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Best estimates made for hydroxychloroquine retinopathy risk
A new study likely makes the best estimate yet of the degree of retinopathy risk that patients who take the antimalarial drug hydroxychloroquine (HCQ) can expect, deriving mainly from the cumulative dose taken during the first 5 years of use, according to a study published in Annals of Internal Medicine.
HCQ works to decrease activity in a patient’s immune system, which is effective in many cases of systemic lupus erythematosus, one of the most common indications for the drug. However, an adverse outcome of treatment can be HCQ retinopathy, a progressive form of vision loss in patients taking HCQ over an extended period (mostly for longer than 5 years). The disease is often asymptomatic, although some patients do present a paracentral scotoma and a decrease in color vision. Patients may also notice flashing shapes in their vision and find that they have difficulty reading. Eventually, HCQ retinopathy can lead to loss of visual acuity, loss of peripheral vision, and loss of night vision.
Researchers from Kaiser Permanente Northern California and Harvard Medical School analyzed 3,325 persons who received HCQ for 5 or more years between 2004 and 2020. Their goal was to both characterize the long-term risk for incident HCQ retinopathy and examine the degree to which average HCQ dose within the first 5 years of treatment serves as a prediction of the risk.
The researchers then estimated the risk for developing retinopathy after 15 years, according to patients’ average dosing levels during the first 5 years of therapy. Overall, 81 participants developed HCQ retinopathy with overall cumulative incidences of 2.5% after 10 years and 8.6% after 15 years; the risk was greater for those given a higher dose during the first 5 years of treatment.
The mechanism of how HCQ toxicity may occur is still not completely known. There is evidence that toxicity happens because HCQ binds to melanin in both the retinal pigment epithelium and uvea in high concentrations. HCQ can interfere with lysosomal function, leading to oxidation and accumulation of lysosomes, which can cause dysfunction of the retinal pigment epithelium.
Progressive retinopathy can continue even after the drug is stopped. “It’s thought to be a very mild but important risk,” said Nilanjana Bose, MD, MBA, a rheumatologist with Memorial Hermann Health System in Houston. “Patients taking HCQ must be screened for retinal issues, most certainly elderly patients and patients with any kind of comorbidities.”
A 2021 joint position statement from the American College of Rheumatology, American Academy of Dermatology, the Rheumatologic Dermatology Society, and the American Academy of Ophthalmology recommends a baseline eye exam within a few months after starting therapy, then additional screening at 5 years on HCQ and annually thereafter.
“Early detection of retinopathy is important in overall visual prognosis, because toxicity can continue even after discontinuation of the medication,” said Rukhsana G. Mirza, MD, professor of ophthalmology and medical education at Northwestern University in Chicago.
“Examination alone is not sufficient to evaluate early changes, and specialized testing must be done. These include color photos, visual field tests, optical coherence tomography, fundus autofluorescence and in some cases, multifocal electroretinogram. Also, the AAO [American Academy of Ophthalmology] has specific recommendations related to Asian patients as they may have a different pattern of retinopathy that must also be considered.”
More accurate risk measurements
This news organization asked study coauthor April Jorge, MD, assistant professor of medicine in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, Boston, to discuss the study, how it correlates to past research, and what it adds that’s new and useful to rheumatologists and ophthalmologists:
Question: Your research found that a higher dose of HCQ in the first 5 years of treatment led to a greater risk of retinopathy. Is there any indication that a lower dose given more frequently, either within that 5-year period or longer, would pose a similar risk?
Answer: In our study, we assessed the HCQ dose in the first 5 years of use but followed patients who continued the medication longer than 5 years, through up to 15 years of use. Therefore, we compared the risk of HCQ retinopathy associated with different HCQ dosages but for the same duration of use. We found that for any dose of HCQ, the risk of retinopathy increases the longer the medication is used. However, patients who used a higher dose of HCQ had a higher risk of developing retinopathy over time.
Although current guidelines recommend avoiding any HCQ dose over 5 mg/kg per day to reduce the risk of retinopathy, we found a higher risk of retinopathy associated with dosing over 6 mg/kg per day than between 5 and 6 mg/kg per day and the lowest risk with dosing under 5 mg/kg per day.
Q: How does your study align with and/or expand upon previous research regarding HCQ risk?
A: An important prior study of hydroxychloroquine retinopathy was the 2014 study by Ronald B. Melles, MD, and Michael F. Marmor, MD, published in JAMA Ophthalmology. Prior to our present study, that was the largest study to use the modern screening method (optical coherence tomography) to detect HCQ retinopathy. That screening tool is more sensitive than older methods, so it can detect early/mild cases of retinopathy that are typically asymptomatic. Compared to older studies, that 2014 study found a much higher risk of HCQ retinopathy than was previously appreciated.
However, that 2014 study did have some key limitations that could affect the risk estimates, such as using prevalent cases. A key feature of our present study is that we took several important steps to generate more accurate risk estimates. This included using an incident user cohort and detecting incident retinopathy cases through serial review of optical coherence tomography (screening) studies.
To achieve a high degree of methodologic rigor in correctly identifying retinopathy outcomes, we had expert ophthalmologists perform masked adjudication of all screening studies, and we assessed the intra-rater reliability of these study interpretations. Therefore, our study adds to the literature more accurate estimates of retinopathy risk. We found a lower cumulative incidence of retinopathy than was identified in the 2014 study, but the risk is still noteworthy.
Also unique to our study, we graded the severity of HCQ retinopathy outcomes. This was important, as we found that the majority of retinopathy cases detected through routine screening are mild and presumed to be asymptomatic. This will likely be reassuring news for patients that we can screen for this adverse event to detect it early and prevent vision loss.
Another important difference was that we assessed the risk of retinopathy associated with using over 6 mg/kg per day, between 5 and 6 mg/kg per day, and less than 5 mg/kg per day, whereas the highest dosing group assessed in the 2014 study included all patients using over 5 mg/kg per day. The risk was considerably higher in the > 6 mg/kg per day group than in the 5-6 mg/kg per day group.
Q: How can rheumatologists and ophthalmologists use this new information specifically to better treat their patients?
A: Our study provides more accurate estimates of the risk of HCQ retinopathy than in prior studies. These risk estimates can be used when rheumatologists (and other clinicians who prescribe HCQ) consider the risks and benefits of this otherwise important and well-tolerated medication. The risk associated with different dose ranges could also inform dosing decisions, since dosing over 6 mg/kg per day may be more of a concern than using doses in the 5-6 mg/kg range. Ophthalmologists can also use these new risk estimates to counsel patients of the importance of HCQ retinopathy screening and can also hopefully provide some reassurance to patients that the risk of severe retinopathy is low as long as they are being monitored.
The study authors were supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Rheumatology Research Foundation. The authors report no relevant financial relationships. Dr. Bose and Dr. Mirza had no relevant disclosures.
A version of this article first appeared on Medscape.com.
A new study likely makes the best estimate yet of the degree of retinopathy risk that patients who take the antimalarial drug hydroxychloroquine (HCQ) can expect, deriving mainly from the cumulative dose taken during the first 5 years of use, according to a study published in Annals of Internal Medicine.
HCQ works to decrease activity in a patient’s immune system, which is effective in many cases of systemic lupus erythematosus, one of the most common indications for the drug. However, an adverse outcome of treatment can be HCQ retinopathy, a progressive form of vision loss in patients taking HCQ over an extended period (mostly for longer than 5 years). The disease is often asymptomatic, although some patients do present a paracentral scotoma and a decrease in color vision. Patients may also notice flashing shapes in their vision and find that they have difficulty reading. Eventually, HCQ retinopathy can lead to loss of visual acuity, loss of peripheral vision, and loss of night vision.
Researchers from Kaiser Permanente Northern California and Harvard Medical School analyzed 3,325 persons who received HCQ for 5 or more years between 2004 and 2020. Their goal was to both characterize the long-term risk for incident HCQ retinopathy and examine the degree to which average HCQ dose within the first 5 years of treatment serves as a prediction of the risk.
The researchers then estimated the risk for developing retinopathy after 15 years, according to patients’ average dosing levels during the first 5 years of therapy. Overall, 81 participants developed HCQ retinopathy with overall cumulative incidences of 2.5% after 10 years and 8.6% after 15 years; the risk was greater for those given a higher dose during the first 5 years of treatment.
The mechanism of how HCQ toxicity may occur is still not completely known. There is evidence that toxicity happens because HCQ binds to melanin in both the retinal pigment epithelium and uvea in high concentrations. HCQ can interfere with lysosomal function, leading to oxidation and accumulation of lysosomes, which can cause dysfunction of the retinal pigment epithelium.
Progressive retinopathy can continue even after the drug is stopped. “It’s thought to be a very mild but important risk,” said Nilanjana Bose, MD, MBA, a rheumatologist with Memorial Hermann Health System in Houston. “Patients taking HCQ must be screened for retinal issues, most certainly elderly patients and patients with any kind of comorbidities.”
A 2021 joint position statement from the American College of Rheumatology, American Academy of Dermatology, the Rheumatologic Dermatology Society, and the American Academy of Ophthalmology recommends a baseline eye exam within a few months after starting therapy, then additional screening at 5 years on HCQ and annually thereafter.
“Early detection of retinopathy is important in overall visual prognosis, because toxicity can continue even after discontinuation of the medication,” said Rukhsana G. Mirza, MD, professor of ophthalmology and medical education at Northwestern University in Chicago.
“Examination alone is not sufficient to evaluate early changes, and specialized testing must be done. These include color photos, visual field tests, optical coherence tomography, fundus autofluorescence and in some cases, multifocal electroretinogram. Also, the AAO [American Academy of Ophthalmology] has specific recommendations related to Asian patients as they may have a different pattern of retinopathy that must also be considered.”
More accurate risk measurements
This news organization asked study coauthor April Jorge, MD, assistant professor of medicine in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, Boston, to discuss the study, how it correlates to past research, and what it adds that’s new and useful to rheumatologists and ophthalmologists:
Question: Your research found that a higher dose of HCQ in the first 5 years of treatment led to a greater risk of retinopathy. Is there any indication that a lower dose given more frequently, either within that 5-year period or longer, would pose a similar risk?
Answer: In our study, we assessed the HCQ dose in the first 5 years of use but followed patients who continued the medication longer than 5 years, through up to 15 years of use. Therefore, we compared the risk of HCQ retinopathy associated with different HCQ dosages but for the same duration of use. We found that for any dose of HCQ, the risk of retinopathy increases the longer the medication is used. However, patients who used a higher dose of HCQ had a higher risk of developing retinopathy over time.
Although current guidelines recommend avoiding any HCQ dose over 5 mg/kg per day to reduce the risk of retinopathy, we found a higher risk of retinopathy associated with dosing over 6 mg/kg per day than between 5 and 6 mg/kg per day and the lowest risk with dosing under 5 mg/kg per day.
Q: How does your study align with and/or expand upon previous research regarding HCQ risk?
A: An important prior study of hydroxychloroquine retinopathy was the 2014 study by Ronald B. Melles, MD, and Michael F. Marmor, MD, published in JAMA Ophthalmology. Prior to our present study, that was the largest study to use the modern screening method (optical coherence tomography) to detect HCQ retinopathy. That screening tool is more sensitive than older methods, so it can detect early/mild cases of retinopathy that are typically asymptomatic. Compared to older studies, that 2014 study found a much higher risk of HCQ retinopathy than was previously appreciated.
However, that 2014 study did have some key limitations that could affect the risk estimates, such as using prevalent cases. A key feature of our present study is that we took several important steps to generate more accurate risk estimates. This included using an incident user cohort and detecting incident retinopathy cases through serial review of optical coherence tomography (screening) studies.
To achieve a high degree of methodologic rigor in correctly identifying retinopathy outcomes, we had expert ophthalmologists perform masked adjudication of all screening studies, and we assessed the intra-rater reliability of these study interpretations. Therefore, our study adds to the literature more accurate estimates of retinopathy risk. We found a lower cumulative incidence of retinopathy than was identified in the 2014 study, but the risk is still noteworthy.
Also unique to our study, we graded the severity of HCQ retinopathy outcomes. This was important, as we found that the majority of retinopathy cases detected through routine screening are mild and presumed to be asymptomatic. This will likely be reassuring news for patients that we can screen for this adverse event to detect it early and prevent vision loss.
Another important difference was that we assessed the risk of retinopathy associated with using over 6 mg/kg per day, between 5 and 6 mg/kg per day, and less than 5 mg/kg per day, whereas the highest dosing group assessed in the 2014 study included all patients using over 5 mg/kg per day. The risk was considerably higher in the > 6 mg/kg per day group than in the 5-6 mg/kg per day group.
Q: How can rheumatologists and ophthalmologists use this new information specifically to better treat their patients?
A: Our study provides more accurate estimates of the risk of HCQ retinopathy than in prior studies. These risk estimates can be used when rheumatologists (and other clinicians who prescribe HCQ) consider the risks and benefits of this otherwise important and well-tolerated medication. The risk associated with different dose ranges could also inform dosing decisions, since dosing over 6 mg/kg per day may be more of a concern than using doses in the 5-6 mg/kg range. Ophthalmologists can also use these new risk estimates to counsel patients of the importance of HCQ retinopathy screening and can also hopefully provide some reassurance to patients that the risk of severe retinopathy is low as long as they are being monitored.
The study authors were supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Rheumatology Research Foundation. The authors report no relevant financial relationships. Dr. Bose and Dr. Mirza had no relevant disclosures.
A version of this article first appeared on Medscape.com.
A new study likely makes the best estimate yet of the degree of retinopathy risk that patients who take the antimalarial drug hydroxychloroquine (HCQ) can expect, deriving mainly from the cumulative dose taken during the first 5 years of use, according to a study published in Annals of Internal Medicine.
HCQ works to decrease activity in a patient’s immune system, which is effective in many cases of systemic lupus erythematosus, one of the most common indications for the drug. However, an adverse outcome of treatment can be HCQ retinopathy, a progressive form of vision loss in patients taking HCQ over an extended period (mostly for longer than 5 years). The disease is often asymptomatic, although some patients do present a paracentral scotoma and a decrease in color vision. Patients may also notice flashing shapes in their vision and find that they have difficulty reading. Eventually, HCQ retinopathy can lead to loss of visual acuity, loss of peripheral vision, and loss of night vision.
Researchers from Kaiser Permanente Northern California and Harvard Medical School analyzed 3,325 persons who received HCQ for 5 or more years between 2004 and 2020. Their goal was to both characterize the long-term risk for incident HCQ retinopathy and examine the degree to which average HCQ dose within the first 5 years of treatment serves as a prediction of the risk.
The researchers then estimated the risk for developing retinopathy after 15 years, according to patients’ average dosing levels during the first 5 years of therapy. Overall, 81 participants developed HCQ retinopathy with overall cumulative incidences of 2.5% after 10 years and 8.6% after 15 years; the risk was greater for those given a higher dose during the first 5 years of treatment.
The mechanism of how HCQ toxicity may occur is still not completely known. There is evidence that toxicity happens because HCQ binds to melanin in both the retinal pigment epithelium and uvea in high concentrations. HCQ can interfere with lysosomal function, leading to oxidation and accumulation of lysosomes, which can cause dysfunction of the retinal pigment epithelium.
Progressive retinopathy can continue even after the drug is stopped. “It’s thought to be a very mild but important risk,” said Nilanjana Bose, MD, MBA, a rheumatologist with Memorial Hermann Health System in Houston. “Patients taking HCQ must be screened for retinal issues, most certainly elderly patients and patients with any kind of comorbidities.”
A 2021 joint position statement from the American College of Rheumatology, American Academy of Dermatology, the Rheumatologic Dermatology Society, and the American Academy of Ophthalmology recommends a baseline eye exam within a few months after starting therapy, then additional screening at 5 years on HCQ and annually thereafter.
“Early detection of retinopathy is important in overall visual prognosis, because toxicity can continue even after discontinuation of the medication,” said Rukhsana G. Mirza, MD, professor of ophthalmology and medical education at Northwestern University in Chicago.
“Examination alone is not sufficient to evaluate early changes, and specialized testing must be done. These include color photos, visual field tests, optical coherence tomography, fundus autofluorescence and in some cases, multifocal electroretinogram. Also, the AAO [American Academy of Ophthalmology] has specific recommendations related to Asian patients as they may have a different pattern of retinopathy that must also be considered.”
More accurate risk measurements
This news organization asked study coauthor April Jorge, MD, assistant professor of medicine in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, Boston, to discuss the study, how it correlates to past research, and what it adds that’s new and useful to rheumatologists and ophthalmologists:
Question: Your research found that a higher dose of HCQ in the first 5 years of treatment led to a greater risk of retinopathy. Is there any indication that a lower dose given more frequently, either within that 5-year period or longer, would pose a similar risk?
Answer: In our study, we assessed the HCQ dose in the first 5 years of use but followed patients who continued the medication longer than 5 years, through up to 15 years of use. Therefore, we compared the risk of HCQ retinopathy associated with different HCQ dosages but for the same duration of use. We found that for any dose of HCQ, the risk of retinopathy increases the longer the medication is used. However, patients who used a higher dose of HCQ had a higher risk of developing retinopathy over time.
Although current guidelines recommend avoiding any HCQ dose over 5 mg/kg per day to reduce the risk of retinopathy, we found a higher risk of retinopathy associated with dosing over 6 mg/kg per day than between 5 and 6 mg/kg per day and the lowest risk with dosing under 5 mg/kg per day.
Q: How does your study align with and/or expand upon previous research regarding HCQ risk?
A: An important prior study of hydroxychloroquine retinopathy was the 2014 study by Ronald B. Melles, MD, and Michael F. Marmor, MD, published in JAMA Ophthalmology. Prior to our present study, that was the largest study to use the modern screening method (optical coherence tomography) to detect HCQ retinopathy. That screening tool is more sensitive than older methods, so it can detect early/mild cases of retinopathy that are typically asymptomatic. Compared to older studies, that 2014 study found a much higher risk of HCQ retinopathy than was previously appreciated.
However, that 2014 study did have some key limitations that could affect the risk estimates, such as using prevalent cases. A key feature of our present study is that we took several important steps to generate more accurate risk estimates. This included using an incident user cohort and detecting incident retinopathy cases through serial review of optical coherence tomography (screening) studies.
To achieve a high degree of methodologic rigor in correctly identifying retinopathy outcomes, we had expert ophthalmologists perform masked adjudication of all screening studies, and we assessed the intra-rater reliability of these study interpretations. Therefore, our study adds to the literature more accurate estimates of retinopathy risk. We found a lower cumulative incidence of retinopathy than was identified in the 2014 study, but the risk is still noteworthy.
Also unique to our study, we graded the severity of HCQ retinopathy outcomes. This was important, as we found that the majority of retinopathy cases detected through routine screening are mild and presumed to be asymptomatic. This will likely be reassuring news for patients that we can screen for this adverse event to detect it early and prevent vision loss.
Another important difference was that we assessed the risk of retinopathy associated with using over 6 mg/kg per day, between 5 and 6 mg/kg per day, and less than 5 mg/kg per day, whereas the highest dosing group assessed in the 2014 study included all patients using over 5 mg/kg per day. The risk was considerably higher in the > 6 mg/kg per day group than in the 5-6 mg/kg per day group.
Q: How can rheumatologists and ophthalmologists use this new information specifically to better treat their patients?
A: Our study provides more accurate estimates of the risk of HCQ retinopathy than in prior studies. These risk estimates can be used when rheumatologists (and other clinicians who prescribe HCQ) consider the risks and benefits of this otherwise important and well-tolerated medication. The risk associated with different dose ranges could also inform dosing decisions, since dosing over 6 mg/kg per day may be more of a concern than using doses in the 5-6 mg/kg range. Ophthalmologists can also use these new risk estimates to counsel patients of the importance of HCQ retinopathy screening and can also hopefully provide some reassurance to patients that the risk of severe retinopathy is low as long as they are being monitored.
The study authors were supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Rheumatology Research Foundation. The authors report no relevant financial relationships. Dr. Bose and Dr. Mirza had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Commentary: Interstitial Lung Disease, Onset Time, and RA, January 2023
Though rheumatoid arthritis (RA)–associated interstitial lung disease (RA-ILD) is a feared complication that can significantly affect morbidity and mortality, the role of methotrexate in treatment and its possible contribution to ILD is yet unknown. Kim and colleagues performed a retrospective analysis of a series of 170 patients with RA-ILD to try to identify risk factors and protective factors for mortality and decline of lung function. Previously known risk factors included older age, smoking, and seropositivity for cyclic citrullinated peptide (CCP). In this series, patients who had exposure to methotrexate after a diagnosis of RA-ILD were found to have less progression of decline in lung function and decreased mortality compared with those who did not, which is a finding that warrants further examination. On the other hand, there was a suggestion that sulfasalazine use is associated with increased mortality, though this finding was not borne out in multivariate analysis.
A different group of authors also examined the association with conventional disease-modifying antirheumatic drugs (DMARD) with ILD progression in a prospective analysis of 143 patients in the multicenter Korean RA-ILD cohort. Patients were classified regarding exposure to methotrexate, leflunomide, or tacrolimus as well as biologic DMARD and glucocorticoid exposure, with a primary outcome of ILD progression based on pulmonary function tests or mortality. The study did not detect any difference in time to ILD progression with methotrexate exposure, though it is not clear that the study would be able to detect a protective effect as was possible in the prior study. However, patients who were exposed to leflunomide had a shorter time to ILD progression than did those who were not, though this did not persist in multivariate analysis, and tacrolimus exposure had a statistically insignificant impact on ILD progression. Because the study is small, other associations which could affect use of leflunomide in these patients were not examined, though prior studies have suggested an association with leflunomide in ILD progression in patients with existing RA-ILD.
Li and colleagues addressed the characteristics and prognosis of late-onset RA (LORA) in people 60 years or older compared with younger-onset RA (YORA) in a prospective cohort study using a Canadian RA registry. Patients in the registry were enrolled early in the course of their illness and clinical characteristics as well as time to Disease Activity Score (DAS28) remission were analyzed. Of note, YORA and LORA patients had similar times to remission but were on less aggressive medication regimens, such as conventional DMARD without biologic DMARD or Janus kinase (JAK) inhibitors. In this registry, a smaller percentage of LORA patients compared with YORA patients were seropositive, which, given the enrollment of patients early in their disease course, may affect the use of biologic DMARD and JAK inhibitors.
Finally, the issue of noninflammatory pain contributing to disease activity and quality of life in RA has received increased scrutiny recently. Choy and colleagues studied disproportionate articular pain (DP) and its response to sarilumab, adalimumab, or placebo in a post hoc analysis of data from prior randomized clinical trials. DP was defined as a tender joint count that exceeded swollen joint count by seven and was present in about 20% of patients in the three randomized clinical trials examined. In these studies, DP was reduced in patients treated with sarilumab compared with placebo or adalimumab. Although this finding is exciting in raising the possibility of an immunologic explanation for DP via interleukin 6 (IL-6), the results should be considered carefully in the context of this post hoc analysis, especially before considering sarilumab or other IL-6 inhibitors as viable treatment options for DP in RA.
Though rheumatoid arthritis (RA)–associated interstitial lung disease (RA-ILD) is a feared complication that can significantly affect morbidity and mortality, the role of methotrexate in treatment and its possible contribution to ILD is yet unknown. Kim and colleagues performed a retrospective analysis of a series of 170 patients with RA-ILD to try to identify risk factors and protective factors for mortality and decline of lung function. Previously known risk factors included older age, smoking, and seropositivity for cyclic citrullinated peptide (CCP). In this series, patients who had exposure to methotrexate after a diagnosis of RA-ILD were found to have less progression of decline in lung function and decreased mortality compared with those who did not, which is a finding that warrants further examination. On the other hand, there was a suggestion that sulfasalazine use is associated with increased mortality, though this finding was not borne out in multivariate analysis.
A different group of authors also examined the association with conventional disease-modifying antirheumatic drugs (DMARD) with ILD progression in a prospective analysis of 143 patients in the multicenter Korean RA-ILD cohort. Patients were classified regarding exposure to methotrexate, leflunomide, or tacrolimus as well as biologic DMARD and glucocorticoid exposure, with a primary outcome of ILD progression based on pulmonary function tests or mortality. The study did not detect any difference in time to ILD progression with methotrexate exposure, though it is not clear that the study would be able to detect a protective effect as was possible in the prior study. However, patients who were exposed to leflunomide had a shorter time to ILD progression than did those who were not, though this did not persist in multivariate analysis, and tacrolimus exposure had a statistically insignificant impact on ILD progression. Because the study is small, other associations which could affect use of leflunomide in these patients were not examined, though prior studies have suggested an association with leflunomide in ILD progression in patients with existing RA-ILD.
Li and colleagues addressed the characteristics and prognosis of late-onset RA (LORA) in people 60 years or older compared with younger-onset RA (YORA) in a prospective cohort study using a Canadian RA registry. Patients in the registry were enrolled early in the course of their illness and clinical characteristics as well as time to Disease Activity Score (DAS28) remission were analyzed. Of note, YORA and LORA patients had similar times to remission but were on less aggressive medication regimens, such as conventional DMARD without biologic DMARD or Janus kinase (JAK) inhibitors. In this registry, a smaller percentage of LORA patients compared with YORA patients were seropositive, which, given the enrollment of patients early in their disease course, may affect the use of biologic DMARD and JAK inhibitors.
Finally, the issue of noninflammatory pain contributing to disease activity and quality of life in RA has received increased scrutiny recently. Choy and colleagues studied disproportionate articular pain (DP) and its response to sarilumab, adalimumab, or placebo in a post hoc analysis of data from prior randomized clinical trials. DP was defined as a tender joint count that exceeded swollen joint count by seven and was present in about 20% of patients in the three randomized clinical trials examined. In these studies, DP was reduced in patients treated with sarilumab compared with placebo or adalimumab. Although this finding is exciting in raising the possibility of an immunologic explanation for DP via interleukin 6 (IL-6), the results should be considered carefully in the context of this post hoc analysis, especially before considering sarilumab or other IL-6 inhibitors as viable treatment options for DP in RA.
Though rheumatoid arthritis (RA)–associated interstitial lung disease (RA-ILD) is a feared complication that can significantly affect morbidity and mortality, the role of methotrexate in treatment and its possible contribution to ILD is yet unknown. Kim and colleagues performed a retrospective analysis of a series of 170 patients with RA-ILD to try to identify risk factors and protective factors for mortality and decline of lung function. Previously known risk factors included older age, smoking, and seropositivity for cyclic citrullinated peptide (CCP). In this series, patients who had exposure to methotrexate after a diagnosis of RA-ILD were found to have less progression of decline in lung function and decreased mortality compared with those who did not, which is a finding that warrants further examination. On the other hand, there was a suggestion that sulfasalazine use is associated with increased mortality, though this finding was not borne out in multivariate analysis.
A different group of authors also examined the association with conventional disease-modifying antirheumatic drugs (DMARD) with ILD progression in a prospective analysis of 143 patients in the multicenter Korean RA-ILD cohort. Patients were classified regarding exposure to methotrexate, leflunomide, or tacrolimus as well as biologic DMARD and glucocorticoid exposure, with a primary outcome of ILD progression based on pulmonary function tests or mortality. The study did not detect any difference in time to ILD progression with methotrexate exposure, though it is not clear that the study would be able to detect a protective effect as was possible in the prior study. However, patients who were exposed to leflunomide had a shorter time to ILD progression than did those who were not, though this did not persist in multivariate analysis, and tacrolimus exposure had a statistically insignificant impact on ILD progression. Because the study is small, other associations which could affect use of leflunomide in these patients were not examined, though prior studies have suggested an association with leflunomide in ILD progression in patients with existing RA-ILD.
Li and colleagues addressed the characteristics and prognosis of late-onset RA (LORA) in people 60 years or older compared with younger-onset RA (YORA) in a prospective cohort study using a Canadian RA registry. Patients in the registry were enrolled early in the course of their illness and clinical characteristics as well as time to Disease Activity Score (DAS28) remission were analyzed. Of note, YORA and LORA patients had similar times to remission but were on less aggressive medication regimens, such as conventional DMARD without biologic DMARD or Janus kinase (JAK) inhibitors. In this registry, a smaller percentage of LORA patients compared with YORA patients were seropositive, which, given the enrollment of patients early in their disease course, may affect the use of biologic DMARD and JAK inhibitors.
Finally, the issue of noninflammatory pain contributing to disease activity and quality of life in RA has received increased scrutiny recently. Choy and colleagues studied disproportionate articular pain (DP) and its response to sarilumab, adalimumab, or placebo in a post hoc analysis of data from prior randomized clinical trials. DP was defined as a tender joint count that exceeded swollen joint count by seven and was present in about 20% of patients in the three randomized clinical trials examined. In these studies, DP was reduced in patients treated with sarilumab compared with placebo or adalimumab. Although this finding is exciting in raising the possibility of an immunologic explanation for DP via interleukin 6 (IL-6), the results should be considered carefully in the context of this post hoc analysis, especially before considering sarilumab or other IL-6 inhibitors as viable treatment options for DP in RA.
Rituximab worsens COVID-19 outcomes in RA
Key clinical point: The use of rituximab in patients with rheumatoid arthritis (RA) was associated with worse COVID-19 outcomes compared with the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARD).
Major finding: The risk for COVID-19-related hospitalization (adjusted odds ratio [aOR] 2.14; 95% CI 1.51-3.04), intensive care unit admission (aOR 5.22; 95% CI 1.77-15.41), and invasive ventilation (aOR 2.74; 95% CI 1.36-5.51) was significantly higher with baseline use of rituximab vs csDMARD.
Study details: The data come from a retrospective cohort study including 69,549 patients with RA, of which 22,956 patients were diagnosed with COVID-19 and 364 patients were exposed to rituximab prior to the first COVID-19 diagnosis.
Disclosures: This study did not report the source of funding. JA Singh reported receiving consulting fees, owning stock options, serving on speaker’s bureaus, and being a member of various committees.
Source: Singh N et al. Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C). Semin Arthritis Rheum. 2022;58:152149 (Dec 8). Doi: 10.1016/j.semarthrit.2022.152149
Key clinical point: The use of rituximab in patients with rheumatoid arthritis (RA) was associated with worse COVID-19 outcomes compared with the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARD).
Major finding: The risk for COVID-19-related hospitalization (adjusted odds ratio [aOR] 2.14; 95% CI 1.51-3.04), intensive care unit admission (aOR 5.22; 95% CI 1.77-15.41), and invasive ventilation (aOR 2.74; 95% CI 1.36-5.51) was significantly higher with baseline use of rituximab vs csDMARD.
Study details: The data come from a retrospective cohort study including 69,549 patients with RA, of which 22,956 patients were diagnosed with COVID-19 and 364 patients were exposed to rituximab prior to the first COVID-19 diagnosis.
Disclosures: This study did not report the source of funding. JA Singh reported receiving consulting fees, owning stock options, serving on speaker’s bureaus, and being a member of various committees.
Source: Singh N et al. Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C). Semin Arthritis Rheum. 2022;58:152149 (Dec 8). Doi: 10.1016/j.semarthrit.2022.152149
Key clinical point: The use of rituximab in patients with rheumatoid arthritis (RA) was associated with worse COVID-19 outcomes compared with the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARD).
Major finding: The risk for COVID-19-related hospitalization (adjusted odds ratio [aOR] 2.14; 95% CI 1.51-3.04), intensive care unit admission (aOR 5.22; 95% CI 1.77-15.41), and invasive ventilation (aOR 2.74; 95% CI 1.36-5.51) was significantly higher with baseline use of rituximab vs csDMARD.
Study details: The data come from a retrospective cohort study including 69,549 patients with RA, of which 22,956 patients were diagnosed with COVID-19 and 364 patients were exposed to rituximab prior to the first COVID-19 diagnosis.
Disclosures: This study did not report the source of funding. JA Singh reported receiving consulting fees, owning stock options, serving on speaker’s bureaus, and being a member of various committees.
Source: Singh N et al. Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C). Semin Arthritis Rheum. 2022;58:152149 (Dec 8). Doi: 10.1016/j.semarthrit.2022.152149
Losing muscle mass tied to physical dysfunction in early RA
Key clinical point: Myopenia was prevalent and associated with physical dysfunction in patients with early rheumatoid arthritis (RA).
Major finding: The prevalence of myopenia was higher in patients with early RA vs matched control individuals (41.3% vs 15.8%; P < .0167) but similar among patients with early and established RA. Myopenia was independently associated with physical dysfunction in patients with early RA (adjusted odds ratio 2.983; 95% CI 1.192-7.465).
Study details: This cross-sectional study included 1008 patients with RA (early RA n = 190; established RA n = 818) and 2017 control individuals who were age- and sex-matched for comparison.
Disclosures: This study was supported by the National Natural Science Foundation of China and other sources. Two authors declared being employees of Shanghai Healthcare Co. Ltd.
Source: Pan J et al. Muscle mass loss is associated with physical dysfunction in patients with early rheumatoid arthritis. Front Nutr. 2022;9:1007184 (Nov 23). Doi: 10.3389/fnut.2022.1007184
Key clinical point: Myopenia was prevalent and associated with physical dysfunction in patients with early rheumatoid arthritis (RA).
Major finding: The prevalence of myopenia was higher in patients with early RA vs matched control individuals (41.3% vs 15.8%; P < .0167) but similar among patients with early and established RA. Myopenia was independently associated with physical dysfunction in patients with early RA (adjusted odds ratio 2.983; 95% CI 1.192-7.465).
Study details: This cross-sectional study included 1008 patients with RA (early RA n = 190; established RA n = 818) and 2017 control individuals who were age- and sex-matched for comparison.
Disclosures: This study was supported by the National Natural Science Foundation of China and other sources. Two authors declared being employees of Shanghai Healthcare Co. Ltd.
Source: Pan J et al. Muscle mass loss is associated with physical dysfunction in patients with early rheumatoid arthritis. Front Nutr. 2022;9:1007184 (Nov 23). Doi: 10.3389/fnut.2022.1007184
Key clinical point: Myopenia was prevalent and associated with physical dysfunction in patients with early rheumatoid arthritis (RA).
Major finding: The prevalence of myopenia was higher in patients with early RA vs matched control individuals (41.3% vs 15.8%; P < .0167) but similar among patients with early and established RA. Myopenia was independently associated with physical dysfunction in patients with early RA (adjusted odds ratio 2.983; 95% CI 1.192-7.465).
Study details: This cross-sectional study included 1008 patients with RA (early RA n = 190; established RA n = 818) and 2017 control individuals who were age- and sex-matched for comparison.
Disclosures: This study was supported by the National Natural Science Foundation of China and other sources. Two authors declared being employees of Shanghai Healthcare Co. Ltd.
Source: Pan J et al. Muscle mass loss is associated with physical dysfunction in patients with early rheumatoid arthritis. Front Nutr. 2022;9:1007184 (Nov 23). Doi: 10.3389/fnut.2022.1007184
Inflammatory activity needs careful monitoring in late-onset rheumatoid arthritis
Key clinical point: Patients with late-onset rheumatoid arthritis (LORA; disease onset at ≥60 years) had poor control of inflammation after diagnosis compared with those with young-onset RA (YORA), with late onset being associated with a greater cumulative inflammatory burden over time.
Major finding: Moderate-high inflammatory activity (P = .018) was more frequent in LORA vs YORA. The median C-reactive protein (P = .039) and interleukin-6 (P = .045) levels at onset were significantly higher in patients with LORA vs YORA, and late-onset was significantly associated with a high cumulative inflammatory activity of RA (odds ratio 4.694; P = .008).
Study details: This was a nested cohort study of a prospective cohort including 110 patients with incident RA (LORA n = 22; YORA n = 88) and 110 age- and sex-matched control individuals.
Disclosures: This study was supported by grants from Fondos FEDER, University of Malaga, and other sources. The authors declared no conflicts of interest.
Source: Mena-Vázquez N et al. Inflammatory profile of incident cases of late-onset compared with young-onset rheumatoid arthritis: A nested cohort study. Front Med (Lausanne). 2022;9:1016159 (Nov 8). Doi: 10.3389/fmed.2022.1016159
Key clinical point: Patients with late-onset rheumatoid arthritis (LORA; disease onset at ≥60 years) had poor control of inflammation after diagnosis compared with those with young-onset RA (YORA), with late onset being associated with a greater cumulative inflammatory burden over time.
Major finding: Moderate-high inflammatory activity (P = .018) was more frequent in LORA vs YORA. The median C-reactive protein (P = .039) and interleukin-6 (P = .045) levels at onset were significantly higher in patients with LORA vs YORA, and late-onset was significantly associated with a high cumulative inflammatory activity of RA (odds ratio 4.694; P = .008).
Study details: This was a nested cohort study of a prospective cohort including 110 patients with incident RA (LORA n = 22; YORA n = 88) and 110 age- and sex-matched control individuals.
Disclosures: This study was supported by grants from Fondos FEDER, University of Malaga, and other sources. The authors declared no conflicts of interest.
Source: Mena-Vázquez N et al. Inflammatory profile of incident cases of late-onset compared with young-onset rheumatoid arthritis: A nested cohort study. Front Med (Lausanne). 2022;9:1016159 (Nov 8). Doi: 10.3389/fmed.2022.1016159
Key clinical point: Patients with late-onset rheumatoid arthritis (LORA; disease onset at ≥60 years) had poor control of inflammation after diagnosis compared with those with young-onset RA (YORA), with late onset being associated with a greater cumulative inflammatory burden over time.
Major finding: Moderate-high inflammatory activity (P = .018) was more frequent in LORA vs YORA. The median C-reactive protein (P = .039) and interleukin-6 (P = .045) levels at onset were significantly higher in patients with LORA vs YORA, and late-onset was significantly associated with a high cumulative inflammatory activity of RA (odds ratio 4.694; P = .008).
Study details: This was a nested cohort study of a prospective cohort including 110 patients with incident RA (LORA n = 22; YORA n = 88) and 110 age- and sex-matched control individuals.
Disclosures: This study was supported by grants from Fondos FEDER, University of Malaga, and other sources. The authors declared no conflicts of interest.
Source: Mena-Vázquez N et al. Inflammatory profile of incident cases of late-onset compared with young-onset rheumatoid arthritis: A nested cohort study. Front Med (Lausanne). 2022;9:1016159 (Nov 8). Doi: 10.3389/fmed.2022.1016159
Anti-protein arginine deiminase antibodies associated with radiographic injury in RA
Key clinical point: Anti-protein arginine deiminase 3/4 (anti-PAD3/4) antibodies could help identify patients with rheumatoid arthritis (RA) having higher radiographic injury and bone erosion.
Major finding: Anti-PAD4 antibody levels were significantly associated with radiographic injury (P = .027). Patients with anti-PAD3/4 double positivity vs double negativity had a significantly higher radiographic injury (mean Simple Erosion Narrowing Score 48.7 vs 19.4; P = .04) and joint erosion (mean Joint Erosion Score 25.7 vs 9.3; P = .037).
Study details: This was a retrospective cross-sectional study including 71 patients with RA.
Disclosures: This study did not receive any specific funding. M Mahler and L Martinez-Prat declared being employees of Werfen, a company selling autoimmune diagnostic tests.
Source: Palterer B et al. Anti-protein arginine deiminase antibodies are distinctly associated with joint and lung involvement in rheumatoid arthritis. Rheumatology (Oxford). 2022 (Nov 28). Doi: 10.1093/rheumatology/keac667
Key clinical point: Anti-protein arginine deiminase 3/4 (anti-PAD3/4) antibodies could help identify patients with rheumatoid arthritis (RA) having higher radiographic injury and bone erosion.
Major finding: Anti-PAD4 antibody levels were significantly associated with radiographic injury (P = .027). Patients with anti-PAD3/4 double positivity vs double negativity had a significantly higher radiographic injury (mean Simple Erosion Narrowing Score 48.7 vs 19.4; P = .04) and joint erosion (mean Joint Erosion Score 25.7 vs 9.3; P = .037).
Study details: This was a retrospective cross-sectional study including 71 patients with RA.
Disclosures: This study did not receive any specific funding. M Mahler and L Martinez-Prat declared being employees of Werfen, a company selling autoimmune diagnostic tests.
Source: Palterer B et al. Anti-protein arginine deiminase antibodies are distinctly associated with joint and lung involvement in rheumatoid arthritis. Rheumatology (Oxford). 2022 (Nov 28). Doi: 10.1093/rheumatology/keac667
Key clinical point: Anti-protein arginine deiminase 3/4 (anti-PAD3/4) antibodies could help identify patients with rheumatoid arthritis (RA) having higher radiographic injury and bone erosion.
Major finding: Anti-PAD4 antibody levels were significantly associated with radiographic injury (P = .027). Patients with anti-PAD3/4 double positivity vs double negativity had a significantly higher radiographic injury (mean Simple Erosion Narrowing Score 48.7 vs 19.4; P = .04) and joint erosion (mean Joint Erosion Score 25.7 vs 9.3; P = .037).
Study details: This was a retrospective cross-sectional study including 71 patients with RA.
Disclosures: This study did not receive any specific funding. M Mahler and L Martinez-Prat declared being employees of Werfen, a company selling autoimmune diagnostic tests.
Source: Palterer B et al. Anti-protein arginine deiminase antibodies are distinctly associated with joint and lung involvement in rheumatoid arthritis. Rheumatology (Oxford). 2022 (Nov 28). Doi: 10.1093/rheumatology/keac667
Methotrexate protective against lung function decline and mortality in patients with RA
Key clinical point: The use of methotrexate was protective against lung function decline and mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).
Major finding: Use of methotrexate was protective against decline in lung function (adjusted odds ratio [aOR] 0.269; P = .014) and mortality (aOR 0.284; P = .029). However, a high erythrocyte sedimentation rate at baseline was a risk factor for decline in lung function (aOR 3.056; P = .021). Age ≥65 years (aOR 2.723; P = .024) and radiologic pattern of usual interstitial pneumonia (UIP) or probable UIP (aOR 3.948; P = .005) were risk factors for mortality.
Study details: The findings are from a retrospective cohort study including 170 patients with RA-ILD who underwent at least one spirometry test and chest computed tomography scan and were treated with methotrexate or oral glucocorticoids.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Kim K et al. Protective effect of methotrexate on lung function and mortality in rheumatoid arthritis–related interstitial lung disease: A retrospective cohort study. Ther Adv Respir Dis. 2022;16:17534666221135314 (Nov 8). Doi: 10.1177/17534666221135314
Key clinical point: The use of methotrexate was protective against lung function decline and mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).
Major finding: Use of methotrexate was protective against decline in lung function (adjusted odds ratio [aOR] 0.269; P = .014) and mortality (aOR 0.284; P = .029). However, a high erythrocyte sedimentation rate at baseline was a risk factor for decline in lung function (aOR 3.056; P = .021). Age ≥65 years (aOR 2.723; P = .024) and radiologic pattern of usual interstitial pneumonia (UIP) or probable UIP (aOR 3.948; P = .005) were risk factors for mortality.
Study details: The findings are from a retrospective cohort study including 170 patients with RA-ILD who underwent at least one spirometry test and chest computed tomography scan and were treated with methotrexate or oral glucocorticoids.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Kim K et al. Protective effect of methotrexate on lung function and mortality in rheumatoid arthritis–related interstitial lung disease: A retrospective cohort study. Ther Adv Respir Dis. 2022;16:17534666221135314 (Nov 8). Doi: 10.1177/17534666221135314
Key clinical point: The use of methotrexate was protective against lung function decline and mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).
Major finding: Use of methotrexate was protective against decline in lung function (adjusted odds ratio [aOR] 0.269; P = .014) and mortality (aOR 0.284; P = .029). However, a high erythrocyte sedimentation rate at baseline was a risk factor for decline in lung function (aOR 3.056; P = .021). Age ≥65 years (aOR 2.723; P = .024) and radiologic pattern of usual interstitial pneumonia (UIP) or probable UIP (aOR 3.948; P = .005) were risk factors for mortality.
Study details: The findings are from a retrospective cohort study including 170 patients with RA-ILD who underwent at least one spirometry test and chest computed tomography scan and were treated with methotrexate or oral glucocorticoids.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Kim K et al. Protective effect of methotrexate on lung function and mortality in rheumatoid arthritis–related interstitial lung disease: A retrospective cohort study. Ther Adv Respir Dis. 2022;16:17534666221135314 (Nov 8). Doi: 10.1177/17534666221135314
Sarilumab improves disproportionate articular pain in RA
Key clinical point: In patients with active rheumatoid arthritis (RA), disproportionate articular pain (DP) was prevalent and sarilumab fared better than adalimumab or placebo in reducing DP and achieving clinical outcomes.
Major finding: At baseline, 23% of patients had DP. At week 24, a numerically lower proportion of patients experienced DP (15% vs 27%) and a higher proportion of patients achieved a Clinical Disease Activity Index of ≤10 (40% vs 17%) and American College of Rheumatology 50 response (42% vs 28%) with sarilumab vs adalimumab, with results being similar for sarilumab vs placebo.
Study details: This post hoc analysis of three phase 3 trials and their open label extension studies included 1531 patients with RA and intolerance or inadequate response to methotrexate/tumor necrosis factor inhibitors who received sarilumab, adalimumab, or placebo.
Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Three authors declared being employees of or holding stock or stock options in Sanofi. Several authors reported ties with Sanofi, Regeneron Pharmaceuticals, and other sources.
Source: Choy E et al. Disproportionate articular pain is a frequent phenomenon in rheumatoid arthritis and responds to treatment with sarilumab. Rheumatology (Oxford). 2022 (Nov 22). Doi: 10.1093/rheumatology/keac659
Key clinical point: In patients with active rheumatoid arthritis (RA), disproportionate articular pain (DP) was prevalent and sarilumab fared better than adalimumab or placebo in reducing DP and achieving clinical outcomes.
Major finding: At baseline, 23% of patients had DP. At week 24, a numerically lower proportion of patients experienced DP (15% vs 27%) and a higher proportion of patients achieved a Clinical Disease Activity Index of ≤10 (40% vs 17%) and American College of Rheumatology 50 response (42% vs 28%) with sarilumab vs adalimumab, with results being similar for sarilumab vs placebo.
Study details: This post hoc analysis of three phase 3 trials and their open label extension studies included 1531 patients with RA and intolerance or inadequate response to methotrexate/tumor necrosis factor inhibitors who received sarilumab, adalimumab, or placebo.
Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Three authors declared being employees of or holding stock or stock options in Sanofi. Several authors reported ties with Sanofi, Regeneron Pharmaceuticals, and other sources.
Source: Choy E et al. Disproportionate articular pain is a frequent phenomenon in rheumatoid arthritis and responds to treatment with sarilumab. Rheumatology (Oxford). 2022 (Nov 22). Doi: 10.1093/rheumatology/keac659
Key clinical point: In patients with active rheumatoid arthritis (RA), disproportionate articular pain (DP) was prevalent and sarilumab fared better than adalimumab or placebo in reducing DP and achieving clinical outcomes.
Major finding: At baseline, 23% of patients had DP. At week 24, a numerically lower proportion of patients experienced DP (15% vs 27%) and a higher proportion of patients achieved a Clinical Disease Activity Index of ≤10 (40% vs 17%) and American College of Rheumatology 50 response (42% vs 28%) with sarilumab vs adalimumab, with results being similar for sarilumab vs placebo.
Study details: This post hoc analysis of three phase 3 trials and their open label extension studies included 1531 patients with RA and intolerance or inadequate response to methotrexate/tumor necrosis factor inhibitors who received sarilumab, adalimumab, or placebo.
Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Three authors declared being employees of or holding stock or stock options in Sanofi. Several authors reported ties with Sanofi, Regeneron Pharmaceuticals, and other sources.
Source: Choy E et al. Disproportionate articular pain is a frequent phenomenon in rheumatoid arthritis and responds to treatment with sarilumab. Rheumatology (Oxford). 2022 (Nov 22). Doi: 10.1093/rheumatology/keac659
Similar prognosis in late- and younger-onset rheumatoid arthritis
Key clinical point: Patients with late-onset rheumatoid arthritis (LORA) and younger-onset rheumatoid arthritis (YORA) had similar prognosis, but patients with LORA who reached remission were more likely to be on a less intensive treatment regimen.
Major finding: Time to remission was similar among patients with LORA and YORA (P = .36). Patients with LORA vs YORA were less likely to be on biologics or Janus kinase inhibitors (16% vs 27%; P = .0039) and more likely to be on a single conventional synthetic disease-modifying antirheumatic drug (34% vs 27%; P = .0039) and oral glucocorticoids (27% vs 13%; P < .0001) at the time of remission.
Study details: This prospective cohort study included 872 patients diagnosed with RA at an age of ≥60 years (LORA; n = 354) or <60 years (YORA; n = 518).
Disclosures: This study was funded by peer-reviewed grants from the Canadian Arthritis Network and others and unrestricted grants from AbbVie, Novartis, and other sources. The authors declared no conflicts of interest.
Source: Li X et al. Late‑onset rheumatoid arthritis has a similar time to remission as younger‑onset rheumatoid arthritis: Results from the Ontario Best Practices Research Initiative. Arthritis Res Ther. 2022;24:255 (Nov 19). Doi: 10.1186/s13075-022-02952-1
Key clinical point: Patients with late-onset rheumatoid arthritis (LORA) and younger-onset rheumatoid arthritis (YORA) had similar prognosis, but patients with LORA who reached remission were more likely to be on a less intensive treatment regimen.
Major finding: Time to remission was similar among patients with LORA and YORA (P = .36). Patients with LORA vs YORA were less likely to be on biologics or Janus kinase inhibitors (16% vs 27%; P = .0039) and more likely to be on a single conventional synthetic disease-modifying antirheumatic drug (34% vs 27%; P = .0039) and oral glucocorticoids (27% vs 13%; P < .0001) at the time of remission.
Study details: This prospective cohort study included 872 patients diagnosed with RA at an age of ≥60 years (LORA; n = 354) or <60 years (YORA; n = 518).
Disclosures: This study was funded by peer-reviewed grants from the Canadian Arthritis Network and others and unrestricted grants from AbbVie, Novartis, and other sources. The authors declared no conflicts of interest.
Source: Li X et al. Late‑onset rheumatoid arthritis has a similar time to remission as younger‑onset rheumatoid arthritis: Results from the Ontario Best Practices Research Initiative. Arthritis Res Ther. 2022;24:255 (Nov 19). Doi: 10.1186/s13075-022-02952-1
Key clinical point: Patients with late-onset rheumatoid arthritis (LORA) and younger-onset rheumatoid arthritis (YORA) had similar prognosis, but patients with LORA who reached remission were more likely to be on a less intensive treatment regimen.
Major finding: Time to remission was similar among patients with LORA and YORA (P = .36). Patients with LORA vs YORA were less likely to be on biologics or Janus kinase inhibitors (16% vs 27%; P = .0039) and more likely to be on a single conventional synthetic disease-modifying antirheumatic drug (34% vs 27%; P = .0039) and oral glucocorticoids (27% vs 13%; P < .0001) at the time of remission.
Study details: This prospective cohort study included 872 patients diagnosed with RA at an age of ≥60 years (LORA; n = 354) or <60 years (YORA; n = 518).
Disclosures: This study was funded by peer-reviewed grants from the Canadian Arthritis Network and others and unrestricted grants from AbbVie, Novartis, and other sources. The authors declared no conflicts of interest.
Source: Li X et al. Late‑onset rheumatoid arthritis has a similar time to remission as younger‑onset rheumatoid arthritis: Results from the Ontario Best Practices Research Initiative. Arthritis Res Ther. 2022;24:255 (Nov 19). Doi: 10.1186/s13075-022-02952-1
Immunomodulators reduce cardiovascular risk in RA
Key clinical point: The addition of a tumor necrosis factor inhibitor (TNFi) or hydroxychloroquine+sulfasalazine (triple therapy) to weekly methotrexate significantly reduced atherosclerotic vascular inflammation in patients with rheumatoid arthritis (RA); however, TNFi was not associated with greater improvements than triple therapy.
Major finding: Over 24 weeks, the arterial target-to-background ratio (TBR) in carotid arteries or aorta reduced significantly with TNFi (Δ −0.24; P = .001) and triple therapy (Δ −0.19; P = .001), with no significant difference in TBR improvement between the two treatment groups (P = .79).
Study details: Findings are from the phase 4 TARGET trial including 115 patients with active RA despite being on weekly methotrexate who were randomly assigned to add TNFi (adalimumab or etanercept) or hydroxychloroquine+sulfasalazine.
Disclosures: This study was funded by the US National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH-NIAMS). The study drug was supplied by AbbVie and Amgen. Four authors declared receiving research support, unrestricted grants, or royalties, being co-inventors on patents, or consulting for various sources unrelated to current study.
Source: Solomon DH et al for the TARGET Trial Consortium. Reducing cardiovascular risk with immunomodulators: A randomised active comparator trial among patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Nov 30). Doi: 10.1136/ard-2022-223302
Key clinical point: The addition of a tumor necrosis factor inhibitor (TNFi) or hydroxychloroquine+sulfasalazine (triple therapy) to weekly methotrexate significantly reduced atherosclerotic vascular inflammation in patients with rheumatoid arthritis (RA); however, TNFi was not associated with greater improvements than triple therapy.
Major finding: Over 24 weeks, the arterial target-to-background ratio (TBR) in carotid arteries or aorta reduced significantly with TNFi (Δ −0.24; P = .001) and triple therapy (Δ −0.19; P = .001), with no significant difference in TBR improvement between the two treatment groups (P = .79).
Study details: Findings are from the phase 4 TARGET trial including 115 patients with active RA despite being on weekly methotrexate who were randomly assigned to add TNFi (adalimumab or etanercept) or hydroxychloroquine+sulfasalazine.
Disclosures: This study was funded by the US National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH-NIAMS). The study drug was supplied by AbbVie and Amgen. Four authors declared receiving research support, unrestricted grants, or royalties, being co-inventors on patents, or consulting for various sources unrelated to current study.
Source: Solomon DH et al for the TARGET Trial Consortium. Reducing cardiovascular risk with immunomodulators: A randomised active comparator trial among patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Nov 30). Doi: 10.1136/ard-2022-223302
Key clinical point: The addition of a tumor necrosis factor inhibitor (TNFi) or hydroxychloroquine+sulfasalazine (triple therapy) to weekly methotrexate significantly reduced atherosclerotic vascular inflammation in patients with rheumatoid arthritis (RA); however, TNFi was not associated with greater improvements than triple therapy.
Major finding: Over 24 weeks, the arterial target-to-background ratio (TBR) in carotid arteries or aorta reduced significantly with TNFi (Δ −0.24; P = .001) and triple therapy (Δ −0.19; P = .001), with no significant difference in TBR improvement between the two treatment groups (P = .79).
Study details: Findings are from the phase 4 TARGET trial including 115 patients with active RA despite being on weekly methotrexate who were randomly assigned to add TNFi (adalimumab or etanercept) or hydroxychloroquine+sulfasalazine.
Disclosures: This study was funded by the US National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH-NIAMS). The study drug was supplied by AbbVie and Amgen. Four authors declared receiving research support, unrestricted grants, or royalties, being co-inventors on patents, or consulting for various sources unrelated to current study.
Source: Solomon DH et al for the TARGET Trial Consortium. Reducing cardiovascular risk with immunomodulators: A randomised active comparator trial among patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Nov 30). Doi: 10.1136/ard-2022-223302