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CVD risk in black SLE patients 18 times higher than in whites
ATLANTA – Black race was the single greatest predictor of cardiovascular disease (CVD) events in systemic lupus erythematosus, with black patients having an 18-fold higher risk than white patients from 2 years before to 8 years after diagnosis, according to a review of 336 patients in the Georgia Lupus Registry that was presented at the annual meeting of the American College of Rheumatology.
The greatest risk was in the first 2 years after diagnosis, which has been reported before in white patients, but not before in a mostly (75%) black cohort.
Lupus is known to strike earlier and be more aggressive in black patients, so “we were expecting racial disparities in incident CVD, but” the magnitude of the increased risk “was very surprising. This study [identifies] a population that needs more attention, more targeted CVD prevention. We have to intervene early and be on top of everything,” especially for black patients, said lead investigator Shivani Garg, MD, an assistant professor of rheumatology at the University of Wisconsin–Madison.
Lipids, blood pressure, and the other usual CVD risk factors, as well as lupus itself, have to be optimally controlled; glucocorticoid use limited as much as possible; and there needs to be improved adherence to hydroxychloroquine, which has been shown to reduce CVD events in lupus patients, she said in an interview.
The 336 patients, mostly women (87%) from the Atlanta area, were diagnosed during 2002-2004 at a mean age of 40 years. Dr. Garg and associates reviewed CVD events – ischemic heart disease, stroke, transient ischemic attack, and peripheral vascular disease – and death over 16 years, beginning 2 years before diagnosis.
About 22% of subjects had a CVD event, most commonly within 2 years after diagnosis. The risk was 500% higher in black patients overall (adjusted hazard ratio, 6.4; 95% confidence interval, 2.4-17.5; P = .0003), and markedly higher in the first 10 years (aHR, 18; 95% CI, 2.2-141; P less than .0001). The findings were not adjusted for socioeconomic factors.
In the first 12 years of the study, the mean age at lupus diagnosis was 46 years and the first CVD event occurred at an average of 48 years. From 12 to 16 years follow-up, the mean age of diagnosis was 38 years, and the first CVD event occurred at 52 years.
Age older than 65 years (aHR, 7.9; 95% CI, 2.2-29) and the presence of disease-associated antibodies (aHR, 2.1; 95% CI, 1.01-4.4) increased CVD risk, which wasn’t surprising, but another predictor – discoid lupus – was unexpected (aHR, 3.2; 95% CI, 1.5-6.8). “A lot of times, we’ve considered discoid rash to be a milder form, but these patients have some kind of chronic, smoldering inflammation that is leading to atherosclerosis,” Dr. Garg said.
At diagnosis, 84% of the subjects had lupus hematologic disorders, 69% immunologic disorders, and 14% a discoid rash. CVD risk factor data were not collected.
There was no external funding, and the investigators reported no disclosures.
SOURCE: Garg S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 805.
ATLANTA – Black race was the single greatest predictor of cardiovascular disease (CVD) events in systemic lupus erythematosus, with black patients having an 18-fold higher risk than white patients from 2 years before to 8 years after diagnosis, according to a review of 336 patients in the Georgia Lupus Registry that was presented at the annual meeting of the American College of Rheumatology.
The greatest risk was in the first 2 years after diagnosis, which has been reported before in white patients, but not before in a mostly (75%) black cohort.
Lupus is known to strike earlier and be more aggressive in black patients, so “we were expecting racial disparities in incident CVD, but” the magnitude of the increased risk “was very surprising. This study [identifies] a population that needs more attention, more targeted CVD prevention. We have to intervene early and be on top of everything,” especially for black patients, said lead investigator Shivani Garg, MD, an assistant professor of rheumatology at the University of Wisconsin–Madison.
Lipids, blood pressure, and the other usual CVD risk factors, as well as lupus itself, have to be optimally controlled; glucocorticoid use limited as much as possible; and there needs to be improved adherence to hydroxychloroquine, which has been shown to reduce CVD events in lupus patients, she said in an interview.
The 336 patients, mostly women (87%) from the Atlanta area, were diagnosed during 2002-2004 at a mean age of 40 years. Dr. Garg and associates reviewed CVD events – ischemic heart disease, stroke, transient ischemic attack, and peripheral vascular disease – and death over 16 years, beginning 2 years before diagnosis.
About 22% of subjects had a CVD event, most commonly within 2 years after diagnosis. The risk was 500% higher in black patients overall (adjusted hazard ratio, 6.4; 95% confidence interval, 2.4-17.5; P = .0003), and markedly higher in the first 10 years (aHR, 18; 95% CI, 2.2-141; P less than .0001). The findings were not adjusted for socioeconomic factors.
In the first 12 years of the study, the mean age at lupus diagnosis was 46 years and the first CVD event occurred at an average of 48 years. From 12 to 16 years follow-up, the mean age of diagnosis was 38 years, and the first CVD event occurred at 52 years.
Age older than 65 years (aHR, 7.9; 95% CI, 2.2-29) and the presence of disease-associated antibodies (aHR, 2.1; 95% CI, 1.01-4.4) increased CVD risk, which wasn’t surprising, but another predictor – discoid lupus – was unexpected (aHR, 3.2; 95% CI, 1.5-6.8). “A lot of times, we’ve considered discoid rash to be a milder form, but these patients have some kind of chronic, smoldering inflammation that is leading to atherosclerosis,” Dr. Garg said.
At diagnosis, 84% of the subjects had lupus hematologic disorders, 69% immunologic disorders, and 14% a discoid rash. CVD risk factor data were not collected.
There was no external funding, and the investigators reported no disclosures.
SOURCE: Garg S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 805.
ATLANTA – Black race was the single greatest predictor of cardiovascular disease (CVD) events in systemic lupus erythematosus, with black patients having an 18-fold higher risk than white patients from 2 years before to 8 years after diagnosis, according to a review of 336 patients in the Georgia Lupus Registry that was presented at the annual meeting of the American College of Rheumatology.
The greatest risk was in the first 2 years after diagnosis, which has been reported before in white patients, but not before in a mostly (75%) black cohort.
Lupus is known to strike earlier and be more aggressive in black patients, so “we were expecting racial disparities in incident CVD, but” the magnitude of the increased risk “was very surprising. This study [identifies] a population that needs more attention, more targeted CVD prevention. We have to intervene early and be on top of everything,” especially for black patients, said lead investigator Shivani Garg, MD, an assistant professor of rheumatology at the University of Wisconsin–Madison.
Lipids, blood pressure, and the other usual CVD risk factors, as well as lupus itself, have to be optimally controlled; glucocorticoid use limited as much as possible; and there needs to be improved adherence to hydroxychloroquine, which has been shown to reduce CVD events in lupus patients, she said in an interview.
The 336 patients, mostly women (87%) from the Atlanta area, were diagnosed during 2002-2004 at a mean age of 40 years. Dr. Garg and associates reviewed CVD events – ischemic heart disease, stroke, transient ischemic attack, and peripheral vascular disease – and death over 16 years, beginning 2 years before diagnosis.
About 22% of subjects had a CVD event, most commonly within 2 years after diagnosis. The risk was 500% higher in black patients overall (adjusted hazard ratio, 6.4; 95% confidence interval, 2.4-17.5; P = .0003), and markedly higher in the first 10 years (aHR, 18; 95% CI, 2.2-141; P less than .0001). The findings were not adjusted for socioeconomic factors.
In the first 12 years of the study, the mean age at lupus diagnosis was 46 years and the first CVD event occurred at an average of 48 years. From 12 to 16 years follow-up, the mean age of diagnosis was 38 years, and the first CVD event occurred at 52 years.
Age older than 65 years (aHR, 7.9; 95% CI, 2.2-29) and the presence of disease-associated antibodies (aHR, 2.1; 95% CI, 1.01-4.4) increased CVD risk, which wasn’t surprising, but another predictor – discoid lupus – was unexpected (aHR, 3.2; 95% CI, 1.5-6.8). “A lot of times, we’ve considered discoid rash to be a milder form, but these patients have some kind of chronic, smoldering inflammation that is leading to atherosclerosis,” Dr. Garg said.
At diagnosis, 84% of the subjects had lupus hematologic disorders, 69% immunologic disorders, and 14% a discoid rash. CVD risk factor data were not collected.
There was no external funding, and the investigators reported no disclosures.
SOURCE: Garg S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 805.
REPORTING FROM ACR 2019
EULAR releases recommendations for management of Sjögren’s syndrome
The European League Against Rheumatism has released its first recommendations for the management of Sjögren’s syndrome with topical and systemic treatments.
First author Manuel Ramos-Casals, MD, PhD, of Hospital Clinic de Barcelona Institut Clinic de Medicina i Dermatologia and colleagues on the multinational, multispecialty EULAR Sjögren Syndrome Task Force Group said the EULAR recommendations “synthesize current thinking” of management for Sjögren’s syndrome, which is complicated by individualized treatment that does not address the systemic disease and for which therapeutic decisions are often made based on expert opinion and personal experience because of a lack of data.
“Sjögren’s syndrome is generally treated through symptom management,” noted Sara McCoy, MD, who is director of the University of Wisconsin Health Sjögren’s Syndrome Clinic and was not involved in the recommendations, which were published in Annals of the Rheumatic Diseases. “Although we have measures to address these symptoms, we do not have any approved therapy that ameliorates the driving cause.”
There is limited high-quality evidence for many of the therapies discussed in the recommendations: In total, 9 randomized controlled trials, 18 prospective studies, and 5 case-control studies were included as evidence in the recommendations, and many involved a small number of patients.
The first overarching recommendation says that patients with Sjögren’s syndrome should be managed at centers of expertise using a multidisciplinary approach, the authors wrote. Two other overarching recommendations focus on how to manage certain patient cases. In cases of dryness, first-line therapy should include topical therapies for symptomatic relief, while clinicians should consider systemic therapies for patients with active systemic disease. All three overarching recommendations had a high level of agreement among task force members.
The task force also offered 12 specific recommendations on disease management, which take an “algorithmic approach” to Sjögren’s syndrome management that is guided by the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), Dr. McCoy said in an interview.
“The EULAR recommendations structure a clear approach to treatment of Sjögren’s manifestations, ranging from oral and ocular sicca management, to treatment of uncommon but severe systemic involvement of Sjögren’s,” she said.
Before treating patients for oral dryness symptoms, clinicians should evaluate salivary function at baseline using unstimulated whole salivary flows. First-line therapeutic approaches for oral dryness can include nonpharmacologic stimulation in cases of mild salivary gland dysfunction, pharmacologic stimulation in cases of moderate dysfunction, and substitution of saliva in cases of severe dysfunction, the authors said.
Ocular dryness should be assessed using ocular staining score followed by ocular surface–disease index, and once identified, it can be managed with artificial tears and ocular gels or ointments as first-line therapy. Topical immunosuppressive-containing drops and autologous serum eye drops are options for more severe or refractory ocular dryness.
Patients who have fatigue or pain associated with Sjögren’s syndrome should have their fatigue or pain scored with the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), and any concomitant disease should also be evaluated. Clinicians should consider acetaminophen and NSAIDs for treatment of acute musculoskeletal pain and other pain-modifying agents, such as hydroxychloroquine in cases of articular pain, despite a lack of evidence showing its efficacy in trials.
For systemic disease, the task force advised matching treatment to the organ(s) involved and using the ESSDAI to evaluate disease severity., They said that “patients presenting with at least moderate activity in one clinical domain, or with a global moderate disease activity score” of 5 or higher can be considered for systemic therapy.
Although many clinicians use glucocorticoids (GCs) for managing Sjögren’s syndrome, there is no evidence of the treatment’s efficacy in systemic disease. The task force recommended using glucocorticoids such as methylprednisolone at the minimum dose and withdrawing use “as soon as possible” in patients with inactive disease. “Based on the potential development of chronic damage in patients with uncontrolled systemic disease, some patients may require long-term therapy with GCs, especially those with severe organ impairments,” Dr. Ramos-Casals and colleagues wrote. “In these patients, the addition of immunosuppressive agents as GC-sparing agents is justified, always weighing the potential benefits and risks.” Because of a lack of head-to-head studies of different immunosuppressive agents, the task force did not recommend one particular agent over another.
One recommendation that contained a high level of evidence was for the use of B-cell targeted therapies for patients with severe, refractory systemic disease. Efficacy of rituximab was mixed in studies totaling more than 400 patients, but generally showed a positive outcome in at least one of the following areas: global response, organ-specific response, ESSDAI reduction, and prednisone reduction. The task force recommended that rituximab “may be considered” in “patients with severe, refractory systemic disease” and may be best for those with symptoms linked to cryoglobulinemic-associated vasculitis, with the potential of using belimumab (Benlysta) as rescue therapy. While systemic organ-specific therapeutic approaches vary, the general rule should be to treat with GCs first, followed by immunosuppressive agents and biologics as second-line therapy in cases refractory to GCs, either sequentially or in combination, the authors said.
For patients with B-cell lymphoma, clinicians should use individualized treatment based on the World Health Organization 2016 histologic subtype and the stage of the disease. While some clinicians employ a “watchful waiting” approach to treating low-grade hematologic neoplasia, “the decision to treat low-grade lymphomas or not must be discussed in a multidisciplinary committee, taking into account the fact that they are linked to the disease activity and are the ultimate stage of autoimmune B-cell activation,” the authors wrote.
The task force also defined a number of future research agenda goals for Sjögren’s syndrome treatment management, including developing personalized therapeutic approaches, finding predictors of biological response to agents used in treatment, and identifying biomarkers of poor outcomes.
In addition, EULAR acknowledged some research gaps exist in the guidelines for particular symptoms of Sjögren’s syndrome, such as in the case of fatigue. “The EULAR recommendations mention the common association of fatigue with Sjögren’s syndrome, though acknowledge that fatigue is more commonly seen in the same demographic cohort as Sjögren’s,” Dr. McCoy said. “Aside from exercise, there remains little available to address this common and burdensome symptom amongst Sjögren’s patients. Overall, this is a pertinent gap in knowledge in our Sjögren’s patients.”
The Sjögren’s syndrome recommendations were funded by EULAR. Many task force members reported relationships with industry in the form of advisory board and speaker’s bureau memberships, consultancies, and grants. Dr. McCoy reported serving on a data monitoring committee for Bristol-Myers Squibb unrelated to the data in the EULAR recommendations.
SOURCE: Ramos-Casals M et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216114
The European League Against Rheumatism has released its first recommendations for the management of Sjögren’s syndrome with topical and systemic treatments.
First author Manuel Ramos-Casals, MD, PhD, of Hospital Clinic de Barcelona Institut Clinic de Medicina i Dermatologia and colleagues on the multinational, multispecialty EULAR Sjögren Syndrome Task Force Group said the EULAR recommendations “synthesize current thinking” of management for Sjögren’s syndrome, which is complicated by individualized treatment that does not address the systemic disease and for which therapeutic decisions are often made based on expert opinion and personal experience because of a lack of data.
“Sjögren’s syndrome is generally treated through symptom management,” noted Sara McCoy, MD, who is director of the University of Wisconsin Health Sjögren’s Syndrome Clinic and was not involved in the recommendations, which were published in Annals of the Rheumatic Diseases. “Although we have measures to address these symptoms, we do not have any approved therapy that ameliorates the driving cause.”
There is limited high-quality evidence for many of the therapies discussed in the recommendations: In total, 9 randomized controlled trials, 18 prospective studies, and 5 case-control studies were included as evidence in the recommendations, and many involved a small number of patients.
The first overarching recommendation says that patients with Sjögren’s syndrome should be managed at centers of expertise using a multidisciplinary approach, the authors wrote. Two other overarching recommendations focus on how to manage certain patient cases. In cases of dryness, first-line therapy should include topical therapies for symptomatic relief, while clinicians should consider systemic therapies for patients with active systemic disease. All three overarching recommendations had a high level of agreement among task force members.
The task force also offered 12 specific recommendations on disease management, which take an “algorithmic approach” to Sjögren’s syndrome management that is guided by the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), Dr. McCoy said in an interview.
“The EULAR recommendations structure a clear approach to treatment of Sjögren’s manifestations, ranging from oral and ocular sicca management, to treatment of uncommon but severe systemic involvement of Sjögren’s,” she said.
Before treating patients for oral dryness symptoms, clinicians should evaluate salivary function at baseline using unstimulated whole salivary flows. First-line therapeutic approaches for oral dryness can include nonpharmacologic stimulation in cases of mild salivary gland dysfunction, pharmacologic stimulation in cases of moderate dysfunction, and substitution of saliva in cases of severe dysfunction, the authors said.
Ocular dryness should be assessed using ocular staining score followed by ocular surface–disease index, and once identified, it can be managed with artificial tears and ocular gels or ointments as first-line therapy. Topical immunosuppressive-containing drops and autologous serum eye drops are options for more severe or refractory ocular dryness.
Patients who have fatigue or pain associated with Sjögren’s syndrome should have their fatigue or pain scored with the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), and any concomitant disease should also be evaluated. Clinicians should consider acetaminophen and NSAIDs for treatment of acute musculoskeletal pain and other pain-modifying agents, such as hydroxychloroquine in cases of articular pain, despite a lack of evidence showing its efficacy in trials.
For systemic disease, the task force advised matching treatment to the organ(s) involved and using the ESSDAI to evaluate disease severity., They said that “patients presenting with at least moderate activity in one clinical domain, or with a global moderate disease activity score” of 5 or higher can be considered for systemic therapy.
Although many clinicians use glucocorticoids (GCs) for managing Sjögren’s syndrome, there is no evidence of the treatment’s efficacy in systemic disease. The task force recommended using glucocorticoids such as methylprednisolone at the minimum dose and withdrawing use “as soon as possible” in patients with inactive disease. “Based on the potential development of chronic damage in patients with uncontrolled systemic disease, some patients may require long-term therapy with GCs, especially those with severe organ impairments,” Dr. Ramos-Casals and colleagues wrote. “In these patients, the addition of immunosuppressive agents as GC-sparing agents is justified, always weighing the potential benefits and risks.” Because of a lack of head-to-head studies of different immunosuppressive agents, the task force did not recommend one particular agent over another.
One recommendation that contained a high level of evidence was for the use of B-cell targeted therapies for patients with severe, refractory systemic disease. Efficacy of rituximab was mixed in studies totaling more than 400 patients, but generally showed a positive outcome in at least one of the following areas: global response, organ-specific response, ESSDAI reduction, and prednisone reduction. The task force recommended that rituximab “may be considered” in “patients with severe, refractory systemic disease” and may be best for those with symptoms linked to cryoglobulinemic-associated vasculitis, with the potential of using belimumab (Benlysta) as rescue therapy. While systemic organ-specific therapeutic approaches vary, the general rule should be to treat with GCs first, followed by immunosuppressive agents and biologics as second-line therapy in cases refractory to GCs, either sequentially or in combination, the authors said.
For patients with B-cell lymphoma, clinicians should use individualized treatment based on the World Health Organization 2016 histologic subtype and the stage of the disease. While some clinicians employ a “watchful waiting” approach to treating low-grade hematologic neoplasia, “the decision to treat low-grade lymphomas or not must be discussed in a multidisciplinary committee, taking into account the fact that they are linked to the disease activity and are the ultimate stage of autoimmune B-cell activation,” the authors wrote.
The task force also defined a number of future research agenda goals for Sjögren’s syndrome treatment management, including developing personalized therapeutic approaches, finding predictors of biological response to agents used in treatment, and identifying biomarkers of poor outcomes.
In addition, EULAR acknowledged some research gaps exist in the guidelines for particular symptoms of Sjögren’s syndrome, such as in the case of fatigue. “The EULAR recommendations mention the common association of fatigue with Sjögren’s syndrome, though acknowledge that fatigue is more commonly seen in the same demographic cohort as Sjögren’s,” Dr. McCoy said. “Aside from exercise, there remains little available to address this common and burdensome symptom amongst Sjögren’s patients. Overall, this is a pertinent gap in knowledge in our Sjögren’s patients.”
The Sjögren’s syndrome recommendations were funded by EULAR. Many task force members reported relationships with industry in the form of advisory board and speaker’s bureau memberships, consultancies, and grants. Dr. McCoy reported serving on a data monitoring committee for Bristol-Myers Squibb unrelated to the data in the EULAR recommendations.
SOURCE: Ramos-Casals M et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216114
The European League Against Rheumatism has released its first recommendations for the management of Sjögren’s syndrome with topical and systemic treatments.
First author Manuel Ramos-Casals, MD, PhD, of Hospital Clinic de Barcelona Institut Clinic de Medicina i Dermatologia and colleagues on the multinational, multispecialty EULAR Sjögren Syndrome Task Force Group said the EULAR recommendations “synthesize current thinking” of management for Sjögren’s syndrome, which is complicated by individualized treatment that does not address the systemic disease and for which therapeutic decisions are often made based on expert opinion and personal experience because of a lack of data.
“Sjögren’s syndrome is generally treated through symptom management,” noted Sara McCoy, MD, who is director of the University of Wisconsin Health Sjögren’s Syndrome Clinic and was not involved in the recommendations, which were published in Annals of the Rheumatic Diseases. “Although we have measures to address these symptoms, we do not have any approved therapy that ameliorates the driving cause.”
There is limited high-quality evidence for many of the therapies discussed in the recommendations: In total, 9 randomized controlled trials, 18 prospective studies, and 5 case-control studies were included as evidence in the recommendations, and many involved a small number of patients.
The first overarching recommendation says that patients with Sjögren’s syndrome should be managed at centers of expertise using a multidisciplinary approach, the authors wrote. Two other overarching recommendations focus on how to manage certain patient cases. In cases of dryness, first-line therapy should include topical therapies for symptomatic relief, while clinicians should consider systemic therapies for patients with active systemic disease. All three overarching recommendations had a high level of agreement among task force members.
The task force also offered 12 specific recommendations on disease management, which take an “algorithmic approach” to Sjögren’s syndrome management that is guided by the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), Dr. McCoy said in an interview.
“The EULAR recommendations structure a clear approach to treatment of Sjögren’s manifestations, ranging from oral and ocular sicca management, to treatment of uncommon but severe systemic involvement of Sjögren’s,” she said.
Before treating patients for oral dryness symptoms, clinicians should evaluate salivary function at baseline using unstimulated whole salivary flows. First-line therapeutic approaches for oral dryness can include nonpharmacologic stimulation in cases of mild salivary gland dysfunction, pharmacologic stimulation in cases of moderate dysfunction, and substitution of saliva in cases of severe dysfunction, the authors said.
Ocular dryness should be assessed using ocular staining score followed by ocular surface–disease index, and once identified, it can be managed with artificial tears and ocular gels or ointments as first-line therapy. Topical immunosuppressive-containing drops and autologous serum eye drops are options for more severe or refractory ocular dryness.
Patients who have fatigue or pain associated with Sjögren’s syndrome should have their fatigue or pain scored with the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), and any concomitant disease should also be evaluated. Clinicians should consider acetaminophen and NSAIDs for treatment of acute musculoskeletal pain and other pain-modifying agents, such as hydroxychloroquine in cases of articular pain, despite a lack of evidence showing its efficacy in trials.
For systemic disease, the task force advised matching treatment to the organ(s) involved and using the ESSDAI to evaluate disease severity., They said that “patients presenting with at least moderate activity in one clinical domain, or with a global moderate disease activity score” of 5 or higher can be considered for systemic therapy.
Although many clinicians use glucocorticoids (GCs) for managing Sjögren’s syndrome, there is no evidence of the treatment’s efficacy in systemic disease. The task force recommended using glucocorticoids such as methylprednisolone at the minimum dose and withdrawing use “as soon as possible” in patients with inactive disease. “Based on the potential development of chronic damage in patients with uncontrolled systemic disease, some patients may require long-term therapy with GCs, especially those with severe organ impairments,” Dr. Ramos-Casals and colleagues wrote. “In these patients, the addition of immunosuppressive agents as GC-sparing agents is justified, always weighing the potential benefits and risks.” Because of a lack of head-to-head studies of different immunosuppressive agents, the task force did not recommend one particular agent over another.
One recommendation that contained a high level of evidence was for the use of B-cell targeted therapies for patients with severe, refractory systemic disease. Efficacy of rituximab was mixed in studies totaling more than 400 patients, but generally showed a positive outcome in at least one of the following areas: global response, organ-specific response, ESSDAI reduction, and prednisone reduction. The task force recommended that rituximab “may be considered” in “patients with severe, refractory systemic disease” and may be best for those with symptoms linked to cryoglobulinemic-associated vasculitis, with the potential of using belimumab (Benlysta) as rescue therapy. While systemic organ-specific therapeutic approaches vary, the general rule should be to treat with GCs first, followed by immunosuppressive agents and biologics as second-line therapy in cases refractory to GCs, either sequentially or in combination, the authors said.
For patients with B-cell lymphoma, clinicians should use individualized treatment based on the World Health Organization 2016 histologic subtype and the stage of the disease. While some clinicians employ a “watchful waiting” approach to treating low-grade hematologic neoplasia, “the decision to treat low-grade lymphomas or not must be discussed in a multidisciplinary committee, taking into account the fact that they are linked to the disease activity and are the ultimate stage of autoimmune B-cell activation,” the authors wrote.
The task force also defined a number of future research agenda goals for Sjögren’s syndrome treatment management, including developing personalized therapeutic approaches, finding predictors of biological response to agents used in treatment, and identifying biomarkers of poor outcomes.
In addition, EULAR acknowledged some research gaps exist in the guidelines for particular symptoms of Sjögren’s syndrome, such as in the case of fatigue. “The EULAR recommendations mention the common association of fatigue with Sjögren’s syndrome, though acknowledge that fatigue is more commonly seen in the same demographic cohort as Sjögren’s,” Dr. McCoy said. “Aside from exercise, there remains little available to address this common and burdensome symptom amongst Sjögren’s patients. Overall, this is a pertinent gap in knowledge in our Sjögren’s patients.”
The Sjögren’s syndrome recommendations were funded by EULAR. Many task force members reported relationships with industry in the form of advisory board and speaker’s bureau memberships, consultancies, and grants. Dr. McCoy reported serving on a data monitoring committee for Bristol-Myers Squibb unrelated to the data in the EULAR recommendations.
SOURCE: Ramos-Casals M et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216114
FROM ANNALS OF THE RHEUMATIC DISEASES
New screening test validated for cognitive impairment in lupus
new research suggests.
In a paper published in Arthritis Care & Research, researchers assessed the validity of the Automated Neuropsychological Assessment Metrics (ANAM) test in 211 adult patients with systemic lupus erythematosus (SLE).
First author Oshrat E. Tayer-Shifman, MD, of the University of Toronto Lupus Clinic and coauthors wrote that current assessment of cognitive impairment in adults with SLE is done using the American College of Rheumatology neuropsychological battery (ACR-NB). However, this approach involves protected tests that require specialized personnel and takes around 1 hour to administer, as well as time for scoring and interpretation.
“For many clinics, these are notable barriers to accessing CI [cognitive impairment] assessment, as health care payers do not cover these costs,” the investigators wrote. And although briefer cognitive screening tools, such as the Montreal Cognitive Assessment, the Controlled Oral Word Association Test, and the Hopkins Verbal Learning Test–Revised, have been examined in studies of patients with SLE, “they also require specialized personnel for administration and interpretation and cannot be self-administered. In addition, their validity for the screening for CI in SLE has not been well established. Thus, there is an unmet need for a screening assessment for CI that is validated for SLE and that can be applied in an ambulatory clinic setting without specialized personnel.”
The full ANAM battery requires about 40 minutes and has been used to screen cognitive performance in a range of clinical contexts.
A total of 96 patients (46%) had CI and 52 (25%) did not, according to the ACR-NB, while the results were indeterminate in the remaining 63 (30%).
The study showed that patients without CI performed significantly better on the majority of the ANAM subtests in comparison with patients who have cognitive impairment. This was particularly evident on mean reaction time and the number of correct responses per minute (a measure of cognitive efficiency), but less so for percentage of correct responses and consistency of response speed.
“Three of the most affected cognitive domains in the CI patients in this cohort, as well as in previous studies, were learning and memory, visual spatial construction, and simple attention and speed of processing,” the researchers wrote.
The investigators created testing models using the subtests that were most discriminative for CI. The two best models included one encompassing the percentage of correct responses, consistency of response speed, and mean reaction time, as well as one encompassing these three factors as well as the number of correct responses per minute. The investigators then derived candidate ANAM composite indices from these two models. For one composite index that used 8 of the 15 ANAM subtests and included five of the six cognitive domains tested on the ACR-NB, a high and a low cutoff value gave an area under the curve of 79%, sensitivity of 80%-89%, specificity of 54%-70%, positive predictive value of 78%-83%, and negative predictive value of 65%-74%.
The composite index performed similarly well among patients with or without neuropsychiatric lupus.
“This approach not only enables us to use a cost-effective screening approach without specialized personnel, but we have reduced the duration of the ANAM battery itself. The ANAM [version 4 General Neuropsychological Screening] full battery requires approximately 40 minutes to administer, while our analyses enable us to limit the number of ANAM subtests used, shortening the testing duration to 20 minutes,” they wrote.
The investigators noted that the study included only individuals with sufficient English language ability to complete the tests, and they also excluded patients with indeterminate cognitive status. “We reasoned that they represented a nonhomogeneous group, and without a clear consensus on the definition of CI in SLE patients, we chose to concentrate on the more clearly defined CI SLE patients.”
The study was supported by grants from the Arthritis Society of Canada, Physician’s Services, the Kathi and Peter Kaiser Family, and the Lou and Marissa Rocca Family. One author was supported by the Arthritis Society and the Canadian Rheumatology Association. No conflicts of interest were declared.
SOURCE: Tayer-Shifman OE et al. Arthritis Care Res. 2019 Oct 18. doi: 10.1002/acr.24096.
new research suggests.
In a paper published in Arthritis Care & Research, researchers assessed the validity of the Automated Neuropsychological Assessment Metrics (ANAM) test in 211 adult patients with systemic lupus erythematosus (SLE).
First author Oshrat E. Tayer-Shifman, MD, of the University of Toronto Lupus Clinic and coauthors wrote that current assessment of cognitive impairment in adults with SLE is done using the American College of Rheumatology neuropsychological battery (ACR-NB). However, this approach involves protected tests that require specialized personnel and takes around 1 hour to administer, as well as time for scoring and interpretation.
“For many clinics, these are notable barriers to accessing CI [cognitive impairment] assessment, as health care payers do not cover these costs,” the investigators wrote. And although briefer cognitive screening tools, such as the Montreal Cognitive Assessment, the Controlled Oral Word Association Test, and the Hopkins Verbal Learning Test–Revised, have been examined in studies of patients with SLE, “they also require specialized personnel for administration and interpretation and cannot be self-administered. In addition, their validity for the screening for CI in SLE has not been well established. Thus, there is an unmet need for a screening assessment for CI that is validated for SLE and that can be applied in an ambulatory clinic setting without specialized personnel.”
The full ANAM battery requires about 40 minutes and has been used to screen cognitive performance in a range of clinical contexts.
A total of 96 patients (46%) had CI and 52 (25%) did not, according to the ACR-NB, while the results were indeterminate in the remaining 63 (30%).
The study showed that patients without CI performed significantly better on the majority of the ANAM subtests in comparison with patients who have cognitive impairment. This was particularly evident on mean reaction time and the number of correct responses per minute (a measure of cognitive efficiency), but less so for percentage of correct responses and consistency of response speed.
“Three of the most affected cognitive domains in the CI patients in this cohort, as well as in previous studies, were learning and memory, visual spatial construction, and simple attention and speed of processing,” the researchers wrote.
The investigators created testing models using the subtests that were most discriminative for CI. The two best models included one encompassing the percentage of correct responses, consistency of response speed, and mean reaction time, as well as one encompassing these three factors as well as the number of correct responses per minute. The investigators then derived candidate ANAM composite indices from these two models. For one composite index that used 8 of the 15 ANAM subtests and included five of the six cognitive domains tested on the ACR-NB, a high and a low cutoff value gave an area under the curve of 79%, sensitivity of 80%-89%, specificity of 54%-70%, positive predictive value of 78%-83%, and negative predictive value of 65%-74%.
The composite index performed similarly well among patients with or without neuropsychiatric lupus.
“This approach not only enables us to use a cost-effective screening approach without specialized personnel, but we have reduced the duration of the ANAM battery itself. The ANAM [version 4 General Neuropsychological Screening] full battery requires approximately 40 minutes to administer, while our analyses enable us to limit the number of ANAM subtests used, shortening the testing duration to 20 minutes,” they wrote.
The investigators noted that the study included only individuals with sufficient English language ability to complete the tests, and they also excluded patients with indeterminate cognitive status. “We reasoned that they represented a nonhomogeneous group, and without a clear consensus on the definition of CI in SLE patients, we chose to concentrate on the more clearly defined CI SLE patients.”
The study was supported by grants from the Arthritis Society of Canada, Physician’s Services, the Kathi and Peter Kaiser Family, and the Lou and Marissa Rocca Family. One author was supported by the Arthritis Society and the Canadian Rheumatology Association. No conflicts of interest were declared.
SOURCE: Tayer-Shifman OE et al. Arthritis Care Res. 2019 Oct 18. doi: 10.1002/acr.24096.
new research suggests.
In a paper published in Arthritis Care & Research, researchers assessed the validity of the Automated Neuropsychological Assessment Metrics (ANAM) test in 211 adult patients with systemic lupus erythematosus (SLE).
First author Oshrat E. Tayer-Shifman, MD, of the University of Toronto Lupus Clinic and coauthors wrote that current assessment of cognitive impairment in adults with SLE is done using the American College of Rheumatology neuropsychological battery (ACR-NB). However, this approach involves protected tests that require specialized personnel and takes around 1 hour to administer, as well as time for scoring and interpretation.
“For many clinics, these are notable barriers to accessing CI [cognitive impairment] assessment, as health care payers do not cover these costs,” the investigators wrote. And although briefer cognitive screening tools, such as the Montreal Cognitive Assessment, the Controlled Oral Word Association Test, and the Hopkins Verbal Learning Test–Revised, have been examined in studies of patients with SLE, “they also require specialized personnel for administration and interpretation and cannot be self-administered. In addition, their validity for the screening for CI in SLE has not been well established. Thus, there is an unmet need for a screening assessment for CI that is validated for SLE and that can be applied in an ambulatory clinic setting without specialized personnel.”
The full ANAM battery requires about 40 minutes and has been used to screen cognitive performance in a range of clinical contexts.
A total of 96 patients (46%) had CI and 52 (25%) did not, according to the ACR-NB, while the results were indeterminate in the remaining 63 (30%).
The study showed that patients without CI performed significantly better on the majority of the ANAM subtests in comparison with patients who have cognitive impairment. This was particularly evident on mean reaction time and the number of correct responses per minute (a measure of cognitive efficiency), but less so for percentage of correct responses and consistency of response speed.
“Three of the most affected cognitive domains in the CI patients in this cohort, as well as in previous studies, were learning and memory, visual spatial construction, and simple attention and speed of processing,” the researchers wrote.
The investigators created testing models using the subtests that were most discriminative for CI. The two best models included one encompassing the percentage of correct responses, consistency of response speed, and mean reaction time, as well as one encompassing these three factors as well as the number of correct responses per minute. The investigators then derived candidate ANAM composite indices from these two models. For one composite index that used 8 of the 15 ANAM subtests and included five of the six cognitive domains tested on the ACR-NB, a high and a low cutoff value gave an area under the curve of 79%, sensitivity of 80%-89%, specificity of 54%-70%, positive predictive value of 78%-83%, and negative predictive value of 65%-74%.
The composite index performed similarly well among patients with or without neuropsychiatric lupus.
“This approach not only enables us to use a cost-effective screening approach without specialized personnel, but we have reduced the duration of the ANAM battery itself. The ANAM [version 4 General Neuropsychological Screening] full battery requires approximately 40 minutes to administer, while our analyses enable us to limit the number of ANAM subtests used, shortening the testing duration to 20 minutes,” they wrote.
The investigators noted that the study included only individuals with sufficient English language ability to complete the tests, and they also excluded patients with indeterminate cognitive status. “We reasoned that they represented a nonhomogeneous group, and without a clear consensus on the definition of CI in SLE patients, we chose to concentrate on the more clearly defined CI SLE patients.”
The study was supported by grants from the Arthritis Society of Canada, Physician’s Services, the Kathi and Peter Kaiser Family, and the Lou and Marissa Rocca Family. One author was supported by the Arthritis Society and the Canadian Rheumatology Association. No conflicts of interest were declared.
SOURCE: Tayer-Shifman OE et al. Arthritis Care Res. 2019 Oct 18. doi: 10.1002/acr.24096.
FROM ARTHRITIS CARE & RESEARCH
Imaging reveals different clinico-pathologic patterns in Takayasu’s, giant cell arteritis
a retrospective cohort study has found.
“Clinical symptoms were not sensitive markers of underlying vascular pathology but were specific when present,” Despina Michailidou, MD, PhD, and colleagues wrote in Annals of the Rheumatic Diseases. “Vascular imaging should be considered in the management of these patients since reliance on the presence of clinical symptoms may not be sensitive to detect vascular pathology within an acceptable window to prevent or minimize damage.”
Dr. Michailidou and coauthors in the Systemic Autoimmunity Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) examined the relationships between clinical presentation and imaging findings in 110 patients involved in an ongoing observational cohort study at the National Institutes of Health, including 56 with Takayasu’s arteritis (TAK) and 54 with giant cell arteritis (GCA). The study included data from 270 visits. Dr. Michailidou conducted the study while she was a research fellow at NIAMS, and she is now a rheumatology fellow at the University of Washington, Seattle.
The team looked at 11 symptoms (lightheadedness, positional lightheadedness, carotidynia, arm claudication vertigo, frontotemporal and posterior headache, posterior neck pain, blurred vision, vision loss, and major CNS events, including stroke, transient ischemic attack, or syncope). These were related to findings on MR angiography (MRA) and 18F-fluorodeoxyglucose PET (FDG-PET).
There were no significant between-group differences in six of the symptoms. However, those with TAK had significantly higher rates of carotidynia (21% vs. 0%), lightheadedness (30% vs. 9%), positional lightheadedness (29% vs. 5%), major CNS events (25% vs. 9%), and arm claudication (52% vs. 28%). Arm claudication was the most common symptom in those with TAK (52%), and blurred vision the most common in patients with GCA (37%).
On the day of evaluation, 8% of patients with TAK reported carotidynia; none of the GCA patients reported this. On FDG-PET, carotidynia was more strongly associated with inflammation of the carotid artery than with damage of the carotid artery on MRA.
The sensitivity of this association was low, which indicates “that an absence of carotidynia could still be associated with imaging abnormalities in the carotid artery, particularly on MRA compared with FDG-PET,” the authors wrote. But specificity was high for both FDG-PET and MRA, suggesting that carotidynia was strongly associated with corresponding carotid artery abnormalities on both FDG-PET and MRA.
More of those with GCA than those with TAK reported posterior neck pain (18% vs. 7%). It was significantly associated with vertebral artery inflammation in those with GCA, but not in those with TAK. There was no significant association with vertebral artery damage in either group.
While sensitivity was low for posterior neck pain and imaging abnormalities, specificity was very high in both groups, which indicates “the presence of posterior neck pain was strongly associated with corresponding vertebral artery abnormalities on both FDG-PET and MRA.”
Posterior headache was present in 5% of GCA patients and was significantly associated with vertebral artery damage, but it was not associated with such damage in patients with TAK.
“While posterior headaches in the occipital region are uncommon in patients with GCA, this study emphasizes that presence of a posterior headache should alert the clinician to the likelihood of associated vascular inflammation and damage in the corresponding vertebral artery,” the researchers wrote.
About 6% of patients with TAK and 10% of those with GCA reported frontotemporal headache. The headache was not associated with carotid PET activity or damage in either group of patients.
“While frontotemporal headaches frequently occur in patients with TAK, and are a cardinal feature of GCA, headaches in this region may reflect inflammation in smaller branches of cranial arteries, rather than the corresponding larger arteries of the neck,” the investigators wrote.
Arm claudication was the most commonly reported symptom overall, present in 52% of those with TAK and 28% of those with GCA. It was more strongly associated with subclavian artery damage on MRA than with inflammation on FDG-PET.
The investigators also assessed the association between specific clinical symptoms and the number of affected neck arteries. Patients with large vessel vasculitis and an increased number of damaged neck arteries on MRA were significantly more likely to experience lightheadedness (odds ratio, 2.61), positional lightheadedness (OR, 3.51), or a major CNS event (OR, 3.23). But those with large vessel vasculitis and inflamed neck arteries on FDG-PET were more likely to experience posterior headache (OR, 2.84).
The study isn’t intended to dictate how MRA and FDG-PET should be employed with these patients, the authors noted.
“Rather, these findings may help clinicians predict imaging pathology in specific vascular territories based on patient-reported symptoms and may inform which type of imaging modality would be the most useful to obtain in certain clinical scenarios, recognizing that additional sequences to detect wall morphology may augment the ability of MR-based assessments to detect vascular inflammation in addition to luminal damage.”
The Division of Intramural Research at NIAMS funded the research. The authors had no financial disclosures.
SOURCE: Michailidou D et al. Ann Rheum Dis. 2019 Oct 24. doi: 10.1136/annrheumdis-2019-216145.
a retrospective cohort study has found.
“Clinical symptoms were not sensitive markers of underlying vascular pathology but were specific when present,” Despina Michailidou, MD, PhD, and colleagues wrote in Annals of the Rheumatic Diseases. “Vascular imaging should be considered in the management of these patients since reliance on the presence of clinical symptoms may not be sensitive to detect vascular pathology within an acceptable window to prevent or minimize damage.”
Dr. Michailidou and coauthors in the Systemic Autoimmunity Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) examined the relationships between clinical presentation and imaging findings in 110 patients involved in an ongoing observational cohort study at the National Institutes of Health, including 56 with Takayasu’s arteritis (TAK) and 54 with giant cell arteritis (GCA). The study included data from 270 visits. Dr. Michailidou conducted the study while she was a research fellow at NIAMS, and she is now a rheumatology fellow at the University of Washington, Seattle.
The team looked at 11 symptoms (lightheadedness, positional lightheadedness, carotidynia, arm claudication vertigo, frontotemporal and posterior headache, posterior neck pain, blurred vision, vision loss, and major CNS events, including stroke, transient ischemic attack, or syncope). These were related to findings on MR angiography (MRA) and 18F-fluorodeoxyglucose PET (FDG-PET).
There were no significant between-group differences in six of the symptoms. However, those with TAK had significantly higher rates of carotidynia (21% vs. 0%), lightheadedness (30% vs. 9%), positional lightheadedness (29% vs. 5%), major CNS events (25% vs. 9%), and arm claudication (52% vs. 28%). Arm claudication was the most common symptom in those with TAK (52%), and blurred vision the most common in patients with GCA (37%).
On the day of evaluation, 8% of patients with TAK reported carotidynia; none of the GCA patients reported this. On FDG-PET, carotidynia was more strongly associated with inflammation of the carotid artery than with damage of the carotid artery on MRA.
The sensitivity of this association was low, which indicates “that an absence of carotidynia could still be associated with imaging abnormalities in the carotid artery, particularly on MRA compared with FDG-PET,” the authors wrote. But specificity was high for both FDG-PET and MRA, suggesting that carotidynia was strongly associated with corresponding carotid artery abnormalities on both FDG-PET and MRA.
More of those with GCA than those with TAK reported posterior neck pain (18% vs. 7%). It was significantly associated with vertebral artery inflammation in those with GCA, but not in those with TAK. There was no significant association with vertebral artery damage in either group.
While sensitivity was low for posterior neck pain and imaging abnormalities, specificity was very high in both groups, which indicates “the presence of posterior neck pain was strongly associated with corresponding vertebral artery abnormalities on both FDG-PET and MRA.”
Posterior headache was present in 5% of GCA patients and was significantly associated with vertebral artery damage, but it was not associated with such damage in patients with TAK.
“While posterior headaches in the occipital region are uncommon in patients with GCA, this study emphasizes that presence of a posterior headache should alert the clinician to the likelihood of associated vascular inflammation and damage in the corresponding vertebral artery,” the researchers wrote.
About 6% of patients with TAK and 10% of those with GCA reported frontotemporal headache. The headache was not associated with carotid PET activity or damage in either group of patients.
“While frontotemporal headaches frequently occur in patients with TAK, and are a cardinal feature of GCA, headaches in this region may reflect inflammation in smaller branches of cranial arteries, rather than the corresponding larger arteries of the neck,” the investigators wrote.
Arm claudication was the most commonly reported symptom overall, present in 52% of those with TAK and 28% of those with GCA. It was more strongly associated with subclavian artery damage on MRA than with inflammation on FDG-PET.
The investigators also assessed the association between specific clinical symptoms and the number of affected neck arteries. Patients with large vessel vasculitis and an increased number of damaged neck arteries on MRA were significantly more likely to experience lightheadedness (odds ratio, 2.61), positional lightheadedness (OR, 3.51), or a major CNS event (OR, 3.23). But those with large vessel vasculitis and inflamed neck arteries on FDG-PET were more likely to experience posterior headache (OR, 2.84).
The study isn’t intended to dictate how MRA and FDG-PET should be employed with these patients, the authors noted.
“Rather, these findings may help clinicians predict imaging pathology in specific vascular territories based on patient-reported symptoms and may inform which type of imaging modality would be the most useful to obtain in certain clinical scenarios, recognizing that additional sequences to detect wall morphology may augment the ability of MR-based assessments to detect vascular inflammation in addition to luminal damage.”
The Division of Intramural Research at NIAMS funded the research. The authors had no financial disclosures.
SOURCE: Michailidou D et al. Ann Rheum Dis. 2019 Oct 24. doi: 10.1136/annrheumdis-2019-216145.
a retrospective cohort study has found.
“Clinical symptoms were not sensitive markers of underlying vascular pathology but were specific when present,” Despina Michailidou, MD, PhD, and colleagues wrote in Annals of the Rheumatic Diseases. “Vascular imaging should be considered in the management of these patients since reliance on the presence of clinical symptoms may not be sensitive to detect vascular pathology within an acceptable window to prevent or minimize damage.”
Dr. Michailidou and coauthors in the Systemic Autoimmunity Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) examined the relationships between clinical presentation and imaging findings in 110 patients involved in an ongoing observational cohort study at the National Institutes of Health, including 56 with Takayasu’s arteritis (TAK) and 54 with giant cell arteritis (GCA). The study included data from 270 visits. Dr. Michailidou conducted the study while she was a research fellow at NIAMS, and she is now a rheumatology fellow at the University of Washington, Seattle.
The team looked at 11 symptoms (lightheadedness, positional lightheadedness, carotidynia, arm claudication vertigo, frontotemporal and posterior headache, posterior neck pain, blurred vision, vision loss, and major CNS events, including stroke, transient ischemic attack, or syncope). These were related to findings on MR angiography (MRA) and 18F-fluorodeoxyglucose PET (FDG-PET).
There were no significant between-group differences in six of the symptoms. However, those with TAK had significantly higher rates of carotidynia (21% vs. 0%), lightheadedness (30% vs. 9%), positional lightheadedness (29% vs. 5%), major CNS events (25% vs. 9%), and arm claudication (52% vs. 28%). Arm claudication was the most common symptom in those with TAK (52%), and blurred vision the most common in patients with GCA (37%).
On the day of evaluation, 8% of patients with TAK reported carotidynia; none of the GCA patients reported this. On FDG-PET, carotidynia was more strongly associated with inflammation of the carotid artery than with damage of the carotid artery on MRA.
The sensitivity of this association was low, which indicates “that an absence of carotidynia could still be associated with imaging abnormalities in the carotid artery, particularly on MRA compared with FDG-PET,” the authors wrote. But specificity was high for both FDG-PET and MRA, suggesting that carotidynia was strongly associated with corresponding carotid artery abnormalities on both FDG-PET and MRA.
More of those with GCA than those with TAK reported posterior neck pain (18% vs. 7%). It was significantly associated with vertebral artery inflammation in those with GCA, but not in those with TAK. There was no significant association with vertebral artery damage in either group.
While sensitivity was low for posterior neck pain and imaging abnormalities, specificity was very high in both groups, which indicates “the presence of posterior neck pain was strongly associated with corresponding vertebral artery abnormalities on both FDG-PET and MRA.”
Posterior headache was present in 5% of GCA patients and was significantly associated with vertebral artery damage, but it was not associated with such damage in patients with TAK.
“While posterior headaches in the occipital region are uncommon in patients with GCA, this study emphasizes that presence of a posterior headache should alert the clinician to the likelihood of associated vascular inflammation and damage in the corresponding vertebral artery,” the researchers wrote.
About 6% of patients with TAK and 10% of those with GCA reported frontotemporal headache. The headache was not associated with carotid PET activity or damage in either group of patients.
“While frontotemporal headaches frequently occur in patients with TAK, and are a cardinal feature of GCA, headaches in this region may reflect inflammation in smaller branches of cranial arteries, rather than the corresponding larger arteries of the neck,” the investigators wrote.
Arm claudication was the most commonly reported symptom overall, present in 52% of those with TAK and 28% of those with GCA. It was more strongly associated with subclavian artery damage on MRA than with inflammation on FDG-PET.
The investigators also assessed the association between specific clinical symptoms and the number of affected neck arteries. Patients with large vessel vasculitis and an increased number of damaged neck arteries on MRA were significantly more likely to experience lightheadedness (odds ratio, 2.61), positional lightheadedness (OR, 3.51), or a major CNS event (OR, 3.23). But those with large vessel vasculitis and inflamed neck arteries on FDG-PET were more likely to experience posterior headache (OR, 2.84).
The study isn’t intended to dictate how MRA and FDG-PET should be employed with these patients, the authors noted.
“Rather, these findings may help clinicians predict imaging pathology in specific vascular territories based on patient-reported symptoms and may inform which type of imaging modality would be the most useful to obtain in certain clinical scenarios, recognizing that additional sequences to detect wall morphology may augment the ability of MR-based assessments to detect vascular inflammation in addition to luminal damage.”
The Division of Intramural Research at NIAMS funded the research. The authors had no financial disclosures.
SOURCE: Michailidou D et al. Ann Rheum Dis. 2019 Oct 24. doi: 10.1136/annrheumdis-2019-216145.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: The associations between findings on MR angiography (MRA) and 18F-fluorodeoxyglucose (FDG) PET and differing clinical symptom presentations in patients with Takayasu’s arteritis and those with giant cell arteritis may be used to predict imaging pathology.
Major finding: Arm claudication was the most commonly reported symptom overall, present in 52% of those with Takayasu’s arteritis and 28% of those with giant cell arteritis. It was more strongly associated with subclavian artery damage on MRA than with inflammation on FDG-PET.
Study details: The cohort comprised 56 patients with Takayasu’s arteritis and 54 with giant cell arteritis who together had made 270 visits.
Disclosures: The Division of Intramural Research at the National Institute of Arthritis and Musculoskeletal and Skin Diseases funded the research. The investigators had no financial disclosures.
Source: Michailidou D et al. Ann Rheum Dis. 2019 Oct 24. doi: 10.1136/annrheumdis-2019-216145.
Macitentan produces similar results in PAH-SSc and IPAH/HPAH
NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.
Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.
“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.
She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.
Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.
Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.
The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.
Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).
About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).
The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.
The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.
The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.
SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.
NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.
Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.
“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.
She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.
Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.
Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.
The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.
Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).
About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).
The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.
The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.
The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.
SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.
NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.
Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.
“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.
She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.
Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.
Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.
The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.
Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).
About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).
The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.
The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.
The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.
SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.
REPORTING FROM CHEST 2019
Many children who present to headache clinics have joint hypermobility
CHARLOTTE, N.C. – according to data presented at the 48th national meeting of the Child Neurology Society. Furthermore, patients with joint hypermobility have a high rate of headache disability, while patients without joint hypermobility have less headache disability, according to Dhwani Sahjwani, MD, a resident at Inova Fairfax Hospital in Falls Church, Va., and colleagues.
While conducting research in the headache clinic at Children’s National Hospital in Washington, D.C., Dr. Sahjwani saw several children with joint hypermobility and a diagnosis of a disorder such as Ehlers-Danlos syndrome. She and her colleagues began analyzing patients to evaluate the potential association between joint hypermobility and headache disability in children. The investigators included pediatric patients examined in the headache clinic at Children’s National Medical Center between October 2018 and January 2019 in their study. All headache clinic patients were enrolled in a patient registry that had been approved by an independent review board.
Dr. Sahjwani and colleagues measured patients’ headache disability with the Headache Impact Test–6 (HIT-6) questionnaire. Scores of 60 or greater on this questionnaire indicate severe headache disability. The researchers assessed joint hypermobility using the Beighton scoring system. In this system, scores greater than 4 indicate joint hypermobility.
Dr. Sahjwani’s group scored 76 patients using the Beighton system and HIT-6 questionnaire. Participants’ median age was 13.7 years. Approximately 26% of patients had Beighton scores that indicated joint hypermobility. About 65% of the patients with joint hypermobility had a diagnosis of migraine without aura. In addition, 80% of patients with joint hypermobility had severe headache disability, according to the HIT-6 disability criteria. The average pain intensity in patients with hypermobile joints was 6.1 out of 10. Among participants without significant joint hypermobility, 90% had mild headache disability.
Patients with joint hypermobility and increased tissue elasticity “tend to have a lower threshold for pain, in general, in all parts of their bodies,” said Dr. Sahjwani. Greater headache severity might be expected in this population, “because they have more pain if they have hypermobile joints or tissue.”
Headache treatments for this population are based solely on the type of headache that each patient has. Patients with joint hypermobility and migraine, for example, are candidates for rescue medication and long-term prophylactic medications. “I don’t think the joint hypermobility is going to change how you manage their headaches,” said Dr. Sahjwani.
The study results suggest that, when children present with severely debilitating headaches, a neurologist should consider examining them for joint hypermobility “to see if they have another diagnosis, such as Ehlers-Danlos syndrome ... that has to be managed in addition to their headaches,” Dr. Sahjwani concluded.
The study was not supported by funding. The authors did not report any disclosures.
SOURCE: Sahjwani D et al. CNS 2019, Abstract 101.
CHARLOTTE, N.C. – according to data presented at the 48th national meeting of the Child Neurology Society. Furthermore, patients with joint hypermobility have a high rate of headache disability, while patients without joint hypermobility have less headache disability, according to Dhwani Sahjwani, MD, a resident at Inova Fairfax Hospital in Falls Church, Va., and colleagues.
While conducting research in the headache clinic at Children’s National Hospital in Washington, D.C., Dr. Sahjwani saw several children with joint hypermobility and a diagnosis of a disorder such as Ehlers-Danlos syndrome. She and her colleagues began analyzing patients to evaluate the potential association between joint hypermobility and headache disability in children. The investigators included pediatric patients examined in the headache clinic at Children’s National Medical Center between October 2018 and January 2019 in their study. All headache clinic patients were enrolled in a patient registry that had been approved by an independent review board.
Dr. Sahjwani and colleagues measured patients’ headache disability with the Headache Impact Test–6 (HIT-6) questionnaire. Scores of 60 or greater on this questionnaire indicate severe headache disability. The researchers assessed joint hypermobility using the Beighton scoring system. In this system, scores greater than 4 indicate joint hypermobility.
Dr. Sahjwani’s group scored 76 patients using the Beighton system and HIT-6 questionnaire. Participants’ median age was 13.7 years. Approximately 26% of patients had Beighton scores that indicated joint hypermobility. About 65% of the patients with joint hypermobility had a diagnosis of migraine without aura. In addition, 80% of patients with joint hypermobility had severe headache disability, according to the HIT-6 disability criteria. The average pain intensity in patients with hypermobile joints was 6.1 out of 10. Among participants without significant joint hypermobility, 90% had mild headache disability.
Patients with joint hypermobility and increased tissue elasticity “tend to have a lower threshold for pain, in general, in all parts of their bodies,” said Dr. Sahjwani. Greater headache severity might be expected in this population, “because they have more pain if they have hypermobile joints or tissue.”
Headache treatments for this population are based solely on the type of headache that each patient has. Patients with joint hypermobility and migraine, for example, are candidates for rescue medication and long-term prophylactic medications. “I don’t think the joint hypermobility is going to change how you manage their headaches,” said Dr. Sahjwani.
The study results suggest that, when children present with severely debilitating headaches, a neurologist should consider examining them for joint hypermobility “to see if they have another diagnosis, such as Ehlers-Danlos syndrome ... that has to be managed in addition to their headaches,” Dr. Sahjwani concluded.
The study was not supported by funding. The authors did not report any disclosures.
SOURCE: Sahjwani D et al. CNS 2019, Abstract 101.
CHARLOTTE, N.C. – according to data presented at the 48th national meeting of the Child Neurology Society. Furthermore, patients with joint hypermobility have a high rate of headache disability, while patients without joint hypermobility have less headache disability, according to Dhwani Sahjwani, MD, a resident at Inova Fairfax Hospital in Falls Church, Va., and colleagues.
While conducting research in the headache clinic at Children’s National Hospital in Washington, D.C., Dr. Sahjwani saw several children with joint hypermobility and a diagnosis of a disorder such as Ehlers-Danlos syndrome. She and her colleagues began analyzing patients to evaluate the potential association between joint hypermobility and headache disability in children. The investigators included pediatric patients examined in the headache clinic at Children’s National Medical Center between October 2018 and January 2019 in their study. All headache clinic patients were enrolled in a patient registry that had been approved by an independent review board.
Dr. Sahjwani and colleagues measured patients’ headache disability with the Headache Impact Test–6 (HIT-6) questionnaire. Scores of 60 or greater on this questionnaire indicate severe headache disability. The researchers assessed joint hypermobility using the Beighton scoring system. In this system, scores greater than 4 indicate joint hypermobility.
Dr. Sahjwani’s group scored 76 patients using the Beighton system and HIT-6 questionnaire. Participants’ median age was 13.7 years. Approximately 26% of patients had Beighton scores that indicated joint hypermobility. About 65% of the patients with joint hypermobility had a diagnosis of migraine without aura. In addition, 80% of patients with joint hypermobility had severe headache disability, according to the HIT-6 disability criteria. The average pain intensity in patients with hypermobile joints was 6.1 out of 10. Among participants without significant joint hypermobility, 90% had mild headache disability.
Patients with joint hypermobility and increased tissue elasticity “tend to have a lower threshold for pain, in general, in all parts of their bodies,” said Dr. Sahjwani. Greater headache severity might be expected in this population, “because they have more pain if they have hypermobile joints or tissue.”
Headache treatments for this population are based solely on the type of headache that each patient has. Patients with joint hypermobility and migraine, for example, are candidates for rescue medication and long-term prophylactic medications. “I don’t think the joint hypermobility is going to change how you manage their headaches,” said Dr. Sahjwani.
The study results suggest that, when children present with severely debilitating headaches, a neurologist should consider examining them for joint hypermobility “to see if they have another diagnosis, such as Ehlers-Danlos syndrome ... that has to be managed in addition to their headaches,” Dr. Sahjwani concluded.
The study was not supported by funding. The authors did not report any disclosures.
SOURCE: Sahjwani D et al. CNS 2019, Abstract 101.
REPORTING FROM CNS 2019
Macitentan, tadalafil combo found effective for newly diagnosed PAH
NEW ORLEANS – Treatment with macitentan and tadalafil can elicit improvements in patients with newly diagnosed pulmonary arterial hypertension (PAH), trial results suggest.
In the phase 4 OPTIMA trial, the combination significantly improved cardiopulmonary hemodynamics, functional class, 6-minute walk distance, and N-terminal pro B-type natriuretic peptide (NT-proBNP).
Olivier Sitbon, MD, PhD, of Université Paris–Sud in France, presented these results at the annual meeting of the American College of Chest Physicians.
The OPTIMA trial (NCT02968901) enrolled 46 adults who were newly diagnosed with PAH and had medium functional ability (WHO functional class II-III). The patients’ mean age was 57.4 ± 14.9 years, and 65% of them were female.
The mean time from PAH diagnosis was 29.6 ± 55.2 days. Patients had idiopathic PAH (63%), PAH associated with connective tissue disease (19.6%), heritable PAH (6.5%), drug- or toxin-induced PAH (4.4%), HIV-associated PAH (2.2%), and “other” PAH (4.4%).
Patients initially received macitentan at 10 mg once daily and tadalafil at 20 mg once daily. After 8 ± 3 days, the tadalafil dose was increased to 40 mg once daily. The median duration of treatment was 19.9 months.
The researchers assessed efficacy at week 16, but patients were monitored for safety until the study was closed by the sponsor. There were 44 patients who remained on study through week 16, and 39 patients completed the study.
Results
The study’s primary endpoint was the change in pulmonary vascular resistance (PVR). The ratio of week 16 to baseline PVR was 0.53, which translates to a significant 47% reduction in PVR. In fact, 87% of patients had a 30% or greater decrease in PVR from baseline to week 16.
Patients had improvements in other endpoints as well. The mean cardiac index increased from 2.2 to 3.1 L/min/m2 (P less than .0001) from baseline to week 16. The mean pulmonary arterial pressure decreased from 50.0 to 42.2 mm Hg (P = .0002), and the mean right atrial pressure decreased from 8.1 to 7.8 mm Hg (P = .7321).
The mean mixed venous oxygen saturation increased from 63.0% to 68.2% (P = .0003). The mean total pulmonary resistance decreased from 1109.4 to 677.4 dynes/sec/cm-5 (P less than .0001).
NT-proBNP decreased 68% from baseline to week 16. The geometric mean ratio was 0.32 (P less than .0001). The 6-minute walk distance increased from 352.2 to 388.1 m (P = .0008).
None of the patients experienced a worsening of WHO functional class from baseline to week 16, and 63% of patients experienced an improvement.
Nearly 94% of patients (n = 43) had at least one adverse event, 28% (n = 13) had serious adverse events, and 6.5% (n = 3) stopped treatment because of adverse events. The most frequent events were peripheral edema (n = 13), headache (n = 11), diarrhea (n = 9), and dyspnea (n = 7).
Three patients died during follow-up, one due to multiorgan failure and two due to underlying disease.
Actelion Pharmaceuticals funded the trial. Dr. Sitbon disclosed relationships with Actelion, Bayer, GSK, Merck, Arena Pharmaceuticals, Gossamer Bio, and Ferrer.
SOURCE: Sitbon O et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.825.
NEW ORLEANS – Treatment with macitentan and tadalafil can elicit improvements in patients with newly diagnosed pulmonary arterial hypertension (PAH), trial results suggest.
In the phase 4 OPTIMA trial, the combination significantly improved cardiopulmonary hemodynamics, functional class, 6-minute walk distance, and N-terminal pro B-type natriuretic peptide (NT-proBNP).
Olivier Sitbon, MD, PhD, of Université Paris–Sud in France, presented these results at the annual meeting of the American College of Chest Physicians.
The OPTIMA trial (NCT02968901) enrolled 46 adults who were newly diagnosed with PAH and had medium functional ability (WHO functional class II-III). The patients’ mean age was 57.4 ± 14.9 years, and 65% of them were female.
The mean time from PAH diagnosis was 29.6 ± 55.2 days. Patients had idiopathic PAH (63%), PAH associated with connective tissue disease (19.6%), heritable PAH (6.5%), drug- or toxin-induced PAH (4.4%), HIV-associated PAH (2.2%), and “other” PAH (4.4%).
Patients initially received macitentan at 10 mg once daily and tadalafil at 20 mg once daily. After 8 ± 3 days, the tadalafil dose was increased to 40 mg once daily. The median duration of treatment was 19.9 months.
The researchers assessed efficacy at week 16, but patients were monitored for safety until the study was closed by the sponsor. There were 44 patients who remained on study through week 16, and 39 patients completed the study.
Results
The study’s primary endpoint was the change in pulmonary vascular resistance (PVR). The ratio of week 16 to baseline PVR was 0.53, which translates to a significant 47% reduction in PVR. In fact, 87% of patients had a 30% or greater decrease in PVR from baseline to week 16.
Patients had improvements in other endpoints as well. The mean cardiac index increased from 2.2 to 3.1 L/min/m2 (P less than .0001) from baseline to week 16. The mean pulmonary arterial pressure decreased from 50.0 to 42.2 mm Hg (P = .0002), and the mean right atrial pressure decreased from 8.1 to 7.8 mm Hg (P = .7321).
The mean mixed venous oxygen saturation increased from 63.0% to 68.2% (P = .0003). The mean total pulmonary resistance decreased from 1109.4 to 677.4 dynes/sec/cm-5 (P less than .0001).
NT-proBNP decreased 68% from baseline to week 16. The geometric mean ratio was 0.32 (P less than .0001). The 6-minute walk distance increased from 352.2 to 388.1 m (P = .0008).
None of the patients experienced a worsening of WHO functional class from baseline to week 16, and 63% of patients experienced an improvement.
Nearly 94% of patients (n = 43) had at least one adverse event, 28% (n = 13) had serious adverse events, and 6.5% (n = 3) stopped treatment because of adverse events. The most frequent events were peripheral edema (n = 13), headache (n = 11), diarrhea (n = 9), and dyspnea (n = 7).
Three patients died during follow-up, one due to multiorgan failure and two due to underlying disease.
Actelion Pharmaceuticals funded the trial. Dr. Sitbon disclosed relationships with Actelion, Bayer, GSK, Merck, Arena Pharmaceuticals, Gossamer Bio, and Ferrer.
SOURCE: Sitbon O et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.825.
NEW ORLEANS – Treatment with macitentan and tadalafil can elicit improvements in patients with newly diagnosed pulmonary arterial hypertension (PAH), trial results suggest.
In the phase 4 OPTIMA trial, the combination significantly improved cardiopulmonary hemodynamics, functional class, 6-minute walk distance, and N-terminal pro B-type natriuretic peptide (NT-proBNP).
Olivier Sitbon, MD, PhD, of Université Paris–Sud in France, presented these results at the annual meeting of the American College of Chest Physicians.
The OPTIMA trial (NCT02968901) enrolled 46 adults who were newly diagnosed with PAH and had medium functional ability (WHO functional class II-III). The patients’ mean age was 57.4 ± 14.9 years, and 65% of them were female.
The mean time from PAH diagnosis was 29.6 ± 55.2 days. Patients had idiopathic PAH (63%), PAH associated with connective tissue disease (19.6%), heritable PAH (6.5%), drug- or toxin-induced PAH (4.4%), HIV-associated PAH (2.2%), and “other” PAH (4.4%).
Patients initially received macitentan at 10 mg once daily and tadalafil at 20 mg once daily. After 8 ± 3 days, the tadalafil dose was increased to 40 mg once daily. The median duration of treatment was 19.9 months.
The researchers assessed efficacy at week 16, but patients were monitored for safety until the study was closed by the sponsor. There were 44 patients who remained on study through week 16, and 39 patients completed the study.
Results
The study’s primary endpoint was the change in pulmonary vascular resistance (PVR). The ratio of week 16 to baseline PVR was 0.53, which translates to a significant 47% reduction in PVR. In fact, 87% of patients had a 30% or greater decrease in PVR from baseline to week 16.
Patients had improvements in other endpoints as well. The mean cardiac index increased from 2.2 to 3.1 L/min/m2 (P less than .0001) from baseline to week 16. The mean pulmonary arterial pressure decreased from 50.0 to 42.2 mm Hg (P = .0002), and the mean right atrial pressure decreased from 8.1 to 7.8 mm Hg (P = .7321).
The mean mixed venous oxygen saturation increased from 63.0% to 68.2% (P = .0003). The mean total pulmonary resistance decreased from 1109.4 to 677.4 dynes/sec/cm-5 (P less than .0001).
NT-proBNP decreased 68% from baseline to week 16. The geometric mean ratio was 0.32 (P less than .0001). The 6-minute walk distance increased from 352.2 to 388.1 m (P = .0008).
None of the patients experienced a worsening of WHO functional class from baseline to week 16, and 63% of patients experienced an improvement.
Nearly 94% of patients (n = 43) had at least one adverse event, 28% (n = 13) had serious adverse events, and 6.5% (n = 3) stopped treatment because of adverse events. The most frequent events were peripheral edema (n = 13), headache (n = 11), diarrhea (n = 9), and dyspnea (n = 7).
Three patients died during follow-up, one due to multiorgan failure and two due to underlying disease.
Actelion Pharmaceuticals funded the trial. Dr. Sitbon disclosed relationships with Actelion, Bayer, GSK, Merck, Arena Pharmaceuticals, Gossamer Bio, and Ferrer.
SOURCE: Sitbon O et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.825.
REPORTING FROM CHEST 2019
Low disease activity a valid target in early SLE, investigators say
, investigators in a small retrospective study have concluded.
Both complete remission (CR) and achievement of a lupus low disease activity state (LLDAS) were independently associated with lower accrual of early damage after 6 months of treatment, according to results of the study, reported in Arthritis Care & Research.
Patients maintaining LLDAS over the next 12 months developed considerably less damage than did those who never achieved LLDAS or who did not maintain LLDAS over time, according to the investigators, led by Alberto Floris, MD, and Matteo Piga, MD, of the AOU University Clinic of Cagliari (Italy).
Based on these findings, maintenance of both CR and LLDAS should be targeted for damage prevention, according to the authors. “Significant differences did not emerge between persistent LLDAS and CR over 12 months in preventing early damage,” they said in their report.
Their retrospective, single-center analysis included 116 adult patients with newly diagnosed SLE who had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of at least 6 at baseline and started treatment at enrollment. The mean age of this patient cohort was approximately 35 years, and about 90% were female.
After 6 months of follow-up, 42% of the cohort achieved LLDAS, defined in part as a SLEDAI-2K of 4 or less with no major organ activity or new disease activity, while 21.6% met CR criteria, which included a SLEDAI-2K of 0.
Achieving LLDAS at that 6-month time point was independently associated with lower damage accrual at 18 months (odds ratio, 0.25; 95% confidence interval, 0.06-0.99; P = .049); likewise, a 6-month CR translated into less damage at 18 months, according to multivariate analysis (OR, 0.07; 95% CI, 0.01-0.59; P = .015).
Those patients in LLDAS at 6 months who maintained that target for another 12 months had significantly less damage when compared with those who lost response or never achieved it, the investigators added.
“Losing the early attained LLDAS and CR may frustrate prevention of damage, and therefore, LLDAS and CR maintenance should be targeted since the first stage of SLE management,” the investigators said in their report.
About 54% of the patients in LLDAS at 6 months achieved CR at an 18-month follow-up time point, while about 21% remained in LLDAS and 25% went on to develop active disease, the investigators said. Among those in CR at 6 months, 60% maintained it at 18 months, while 40% worsened to either LLDAS or active disease.
Dr. Floris, Dr. Piga, and coauthors reported no funding or competing interests related to their research.
SOURCE: Floris A et al. Arthritis Care Res. 2019 Oct 10. doi: 10.1002/acr.24086.
, investigators in a small retrospective study have concluded.
Both complete remission (CR) and achievement of a lupus low disease activity state (LLDAS) were independently associated with lower accrual of early damage after 6 months of treatment, according to results of the study, reported in Arthritis Care & Research.
Patients maintaining LLDAS over the next 12 months developed considerably less damage than did those who never achieved LLDAS or who did not maintain LLDAS over time, according to the investigators, led by Alberto Floris, MD, and Matteo Piga, MD, of the AOU University Clinic of Cagliari (Italy).
Based on these findings, maintenance of both CR and LLDAS should be targeted for damage prevention, according to the authors. “Significant differences did not emerge between persistent LLDAS and CR over 12 months in preventing early damage,” they said in their report.
Their retrospective, single-center analysis included 116 adult patients with newly diagnosed SLE who had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of at least 6 at baseline and started treatment at enrollment. The mean age of this patient cohort was approximately 35 years, and about 90% were female.
After 6 months of follow-up, 42% of the cohort achieved LLDAS, defined in part as a SLEDAI-2K of 4 or less with no major organ activity or new disease activity, while 21.6% met CR criteria, which included a SLEDAI-2K of 0.
Achieving LLDAS at that 6-month time point was independently associated with lower damage accrual at 18 months (odds ratio, 0.25; 95% confidence interval, 0.06-0.99; P = .049); likewise, a 6-month CR translated into less damage at 18 months, according to multivariate analysis (OR, 0.07; 95% CI, 0.01-0.59; P = .015).
Those patients in LLDAS at 6 months who maintained that target for another 12 months had significantly less damage when compared with those who lost response or never achieved it, the investigators added.
“Losing the early attained LLDAS and CR may frustrate prevention of damage, and therefore, LLDAS and CR maintenance should be targeted since the first stage of SLE management,” the investigators said in their report.
About 54% of the patients in LLDAS at 6 months achieved CR at an 18-month follow-up time point, while about 21% remained in LLDAS and 25% went on to develop active disease, the investigators said. Among those in CR at 6 months, 60% maintained it at 18 months, while 40% worsened to either LLDAS or active disease.
Dr. Floris, Dr. Piga, and coauthors reported no funding or competing interests related to their research.
SOURCE: Floris A et al. Arthritis Care Res. 2019 Oct 10. doi: 10.1002/acr.24086.
, investigators in a small retrospective study have concluded.
Both complete remission (CR) and achievement of a lupus low disease activity state (LLDAS) were independently associated with lower accrual of early damage after 6 months of treatment, according to results of the study, reported in Arthritis Care & Research.
Patients maintaining LLDAS over the next 12 months developed considerably less damage than did those who never achieved LLDAS or who did not maintain LLDAS over time, according to the investigators, led by Alberto Floris, MD, and Matteo Piga, MD, of the AOU University Clinic of Cagliari (Italy).
Based on these findings, maintenance of both CR and LLDAS should be targeted for damage prevention, according to the authors. “Significant differences did not emerge between persistent LLDAS and CR over 12 months in preventing early damage,” they said in their report.
Their retrospective, single-center analysis included 116 adult patients with newly diagnosed SLE who had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of at least 6 at baseline and started treatment at enrollment. The mean age of this patient cohort was approximately 35 years, and about 90% were female.
After 6 months of follow-up, 42% of the cohort achieved LLDAS, defined in part as a SLEDAI-2K of 4 or less with no major organ activity or new disease activity, while 21.6% met CR criteria, which included a SLEDAI-2K of 0.
Achieving LLDAS at that 6-month time point was independently associated with lower damage accrual at 18 months (odds ratio, 0.25; 95% confidence interval, 0.06-0.99; P = .049); likewise, a 6-month CR translated into less damage at 18 months, according to multivariate analysis (OR, 0.07; 95% CI, 0.01-0.59; P = .015).
Those patients in LLDAS at 6 months who maintained that target for another 12 months had significantly less damage when compared with those who lost response or never achieved it, the investigators added.
“Losing the early attained LLDAS and CR may frustrate prevention of damage, and therefore, LLDAS and CR maintenance should be targeted since the first stage of SLE management,” the investigators said in their report.
About 54% of the patients in LLDAS at 6 months achieved CR at an 18-month follow-up time point, while about 21% remained in LLDAS and 25% went on to develop active disease, the investigators said. Among those in CR at 6 months, 60% maintained it at 18 months, while 40% worsened to either LLDAS or active disease.
Dr. Floris, Dr. Piga, and coauthors reported no funding or competing interests related to their research.
SOURCE: Floris A et al. Arthritis Care Res. 2019 Oct 10. doi: 10.1002/acr.24086.
FROM ARTHRITIS CARE & RESEARCH
Rituximab bests mycophenolate in pemphigus vulgaris
MADRID – Pascal Joly, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Not only did rituximab prove superior in terms of efficacy in the PEMPHIX trial, with a five times greater likelihood of achieving a complete remission lasting for at least 16 weeks while off oral corticosteroids than with mycophenolate mofetil in the 52-week study, but the total number of disease flares in the mycophenolate mofetil group was five times higher. Moreover, rituximab-treated patients received a markedly lower cumulative dose of prednisone as well.
“Rituximab has a superior overall benefit-risk profile, compared to mycophenolate mofetil, in patients with moderate to severe pemphigus vulgaris,” concluded Dr. Joly, professor of dermatology at the University of Rouen (France) and president of the French Society of Dermatology.
The study was undertaken because mycophenolate mofetil is commonly used as a corticosteroid-sparing drug in patients with pemphigus vulgaris, even though its efficacy for the treatment of this rare, severe autoimmune blistering disease is unproven, he explained.
In contrast, rituximab was approved by the Food and Drug Administration and European regulators for treatment of pemphigus vulgaris on the strength of the pivotal phase 3 Ritux 3 trial – also led by Dr. Joly – which demonstrated the superiority of this intravenously administered anti-CD20 monoclonal antibody plus short-term prednisone over high-dose corticosteroid monotherapy, which for decades had been the standard treatment despite its considerable toxicity burden (Lancet. 2017 May 20;389[10083]:2031-40).
An independently conducted analysis of Ritux 3 recently concluded that rituximab plus short-term prednisone was more effective than prednisone alone, with a lower risk of life-threatening, corticosteroid-related adverse events and less cumulative corticosteroid exposure (Br J Dermatol. 2019 Sep 5. doi: 10.1111/bjd.18482).
Also, an international panel of 93 pemphigus experts has declared that rituximab should be considered an evidence-based first-line therapy for moderate to-severe pemphigus (J Am Acad Dermatol. 2018 Feb 10. doi: 10.1016/j.jaad.2018.02.021).
The phase 3, placebo-controlled PEMPHIX trial randomized 135 patients with moderate or severe pemphigus at 49 academic medical centers in the United States and nine other countries to double-blind rituximab or mycophenolate mofetil on top of background oral prednisone at 1.0-1.5 mg/kg per day, with the steroid to be tapered and discontinued within 4-6 months.
The primary endpoint of the study was the proportion of patients in each study arm at week 52 who had achieved a sustained complete remission lasting for at least 16 weeks while off prednisone. The rate was 40.3% in the rituximab group and 9.5% with mycophenolate mofetil, for a 383% increased likelihood of sustained complete remission in the rituximab group.
In addition, all of the study’s secondary endpoints significantly favored rituximab. The median cumulative dose of corticosteroid was 2.7 g through 52 weeks in the rituximab arm, compared with 4 g with mycophenolate mofetil. The total number of disease flares over 52 weeks was 6 in the rituximab group and 44 in the mycophenolate arm. Five rituximab-treated patients experienced disease flares, as did 26 on mycophenolate. Thus, the likelihood of a flare was seven times lower with rituximab.
Scores on the Dermatology Life Quality Index improved by an average of 8.87 points from baseline to week 52 in the rituximab group versus 6 points with mycophenolate. And 62.7% of rituximab-treated patients had a week-52 Dermatology Life Quality Index score of 0, meaning no impact of the disease on their quality of life, compared with 25% of the mycophenolate group.
Dr. Joly characterized the safety profile of rituximab as “manageable, with acceptable tolerability.” About 9% of the rituximab group and 7.4% of mycophenolate-treated patients had one or more treatment-related adverse events, a nonsignificant difference. The rate of treatment-related serious infections was 3.0% with rituximab and 2.9% with mycophenolate. Serious infusion reactions leading to study withdrawal occurred in three patients on rituximab and one on mycophenolate. The rate of grade 3 or worse corticosteroid-related adverse events was 1.5% with rituximab and significantly greater at 7.4% with mycophenolate.
An additional 48-week safety assessment beyond the 52-week primary outcome is ongoing.
Asked what future role he sees for mycophenolate in pemphigus vulgaris, Dr. Joly replied that the only study in the literature that shows the drug outperforms placebo was seriously flawed. “In the future, it’s very likely that the indications for use of mycophenolate in pemphigus vulgaris will be fewer and fewer,” the dermatologist added.
In reply to a question about the merits of routine antibiotic prophylaxis against pneumocystis carinii pneumonia in patients taking rituximab for pemphigus vulgaris, Dr. Joly said the incidence isn’t sufficiently high to justify such practice. After all, he noted, there were no cases of pneumocystis carinii pneumonia in rituximab-treated patients in PEMPHIX and only one in Ritux 3.
EADV Scientific Programming Committee Chair Brigitte Dreno, MD, PhD, professor and head of dermatology at University Hospital in Nantes, France, inquired as to whether there’s a role for maintenance therapy in a potent rituximab-based treatment strategy such as utilized in PEMPHIX.
Definitely, Dr. Joly replied. However, further study is required to work out the best maintenance program.
“There are many arguments for maintenance therapy in these patients. For one, the frequency of relapses increases with the length of follow-up. Also, anti–desmoglein-specific T cells can still be detected after rituximab therapy, even in patients in complete remission. So there is a need for maintenance therapy, perhaps at months 6, 12, and 18, but the optimal regimen isn’t determined yet,” according to Dr. Joly.
PEMPHIX was sponsored by F. Hoffmann-La Roche. Dr. Joly reported serving as a consultant to Roche, Amgen, Principia Biopharma, and Argenx.
MADRID – Pascal Joly, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Not only did rituximab prove superior in terms of efficacy in the PEMPHIX trial, with a five times greater likelihood of achieving a complete remission lasting for at least 16 weeks while off oral corticosteroids than with mycophenolate mofetil in the 52-week study, but the total number of disease flares in the mycophenolate mofetil group was five times higher. Moreover, rituximab-treated patients received a markedly lower cumulative dose of prednisone as well.
“Rituximab has a superior overall benefit-risk profile, compared to mycophenolate mofetil, in patients with moderate to severe pemphigus vulgaris,” concluded Dr. Joly, professor of dermatology at the University of Rouen (France) and president of the French Society of Dermatology.
The study was undertaken because mycophenolate mofetil is commonly used as a corticosteroid-sparing drug in patients with pemphigus vulgaris, even though its efficacy for the treatment of this rare, severe autoimmune blistering disease is unproven, he explained.
In contrast, rituximab was approved by the Food and Drug Administration and European regulators for treatment of pemphigus vulgaris on the strength of the pivotal phase 3 Ritux 3 trial – also led by Dr. Joly – which demonstrated the superiority of this intravenously administered anti-CD20 monoclonal antibody plus short-term prednisone over high-dose corticosteroid monotherapy, which for decades had been the standard treatment despite its considerable toxicity burden (Lancet. 2017 May 20;389[10083]:2031-40).
An independently conducted analysis of Ritux 3 recently concluded that rituximab plus short-term prednisone was more effective than prednisone alone, with a lower risk of life-threatening, corticosteroid-related adverse events and less cumulative corticosteroid exposure (Br J Dermatol. 2019 Sep 5. doi: 10.1111/bjd.18482).
Also, an international panel of 93 pemphigus experts has declared that rituximab should be considered an evidence-based first-line therapy for moderate to-severe pemphigus (J Am Acad Dermatol. 2018 Feb 10. doi: 10.1016/j.jaad.2018.02.021).
The phase 3, placebo-controlled PEMPHIX trial randomized 135 patients with moderate or severe pemphigus at 49 academic medical centers in the United States and nine other countries to double-blind rituximab or mycophenolate mofetil on top of background oral prednisone at 1.0-1.5 mg/kg per day, with the steroid to be tapered and discontinued within 4-6 months.
The primary endpoint of the study was the proportion of patients in each study arm at week 52 who had achieved a sustained complete remission lasting for at least 16 weeks while off prednisone. The rate was 40.3% in the rituximab group and 9.5% with mycophenolate mofetil, for a 383% increased likelihood of sustained complete remission in the rituximab group.
In addition, all of the study’s secondary endpoints significantly favored rituximab. The median cumulative dose of corticosteroid was 2.7 g through 52 weeks in the rituximab arm, compared with 4 g with mycophenolate mofetil. The total number of disease flares over 52 weeks was 6 in the rituximab group and 44 in the mycophenolate arm. Five rituximab-treated patients experienced disease flares, as did 26 on mycophenolate. Thus, the likelihood of a flare was seven times lower with rituximab.
Scores on the Dermatology Life Quality Index improved by an average of 8.87 points from baseline to week 52 in the rituximab group versus 6 points with mycophenolate. And 62.7% of rituximab-treated patients had a week-52 Dermatology Life Quality Index score of 0, meaning no impact of the disease on their quality of life, compared with 25% of the mycophenolate group.
Dr. Joly characterized the safety profile of rituximab as “manageable, with acceptable tolerability.” About 9% of the rituximab group and 7.4% of mycophenolate-treated patients had one or more treatment-related adverse events, a nonsignificant difference. The rate of treatment-related serious infections was 3.0% with rituximab and 2.9% with mycophenolate. Serious infusion reactions leading to study withdrawal occurred in three patients on rituximab and one on mycophenolate. The rate of grade 3 or worse corticosteroid-related adverse events was 1.5% with rituximab and significantly greater at 7.4% with mycophenolate.
An additional 48-week safety assessment beyond the 52-week primary outcome is ongoing.
Asked what future role he sees for mycophenolate in pemphigus vulgaris, Dr. Joly replied that the only study in the literature that shows the drug outperforms placebo was seriously flawed. “In the future, it’s very likely that the indications for use of mycophenolate in pemphigus vulgaris will be fewer and fewer,” the dermatologist added.
In reply to a question about the merits of routine antibiotic prophylaxis against pneumocystis carinii pneumonia in patients taking rituximab for pemphigus vulgaris, Dr. Joly said the incidence isn’t sufficiently high to justify such practice. After all, he noted, there were no cases of pneumocystis carinii pneumonia in rituximab-treated patients in PEMPHIX and only one in Ritux 3.
EADV Scientific Programming Committee Chair Brigitte Dreno, MD, PhD, professor and head of dermatology at University Hospital in Nantes, France, inquired as to whether there’s a role for maintenance therapy in a potent rituximab-based treatment strategy such as utilized in PEMPHIX.
Definitely, Dr. Joly replied. However, further study is required to work out the best maintenance program.
“There are many arguments for maintenance therapy in these patients. For one, the frequency of relapses increases with the length of follow-up. Also, anti–desmoglein-specific T cells can still be detected after rituximab therapy, even in patients in complete remission. So there is a need for maintenance therapy, perhaps at months 6, 12, and 18, but the optimal regimen isn’t determined yet,” according to Dr. Joly.
PEMPHIX was sponsored by F. Hoffmann-La Roche. Dr. Joly reported serving as a consultant to Roche, Amgen, Principia Biopharma, and Argenx.
MADRID – Pascal Joly, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Not only did rituximab prove superior in terms of efficacy in the PEMPHIX trial, with a five times greater likelihood of achieving a complete remission lasting for at least 16 weeks while off oral corticosteroids than with mycophenolate mofetil in the 52-week study, but the total number of disease flares in the mycophenolate mofetil group was five times higher. Moreover, rituximab-treated patients received a markedly lower cumulative dose of prednisone as well.
“Rituximab has a superior overall benefit-risk profile, compared to mycophenolate mofetil, in patients with moderate to severe pemphigus vulgaris,” concluded Dr. Joly, professor of dermatology at the University of Rouen (France) and president of the French Society of Dermatology.
The study was undertaken because mycophenolate mofetil is commonly used as a corticosteroid-sparing drug in patients with pemphigus vulgaris, even though its efficacy for the treatment of this rare, severe autoimmune blistering disease is unproven, he explained.
In contrast, rituximab was approved by the Food and Drug Administration and European regulators for treatment of pemphigus vulgaris on the strength of the pivotal phase 3 Ritux 3 trial – also led by Dr. Joly – which demonstrated the superiority of this intravenously administered anti-CD20 monoclonal antibody plus short-term prednisone over high-dose corticosteroid monotherapy, which for decades had been the standard treatment despite its considerable toxicity burden (Lancet. 2017 May 20;389[10083]:2031-40).
An independently conducted analysis of Ritux 3 recently concluded that rituximab plus short-term prednisone was more effective than prednisone alone, with a lower risk of life-threatening, corticosteroid-related adverse events and less cumulative corticosteroid exposure (Br J Dermatol. 2019 Sep 5. doi: 10.1111/bjd.18482).
Also, an international panel of 93 pemphigus experts has declared that rituximab should be considered an evidence-based first-line therapy for moderate to-severe pemphigus (J Am Acad Dermatol. 2018 Feb 10. doi: 10.1016/j.jaad.2018.02.021).
The phase 3, placebo-controlled PEMPHIX trial randomized 135 patients with moderate or severe pemphigus at 49 academic medical centers in the United States and nine other countries to double-blind rituximab or mycophenolate mofetil on top of background oral prednisone at 1.0-1.5 mg/kg per day, with the steroid to be tapered and discontinued within 4-6 months.
The primary endpoint of the study was the proportion of patients in each study arm at week 52 who had achieved a sustained complete remission lasting for at least 16 weeks while off prednisone. The rate was 40.3% in the rituximab group and 9.5% with mycophenolate mofetil, for a 383% increased likelihood of sustained complete remission in the rituximab group.
In addition, all of the study’s secondary endpoints significantly favored rituximab. The median cumulative dose of corticosteroid was 2.7 g through 52 weeks in the rituximab arm, compared with 4 g with mycophenolate mofetil. The total number of disease flares over 52 weeks was 6 in the rituximab group and 44 in the mycophenolate arm. Five rituximab-treated patients experienced disease flares, as did 26 on mycophenolate. Thus, the likelihood of a flare was seven times lower with rituximab.
Scores on the Dermatology Life Quality Index improved by an average of 8.87 points from baseline to week 52 in the rituximab group versus 6 points with mycophenolate. And 62.7% of rituximab-treated patients had a week-52 Dermatology Life Quality Index score of 0, meaning no impact of the disease on their quality of life, compared with 25% of the mycophenolate group.
Dr. Joly characterized the safety profile of rituximab as “manageable, with acceptable tolerability.” About 9% of the rituximab group and 7.4% of mycophenolate-treated patients had one or more treatment-related adverse events, a nonsignificant difference. The rate of treatment-related serious infections was 3.0% with rituximab and 2.9% with mycophenolate. Serious infusion reactions leading to study withdrawal occurred in three patients on rituximab and one on mycophenolate. The rate of grade 3 or worse corticosteroid-related adverse events was 1.5% with rituximab and significantly greater at 7.4% with mycophenolate.
An additional 48-week safety assessment beyond the 52-week primary outcome is ongoing.
Asked what future role he sees for mycophenolate in pemphigus vulgaris, Dr. Joly replied that the only study in the literature that shows the drug outperforms placebo was seriously flawed. “In the future, it’s very likely that the indications for use of mycophenolate in pemphigus vulgaris will be fewer and fewer,” the dermatologist added.
In reply to a question about the merits of routine antibiotic prophylaxis against pneumocystis carinii pneumonia in patients taking rituximab for pemphigus vulgaris, Dr. Joly said the incidence isn’t sufficiently high to justify such practice. After all, he noted, there were no cases of pneumocystis carinii pneumonia in rituximab-treated patients in PEMPHIX and only one in Ritux 3.
EADV Scientific Programming Committee Chair Brigitte Dreno, MD, PhD, professor and head of dermatology at University Hospital in Nantes, France, inquired as to whether there’s a role for maintenance therapy in a potent rituximab-based treatment strategy such as utilized in PEMPHIX.
Definitely, Dr. Joly replied. However, further study is required to work out the best maintenance program.
“There are many arguments for maintenance therapy in these patients. For one, the frequency of relapses increases with the length of follow-up. Also, anti–desmoglein-specific T cells can still be detected after rituximab therapy, even in patients in complete remission. So there is a need for maintenance therapy, perhaps at months 6, 12, and 18, but the optimal regimen isn’t determined yet,” according to Dr. Joly.
PEMPHIX was sponsored by F. Hoffmann-La Roche. Dr. Joly reported serving as a consultant to Roche, Amgen, Principia Biopharma, and Argenx.
REPORTING FROM THE EADV CONGRESS
Expanding Medicaid did not reduce preventable hospitalizations for lupus patients
A new study has found that, although the Affordable Care Act (ACA) increased health insurance coverage in states that expanded their Medicaid program, the expansion did not translate into improved access to care or decreased preventable hospitalizations of patients with systemic lupus erythematosus (SLE).
“Our findings emphasize the importance of addressing systemic problems with American healthcare delivery at multiple levels,” wrote Elizabeth A. Brown, PhD, of the Medical University of South Carolina, Charleston, and her coauthors. The study was published in Arthritis Care & Research.
To examine the effects of the ACA’s Medicaid expansion on lupus patients when it was implemented Jan. 1, 2014, the researchers launched a retrospective, quasi‐experimental study using administrative data from eight states to compare eight quarterly time points in the 2 years prior to implementation against seven quarterly time points in the 2 years after implementation. Four states expanded Medicaid under the ACA – Arizona, Kentucky, New Jersey, and New York – and four of them did not – Florida, Georgia, South Carolina, and Wisconsin.
During the study period, there were 204,150 lupus hospitalizations across all eight states during the 15 quarters, 53% of which occurred in the four states that did not expand Medicaid. Although the investigators’ base model found that the probability of a preventable hospitalization did not increase over time (odds ratio, 1.004; 95% confidence interval, 0.996-1.013), the four expansion states had significantly higher odds of having preventable hospitalizations in the final adjusted model (OR, 1.302; 95% CI, 1.119-1.515).
Variables that contributed to higher odds of a preventable hospitalization included age: Lupus patients who were 55-64 years old had considerably higher odds for preventable lupus hospitalizations than did patients who were 20-34 years old (OR, 1.488; 95% CI, 1.415-1.564). In addition, those with a median household income under $42,000 had higher odds of hospitalization when compared with those making over $68,000 (OR, 1.138; 95% CI, 1.415-1.564), as did those on Medicaid compared with those on private insurance (OR, 1.298; 95% CI, 1.238-1.361).
The authors acknowledged their study’s limitations, including relying on potential coding errors within administrative data. In addition, they were unable to factor in Medicaid marketing, enrollment strategies, or other related actions undertaken in each of the eight states.
The study was partially supported by the South Carolina Clinical & Translational Research Institute via a National Center for Advancing Translational Sciences grant. The authors reported no conflicts of interest.
SOURCE: Brown EA et al. Arthritis Care Res. 2019 Sept 28. doi: 10.1002/acr.24080
A new study has found that, although the Affordable Care Act (ACA) increased health insurance coverage in states that expanded their Medicaid program, the expansion did not translate into improved access to care or decreased preventable hospitalizations of patients with systemic lupus erythematosus (SLE).
“Our findings emphasize the importance of addressing systemic problems with American healthcare delivery at multiple levels,” wrote Elizabeth A. Brown, PhD, of the Medical University of South Carolina, Charleston, and her coauthors. The study was published in Arthritis Care & Research.
To examine the effects of the ACA’s Medicaid expansion on lupus patients when it was implemented Jan. 1, 2014, the researchers launched a retrospective, quasi‐experimental study using administrative data from eight states to compare eight quarterly time points in the 2 years prior to implementation against seven quarterly time points in the 2 years after implementation. Four states expanded Medicaid under the ACA – Arizona, Kentucky, New Jersey, and New York – and four of them did not – Florida, Georgia, South Carolina, and Wisconsin.
During the study period, there were 204,150 lupus hospitalizations across all eight states during the 15 quarters, 53% of which occurred in the four states that did not expand Medicaid. Although the investigators’ base model found that the probability of a preventable hospitalization did not increase over time (odds ratio, 1.004; 95% confidence interval, 0.996-1.013), the four expansion states had significantly higher odds of having preventable hospitalizations in the final adjusted model (OR, 1.302; 95% CI, 1.119-1.515).
Variables that contributed to higher odds of a preventable hospitalization included age: Lupus patients who were 55-64 years old had considerably higher odds for preventable lupus hospitalizations than did patients who were 20-34 years old (OR, 1.488; 95% CI, 1.415-1.564). In addition, those with a median household income under $42,000 had higher odds of hospitalization when compared with those making over $68,000 (OR, 1.138; 95% CI, 1.415-1.564), as did those on Medicaid compared with those on private insurance (OR, 1.298; 95% CI, 1.238-1.361).
The authors acknowledged their study’s limitations, including relying on potential coding errors within administrative data. In addition, they were unable to factor in Medicaid marketing, enrollment strategies, or other related actions undertaken in each of the eight states.
The study was partially supported by the South Carolina Clinical & Translational Research Institute via a National Center for Advancing Translational Sciences grant. The authors reported no conflicts of interest.
SOURCE: Brown EA et al. Arthritis Care Res. 2019 Sept 28. doi: 10.1002/acr.24080
A new study has found that, although the Affordable Care Act (ACA) increased health insurance coverage in states that expanded their Medicaid program, the expansion did not translate into improved access to care or decreased preventable hospitalizations of patients with systemic lupus erythematosus (SLE).
“Our findings emphasize the importance of addressing systemic problems with American healthcare delivery at multiple levels,” wrote Elizabeth A. Brown, PhD, of the Medical University of South Carolina, Charleston, and her coauthors. The study was published in Arthritis Care & Research.
To examine the effects of the ACA’s Medicaid expansion on lupus patients when it was implemented Jan. 1, 2014, the researchers launched a retrospective, quasi‐experimental study using administrative data from eight states to compare eight quarterly time points in the 2 years prior to implementation against seven quarterly time points in the 2 years after implementation. Four states expanded Medicaid under the ACA – Arizona, Kentucky, New Jersey, and New York – and four of them did not – Florida, Georgia, South Carolina, and Wisconsin.
During the study period, there were 204,150 lupus hospitalizations across all eight states during the 15 quarters, 53% of which occurred in the four states that did not expand Medicaid. Although the investigators’ base model found that the probability of a preventable hospitalization did not increase over time (odds ratio, 1.004; 95% confidence interval, 0.996-1.013), the four expansion states had significantly higher odds of having preventable hospitalizations in the final adjusted model (OR, 1.302; 95% CI, 1.119-1.515).
Variables that contributed to higher odds of a preventable hospitalization included age: Lupus patients who were 55-64 years old had considerably higher odds for preventable lupus hospitalizations than did patients who were 20-34 years old (OR, 1.488; 95% CI, 1.415-1.564). In addition, those with a median household income under $42,000 had higher odds of hospitalization when compared with those making over $68,000 (OR, 1.138; 95% CI, 1.415-1.564), as did those on Medicaid compared with those on private insurance (OR, 1.298; 95% CI, 1.238-1.361).
The authors acknowledged their study’s limitations, including relying on potential coding errors within administrative data. In addition, they were unable to factor in Medicaid marketing, enrollment strategies, or other related actions undertaken in each of the eight states.
The study was partially supported by the South Carolina Clinical & Translational Research Institute via a National Center for Advancing Translational Sciences grant. The authors reported no conflicts of interest.
SOURCE: Brown EA et al. Arthritis Care Res. 2019 Sept 28. doi: 10.1002/acr.24080
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Expanded Medicaid coverage under the Affordable Care Act did not lead to decreased odds of preventable hospitalizations for lupus patients.
Major finding: After adjusted analysis, the four states with expanded Medicaid had significantly higher odds of having preventable hospitalizations than did the four that did not expand Medicaid (odds ratio, 1.302; 95% confidence interval, 1.119-1.515).
Study details: A retrospective, quasi‐experimental study using data from eight states, four that expanded Medicaid under the ACA and four that did not.
Disclosures: The study was partially supported by the South Carolina Clinical & Translational Research Institute via a National Center for Advancing Translational Sciences grant. The authors reported no conflicts of interest.
Source: Brown EA et al. Arthritis Care Res. 2019 Sept 28. doi: 10.1002/acr.24080.