acute CPPD (who experienced 0-4 attacks per month), and two patients with mixed CPPD. All participants had been treated with colchicine, and 20 had been treated also with prednisone and 24 with anakinra. Patients had stopped anakinra because it was either ineffective (n = 13) or poorly tolerated (n = 11).

Tocilizumab was administered intravenously in 46 patients and subcutaneously in nine patients for a median duration of 16.5 months (range, 0.8-76.4 months). The median VAS for pain (0- to 100-mm scale) dropped from 60 mm at baseline to 40 mm at 3 months and 30 mm at 6 months. There were 21 adverse events, including 8 cytopenias, 6 transaminase elevations, 4 infections (two severe), and 3 injection-site reactions. After a median of 7.8 months, 26 patients discontinued tocilizumab because of lack of efficacy in 15 patients and intolerance in 11. Among those who continued on tocilizumab, the median length of treatment was 26.0 months (range, 3-76.5 months).

 

Comments on the Study

The study population had some unusual characteristics, according to G-CAN President Robert Terkeltaub, MD, who was asked to comment on the study. “Almost half the patients had received anakinra and then, basically, they failed. In about half of the people who got anakinra, it didn’t work, and in the other half, it wasn’t well tolerated. It’s just rather odd. I find anakinra reasonably well tolerated by people, but we’re dealing with an older population of patients, and the subcutaneous administration of anakinra sometimes can give you injection site reactions, but people started off with a pain level that was close to what we register as severe pain, and the pain level decreased,” he said.

Treatment decisions can be difficult in patients with chronic or acute recurrent CPPD, said Terkeltaub, professor of medicine at the University of California, San Diego. “What’s the lesser evil? Putting people on chronic prednisone is really hard on patients or using a biologic that’s more of an immunologic scalpel here, and more selective, and trying to get people through a long course of therapy. If you have chronic arthritis, it took a while for it to get chronic, and it generally doesn’t go away overnight.”

Terkeltaub also pointed out the gastrointestinal side effects of IL-6r inhibitors, which can include diverticulitis, but there are also concerns over infections and lipid and liver abnormalities. Subcutaneously injected tocilizumab also has a longer half-life than something like anakinra.

Beyond the retrospective nature of the study and the limits it imposes on conclusions that can be drawn, Terkeltaub noted a lack of data on the number of “inflamed joints [in each patient] and what the functioning of the patients was.”

Still, the findings are encouraging. “What I can glean from this study is that the first biologic drug might be an IL-6 inhibitor, but you really need prospective, controlled, blinded clinical trials to know, and it’s hard. It’s just hard to do those trials” because patients tend to be of advanced age, Terkeltaub said.

Latourte said a randomized controlled trial of tocilizumab vs placebo, called TociCCAre, is planned to begin in France in 2025.

Latourte has financial relationships with Fresenius Kabi, Roche Chugai, AbbVie, Arsylab, Celltrion, Janssen, Nordic, Pfizer, UCB, Amgen, Biogen, Galapagos, and Eli Lilly. Terkeltaub had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Achieving serum urate to below 6 mg/dL with urate-lowering therapy (ULT) in patients with gout and chronic kidney disease (CKD) stage III is not linked to an increased risk for severe or end-stage kidney disease.

METHODOLOGY:

• Researchers emulated analyses of a hypothetical target trial using a cloning, censoring, and weighting approach to evaluate the association between achieving target serum urate level with ULT and the progression of CKD in patients with gout and CKD stage III.
• They included 14,972 patients (mean age, 73.1 years; 37.7% women) from a general practice database who had a mean baseline serum urate level of 8.9 mg/dL and initiated ULTs such as allopurinol or febuxostat.
• Participants were divided into two groups: Those who achieved a target serum urate level < 6 mg/dL and those who did not within 1 year after the initiation of ULT; the mean follow-up duration was a little more than 3 years in both groups.
• The primary outcome was the occurrence of severe or end-stage kidney disease over 5 years of initiating ULT, defined by an estimated glomerular filtration rate below 30 mL/min per 1.73 m² on two occasions more than 90 days apart within 1 year, or at least one Read code for CKD stages IV or V, dialysis, or kidney transplant.
• A prespecified noninferiority margin for the hazard ratio was set at 1.2 to compare the outcomes between those who achieved the target serum urate level < 6 mg/dL and those who did not.

TAKEAWAY:

• Among the patients who initiated ULT, 31.8% achieved a target serum urate level < 6 mg/dL within 1 year.
• The 5-year risk for severe or end-stage kidney disease was lower (10.32%) in participants with gout and stage III CKD who achieved the target serum urate level than in those who did not (12.73%).
• The adjusted 5-year risk difference for severe to end-stage kidney disease was not inferior in patients who achieved the target serum urate level vs those who did not (adjusted hazard ratio [aHR], 0.89; 95% CI, 0.80-0.98; P for noninferiority < .001); results were consistent for end-stage kidney disease alone (aHR, 0.67; P for noninferiority = .001).
• Similarly, in participants with gout and CKD stages II-III, the 5-year risks for severe or end-stage kidney disease (aHR, 0.91) and end-stage kidney disease alone (aHR, 0.73) were noninferior in the group that did vs that did not achieve target serum urate levels, with P for noninferiority being < .001 and .003, respectively.

IN PRACTICE:

“Our findings suggest that lowering serum urate levels to < 6 mg/dL is generally well tolerated and may even slow CKD progression in these individuals. Initiatives to optimize the use and adherence to ULT could benefit clinicians and patients,” the authors wrote.

SOURCE:

This study was led by Yilun Wang, MD, PhD, Xiangya Hospital, Central South University, Changsha, China. It was published online in JAMA Internal Medicine.

LIMITATIONS:

Residual confounding may still have been present despite rigorous methods to control it, as is common in observational studies. Participants who achieved target serum urate levels may have received better healthcare, adhered to other treatments more consistently, and used ULT for a longer duration. The findings may have limited generalizability, as participants who did not achieve target serum urate levels prior to initiation were excluded.

DISCLOSURES:

This study was supported by the China National Key Research and Development Plan, the National Natural Science Foundation of China, the Project Program of the National Clinical Research Center for Geriatric Disorders, and other sources. Two authors reported receiving personal fees and/or grants from multiple pharmaceutical companies.

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:

Achieving serum urate to below 6 mg/dL with urate-lowering therapy (ULT) in patients with gout and chronic kidney disease (CKD) stage III is not linked to an increased risk for severe or end-stage kidney disease.

METHODOLOGY:

• Researchers emulated analyses of a hypothetical target trial using a cloning, censoring, and weighting approach to evaluate the association between achieving target serum urate level with ULT and the progression of CKD in patients with gout and CKD stage III.
• They included 14,972 patients (mean age, 73.1 years; 37.7% women) from a general practice database who had a mean baseline serum urate level of 8.9 mg/dL and initiated ULTs such as allopurinol or febuxostat.
• Participants were divided into two groups: Those who achieved a target serum urate level < 6 mg/dL and those who did not within 1 year after the initiation of ULT; the mean follow-up duration was a little more than 3 years in both groups.
• The primary outcome was the occurrence of severe or end-stage kidney disease over 5 years of initiating ULT, defined by an estimated glomerular filtration rate below 30 mL/min per 1.73 m² on two occasions more than 90 days apart within 1 year, or at least one Read code for CKD stages IV or V, dialysis, or kidney transplant.
• A prespecified noninferiority margin for the hazard ratio was set at 1.2 to compare the outcomes between those who achieved the target serum urate level < 6 mg/dL and those who did not.

TAKEAWAY:

• Among the patients who initiated ULT, 31.8% achieved a target serum urate level < 6 mg/dL within 1 year.
• The 5-year risk for severe or end-stage kidney disease was lower (10.32%) in participants with gout and stage III CKD who achieved the target serum urate level than in those who did not (12.73%).
• The adjusted 5-year risk difference for severe to end-stage kidney disease was not inferior in patients who achieved the target serum urate level vs those who did not (adjusted hazard ratio [aHR], 0.89; 95% CI, 0.80-0.98; P for noninferiority < .001); results were consistent for end-stage kidney disease alone (aHR, 0.67; P for noninferiority = .001).
• Similarly, in participants with gout and CKD stages II-III, the 5-year risks for severe or end-stage kidney disease (aHR, 0.91) and end-stage kidney disease alone (aHR, 0.73) were noninferior in the group that did vs that did not achieve target serum urate levels, with P for noninferiority being < .001 and .003, respectively.

IN PRACTICE:

“Our findings suggest that lowering serum urate levels to < 6 mg/dL is generally well tolerated and may even slow CKD progression in these individuals. Initiatives to optimize the use and adherence to ULT could benefit clinicians and patients,” the authors wrote.

SOURCE:

This study was led by Yilun Wang, MD, PhD, Xiangya Hospital, Central South University, Changsha, China. It was published online in JAMA Internal Medicine.

LIMITATIONS:

Residual confounding may still have been present despite rigorous methods to control it, as is common in observational studies. Participants who achieved target serum urate levels may have received better healthcare, adhered to other treatments more consistently, and used ULT for a longer duration. The findings may have limited generalizability, as participants who did not achieve target serum urate levels prior to initiation were excluded.

DISCLOSURES:

This study was supported by the China National Key Research and Development Plan, the National Natural Science Foundation of China, the Project Program of the National Clinical Research Center for Geriatric Disorders, and other sources. Two authors reported receiving personal fees and/or grants from multiple pharmaceutical companies.

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:

Achieving serum urate to below 6 mg/dL with urate-lowering therapy (ULT) in patients with gout and chronic kidney disease (CKD) stage III is not linked to an increased risk for severe or end-stage kidney disease.

METHODOLOGY:

• Researchers emulated analyses of a hypothetical target trial using a cloning, censoring, and weighting approach to evaluate the association between achieving target serum urate level with ULT and the progression of CKD in patients with gout and CKD stage III.
• They included 14,972 patients (mean age, 73.1 years; 37.7% women) from a general practice database who had a mean baseline serum urate level of 8.9 mg/dL and initiated ULTs such as allopurinol or febuxostat.
• Participants were divided into two groups: Those who achieved a target serum urate level < 6 mg/dL and those who did not within 1 year after the initiation of ULT; the mean follow-up duration was a little more than 3 years in both groups.
• The primary outcome was the occurrence of severe or end-stage kidney disease over 5 years of initiating ULT, defined by an estimated glomerular filtration rate below 30 mL/min per 1.73 m² on two occasions more than 90 days apart within 1 year, or at least one Read code for CKD stages IV or V, dialysis, or kidney transplant.
• A prespecified noninferiority margin for the hazard ratio was set at 1.2 to compare the outcomes between those who achieved the target serum urate level < 6 mg/dL and those who did not.

TAKEAWAY:

• Among the patients who initiated ULT, 31.8% achieved a target serum urate level < 6 mg/dL within 1 year.
• The 5-year risk for severe or end-stage kidney disease was lower (10.32%) in participants with gout and stage III CKD who achieved the target serum urate level than in those who did not (12.73%).
• The adjusted 5-year risk difference for severe to end-stage kidney disease was not inferior in patients who achieved the target serum urate level vs those who did not (adjusted hazard ratio [aHR], 0.89; 95% CI, 0.80-0.98; P for noninferiority < .001); results were consistent for end-stage kidney disease alone (aHR, 0.67; P for noninferiority = .001).
• Similarly, in participants with gout and CKD stages II-III, the 5-year risks for severe or end-stage kidney disease (aHR, 0.91) and end-stage kidney disease alone (aHR, 0.73) were noninferior in the group that did vs that did not achieve target serum urate levels, with P for noninferiority being < .001 and .003, respectively.

IN PRACTICE:

“Our findings suggest that lowering serum urate levels to < 6 mg/dL is generally well tolerated and may even slow CKD progression in these individuals. Initiatives to optimize the use and adherence to ULT could benefit clinicians and patients,” the authors wrote.

SOURCE:

This study was led by Yilun Wang, MD, PhD, Xiangya Hospital, Central South University, Changsha, China. It was published online in JAMA Internal Medicine.

LIMITATIONS:

Residual confounding may still have been present despite rigorous methods to control it, as is common in observational studies. Participants who achieved target serum urate levels may have received better healthcare, adhered to other treatments more consistently, and used ULT for a longer duration. The findings may have limited generalizability, as participants who did not achieve target serum urate levels prior to initiation were excluded.

DISCLOSURES:

This study was supported by the China National Key Research and Development Plan, the National Natural Science Foundation of China, the Project Program of the National Clinical Research Center for Geriatric Disorders, and other sources. Two authors reported receiving personal fees and/or grants from multiple pharmaceutical companies.

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.