Rheumatology News

TOPLINE:

A diagnostic model based on the concentrations of four metabolites and one lipid ratio can reliably predict cancer in patients with rheumatic and musculoskeletal diseases (RMDs) or paraneoplasia, providing high sensitivity and specificity.

METHODOLOGY:

• The metabolome profile can differentiate between nonspecific inflammatory symptoms such as those associated with paraneoplastic conditions or RMDs, which can help accelerate cancer diagnosis and treatment.
• To assess if changes in the serum metabolome profile could indicate cancer in patients with RMD, researchers performed nuclear magnetic resonance analysis of the sera of patients with rheumatoid arthritis (RA) with a history of invasive cancer (n = 56; age, 69.9 years; 76.8% women) or without such history (n = 52; age, 56.1 years; 57.7% women).
• Blinded validation was conducted in a cohort of patients with RA or spondyloarthritis with or without a history of invasive cancer.
• Additionally, the model performance was tested in a cohort of patients having RA or spondyloarthritis with active cancer or cancer treatment, pulmonary and lymphoid type cancers, paraneoplastic syndromes, and facultative solid noninvasive precancerous lesions and nonmelanoma skin cancer; in samples prior to the development of malignancy; and in a cohort of patients with systemic lupus erythematosus (SLE).
• The final model comprised five variables. The goodness of fit of the model was described using the area under the receiver operating characteristic curve (AUC).

TAKEAWAY:

• Based on the concentrations of acetate, creatine, glycine, and formate and the L1/L6 lipid ratio, the diagnostic model yielded an excellent AUC (0.987) and high sensitivity (0.932) and specificity (0.946) for cancer diagnosis in patients with RA.
• The diagnostic model yielded an AUC of 0.937 in the blinded validation cohort of patients with RA and an AUC of 0.927 in the merged RA and spondyloarthritis cohort.
• Although the diagnostic model accurately diagnosed cancer in all the patients with paraneoplasia, it could do so accurately in only 50% of patients with noninvasive or in situ precancerous lesions and nonmelanoma skin cancers.
• The performance of the model was poor in the SLE cohort (AUC, 0.656), and it could not identify patients at risk for later invasive cancer development.

IN PRACTICE:

“This limited-invasive assay has considerable potential of high clinical value to facilitate timely diagnosis of cancer in paraneoplastic rheumatic syndromes as well as become a valuable active surveillance tool in RA and SpA [spondyloarthritis] patients with a high risk of developing cancer,” the authors wrote.

SOURCE:

The study, led by Karolina Gente, MHBA, Heidelberg University Hospital, Heidelberg, Germany, was published online on April 1, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The limited invasiveness during sampling might account for the model’s inability to identify three early-stage, low-grade tumors and its nonreliability in identifying noninvasive facultative precancerous lesions and nonmelanoma skin cancers. Given its poor performance in the SLE cohort, the model may not be suitable for universal application in more systemic rheumatic diseases.

DISCLOSURES:

This study was supported by an unrestricted investigator-initiated grant from the Foundation Commission of the Medical Faculty, University of Heidelberg, Germany. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A diagnostic model based on the concentrations of four metabolites and one lipid ratio can reliably predict cancer in patients with rheumatic and musculoskeletal diseases (RMDs) or paraneoplasia, providing high sensitivity and specificity.

METHODOLOGY:

• The metabolome profile can differentiate between nonspecific inflammatory symptoms such as those associated with paraneoplastic conditions or RMDs, which can help accelerate cancer diagnosis and treatment.
• To assess if changes in the serum metabolome profile could indicate cancer in patients with RMD, researchers performed nuclear magnetic resonance analysis of the sera of patients with rheumatoid arthritis (RA) with a history of invasive cancer (n = 56; age, 69.9 years; 76.8% women) or without such history (n = 52; age, 56.1 years; 57.7% women).
• Blinded validation was conducted in a cohort of patients with RA or spondyloarthritis with or without a history of invasive cancer.
• Additionally, the model performance was tested in a cohort of patients having RA or spondyloarthritis with active cancer or cancer treatment, pulmonary and lymphoid type cancers, paraneoplastic syndromes, and facultative solid noninvasive precancerous lesions and nonmelanoma skin cancer; in samples prior to the development of malignancy; and in a cohort of patients with systemic lupus erythematosus (SLE).
• The final model comprised five variables. The goodness of fit of the model was described using the area under the receiver operating characteristic curve (AUC).

TAKEAWAY:

• Based on the concentrations of acetate, creatine, glycine, and formate and the L1/L6 lipid ratio, the diagnostic model yielded an excellent AUC (0.987) and high sensitivity (0.932) and specificity (0.946) for cancer diagnosis in patients with RA.
• The diagnostic model yielded an AUC of 0.937 in the blinded validation cohort of patients with RA and an AUC of 0.927 in the merged RA and spondyloarthritis cohort.
• Although the diagnostic model accurately diagnosed cancer in all the patients with paraneoplasia, it could do so accurately in only 50% of patients with noninvasive or in situ precancerous lesions and nonmelanoma skin cancers.
• The performance of the model was poor in the SLE cohort (AUC, 0.656), and it could not identify patients at risk for later invasive cancer development.

IN PRACTICE:

“This limited-invasive assay has considerable potential of high clinical value to facilitate timely diagnosis of cancer in paraneoplastic rheumatic syndromes as well as become a valuable active surveillance tool in RA and SpA [spondyloarthritis] patients with a high risk of developing cancer,” the authors wrote.

SOURCE:

The study, led by Karolina Gente, MHBA, Heidelberg University Hospital, Heidelberg, Germany, was published online on April 1, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The limited invasiveness during sampling might account for the model’s inability to identify three early-stage, low-grade tumors and its nonreliability in identifying noninvasive facultative precancerous lesions and nonmelanoma skin cancers. Given its poor performance in the SLE cohort, the model may not be suitable for universal application in more systemic rheumatic diseases.

DISCLOSURES:

This study was supported by an unrestricted investigator-initiated grant from the Foundation Commission of the Medical Faculty, University of Heidelberg, Germany. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A diagnostic model based on the concentrations of four metabolites and one lipid ratio can reliably predict cancer in patients with rheumatic and musculoskeletal diseases (RMDs) or paraneoplasia, providing high sensitivity and specificity.

METHODOLOGY:

• The metabolome profile can differentiate between nonspecific inflammatory symptoms such as those associated with paraneoplastic conditions or RMDs, which can help accelerate cancer diagnosis and treatment.
• To assess if changes in the serum metabolome profile could indicate cancer in patients with RMD, researchers performed nuclear magnetic resonance analysis of the sera of patients with rheumatoid arthritis (RA) with a history of invasive cancer (n = 56; age, 69.9 years; 76.8% women) or without such history (n = 52; age, 56.1 years; 57.7% women).
• Blinded validation was conducted in a cohort of patients with RA or spondyloarthritis with or without a history of invasive cancer.
• Additionally, the model performance was tested in a cohort of patients having RA or spondyloarthritis with active cancer or cancer treatment, pulmonary and lymphoid type cancers, paraneoplastic syndromes, and facultative solid noninvasive precancerous lesions and nonmelanoma skin cancer; in samples prior to the development of malignancy; and in a cohort of patients with systemic lupus erythematosus (SLE).
• The final model comprised five variables. The goodness of fit of the model was described using the area under the receiver operating characteristic curve (AUC).

TAKEAWAY:

• Based on the concentrations of acetate, creatine, glycine, and formate and the L1/L6 lipid ratio, the diagnostic model yielded an excellent AUC (0.987) and high sensitivity (0.932) and specificity (0.946) for cancer diagnosis in patients with RA.
• The diagnostic model yielded an AUC of 0.937 in the blinded validation cohort of patients with RA and an AUC of 0.927 in the merged RA and spondyloarthritis cohort.
• Although the diagnostic model accurately diagnosed cancer in all the patients with paraneoplasia, it could do so accurately in only 50% of patients with noninvasive or in situ precancerous lesions and nonmelanoma skin cancers.
• The performance of the model was poor in the SLE cohort (AUC, 0.656), and it could not identify patients at risk for later invasive cancer development.

IN PRACTICE:

“This limited-invasive assay has considerable potential of high clinical value to facilitate timely diagnosis of cancer in paraneoplastic rheumatic syndromes as well as become a valuable active surveillance tool in RA and SpA [spondyloarthritis] patients with a high risk of developing cancer,” the authors wrote.

SOURCE:

The study, led by Karolina Gente, MHBA, Heidelberg University Hospital, Heidelberg, Germany, was published online on April 1, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The limited invasiveness during sampling might account for the model’s inability to identify three early-stage, low-grade tumors and its nonreliability in identifying noninvasive facultative precancerous lesions and nonmelanoma skin cancers. Given its poor performance in the SLE cohort, the model may not be suitable for universal application in more systemic rheumatic diseases.

DISCLOSURES:

This study was supported by an unrestricted investigator-initiated grant from the Foundation Commission of the Medical Faculty, University of Heidelberg, Germany. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Treatment with biologic disease-modifying antirheumatic drugs (bDMARDs), particularly tocilizumab, can suppress inflammation and preserve renal function in a majority of patients with chronic inflammatory disorders who develop serum amyloid alpha (SAA) amyloidosis.

METHODOLOGY:

• AA amyloidosis, characterized by the misfolding of the SAA protein, is observed in patients with inflammatory diseases and can lead to progressive organ damage, including chronic kidney disease, malabsorption with cachexia, and cardiac failure.
• This monocentric, retrospective analysis assessed the effect of bDMARD therapy on inflammatory biomarker levels and renal outcomes in 83 patients with AA amyloidosis who were followed for a mean period of 4.82 years.
• The patients were stratified into three major subgroups depending on the cause of AA amyloidosis:
• Chronic inflammatory diseases (cid + AA; n = 34) such as rheumatoid arthritis, Crohn’s disease, and chronic infections
• Autoinflammatory syndromes (auto + AA; n = 24) such as familial Mediterranean fever (FMF) and cryopyrin-associated periodic syndrome (CAPS)
• Idiopathic AA (idio + AA; n = 25), wherein the primary disease could not be identified
• Tocilizumab was the most commonly used bDMARD in patients with cid + AA and idio + AA amyloidosis, and interleukin-1 inhibitors were prescribed to patients with auto + AA amyloidosis because tocilizumab has not been approved yet for FMF or CAPS treatment.
• All patients with AA amyloidosis had renal involvement, as confirmed by kidney biopsy.

TAKEAWAY:

• After bDMARD therapy, C-reactive protein levels reduced significantly from baseline to the last-documented visit in all subgroups, while SAA levels declined in the subgroups cid + AA and idio + AA and proteinuria dropped in the subgroups auto + AA and idio + AA.
• bDMARDs prevented progression to end-stage renal disease (ESRD) in 75% of the patients in the overall cohort, with progression to ESRD being prevented in 60% of patients with cid + AA, 88% of patients with auto + AA, and 81% of patients with idio + AA.
• Tocilizumab was more effective than other bDMARDs in preventing renal progression to ESRD (P = .0006), with a similar pattern observed for the subgroups cid + AA (P = .0126) and idio + AA (P = .0259).
• None of the patients receiving tocilizumab died during the nearly 5-year follow-up period.

IN PRACTICE:

“The data suggest preferential use of IL [interleukin]-1 inhibitors and tocilizumab for clinical use in the treatment of AA amyloidosis depending on the respective underlying diseases,” the authors wrote.

SOURCE:

This study, led by Peter Kvacskay, MD, of Heidelberg University Hospital, Heidelberg, Germany, was published online on April 23 in Annals of the Rheumatic Diseases.

LIMITATIONS:

Authors acknowledged the retrospective nature of the analysis and missing data of single patients during the long-term follow-up as major limitations. Furthermore, the cid + AA subgroup was heterogeneous in terms of the pathophysiology of their underlying primary disease.

DISCLOSURES:

This study did not report any source of funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Treatment with biologic disease-modifying antirheumatic drugs (bDMARDs), particularly tocilizumab, can suppress inflammation and preserve renal function in a majority of patients with chronic inflammatory disorders who develop serum amyloid alpha (SAA) amyloidosis.

METHODOLOGY:

• AA amyloidosis, characterized by the misfolding of the SAA protein, is observed in patients with inflammatory diseases and can lead to progressive organ damage, including chronic kidney disease, malabsorption with cachexia, and cardiac failure.
• This monocentric, retrospective analysis assessed the effect of bDMARD therapy on inflammatory biomarker levels and renal outcomes in 83 patients with AA amyloidosis who were followed for a mean period of 4.82 years.
• The patients were stratified into three major subgroups depending on the cause of AA amyloidosis:
• Chronic inflammatory diseases (cid + AA; n = 34) such as rheumatoid arthritis, Crohn’s disease, and chronic infections
• Autoinflammatory syndromes (auto + AA; n = 24) such as familial Mediterranean fever (FMF) and cryopyrin-associated periodic syndrome (CAPS)
• Idiopathic AA (idio + AA; n = 25), wherein the primary disease could not be identified
• Tocilizumab was the most commonly used bDMARD in patients with cid + AA and idio + AA amyloidosis, and interleukin-1 inhibitors were prescribed to patients with auto + AA amyloidosis because tocilizumab has not been approved yet for FMF or CAPS treatment.
• All patients with AA amyloidosis had renal involvement, as confirmed by kidney biopsy.

TAKEAWAY:

• After bDMARD therapy, C-reactive protein levels reduced significantly from baseline to the last-documented visit in all subgroups, while SAA levels declined in the subgroups cid + AA and idio + AA and proteinuria dropped in the subgroups auto + AA and idio + AA.
• bDMARDs prevented progression to end-stage renal disease (ESRD) in 75% of the patients in the overall cohort, with progression to ESRD being prevented in 60% of patients with cid + AA, 88% of patients with auto + AA, and 81% of patients with idio + AA.
• Tocilizumab was more effective than other bDMARDs in preventing renal progression to ESRD (P = .0006), with a similar pattern observed for the subgroups cid + AA (P = .0126) and idio + AA (P = .0259).
• None of the patients receiving tocilizumab died during the nearly 5-year follow-up period.

IN PRACTICE:

“The data suggest preferential use of IL [interleukin]-1 inhibitors and tocilizumab for clinical use in the treatment of AA amyloidosis depending on the respective underlying diseases,” the authors wrote.

SOURCE:

This study, led by Peter Kvacskay, MD, of Heidelberg University Hospital, Heidelberg, Germany, was published online on April 23 in Annals of the Rheumatic Diseases.

LIMITATIONS:

Authors acknowledged the retrospective nature of the analysis and missing data of single patients during the long-term follow-up as major limitations. Furthermore, the cid + AA subgroup was heterogeneous in terms of the pathophysiology of their underlying primary disease.

DISCLOSURES:

This study did not report any source of funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Treatment with biologic disease-modifying antirheumatic drugs (bDMARDs), particularly tocilizumab, can suppress inflammation and preserve renal function in a majority of patients with chronic inflammatory disorders who develop serum amyloid alpha (SAA) amyloidosis.

METHODOLOGY:

• AA amyloidosis, characterized by the misfolding of the SAA protein, is observed in patients with inflammatory diseases and can lead to progressive organ damage, including chronic kidney disease, malabsorption with cachexia, and cardiac failure.
• This monocentric, retrospective analysis assessed the effect of bDMARD therapy on inflammatory biomarker levels and renal outcomes in 83 patients with AA amyloidosis who were followed for a mean period of 4.82 years.
• The patients were stratified into three major subgroups depending on the cause of AA amyloidosis:
• Chronic inflammatory diseases (cid + AA; n = 34) such as rheumatoid arthritis, Crohn’s disease, and chronic infections
• Autoinflammatory syndromes (auto + AA; n = 24) such as familial Mediterranean fever (FMF) and cryopyrin-associated periodic syndrome (CAPS)
• Idiopathic AA (idio + AA; n = 25), wherein the primary disease could not be identified
• Tocilizumab was the most commonly used bDMARD in patients with cid + AA and idio + AA amyloidosis, and interleukin-1 inhibitors were prescribed to patients with auto + AA amyloidosis because tocilizumab has not been approved yet for FMF or CAPS treatment.
• All patients with AA amyloidosis had renal involvement, as confirmed by kidney biopsy.

TAKEAWAY:

• After bDMARD therapy, C-reactive protein levels reduced significantly from baseline to the last-documented visit in all subgroups, while SAA levels declined in the subgroups cid + AA and idio + AA and proteinuria dropped in the subgroups auto + AA and idio + AA.
• bDMARDs prevented progression to end-stage renal disease (ESRD) in 75% of the patients in the overall cohort, with progression to ESRD being prevented in 60% of patients with cid + AA, 88% of patients with auto + AA, and 81% of patients with idio + AA.
• Tocilizumab was more effective than other bDMARDs in preventing renal progression to ESRD (P = .0006), with a similar pattern observed for the subgroups cid + AA (P = .0126) and idio + AA (P = .0259).
• None of the patients receiving tocilizumab died during the nearly 5-year follow-up period.

IN PRACTICE:

“The data suggest preferential use of IL [interleukin]-1 inhibitors and tocilizumab for clinical use in the treatment of AA amyloidosis depending on the respective underlying diseases,” the authors wrote.

SOURCE:

This study, led by Peter Kvacskay, MD, of Heidelberg University Hospital, Heidelberg, Germany, was published online on April 23 in Annals of the Rheumatic Diseases.

LIMITATIONS:

Authors acknowledged the retrospective nature of the analysis and missing data of single patients during the long-term follow-up as major limitations. Furthermore, the cid + AA subgroup was heterogeneous in terms of the pathophysiology of their underlying primary disease.

DISCLOSURES:

This study did not report any source of funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Temporal artery ultrasound alone was sufficient to accurately diagnose giant cell arteritis (GCA) in over half of patients in a new prospective study.

The findings provide further evidence that “[ultrasound] of temporal arteries could really take the place of traditional temporal artery biopsy (TAB)” in patients with high clinical suspicion of GCA, lead author Guillaume Denis, MD, of the Centre Hospitalier de Rochefort in Rochefort, France, told this news organization.

The European Alliance of Associations for Rheumatology (EULAR) already recommends ultrasound as a first-line diagnostic tool for patients with suspected large vessel vasculitis, and the 2022 American College of Rheumatology (ACR)/EULAR classification criteria for GCA weighs positive TAB or temporal artery halo sign on ultrasound equally.

Dmytro Zinkevych | Dreamstime

Methodology

In the study, researchers recruited 165 individuals with high clinical suspicion of GCA from August 2016 through February 2020 at six French hospitals. Only patients older than 50 years of age and with biologic inflammatory syndrome with C-reactive protein elevation (≥ 6 mg/L) qualified for the study. Patients also needed to have at least one of these factors:

• Clinical signs of GCA (abnormal temporal arteries, scalp hyperesthesia, jaw claudication, or vision loss)
• General signs of GCA (headache, fever, or impaired general condition)
• Large-vessel vasculitis visible on imaging (CT angiography [CTA], MR angiography [MRA], and/or PET/CT)

All participants underwent a color Doppler ultrasound of the temporal artery, performed less than 1 week after the initiation of corticosteroid therapy. (Previous research demonstrated that corticosteroids can change the hallmark halo sign of vasculitis detectable via ultrasound as early as 1 week after initiation of therapy, the authors noted.) In this study, the time between consultation with a specialist and ultrasound was less than 1 day.

“Patients with halo signs detected around the lumen of both temporal arteries (that is, bilateral temporal halo sign) were considered as ultrasound-positive,” Guillaume Denis, MD, and colleagues explained. “Patients with no halo sign, or bilateral halo signs in the axillary arteries, or a unilateral halo sign in the temporal artery were considered as ultrasound-negative.”

The findings were published in Annals of Internal Medicine on May 7.
 

Results

In total, 73 participants (44%) had positive ultrasounds and were diagnosed with GCA. These patients also underwent a second ultrasound a month later to document if the halo sign remained unchanged, reduced, or disappeared.

The remaining 92 patients with negative ultrasound results underwent TAB, which was conducted on average 4.5 days after the ultrasound. A total of 28 patients (30%) had a positive TAB result. Physicians diagnosed 35 TAB-negative patients with GCA using clinical, imaging, and biologic data, and 29 patients received alternative diagnoses. These other diagnoses included polymyalgia rheumatica, infectious diseases, cancer, and other systemic inflammatory rheumatic diseases.

All patients diagnosed with GCA via ultrasound had their diagnoses reconfirmed at 1 month and for up to 2 years of follow-up.

“In summary, our study showed that the use of temporal artery ultrasound may be an efficient way to make the diagnosis of GCA in patients with high clinical suspicion and to reduce imaging costs and the need for biopsy, thereby limiting complications and the need for a surgeon,” the authors concluded.
 

Qualifications and Limitations

While over half of patients ultimately diagnosed with GCA were diagnosed using ultrasound, that percentage was “a bit lower than expected,” said Mark Matza, MD, MBA, the co-clinical director of rheumatology at Massachusetts General Hospital in Boston. By comparison, one systematic review calculated ultrasound’s pooled sensitivity at 88% and pooled specificity at 96% for the diagnosis of GCA.

“In this [current] study, 30% of patients who had negative ultrasound were then found to have positive biopsy, indicating that ultrasound missed a substantial portion of patients who were ultimately diagnosed with GCA,” he continued.

Ultrasound is “very operator dependent,” he added, and there has been “variability in test performance of ultrasound.”

The authors acknowledged that techniques for ultrasound of the temporal arteries have also evolved over the study period, and thus, findings may not have been consistent.

However, about one in four patients with GCA were diagnosed after having both negative ultrasound and TAB results.

“One of the things that this paper shows is that even the gold standard of temporal artery biopsy isn’t 100% either,” noted Minna Kohler, MD, who directs the rheumatology musculoskeletal ultrasound program at Massachusetts General Hospital. “That’s why clinically, there is an increasing emphasis on using multimodality imaging to assist in the diagnosis of GCA along with a physician’s clinical intuition,” she said.

Massachusetts General Hospital/Harvard Medical School

A version of this article appeared on Medscape.com.

Temporal artery ultrasound alone was sufficient to accurately diagnose giant cell arteritis (GCA) in over half of patients in a new prospective study.

The findings provide further evidence that “[ultrasound] of temporal arteries could really take the place of traditional temporal artery biopsy (TAB)” in patients with high clinical suspicion of GCA, lead author Guillaume Denis, MD, of the Centre Hospitalier de Rochefort in Rochefort, France, told this news organization.

The European Alliance of Associations for Rheumatology (EULAR) already recommends ultrasound as a first-line diagnostic tool for patients with suspected large vessel vasculitis, and the 2022 American College of Rheumatology (ACR)/EULAR classification criteria for GCA weighs positive TAB or temporal artery halo sign on ultrasound equally.

Dmytro Zinkevych | Dreamstime

Methodology

In the study, researchers recruited 165 individuals with high clinical suspicion of GCA from August 2016 through February 2020 at six French hospitals. Only patients older than 50 years of age and with biologic inflammatory syndrome with C-reactive protein elevation (≥ 6 mg/L) qualified for the study. Patients also needed to have at least one of these factors:

• Clinical signs of GCA (abnormal temporal arteries, scalp hyperesthesia, jaw claudication, or vision loss)
• General signs of GCA (headache, fever, or impaired general condition)
• Large-vessel vasculitis visible on imaging (CT angiography [CTA], MR angiography [MRA], and/or PET/CT)

All participants underwent a color Doppler ultrasound of the temporal artery, performed less than 1 week after the initiation of corticosteroid therapy. (Previous research demonstrated that corticosteroids can change the hallmark halo sign of vasculitis detectable via ultrasound as early as 1 week after initiation of therapy, the authors noted.) In this study, the time between consultation with a specialist and ultrasound was less than 1 day.

“Patients with halo signs detected around the lumen of both temporal arteries (that is, bilateral temporal halo sign) were considered as ultrasound-positive,” Guillaume Denis, MD, and colleagues explained. “Patients with no halo sign, or bilateral halo signs in the axillary arteries, or a unilateral halo sign in the temporal artery were considered as ultrasound-negative.”

The findings were published in Annals of Internal Medicine on May 7.
 

Results

In total, 73 participants (44%) had positive ultrasounds and were diagnosed with GCA. These patients also underwent a second ultrasound a month later to document if the halo sign remained unchanged, reduced, or disappeared.

The remaining 92 patients with negative ultrasound results underwent TAB, which was conducted on average 4.5 days after the ultrasound. A total of 28 patients (30%) had a positive TAB result. Physicians diagnosed 35 TAB-negative patients with GCA using clinical, imaging, and biologic data, and 29 patients received alternative diagnoses. These other diagnoses included polymyalgia rheumatica, infectious diseases, cancer, and other systemic inflammatory rheumatic diseases.

All patients diagnosed with GCA via ultrasound had their diagnoses reconfirmed at 1 month and for up to 2 years of follow-up.

“In summary, our study showed that the use of temporal artery ultrasound may be an efficient way to make the diagnosis of GCA in patients with high clinical suspicion and to reduce imaging costs and the need for biopsy, thereby limiting complications and the need for a surgeon,” the authors concluded.
 

Qualifications and Limitations

While over half of patients ultimately diagnosed with GCA were diagnosed using ultrasound, that percentage was “a bit lower than expected,” said Mark Matza, MD, MBA, the co-clinical director of rheumatology at Massachusetts General Hospital in Boston. By comparison, one systematic review calculated ultrasound’s pooled sensitivity at 88% and pooled specificity at 96% for the diagnosis of GCA.

“In this [current] study, 30% of patients who had negative ultrasound were then found to have positive biopsy, indicating that ultrasound missed a substantial portion of patients who were ultimately diagnosed with GCA,” he continued.

Ultrasound is “very operator dependent,” he added, and there has been “variability in test performance of ultrasound.”

The authors acknowledged that techniques for ultrasound of the temporal arteries have also evolved over the study period, and thus, findings may not have been consistent.

However, about one in four patients with GCA were diagnosed after having both negative ultrasound and TAB results.

“One of the things that this paper shows is that even the gold standard of temporal artery biopsy isn’t 100% either,” noted Minna Kohler, MD, who directs the rheumatology musculoskeletal ultrasound program at Massachusetts General Hospital. “That’s why clinically, there is an increasing emphasis on using multimodality imaging to assist in the diagnosis of GCA along with a physician’s clinical intuition,” she said.

Massachusetts General Hospital/Harvard Medical School

A version of this article appeared on Medscape.com.

Temporal artery ultrasound alone was sufficient to accurately diagnose giant cell arteritis (GCA) in over half of patients in a new prospective study.

The findings provide further evidence that “[ultrasound] of temporal arteries could really take the place of traditional temporal artery biopsy (TAB)” in patients with high clinical suspicion of GCA, lead author Guillaume Denis, MD, of the Centre Hospitalier de Rochefort in Rochefort, France, told this news organization.

The European Alliance of Associations for Rheumatology (EULAR) already recommends ultrasound as a first-line diagnostic tool for patients with suspected large vessel vasculitis, and the 2022 American College of Rheumatology (ACR)/EULAR classification criteria for GCA weighs positive TAB or temporal artery halo sign on ultrasound equally.

Dmytro Zinkevych | Dreamstime

Methodology

In the study, researchers recruited 165 individuals with high clinical suspicion of GCA from August 2016 through February 2020 at six French hospitals. Only patients older than 50 years of age and with biologic inflammatory syndrome with C-reactive protein elevation (≥ 6 mg/L) qualified for the study. Patients also needed to have at least one of these factors:

• Clinical signs of GCA (abnormal temporal arteries, scalp hyperesthesia, jaw claudication, or vision loss)
• General signs of GCA (headache, fever, or impaired general condition)
• Large-vessel vasculitis visible on imaging (CT angiography [CTA], MR angiography [MRA], and/or PET/CT)

All participants underwent a color Doppler ultrasound of the temporal artery, performed less than 1 week after the initiation of corticosteroid therapy. (Previous research demonstrated that corticosteroids can change the hallmark halo sign of vasculitis detectable via ultrasound as early as 1 week after initiation of therapy, the authors noted.) In this study, the time between consultation with a specialist and ultrasound was less than 1 day.

“Patients with halo signs detected around the lumen of both temporal arteries (that is, bilateral temporal halo sign) were considered as ultrasound-positive,” Guillaume Denis, MD, and colleagues explained. “Patients with no halo sign, or bilateral halo signs in the axillary arteries, or a unilateral halo sign in the temporal artery were considered as ultrasound-negative.”

The findings were published in Annals of Internal Medicine on May 7.
 

Results

In total, 73 participants (44%) had positive ultrasounds and were diagnosed with GCA. These patients also underwent a second ultrasound a month later to document if the halo sign remained unchanged, reduced, or disappeared.

The remaining 92 patients with negative ultrasound results underwent TAB, which was conducted on average 4.5 days after the ultrasound. A total of 28 patients (30%) had a positive TAB result. Physicians diagnosed 35 TAB-negative patients with GCA using clinical, imaging, and biologic data, and 29 patients received alternative diagnoses. These other diagnoses included polymyalgia rheumatica, infectious diseases, cancer, and other systemic inflammatory rheumatic diseases.

All patients diagnosed with GCA via ultrasound had their diagnoses reconfirmed at 1 month and for up to 2 years of follow-up.

“In summary, our study showed that the use of temporal artery ultrasound may be an efficient way to make the diagnosis of GCA in patients with high clinical suspicion and to reduce imaging costs and the need for biopsy, thereby limiting complications and the need for a surgeon,” the authors concluded.
 

Qualifications and Limitations

While over half of patients ultimately diagnosed with GCA were diagnosed using ultrasound, that percentage was “a bit lower than expected,” said Mark Matza, MD, MBA, the co-clinical director of rheumatology at Massachusetts General Hospital in Boston. By comparison, one systematic review calculated ultrasound’s pooled sensitivity at 88% and pooled specificity at 96% for the diagnosis of GCA.

“In this [current] study, 30% of patients who had negative ultrasound were then found to have positive biopsy, indicating that ultrasound missed a substantial portion of patients who were ultimately diagnosed with GCA,” he continued.

Ultrasound is “very operator dependent,” he added, and there has been “variability in test performance of ultrasound.”

The authors acknowledged that techniques for ultrasound of the temporal arteries have also evolved over the study period, and thus, findings may not have been consistent.

However, about one in four patients with GCA were diagnosed after having both negative ultrasound and TAB results.

“One of the things that this paper shows is that even the gold standard of temporal artery biopsy isn’t 100% either,” noted Minna Kohler, MD, who directs the rheumatology musculoskeletal ultrasound program at Massachusetts General Hospital. “That’s why clinically, there is an increasing emphasis on using multimodality imaging to assist in the diagnosis of GCA along with a physician’s clinical intuition,” she said.

Massachusetts General Hospital/Harvard Medical School

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its primary endpoint, but there could still be people with moderate to severe RA who might benefit from treatment with the drug, according to information reported at the British Society for Rheumatology annual meeting.

The primary endpoint for the phase 2A trial was the least squares mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) from baseline to 12 weeks of treatment. This was reduced by −1.03 with nipocalimab and by −0.58 with placebo, giving a mean difference of just −0.45 (P = .224).

However, one of the key secondary endpoints was the proportion of patients who had 20% improvement in American College of Rheumatology response criteria (ACR20). Results for this endpoint showed a greater difference in response to nipocalimab vs placebo, with a respective 45.5% and 20.0% (P = .055) of individuals achieving ACR20.

Moreover, an analysis stratifying for anti-citrullinated protein autoantibody (ACPA) levels at baseline found that people with higher levels had a better response to nipocalimab.
 

Choice of Endpoint

“The way this study was powered was to look at a change between the treatment groups of a DAS28-CRP reduction of 1.0,” said Peter C. Taylor, BMBCh, PhD, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England.

DAS28-CRP was often chosen as the primary endpoint in small proof-of-concept studies, such as IRIS-RA, because it was a “measure of continuous change [that] theoretically, would allow greater sensitivity to change,” Dr. Taylor added.

Sara Freeman/Medscape Medical News

Proof of Concept

IRIS-RA was billed as a “proof-of-concept” study because it was the first time that a monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn) was being tested in an RA population.

The study was a randomized double-blind trial in which 33 people with moderate to severe RA who had an inadequate response to tumor necrosis factor (TNF) inhibitors were treated with nipocalimab at a dose of 15 mg/kg given intravenously every 2 weeks, and 20 received a matching placebo. Participants were treated for 10 weeks, and then the primary follow-up was at 12 weeks, with additional follow-up for safety undertaken at 18 weeks.

Nipocalimab is a fully human, immunoglobulin G1 (IgG1) monoclonal antibody that is designed to selectively block the FcRn. By doing so, it essentially stops IgG from being recycled within the immune system, and this in turn lowers IgG levels. That includes potentially harmful ACPAs, among other pathogenic antibodies, Dr. Taylor and fellow investigators explained in their abstract.

“We’ve known for a long time that ACPA have prognostic value, but there’s been controversy about whether or not ACPA are actually pathogenic,” Dr. Taylor said. “So, one of the hypotheses that this study gives rise to is that by blocking FcRn, and thereby reducing, potentially, the concentration of ACPA in the blood, will we actually have efficacy in patients?”
 

Are ACPA Really Lowered?

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in Leeds, England, questioned the reduction in antibody levels during the discussion that followed.

Although these data had not been presented, Dr. Emery observed that the reduction in IgG was actually greater than that in ACPA, “which is fairly critical. Is it feasible to look to selectively lower normal immunoglobulin over pathogenic autoantibodies?”

Dr. Emery also wanted to know if there “was a floor on the reduction of immunoglobulin” with long-term therapy, “which would be a worry.”

Dr. Taylor responded that total IgG had been reduced by about 65% and ACPA by about 40%. Why this difference exists is not yet clear. It could be because ACPA are part of complexed antibodies.

“Most of these patients are rheumatoid factor [RF]–positive,” said Taylor, pointing out that although IgM “wouldn’t normally be affected by FcRn blockade,” there was a 10% reduction in RF IgM, probably because it was complexed to IgG.

“So, the hypothesis here is that if you look at the clearance of complexes, they’re handled differently in the cytoplasm from the clearance of monomeric IgG. But that’s a hypothesis. It needs further investigation. In vitro, there’s very good, confirmatory evidence to support that. But we’ve yet to explore that more fully in vivo,” Dr. Taylor said.

As for long-term effects, Dr. Taylor responded: “All I can tell you is [that] after the 10-week intervention, that up to an 18-week observation period, immunoglobulin levels recovered very rapidly afterwards. And you mustn’t forget that other isotypes are not affected, unlike rituximab.”
 

Safety and Other Results

With regard to safety, 27 (82%) of nipocalimab- and 12 (60%) of placebo-treated participants experienced at least one treatment-emergent adverse event (TEAE). The most common, occurring in 10% or more of cases, were RA flares (36.4% for nipocalimab vs 15.0% with placebo), headache (12.1% vs 5.0%), and COVID-19 (12.1% vs 0.0%).

There were three serious TEAEs, all in the nipocalimab-treatment group: One was an infection of a burn that had been present at inclusion, another was a deep vein thrombosis that resolved with apixaban treatment, and the other was an infusion-related reaction that resolved with supportive treatment.

Another notable efficacy finding was the proportion of patients achieving DAS28-CRP remission at 12 weeks in the nipocalimab vs the placebo group was substantially greater if considering only people with high baseline ACPA levels, at a respective 40.0% vs 16.7%, when compared with the total population (21.2% vs 10.0%).

Similar findings were seen for the proportion of patients achieving an ACR50, and there were numerically greater reductions in the components of the ACR response criteria such as tender and swollen joints with nipocalimab vs placebo. All of these were exploratory observations, Dr. Taylor emphasized.
 

Combination and Further Trials

Further trials of nipocalimab are planned or are already ongoing in systemic lupus erythematosus, active lupus nephritis, Sjögren disease, and five other diseases.

In RA, nipocalimab is now being tested in combination with the TNF inhibitor certolizumab pegol (Cimzia) in the DAISY-RA trial. This is another proof-of-concept, phase 2A trial with a target accrual of 104 patients.

The IRIS-RA study was funded by Janssen Research & Development. Dr. Taylor serves as a consultant to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB and received research funding from Galapagos, among others. Dr. Emery received research grants paid to his institution from AbbVie, Bristol Myers Squibb (BMS), Pfizer, MSD, and Roche; received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche, and UCB; and has undertaken clinical trials and provided expert advice to Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, and Lilly.
 

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its primary endpoint, but there could still be people with moderate to severe RA who might benefit from treatment with the drug, according to information reported at the British Society for Rheumatology annual meeting.

The primary endpoint for the phase 2A trial was the least squares mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) from baseline to 12 weeks of treatment. This was reduced by −1.03 with nipocalimab and by −0.58 with placebo, giving a mean difference of just −0.45 (P = .224).

However, one of the key secondary endpoints was the proportion of patients who had 20% improvement in American College of Rheumatology response criteria (ACR20). Results for this endpoint showed a greater difference in response to nipocalimab vs placebo, with a respective 45.5% and 20.0% (P = .055) of individuals achieving ACR20.

Moreover, an analysis stratifying for anti-citrullinated protein autoantibody (ACPA) levels at baseline found that people with higher levels had a better response to nipocalimab.
 

Choice of Endpoint

“The way this study was powered was to look at a change between the treatment groups of a DAS28-CRP reduction of 1.0,” said Peter C. Taylor, BMBCh, PhD, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England.

DAS28-CRP was often chosen as the primary endpoint in small proof-of-concept studies, such as IRIS-RA, because it was a “measure of continuous change [that] theoretically, would allow greater sensitivity to change,” Dr. Taylor added.

Sara Freeman/Medscape Medical News

Proof of Concept

IRIS-RA was billed as a “proof-of-concept” study because it was the first time that a monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn) was being tested in an RA population.

The study was a randomized double-blind trial in which 33 people with moderate to severe RA who had an inadequate response to tumor necrosis factor (TNF) inhibitors were treated with nipocalimab at a dose of 15 mg/kg given intravenously every 2 weeks, and 20 received a matching placebo. Participants were treated for 10 weeks, and then the primary follow-up was at 12 weeks, with additional follow-up for safety undertaken at 18 weeks.

Nipocalimab is a fully human, immunoglobulin G1 (IgG1) monoclonal antibody that is designed to selectively block the FcRn. By doing so, it essentially stops IgG from being recycled within the immune system, and this in turn lowers IgG levels. That includes potentially harmful ACPAs, among other pathogenic antibodies, Dr. Taylor and fellow investigators explained in their abstract.

“We’ve known for a long time that ACPA have prognostic value, but there’s been controversy about whether or not ACPA are actually pathogenic,” Dr. Taylor said. “So, one of the hypotheses that this study gives rise to is that by blocking FcRn, and thereby reducing, potentially, the concentration of ACPA in the blood, will we actually have efficacy in patients?”
 

Are ACPA Really Lowered?

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in Leeds, England, questioned the reduction in antibody levels during the discussion that followed.

Although these data had not been presented, Dr. Emery observed that the reduction in IgG was actually greater than that in ACPA, “which is fairly critical. Is it feasible to look to selectively lower normal immunoglobulin over pathogenic autoantibodies?”

Dr. Emery also wanted to know if there “was a floor on the reduction of immunoglobulin” with long-term therapy, “which would be a worry.”

Dr. Taylor responded that total IgG had been reduced by about 65% and ACPA by about 40%. Why this difference exists is not yet clear. It could be because ACPA are part of complexed antibodies.

“Most of these patients are rheumatoid factor [RF]–positive,” said Taylor, pointing out that although IgM “wouldn’t normally be affected by FcRn blockade,” there was a 10% reduction in RF IgM, probably because it was complexed to IgG.

“So, the hypothesis here is that if you look at the clearance of complexes, they’re handled differently in the cytoplasm from the clearance of monomeric IgG. But that’s a hypothesis. It needs further investigation. In vitro, there’s very good, confirmatory evidence to support that. But we’ve yet to explore that more fully in vivo,” Dr. Taylor said.

As for long-term effects, Dr. Taylor responded: “All I can tell you is [that] after the 10-week intervention, that up to an 18-week observation period, immunoglobulin levels recovered very rapidly afterwards. And you mustn’t forget that other isotypes are not affected, unlike rituximab.”
 

Safety and Other Results

With regard to safety, 27 (82%) of nipocalimab- and 12 (60%) of placebo-treated participants experienced at least one treatment-emergent adverse event (TEAE). The most common, occurring in 10% or more of cases, were RA flares (36.4% for nipocalimab vs 15.0% with placebo), headache (12.1% vs 5.0%), and COVID-19 (12.1% vs 0.0%).

There were three serious TEAEs, all in the nipocalimab-treatment group: One was an infection of a burn that had been present at inclusion, another was a deep vein thrombosis that resolved with apixaban treatment, and the other was an infusion-related reaction that resolved with supportive treatment.

Another notable efficacy finding was the proportion of patients achieving DAS28-CRP remission at 12 weeks in the nipocalimab vs the placebo group was substantially greater if considering only people with high baseline ACPA levels, at a respective 40.0% vs 16.7%, when compared with the total population (21.2% vs 10.0%).

Similar findings were seen for the proportion of patients achieving an ACR50, and there were numerically greater reductions in the components of the ACR response criteria such as tender and swollen joints with nipocalimab vs placebo. All of these were exploratory observations, Dr. Taylor emphasized.
 

Combination and Further Trials

Further trials of nipocalimab are planned or are already ongoing in systemic lupus erythematosus, active lupus nephritis, Sjögren disease, and five other diseases.

In RA, nipocalimab is now being tested in combination with the TNF inhibitor certolizumab pegol (Cimzia) in the DAISY-RA trial. This is another proof-of-concept, phase 2A trial with a target accrual of 104 patients.

The IRIS-RA study was funded by Janssen Research & Development. Dr. Taylor serves as a consultant to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB and received research funding from Galapagos, among others. Dr. Emery received research grants paid to his institution from AbbVie, Bristol Myers Squibb (BMS), Pfizer, MSD, and Roche; received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche, and UCB; and has undertaken clinical trials and provided expert advice to Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, and Lilly.
 

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its primary endpoint, but there could still be people with moderate to severe RA who might benefit from treatment with the drug, according to information reported at the British Society for Rheumatology annual meeting.

The primary endpoint for the phase 2A trial was the least squares mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) from baseline to 12 weeks of treatment. This was reduced by −1.03 with nipocalimab and by −0.58 with placebo, giving a mean difference of just −0.45 (P = .224).

However, one of the key secondary endpoints was the proportion of patients who had 20% improvement in American College of Rheumatology response criteria (ACR20). Results for this endpoint showed a greater difference in response to nipocalimab vs placebo, with a respective 45.5% and 20.0% (P = .055) of individuals achieving ACR20.

Moreover, an analysis stratifying for anti-citrullinated protein autoantibody (ACPA) levels at baseline found that people with higher levels had a better response to nipocalimab.
 

Choice of Endpoint

“The way this study was powered was to look at a change between the treatment groups of a DAS28-CRP reduction of 1.0,” said Peter C. Taylor, BMBCh, PhD, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England.

DAS28-CRP was often chosen as the primary endpoint in small proof-of-concept studies, such as IRIS-RA, because it was a “measure of continuous change [that] theoretically, would allow greater sensitivity to change,” Dr. Taylor added.

Sara Freeman/Medscape Medical News

Proof of Concept

IRIS-RA was billed as a “proof-of-concept” study because it was the first time that a monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn) was being tested in an RA population.

The study was a randomized double-blind trial in which 33 people with moderate to severe RA who had an inadequate response to tumor necrosis factor (TNF) inhibitors were treated with nipocalimab at a dose of 15 mg/kg given intravenously every 2 weeks, and 20 received a matching placebo. Participants were treated for 10 weeks, and then the primary follow-up was at 12 weeks, with additional follow-up for safety undertaken at 18 weeks.

Nipocalimab is a fully human, immunoglobulin G1 (IgG1) monoclonal antibody that is designed to selectively block the FcRn. By doing so, it essentially stops IgG from being recycled within the immune system, and this in turn lowers IgG levels. That includes potentially harmful ACPAs, among other pathogenic antibodies, Dr. Taylor and fellow investigators explained in their abstract.

“We’ve known for a long time that ACPA have prognostic value, but there’s been controversy about whether or not ACPA are actually pathogenic,” Dr. Taylor said. “So, one of the hypotheses that this study gives rise to is that by blocking FcRn, and thereby reducing, potentially, the concentration of ACPA in the blood, will we actually have efficacy in patients?”
 

Are ACPA Really Lowered?

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in Leeds, England, questioned the reduction in antibody levels during the discussion that followed.

Although these data had not been presented, Dr. Emery observed that the reduction in IgG was actually greater than that in ACPA, “which is fairly critical. Is it feasible to look to selectively lower normal immunoglobulin over pathogenic autoantibodies?”

Dr. Emery also wanted to know if there “was a floor on the reduction of immunoglobulin” with long-term therapy, “which would be a worry.”

Dr. Taylor responded that total IgG had been reduced by about 65% and ACPA by about 40%. Why this difference exists is not yet clear. It could be because ACPA are part of complexed antibodies.

“Most of these patients are rheumatoid factor [RF]–positive,” said Taylor, pointing out that although IgM “wouldn’t normally be affected by FcRn blockade,” there was a 10% reduction in RF IgM, probably because it was complexed to IgG.

“So, the hypothesis here is that if you look at the clearance of complexes, they’re handled differently in the cytoplasm from the clearance of monomeric IgG. But that’s a hypothesis. It needs further investigation. In vitro, there’s very good, confirmatory evidence to support that. But we’ve yet to explore that more fully in vivo,” Dr. Taylor said.

As for long-term effects, Dr. Taylor responded: “All I can tell you is [that] after the 10-week intervention, that up to an 18-week observation period, immunoglobulin levels recovered very rapidly afterwards. And you mustn’t forget that other isotypes are not affected, unlike rituximab.”
 

Safety and Other Results

With regard to safety, 27 (82%) of nipocalimab- and 12 (60%) of placebo-treated participants experienced at least one treatment-emergent adverse event (TEAE). The most common, occurring in 10% or more of cases, were RA flares (36.4% for nipocalimab vs 15.0% with placebo), headache (12.1% vs 5.0%), and COVID-19 (12.1% vs 0.0%).

There were three serious TEAEs, all in the nipocalimab-treatment group: One was an infection of a burn that had been present at inclusion, another was a deep vein thrombosis that resolved with apixaban treatment, and the other was an infusion-related reaction that resolved with supportive treatment.

Another notable efficacy finding was the proportion of patients achieving DAS28-CRP remission at 12 weeks in the nipocalimab vs the placebo group was substantially greater if considering only people with high baseline ACPA levels, at a respective 40.0% vs 16.7%, when compared with the total population (21.2% vs 10.0%).

Similar findings were seen for the proportion of patients achieving an ACR50, and there were numerically greater reductions in the components of the ACR response criteria such as tender and swollen joints with nipocalimab vs placebo. All of these were exploratory observations, Dr. Taylor emphasized.
 

Combination and Further Trials

Further trials of nipocalimab are planned or are already ongoing in systemic lupus erythematosus, active lupus nephritis, Sjögren disease, and five other diseases.

In RA, nipocalimab is now being tested in combination with the TNF inhibitor certolizumab pegol (Cimzia) in the DAISY-RA trial. This is another proof-of-concept, phase 2A trial with a target accrual of 104 patients.

The IRIS-RA study was funded by Janssen Research & Development. Dr. Taylor serves as a consultant to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB and received research funding from Galapagos, among others. Dr. Emery received research grants paid to his institution from AbbVie, Bristol Myers Squibb (BMS), Pfizer, MSD, and Roche; received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche, and UCB; and has undertaken clinical trials and provided expert advice to Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, and Lilly.
 

A version of this article appeared on Medscape.com.

Physicians are leaving healthcare in droves, “not because they don’t want to practice ... but because the system is making it more and more difficult for them to care for their patients,” Bruce Scott, MD, president-elect of the American Medical Association (AMA), said at a press conference May 9 at the National Rural Health Association’s Annual Conference in New Orleans. 

He said that shrinking reimbursement rates and excessive administrative tasks are pushing doctors out of the workforce, exacerbating physician shortages in rural locations where 46 million Americans live. 

Rural areas have about one tenth of the specialists that urban areas do, and 65% of rural communities do not have enough primary care doctors, according to federal data. A recent Centers for Disease Control and Prevention report found that people living in rural areas are more likely to die early from preventable causes than their urban counterparts, said Dr. Scott. 

He said the AMA wants Congress to pass legislation to incentivize more physicians to work in rural areas and expand the number of rural and primary care residency spots. Historically, 80% of residents practice within 80 miles of where they complete residency, he said. 

Dr. Scott also hopes Congress will revise the J-1 visa rules to allow qualified international medical graduates to continue to practice in the United States. He’d like to see the pandemic telehealth flexibilities made permanent because these loosened guidelines greatly improved care access for rural areas in recent years. 

Lower Pay Affects Care in Rural, Urban Areas

Decreased reimbursements also have hit rural and urban doctors in independent practice particularly hard, Dr. Scott said. When adjusted for inflation, the current Medicare payment rate for physicians has dropped 29% since 2001, he said. Now that commercial payers tie their reimbursement models to the Medicare rate, physicians are experiencing “severe” financial stress amid rising practice costs and student loan debt. 

He shared anecdotes about how these issues have affected his private otolaryngology practice in Louisville, Kentucky, a state where more than 2 million people live in federally designated primary care professional shortage areas. 

“A major insurance company that controls over 60% of the private payer market in rural Kentucky [recently] offered us ... surgical rates less than they paid us 6 years ago,” he said. 

Dr. Scott said physicians must make difficult choices. “Do we not invest in the latest physical equipment? Do we reduce our number of employees? Do we perhaps stop accepting new Medicare patients?”

He noted that physicians now spend twice as much time on prior authorizations and other administrative tasks as they do on direct patient care. According to a 2022 AMA survey, 33% of physicians reported that the cumbersome prior authorization process led to a serious adverse event for a patient. Eighty percent reported it caused their patient to forgo treatment altogether.

Dr. Scott, who will be sworn in as AMA president in June, said he experiences the frustration daily. 

“I have to get on the phone and justify to an insurance person who rarely has gone to medical school, has never seen the patient, and heck, in my case, sometimes they can’t even say otolaryngology, much less tell me what the appropriate care is for my patient,” he said.

When asked about the impact of private equity in healthcare, Dr. Scott said there is room for all different modes of practice, but private equity could bring a unique benefit. 

“They have deeper pockets to potentially invest in telehealth technology, AI, and better computer systems,” he said. 

But, he said, some private equity-owned systems have abandoned rural areas, and in other regions they “push the physicians to move faster, see more patients, and do the things that are profit-driven.

“The key is to continue to provide ... quality medical care that is determined by an individual physician in consultation with the patient.”
 

A version of this article appeared on Medscape.com.

Physicians are leaving healthcare in droves, “not because they don’t want to practice ... but because the system is making it more and more difficult for them to care for their patients,” Bruce Scott, MD, president-elect of the American Medical Association (AMA), said at a press conference May 9 at the National Rural Health Association’s Annual Conference in New Orleans. 

He said that shrinking reimbursement rates and excessive administrative tasks are pushing doctors out of the workforce, exacerbating physician shortages in rural locations where 46 million Americans live. 

Rural areas have about one tenth of the specialists that urban areas do, and 65% of rural communities do not have enough primary care doctors, according to federal data. A recent Centers for Disease Control and Prevention report found that people living in rural areas are more likely to die early from preventable causes than their urban counterparts, said Dr. Scott. 

He said the AMA wants Congress to pass legislation to incentivize more physicians to work in rural areas and expand the number of rural and primary care residency spots. Historically, 80% of residents practice within 80 miles of where they complete residency, he said. 

Dr. Scott also hopes Congress will revise the J-1 visa rules to allow qualified international medical graduates to continue to practice in the United States. He’d like to see the pandemic telehealth flexibilities made permanent because these loosened guidelines greatly improved care access for rural areas in recent years. 

Lower Pay Affects Care in Rural, Urban Areas

Decreased reimbursements also have hit rural and urban doctors in independent practice particularly hard, Dr. Scott said. When adjusted for inflation, the current Medicare payment rate for physicians has dropped 29% since 2001, he said. Now that commercial payers tie their reimbursement models to the Medicare rate, physicians are experiencing “severe” financial stress amid rising practice costs and student loan debt. 

He shared anecdotes about how these issues have affected his private otolaryngology practice in Louisville, Kentucky, a state where more than 2 million people live in federally designated primary care professional shortage areas. 

“A major insurance company that controls over 60% of the private payer market in rural Kentucky [recently] offered us ... surgical rates less than they paid us 6 years ago,” he said. 

Dr. Scott said physicians must make difficult choices. “Do we not invest in the latest physical equipment? Do we reduce our number of employees? Do we perhaps stop accepting new Medicare patients?”

He noted that physicians now spend twice as much time on prior authorizations and other administrative tasks as they do on direct patient care. According to a 2022 AMA survey, 33% of physicians reported that the cumbersome prior authorization process led to a serious adverse event for a patient. Eighty percent reported it caused their patient to forgo treatment altogether.

Dr. Scott, who will be sworn in as AMA president in June, said he experiences the frustration daily. 

“I have to get on the phone and justify to an insurance person who rarely has gone to medical school, has never seen the patient, and heck, in my case, sometimes they can’t even say otolaryngology, much less tell me what the appropriate care is for my patient,” he said.

When asked about the impact of private equity in healthcare, Dr. Scott said there is room for all different modes of practice, but private equity could bring a unique benefit. 

“They have deeper pockets to potentially invest in telehealth technology, AI, and better computer systems,” he said. 

But, he said, some private equity-owned systems have abandoned rural areas, and in other regions they “push the physicians to move faster, see more patients, and do the things that are profit-driven.

“The key is to continue to provide ... quality medical care that is determined by an individual physician in consultation with the patient.”
 

A version of this article appeared on Medscape.com.

Physicians are leaving healthcare in droves, “not because they don’t want to practice ... but because the system is making it more and more difficult for them to care for their patients,” Bruce Scott, MD, president-elect of the American Medical Association (AMA), said at a press conference May 9 at the National Rural Health Association’s Annual Conference in New Orleans. 

He said that shrinking reimbursement rates and excessive administrative tasks are pushing doctors out of the workforce, exacerbating physician shortages in rural locations where 46 million Americans live. 

Rural areas have about one tenth of the specialists that urban areas do, and 65% of rural communities do not have enough primary care doctors, according to federal data. A recent Centers for Disease Control and Prevention report found that people living in rural areas are more likely to die early from preventable causes than their urban counterparts, said Dr. Scott. 

He said the AMA wants Congress to pass legislation to incentivize more physicians to work in rural areas and expand the number of rural and primary care residency spots. Historically, 80% of residents practice within 80 miles of where they complete residency, he said. 

Dr. Scott also hopes Congress will revise the J-1 visa rules to allow qualified international medical graduates to continue to practice in the United States. He’d like to see the pandemic telehealth flexibilities made permanent because these loosened guidelines greatly improved care access for rural areas in recent years. 

Lower Pay Affects Care in Rural, Urban Areas

Decreased reimbursements also have hit rural and urban doctors in independent practice particularly hard, Dr. Scott said. When adjusted for inflation, the current Medicare payment rate for physicians has dropped 29% since 2001, he said. Now that commercial payers tie their reimbursement models to the Medicare rate, physicians are experiencing “severe” financial stress amid rising practice costs and student loan debt. 

He shared anecdotes about how these issues have affected his private otolaryngology practice in Louisville, Kentucky, a state where more than 2 million people live in federally designated primary care professional shortage areas. 

“A major insurance company that controls over 60% of the private payer market in rural Kentucky [recently] offered us ... surgical rates less than they paid us 6 years ago,” he said. 

Dr. Scott said physicians must make difficult choices. “Do we not invest in the latest physical equipment? Do we reduce our number of employees? Do we perhaps stop accepting new Medicare patients?”

He noted that physicians now spend twice as much time on prior authorizations and other administrative tasks as they do on direct patient care. According to a 2022 AMA survey, 33% of physicians reported that the cumbersome prior authorization process led to a serious adverse event for a patient. Eighty percent reported it caused their patient to forgo treatment altogether.

Dr. Scott, who will be sworn in as AMA president in June, said he experiences the frustration daily. 

“I have to get on the phone and justify to an insurance person who rarely has gone to medical school, has never seen the patient, and heck, in my case, sometimes they can’t even say otolaryngology, much less tell me what the appropriate care is for my patient,” he said.

When asked about the impact of private equity in healthcare, Dr. Scott said there is room for all different modes of practice, but private equity could bring a unique benefit. 

“They have deeper pockets to potentially invest in telehealth technology, AI, and better computer systems,” he said. 

But, he said, some private equity-owned systems have abandoned rural areas, and in other regions they “push the physicians to move faster, see more patients, and do the things that are profit-driven.

“The key is to continue to provide ... quality medical care that is determined by an individual physician in consultation with the patient.”
 

A version of this article appeared on Medscape.com.

Like it or not, artificial intelligence (AI) is coming to medicine. For many physicians — maybe you — it’s already here.

More than a third of physicians use AI in their practice. And the vast majority of healthcare companies — 94%, according to Morgan Stanley — use some kind of AI machine learning.

“It’s incumbent on physicians, as well as physicians in training, to become familiar with at least the basics [of AI],” said internist Matthew DeCamp, MD, PhD, an associate professor in the Center for Bioethics and Humanities at the University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Understanding AI can help you leverage it safely and effectively — plus “make better-informed decisions about whether or not to use it in [your] practice,” Dr. DeCamp said.

“Frankly, the people who are deciding whether to implement algorithms in our day-to-day lives are oftentimes not physicians,” noted Ravi B. Parikh, MD, an assistant professor at the University of Pennsylvania and director of augmented and artificial intelligence at the Penn Center for Cancer Care Innovation, Philadelphia. Yet, physicians are most qualified to assess an AI tool’s usefulness in clinical practice.

That brings us to the best starting place for your AI education: Your own institution. Find out what AI tools your organization is implementing — and how you can influence them.

“Getting involved with our hospital data governance is the best way not only to learn practically what these AI tools do but also to influence the development process in positive ways,” Dr. Parikh said.

From there, consider the following resources to enhance your AI knowledge.
 

Get a Lay of the Land: Free Primers

Many clinical societies and interest groups have put out AI primers, an easy way to get a broad overview of the technology. The following were recommended or developed by the experts we spoke to, and all are free:

• The American Medical Association’s (AMA’s) framework for advancing healthcare AI lays out actionable guidance. Ask three key questions, the AMA recommends: Does it work? Does it work for my patients? Does it improve health outcomes?
• The Coalition for Health AI’s Blueprint for Trustworthy AI Implementation Guidance and Assurance for Healthcare provides a high-level summary of how to evaluate AI in healthcare, plus steps for implementing it. AI systems should be useful, safe, accountable, explainable, fair, and secure, the report asserted.
• The National Academy of Medicine’s draft code of conduct for AI in healthcare proposes core principles and commitments. These “reflect simple guideposts to guide and gauge behavior in a complex system and provide a starting point for real-time decision-making,” the report said.
• Health AI Partnership — a collaboration of Duke Health and Microsoft — outlines eight key decision points to consider at any stage of AI implementation, whether you’re still planning how to use it or you’ve started but want to improve it. The site also provides a breakdown of standards by regulatory agencies, organizations, and oversight bodies — so you can make sure your practices align with their guidance.

Make the Most of Conferences

Next time you’re at a conference, check the agenda for sessions on AI. “For someone who’s interested in this, I would be looking for content in my next national meeting because, undoubtedly, it’s going to be there,” said Dr. DeCamp. In a fast-moving field like AI, it’s a great way to get fresh, up-to-the-moment insights.

Listen to This Podcast

The New England Journal of Medicine’s free monthly podcast AI Grand Rounds is made for researchers and clinicians. Available on Apple, Spotify, and YouTube, the pod is good for “someone who’s looking to see both where the field is going [and to hear] a retrospective on big-name papers,” said Dr. Parikh . Episodes run for about an hour.

To learn about the challenges of applying AI to biology: Listen to Daphne Koller, PhD, founder of AI-driven drug discovery and development company insitro. For insights on the potential of AI in medicine, tune into the one with Eric Horvitz, MD, PhD, Microsoft’s chief scientific officer.
 

Consider a Class

Look for courses that focus on AI applications in clinical practice rather than a deep dive into theory. (You need to understand how these tools will influence your work, not the intricacies of large language model development.) Be wary of corporate-funded training that centers on one product , which could present conflicts of interest, said Dr. DeCamp. See the chart for courses that meet these criteria.

A version of this article appeared on Medscape.com.

Like it or not, artificial intelligence (AI) is coming to medicine. For many physicians — maybe you — it’s already here.

More than a third of physicians use AI in their practice. And the vast majority of healthcare companies — 94%, according to Morgan Stanley — use some kind of AI machine learning.

“It’s incumbent on physicians, as well as physicians in training, to become familiar with at least the basics [of AI],” said internist Matthew DeCamp, MD, PhD, an associate professor in the Center for Bioethics and Humanities at the University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Understanding AI can help you leverage it safely and effectively — plus “make better-informed decisions about whether or not to use it in [your] practice,” Dr. DeCamp said.

“Frankly, the people who are deciding whether to implement algorithms in our day-to-day lives are oftentimes not physicians,” noted Ravi B. Parikh, MD, an assistant professor at the University of Pennsylvania and director of augmented and artificial intelligence at the Penn Center for Cancer Care Innovation, Philadelphia. Yet, physicians are most qualified to assess an AI tool’s usefulness in clinical practice.

That brings us to the best starting place for your AI education: Your own institution. Find out what AI tools your organization is implementing — and how you can influence them.

“Getting involved with our hospital data governance is the best way not only to learn practically what these AI tools do but also to influence the development process in positive ways,” Dr. Parikh said.

From there, consider the following resources to enhance your AI knowledge.
 

Get a Lay of the Land: Free Primers

Many clinical societies and interest groups have put out AI primers, an easy way to get a broad overview of the technology. The following were recommended or developed by the experts we spoke to, and all are free:

• The American Medical Association’s (AMA’s) framework for advancing healthcare AI lays out actionable guidance. Ask three key questions, the AMA recommends: Does it work? Does it work for my patients? Does it improve health outcomes?
• The Coalition for Health AI’s Blueprint for Trustworthy AI Implementation Guidance and Assurance for Healthcare provides a high-level summary of how to evaluate AI in healthcare, plus steps for implementing it. AI systems should be useful, safe, accountable, explainable, fair, and secure, the report asserted.
• The National Academy of Medicine’s draft code of conduct for AI in healthcare proposes core principles and commitments. These “reflect simple guideposts to guide and gauge behavior in a complex system and provide a starting point for real-time decision-making,” the report said.
• Health AI Partnership — a collaboration of Duke Health and Microsoft — outlines eight key decision points to consider at any stage of AI implementation, whether you’re still planning how to use it or you’ve started but want to improve it. The site also provides a breakdown of standards by regulatory agencies, organizations, and oversight bodies — so you can make sure your practices align with their guidance.

Make the Most of Conferences

Next time you’re at a conference, check the agenda for sessions on AI. “For someone who’s interested in this, I would be looking for content in my next national meeting because, undoubtedly, it’s going to be there,” said Dr. DeCamp. In a fast-moving field like AI, it’s a great way to get fresh, up-to-the-moment insights.

Listen to This Podcast

The New England Journal of Medicine’s free monthly podcast AI Grand Rounds is made for researchers and clinicians. Available on Apple, Spotify, and YouTube, the pod is good for “someone who’s looking to see both where the field is going [and to hear] a retrospective on big-name papers,” said Dr. Parikh . Episodes run for about an hour.

To learn about the challenges of applying AI to biology: Listen to Daphne Koller, PhD, founder of AI-driven drug discovery and development company insitro. For insights on the potential of AI in medicine, tune into the one with Eric Horvitz, MD, PhD, Microsoft’s chief scientific officer.
 

Consider a Class

Look for courses that focus on AI applications in clinical practice rather than a deep dive into theory. (You need to understand how these tools will influence your work, not the intricacies of large language model development.) Be wary of corporate-funded training that centers on one product , which could present conflicts of interest, said Dr. DeCamp. See the chart for courses that meet these criteria.

A version of this article appeared on Medscape.com.

Like it or not, artificial intelligence (AI) is coming to medicine. For many physicians — maybe you — it’s already here.

More than a third of physicians use AI in their practice. And the vast majority of healthcare companies — 94%, according to Morgan Stanley — use some kind of AI machine learning.

“It’s incumbent on physicians, as well as physicians in training, to become familiar with at least the basics [of AI],” said internist Matthew DeCamp, MD, PhD, an associate professor in the Center for Bioethics and Humanities at the University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Understanding AI can help you leverage it safely and effectively — plus “make better-informed decisions about whether or not to use it in [your] practice,” Dr. DeCamp said.

“Frankly, the people who are deciding whether to implement algorithms in our day-to-day lives are oftentimes not physicians,” noted Ravi B. Parikh, MD, an assistant professor at the University of Pennsylvania and director of augmented and artificial intelligence at the Penn Center for Cancer Care Innovation, Philadelphia. Yet, physicians are most qualified to assess an AI tool’s usefulness in clinical practice.

That brings us to the best starting place for your AI education: Your own institution. Find out what AI tools your organization is implementing — and how you can influence them.

“Getting involved with our hospital data governance is the best way not only to learn practically what these AI tools do but also to influence the development process in positive ways,” Dr. Parikh said.

From there, consider the following resources to enhance your AI knowledge.
 

Get a Lay of the Land: Free Primers

Many clinical societies and interest groups have put out AI primers, an easy way to get a broad overview of the technology. The following were recommended or developed by the experts we spoke to, and all are free:

• The American Medical Association’s (AMA’s) framework for advancing healthcare AI lays out actionable guidance. Ask three key questions, the AMA recommends: Does it work? Does it work for my patients? Does it improve health outcomes?
• The Coalition for Health AI’s Blueprint for Trustworthy AI Implementation Guidance and Assurance for Healthcare provides a high-level summary of how to evaluate AI in healthcare, plus steps for implementing it. AI systems should be useful, safe, accountable, explainable, fair, and secure, the report asserted.
• The National Academy of Medicine’s draft code of conduct for AI in healthcare proposes core principles and commitments. These “reflect simple guideposts to guide and gauge behavior in a complex system and provide a starting point for real-time decision-making,” the report said.
• Health AI Partnership — a collaboration of Duke Health and Microsoft — outlines eight key decision points to consider at any stage of AI implementation, whether you’re still planning how to use it or you’ve started but want to improve it. The site also provides a breakdown of standards by regulatory agencies, organizations, and oversight bodies — so you can make sure your practices align with their guidance.

Make the Most of Conferences

Next time you’re at a conference, check the agenda for sessions on AI. “For someone who’s interested in this, I would be looking for content in my next national meeting because, undoubtedly, it’s going to be there,” said Dr. DeCamp. In a fast-moving field like AI, it’s a great way to get fresh, up-to-the-moment insights.

Listen to This Podcast

The New England Journal of Medicine’s free monthly podcast AI Grand Rounds is made for researchers and clinicians. Available on Apple, Spotify, and YouTube, the pod is good for “someone who’s looking to see both where the field is going [and to hear] a retrospective on big-name papers,” said Dr. Parikh . Episodes run for about an hour.

To learn about the challenges of applying AI to biology: Listen to Daphne Koller, PhD, founder of AI-driven drug discovery and development company insitro. For insights on the potential of AI in medicine, tune into the one with Eric Horvitz, MD, PhD, Microsoft’s chief scientific officer.
 

Consider a Class

Look for courses that focus on AI applications in clinical practice rather than a deep dive into theory. (You need to understand how these tools will influence your work, not the intricacies of large language model development.) Be wary of corporate-funded training that centers on one product , which could present conflicts of interest, said Dr. DeCamp. See the chart for courses that meet these criteria.

A version of this article appeared on Medscape.com.

VIENNA — Data do not back the use of diacerein or resveratrol for managing the pain of knee osteoarthritis (OA), according to the results of two well-performed, multicenter, double-blind, randomized controlled clinical trials.

During the News in Therapies session at the OARSI 2024 World Congress, the null findings of the DICKENS study and ARTHROL trial were presented alongside a reappraisal of the possible role of botulinum toxin.
 

DICKENS Study of Diacerein

“The role of diacerein in the treatment of OA is controversial,” acknowledged Dawn Aitken, PhD, associate professor at the University of Tasmania in Hobart, Tasmania, Australia. “There are only a few acceptable quality trials to date, and the results are inconsistent,” Dr. Aitken added.

Indeed, a Cochrane review performed in 2014 had concluded that there was “low-quality evidence that diacerein had a small beneficial effect on pain,” she said. The reported overall effect size on a 100-mm visual analog scale, based on a meta-analysis of 10 trials, has been just −8.65 mm, equating to just a 9% pain reduction.

Bruce Jancin/MDedge News

ARTHROL Trial of Resveratrol

Similarly, negative results were reported for resveratrol from the ARTHROL trial, with 55% of the resveratrol- and 55% of placebo-treated individuals achieving a 20% reduction in knee pain intensity at 3 months. The actual change in knee pain from baseline to 3 months was −15.7 for resveratrol and −15.2 for placebo on a numerical rating scale that went from 0 (no pain) up to 100 (worst pain).

Resveratrol is found naturally in grapes, peanuts, pine cones, and Chinese knotweed, and there is a growing body of evidence that it may have pleiotropic effects, said investigator Christelle Nguyen, PhD, MD, a professor of physical and rehabilitation medicine at Université Paris Cité, Paris, France.

It’s available in a powder form over the counter as a treatment for multiple ailments, but more recently, became available as an oral formulation. Dr. Nguyen and colleagues wanted to know if this would make a difference to OA knee pain when added to usual care.

A double-blind, multicenter, placebo-controlled randomized trial was therefore conducted that involved 142 people with knee OA who had been experiencing knee pain for at least 1 month. The participants were equally randomly allocated to receive either oral resveratrol given as two caplets of 20 mg twice daily for the first week, then once daily for a total of 6 months, or a matched placebo.

There was also no effect of resveratrol vs placebo on a host of secondary outcomes measured at 3 and 6 months.

The interpretation is that oral resveratrol may not be effective in this indication or have a biologic effect on the pain pathway, Dr. Nguyen said.

Sara Freeman/Medscape Medical News

Botulinum Toxin: Over But Not Out?

Dr. Nguyen separately reported data from a new systematic review and meta-analysis on the use of intra-articular (IA) botulinum toxin type A (BoNT-A) for knee OA pain.

Seven of the 14 randomized controlled trials included in the meta-analysis had looked specifically at knee OA outcomes in the short, intermediate, and long term.

Results showed a nonsignificant trend favoring BoNT-A use, with the standard mean difference in pain of 0.35 (−0.82; 0.12), −0.27 (−0.61; 0.08), and −0.43 (−1.12; 0.26) for short-, intermediate-, and long-term use, respectively.

In contrast, pain reductions were seen with BoNT-A in three trials that included people with OA of the shoulder or base of the thumb. This begs the question as to whether botulinum toxin may still have a role to play, Dr. Nguyen said in an interview.

“It seems like there may be a positive effect for the shoulder joint and base of the thumb,” she told this news organization.

“So, basically, we found differences between large and small to intermediate joints,” Dr. Nguyen added. “It questions the dilution of botulinum toxin into the joint. If it’s a big joint, maybe the dilution is too high,” she suggested.

This hypothesis will be tested in the upcoming RHIBOT II trial that will begin recruitment later this year. This is a follow-on from the RHIBOT trial that was published in The Lancet Rheumatology 2 years ago.

Meanwhile, the use of botulinum toxin is off-label, Dr. Nguyen said. “We use it in our clinics only when first-line treatment had failed for base of thumb OA.” It’s not offered as a stand-alone intervention, and the IA injections need to be given by someone with experience, she said.
 

Methodologically Sound Studies

Commenting on the studies, Nancy E. Lane, MD, said: “There have been small botulinum studies before but not powered enough so that you could confirm or refute hypotheses.”

Dr. Lane, endowed professor of medicine, rheumatology, and aging research and director for the Center for Musculoskeletal Health at the University of California Davis School of Medicine, Sacramento, California, added: “Similarly for resveratrol, there have been lots of studies.”

Moreover, Dr. Lane observed that the studies were “really well-designed. They were well-powered. The subjects were selected in such a way that was good rigor in the methodologic design, and there were enough people in the studies so that you could really believe the results.”

The take-home is probably that these approaches do not work, Dr. Lane said, “at least when you apply them to moderate-severe knee OA patients, they don’t seem to make a difference.”

The congress was sponsored by the Osteoarthritis Research Society International.

The DICKENS study of diacerein was an investigator-initiated trial that was funded by the National Health and Medical Research Council of Australia. TRB Chemedica International S.A. provided diacerein free of charge for the trial but was not involved in the implementation or data analysis. Dr. Aitken had no conflicts of interest to disclose.

The ARTHROL trial of oral resveratrol was funded by the French Ministry of Health and Solidarity (Ministré des Solidarités et de la Santé). Yvery Laboratory provided the resveratrol caplet and matching placebo free of charge. Dr. Nguyen has financial relationships with Actelion, Grünenthal, Ipsen, Lilly, Meda, Merz, Novartis, Preciphar, Sandoz, Takeda, Thuasne, and UCB.

Dr. Lane had no relevant conflicts of interest to declare.

A version of this article appeared on Medscape.com.

VIENNA — Data do not back the use of diacerein or resveratrol for managing the pain of knee osteoarthritis (OA), according to the results of two well-performed, multicenter, double-blind, randomized controlled clinical trials.

During the News in Therapies session at the OARSI 2024 World Congress, the null findings of the DICKENS study and ARTHROL trial were presented alongside a reappraisal of the possible role of botulinum toxin.
 

DICKENS Study of Diacerein

“The role of diacerein in the treatment of OA is controversial,” acknowledged Dawn Aitken, PhD, associate professor at the University of Tasmania in Hobart, Tasmania, Australia. “There are only a few acceptable quality trials to date, and the results are inconsistent,” Dr. Aitken added.

Indeed, a Cochrane review performed in 2014 had concluded that there was “low-quality evidence that diacerein had a small beneficial effect on pain,” she said. The reported overall effect size on a 100-mm visual analog scale, based on a meta-analysis of 10 trials, has been just −8.65 mm, equating to just a 9% pain reduction.

Bruce Jancin/MDedge News

ARTHROL Trial of Resveratrol

Similarly, negative results were reported for resveratrol from the ARTHROL trial, with 55% of the resveratrol- and 55% of placebo-treated individuals achieving a 20% reduction in knee pain intensity at 3 months. The actual change in knee pain from baseline to 3 months was −15.7 for resveratrol and −15.2 for placebo on a numerical rating scale that went from 0 (no pain) up to 100 (worst pain).

Resveratrol is found naturally in grapes, peanuts, pine cones, and Chinese knotweed, and there is a growing body of evidence that it may have pleiotropic effects, said investigator Christelle Nguyen, PhD, MD, a professor of physical and rehabilitation medicine at Université Paris Cité, Paris, France.

It’s available in a powder form over the counter as a treatment for multiple ailments, but more recently, became available as an oral formulation. Dr. Nguyen and colleagues wanted to know if this would make a difference to OA knee pain when added to usual care.

A double-blind, multicenter, placebo-controlled randomized trial was therefore conducted that involved 142 people with knee OA who had been experiencing knee pain for at least 1 month. The participants were equally randomly allocated to receive either oral resveratrol given as two caplets of 20 mg twice daily for the first week, then once daily for a total of 6 months, or a matched placebo.

There was also no effect of resveratrol vs placebo on a host of secondary outcomes measured at 3 and 6 months.

The interpretation is that oral resveratrol may not be effective in this indication or have a biologic effect on the pain pathway, Dr. Nguyen said.

Sara Freeman/Medscape Medical News

Botulinum Toxin: Over But Not Out?

Dr. Nguyen separately reported data from a new systematic review and meta-analysis on the use of intra-articular (IA) botulinum toxin type A (BoNT-A) for knee OA pain.

Seven of the 14 randomized controlled trials included in the meta-analysis had looked specifically at knee OA outcomes in the short, intermediate, and long term.

Results showed a nonsignificant trend favoring BoNT-A use, with the standard mean difference in pain of 0.35 (−0.82; 0.12), −0.27 (−0.61; 0.08), and −0.43 (−1.12; 0.26) for short-, intermediate-, and long-term use, respectively.

In contrast, pain reductions were seen with BoNT-A in three trials that included people with OA of the shoulder or base of the thumb. This begs the question as to whether botulinum toxin may still have a role to play, Dr. Nguyen said in an interview.

“It seems like there may be a positive effect for the shoulder joint and base of the thumb,” she told this news organization.

“So, basically, we found differences between large and small to intermediate joints,” Dr. Nguyen added. “It questions the dilution of botulinum toxin into the joint. If it’s a big joint, maybe the dilution is too high,” she suggested.

This hypothesis will be tested in the upcoming RHIBOT II trial that will begin recruitment later this year. This is a follow-on from the RHIBOT trial that was published in The Lancet Rheumatology 2 years ago.

Meanwhile, the use of botulinum toxin is off-label, Dr. Nguyen said. “We use it in our clinics only when first-line treatment had failed for base of thumb OA.” It’s not offered as a stand-alone intervention, and the IA injections need to be given by someone with experience, she said.
 

Methodologically Sound Studies

Commenting on the studies, Nancy E. Lane, MD, said: “There have been small botulinum studies before but not powered enough so that you could confirm or refute hypotheses.”

Dr. Lane, endowed professor of medicine, rheumatology, and aging research and director for the Center for Musculoskeletal Health at the University of California Davis School of Medicine, Sacramento, California, added: “Similarly for resveratrol, there have been lots of studies.”

Moreover, Dr. Lane observed that the studies were “really well-designed. They were well-powered. The subjects were selected in such a way that was good rigor in the methodologic design, and there were enough people in the studies so that you could really believe the results.”

The take-home is probably that these approaches do not work, Dr. Lane said, “at least when you apply them to moderate-severe knee OA patients, they don’t seem to make a difference.”

The congress was sponsored by the Osteoarthritis Research Society International.

The DICKENS study of diacerein was an investigator-initiated trial that was funded by the National Health and Medical Research Council of Australia. TRB Chemedica International S.A. provided diacerein free of charge for the trial but was not involved in the implementation or data analysis. Dr. Aitken had no conflicts of interest to disclose.

The ARTHROL trial of oral resveratrol was funded by the French Ministry of Health and Solidarity (Ministré des Solidarités et de la Santé). Yvery Laboratory provided the resveratrol caplet and matching placebo free of charge. Dr. Nguyen has financial relationships with Actelion, Grünenthal, Ipsen, Lilly, Meda, Merz, Novartis, Preciphar, Sandoz, Takeda, Thuasne, and UCB.

Dr. Lane had no relevant conflicts of interest to declare.

A version of this article appeared on Medscape.com.

VIENNA — Data do not back the use of diacerein or resveratrol for managing the pain of knee osteoarthritis (OA), according to the results of two well-performed, multicenter, double-blind, randomized controlled clinical trials.

During the News in Therapies session at the OARSI 2024 World Congress, the null findings of the DICKENS study and ARTHROL trial were presented alongside a reappraisal of the possible role of botulinum toxin.
 

DICKENS Study of Diacerein

“The role of diacerein in the treatment of OA is controversial,” acknowledged Dawn Aitken, PhD, associate professor at the University of Tasmania in Hobart, Tasmania, Australia. “There are only a few acceptable quality trials to date, and the results are inconsistent,” Dr. Aitken added.

Indeed, a Cochrane review performed in 2014 had concluded that there was “low-quality evidence that diacerein had a small beneficial effect on pain,” she said. The reported overall effect size on a 100-mm visual analog scale, based on a meta-analysis of 10 trials, has been just −8.65 mm, equating to just a 9% pain reduction.

Bruce Jancin/MDedge News

ARTHROL Trial of Resveratrol

Similarly, negative results were reported for resveratrol from the ARTHROL trial, with 55% of the resveratrol- and 55% of placebo-treated individuals achieving a 20% reduction in knee pain intensity at 3 months. The actual change in knee pain from baseline to 3 months was −15.7 for resveratrol and −15.2 for placebo on a numerical rating scale that went from 0 (no pain) up to 100 (worst pain).

Resveratrol is found naturally in grapes, peanuts, pine cones, and Chinese knotweed, and there is a growing body of evidence that it may have pleiotropic effects, said investigator Christelle Nguyen, PhD, MD, a professor of physical and rehabilitation medicine at Université Paris Cité, Paris, France.

It’s available in a powder form over the counter as a treatment for multiple ailments, but more recently, became available as an oral formulation. Dr. Nguyen and colleagues wanted to know if this would make a difference to OA knee pain when added to usual care.

A double-blind, multicenter, placebo-controlled randomized trial was therefore conducted that involved 142 people with knee OA who had been experiencing knee pain for at least 1 month. The participants were equally randomly allocated to receive either oral resveratrol given as two caplets of 20 mg twice daily for the first week, then once daily for a total of 6 months, or a matched placebo.

There was also no effect of resveratrol vs placebo on a host of secondary outcomes measured at 3 and 6 months.

The interpretation is that oral resveratrol may not be effective in this indication or have a biologic effect on the pain pathway, Dr. Nguyen said.

Sara Freeman/Medscape Medical News

Botulinum Toxin: Over But Not Out?

Dr. Nguyen separately reported data from a new systematic review and meta-analysis on the use of intra-articular (IA) botulinum toxin type A (BoNT-A) for knee OA pain.

Seven of the 14 randomized controlled trials included in the meta-analysis had looked specifically at knee OA outcomes in the short, intermediate, and long term.

Results showed a nonsignificant trend favoring BoNT-A use, with the standard mean difference in pain of 0.35 (−0.82; 0.12), −0.27 (−0.61; 0.08), and −0.43 (−1.12; 0.26) for short-, intermediate-, and long-term use, respectively.

In contrast, pain reductions were seen with BoNT-A in three trials that included people with OA of the shoulder or base of the thumb. This begs the question as to whether botulinum toxin may still have a role to play, Dr. Nguyen said in an interview.

“It seems like there may be a positive effect for the shoulder joint and base of the thumb,” she told this news organization.

“So, basically, we found differences between large and small to intermediate joints,” Dr. Nguyen added. “It questions the dilution of botulinum toxin into the joint. If it’s a big joint, maybe the dilution is too high,” she suggested.

This hypothesis will be tested in the upcoming RHIBOT II trial that will begin recruitment later this year. This is a follow-on from the RHIBOT trial that was published in The Lancet Rheumatology 2 years ago.

Meanwhile, the use of botulinum toxin is off-label, Dr. Nguyen said. “We use it in our clinics only when first-line treatment had failed for base of thumb OA.” It’s not offered as a stand-alone intervention, and the IA injections need to be given by someone with experience, she said.
 

Methodologically Sound Studies

Commenting on the studies, Nancy E. Lane, MD, said: “There have been small botulinum studies before but not powered enough so that you could confirm or refute hypotheses.”

Dr. Lane, endowed professor of medicine, rheumatology, and aging research and director for the Center for Musculoskeletal Health at the University of California Davis School of Medicine, Sacramento, California, added: “Similarly for resveratrol, there have been lots of studies.”

Moreover, Dr. Lane observed that the studies were “really well-designed. They were well-powered. The subjects were selected in such a way that was good rigor in the methodologic design, and there were enough people in the studies so that you could really believe the results.”

The take-home is probably that these approaches do not work, Dr. Lane said, “at least when you apply them to moderate-severe knee OA patients, they don’t seem to make a difference.”

The congress was sponsored by the Osteoarthritis Research Society International.

The DICKENS study of diacerein was an investigator-initiated trial that was funded by the National Health and Medical Research Council of Australia. TRB Chemedica International S.A. provided diacerein free of charge for the trial but was not involved in the implementation or data analysis. Dr. Aitken had no conflicts of interest to disclose.

The ARTHROL trial of oral resveratrol was funded by the French Ministry of Health and Solidarity (Ministré des Solidarités et de la Santé). Yvery Laboratory provided the resveratrol caplet and matching placebo free of charge. Dr. Nguyen has financial relationships with Actelion, Grünenthal, Ipsen, Lilly, Meda, Merz, Novartis, Preciphar, Sandoz, Takeda, Thuasne, and UCB.

Dr. Lane had no relevant conflicts of interest to declare.

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — Four in five people with rheumatoid arthritis (RA) fall into “at risk” categories for the initiation of Janus kinase (JAK) inhibitors set by the European Medicines Agency (EMA), according to data from the long-running British Society for Rheumatology (BSR) Biologics Register in RA (BSRBR-RA).

The EMA decided in January 2023 to implement measures to reduce the risk for serious side effects with JAK inhibitors in the treatment of chronic inflammatory diseases. The EMA’s recommendations advise that JAK inhibitors “should be used in the following patients only if no suitable treatment alternatives are available: those aged 65 years or above, those at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past, and those at increased risk of cancer.” The guidance also says to use JAK inhibitors “with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism [VTE]) ... [and that] the doses should be reduced in patient groups who are at risk of VTE, cancer, or major cardiovascular problems, where possible.”

To gauge the potential impact of the EMA’s decision, researchers analyzed BSRBR-RA data from 1341 individuals with RA who had started treatment with a JAK inhibitor before the agency issued its new recommendations. Among these individuals, 1075 (80.2%) met ≥ 1 EMA risk criterion. Half (54%) were current or past smokers, 44% had an increased risk for major cardiovascular events such as heart attack or stroke, 39% were 65 years or older, and 10% had an increased risk for cancer.

Nearly half (49%) of the study population who met ≥ 1 EMA risk criterion had received only one (31%) or no (18%) prior biologic disease-modifying antirheumatic drug (bDMARD), Zixing Tian, a PhD student at the University of Manchester in England, reported at the  annual meeting of the British Society for Rheumatology. Of the remainder, 23% had received two prior bDMARDs, and 28% had previously received three or more bDMARDs.

Sara Freeman/Medscape Medical News

Considerable Implications

There are potentially two ways of interpreting these data, suggested Ken Baker, BMBCh, PhD, senior clinical fellow and honorary consultant rheumatologist at Newcastle University in Newcastle upon Tyne, England.

“One is that rheumatologists starting these treatments are throwing caution to the wind and ignoring all guidance,” Dr. Baker said.

“The second is perhaps that the EMA guidance is difficult to implement in practice when it involves lots of the comorbidities and risk factors that commonly affect patients with rheumatoid arthritis.”

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in England, also commented on the findings.

Were Cautions Warranted?

Like the US Food and Drug Administration, the EMA has concerns over the use of JAK inhibitors because of the drugs’ potential to increase the risk for serious side effects such as VTE, major adverse cardiovascular events, cancer, and all-cause mortality relative to tumor necrosis factor–alpha inhibitors.

Initially, the EMA issued cautions that only related to the use of tofacitinib (Xeljanz), which was the first JAK inhibitor to gain approval for RA and other chronic inflammatory diseases in Europe, but this expanded to include baricitinib (Olumiant) and most recently any member of the drug class, including abrocitinib (Cibinqo), filgotinib (Jyseleca), and upadacitinib (Rinvoq).

The EMA has done a responsible job of looking at the available data and issuing cautions to protect the populations of patients who may be exposed to these drugs, Peter C. Taylor, BMBCh, PhD, told this news organization. However, they are also severely restricting the populations of patients who can be treated with them. “It’s a complicated situation,” he said.

Shared Decision

“The issue for benefit and risk is there for any drug we use,” said Dr. Taylor, noting that there are over-the-counter drugs that can be “far more dangerous” than JAK inhibitors in terms of cardiovascular risk.

“In my opinion, the really key thing is to be able to communicate the issues with integrity, in a manner that the patient understands, to make sure that the risk is acceptable to them,” Dr. Taylor said.

It is all about optimizing treatment for an individual and proactively managing any other factors that may increase their personal risk for unwanted effects, Maya Buch, MBChB, PhD, professor of rheumatology and honorary consultant rheumatologist at the University of Manchester, said during a debate at the meeting.

“We still have unmet needs for our patient population. Patients aren’t achieving the goals and endpoints that we need,” Dr. Buch said.

“Don’t lose sight of the positive attributes that we’ve seen with JAK inhibitors,” she advised.

“We presume we know what the patient thinks when it comes to a matter of risk assessment, but it is always about tailoring treatment to that individual, and we are sometimes surprised in terms of what the patients want, even in the face of apparent higher risk,” Dr. Buch added.
 

Judicious Use

Iain McInnes, MBChB, PhD, observed during the same debate that it was “hard to argue that drugs are generally unsafe when they have already been approved. It’s also challenging to suggest they are not useful when they are being used.”

Sara Freeman/Medscape Medical News

Dr. McInnes, honorary consultant rheumatologist and vice principal and head of the College of Medical Veterinary & Life Sciences at the University of Glasgow in Scotland, pointed out that the EMA warnings assume that all JAK inhibitors are the same, but is that really the case? This is complex biochemistry, and could newer JAK inhibitors have an improved safety profile?

“There is no free ride in the immune system, and we should bear that in mind,” Dr. McInnes said. “These drugs work ... but we are absolutely flitting along the boundaries of the safety/efficacy window.”

Dr. McInnes told this news organization that clinicians do have to be cautious.

“There’s a paradox in that the very age group that the regulators are now asking us to be cautious about prescribing is pushing JAK inhibitors later and later in the disease course,” he said. This is a time when people would already have other risks for cardiovascular and other events.

“Overall, if used within the regulatory advice, Janus kinase inhibitors are a really useful drug class.”

The BSRBR-RA is funded by a grant from the BSR. The BSR currently receives funding from AbbVie, Amgen, Celltrion, Eli Lilly, Pfizer, Samsung Bioepis, Sanofi, and Sandoz and in the past from Hospira, Merck Sharp & Dohme (MSD), Roche, SOBI, and UCB. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR-RA. All decisions concerning study design, data capture, analyses, interpretation, and publication are made autonomously of any industrial contribution. Ms. Tian had no conflicts of interest to report. Dr. Emery disclosed ties to AbbVie, Bristol Myers Squibb (BMS), Eli Lilly, Pfizer, MSD, Novartis, Roche, Sandoz, Samsung, and UCB. Dr. Taylor disclosed ties to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB. Dr. Buch disclosed ties to Gilead, AbbVie, Arxx Therapeutics, Boehringer Ingelheim, CESAS Medical, Galapagos, Gilead, MediStreams, and Pfizer. Dr. McInnes disclosed ties to AbbVie, AstraZeneca, Boehringer Ingelheim, Compugen, Cabaletta Bio, Causeway, Dexterra, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, and UCB.

A version of this article appeared on Medscape.com .

LIVERPOOL, ENGLAND — Four in five people with rheumatoid arthritis (RA) fall into “at risk” categories for the initiation of Janus kinase (JAK) inhibitors set by the European Medicines Agency (EMA), according to data from the long-running British Society for Rheumatology (BSR) Biologics Register in RA (BSRBR-RA).

The EMA decided in January 2023 to implement measures to reduce the risk for serious side effects with JAK inhibitors in the treatment of chronic inflammatory diseases. The EMA’s recommendations advise that JAK inhibitors “should be used in the following patients only if no suitable treatment alternatives are available: those aged 65 years or above, those at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past, and those at increased risk of cancer.” The guidance also says to use JAK inhibitors “with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism [VTE]) ... [and that] the doses should be reduced in patient groups who are at risk of VTE, cancer, or major cardiovascular problems, where possible.”

To gauge the potential impact of the EMA’s decision, researchers analyzed BSRBR-RA data from 1341 individuals with RA who had started treatment with a JAK inhibitor before the agency issued its new recommendations. Among these individuals, 1075 (80.2%) met ≥ 1 EMA risk criterion. Half (54%) were current or past smokers, 44% had an increased risk for major cardiovascular events such as heart attack or stroke, 39% were 65 years or older, and 10% had an increased risk for cancer.

Nearly half (49%) of the study population who met ≥ 1 EMA risk criterion had received only one (31%) or no (18%) prior biologic disease-modifying antirheumatic drug (bDMARD), Zixing Tian, a PhD student at the University of Manchester in England, reported at the  annual meeting of the British Society for Rheumatology. Of the remainder, 23% had received two prior bDMARDs, and 28% had previously received three or more bDMARDs.

Sara Freeman/Medscape Medical News

Considerable Implications

There are potentially two ways of interpreting these data, suggested Ken Baker, BMBCh, PhD, senior clinical fellow and honorary consultant rheumatologist at Newcastle University in Newcastle upon Tyne, England.

“One is that rheumatologists starting these treatments are throwing caution to the wind and ignoring all guidance,” Dr. Baker said.

“The second is perhaps that the EMA guidance is difficult to implement in practice when it involves lots of the comorbidities and risk factors that commonly affect patients with rheumatoid arthritis.”

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in England, also commented on the findings.

Were Cautions Warranted?

Like the US Food and Drug Administration, the EMA has concerns over the use of JAK inhibitors because of the drugs’ potential to increase the risk for serious side effects such as VTE, major adverse cardiovascular events, cancer, and all-cause mortality relative to tumor necrosis factor–alpha inhibitors.

Initially, the EMA issued cautions that only related to the use of tofacitinib (Xeljanz), which was the first JAK inhibitor to gain approval for RA and other chronic inflammatory diseases in Europe, but this expanded to include baricitinib (Olumiant) and most recently any member of the drug class, including abrocitinib (Cibinqo), filgotinib (Jyseleca), and upadacitinib (Rinvoq).

The EMA has done a responsible job of looking at the available data and issuing cautions to protect the populations of patients who may be exposed to these drugs, Peter C. Taylor, BMBCh, PhD, told this news organization. However, they are also severely restricting the populations of patients who can be treated with them. “It’s a complicated situation,” he said.

Shared Decision

“The issue for benefit and risk is there for any drug we use,” said Dr. Taylor, noting that there are over-the-counter drugs that can be “far more dangerous” than JAK inhibitors in terms of cardiovascular risk.

“In my opinion, the really key thing is to be able to communicate the issues with integrity, in a manner that the patient understands, to make sure that the risk is acceptable to them,” Dr. Taylor said.

It is all about optimizing treatment for an individual and proactively managing any other factors that may increase their personal risk for unwanted effects, Maya Buch, MBChB, PhD, professor of rheumatology and honorary consultant rheumatologist at the University of Manchester, said during a debate at the meeting.

“We still have unmet needs for our patient population. Patients aren’t achieving the goals and endpoints that we need,” Dr. Buch said.

“Don’t lose sight of the positive attributes that we’ve seen with JAK inhibitors,” she advised.

“We presume we know what the patient thinks when it comes to a matter of risk assessment, but it is always about tailoring treatment to that individual, and we are sometimes surprised in terms of what the patients want, even in the face of apparent higher risk,” Dr. Buch added.
 

Judicious Use

Iain McInnes, MBChB, PhD, observed during the same debate that it was “hard to argue that drugs are generally unsafe when they have already been approved. It’s also challenging to suggest they are not useful when they are being used.”

Sara Freeman/Medscape Medical News

Dr. McInnes, honorary consultant rheumatologist and vice principal and head of the College of Medical Veterinary & Life Sciences at the University of Glasgow in Scotland, pointed out that the EMA warnings assume that all JAK inhibitors are the same, but is that really the case? This is complex biochemistry, and could newer JAK inhibitors have an improved safety profile?

“There is no free ride in the immune system, and we should bear that in mind,” Dr. McInnes said. “These drugs work ... but we are absolutely flitting along the boundaries of the safety/efficacy window.”

Dr. McInnes told this news organization that clinicians do have to be cautious.

“There’s a paradox in that the very age group that the regulators are now asking us to be cautious about prescribing is pushing JAK inhibitors later and later in the disease course,” he said. This is a time when people would already have other risks for cardiovascular and other events.

“Overall, if used within the regulatory advice, Janus kinase inhibitors are a really useful drug class.”

The BSRBR-RA is funded by a grant from the BSR. The BSR currently receives funding from AbbVie, Amgen, Celltrion, Eli Lilly, Pfizer, Samsung Bioepis, Sanofi, and Sandoz and in the past from Hospira, Merck Sharp & Dohme (MSD), Roche, SOBI, and UCB. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR-RA. All decisions concerning study design, data capture, analyses, interpretation, and publication are made autonomously of any industrial contribution. Ms. Tian had no conflicts of interest to report. Dr. Emery disclosed ties to AbbVie, Bristol Myers Squibb (BMS), Eli Lilly, Pfizer, MSD, Novartis, Roche, Sandoz, Samsung, and UCB. Dr. Taylor disclosed ties to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB. Dr. Buch disclosed ties to Gilead, AbbVie, Arxx Therapeutics, Boehringer Ingelheim, CESAS Medical, Galapagos, Gilead, MediStreams, and Pfizer. Dr. McInnes disclosed ties to AbbVie, AstraZeneca, Boehringer Ingelheim, Compugen, Cabaletta Bio, Causeway, Dexterra, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, and UCB.

A version of this article appeared on Medscape.com .

LIVERPOOL, ENGLAND — Four in five people with rheumatoid arthritis (RA) fall into “at risk” categories for the initiation of Janus kinase (JAK) inhibitors set by the European Medicines Agency (EMA), according to data from the long-running British Society for Rheumatology (BSR) Biologics Register in RA (BSRBR-RA).

The EMA decided in January 2023 to implement measures to reduce the risk for serious side effects with JAK inhibitors in the treatment of chronic inflammatory diseases. The EMA’s recommendations advise that JAK inhibitors “should be used in the following patients only if no suitable treatment alternatives are available: those aged 65 years or above, those at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past, and those at increased risk of cancer.” The guidance also says to use JAK inhibitors “with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism [VTE]) ... [and that] the doses should be reduced in patient groups who are at risk of VTE, cancer, or major cardiovascular problems, where possible.”

To gauge the potential impact of the EMA’s decision, researchers analyzed BSRBR-RA data from 1341 individuals with RA who had started treatment with a JAK inhibitor before the agency issued its new recommendations. Among these individuals, 1075 (80.2%) met ≥ 1 EMA risk criterion. Half (54%) were current or past smokers, 44% had an increased risk for major cardiovascular events such as heart attack or stroke, 39% were 65 years or older, and 10% had an increased risk for cancer.

Nearly half (49%) of the study population who met ≥ 1 EMA risk criterion had received only one (31%) or no (18%) prior biologic disease-modifying antirheumatic drug (bDMARD), Zixing Tian, a PhD student at the University of Manchester in England, reported at the  annual meeting of the British Society for Rheumatology. Of the remainder, 23% had received two prior bDMARDs, and 28% had previously received three or more bDMARDs.

Sara Freeman/Medscape Medical News

Considerable Implications

There are potentially two ways of interpreting these data, suggested Ken Baker, BMBCh, PhD, senior clinical fellow and honorary consultant rheumatologist at Newcastle University in Newcastle upon Tyne, England.

“One is that rheumatologists starting these treatments are throwing caution to the wind and ignoring all guidance,” Dr. Baker said.

“The second is perhaps that the EMA guidance is difficult to implement in practice when it involves lots of the comorbidities and risk factors that commonly affect patients with rheumatoid arthritis.”

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in England, also commented on the findings.

Were Cautions Warranted?

Like the US Food and Drug Administration, the EMA has concerns over the use of JAK inhibitors because of the drugs’ potential to increase the risk for serious side effects such as VTE, major adverse cardiovascular events, cancer, and all-cause mortality relative to tumor necrosis factor–alpha inhibitors.

Initially, the EMA issued cautions that only related to the use of tofacitinib (Xeljanz), which was the first JAK inhibitor to gain approval for RA and other chronic inflammatory diseases in Europe, but this expanded to include baricitinib (Olumiant) and most recently any member of the drug class, including abrocitinib (Cibinqo), filgotinib (Jyseleca), and upadacitinib (Rinvoq).

The EMA has done a responsible job of looking at the available data and issuing cautions to protect the populations of patients who may be exposed to these drugs, Peter C. Taylor, BMBCh, PhD, told this news organization. However, they are also severely restricting the populations of patients who can be treated with them. “It’s a complicated situation,” he said.

Shared Decision

“The issue for benefit and risk is there for any drug we use,” said Dr. Taylor, noting that there are over-the-counter drugs that can be “far more dangerous” than JAK inhibitors in terms of cardiovascular risk.

“In my opinion, the really key thing is to be able to communicate the issues with integrity, in a manner that the patient understands, to make sure that the risk is acceptable to them,” Dr. Taylor said.

It is all about optimizing treatment for an individual and proactively managing any other factors that may increase their personal risk for unwanted effects, Maya Buch, MBChB, PhD, professor of rheumatology and honorary consultant rheumatologist at the University of Manchester, said during a debate at the meeting.

“We still have unmet needs for our patient population. Patients aren’t achieving the goals and endpoints that we need,” Dr. Buch said.

“Don’t lose sight of the positive attributes that we’ve seen with JAK inhibitors,” she advised.

“We presume we know what the patient thinks when it comes to a matter of risk assessment, but it is always about tailoring treatment to that individual, and we are sometimes surprised in terms of what the patients want, even in the face of apparent higher risk,” Dr. Buch added.
 

Judicious Use

Iain McInnes, MBChB, PhD, observed during the same debate that it was “hard to argue that drugs are generally unsafe when they have already been approved. It’s also challenging to suggest they are not useful when they are being used.”

Sara Freeman/Medscape Medical News

Dr. McInnes, honorary consultant rheumatologist and vice principal and head of the College of Medical Veterinary & Life Sciences at the University of Glasgow in Scotland, pointed out that the EMA warnings assume that all JAK inhibitors are the same, but is that really the case? This is complex biochemistry, and could newer JAK inhibitors have an improved safety profile?

“There is no free ride in the immune system, and we should bear that in mind,” Dr. McInnes said. “These drugs work ... but we are absolutely flitting along the boundaries of the safety/efficacy window.”

Dr. McInnes told this news organization that clinicians do have to be cautious.

“There’s a paradox in that the very age group that the regulators are now asking us to be cautious about prescribing is pushing JAK inhibitors later and later in the disease course,” he said. This is a time when people would already have other risks for cardiovascular and other events.

“Overall, if used within the regulatory advice, Janus kinase inhibitors are a really useful drug class.”

The BSRBR-RA is funded by a grant from the BSR. The BSR currently receives funding from AbbVie, Amgen, Celltrion, Eli Lilly, Pfizer, Samsung Bioepis, Sanofi, and Sandoz and in the past from Hospira, Merck Sharp & Dohme (MSD), Roche, SOBI, and UCB. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR-RA. All decisions concerning study design, data capture, analyses, interpretation, and publication are made autonomously of any industrial contribution. Ms. Tian had no conflicts of interest to report. Dr. Emery disclosed ties to AbbVie, Bristol Myers Squibb (BMS), Eli Lilly, Pfizer, MSD, Novartis, Roche, Sandoz, Samsung, and UCB. Dr. Taylor disclosed ties to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB. Dr. Buch disclosed ties to Gilead, AbbVie, Arxx Therapeutics, Boehringer Ingelheim, CESAS Medical, Galapagos, Gilead, MediStreams, and Pfizer. Dr. McInnes disclosed ties to AbbVie, AstraZeneca, Boehringer Ingelheim, Compugen, Cabaletta Bio, Causeway, Dexterra, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, and UCB.

A version of this article appeared on Medscape.com .

New guidelines to manage peripheral neuropathy related to Sjögren disease have been developed by a multidisciplinary team of physicians from across medicine.

The guidelines will provide an evidence-based resource for the assessment, diagnosis, and treatment of various peripheral neuropathies related to the disorder.

Up until now, the field has been “haphazard and chaotic,” lead author George Sarka, MD, DrPH, MPH, director of the CME Committee for MemorialCare, Saddleback Medical Center, Laguna Hills, California, and member of the Sjögren Foundation PNS Guidelines Topic Review Group (TRG), told this news organization.

Dr. Sarka discussed the initiative at the American Academy of Neurology 2024 annual meeting.


 

Severe, Complex Illness

Sjögren disease is the second most common autoimmune rheumatic disorder after rheumatoid arthritis, affecting an estimated 4 million Americans. Women make up most of the patient population at a ratio of 9:1.

The condition typically affects the mucous membranes and moisture-secreting glands of the eyes and mouth, resulting in decreased tears and saliva. But peripheral nervous system (PNS) manifestations often precede these symptoms and can occur in up to 60% of Sjögren disease cases.

“Traditionally, Sjögren’s was looked at as a dry eye and dry mouth disease, but we realize now that it’s so much broader than that,” said Dr. Sarka. “It’s a severe, systemic, and complex illness that can affect any body organ or system, and the nervous system is frequently affected.”

PNS manifestations cause more than mere discomfort; they can lead to diagnostic and management challenges, costly treatments, and diminished quality of life.

Getting a proper diagnosis goes a long way toward improving the quality of life for these patients, Steven Mandel, MD, clinical professor of neurology at the Zucker School of Medicine at Hofstra-Northwell, adjunct clinical professor of medicine at NY Medical College, New York City, and member of the TRG, told this news organization.

The problem is, doctors don’t always think an autoimmune disorder is causing the symptoms, said Dr. Sarka. “There’s an old adage in neurology that if you don’t think about it, you’re going to miss it; you have to ask, and that’s what we’re trying to get people to do.”

The condition often accompanies other immune system disorders such as rheumatoid arthritis and lupus. But as patients are referred back and forth between ophthalmologists, rheumatologists, and neurologists, the condition is often missed. “It could be 4 or 5 years before a definitive diagnosis of Sjögren’s is made,” said Dr. Sarka.

He believes the education system is partly to blame. “Medical schools have been very deficient in teaching people about recognizing Sjögren disease.”

That leaves many physicians at a loss about “what to do with these patients when they walk in the door,” said Dr. Mandel. “They don’t know how to manage them; they don’t know how to diagnose them; and they don’t know how to treat them.”

Developing guidelines with multispecialty collaboration was “absolutely critical” in addressing this knowledge gap, Dr. Mandel added. That process involved “a very rigorous and transparent methodology so that it would be accepted by all the professionals involved in Sjögren’s,” he said.

The process took 3 years and involved amassing and grading the evidence, getting consensus from committee members, developing recommendations, and getting feedback and external review.
 

Scant Evidence

An early literature search revealed very little evidence on PNS manifestations in patients with Sjögren disease, so the guideline committee “leaned very heavily on expert opinion” to develop recommendations, Kathy Hammitt, MA, vice president of Medical and Scientific Affairs, Sjögren’s Foundation, told this news organization.

The literature search also showed different terms are used to describe PNS, “which is where the chaos comes in,” said Dr. Sarka.

Experts from different specialties worked together to define and align nomenclature used by various specialists. They developed definitions for seven PNS categories including mononeuropathy, large fiber neuropathy, small fiber neuropathy, demyelinating polyradiculoneuropathy, ganglionopathy, vasculitis neuropathy, and autoimmune nervous system neuropathy.

The guidelines pertaining to PNS manifestations encompass a spectrum of neurologic abnormalities, including cranial neuropathies (trigeminal neuropathy or acute facial neuropathy), polyneuropathies (large fiber neuropathy, small fiber neuropathy, demyelinating polyradiculoneuropathy, vasculitis neuropathy, or ganglionopathy), and autonomic nervous system (ANS) neuropathies (postural tachycardia, orthostatic hypotension, or autonomic dysfunction).
 

Key Steps

The guidelines address two key steps for each PNS manifestation — the workup and evaluation of patients with suspected ANS manifestation including standard evaluations, diagnostic tests, and treatment. The experts developed 31 best practices for diagnosis and workup and 20 treatment recommendations.

Initial assessment of potential ANS involvement includes asking patients about orthostatic postural lightheadedness and difficulties with digestion, urination, sweating, and sexual function.

Treatment of autoimmune diseases typically focuses on relieving symptoms and can include steroids, the anticonvulsant gabapentin, the monoclonal antibody rituximab, and intravenous immunoglobulin. “The type of neuropathy will mandate or suggest certain therapies over others,” said Dr. Sarka, adding that a patient can have more than one neuropathy.

Therapeutics for Sjögren disease is another example of an area that has been “very haphazard,” he added.

The guidelines are aimed not just at specialists but also at general practitioners who treat many of these patients. But Dr. Hammitt emphasized that neurologists can be “instrumental” in identifying Sjögren disease in patients with PNS symptoms.

“Our hope is that specialists — in this case, neurologists — will recognize the potential for this condition in their PNS patients and ensure referral to a rheumatologist or knowledgeable family practitioner to manage overall care.”

The committee will soon submit its manuscript to the AAN for publication.

“Once published, we will have a robust dissemination strategy to ensure that providers, patients, and policymakers are aware of, and use, this very valuable resource,” said Dr. Hammitt.

No conflicts of interest were reported.

A version of this article appeared on Medscape.com.

New guidelines to manage peripheral neuropathy related to Sjögren disease have been developed by a multidisciplinary team of physicians from across medicine.

The guidelines will provide an evidence-based resource for the assessment, diagnosis, and treatment of various peripheral neuropathies related to the disorder.

Up until now, the field has been “haphazard and chaotic,” lead author George Sarka, MD, DrPH, MPH, director of the CME Committee for MemorialCare, Saddleback Medical Center, Laguna Hills, California, and member of the Sjögren Foundation PNS Guidelines Topic Review Group (TRG), told this news organization.

Dr. Sarka discussed the initiative at the American Academy of Neurology 2024 annual meeting.