User login
Belimumab may improve skin in scleroderma
MAUI, HAWAII – Belimumab shows promise as a novel biologic treatment for skin involvement in early diffuse cutaneous systemic sclerosis, Janet E. Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
She highlighted a single-center, double-blind, placebo-controlled, New York pilot study including 20 patients with early diffuse cutaneous systemic sclerosis and moderate skin involvement. Participants had recently started on background mycophenolate mofetil (MMF) at 1,000 mg twice daily and were then randomized to add-on belimumab (Benlysta) at the dosing approved for systemic lupus erythematosus or to infusions of normal saline.
At 52 weeks, the modified Rodnan skin thickness score (mRSS) decreased by a median of 10 points from a baseline of 27 in the belimumab group, compared with just a 3-point reduction in controls on MMF plus placebo.
This small study raises several key points. It definitely warrants confirmation in a large phase 3 trial, according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Care, both in London.
For one thing, the pilot study makes a good case for multidrug therapy in scleroderma. “In rheumatoid arthritis, if in general one drug is not as good as two, why would we ever think, in our most difficult-to-treat disease, one drug would be okay?” the rheumatologist observed.
The belimumab study also highlights the role of abnormalities in B-cell function in the pathogenesis of skin involvement in early diffuse cutaneous systemic sclerosis. Belimumab is a fully human monoclonal antibody which binds to soluble B-lymphocyte stimulator and inhibits autoantibody production.
Belimumab’s mechanism of benefit was as expected: The improvement in skin scores in the belimumab group was accompanied by decreased expression of profibrotic genes and B-cell signaling, changes that didn’t occur in the controls on MMF alone.
The belimumab study makes another important point: MMF, despite its growing popularity for treatment of skin manifestations of scleroderma, is actually a wimpy drug for that purpose, achieving a mere 3-point reduction in mRSS.
“To be quite honest, mycophenolate mofetil is not all that great on skin,” Dr. Pope said.
Nonetheless, when she and her coworkers recently polled 170 scleroderma experts as to their favored treatments directed at various target organs impaired by the disease, as she had previously done in 2012, a clear trend was evident. “There’s a shift in that mycophenolate mofetil is moving to first-line treatment across the board for skin,” Dr. Pope observed.
Indeed, in the more recent survey, 71% of the experts agreed upon a scleroderma skin involvement treatment algorithm in which the first-line treatment for severe skin disease as defined by an mRSS of 32 was MMF, with methotrexate as second line, intravenous cyclophosphamide third, and autologous stem cell transplantation as fourth line for the small number of patients who qualify for it.
For moderate skin involvement, with an mRSS of 24, methotrexate was endorsed as first line, although by the narrowest of margins, over MMF, with intravenous cyclophosphamide as third line. For mild disease, with an mRSS of 10, methotrexate again narrowly beat out MMF by expert consensus as the preferred first-line therapy.
When asked about concomitant use of corticosteroids for treatment of skin involvement, 35% of experts said they never prescribe them for that indication, 33% do so occasionally, 19% sometimes, and 13% routinely. There was an even split on dosing among those who prescribe steroids: 49% suggested using prednisone at less than 7.5 mg/day, and 51% recommended 7.5-20 mg/day.
The purpose in polling the experts, who were drawn from the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research Group, was to provide treatment guidance to general rheumatologists and dermatologists who may not see many patients with scleroderma. In contrast, the great majority of the polled experts see more than 50 scleroderma patients per year. And they had a high level of total agreement for treatment algorithms addressing not only skin disease, but also pulmonary arterial hypertension, interstitial lung disease, Raynaud’s phenomenon, renal crisis, digital ulcers, inflammatory arthritis, cardiac involvement, and gastrointestinal disease, Dr. Pope noted.
She attributed the experts’ rising enthusiasm for MMF for scleroderma skin involvement to the results of the Scleroderma Lung Study II, the first randomized, controlled trial to compare MMF and cyclophosphamide for the treatment of symptomatic scleroderma interstitial lung disease. Two years of MMF improved forced vital capacity as much as 1 year of oral cyclophosphamide. At 2 years of follow-up, the mRSS dropped modestly from baseline by an average of 6.1 points in the cyclophosphamide group and 2.9 points with MMF, a nonsignificant difference. But the incidence of serious adverse events was roughly three times higher and deaths were twice as frequent in the cyclophosphamide group.
“I think mycophenolate mofetil is surging for treatment of skin because of the lung protection and it was safer, but it’s hard for me to know if the deaths were more common in the cyclophosphamide group because of the cyclophosphamide or because of no treatment in year 2,” Dr. Pope commented.
She reported receiving research grants from Bristol-Myers Squibb, Merck, Roche, Seattle Genetics, and UCB, and serving as a consultant to more than a dozen pharmaceutical companies.
MAUI, HAWAII – Belimumab shows promise as a novel biologic treatment for skin involvement in early diffuse cutaneous systemic sclerosis, Janet E. Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
She highlighted a single-center, double-blind, placebo-controlled, New York pilot study including 20 patients with early diffuse cutaneous systemic sclerosis and moderate skin involvement. Participants had recently started on background mycophenolate mofetil (MMF) at 1,000 mg twice daily and were then randomized to add-on belimumab (Benlysta) at the dosing approved for systemic lupus erythematosus or to infusions of normal saline.
At 52 weeks, the modified Rodnan skin thickness score (mRSS) decreased by a median of 10 points from a baseline of 27 in the belimumab group, compared with just a 3-point reduction in controls on MMF plus placebo.
This small study raises several key points. It definitely warrants confirmation in a large phase 3 trial, according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Care, both in London.
For one thing, the pilot study makes a good case for multidrug therapy in scleroderma. “In rheumatoid arthritis, if in general one drug is not as good as two, why would we ever think, in our most difficult-to-treat disease, one drug would be okay?” the rheumatologist observed.
The belimumab study also highlights the role of abnormalities in B-cell function in the pathogenesis of skin involvement in early diffuse cutaneous systemic sclerosis. Belimumab is a fully human monoclonal antibody which binds to soluble B-lymphocyte stimulator and inhibits autoantibody production.
Belimumab’s mechanism of benefit was as expected: The improvement in skin scores in the belimumab group was accompanied by decreased expression of profibrotic genes and B-cell signaling, changes that didn’t occur in the controls on MMF alone.
The belimumab study makes another important point: MMF, despite its growing popularity for treatment of skin manifestations of scleroderma, is actually a wimpy drug for that purpose, achieving a mere 3-point reduction in mRSS.
“To be quite honest, mycophenolate mofetil is not all that great on skin,” Dr. Pope said.
Nonetheless, when she and her coworkers recently polled 170 scleroderma experts as to their favored treatments directed at various target organs impaired by the disease, as she had previously done in 2012, a clear trend was evident. “There’s a shift in that mycophenolate mofetil is moving to first-line treatment across the board for skin,” Dr. Pope observed.
Indeed, in the more recent survey, 71% of the experts agreed upon a scleroderma skin involvement treatment algorithm in which the first-line treatment for severe skin disease as defined by an mRSS of 32 was MMF, with methotrexate as second line, intravenous cyclophosphamide third, and autologous stem cell transplantation as fourth line for the small number of patients who qualify for it.
For moderate skin involvement, with an mRSS of 24, methotrexate was endorsed as first line, although by the narrowest of margins, over MMF, with intravenous cyclophosphamide as third line. For mild disease, with an mRSS of 10, methotrexate again narrowly beat out MMF by expert consensus as the preferred first-line therapy.
When asked about concomitant use of corticosteroids for treatment of skin involvement, 35% of experts said they never prescribe them for that indication, 33% do so occasionally, 19% sometimes, and 13% routinely. There was an even split on dosing among those who prescribe steroids: 49% suggested using prednisone at less than 7.5 mg/day, and 51% recommended 7.5-20 mg/day.
The purpose in polling the experts, who were drawn from the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research Group, was to provide treatment guidance to general rheumatologists and dermatologists who may not see many patients with scleroderma. In contrast, the great majority of the polled experts see more than 50 scleroderma patients per year. And they had a high level of total agreement for treatment algorithms addressing not only skin disease, but also pulmonary arterial hypertension, interstitial lung disease, Raynaud’s phenomenon, renal crisis, digital ulcers, inflammatory arthritis, cardiac involvement, and gastrointestinal disease, Dr. Pope noted.
She attributed the experts’ rising enthusiasm for MMF for scleroderma skin involvement to the results of the Scleroderma Lung Study II, the first randomized, controlled trial to compare MMF and cyclophosphamide for the treatment of symptomatic scleroderma interstitial lung disease. Two years of MMF improved forced vital capacity as much as 1 year of oral cyclophosphamide. At 2 years of follow-up, the mRSS dropped modestly from baseline by an average of 6.1 points in the cyclophosphamide group and 2.9 points with MMF, a nonsignificant difference. But the incidence of serious adverse events was roughly three times higher and deaths were twice as frequent in the cyclophosphamide group.
“I think mycophenolate mofetil is surging for treatment of skin because of the lung protection and it was safer, but it’s hard for me to know if the deaths were more common in the cyclophosphamide group because of the cyclophosphamide or because of no treatment in year 2,” Dr. Pope commented.
She reported receiving research grants from Bristol-Myers Squibb, Merck, Roche, Seattle Genetics, and UCB, and serving as a consultant to more than a dozen pharmaceutical companies.
MAUI, HAWAII – Belimumab shows promise as a novel biologic treatment for skin involvement in early diffuse cutaneous systemic sclerosis, Janet E. Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
She highlighted a single-center, double-blind, placebo-controlled, New York pilot study including 20 patients with early diffuse cutaneous systemic sclerosis and moderate skin involvement. Participants had recently started on background mycophenolate mofetil (MMF) at 1,000 mg twice daily and were then randomized to add-on belimumab (Benlysta) at the dosing approved for systemic lupus erythematosus or to infusions of normal saline.
At 52 weeks, the modified Rodnan skin thickness score (mRSS) decreased by a median of 10 points from a baseline of 27 in the belimumab group, compared with just a 3-point reduction in controls on MMF plus placebo.
This small study raises several key points. It definitely warrants confirmation in a large phase 3 trial, according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Care, both in London.
For one thing, the pilot study makes a good case for multidrug therapy in scleroderma. “In rheumatoid arthritis, if in general one drug is not as good as two, why would we ever think, in our most difficult-to-treat disease, one drug would be okay?” the rheumatologist observed.
The belimumab study also highlights the role of abnormalities in B-cell function in the pathogenesis of skin involvement in early diffuse cutaneous systemic sclerosis. Belimumab is a fully human monoclonal antibody which binds to soluble B-lymphocyte stimulator and inhibits autoantibody production.
Belimumab’s mechanism of benefit was as expected: The improvement in skin scores in the belimumab group was accompanied by decreased expression of profibrotic genes and B-cell signaling, changes that didn’t occur in the controls on MMF alone.
The belimumab study makes another important point: MMF, despite its growing popularity for treatment of skin manifestations of scleroderma, is actually a wimpy drug for that purpose, achieving a mere 3-point reduction in mRSS.
“To be quite honest, mycophenolate mofetil is not all that great on skin,” Dr. Pope said.
Nonetheless, when she and her coworkers recently polled 170 scleroderma experts as to their favored treatments directed at various target organs impaired by the disease, as she had previously done in 2012, a clear trend was evident. “There’s a shift in that mycophenolate mofetil is moving to first-line treatment across the board for skin,” Dr. Pope observed.
Indeed, in the more recent survey, 71% of the experts agreed upon a scleroderma skin involvement treatment algorithm in which the first-line treatment for severe skin disease as defined by an mRSS of 32 was MMF, with methotrexate as second line, intravenous cyclophosphamide third, and autologous stem cell transplantation as fourth line for the small number of patients who qualify for it.
For moderate skin involvement, with an mRSS of 24, methotrexate was endorsed as first line, although by the narrowest of margins, over MMF, with intravenous cyclophosphamide as third line. For mild disease, with an mRSS of 10, methotrexate again narrowly beat out MMF by expert consensus as the preferred first-line therapy.
When asked about concomitant use of corticosteroids for treatment of skin involvement, 35% of experts said they never prescribe them for that indication, 33% do so occasionally, 19% sometimes, and 13% routinely. There was an even split on dosing among those who prescribe steroids: 49% suggested using prednisone at less than 7.5 mg/day, and 51% recommended 7.5-20 mg/day.
The purpose in polling the experts, who were drawn from the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research Group, was to provide treatment guidance to general rheumatologists and dermatologists who may not see many patients with scleroderma. In contrast, the great majority of the polled experts see more than 50 scleroderma patients per year. And they had a high level of total agreement for treatment algorithms addressing not only skin disease, but also pulmonary arterial hypertension, interstitial lung disease, Raynaud’s phenomenon, renal crisis, digital ulcers, inflammatory arthritis, cardiac involvement, and gastrointestinal disease, Dr. Pope noted.
She attributed the experts’ rising enthusiasm for MMF for scleroderma skin involvement to the results of the Scleroderma Lung Study II, the first randomized, controlled trial to compare MMF and cyclophosphamide for the treatment of symptomatic scleroderma interstitial lung disease. Two years of MMF improved forced vital capacity as much as 1 year of oral cyclophosphamide. At 2 years of follow-up, the mRSS dropped modestly from baseline by an average of 6.1 points in the cyclophosphamide group and 2.9 points with MMF, a nonsignificant difference. But the incidence of serious adverse events was roughly three times higher and deaths were twice as frequent in the cyclophosphamide group.
“I think mycophenolate mofetil is surging for treatment of skin because of the lung protection and it was safer, but it’s hard for me to know if the deaths were more common in the cyclophosphamide group because of the cyclophosphamide or because of no treatment in year 2,” Dr. Pope commented.
She reported receiving research grants from Bristol-Myers Squibb, Merck, Roche, Seattle Genetics, and UCB, and serving as a consultant to more than a dozen pharmaceutical companies.
REPORTING FROM RWCS 2020
Vascular biomarkers predict pulmonary hypertension in systemic sclerosis
Levels of three vascular biomarkers – hepatocyte growth factor, soluble Flt-1, and platelet-derived growth factor – were elevated a mean of 3 years before systemic sclerosis (SSc) patients developed pulmonary hypertension (PH) in a prospective cohort of 300 subjects.
However, the associations with PH were not very robust. For instance, above an optimal cut point of 9.89 pg/mL for platelet-derived growth factor (PlGF), the sensitivity for future PH was 82%, specificity 56%, and area under the curve (AUC) 0.69. An elevation above the optimal cut point for soluble Flt-1 (sFlt1) – 93.8 pg/mL – was 71% specific and 51% sensitive, with an AUC of 0.61.
Adding PlGF and sFlt1 elevations to carbon monoxide diffusing capacity, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) level, and percent forced vital capacity to predict PH increased the AUC modestly, from 0.72 to 0.77.
The data suggest, perhaps, an early warning system for PH. “Once vascular biomarkers are observed to be elevated, the frequency of other screening tests (e.g., NT-proBNP, DLCO) may be increased in a more cost-effective approach,” wrote investigators led by rheumatologist Christopher Mecoli, MD, an assistant professor at Johns Hopkins University, Baltimore, in Arthritis & Rheumatology.
“In the end, the authors did not overstate the case and cautiously recommended that using biomarkers might be useful in the future. The finding that when there are increased numbers of abnormalities of vascular markers, there would be an increased probability of pulmonary hypertension, makes sense.” However, “this was a major fishing expedition, and the data are certainly not sufficient to suggest anything clinical but are of some interest with respect to the general hypothesis,” said rheumatologist Daniel Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, when asked for comment.
The subjects were followed for at least 5 years and had no evidence of PH at study entry. Levels of P1GF, sFlt-1, hepatocyte growth factor (HGF), soluble endoglin, and endostatin were assessed at baseline and at regular intervals thereafter. A total of 46 patients (15%) developed PH after a mean of 3 years.
Risk of PH was associated with baseline elevations of HGF (hazard ratio, 1.99; 95% CI, 1.24-3.17; P = .004); sFlt1 (HR, 3.04; 95% CI, 1.29-7.14; P = .011); and PlGF (HR, 2.74; 95% CI, 1.32-5.69; P = .007).
Just 2 of 25 patients (8%) with no biomarkers elevated at baseline developed PH versus 12 of 29 (42%) with all five elevated. That translated to a dose-response relationship, with each additional elevated biomarker increasing the risk of PH by 78% (95% CI, 1.2-2.6; P = .004).
“There [was] no consistent trend of increasing biomarker levels over time as patients approach[ed] a diagnosis of [PH]. ... Serial testing may have value in patients with early disease to first detect elevations in biomarkers,” but “once elevated, the utility of serially monitoring appears low,” the investigators wrote.
It’s not surprising that “a higher number of elevated biomarkers relating to vascular dysfunction would correspond to a higher risk of PH,” the team wrote. However, “while these biomarkers hold promise in the risk stratification of SSc patients, many more vascular molecules exist which may have similar or greater value.”
There was no substantial correlation between any biomarker and disease duration, age at enrollment, or age at diagnosis, and no significant difference in biomarker level based on patient comorbidities. No biomarker was significantly associated with medication use at cohort entry, and none were significantly associated with the risk of ischemic digital lesions.
The majority of patients were white women. At enrollment, the average age was 52 years, and subjects had SSc for a mean of 10 years.
The work was funded by the National Institutes of Health, among others. Investigator disclosures were not reported.
SOURCE: Mecoli C et al. Arthritis Rheumatol. 2020 Mar 21. doi: 10.1002/art.41265.
Levels of three vascular biomarkers – hepatocyte growth factor, soluble Flt-1, and platelet-derived growth factor – were elevated a mean of 3 years before systemic sclerosis (SSc) patients developed pulmonary hypertension (PH) in a prospective cohort of 300 subjects.
However, the associations with PH were not very robust. For instance, above an optimal cut point of 9.89 pg/mL for platelet-derived growth factor (PlGF), the sensitivity for future PH was 82%, specificity 56%, and area under the curve (AUC) 0.69. An elevation above the optimal cut point for soluble Flt-1 (sFlt1) – 93.8 pg/mL – was 71% specific and 51% sensitive, with an AUC of 0.61.
Adding PlGF and sFlt1 elevations to carbon monoxide diffusing capacity, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) level, and percent forced vital capacity to predict PH increased the AUC modestly, from 0.72 to 0.77.
The data suggest, perhaps, an early warning system for PH. “Once vascular biomarkers are observed to be elevated, the frequency of other screening tests (e.g., NT-proBNP, DLCO) may be increased in a more cost-effective approach,” wrote investigators led by rheumatologist Christopher Mecoli, MD, an assistant professor at Johns Hopkins University, Baltimore, in Arthritis & Rheumatology.
“In the end, the authors did not overstate the case and cautiously recommended that using biomarkers might be useful in the future. The finding that when there are increased numbers of abnormalities of vascular markers, there would be an increased probability of pulmonary hypertension, makes sense.” However, “this was a major fishing expedition, and the data are certainly not sufficient to suggest anything clinical but are of some interest with respect to the general hypothesis,” said rheumatologist Daniel Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, when asked for comment.
The subjects were followed for at least 5 years and had no evidence of PH at study entry. Levels of P1GF, sFlt-1, hepatocyte growth factor (HGF), soluble endoglin, and endostatin were assessed at baseline and at regular intervals thereafter. A total of 46 patients (15%) developed PH after a mean of 3 years.
Risk of PH was associated with baseline elevations of HGF (hazard ratio, 1.99; 95% CI, 1.24-3.17; P = .004); sFlt1 (HR, 3.04; 95% CI, 1.29-7.14; P = .011); and PlGF (HR, 2.74; 95% CI, 1.32-5.69; P = .007).
Just 2 of 25 patients (8%) with no biomarkers elevated at baseline developed PH versus 12 of 29 (42%) with all five elevated. That translated to a dose-response relationship, with each additional elevated biomarker increasing the risk of PH by 78% (95% CI, 1.2-2.6; P = .004).
“There [was] no consistent trend of increasing biomarker levels over time as patients approach[ed] a diagnosis of [PH]. ... Serial testing may have value in patients with early disease to first detect elevations in biomarkers,” but “once elevated, the utility of serially monitoring appears low,” the investigators wrote.
It’s not surprising that “a higher number of elevated biomarkers relating to vascular dysfunction would correspond to a higher risk of PH,” the team wrote. However, “while these biomarkers hold promise in the risk stratification of SSc patients, many more vascular molecules exist which may have similar or greater value.”
There was no substantial correlation between any biomarker and disease duration, age at enrollment, or age at diagnosis, and no significant difference in biomarker level based on patient comorbidities. No biomarker was significantly associated with medication use at cohort entry, and none were significantly associated with the risk of ischemic digital lesions.
The majority of patients were white women. At enrollment, the average age was 52 years, and subjects had SSc for a mean of 10 years.
The work was funded by the National Institutes of Health, among others. Investigator disclosures were not reported.
SOURCE: Mecoli C et al. Arthritis Rheumatol. 2020 Mar 21. doi: 10.1002/art.41265.
Levels of three vascular biomarkers – hepatocyte growth factor, soluble Flt-1, and platelet-derived growth factor – were elevated a mean of 3 years before systemic sclerosis (SSc) patients developed pulmonary hypertension (PH) in a prospective cohort of 300 subjects.
However, the associations with PH were not very robust. For instance, above an optimal cut point of 9.89 pg/mL for platelet-derived growth factor (PlGF), the sensitivity for future PH was 82%, specificity 56%, and area under the curve (AUC) 0.69. An elevation above the optimal cut point for soluble Flt-1 (sFlt1) – 93.8 pg/mL – was 71% specific and 51% sensitive, with an AUC of 0.61.
Adding PlGF and sFlt1 elevations to carbon monoxide diffusing capacity, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) level, and percent forced vital capacity to predict PH increased the AUC modestly, from 0.72 to 0.77.
The data suggest, perhaps, an early warning system for PH. “Once vascular biomarkers are observed to be elevated, the frequency of other screening tests (e.g., NT-proBNP, DLCO) may be increased in a more cost-effective approach,” wrote investigators led by rheumatologist Christopher Mecoli, MD, an assistant professor at Johns Hopkins University, Baltimore, in Arthritis & Rheumatology.
“In the end, the authors did not overstate the case and cautiously recommended that using biomarkers might be useful in the future. The finding that when there are increased numbers of abnormalities of vascular markers, there would be an increased probability of pulmonary hypertension, makes sense.” However, “this was a major fishing expedition, and the data are certainly not sufficient to suggest anything clinical but are of some interest with respect to the general hypothesis,” said rheumatologist Daniel Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, when asked for comment.
The subjects were followed for at least 5 years and had no evidence of PH at study entry. Levels of P1GF, sFlt-1, hepatocyte growth factor (HGF), soluble endoglin, and endostatin were assessed at baseline and at regular intervals thereafter. A total of 46 patients (15%) developed PH after a mean of 3 years.
Risk of PH was associated with baseline elevations of HGF (hazard ratio, 1.99; 95% CI, 1.24-3.17; P = .004); sFlt1 (HR, 3.04; 95% CI, 1.29-7.14; P = .011); and PlGF (HR, 2.74; 95% CI, 1.32-5.69; P = .007).
Just 2 of 25 patients (8%) with no biomarkers elevated at baseline developed PH versus 12 of 29 (42%) with all five elevated. That translated to a dose-response relationship, with each additional elevated biomarker increasing the risk of PH by 78% (95% CI, 1.2-2.6; P = .004).
“There [was] no consistent trend of increasing biomarker levels over time as patients approach[ed] a diagnosis of [PH]. ... Serial testing may have value in patients with early disease to first detect elevations in biomarkers,” but “once elevated, the utility of serially monitoring appears low,” the investigators wrote.
It’s not surprising that “a higher number of elevated biomarkers relating to vascular dysfunction would correspond to a higher risk of PH,” the team wrote. However, “while these biomarkers hold promise in the risk stratification of SSc patients, many more vascular molecules exist which may have similar or greater value.”
There was no substantial correlation between any biomarker and disease duration, age at enrollment, or age at diagnosis, and no significant difference in biomarker level based on patient comorbidities. No biomarker was significantly associated with medication use at cohort entry, and none were significantly associated with the risk of ischemic digital lesions.
The majority of patients were white women. At enrollment, the average age was 52 years, and subjects had SSc for a mean of 10 years.
The work was funded by the National Institutes of Health, among others. Investigator disclosures were not reported.
SOURCE: Mecoli C et al. Arthritis Rheumatol. 2020 Mar 21. doi: 10.1002/art.41265.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Levels of three vascular biomarkers – hepatocyte growth factor, soluble Flt-1, and platelet-derived growth factor – were elevated a mean of 3 years before systemic sclerosis patients developed pulmonary hypertension.
Major finding: The associations with pulmonary hypertension were not very robust. For instance, above an optimal cut point of 9.89 pg/mL for platelet-derived growth factor, the sensitivity for future pulmonary hypertension was 82%, specificity 56%, and area under the curve 0.69. An elevation above the optimal cut point for soluble Flt-1 – 93.8 pg/mL – was 71% specific and 51% sensitive, with an area under the curve of 0.61.
Study details: A prospective cohort of 300 patients
Disclosures: The work was funded by the National Institutes of Health, among others. Investigator disclosures weren’t reported.
Source: Mecoli C et al. Arthritis Rheumatol. 2020 Mar 21. doi: 10.1002/art.41265.
Leflunomide-hydroxychloroquine combination for Sjögren’s shows potential
according to results from a phase 2a, randomized clinical trial published in Lancet Rheumatology.
The combination’s statistically significant effect on the European League Against Rheumatism (EULAR) Sjögren’s syndrome disease activity index (ESSDAI) score at 24 weeks, the primary endpoint of the small, double-blind, placebo-controlled trial, suggests that the combination should be studied further in larger trials, according to first author Eefje Hanna Martine van der Heijden, MD, a rheumatologist at University Medical Center Utrecht (the Netherlands), and colleagues.
The investigators decided to study leflunomide and hydroxychloroquine, which target overlapping and distinct immunopathologic pathways, because data support the safety of each drug individually, and a previous in vitro study by the authors indicated that they have complementary effects when administered together.
“To our knowledge, this is the first randomized, placebo-controlled clinical trial in patients with primary Sjögren’s syndrome that shows significant clinical efficacy, as measured by ESSDAI, and is associated with significant improvements in other clinical parameters, including dryness and fatigue,” the investigators wrote.
Dr. van der Heijden and colleagues screened 37 patients from the outpatient clinic of their medical center and enrolled 29 (28 women) who met American-European Consensus Criteria into their study. They had moderate to active disease, defined as an ESSDAI score of 5 or higher, and a lymphocytic focus score of 1 or higher in labial salivary gland biopsy specimens that were obtained before inclusion. The population’s average age was approximately 54 years. They had an average disease duration of about 8 years, a mean ESSDAI score of about 9, and mean EULAR Sjögren’s syndrome patient reported index (ESSPRI) score of 6.7. A total of 21 patients were randomized to leflunomide 20 mg and hydroxychloroquine 400 mg daily, and 8 patients were randomized to placebos. Baseline characteristics were similar between groups, but mean serum IgG level was 19.4 g/L in the treatment group and 13.8 g/L in the placebo group. One patient in the placebo group developed polymyalgia rheumatica and required high-dose prednisone treatment. The investigators excluded this patient from the primary analysis.
At 24 weeks, the mean difference in ESSDAI score in the leflunomide-hydroxychloroquine group, compared with the placebo group, was –4.35 points after adjustment for baseline values. This difference was statistically significant.
Secondary endpoints in the study showed inconsistent statistically significant differences between the treatment groups at 8, 16, and 24 weeks. The total ESSPRI score at 16 weeks was 1.66 points lower in the treatment group than in the placebo group. Stimulated whole saliva production was increased in the leflunomide-hydroxychloroquine group at 16 weeks, compared with the placebo group. Unstimulated whole saliva production at 24 weeks was higher in the leflunomide-hydroxychloroquine group than in controls. The investigators found no differences between groups in visual analog scores for ocular or oral dryness.
No patient in the leflunomide-hydroxychloroquine group had a serious adverse event. Two serious adverse events (hospital admission for pancreatitis and hospital admission for nephrolithiasis) occurred in the placebo group. The most common adverse events in the leflunomide-hydroxychloroquine group were GI discomfort (52% vs. 25% in the placebo group), modest transient increases in ALT (48% vs. 13%), and short episodes of general malaise and shivering (43% vs. 13%).
In an accompanying editorial, Astrid Rasmussen, MD, PhD, of the Oklahoma Sjögren’s Syndrome Center of Research Translation at the Oklahoma Medical Research Foundation in Oklahoma City, wrote that the trial by Dr. van der Heijden and colleagues was limited by a small sample size and short duration. In addition, some of the findings were unexplained, such as modest changes in secondary endpoints and a concomitant decrease in ESSDAI scores at 8 weeks for both study groups.
Nevertheless, the study provides reason to think in new ways about old drugs, wrote Dr. Rasmussen. “Combination or sequential use of existing agents that target different aspects of immune dysregulation, while having acceptable safety profiles and cost-benefit ratios, should represent an avenue of further exploration. Just as importantly, subphenotyping patients on the basis of their underlying pathogenic processes and identifying sensitive outcome measures could transform the current enthusiasm for identifying effective treatments for Sjögren’s syndrome into a reality for the patients that need them the most.”
The study was funded by ZonMw. The authors of the study reported no conflicts of interest. Dr. Rasmussen reported having no conflicts of interest.
SOURCE: van der Heijden EHM et al. Lancet Rheumatol. 2020 Mar 26. doi: 10.1016/S2665-9913(20)30057-6.
according to results from a phase 2a, randomized clinical trial published in Lancet Rheumatology.
The combination’s statistically significant effect on the European League Against Rheumatism (EULAR) Sjögren’s syndrome disease activity index (ESSDAI) score at 24 weeks, the primary endpoint of the small, double-blind, placebo-controlled trial, suggests that the combination should be studied further in larger trials, according to first author Eefje Hanna Martine van der Heijden, MD, a rheumatologist at University Medical Center Utrecht (the Netherlands), and colleagues.
The investigators decided to study leflunomide and hydroxychloroquine, which target overlapping and distinct immunopathologic pathways, because data support the safety of each drug individually, and a previous in vitro study by the authors indicated that they have complementary effects when administered together.
“To our knowledge, this is the first randomized, placebo-controlled clinical trial in patients with primary Sjögren’s syndrome that shows significant clinical efficacy, as measured by ESSDAI, and is associated with significant improvements in other clinical parameters, including dryness and fatigue,” the investigators wrote.
Dr. van der Heijden and colleagues screened 37 patients from the outpatient clinic of their medical center and enrolled 29 (28 women) who met American-European Consensus Criteria into their study. They had moderate to active disease, defined as an ESSDAI score of 5 or higher, and a lymphocytic focus score of 1 or higher in labial salivary gland biopsy specimens that were obtained before inclusion. The population’s average age was approximately 54 years. They had an average disease duration of about 8 years, a mean ESSDAI score of about 9, and mean EULAR Sjögren’s syndrome patient reported index (ESSPRI) score of 6.7. A total of 21 patients were randomized to leflunomide 20 mg and hydroxychloroquine 400 mg daily, and 8 patients were randomized to placebos. Baseline characteristics were similar between groups, but mean serum IgG level was 19.4 g/L in the treatment group and 13.8 g/L in the placebo group. One patient in the placebo group developed polymyalgia rheumatica and required high-dose prednisone treatment. The investigators excluded this patient from the primary analysis.
At 24 weeks, the mean difference in ESSDAI score in the leflunomide-hydroxychloroquine group, compared with the placebo group, was –4.35 points after adjustment for baseline values. This difference was statistically significant.
Secondary endpoints in the study showed inconsistent statistically significant differences between the treatment groups at 8, 16, and 24 weeks. The total ESSPRI score at 16 weeks was 1.66 points lower in the treatment group than in the placebo group. Stimulated whole saliva production was increased in the leflunomide-hydroxychloroquine group at 16 weeks, compared with the placebo group. Unstimulated whole saliva production at 24 weeks was higher in the leflunomide-hydroxychloroquine group than in controls. The investigators found no differences between groups in visual analog scores for ocular or oral dryness.
No patient in the leflunomide-hydroxychloroquine group had a serious adverse event. Two serious adverse events (hospital admission for pancreatitis and hospital admission for nephrolithiasis) occurred in the placebo group. The most common adverse events in the leflunomide-hydroxychloroquine group were GI discomfort (52% vs. 25% in the placebo group), modest transient increases in ALT (48% vs. 13%), and short episodes of general malaise and shivering (43% vs. 13%).
In an accompanying editorial, Astrid Rasmussen, MD, PhD, of the Oklahoma Sjögren’s Syndrome Center of Research Translation at the Oklahoma Medical Research Foundation in Oklahoma City, wrote that the trial by Dr. van der Heijden and colleagues was limited by a small sample size and short duration. In addition, some of the findings were unexplained, such as modest changes in secondary endpoints and a concomitant decrease in ESSDAI scores at 8 weeks for both study groups.
Nevertheless, the study provides reason to think in new ways about old drugs, wrote Dr. Rasmussen. “Combination or sequential use of existing agents that target different aspects of immune dysregulation, while having acceptable safety profiles and cost-benefit ratios, should represent an avenue of further exploration. Just as importantly, subphenotyping patients on the basis of their underlying pathogenic processes and identifying sensitive outcome measures could transform the current enthusiasm for identifying effective treatments for Sjögren’s syndrome into a reality for the patients that need them the most.”
The study was funded by ZonMw. The authors of the study reported no conflicts of interest. Dr. Rasmussen reported having no conflicts of interest.
SOURCE: van der Heijden EHM et al. Lancet Rheumatol. 2020 Mar 26. doi: 10.1016/S2665-9913(20)30057-6.
according to results from a phase 2a, randomized clinical trial published in Lancet Rheumatology.
The combination’s statistically significant effect on the European League Against Rheumatism (EULAR) Sjögren’s syndrome disease activity index (ESSDAI) score at 24 weeks, the primary endpoint of the small, double-blind, placebo-controlled trial, suggests that the combination should be studied further in larger trials, according to first author Eefje Hanna Martine van der Heijden, MD, a rheumatologist at University Medical Center Utrecht (the Netherlands), and colleagues.
The investigators decided to study leflunomide and hydroxychloroquine, which target overlapping and distinct immunopathologic pathways, because data support the safety of each drug individually, and a previous in vitro study by the authors indicated that they have complementary effects when administered together.
“To our knowledge, this is the first randomized, placebo-controlled clinical trial in patients with primary Sjögren’s syndrome that shows significant clinical efficacy, as measured by ESSDAI, and is associated with significant improvements in other clinical parameters, including dryness and fatigue,” the investigators wrote.
Dr. van der Heijden and colleagues screened 37 patients from the outpatient clinic of their medical center and enrolled 29 (28 women) who met American-European Consensus Criteria into their study. They had moderate to active disease, defined as an ESSDAI score of 5 or higher, and a lymphocytic focus score of 1 or higher in labial salivary gland biopsy specimens that were obtained before inclusion. The population’s average age was approximately 54 years. They had an average disease duration of about 8 years, a mean ESSDAI score of about 9, and mean EULAR Sjögren’s syndrome patient reported index (ESSPRI) score of 6.7. A total of 21 patients were randomized to leflunomide 20 mg and hydroxychloroquine 400 mg daily, and 8 patients were randomized to placebos. Baseline characteristics were similar between groups, but mean serum IgG level was 19.4 g/L in the treatment group and 13.8 g/L in the placebo group. One patient in the placebo group developed polymyalgia rheumatica and required high-dose prednisone treatment. The investigators excluded this patient from the primary analysis.
At 24 weeks, the mean difference in ESSDAI score in the leflunomide-hydroxychloroquine group, compared with the placebo group, was –4.35 points after adjustment for baseline values. This difference was statistically significant.
Secondary endpoints in the study showed inconsistent statistically significant differences between the treatment groups at 8, 16, and 24 weeks. The total ESSPRI score at 16 weeks was 1.66 points lower in the treatment group than in the placebo group. Stimulated whole saliva production was increased in the leflunomide-hydroxychloroquine group at 16 weeks, compared with the placebo group. Unstimulated whole saliva production at 24 weeks was higher in the leflunomide-hydroxychloroquine group than in controls. The investigators found no differences between groups in visual analog scores for ocular or oral dryness.
No patient in the leflunomide-hydroxychloroquine group had a serious adverse event. Two serious adverse events (hospital admission for pancreatitis and hospital admission for nephrolithiasis) occurred in the placebo group. The most common adverse events in the leflunomide-hydroxychloroquine group were GI discomfort (52% vs. 25% in the placebo group), modest transient increases in ALT (48% vs. 13%), and short episodes of general malaise and shivering (43% vs. 13%).
In an accompanying editorial, Astrid Rasmussen, MD, PhD, of the Oklahoma Sjögren’s Syndrome Center of Research Translation at the Oklahoma Medical Research Foundation in Oklahoma City, wrote that the trial by Dr. van der Heijden and colleagues was limited by a small sample size and short duration. In addition, some of the findings were unexplained, such as modest changes in secondary endpoints and a concomitant decrease in ESSDAI scores at 8 weeks for both study groups.
Nevertheless, the study provides reason to think in new ways about old drugs, wrote Dr. Rasmussen. “Combination or sequential use of existing agents that target different aspects of immune dysregulation, while having acceptable safety profiles and cost-benefit ratios, should represent an avenue of further exploration. Just as importantly, subphenotyping patients on the basis of their underlying pathogenic processes and identifying sensitive outcome measures could transform the current enthusiasm for identifying effective treatments for Sjögren’s syndrome into a reality for the patients that need them the most.”
The study was funded by ZonMw. The authors of the study reported no conflicts of interest. Dr. Rasmussen reported having no conflicts of interest.
SOURCE: van der Heijden EHM et al. Lancet Rheumatol. 2020 Mar 26. doi: 10.1016/S2665-9913(20)30057-6.
FROM LANCET RHEUMATOLOGY
Dawn of new lupus nephritis treatment after AURORA trial
The calcineurin inhibitor is the first novel agent to demonstrate effectiveness in the treatment of people with lupus nephritis, a disease that can lead to irreversible kidney damage, kidney failure, and even death.
“We believe that voclosporin – as an add-on therapy – will help more patients achieve remission,” said Keisha Gibson, MD, MPH, chief of pediatric nephrology at the UNC Kidney Center in Chapel Hill, North Carolina, who led the study and presented the findings during a virtual session at the National Kidney Foundation 2020 Spring Clinical Meetings.
The burden that lupus places on patients and the health system is high, she reported. Patients with lupus and uncontrolled kidney disease frequently have complications that require hospitalization, can suffer complete or partial loss of income, and can become temporarily disabled. And up to 50% of lupus patients will develop lupus nephritis.
“When we are lucky and see early treatment responses in our patients, we know that their long-term outcomes, measured by proteinuria reduction, are quite good,” said Gibson. “Unfortunately, in 10% to 30% of patients, despite standard-of-care therapies, we see progression to end-stage kidney disease within 15 years of diagnosis. This confers a huge cost to overall health and quality of life, and is an excess burden to the healthcare system.
“It is clear that one of the biggest risk factors for these patients who have kidney disease that is progressing to kidney failure is an inability to control the inflammation and chronic damage from uncontrolled disease,” she told Medscape Medical News.
“While there have certainly been a few advances in the care of patients with lupus disease, I believe that this therapy may help move the needle, specifically for patients with kidney involvement from their lupus disease,” she added.
Renal Response Much Higher With Voclosporin
The typical standard of care for patients with active lupus and kidney disease is either a combination of cyclophosphamide plus steroids or a combination of mycophenolate mofetil plus steroids.
The global, double-blind, randomized, placebo-controlled trial compared the effectiveness and safety of twice-daily oral voclosporin 23.7 mg with placebo. All 357 study participants also received mycophenolate 2 g daily and rapidly tapered low-dose oral corticosteroids.
At 1 year, the renal response rate was higher in the voclosporin group than in the placebo group (40.8% vs 22.5%; odds ratio, 2.65; P < .001).
“AURORA patients achieved low levels of protein twice as quickly as patients on standard of care,” the researchers write in their abstract. Median time to the achievement of a urine protein to creatinine ratio below 0.5 mg/mg was significantly and clinically better with voclosporin than with placebo (169 vs 372 days; log rank P < .001).
And voclosporin was well tolerated. The percentage of serious adverse events was similar in the voclosporin and placebo groups (20.8% vs 21.3%), with infection being the most common serious event (10.1% vs 11.2%).
In the voclosporin group, there were no significant differences between baseline and 1 year estimated glomerular filtration rates (eGFR), blood pressure, lipid levels, or sugar levels.
And there were fewer deaths in the voclosporin group than in the placebo group (1 vs 5).
Benefits were seen in all subgroups, including age, sex, race, biopsy class, geographic region of origin, and mycophenolate exposure at screening, Gibson reported.
Promise of a New Treatment
The promise of a new treatment is exciting for the field, said Joseph Vassalotti, MD, chief medical officer of the National Kidney Foundation.
However, it’s important to note that “this study is applicable only to patients with lupus nephritis with preserved kidney function,” he added.
An “eGFR less than 45 mL/min per 1.73 m2 was implied as an exclusion criteria, so I would say it certainly doesn’t apply to patients with impaired kidney function,” he said, pointing out that this will be clearer when the final data are published.
The study cohort was heterogeneous; 86% of participants had class 3 or 4 biopsy findings and 14% had class 5, so the superiority of voclosporin is convincing, he said.
“We look forward to full publication and more details,” he told Medscape Medical News. “They do have an extension study, and it will be interesting to see how that plays out.”
Voclosporin was granted Fast Track designation by the US Food and Drug Administration in 2016, and these positive phase 3 results mean that a New Drug Application will likely be filed in the next few months. If approved, the drug could be on the market by 2021, according to a press release from Aurinia.
Nephrologists are familiar with calcineurin inhibitors, so it will be interesting to see, given the success of this trial, if voclosporin has a potential role in other kidney diseases, “such as minimal change disease,” said Vassalotti.
He added that there are concerns, unrelated to the AURORA trial, about the supply of hydroxychloroquine, which is also used for the treatment of lupus nephritis. “An overarching concern is that the supply will be limited now that the drug is being studied and used as prophylaxis after exposure to SARS-CoV-2 and as a treatment for COVID-19, creating challenges for patients with lupus nephritis trying to obtain their needed medication,” he said.
Gibson reports no relevant financial relationships. Two coauthors work for the drugmaker, Aurinia. Vassalotti reports no relevant financial relationships.
This article first appeared on Medscape.com.
The calcineurin inhibitor is the first novel agent to demonstrate effectiveness in the treatment of people with lupus nephritis, a disease that can lead to irreversible kidney damage, kidney failure, and even death.
“We believe that voclosporin – as an add-on therapy – will help more patients achieve remission,” said Keisha Gibson, MD, MPH, chief of pediatric nephrology at the UNC Kidney Center in Chapel Hill, North Carolina, who led the study and presented the findings during a virtual session at the National Kidney Foundation 2020 Spring Clinical Meetings.
The burden that lupus places on patients and the health system is high, she reported. Patients with lupus and uncontrolled kidney disease frequently have complications that require hospitalization, can suffer complete or partial loss of income, and can become temporarily disabled. And up to 50% of lupus patients will develop lupus nephritis.
“When we are lucky and see early treatment responses in our patients, we know that their long-term outcomes, measured by proteinuria reduction, are quite good,” said Gibson. “Unfortunately, in 10% to 30% of patients, despite standard-of-care therapies, we see progression to end-stage kidney disease within 15 years of diagnosis. This confers a huge cost to overall health and quality of life, and is an excess burden to the healthcare system.
“It is clear that one of the biggest risk factors for these patients who have kidney disease that is progressing to kidney failure is an inability to control the inflammation and chronic damage from uncontrolled disease,” she told Medscape Medical News.
“While there have certainly been a few advances in the care of patients with lupus disease, I believe that this therapy may help move the needle, specifically for patients with kidney involvement from their lupus disease,” she added.
Renal Response Much Higher With Voclosporin
The typical standard of care for patients with active lupus and kidney disease is either a combination of cyclophosphamide plus steroids or a combination of mycophenolate mofetil plus steroids.
The global, double-blind, randomized, placebo-controlled trial compared the effectiveness and safety of twice-daily oral voclosporin 23.7 mg with placebo. All 357 study participants also received mycophenolate 2 g daily and rapidly tapered low-dose oral corticosteroids.
At 1 year, the renal response rate was higher in the voclosporin group than in the placebo group (40.8% vs 22.5%; odds ratio, 2.65; P < .001).
“AURORA patients achieved low levels of protein twice as quickly as patients on standard of care,” the researchers write in their abstract. Median time to the achievement of a urine protein to creatinine ratio below 0.5 mg/mg was significantly and clinically better with voclosporin than with placebo (169 vs 372 days; log rank P < .001).
And voclosporin was well tolerated. The percentage of serious adverse events was similar in the voclosporin and placebo groups (20.8% vs 21.3%), with infection being the most common serious event (10.1% vs 11.2%).
In the voclosporin group, there were no significant differences between baseline and 1 year estimated glomerular filtration rates (eGFR), blood pressure, lipid levels, or sugar levels.
And there were fewer deaths in the voclosporin group than in the placebo group (1 vs 5).
Benefits were seen in all subgroups, including age, sex, race, biopsy class, geographic region of origin, and mycophenolate exposure at screening, Gibson reported.
Promise of a New Treatment
The promise of a new treatment is exciting for the field, said Joseph Vassalotti, MD, chief medical officer of the National Kidney Foundation.
However, it’s important to note that “this study is applicable only to patients with lupus nephritis with preserved kidney function,” he added.
An “eGFR less than 45 mL/min per 1.73 m2 was implied as an exclusion criteria, so I would say it certainly doesn’t apply to patients with impaired kidney function,” he said, pointing out that this will be clearer when the final data are published.
The study cohort was heterogeneous; 86% of participants had class 3 or 4 biopsy findings and 14% had class 5, so the superiority of voclosporin is convincing, he said.
“We look forward to full publication and more details,” he told Medscape Medical News. “They do have an extension study, and it will be interesting to see how that plays out.”
Voclosporin was granted Fast Track designation by the US Food and Drug Administration in 2016, and these positive phase 3 results mean that a New Drug Application will likely be filed in the next few months. If approved, the drug could be on the market by 2021, according to a press release from Aurinia.
Nephrologists are familiar with calcineurin inhibitors, so it will be interesting to see, given the success of this trial, if voclosporin has a potential role in other kidney diseases, “such as minimal change disease,” said Vassalotti.
He added that there are concerns, unrelated to the AURORA trial, about the supply of hydroxychloroquine, which is also used for the treatment of lupus nephritis. “An overarching concern is that the supply will be limited now that the drug is being studied and used as prophylaxis after exposure to SARS-CoV-2 and as a treatment for COVID-19, creating challenges for patients with lupus nephritis trying to obtain their needed medication,” he said.
Gibson reports no relevant financial relationships. Two coauthors work for the drugmaker, Aurinia. Vassalotti reports no relevant financial relationships.
This article first appeared on Medscape.com.
The calcineurin inhibitor is the first novel agent to demonstrate effectiveness in the treatment of people with lupus nephritis, a disease that can lead to irreversible kidney damage, kidney failure, and even death.
“We believe that voclosporin – as an add-on therapy – will help more patients achieve remission,” said Keisha Gibson, MD, MPH, chief of pediatric nephrology at the UNC Kidney Center in Chapel Hill, North Carolina, who led the study and presented the findings during a virtual session at the National Kidney Foundation 2020 Spring Clinical Meetings.
The burden that lupus places on patients and the health system is high, she reported. Patients with lupus and uncontrolled kidney disease frequently have complications that require hospitalization, can suffer complete or partial loss of income, and can become temporarily disabled. And up to 50% of lupus patients will develop lupus nephritis.
“When we are lucky and see early treatment responses in our patients, we know that their long-term outcomes, measured by proteinuria reduction, are quite good,” said Gibson. “Unfortunately, in 10% to 30% of patients, despite standard-of-care therapies, we see progression to end-stage kidney disease within 15 years of diagnosis. This confers a huge cost to overall health and quality of life, and is an excess burden to the healthcare system.
“It is clear that one of the biggest risk factors for these patients who have kidney disease that is progressing to kidney failure is an inability to control the inflammation and chronic damage from uncontrolled disease,” she told Medscape Medical News.
“While there have certainly been a few advances in the care of patients with lupus disease, I believe that this therapy may help move the needle, specifically for patients with kidney involvement from their lupus disease,” she added.
Renal Response Much Higher With Voclosporin
The typical standard of care for patients with active lupus and kidney disease is either a combination of cyclophosphamide plus steroids or a combination of mycophenolate mofetil plus steroids.
The global, double-blind, randomized, placebo-controlled trial compared the effectiveness and safety of twice-daily oral voclosporin 23.7 mg with placebo. All 357 study participants also received mycophenolate 2 g daily and rapidly tapered low-dose oral corticosteroids.
At 1 year, the renal response rate was higher in the voclosporin group than in the placebo group (40.8% vs 22.5%; odds ratio, 2.65; P < .001).
“AURORA patients achieved low levels of protein twice as quickly as patients on standard of care,” the researchers write in their abstract. Median time to the achievement of a urine protein to creatinine ratio below 0.5 mg/mg was significantly and clinically better with voclosporin than with placebo (169 vs 372 days; log rank P < .001).
And voclosporin was well tolerated. The percentage of serious adverse events was similar in the voclosporin and placebo groups (20.8% vs 21.3%), with infection being the most common serious event (10.1% vs 11.2%).
In the voclosporin group, there were no significant differences between baseline and 1 year estimated glomerular filtration rates (eGFR), blood pressure, lipid levels, or sugar levels.
And there were fewer deaths in the voclosporin group than in the placebo group (1 vs 5).
Benefits were seen in all subgroups, including age, sex, race, biopsy class, geographic region of origin, and mycophenolate exposure at screening, Gibson reported.
Promise of a New Treatment
The promise of a new treatment is exciting for the field, said Joseph Vassalotti, MD, chief medical officer of the National Kidney Foundation.
However, it’s important to note that “this study is applicable only to patients with lupus nephritis with preserved kidney function,” he added.
An “eGFR less than 45 mL/min per 1.73 m2 was implied as an exclusion criteria, so I would say it certainly doesn’t apply to patients with impaired kidney function,” he said, pointing out that this will be clearer when the final data are published.
The study cohort was heterogeneous; 86% of participants had class 3 or 4 biopsy findings and 14% had class 5, so the superiority of voclosporin is convincing, he said.
“We look forward to full publication and more details,” he told Medscape Medical News. “They do have an extension study, and it will be interesting to see how that plays out.”
Voclosporin was granted Fast Track designation by the US Food and Drug Administration in 2016, and these positive phase 3 results mean that a New Drug Application will likely be filed in the next few months. If approved, the drug could be on the market by 2021, according to a press release from Aurinia.
Nephrologists are familiar with calcineurin inhibitors, so it will be interesting to see, given the success of this trial, if voclosporin has a potential role in other kidney diseases, “such as minimal change disease,” said Vassalotti.
He added that there are concerns, unrelated to the AURORA trial, about the supply of hydroxychloroquine, which is also used for the treatment of lupus nephritis. “An overarching concern is that the supply will be limited now that the drug is being studied and used as prophylaxis after exposure to SARS-CoV-2 and as a treatment for COVID-19, creating challenges for patients with lupus nephritis trying to obtain their needed medication,” he said.
Gibson reports no relevant financial relationships. Two coauthors work for the drugmaker, Aurinia. Vassalotti reports no relevant financial relationships.
This article first appeared on Medscape.com.
Rheumatologists seek to reassure amid hydroxychloroquine shortage
Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.
The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.
Now
In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.
Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity.
Questions about hydroxychloroquine shortage
Q: What is the current situation with hydroxychloroquine in your practice?
A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.
Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?
A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.
Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.
Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.
The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.
Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?
A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.
Q: Are there pharmacy restrictions on prescription amounts?
A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
Colchicine COVID-19 trial underway
Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too.
Q: What is the general availability of colchicine and its susceptibility to shortage?
A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.
The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.
Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?
A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.
The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.
While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.
Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.
The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.
Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.
So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.
Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.
This article was reformatted on 3/30/2020 for clarity.
Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.
The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.
Now
In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.
Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity.
Questions about hydroxychloroquine shortage
Q: What is the current situation with hydroxychloroquine in your practice?
A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.
Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?
A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.
Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.
Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.
The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.
Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?
A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.
Q: Are there pharmacy restrictions on prescription amounts?
A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
Colchicine COVID-19 trial underway
Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too.
Q: What is the general availability of colchicine and its susceptibility to shortage?
A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.
The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.
Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?
A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.
The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.
While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.
Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.
The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.
Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.
So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.
Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.
This article was reformatted on 3/30/2020 for clarity.
Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.
The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.
Now
In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.
Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity.
Questions about hydroxychloroquine shortage
Q: What is the current situation with hydroxychloroquine in your practice?
A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.
Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?
A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.
Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.
Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.
The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.
Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?
A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.
Q: Are there pharmacy restrictions on prescription amounts?
A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
Colchicine COVID-19 trial underway
Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too.
Q: What is the general availability of colchicine and its susceptibility to shortage?
A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.
The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.
Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?
A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.
The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.
While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.
Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.
The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.
Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.
So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.
Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.
This article was reformatted on 3/30/2020 for clarity.
Amid hydroxychloroquine hopes, lupus patients face shortages
For almost a quarter century, Julie Powers, a 48-year-old non-profit professional from Maryland, has been taking the same medication for her lupus — and until recently, she never worried that her supply would run out. Now she’s terrified that she might lose access to a drug that prevents her immune system from attacking her heart, lungs, and skin. She describes a feeling akin to being underwater, near drowning: “That’s what my life would be like,” she said. “I’ll suffocate.”
Powers’ concerns began roughly a week ago when she learned that her lupus drug, hydroxychloroquine (hi-DROCK-see-KLORA-quin), may be helpful in the treatment of Covid-19, the illness caused by the SARS-CoV-2 virus now racing across the planet. The medication was already being used around world to treat Covid-19 patients, but evidence of its effectiveness was largely anecdotal. Then, on March 16, a renowned infectious disease specialist, Didier Raoult, announced the results of a small clinical trial in France showing that patients receiving a combination of hydroxychloroquine and the common antibiotic azithromycin had notably lower levels of the virus in their bloodstream than those who did not receive the medication.
In the last week, this once obscure drug has been thrust into the national spotlight with everyone from doctors, to laypeople, to the U.S. president weighing in. The attention has so dramatically driven up demand that pharmacists are reporting depleted stocks of the drug, leaving many of the roughly 1.5 million lupus patients across the country unable to get their prescriptions filled. They now face an uncertain future as the public clings to one of the first signs of hope to appear since the coronavirus began sweeping across the U.S.
But scientists and physicians caution that this hope is based on studies that have been conducted outside of traditional scientific timelines. “The paper is interesting and certainly would warrant future more definitive studies,” Jeff Sparks, a rheumatologist and researcher at Harvard Medical School, said of the French study. “It might even be enough data to use the regimen off-label for sick and hospitalized patients.
“However,” he added, “it does not prove that the regimen actually works.”
Despite efforts to pin blame for the shortages on Trump alone, however, hydroxychloroquine scarcity was already setting in weeks ago, as doctors began responding on their own to percolating and preliminary research. Some evidence suggests that many doctors are now writing prescriptions prophylactically for patients with no known illness — as well as for themselves and family members — prompting at least one state pharmacy board to call an emergency meeting, scheduled for Sunday morning. The board planned to bar pharmacists from dispensing chloroquine or hydroxychloroquine for anyone other than confirmed Covid-19 patients without approval of the board's director.
A prolonged shortfall in supplies would likely have grave implications for people who depend on it — including Powers, who believes that she would not be alive today without the drug. “I guarantee you, it has saved my life,” she said. “It’s the only thing that’s protecting my organs. There’s nothing else.” Like others, she hopes that pharmaceutical companies that manufacture versions of the drug will be able to quickly ramp up production — something several have already promised to do. In the meantime, Powers has a message for the American public — one echoed by most lupus doctors: When it comes to hydroxychloroquine: “If you don’t need it, don’t get it.”
The origins of hydroxychloroquine can be traced back hundreds of years to South America, where the bark of the cinchona tree appears to have been used by Andean populations to treat shivering. European missionaries eventually brought the bark to Europe, where it was used to treat malaria. In 1820, French researchers isolated the substance in the bark responsible for its beneficial effects. They named it “quinine.” When the supply from South America began to dry up, the British and Dutch decided to grow the tree on plantations.
Over time, synthetic versions were developed, including a drug called chloroquine, which was created in the midst of World War II in an effort to spare overseas American troops from malaria. As it turned out, troops with rashes and arthritis saw an improvement in symptoms after using this anti-malarial medication. After the war, a related drug was created, one with fewer side-effects when taken long-term: hydroxychloroquine. It went on to be used to treat many types of autoimmune diseases, including rheumatoid arthritis and lupus. The latter, which disproportionately affects women, used to cut lives short — typically from failure of the kidneys. Those numbers have been reduced with strict management of the disease, but the Lupus Foundation of America estimates that 10 to 15 percent of patients die prematurely due to complications of the disease.
Jinoos Yazdany, a researcher and chief of the Division of Rheumatology at Zuckerberg San Francisco General Hospital, added that there is strong clinical trial data demonstrating that taking a group of lupus patients off of hydroxychloroquine results in lupus flares. “I am less concerned about a short interruption of a few weeks,” she said in an email message, “but anything longer than a month puts patients at risk.”
Whether or not that will happen is unclear, but Sparks said he has been receiving a raft queries from both lupus and non-lupus patients eager to know more about — and access — hydroxychloroquine: “Can I use this? Should I stockpile it? Can I get refills?” Sparks compares the current medication shortage to the ventilator shortage, where manufacturers make just enough of a certain supply to meet the demand. “We don’t have stockpiles of hydroxychloroquine sitting around,” he said.
Blazer understands that people are scared and says it’s natural that they would want to protect themselves. But she said, the medicine is a limited resource and should be reserved for people with a rheumatological disease or active Covid-19 infection. In order to minimize fallout from the pandemic, she says, “we all have to function as a community.”
As it turns out, there is an extreme paucity of data when it comes to hydroxychloroquine and Covid-19. On March 10, the Journal of Critical Care published online a systematic review of the safety and the effectiveness of hydroxychloroquine and chloroquine in treating Covid-19. The authors’ goal was to identify and summarize all available scientific evidence as of March 1 by searching scientific databases. They found six articles. (In contrast, a search of the database PubMed for hydroxychloroquine and lupus yields 1,654 results.)
“The articles themselves were kind of a menagerie of things that you don’t want to get data from,” said Michael Putman, a rheumatologist at Northwestern University, McGaw Medical Center, in his rheumatology podcast. The study authors found one narrative letter, one test tube study, one editorial, two national guidelines, and one expert consensus paper from China. Conspicuously missing were randomized controlled trials, which randomly assign human participants to an experimental group or a control group, with the experimental group receiving the treatment in question.
“It is kind of scary that that is all the data we had until March 1, for a drug that we are currently talking about rolling out en masse to the world,” said Putman.
Shortly after the systematic review appeared online, Didier Raoult announced the results of his team’s clinical trial. (The paper is now available online.) At first blush, the results are striking. Six days into the study, 70 percent of patients who received hydroxychloroquine were “virologically cured,” as evidenced from samples taken from the back of each patient’s nose. In contrast, just 12.5 percent of the control group, which did not receive the drug cocktail, were free of the virus.
A second potential issue: Patients who refused the treatment or had exclusion criteria served as controls. “It’s hard for me to describe just how problematic this is,” said Putman in his podcast. Ideally patients would be randomly assigned to one of the two treatment groups, said Putman. Patients with exclusion criteria — those unable to take the medication — are not the same as patients who are able to take it, he says. And the same is true for patients who refuse a drug vs. those who don’t.
Whether these and other potential problems with the research will prove salient in coming weeks and months is impossible to know — and most researchers concede that even amid lingering uncertainties, time is of the essence in the frantic hunt to find ways to slow the fast-moving Covid-19 pandemic. “A lot of this,” Kim said, “is the rush of trying to get something out.” On Friday, the University of Minnesota announced the launch of a 1,500-person trial aimed at further exploring the efficacy of hydroxychloroquine against SARS-CoV-2. And drug makers Novartis, Mylan, and Teva announced last week that they were fast-tracking production, with additional plans to donate hundreds of millions of tablets to hospitals around the country to help combat Covid-19 infections.
Still, reports of shortages are mounting. “It’s gone. It’s not in the pharmacy now,'' a physician in Queens told The Washington Post on Friday. The doctor admitted taking the drug himself in the hope of staving off infection, and that he’d prescribed it to 30 patients as a prophylactic.
These sorts of fast-multiplying, ad hoc transactions, are what worry lupus patients like Julie Powers. For now, she says she has enough hydroxychloroquine to last 90 days, and she added that her pharmacist in the Washington, D.C. area is currently hiding the medicine to be sure her regular lupus patients can get their prescriptions refilled.
Powers sounds almost amazed when she describes what that means to her: “I can walk outside,” she said, “and I can live.”
Sara Talpos is a senior editor at Undark and a freelance writer whose recent work has been published in Science, Mosaic, and the Kenyon Review’s special issue on science writing.
Disclosure: The author’s spouse is a rheumatologist at Michigan Medicine.
UPDATES: This story has been updated to clarify Alfred Kim's view on several patients who dropped out of a small French study on the efficacy of using hydroxychloroquine to treat Covid-19 cases. The piece was also edited to include information noting that one state pharmacy board is now taking steps to curtail prescriptions of hydroxychloroquine and chloroquine for Covid-19 prophylaxis.
This article was originally published on Undark. Read the original article.
For almost a quarter century, Julie Powers, a 48-year-old non-profit professional from Maryland, has been taking the same medication for her lupus — and until recently, she never worried that her supply would run out. Now she’s terrified that she might lose access to a drug that prevents her immune system from attacking her heart, lungs, and skin. She describes a feeling akin to being underwater, near drowning: “That’s what my life would be like,” she said. “I’ll suffocate.”
Powers’ concerns began roughly a week ago when she learned that her lupus drug, hydroxychloroquine (hi-DROCK-see-KLORA-quin), may be helpful in the treatment of Covid-19, the illness caused by the SARS-CoV-2 virus now racing across the planet. The medication was already being used around world to treat Covid-19 patients, but evidence of its effectiveness was largely anecdotal. Then, on March 16, a renowned infectious disease specialist, Didier Raoult, announced the results of a small clinical trial in France showing that patients receiving a combination of hydroxychloroquine and the common antibiotic azithromycin had notably lower levels of the virus in their bloodstream than those who did not receive the medication.
In the last week, this once obscure drug has been thrust into the national spotlight with everyone from doctors, to laypeople, to the U.S. president weighing in. The attention has so dramatically driven up demand that pharmacists are reporting depleted stocks of the drug, leaving many of the roughly 1.5 million lupus patients across the country unable to get their prescriptions filled. They now face an uncertain future as the public clings to one of the first signs of hope to appear since the coronavirus began sweeping across the U.S.
But scientists and physicians caution that this hope is based on studies that have been conducted outside of traditional scientific timelines. “The paper is interesting and certainly would warrant future more definitive studies,” Jeff Sparks, a rheumatologist and researcher at Harvard Medical School, said of the French study. “It might even be enough data to use the regimen off-label for sick and hospitalized patients.
“However,” he added, “it does not prove that the regimen actually works.”
Despite efforts to pin blame for the shortages on Trump alone, however, hydroxychloroquine scarcity was already setting in weeks ago, as doctors began responding on their own to percolating and preliminary research. Some evidence suggests that many doctors are now writing prescriptions prophylactically for patients with no known illness — as well as for themselves and family members — prompting at least one state pharmacy board to call an emergency meeting, scheduled for Sunday morning. The board planned to bar pharmacists from dispensing chloroquine or hydroxychloroquine for anyone other than confirmed Covid-19 patients without approval of the board's director.
A prolonged shortfall in supplies would likely have grave implications for people who depend on it — including Powers, who believes that she would not be alive today without the drug. “I guarantee you, it has saved my life,” she said. “It’s the only thing that’s protecting my organs. There’s nothing else.” Like others, she hopes that pharmaceutical companies that manufacture versions of the drug will be able to quickly ramp up production — something several have already promised to do. In the meantime, Powers has a message for the American public — one echoed by most lupus doctors: When it comes to hydroxychloroquine: “If you don’t need it, don’t get it.”
The origins of hydroxychloroquine can be traced back hundreds of years to South America, where the bark of the cinchona tree appears to have been used by Andean populations to treat shivering. European missionaries eventually brought the bark to Europe, where it was used to treat malaria. In 1820, French researchers isolated the substance in the bark responsible for its beneficial effects. They named it “quinine.” When the supply from South America began to dry up, the British and Dutch decided to grow the tree on plantations.
Over time, synthetic versions were developed, including a drug called chloroquine, which was created in the midst of World War II in an effort to spare overseas American troops from malaria. As it turned out, troops with rashes and arthritis saw an improvement in symptoms after using this anti-malarial medication. After the war, a related drug was created, one with fewer side-effects when taken long-term: hydroxychloroquine. It went on to be used to treat many types of autoimmune diseases, including rheumatoid arthritis and lupus. The latter, which disproportionately affects women, used to cut lives short — typically from failure of the kidneys. Those numbers have been reduced with strict management of the disease, but the Lupus Foundation of America estimates that 10 to 15 percent of patients die prematurely due to complications of the disease.
Jinoos Yazdany, a researcher and chief of the Division of Rheumatology at Zuckerberg San Francisco General Hospital, added that there is strong clinical trial data demonstrating that taking a group of lupus patients off of hydroxychloroquine results in lupus flares. “I am less concerned about a short interruption of a few weeks,” she said in an email message, “but anything longer than a month puts patients at risk.”
Whether or not that will happen is unclear, but Sparks said he has been receiving a raft queries from both lupus and non-lupus patients eager to know more about — and access — hydroxychloroquine: “Can I use this? Should I stockpile it? Can I get refills?” Sparks compares the current medication shortage to the ventilator shortage, where manufacturers make just enough of a certain supply to meet the demand. “We don’t have stockpiles of hydroxychloroquine sitting around,” he said.
Blazer understands that people are scared and says it’s natural that they would want to protect themselves. But she said, the medicine is a limited resource and should be reserved for people with a rheumatological disease or active Covid-19 infection. In order to minimize fallout from the pandemic, she says, “we all have to function as a community.”
As it turns out, there is an extreme paucity of data when it comes to hydroxychloroquine and Covid-19. On March 10, the Journal of Critical Care published online a systematic review of the safety and the effectiveness of hydroxychloroquine and chloroquine in treating Covid-19. The authors’ goal was to identify and summarize all available scientific evidence as of March 1 by searching scientific databases. They found six articles. (In contrast, a search of the database PubMed for hydroxychloroquine and lupus yields 1,654 results.)
“The articles themselves were kind of a menagerie of things that you don’t want to get data from,” said Michael Putman, a rheumatologist at Northwestern University, McGaw Medical Center, in his rheumatology podcast. The study authors found one narrative letter, one test tube study, one editorial, two national guidelines, and one expert consensus paper from China. Conspicuously missing were randomized controlled trials, which randomly assign human participants to an experimental group or a control group, with the experimental group receiving the treatment in question.
“It is kind of scary that that is all the data we had until March 1, for a drug that we are currently talking about rolling out en masse to the world,” said Putman.
Shortly after the systematic review appeared online, Didier Raoult announced the results of his team’s clinical trial. (The paper is now available online.) At first blush, the results are striking. Six days into the study, 70 percent of patients who received hydroxychloroquine were “virologically cured,” as evidenced from samples taken from the back of each patient’s nose. In contrast, just 12.5 percent of the control group, which did not receive the drug cocktail, were free of the virus.
A second potential issue: Patients who refused the treatment or had exclusion criteria served as controls. “It’s hard for me to describe just how problematic this is,” said Putman in his podcast. Ideally patients would be randomly assigned to one of the two treatment groups, said Putman. Patients with exclusion criteria — those unable to take the medication — are not the same as patients who are able to take it, he says. And the same is true for patients who refuse a drug vs. those who don’t.
Whether these and other potential problems with the research will prove salient in coming weeks and months is impossible to know — and most researchers concede that even amid lingering uncertainties, time is of the essence in the frantic hunt to find ways to slow the fast-moving Covid-19 pandemic. “A lot of this,” Kim said, “is the rush of trying to get something out.” On Friday, the University of Minnesota announced the launch of a 1,500-person trial aimed at further exploring the efficacy of hydroxychloroquine against SARS-CoV-2. And drug makers Novartis, Mylan, and Teva announced last week that they were fast-tracking production, with additional plans to donate hundreds of millions of tablets to hospitals around the country to help combat Covid-19 infections.
Still, reports of shortages are mounting. “It’s gone. It’s not in the pharmacy now,'' a physician in Queens told The Washington Post on Friday. The doctor admitted taking the drug himself in the hope of staving off infection, and that he’d prescribed it to 30 patients as a prophylactic.
These sorts of fast-multiplying, ad hoc transactions, are what worry lupus patients like Julie Powers. For now, she says she has enough hydroxychloroquine to last 90 days, and she added that her pharmacist in the Washington, D.C. area is currently hiding the medicine to be sure her regular lupus patients can get their prescriptions refilled.
Powers sounds almost amazed when she describes what that means to her: “I can walk outside,” she said, “and I can live.”
Sara Talpos is a senior editor at Undark and a freelance writer whose recent work has been published in Science, Mosaic, and the Kenyon Review’s special issue on science writing.
Disclosure: The author’s spouse is a rheumatologist at Michigan Medicine.
UPDATES: This story has been updated to clarify Alfred Kim's view on several patients who dropped out of a small French study on the efficacy of using hydroxychloroquine to treat Covid-19 cases. The piece was also edited to include information noting that one state pharmacy board is now taking steps to curtail prescriptions of hydroxychloroquine and chloroquine for Covid-19 prophylaxis.
This article was originally published on Undark. Read the original article.
For almost a quarter century, Julie Powers, a 48-year-old non-profit professional from Maryland, has been taking the same medication for her lupus — and until recently, she never worried that her supply would run out. Now she’s terrified that she might lose access to a drug that prevents her immune system from attacking her heart, lungs, and skin. She describes a feeling akin to being underwater, near drowning: “That’s what my life would be like,” she said. “I’ll suffocate.”
Powers’ concerns began roughly a week ago when she learned that her lupus drug, hydroxychloroquine (hi-DROCK-see-KLORA-quin), may be helpful in the treatment of Covid-19, the illness caused by the SARS-CoV-2 virus now racing across the planet. The medication was already being used around world to treat Covid-19 patients, but evidence of its effectiveness was largely anecdotal. Then, on March 16, a renowned infectious disease specialist, Didier Raoult, announced the results of a small clinical trial in France showing that patients receiving a combination of hydroxychloroquine and the common antibiotic azithromycin had notably lower levels of the virus in their bloodstream than those who did not receive the medication.
In the last week, this once obscure drug has been thrust into the national spotlight with everyone from doctors, to laypeople, to the U.S. president weighing in. The attention has so dramatically driven up demand that pharmacists are reporting depleted stocks of the drug, leaving many of the roughly 1.5 million lupus patients across the country unable to get their prescriptions filled. They now face an uncertain future as the public clings to one of the first signs of hope to appear since the coronavirus began sweeping across the U.S.
But scientists and physicians caution that this hope is based on studies that have been conducted outside of traditional scientific timelines. “The paper is interesting and certainly would warrant future more definitive studies,” Jeff Sparks, a rheumatologist and researcher at Harvard Medical School, said of the French study. “It might even be enough data to use the regimen off-label for sick and hospitalized patients.
“However,” he added, “it does not prove that the regimen actually works.”
Despite efforts to pin blame for the shortages on Trump alone, however, hydroxychloroquine scarcity was already setting in weeks ago, as doctors began responding on their own to percolating and preliminary research. Some evidence suggests that many doctors are now writing prescriptions prophylactically for patients with no known illness — as well as for themselves and family members — prompting at least one state pharmacy board to call an emergency meeting, scheduled for Sunday morning. The board planned to bar pharmacists from dispensing chloroquine or hydroxychloroquine for anyone other than confirmed Covid-19 patients without approval of the board's director.
A prolonged shortfall in supplies would likely have grave implications for people who depend on it — including Powers, who believes that she would not be alive today without the drug. “I guarantee you, it has saved my life,” she said. “It’s the only thing that’s protecting my organs. There’s nothing else.” Like others, she hopes that pharmaceutical companies that manufacture versions of the drug will be able to quickly ramp up production — something several have already promised to do. In the meantime, Powers has a message for the American public — one echoed by most lupus doctors: When it comes to hydroxychloroquine: “If you don’t need it, don’t get it.”
The origins of hydroxychloroquine can be traced back hundreds of years to South America, where the bark of the cinchona tree appears to have been used by Andean populations to treat shivering. European missionaries eventually brought the bark to Europe, where it was used to treat malaria. In 1820, French researchers isolated the substance in the bark responsible for its beneficial effects. They named it “quinine.” When the supply from South America began to dry up, the British and Dutch decided to grow the tree on plantations.
Over time, synthetic versions were developed, including a drug called chloroquine, which was created in the midst of World War II in an effort to spare overseas American troops from malaria. As it turned out, troops with rashes and arthritis saw an improvement in symptoms after using this anti-malarial medication. After the war, a related drug was created, one with fewer side-effects when taken long-term: hydroxychloroquine. It went on to be used to treat many types of autoimmune diseases, including rheumatoid arthritis and lupus. The latter, which disproportionately affects women, used to cut lives short — typically from failure of the kidneys. Those numbers have been reduced with strict management of the disease, but the Lupus Foundation of America estimates that 10 to 15 percent of patients die prematurely due to complications of the disease.
Jinoos Yazdany, a researcher and chief of the Division of Rheumatology at Zuckerberg San Francisco General Hospital, added that there is strong clinical trial data demonstrating that taking a group of lupus patients off of hydroxychloroquine results in lupus flares. “I am less concerned about a short interruption of a few weeks,” she said in an email message, “but anything longer than a month puts patients at risk.”
Whether or not that will happen is unclear, but Sparks said he has been receiving a raft queries from both lupus and non-lupus patients eager to know more about — and access — hydroxychloroquine: “Can I use this? Should I stockpile it? Can I get refills?” Sparks compares the current medication shortage to the ventilator shortage, where manufacturers make just enough of a certain supply to meet the demand. “We don’t have stockpiles of hydroxychloroquine sitting around,” he said.
Blazer understands that people are scared and says it’s natural that they would want to protect themselves. But she said, the medicine is a limited resource and should be reserved for people with a rheumatological disease or active Covid-19 infection. In order to minimize fallout from the pandemic, she says, “we all have to function as a community.”
As it turns out, there is an extreme paucity of data when it comes to hydroxychloroquine and Covid-19. On March 10, the Journal of Critical Care published online a systematic review of the safety and the effectiveness of hydroxychloroquine and chloroquine in treating Covid-19. The authors’ goal was to identify and summarize all available scientific evidence as of March 1 by searching scientific databases. They found six articles. (In contrast, a search of the database PubMed for hydroxychloroquine and lupus yields 1,654 results.)
“The articles themselves were kind of a menagerie of things that you don’t want to get data from,” said Michael Putman, a rheumatologist at Northwestern University, McGaw Medical Center, in his rheumatology podcast. The study authors found one narrative letter, one test tube study, one editorial, two national guidelines, and one expert consensus paper from China. Conspicuously missing were randomized controlled trials, which randomly assign human participants to an experimental group or a control group, with the experimental group receiving the treatment in question.
“It is kind of scary that that is all the data we had until March 1, for a drug that we are currently talking about rolling out en masse to the world,” said Putman.
Shortly after the systematic review appeared online, Didier Raoult announced the results of his team’s clinical trial. (The paper is now available online.) At first blush, the results are striking. Six days into the study, 70 percent of patients who received hydroxychloroquine were “virologically cured,” as evidenced from samples taken from the back of each patient’s nose. In contrast, just 12.5 percent of the control group, which did not receive the drug cocktail, were free of the virus.
A second potential issue: Patients who refused the treatment or had exclusion criteria served as controls. “It’s hard for me to describe just how problematic this is,” said Putman in his podcast. Ideally patients would be randomly assigned to one of the two treatment groups, said Putman. Patients with exclusion criteria — those unable to take the medication — are not the same as patients who are able to take it, he says. And the same is true for patients who refuse a drug vs. those who don’t.
Whether these and other potential problems with the research will prove salient in coming weeks and months is impossible to know — and most researchers concede that even amid lingering uncertainties, time is of the essence in the frantic hunt to find ways to slow the fast-moving Covid-19 pandemic. “A lot of this,” Kim said, “is the rush of trying to get something out.” On Friday, the University of Minnesota announced the launch of a 1,500-person trial aimed at further exploring the efficacy of hydroxychloroquine against SARS-CoV-2. And drug makers Novartis, Mylan, and Teva announced last week that they were fast-tracking production, with additional plans to donate hundreds of millions of tablets to hospitals around the country to help combat Covid-19 infections.
Still, reports of shortages are mounting. “It’s gone. It’s not in the pharmacy now,'' a physician in Queens told The Washington Post on Friday. The doctor admitted taking the drug himself in the hope of staving off infection, and that he’d prescribed it to 30 patients as a prophylactic.
These sorts of fast-multiplying, ad hoc transactions, are what worry lupus patients like Julie Powers. For now, she says she has enough hydroxychloroquine to last 90 days, and she added that her pharmacist in the Washington, D.C. area is currently hiding the medicine to be sure her regular lupus patients can get their prescriptions refilled.
Powers sounds almost amazed when she describes what that means to her: “I can walk outside,” she said, “and I can live.”
Sara Talpos is a senior editor at Undark and a freelance writer whose recent work has been published in Science, Mosaic, and the Kenyon Review’s special issue on science writing.
Disclosure: The author’s spouse is a rheumatologist at Michigan Medicine.
UPDATES: This story has been updated to clarify Alfred Kim's view on several patients who dropped out of a small French study on the efficacy of using hydroxychloroquine to treat Covid-19 cases. The piece was also edited to include information noting that one state pharmacy board is now taking steps to curtail prescriptions of hydroxychloroquine and chloroquine for Covid-19 prophylaxis.
This article was originally published on Undark. Read the original article.
Expect to encounter more rheumatology/primary immunodeficiency overlap
MAUI, HAWAII – An underlying primary immunodeficiency is far more common among patients in rheumatologists’ offices than is generally appreciated, Anna Postolova, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
“Autoimmunity and immunodeficiency are often incorrectly thought to be mutually exclusive, but I hope to convey to you that they actually run together more than we think, and more than you realize. In the immunodeficiency community, we’re now realizing that autoimmunity can be the first presentation of an immunodeficiency disease,” according to Dr. Postolova, a dual rheumatologist and allergist/immunologist at Stanford (Calif.) University.
She cited a major retrospective study of 2,183 consecutive patients with primary immunodeficiencies (PIDs), mean age 25.8 years, enrolled in a French national PID registry. Of these patients, 26% had at least one autoimmune or inflammatory condition. The French investigators, all immunologists, categorized 12.8% of the PID patients as having rheumatologic disorders, but Dr. Postolova is convinced this figure would have been substantially higher had a rheumatologist been on the research team. That’s because vasculitis and inflammatory eye disorders weren’t included in the rheumatologic disease category, and psoriatic arthritis was probably present but undiagnosed in some psoriasis patients grouped in the skin disease category.
“Our results demonstrate that autoimmune and inflammatory diseases are much more frequent by a factor of at least 10 in patients with PIDs than in the general population,” the French investigators observed.
Indeed, the relative risks of vasculitis, inflammatory eye disease, and skin disease in patients with PID were increased 13-, 7-, and 10-fold, respectively. French children with PID were at 40-fold increased risk for rheumatoid arthritis and 80-fold elevated risk for inflammatory bowel disease.
Among the PID patients with at least one autoimmune or inflammatory condition, 31.6% had more than one. And therein lies a clue for rheumatologists.
“You might have some patients in your panel who have both arthritis and vasculitis, for example. It’s not that common for our patients to have two of our diseases, but those are the ones who might have an immune dysregulatory inborn error of metabolism mutation that’s driving their disease – and we’re now able to look into that,” Dr. Postolova explained.
At present, more than 300 identified single-gene inborn errors of immunity have been identified, some of which can manifest variously as systemic lupus erythematosus (SLE), arthritis, vasculitis, and/or cytopenias, she noted.
In the French study, onset of autoimmune or inflammatory manifestations of PID occurred across the age spectrum. The age of onset was earlier with T-cell and innate immunity deficiencies than in patients with B-cell deficiencies. The prevalence of an autoimmune or inflammatory disorder was greater than 40% in PID patients age 50 years or older.
“What I want to hammer home is these patients with PID are no longer succumbing to their infections. They’re being identified as having an immunodeficiency, they’re going on antibiotics, they’re strictly monitored, and they’re growing older. And as their aberrant immune system fights an infection, they have more and more time to dysregulate and develop one of our diseases. So in the coming years I think you’re going to see a lot more of these patients show up in your rheumatology clinic because they are getting older,” Dr. Postolova said.
Red flags for underlying PID
Recurrent infections are a hallmark of PIDs. And mutations that cause increased infections can alter central and peripheral tolerance, affecting cell growth, signaling, and survival, which in turn affects immunity.
“As we use biologics in our patients with rheumatologic diseases, I think there’s a cohort of patients we’re starting to identify who are getting very serious recurrent infections. It’s not every patient. But that patient who’s had three or four serious infections, that’s the patient who I think we’ll be able to identify in our clinics through an immunodeficiency evaluation. Likewise, the patients who are not responding to multiple different drugs, that’s where I’d stop and think about an underlying immune deficiency,” she said.
A show of hands indicated only about 25% of her audience of rheumatologists routinely ask new patients if they have a personal or family history of recurrent infections. That should be routine practice, in Dr. Postolova’s view. The 10 warning signs of PID for adults put forth by the Jeffrey Modell Foundation focus on a family or personal history of recurrent ear or sinus infections, deep skin abscesses, pneumonia, viral infections, persistent thrush, or chronic diarrhea with weight loss.
Testing for PID
It’s “absolutely appropriate” to start a work-up for suspected immunodeficiency in a rheumatology clinic, according to Dr. Postolova.
“I think every allergist/immunologist would be grateful if you can just order a quantitative immunoglobulin panel as well as specific antibody titer responses to tetanus, diphtheria, pneumococcal vaccine, and an IgG subclass analysis. That’s half of an immunologist’s initial assessment,” she said.
Corticosteroids and other disease-modifying antirheumatic drugs (DMARDs) affect flow cytometry test results. It’s best to hold off on testing until after a patient has been off therapy for 2-3 months. Similarly, treatment with intravenous immunoglobulin (IVIg) will confound measurement of vaccine antibody titers, so it’s recommended to wait for 3-6 months off IVIg before testing.
Genetic testing for PID has become a lot simpler and more affordable. Numerous companies have developed test kits featuring relatively small panels of selected genes of interest. Dr. Postolova often uses Invitae, a Bay Area company that has a 207-gene panel covered by most insurers with an out-of-pocket cost to the patient of $250.
“Upfront when I have a complicated patient where I am concerned about the possibility of immunodeficiency, I will ask if that’s something they can afford and if they want to move forward with it. Also, Invitae has a patient assistance program. I’ve found this helpful in some of my very complicated patients,” she said.
Get to know your local allergist/immunologist
Many allergist/immunologists have overcome their traditional reservations about immunosuppressing an immunosuppressed individual and are now treating PID/autoimmune disease–overlap patients with the very drugs rheumatologists use every day, including standard DMARDs, rituximab, abatacept, anakinra, and tumor necrosis factor inhibitors.
“I encourage you to work with your allergist/immunologist for these patients because they’re going to need help,” according to Dr. Postolova. “The people in this room are the most equipped to treat the overlap patients because allergists and immunologists don’t really have the training to use these drugs. A lot of them do use them, but you have a better handle on these drugs than other people.”
Dr. Postolova reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – An underlying primary immunodeficiency is far more common among patients in rheumatologists’ offices than is generally appreciated, Anna Postolova, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
“Autoimmunity and immunodeficiency are often incorrectly thought to be mutually exclusive, but I hope to convey to you that they actually run together more than we think, and more than you realize. In the immunodeficiency community, we’re now realizing that autoimmunity can be the first presentation of an immunodeficiency disease,” according to Dr. Postolova, a dual rheumatologist and allergist/immunologist at Stanford (Calif.) University.
She cited a major retrospective study of 2,183 consecutive patients with primary immunodeficiencies (PIDs), mean age 25.8 years, enrolled in a French national PID registry. Of these patients, 26% had at least one autoimmune or inflammatory condition. The French investigators, all immunologists, categorized 12.8% of the PID patients as having rheumatologic disorders, but Dr. Postolova is convinced this figure would have been substantially higher had a rheumatologist been on the research team. That’s because vasculitis and inflammatory eye disorders weren’t included in the rheumatologic disease category, and psoriatic arthritis was probably present but undiagnosed in some psoriasis patients grouped in the skin disease category.
“Our results demonstrate that autoimmune and inflammatory diseases are much more frequent by a factor of at least 10 in patients with PIDs than in the general population,” the French investigators observed.
Indeed, the relative risks of vasculitis, inflammatory eye disease, and skin disease in patients with PID were increased 13-, 7-, and 10-fold, respectively. French children with PID were at 40-fold increased risk for rheumatoid arthritis and 80-fold elevated risk for inflammatory bowel disease.
Among the PID patients with at least one autoimmune or inflammatory condition, 31.6% had more than one. And therein lies a clue for rheumatologists.
“You might have some patients in your panel who have both arthritis and vasculitis, for example. It’s not that common for our patients to have two of our diseases, but those are the ones who might have an immune dysregulatory inborn error of metabolism mutation that’s driving their disease – and we’re now able to look into that,” Dr. Postolova explained.
At present, more than 300 identified single-gene inborn errors of immunity have been identified, some of which can manifest variously as systemic lupus erythematosus (SLE), arthritis, vasculitis, and/or cytopenias, she noted.
In the French study, onset of autoimmune or inflammatory manifestations of PID occurred across the age spectrum. The age of onset was earlier with T-cell and innate immunity deficiencies than in patients with B-cell deficiencies. The prevalence of an autoimmune or inflammatory disorder was greater than 40% in PID patients age 50 years or older.
“What I want to hammer home is these patients with PID are no longer succumbing to their infections. They’re being identified as having an immunodeficiency, they’re going on antibiotics, they’re strictly monitored, and they’re growing older. And as their aberrant immune system fights an infection, they have more and more time to dysregulate and develop one of our diseases. So in the coming years I think you’re going to see a lot more of these patients show up in your rheumatology clinic because they are getting older,” Dr. Postolova said.
Red flags for underlying PID
Recurrent infections are a hallmark of PIDs. And mutations that cause increased infections can alter central and peripheral tolerance, affecting cell growth, signaling, and survival, which in turn affects immunity.
“As we use biologics in our patients with rheumatologic diseases, I think there’s a cohort of patients we’re starting to identify who are getting very serious recurrent infections. It’s not every patient. But that patient who’s had three or four serious infections, that’s the patient who I think we’ll be able to identify in our clinics through an immunodeficiency evaluation. Likewise, the patients who are not responding to multiple different drugs, that’s where I’d stop and think about an underlying immune deficiency,” she said.
A show of hands indicated only about 25% of her audience of rheumatologists routinely ask new patients if they have a personal or family history of recurrent infections. That should be routine practice, in Dr. Postolova’s view. The 10 warning signs of PID for adults put forth by the Jeffrey Modell Foundation focus on a family or personal history of recurrent ear or sinus infections, deep skin abscesses, pneumonia, viral infections, persistent thrush, or chronic diarrhea with weight loss.
Testing for PID
It’s “absolutely appropriate” to start a work-up for suspected immunodeficiency in a rheumatology clinic, according to Dr. Postolova.
“I think every allergist/immunologist would be grateful if you can just order a quantitative immunoglobulin panel as well as specific antibody titer responses to tetanus, diphtheria, pneumococcal vaccine, and an IgG subclass analysis. That’s half of an immunologist’s initial assessment,” she said.
Corticosteroids and other disease-modifying antirheumatic drugs (DMARDs) affect flow cytometry test results. It’s best to hold off on testing until after a patient has been off therapy for 2-3 months. Similarly, treatment with intravenous immunoglobulin (IVIg) will confound measurement of vaccine antibody titers, so it’s recommended to wait for 3-6 months off IVIg before testing.
Genetic testing for PID has become a lot simpler and more affordable. Numerous companies have developed test kits featuring relatively small panels of selected genes of interest. Dr. Postolova often uses Invitae, a Bay Area company that has a 207-gene panel covered by most insurers with an out-of-pocket cost to the patient of $250.
“Upfront when I have a complicated patient where I am concerned about the possibility of immunodeficiency, I will ask if that’s something they can afford and if they want to move forward with it. Also, Invitae has a patient assistance program. I’ve found this helpful in some of my very complicated patients,” she said.
Get to know your local allergist/immunologist
Many allergist/immunologists have overcome their traditional reservations about immunosuppressing an immunosuppressed individual and are now treating PID/autoimmune disease–overlap patients with the very drugs rheumatologists use every day, including standard DMARDs, rituximab, abatacept, anakinra, and tumor necrosis factor inhibitors.
“I encourage you to work with your allergist/immunologist for these patients because they’re going to need help,” according to Dr. Postolova. “The people in this room are the most equipped to treat the overlap patients because allergists and immunologists don’t really have the training to use these drugs. A lot of them do use them, but you have a better handle on these drugs than other people.”
Dr. Postolova reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – An underlying primary immunodeficiency is far more common among patients in rheumatologists’ offices than is generally appreciated, Anna Postolova, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
“Autoimmunity and immunodeficiency are often incorrectly thought to be mutually exclusive, but I hope to convey to you that they actually run together more than we think, and more than you realize. In the immunodeficiency community, we’re now realizing that autoimmunity can be the first presentation of an immunodeficiency disease,” according to Dr. Postolova, a dual rheumatologist and allergist/immunologist at Stanford (Calif.) University.
She cited a major retrospective study of 2,183 consecutive patients with primary immunodeficiencies (PIDs), mean age 25.8 years, enrolled in a French national PID registry. Of these patients, 26% had at least one autoimmune or inflammatory condition. The French investigators, all immunologists, categorized 12.8% of the PID patients as having rheumatologic disorders, but Dr. Postolova is convinced this figure would have been substantially higher had a rheumatologist been on the research team. That’s because vasculitis and inflammatory eye disorders weren’t included in the rheumatologic disease category, and psoriatic arthritis was probably present but undiagnosed in some psoriasis patients grouped in the skin disease category.
“Our results demonstrate that autoimmune and inflammatory diseases are much more frequent by a factor of at least 10 in patients with PIDs than in the general population,” the French investigators observed.
Indeed, the relative risks of vasculitis, inflammatory eye disease, and skin disease in patients with PID were increased 13-, 7-, and 10-fold, respectively. French children with PID were at 40-fold increased risk for rheumatoid arthritis and 80-fold elevated risk for inflammatory bowel disease.
Among the PID patients with at least one autoimmune or inflammatory condition, 31.6% had more than one. And therein lies a clue for rheumatologists.
“You might have some patients in your panel who have both arthritis and vasculitis, for example. It’s not that common for our patients to have two of our diseases, but those are the ones who might have an immune dysregulatory inborn error of metabolism mutation that’s driving their disease – and we’re now able to look into that,” Dr. Postolova explained.
At present, more than 300 identified single-gene inborn errors of immunity have been identified, some of which can manifest variously as systemic lupus erythematosus (SLE), arthritis, vasculitis, and/or cytopenias, she noted.
In the French study, onset of autoimmune or inflammatory manifestations of PID occurred across the age spectrum. The age of onset was earlier with T-cell and innate immunity deficiencies than in patients with B-cell deficiencies. The prevalence of an autoimmune or inflammatory disorder was greater than 40% in PID patients age 50 years or older.
“What I want to hammer home is these patients with PID are no longer succumbing to their infections. They’re being identified as having an immunodeficiency, they’re going on antibiotics, they’re strictly monitored, and they’re growing older. And as their aberrant immune system fights an infection, they have more and more time to dysregulate and develop one of our diseases. So in the coming years I think you’re going to see a lot more of these patients show up in your rheumatology clinic because they are getting older,” Dr. Postolova said.
Red flags for underlying PID
Recurrent infections are a hallmark of PIDs. And mutations that cause increased infections can alter central and peripheral tolerance, affecting cell growth, signaling, and survival, which in turn affects immunity.
“As we use biologics in our patients with rheumatologic diseases, I think there’s a cohort of patients we’re starting to identify who are getting very serious recurrent infections. It’s not every patient. But that patient who’s had three or four serious infections, that’s the patient who I think we’ll be able to identify in our clinics through an immunodeficiency evaluation. Likewise, the patients who are not responding to multiple different drugs, that’s where I’d stop and think about an underlying immune deficiency,” she said.
A show of hands indicated only about 25% of her audience of rheumatologists routinely ask new patients if they have a personal or family history of recurrent infections. That should be routine practice, in Dr. Postolova’s view. The 10 warning signs of PID for adults put forth by the Jeffrey Modell Foundation focus on a family or personal history of recurrent ear or sinus infections, deep skin abscesses, pneumonia, viral infections, persistent thrush, or chronic diarrhea with weight loss.
Testing for PID
It’s “absolutely appropriate” to start a work-up for suspected immunodeficiency in a rheumatology clinic, according to Dr. Postolova.
“I think every allergist/immunologist would be grateful if you can just order a quantitative immunoglobulin panel as well as specific antibody titer responses to tetanus, diphtheria, pneumococcal vaccine, and an IgG subclass analysis. That’s half of an immunologist’s initial assessment,” she said.
Corticosteroids and other disease-modifying antirheumatic drugs (DMARDs) affect flow cytometry test results. It’s best to hold off on testing until after a patient has been off therapy for 2-3 months. Similarly, treatment with intravenous immunoglobulin (IVIg) will confound measurement of vaccine antibody titers, so it’s recommended to wait for 3-6 months off IVIg before testing.
Genetic testing for PID has become a lot simpler and more affordable. Numerous companies have developed test kits featuring relatively small panels of selected genes of interest. Dr. Postolova often uses Invitae, a Bay Area company that has a 207-gene panel covered by most insurers with an out-of-pocket cost to the patient of $250.
“Upfront when I have a complicated patient where I am concerned about the possibility of immunodeficiency, I will ask if that’s something they can afford and if they want to move forward with it. Also, Invitae has a patient assistance program. I’ve found this helpful in some of my very complicated patients,” she said.
Get to know your local allergist/immunologist
Many allergist/immunologists have overcome their traditional reservations about immunosuppressing an immunosuppressed individual and are now treating PID/autoimmune disease–overlap patients with the very drugs rheumatologists use every day, including standard DMARDs, rituximab, abatacept, anakinra, and tumor necrosis factor inhibitors.
“I encourage you to work with your allergist/immunologist for these patients because they’re going to need help,” according to Dr. Postolova. “The people in this room are the most equipped to treat the overlap patients because allergists and immunologists don’t really have the training to use these drugs. A lot of them do use them, but you have a better handle on these drugs than other people.”
Dr. Postolova reported having no financial conflicts regarding her presentation.
EXPERT ANALYSIS FROM RWCS 2020
African Americans with SLE face increased risk of CVD hospitalizations
PHOENIX – African Americans with systemic lupus erythematosus are more likely to experience recurrent hospitalizations for cardiovascular disease, compared with other racial/ethnic groups, results from a single-state registry study found.
“SLE is an autoimmune disease that causes inflammation affecting multiple organ systems including the cardiovascular system,” Meghan Angley, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “Therefore, individuals with SLE are at risk for early CVD. African Americans represent the racial group at greatest risk for SLE.”
According to Ms. Angley, with the department of epidemiology at Emory University, Atlanta, white women with SLE have CVD associated mortality 12 years earlier than their non-SLE counterparts, while African American women with SLE have CVD-associated mortality 19 years earlier than their non-SLE counterparts. “We know that recurrent hospitalizations for CVD are associated with mortality,” she said. “These represent potential points of identification of high-risk individuals and also points of interventions.”
In order to study racial disparities across recurrent hospitalizations for cardiovascular disease in an SLE population, Ms. Angley and her colleagues drew from the Georgia Lupus Registry, which is a population-based registry of patients with validated SLE in two Georgia counties. They included all cases diagnosed between 2000 and 2004. The registry was linked to records of all inpatient hospitalizations in Georgia between 2000 and 2013. The researchers used ICD-9 codes to identify hospitalizations for coronary heart disease, peripheral artery disease, cerebrovascular disease, and heart failure and used the Prentice-Williams-Peterson model for recurrent time-to-event analysis. Specifically, they looked at the total time scale from the point of diagnosis to each of the subsequent CVD hospitalizations and truncated the number of hospitalizations at three to maintain stable modeling estimates. The analysis was censored at the time of patient death or at the end of 2013 and adjusted for sex and age at diagnosis.
The sample included 417 African Americans with SLE and 149 non–African Americans with the disease. Most (86%) were female, and the non–African American group was slightly more likely to have been diagnosed with SLE after the age of 45 years, compared with the African American group (36% vs. 30%, respectively).
Ms. Angley and her colleagues found that 24% of African Americans had at least one CVD hospitalization, and 14% had at least two, while 13% of non–African Americans had at least one CVD hospitalization, and 5% had at least two. Among those in the African American group, reasons for hospitalizations were congestive heart failure, (58%), cerebrovascular disease (27%), coronary heart disease (18%), and peripheral artery disease (2%). Among those in the non–African American group, reasons for hospitalizations were congestive heart failure (38%), coronary heart disease (38%), cerebrovascular disease (25%), and peripheral artery disease (6%).
Overall, African American race was associated with recurrent hospitalizations (adjusted hazard ratio, 1.9). In an event-specific stratified analysis, the association between African American race and the hazard of recurrence became even more pronounced with each event (hospitalization 1 aHR, 1.2; hospitalization 2 aHR, 1.5; hospitalization 3 aHR, 1.9). The researchers also observed that African Americans were hospitalized sooner, compared with non–African Americans: a median of 3.68 versus 4.61 years for hospitalization 1, 3.73 years versus 5.98 years for hospitalization 2, and 4.84 years versus 8.14 years for hospitalization 3.
“African Americans with SLE are more likely to experience recurrent hospitalizations for CVD,” Ms. Angley concluded at the meeting, which was sponsored by the American Heart Association. “The events occur sooner after diagnosis than in non–African Americans, suggesting that African Americans may be more vulnerable to the cardiovascular complications of SLE. Our next steps include examining potential reasons for these disparities, such as looking at primary care patterns over time, SLE severity over time, and treatment at CVD hospitalizations.”
In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, called for additional research to determine the reasons for disparities that were observed between African Americans with SLE and their non–African American counterparts. “We need to figure out why and address it,” said Dr. Brown, who is a cardiologist and physician-scientist at Mayo Clinic, Rochester, Minn. “We recognize that social determinants of health, such as insurance, socioeconomic factors, and psychosocial factors, can contribute. We need to figure out the additional steps we need to take in order to close that gap.”
Ms. Angley reported having no disclosures. The study was funded by grants from the Centers for Disease Control and Prevention and by the National Institutes of Health.
SOURCE: Angley M et al. Epi/Lifestyle 2020, Abstract 5.
PHOENIX – African Americans with systemic lupus erythematosus are more likely to experience recurrent hospitalizations for cardiovascular disease, compared with other racial/ethnic groups, results from a single-state registry study found.
“SLE is an autoimmune disease that causes inflammation affecting multiple organ systems including the cardiovascular system,” Meghan Angley, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “Therefore, individuals with SLE are at risk for early CVD. African Americans represent the racial group at greatest risk for SLE.”
According to Ms. Angley, with the department of epidemiology at Emory University, Atlanta, white women with SLE have CVD associated mortality 12 years earlier than their non-SLE counterparts, while African American women with SLE have CVD-associated mortality 19 years earlier than their non-SLE counterparts. “We know that recurrent hospitalizations for CVD are associated with mortality,” she said. “These represent potential points of identification of high-risk individuals and also points of interventions.”
In order to study racial disparities across recurrent hospitalizations for cardiovascular disease in an SLE population, Ms. Angley and her colleagues drew from the Georgia Lupus Registry, which is a population-based registry of patients with validated SLE in two Georgia counties. They included all cases diagnosed between 2000 and 2004. The registry was linked to records of all inpatient hospitalizations in Georgia between 2000 and 2013. The researchers used ICD-9 codes to identify hospitalizations for coronary heart disease, peripheral artery disease, cerebrovascular disease, and heart failure and used the Prentice-Williams-Peterson model for recurrent time-to-event analysis. Specifically, they looked at the total time scale from the point of diagnosis to each of the subsequent CVD hospitalizations and truncated the number of hospitalizations at three to maintain stable modeling estimates. The analysis was censored at the time of patient death or at the end of 2013 and adjusted for sex and age at diagnosis.
The sample included 417 African Americans with SLE and 149 non–African Americans with the disease. Most (86%) were female, and the non–African American group was slightly more likely to have been diagnosed with SLE after the age of 45 years, compared with the African American group (36% vs. 30%, respectively).
Ms. Angley and her colleagues found that 24% of African Americans had at least one CVD hospitalization, and 14% had at least two, while 13% of non–African Americans had at least one CVD hospitalization, and 5% had at least two. Among those in the African American group, reasons for hospitalizations were congestive heart failure, (58%), cerebrovascular disease (27%), coronary heart disease (18%), and peripheral artery disease (2%). Among those in the non–African American group, reasons for hospitalizations were congestive heart failure (38%), coronary heart disease (38%), cerebrovascular disease (25%), and peripheral artery disease (6%).
Overall, African American race was associated with recurrent hospitalizations (adjusted hazard ratio, 1.9). In an event-specific stratified analysis, the association between African American race and the hazard of recurrence became even more pronounced with each event (hospitalization 1 aHR, 1.2; hospitalization 2 aHR, 1.5; hospitalization 3 aHR, 1.9). The researchers also observed that African Americans were hospitalized sooner, compared with non–African Americans: a median of 3.68 versus 4.61 years for hospitalization 1, 3.73 years versus 5.98 years for hospitalization 2, and 4.84 years versus 8.14 years for hospitalization 3.
“African Americans with SLE are more likely to experience recurrent hospitalizations for CVD,” Ms. Angley concluded at the meeting, which was sponsored by the American Heart Association. “The events occur sooner after diagnosis than in non–African Americans, suggesting that African Americans may be more vulnerable to the cardiovascular complications of SLE. Our next steps include examining potential reasons for these disparities, such as looking at primary care patterns over time, SLE severity over time, and treatment at CVD hospitalizations.”
In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, called for additional research to determine the reasons for disparities that were observed between African Americans with SLE and their non–African American counterparts. “We need to figure out why and address it,” said Dr. Brown, who is a cardiologist and physician-scientist at Mayo Clinic, Rochester, Minn. “We recognize that social determinants of health, such as insurance, socioeconomic factors, and psychosocial factors, can contribute. We need to figure out the additional steps we need to take in order to close that gap.”
Ms. Angley reported having no disclosures. The study was funded by grants from the Centers for Disease Control and Prevention and by the National Institutes of Health.
SOURCE: Angley M et al. Epi/Lifestyle 2020, Abstract 5.
PHOENIX – African Americans with systemic lupus erythematosus are more likely to experience recurrent hospitalizations for cardiovascular disease, compared with other racial/ethnic groups, results from a single-state registry study found.
“SLE is an autoimmune disease that causes inflammation affecting multiple organ systems including the cardiovascular system,” Meghan Angley, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “Therefore, individuals with SLE are at risk for early CVD. African Americans represent the racial group at greatest risk for SLE.”
According to Ms. Angley, with the department of epidemiology at Emory University, Atlanta, white women with SLE have CVD associated mortality 12 years earlier than their non-SLE counterparts, while African American women with SLE have CVD-associated mortality 19 years earlier than their non-SLE counterparts. “We know that recurrent hospitalizations for CVD are associated with mortality,” she said. “These represent potential points of identification of high-risk individuals and also points of interventions.”
In order to study racial disparities across recurrent hospitalizations for cardiovascular disease in an SLE population, Ms. Angley and her colleagues drew from the Georgia Lupus Registry, which is a population-based registry of patients with validated SLE in two Georgia counties. They included all cases diagnosed between 2000 and 2004. The registry was linked to records of all inpatient hospitalizations in Georgia between 2000 and 2013. The researchers used ICD-9 codes to identify hospitalizations for coronary heart disease, peripheral artery disease, cerebrovascular disease, and heart failure and used the Prentice-Williams-Peterson model for recurrent time-to-event analysis. Specifically, they looked at the total time scale from the point of diagnosis to each of the subsequent CVD hospitalizations and truncated the number of hospitalizations at three to maintain stable modeling estimates. The analysis was censored at the time of patient death or at the end of 2013 and adjusted for sex and age at diagnosis.
The sample included 417 African Americans with SLE and 149 non–African Americans with the disease. Most (86%) were female, and the non–African American group was slightly more likely to have been diagnosed with SLE after the age of 45 years, compared with the African American group (36% vs. 30%, respectively).
Ms. Angley and her colleagues found that 24% of African Americans had at least one CVD hospitalization, and 14% had at least two, while 13% of non–African Americans had at least one CVD hospitalization, and 5% had at least two. Among those in the African American group, reasons for hospitalizations were congestive heart failure, (58%), cerebrovascular disease (27%), coronary heart disease (18%), and peripheral artery disease (2%). Among those in the non–African American group, reasons for hospitalizations were congestive heart failure (38%), coronary heart disease (38%), cerebrovascular disease (25%), and peripheral artery disease (6%).
Overall, African American race was associated with recurrent hospitalizations (adjusted hazard ratio, 1.9). In an event-specific stratified analysis, the association between African American race and the hazard of recurrence became even more pronounced with each event (hospitalization 1 aHR, 1.2; hospitalization 2 aHR, 1.5; hospitalization 3 aHR, 1.9). The researchers also observed that African Americans were hospitalized sooner, compared with non–African Americans: a median of 3.68 versus 4.61 years for hospitalization 1, 3.73 years versus 5.98 years for hospitalization 2, and 4.84 years versus 8.14 years for hospitalization 3.
“African Americans with SLE are more likely to experience recurrent hospitalizations for CVD,” Ms. Angley concluded at the meeting, which was sponsored by the American Heart Association. “The events occur sooner after diagnosis than in non–African Americans, suggesting that African Americans may be more vulnerable to the cardiovascular complications of SLE. Our next steps include examining potential reasons for these disparities, such as looking at primary care patterns over time, SLE severity over time, and treatment at CVD hospitalizations.”
In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, called for additional research to determine the reasons for disparities that were observed between African Americans with SLE and their non–African American counterparts. “We need to figure out why and address it,” said Dr. Brown, who is a cardiologist and physician-scientist at Mayo Clinic, Rochester, Minn. “We recognize that social determinants of health, such as insurance, socioeconomic factors, and psychosocial factors, can contribute. We need to figure out the additional steps we need to take in order to close that gap.”
Ms. Angley reported having no disclosures. The study was funded by grants from the Centers for Disease Control and Prevention and by the National Institutes of Health.
SOURCE: Angley M et al. Epi/Lifestyle 2020, Abstract 5.
REPORTING FROM EPI/LIFESTYLE 2020
High CV event risk seen in SLE patients with ACC/AHA-defined hypertension
, results of a retrospective, single-center investigation suggest.
Risk of atherosclerotic vascular events was increased by 73% for patients with systemic lupus erythematosus (SLE) who sustained a mean blood pressure of 130/80 to 139/89 mm Hg over 2 years in the study, which included 1,532 patients treated at a clinic in Toronto.
Management of hypertension in SLE patients should start early, and should aim to achieve levels below 130/80 mm Hg, according to the investigators, led by Konstantinos Tselios, MD, PhD, of the Centre for Prognosis Studies in the Rheumatic Diseases at the University of Toronto.
“The findings of the present study support that the target BP should be less than 130/80 mm Hg in all patients with lupus in order to minimize their cardiovascular risk,” Dr. Tselios and coauthors said in their study, which appears in Annals of the Rheumatic Diseases.
Despite the limitations inherent in a retrospective, observational study, this work by Dr. Tselios and colleagues may help inform the care of patients with SLE, according to C. Michael Stein, MBChB, professor of medicine at Vanderbilt University in Nashville, Tenn.
“It’s really interesting data that’s important and helps us think in terms of figuring out what may be reasonable to do for a particular patient,” Dr. Stein said in an interview.
Starting antihypertensive management early and aiming at levels below 130/80 mm Hg is a strategy that should be “reasonable” for most patients with SLE, said Dr. Stein, adding that the approach specified in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines are appropriate to follow. In those guidelines, the threshold for diagnosis of hypertension was lowered to 130/80 mm Hg.
“You can start with risk factor modification, in terms of losing weight, exercising, stopping alcohol, and decreasing salt in the diet to see if you can get the blood pressure down, though it may come down to drug therapy for many patients, I believe,” Dr. Stein said.
Authors of those 2017 ACC/AHA guidelines made no recommendations for patients with SLE or other connective tissue diseases, despite including a section devoted to specific patient subgroups and comorbidities of interest, Dr. Tselios and coauthors noted in their report.
Management of hypertension in patients with lupus may be “delayed” in patients with blood pressures reaching the current hypertension threshold, according to Dr. Tselios and colleagues, due in part to difficulties in cardiovascular risk calculation in SLE patients, as well as current risk considerations outlined in the guidelines.
“On the basis of the recent guidelines, the patient with typical lupus (young female with no traditional atherosclerotic risk factors) would be considered as a low-risk individual and not offered treatment for a BP of 130-139/80-89 mm Hg,” they said in their report.
Accordingly, Dr. Tselios and colleagues sought to determine whether the new hypertension definition predicted atherosclerotic vascular events, including new-onset angina, acute myocardial infarction, cerebrovascular events, revascularization procedures, heart failure, or peripheral vascular disease requiring angioplasty, in patients with SLE treated at a Canadian clinic.
Their analysis comprised 1,532 patients with SLE who had at least 2 years of follow-up and had no prior atherosclerotic events on record. Over a mean follow-up of nearly 11 years, there were 124 such events documented in those patients.
With a mean follow-up of nearly 11 years, the incidence of atherosclerotic events was 18.9 per 1,000 patient-years for patients with blood pressure ≥ 140/90 mm Hg, 11.5 per 1,000 patient-years for the 130-139/80-89 mm Hg group, and 4.5 per 1,000 patient-years for those with blood pressures of 130/80 mm Hg or lower, with differences that were statistically significant between groups, according to the report.
An adjusted blood pressure of 130-139/80-89 mm Hg over the first 2 years since enrollment in the clinic was independently associated with the occurrence of an atherosclerotic event, with a hazard ratio of 1.73 (95% confidence interval, 1.13-2.69, P = 0.011), according to results of a multivariable analysis.
Those findings support targeting a blood pressure below 130/80 mm Hg in all patients with lupus, according to Dr. Tselios and coauthors.
“It seems reasonable that clinicians should not rely on CV risk calculators in SLE and commence treatment as soon as possible in cases of sustained BP elevation above the threshold of 130/80 mm Hg,” they wrote in their report.
How low to go remains unclear, however, as targeting lower levels of blood pressure might be unsafe in certain groups, such as those SLE patients with prior heart disease or heart failure; nevertheless, recent observational data from non-SLE populations suggest that effective treatment to levels lower than 130/80 mm Hg would “further reduce the incidence of atherosclerotic events in SLE,” the authors said in a discussion of their results.
Dr. Tselios and coauthors said they had no competing interests relative to the study. They reported funding for the University of Toronto Lupus Clinic from the University Health Network, Lou & Marissa Rocca, Mark & Diana Bozzo, and the Lupus Foundation of Ontario.
SOURCE: Tselios K et al. Ann Rheum Dis. 2020 Mar 10. doi: 10.1136/annrheumdis-2019-216764
, results of a retrospective, single-center investigation suggest.
Risk of atherosclerotic vascular events was increased by 73% for patients with systemic lupus erythematosus (SLE) who sustained a mean blood pressure of 130/80 to 139/89 mm Hg over 2 years in the study, which included 1,532 patients treated at a clinic in Toronto.
Management of hypertension in SLE patients should start early, and should aim to achieve levels below 130/80 mm Hg, according to the investigators, led by Konstantinos Tselios, MD, PhD, of the Centre for Prognosis Studies in the Rheumatic Diseases at the University of Toronto.
“The findings of the present study support that the target BP should be less than 130/80 mm Hg in all patients with lupus in order to minimize their cardiovascular risk,” Dr. Tselios and coauthors said in their study, which appears in Annals of the Rheumatic Diseases.
Despite the limitations inherent in a retrospective, observational study, this work by Dr. Tselios and colleagues may help inform the care of patients with SLE, according to C. Michael Stein, MBChB, professor of medicine at Vanderbilt University in Nashville, Tenn.
“It’s really interesting data that’s important and helps us think in terms of figuring out what may be reasonable to do for a particular patient,” Dr. Stein said in an interview.
Starting antihypertensive management early and aiming at levels below 130/80 mm Hg is a strategy that should be “reasonable” for most patients with SLE, said Dr. Stein, adding that the approach specified in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines are appropriate to follow. In those guidelines, the threshold for diagnosis of hypertension was lowered to 130/80 mm Hg.
“You can start with risk factor modification, in terms of losing weight, exercising, stopping alcohol, and decreasing salt in the diet to see if you can get the blood pressure down, though it may come down to drug therapy for many patients, I believe,” Dr. Stein said.
Authors of those 2017 ACC/AHA guidelines made no recommendations for patients with SLE or other connective tissue diseases, despite including a section devoted to specific patient subgroups and comorbidities of interest, Dr. Tselios and coauthors noted in their report.
Management of hypertension in patients with lupus may be “delayed” in patients with blood pressures reaching the current hypertension threshold, according to Dr. Tselios and colleagues, due in part to difficulties in cardiovascular risk calculation in SLE patients, as well as current risk considerations outlined in the guidelines.
“On the basis of the recent guidelines, the patient with typical lupus (young female with no traditional atherosclerotic risk factors) would be considered as a low-risk individual and not offered treatment for a BP of 130-139/80-89 mm Hg,” they said in their report.
Accordingly, Dr. Tselios and colleagues sought to determine whether the new hypertension definition predicted atherosclerotic vascular events, including new-onset angina, acute myocardial infarction, cerebrovascular events, revascularization procedures, heart failure, or peripheral vascular disease requiring angioplasty, in patients with SLE treated at a Canadian clinic.
Their analysis comprised 1,532 patients with SLE who had at least 2 years of follow-up and had no prior atherosclerotic events on record. Over a mean follow-up of nearly 11 years, there were 124 such events documented in those patients.
With a mean follow-up of nearly 11 years, the incidence of atherosclerotic events was 18.9 per 1,000 patient-years for patients with blood pressure ≥ 140/90 mm Hg, 11.5 per 1,000 patient-years for the 130-139/80-89 mm Hg group, and 4.5 per 1,000 patient-years for those with blood pressures of 130/80 mm Hg or lower, with differences that were statistically significant between groups, according to the report.
An adjusted blood pressure of 130-139/80-89 mm Hg over the first 2 years since enrollment in the clinic was independently associated with the occurrence of an atherosclerotic event, with a hazard ratio of 1.73 (95% confidence interval, 1.13-2.69, P = 0.011), according to results of a multivariable analysis.
Those findings support targeting a blood pressure below 130/80 mm Hg in all patients with lupus, according to Dr. Tselios and coauthors.
“It seems reasonable that clinicians should not rely on CV risk calculators in SLE and commence treatment as soon as possible in cases of sustained BP elevation above the threshold of 130/80 mm Hg,” they wrote in their report.
How low to go remains unclear, however, as targeting lower levels of blood pressure might be unsafe in certain groups, such as those SLE patients with prior heart disease or heart failure; nevertheless, recent observational data from non-SLE populations suggest that effective treatment to levels lower than 130/80 mm Hg would “further reduce the incidence of atherosclerotic events in SLE,” the authors said in a discussion of their results.
Dr. Tselios and coauthors said they had no competing interests relative to the study. They reported funding for the University of Toronto Lupus Clinic from the University Health Network, Lou & Marissa Rocca, Mark & Diana Bozzo, and the Lupus Foundation of Ontario.
SOURCE: Tselios K et al. Ann Rheum Dis. 2020 Mar 10. doi: 10.1136/annrheumdis-2019-216764
, results of a retrospective, single-center investigation suggest.
Risk of atherosclerotic vascular events was increased by 73% for patients with systemic lupus erythematosus (SLE) who sustained a mean blood pressure of 130/80 to 139/89 mm Hg over 2 years in the study, which included 1,532 patients treated at a clinic in Toronto.
Management of hypertension in SLE patients should start early, and should aim to achieve levels below 130/80 mm Hg, according to the investigators, led by Konstantinos Tselios, MD, PhD, of the Centre for Prognosis Studies in the Rheumatic Diseases at the University of Toronto.
“The findings of the present study support that the target BP should be less than 130/80 mm Hg in all patients with lupus in order to minimize their cardiovascular risk,” Dr. Tselios and coauthors said in their study, which appears in Annals of the Rheumatic Diseases.
Despite the limitations inherent in a retrospective, observational study, this work by Dr. Tselios and colleagues may help inform the care of patients with SLE, according to C. Michael Stein, MBChB, professor of medicine at Vanderbilt University in Nashville, Tenn.
“It’s really interesting data that’s important and helps us think in terms of figuring out what may be reasonable to do for a particular patient,” Dr. Stein said in an interview.
Starting antihypertensive management early and aiming at levels below 130/80 mm Hg is a strategy that should be “reasonable” for most patients with SLE, said Dr. Stein, adding that the approach specified in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines are appropriate to follow. In those guidelines, the threshold for diagnosis of hypertension was lowered to 130/80 mm Hg.
“You can start with risk factor modification, in terms of losing weight, exercising, stopping alcohol, and decreasing salt in the diet to see if you can get the blood pressure down, though it may come down to drug therapy for many patients, I believe,” Dr. Stein said.
Authors of those 2017 ACC/AHA guidelines made no recommendations for patients with SLE or other connective tissue diseases, despite including a section devoted to specific patient subgroups and comorbidities of interest, Dr. Tselios and coauthors noted in their report.
Management of hypertension in patients with lupus may be “delayed” in patients with blood pressures reaching the current hypertension threshold, according to Dr. Tselios and colleagues, due in part to difficulties in cardiovascular risk calculation in SLE patients, as well as current risk considerations outlined in the guidelines.
“On the basis of the recent guidelines, the patient with typical lupus (young female with no traditional atherosclerotic risk factors) would be considered as a low-risk individual and not offered treatment for a BP of 130-139/80-89 mm Hg,” they said in their report.
Accordingly, Dr. Tselios and colleagues sought to determine whether the new hypertension definition predicted atherosclerotic vascular events, including new-onset angina, acute myocardial infarction, cerebrovascular events, revascularization procedures, heart failure, or peripheral vascular disease requiring angioplasty, in patients with SLE treated at a Canadian clinic.
Their analysis comprised 1,532 patients with SLE who had at least 2 years of follow-up and had no prior atherosclerotic events on record. Over a mean follow-up of nearly 11 years, there were 124 such events documented in those patients.
With a mean follow-up of nearly 11 years, the incidence of atherosclerotic events was 18.9 per 1,000 patient-years for patients with blood pressure ≥ 140/90 mm Hg, 11.5 per 1,000 patient-years for the 130-139/80-89 mm Hg group, and 4.5 per 1,000 patient-years for those with blood pressures of 130/80 mm Hg or lower, with differences that were statistically significant between groups, according to the report.
An adjusted blood pressure of 130-139/80-89 mm Hg over the first 2 years since enrollment in the clinic was independently associated with the occurrence of an atherosclerotic event, with a hazard ratio of 1.73 (95% confidence interval, 1.13-2.69, P = 0.011), according to results of a multivariable analysis.
Those findings support targeting a blood pressure below 130/80 mm Hg in all patients with lupus, according to Dr. Tselios and coauthors.
“It seems reasonable that clinicians should not rely on CV risk calculators in SLE and commence treatment as soon as possible in cases of sustained BP elevation above the threshold of 130/80 mm Hg,” they wrote in their report.
How low to go remains unclear, however, as targeting lower levels of blood pressure might be unsafe in certain groups, such as those SLE patients with prior heart disease or heart failure; nevertheless, recent observational data from non-SLE populations suggest that effective treatment to levels lower than 130/80 mm Hg would “further reduce the incidence of atherosclerotic events in SLE,” the authors said in a discussion of their results.
Dr. Tselios and coauthors said they had no competing interests relative to the study. They reported funding for the University of Toronto Lupus Clinic from the University Health Network, Lou & Marissa Rocca, Mark & Diana Bozzo, and the Lupus Foundation of Ontario.
SOURCE: Tselios K et al. Ann Rheum Dis. 2020 Mar 10. doi: 10.1136/annrheumdis-2019-216764
FROM ANNALS OF THE RHEUMATIC DISEASES
Use of mHealth technology lags in lupus care, research
Most mobile apps are poor in quality, review finds.
and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”
The authors’ review of 19 mHealth apps on Google Play and the Apple App Store (and 1 not on either platform) gave an overall average score of 2.3 out of a possible 5.0 from individual mean scores for engagement, functionality, aesthetics, and information quality on the 23-item Mobile App Rating Scale, each item of which is rated on a 0-5 point scale. Overall, 10 apps offered educational content, 7 offered tools for tracking patient-reported symptoms, 5 offered interactive online communities, 1 offered emojis to share through text messages or email for the purpose of entertainment, and 1 could not be fully evaluated.
The researchers noted that “most apps scored poorly based on design, user interface, functionality, and credibility,” with mean scores of 2.5 for engagement, 2.9 for functionality, 2.2 for aesthetics, and 1.6 for information. “The majority of the apps provided low-quality information from questionable sources (i.e., sources were not cited or their legitimacy was unknown or unverifiable),” they wrote.
The three highest-rated apps – LupusMinder (overall mean score, 3.3), Lupus Corner Health Manager (3.2), and PatientsLikeMe (3.1) – all focused on tracking patient-reported outcomes, but none used validated outcome measures; offered connectivity with wearable devices; or passively collected data such as step count, walking distances, flights climbed, calories expenditure, or sleep monitoring. However, two did have social network components and interactive support groups. Despite these apps’ interactivity and customizability, none offered “features for patients to create and track goals, directly connect with a physician or expert in the field, or synchronize data with electronic health records. None of the apps provided patients with feedback.”
The authors wrote that the Lupus Corner Health Manager was “the only one that addresses the majority of the preferences of SLE patients identified in our literature review. This app provides educational material, a symptom and medication tracker, and a discussion group for communicating with others living with lupus – all key features of mHealth technologies in the management of chronic diseases.”
However, they noted that the “ideal mHealth app for patients with SLE would incorporate evidence-based educational material, customizable symptom and medication trackers, logs for personalized health goals, and connectivity with external hardware devices to enrich data collection. Additional useful features would include gamification components to engage users, the provision of tailored feedback based on collected data, and secure mechanisms of communication and data access between users and health care providers to facilitate treatment planning and coordination of care.”
In the systematic literature review, the researchers identified a total of 21 original research studies “related to the development or use of mHealth technologies targeting people of all ages with an SLE diagnosis,” including 2 randomized trials, 10 observational studies, 4 qualitative studies, 3 review articles, and 2 study protocols for future randomized trials.
These papers most often focused on developing and using mHealth for providing patient information (11 papers), followed by mHealth interventions (5); study protocols (2); and developing mHealth apps, websites, or mHealth interventions (3).
Seven studies implemented mHealth technologies, including two with wearable devices, two with text-messaging interventions, and three that used web-based systems. These had mixed results and small samples sizes ranging from 9 to 41 patients, making their interpretation difficult, the authors wrote. A total of 11 studies examined the development of mHealth technologies, including 7 that recognized “the need for more interactive educational platforms with high-quality information,” 2 that described a need for “novel methods of disease monitoring,” and 2 that revealed “a need for sources of support such as virtual communities.”
“Though our systematic literature review found that patients seek to use mHealth technologies to aid with disease management, we identified few studies exploring mHealth-based interventions to improve health outcomes, with the limited published literature devoted to the use of mHealth platforms to provide educational information,” Mr. Dantas and associates wrote.
The lack of evidence for mHealth technologies in SLE patients “contrast with the robust evidence supporting the effectiveness of mHealth interventions in improving outcomes in several chronic conditions,” such as chronic low back and musculoskeletal pain and blood pressure control, they noted.
The authors reported no potential conflicts of interest. The study authors received funding from the Saõ Paulo Research Foundation, the National Center for Complementary and Integrative Health, and the National Center for Advancing Translational Sciences.
SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.
Most mobile apps are poor in quality, review finds.
Most mobile apps are poor in quality, review finds.
and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”
The authors’ review of 19 mHealth apps on Google Play and the Apple App Store (and 1 not on either platform) gave an overall average score of 2.3 out of a possible 5.0 from individual mean scores for engagement, functionality, aesthetics, and information quality on the 23-item Mobile App Rating Scale, each item of which is rated on a 0-5 point scale. Overall, 10 apps offered educational content, 7 offered tools for tracking patient-reported symptoms, 5 offered interactive online communities, 1 offered emojis to share through text messages or email for the purpose of entertainment, and 1 could not be fully evaluated.
The researchers noted that “most apps scored poorly based on design, user interface, functionality, and credibility,” with mean scores of 2.5 for engagement, 2.9 for functionality, 2.2 for aesthetics, and 1.6 for information. “The majority of the apps provided low-quality information from questionable sources (i.e., sources were not cited or their legitimacy was unknown or unverifiable),” they wrote.
The three highest-rated apps – LupusMinder (overall mean score, 3.3), Lupus Corner Health Manager (3.2), and PatientsLikeMe (3.1) – all focused on tracking patient-reported outcomes, but none used validated outcome measures; offered connectivity with wearable devices; or passively collected data such as step count, walking distances, flights climbed, calories expenditure, or sleep monitoring. However, two did have social network components and interactive support groups. Despite these apps’ interactivity and customizability, none offered “features for patients to create and track goals, directly connect with a physician or expert in the field, or synchronize data with electronic health records. None of the apps provided patients with feedback.”
The authors wrote that the Lupus Corner Health Manager was “the only one that addresses the majority of the preferences of SLE patients identified in our literature review. This app provides educational material, a symptom and medication tracker, and a discussion group for communicating with others living with lupus – all key features of mHealth technologies in the management of chronic diseases.”
However, they noted that the “ideal mHealth app for patients with SLE would incorporate evidence-based educational material, customizable symptom and medication trackers, logs for personalized health goals, and connectivity with external hardware devices to enrich data collection. Additional useful features would include gamification components to engage users, the provision of tailored feedback based on collected data, and secure mechanisms of communication and data access between users and health care providers to facilitate treatment planning and coordination of care.”
In the systematic literature review, the researchers identified a total of 21 original research studies “related to the development or use of mHealth technologies targeting people of all ages with an SLE diagnosis,” including 2 randomized trials, 10 observational studies, 4 qualitative studies, 3 review articles, and 2 study protocols for future randomized trials.
These papers most often focused on developing and using mHealth for providing patient information (11 papers), followed by mHealth interventions (5); study protocols (2); and developing mHealth apps, websites, or mHealth interventions (3).
Seven studies implemented mHealth technologies, including two with wearable devices, two with text-messaging interventions, and three that used web-based systems. These had mixed results and small samples sizes ranging from 9 to 41 patients, making their interpretation difficult, the authors wrote. A total of 11 studies examined the development of mHealth technologies, including 7 that recognized “the need for more interactive educational platforms with high-quality information,” 2 that described a need for “novel methods of disease monitoring,” and 2 that revealed “a need for sources of support such as virtual communities.”
“Though our systematic literature review found that patients seek to use mHealth technologies to aid with disease management, we identified few studies exploring mHealth-based interventions to improve health outcomes, with the limited published literature devoted to the use of mHealth platforms to provide educational information,” Mr. Dantas and associates wrote.
The lack of evidence for mHealth technologies in SLE patients “contrast with the robust evidence supporting the effectiveness of mHealth interventions in improving outcomes in several chronic conditions,” such as chronic low back and musculoskeletal pain and blood pressure control, they noted.
The authors reported no potential conflicts of interest. The study authors received funding from the Saõ Paulo Research Foundation, the National Center for Complementary and Integrative Health, and the National Center for Advancing Translational Sciences.
SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.
and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”
The authors’ review of 19 mHealth apps on Google Play and the Apple App Store (and 1 not on either platform) gave an overall average score of 2.3 out of a possible 5.0 from individual mean scores for engagement, functionality, aesthetics, and information quality on the 23-item Mobile App Rating Scale, each item of which is rated on a 0-5 point scale. Overall, 10 apps offered educational content, 7 offered tools for tracking patient-reported symptoms, 5 offered interactive online communities, 1 offered emojis to share through text messages or email for the purpose of entertainment, and 1 could not be fully evaluated.
The researchers noted that “most apps scored poorly based on design, user interface, functionality, and credibility,” with mean scores of 2.5 for engagement, 2.9 for functionality, 2.2 for aesthetics, and 1.6 for information. “The majority of the apps provided low-quality information from questionable sources (i.e., sources were not cited or their legitimacy was unknown or unverifiable),” they wrote.
The three highest-rated apps – LupusMinder (overall mean score, 3.3), Lupus Corner Health Manager (3.2), and PatientsLikeMe (3.1) – all focused on tracking patient-reported outcomes, but none used validated outcome measures; offered connectivity with wearable devices; or passively collected data such as step count, walking distances, flights climbed, calories expenditure, or sleep monitoring. However, two did have social network components and interactive support groups. Despite these apps’ interactivity and customizability, none offered “features for patients to create and track goals, directly connect with a physician or expert in the field, or synchronize data with electronic health records. None of the apps provided patients with feedback.”
The authors wrote that the Lupus Corner Health Manager was “the only one that addresses the majority of the preferences of SLE patients identified in our literature review. This app provides educational material, a symptom and medication tracker, and a discussion group for communicating with others living with lupus – all key features of mHealth technologies in the management of chronic diseases.”
However, they noted that the “ideal mHealth app for patients with SLE would incorporate evidence-based educational material, customizable symptom and medication trackers, logs for personalized health goals, and connectivity with external hardware devices to enrich data collection. Additional useful features would include gamification components to engage users, the provision of tailored feedback based on collected data, and secure mechanisms of communication and data access between users and health care providers to facilitate treatment planning and coordination of care.”
In the systematic literature review, the researchers identified a total of 21 original research studies “related to the development or use of mHealth technologies targeting people of all ages with an SLE diagnosis,” including 2 randomized trials, 10 observational studies, 4 qualitative studies, 3 review articles, and 2 study protocols for future randomized trials.
These papers most often focused on developing and using mHealth for providing patient information (11 papers), followed by mHealth interventions (5); study protocols (2); and developing mHealth apps, websites, or mHealth interventions (3).
Seven studies implemented mHealth technologies, including two with wearable devices, two with text-messaging interventions, and three that used web-based systems. These had mixed results and small samples sizes ranging from 9 to 41 patients, making their interpretation difficult, the authors wrote. A total of 11 studies examined the development of mHealth technologies, including 7 that recognized “the need for more interactive educational platforms with high-quality information,” 2 that described a need for “novel methods of disease monitoring,” and 2 that revealed “a need for sources of support such as virtual communities.”
“Though our systematic literature review found that patients seek to use mHealth technologies to aid with disease management, we identified few studies exploring mHealth-based interventions to improve health outcomes, with the limited published literature devoted to the use of mHealth platforms to provide educational information,” Mr. Dantas and associates wrote.
The lack of evidence for mHealth technologies in SLE patients “contrast with the robust evidence supporting the effectiveness of mHealth interventions in improving outcomes in several chronic conditions,” such as chronic low back and musculoskeletal pain and blood pressure control, they noted.
The authors reported no potential conflicts of interest. The study authors received funding from the Saõ Paulo Research Foundation, the National Center for Complementary and Integrative Health, and the National Center for Advancing Translational Sciences.
SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.
FROM LUPUS