User login
Gut bacterium R. gnavus linked to lupus flares
SAN FRANCISCO –
Not only that, but those patients also had highly elevated antibodies to an endotoxin-like antigen released by one particular R. gnavus strain.
That antigen is “very proinflammatory, very immunogenic. We are wondering if this is actually [what drives] the immune activation that results in immune complexes in the glomeruli” of patients with lupus nephritis, said investigator Gregg Silverman, MD, a professor of medicine and pathology and head of the laboratory of B-cell immunobiology at New York University.
R. gnavus is an obligate anaerobe found in the guts of most people, but in lupus, it might be a problem.
“We are finding a very specific relationship with lupus patients and this bacteria – and this particular antibody,” Dr. Silverman explained in an interview at an international congress on systemic lupus erythematosus. “There’s an expansion of this particular bug, but also a contraction of others” as disease activity progresses.
“It speaks to an imbalance,” he added, and it suggests a role for probiotics or even fecal transplants to restore order.
“What if instead of killing the immune system” in lupus treatment, “we should be reducing or removing a single bacterium or a single molecule?” he asked.
Dr. Silverman is one of many researchers working to unravel the role of the human microbiome in both disease and health. His findings are preliminary, and, as he cautioned, correlation is not causation. But the implications are remarkable, Dr. Silverman noted.
SAN FRANCISCO –
Not only that, but those patients also had highly elevated antibodies to an endotoxin-like antigen released by one particular R. gnavus strain.
That antigen is “very proinflammatory, very immunogenic. We are wondering if this is actually [what drives] the immune activation that results in immune complexes in the glomeruli” of patients with lupus nephritis, said investigator Gregg Silverman, MD, a professor of medicine and pathology and head of the laboratory of B-cell immunobiology at New York University.
R. gnavus is an obligate anaerobe found in the guts of most people, but in lupus, it might be a problem.
“We are finding a very specific relationship with lupus patients and this bacteria – and this particular antibody,” Dr. Silverman explained in an interview at an international congress on systemic lupus erythematosus. “There’s an expansion of this particular bug, but also a contraction of others” as disease activity progresses.
“It speaks to an imbalance,” he added, and it suggests a role for probiotics or even fecal transplants to restore order.
“What if instead of killing the immune system” in lupus treatment, “we should be reducing or removing a single bacterium or a single molecule?” he asked.
Dr. Silverman is one of many researchers working to unravel the role of the human microbiome in both disease and health. His findings are preliminary, and, as he cautioned, correlation is not causation. But the implications are remarkable, Dr. Silverman noted.
SAN FRANCISCO –
Not only that, but those patients also had highly elevated antibodies to an endotoxin-like antigen released by one particular R. gnavus strain.
That antigen is “very proinflammatory, very immunogenic. We are wondering if this is actually [what drives] the immune activation that results in immune complexes in the glomeruli” of patients with lupus nephritis, said investigator Gregg Silverman, MD, a professor of medicine and pathology and head of the laboratory of B-cell immunobiology at New York University.
R. gnavus is an obligate anaerobe found in the guts of most people, but in lupus, it might be a problem.
“We are finding a very specific relationship with lupus patients and this bacteria – and this particular antibody,” Dr. Silverman explained in an interview at an international congress on systemic lupus erythematosus. “There’s an expansion of this particular bug, but also a contraction of others” as disease activity progresses.
“It speaks to an imbalance,” he added, and it suggests a role for probiotics or even fecal transplants to restore order.
“What if instead of killing the immune system” in lupus treatment, “we should be reducing or removing a single bacterium or a single molecule?” he asked.
Dr. Silverman is one of many researchers working to unravel the role of the human microbiome in both disease and health. His findings are preliminary, and, as he cautioned, correlation is not causation. But the implications are remarkable, Dr. Silverman noted.
REPORTING FROM LUPUS 2019
Combo B-cell depletion advances in SLE
SAN FRANCISCO – The sequential combination of rituximab followed directly by maintenance belimumab shows considerable promise as a strategy to address the aberrant B-cell immunology present in systemic lupus erythematosus (SLE) – and thereby improve clinical outcomes, Y.K. Onno Teng, MD, PhD, reported at an international congress on systemic lupus erythematosus.
Dr. Teng, a nephrologist and clinical trialist at Leiden (the Netherlands) University, and his coworkers were pioneers of this one-two punch, in which a two-dose course of rituximab (Rituxan) is given to deplete CD20-positive B-cells, followed by long-term maintenance belimumab (Benlysta) to inhibit repopulation of specific problematic types of B-cells. The rationale for the use of belimumab here lies in the observation that the initial B-cell depletion induced by rituximab triggers a surge in B lymphocyte stimulator (BLyS), which signals the bone marrow to start making more B-cells. And belimumab famously inhibits BLyS, also known as B-cell activating factor, or BAFF.
Dr. Teng presented the 2-year extended results of Synergistic B-cell Immunomodulation in SLE (SYNBIoSe-1), a phase 2a, open-label, single-arm, proof-of-concept study whose 24-week immunologic results have previously been reported (J Autoimmun. 2018 Jul;91:45-54).
Based in part upon the encouraging SYNBIoSe-1 findings as well as the sound mechanistic rationale for this treatment strategy, the combination of rituximab and belimumab is picking up steam in the research world as a potentially important treatment advance in SLE. Currently underway in patients with nonrenal SLE is the phase 3, GlaxoSmithKline-sponsored, global BLISS-BELIEVE trial, as well as the phase 2 BEAT-LUPUS study, a University College London–based randomized trial of rituximab plus either placebo or belimumab. Also, Dr. Teng and his coworkers are now conducting SYNBIoSe-2, in which patients with lupus nephritis are being randomized to standard therapy with glucocorticoids and mycophenolate or to rituximab, belimumab, and mycophenolate.
SYNBIoSe-2 is a further exploration of the encouraging signal of efficacy for lupus nephritis noted in SYNBIoSe-1. Of the 12 participants in SYNBIoSe-1 who had baseline active lupus nephritis, 8 had a positive renal response to the rituximab/belimumab combo, including 6 patients who achieved a prolonged complete renal response through 104 weeks of follow-up.
SYNBIoSe-1 included 15 patients, all with severe refractory SLE as shown by a median 11-year disease duration and a baseline SLE Disease Activity Index score of 18. Two-thirds of patients achieved sustained low-level disease activity, interrupted in one case by a single major disease flare. Two patients stopped treatment because of a lack of response. Several others left the study because they were doing so well on treatment that they decided the time was right to become pregnant.
Immunologically, patients showed an 84% reduction in B-cell repopulation over the course of 2 years. Particularly striking was the long-term inhibition of double-negative B-cells and IgD-positive naive B-cells, which Dr. Teng described as “very trigger happy” in that they readily become transformed into activated antibody-producing cells.
Sustained specific reductions in anti-double-stranded DNA autoantibodies and other pathogenic antinuclear antibodies were also documented through 104 weeks.
SYNBIoSe-1 results at odds with CALIBRATE trial results
The favorable impact of the rituximab/belimumab combo on lupus nephritis seen in SYNBIoSe-1 is at odds with the results of CALIBRATE, a U.S. study in which 43 patients with active lupus nephritis despite conventional treatment were randomized open label to induction therapy with two doses of rituximab on top of standard background therapy, followed by either belimumab and prednisone or prednisone alone. In CALIBRATE, the anti-BLyS biologic didn’t improve clinical outcomes. Dr. Teng said he believes he knows why.
“There was an important difference in background immunosuppression in the two studies. We used mycophenolate in SYNBIoSe-1, while they used cyclophosphamide in CALIBRATE,” he noted. “Other investigators have shown that mycophenolate mostly depletes plasma cells, whereas cyclophosphamide is very much depleting proliferating cells, predominantly the B-cell population and to a lesser extent the plasma cell population. I think this phenomenon might explain why adding BLyS inhibition to patients treated with CellCept [mycophenolate] might be of more added value than adding it to cyclophosphamide therapy.”
Dr. Teng reported having no financial conflicts regarding the SYNBIoSe-1 study, which was funded by research grants from the Dutch Kidney Foundation and the Netherlands Organization for Health Research and Development.
SAN FRANCISCO – The sequential combination of rituximab followed directly by maintenance belimumab shows considerable promise as a strategy to address the aberrant B-cell immunology present in systemic lupus erythematosus (SLE) – and thereby improve clinical outcomes, Y.K. Onno Teng, MD, PhD, reported at an international congress on systemic lupus erythematosus.
Dr. Teng, a nephrologist and clinical trialist at Leiden (the Netherlands) University, and his coworkers were pioneers of this one-two punch, in which a two-dose course of rituximab (Rituxan) is given to deplete CD20-positive B-cells, followed by long-term maintenance belimumab (Benlysta) to inhibit repopulation of specific problematic types of B-cells. The rationale for the use of belimumab here lies in the observation that the initial B-cell depletion induced by rituximab triggers a surge in B lymphocyte stimulator (BLyS), which signals the bone marrow to start making more B-cells. And belimumab famously inhibits BLyS, also known as B-cell activating factor, or BAFF.
Dr. Teng presented the 2-year extended results of Synergistic B-cell Immunomodulation in SLE (SYNBIoSe-1), a phase 2a, open-label, single-arm, proof-of-concept study whose 24-week immunologic results have previously been reported (J Autoimmun. 2018 Jul;91:45-54).
Based in part upon the encouraging SYNBIoSe-1 findings as well as the sound mechanistic rationale for this treatment strategy, the combination of rituximab and belimumab is picking up steam in the research world as a potentially important treatment advance in SLE. Currently underway in patients with nonrenal SLE is the phase 3, GlaxoSmithKline-sponsored, global BLISS-BELIEVE trial, as well as the phase 2 BEAT-LUPUS study, a University College London–based randomized trial of rituximab plus either placebo or belimumab. Also, Dr. Teng and his coworkers are now conducting SYNBIoSe-2, in which patients with lupus nephritis are being randomized to standard therapy with glucocorticoids and mycophenolate or to rituximab, belimumab, and mycophenolate.
SYNBIoSe-2 is a further exploration of the encouraging signal of efficacy for lupus nephritis noted in SYNBIoSe-1. Of the 12 participants in SYNBIoSe-1 who had baseline active lupus nephritis, 8 had a positive renal response to the rituximab/belimumab combo, including 6 patients who achieved a prolonged complete renal response through 104 weeks of follow-up.
SYNBIoSe-1 included 15 patients, all with severe refractory SLE as shown by a median 11-year disease duration and a baseline SLE Disease Activity Index score of 18. Two-thirds of patients achieved sustained low-level disease activity, interrupted in one case by a single major disease flare. Two patients stopped treatment because of a lack of response. Several others left the study because they were doing so well on treatment that they decided the time was right to become pregnant.
Immunologically, patients showed an 84% reduction in B-cell repopulation over the course of 2 years. Particularly striking was the long-term inhibition of double-negative B-cells and IgD-positive naive B-cells, which Dr. Teng described as “very trigger happy” in that they readily become transformed into activated antibody-producing cells.
Sustained specific reductions in anti-double-stranded DNA autoantibodies and other pathogenic antinuclear antibodies were also documented through 104 weeks.
SYNBIoSe-1 results at odds with CALIBRATE trial results
The favorable impact of the rituximab/belimumab combo on lupus nephritis seen in SYNBIoSe-1 is at odds with the results of CALIBRATE, a U.S. study in which 43 patients with active lupus nephritis despite conventional treatment were randomized open label to induction therapy with two doses of rituximab on top of standard background therapy, followed by either belimumab and prednisone or prednisone alone. In CALIBRATE, the anti-BLyS biologic didn’t improve clinical outcomes. Dr. Teng said he believes he knows why.
“There was an important difference in background immunosuppression in the two studies. We used mycophenolate in SYNBIoSe-1, while they used cyclophosphamide in CALIBRATE,” he noted. “Other investigators have shown that mycophenolate mostly depletes plasma cells, whereas cyclophosphamide is very much depleting proliferating cells, predominantly the B-cell population and to a lesser extent the plasma cell population. I think this phenomenon might explain why adding BLyS inhibition to patients treated with CellCept [mycophenolate] might be of more added value than adding it to cyclophosphamide therapy.”
Dr. Teng reported having no financial conflicts regarding the SYNBIoSe-1 study, which was funded by research grants from the Dutch Kidney Foundation and the Netherlands Organization for Health Research and Development.
SAN FRANCISCO – The sequential combination of rituximab followed directly by maintenance belimumab shows considerable promise as a strategy to address the aberrant B-cell immunology present in systemic lupus erythematosus (SLE) – and thereby improve clinical outcomes, Y.K. Onno Teng, MD, PhD, reported at an international congress on systemic lupus erythematosus.
Dr. Teng, a nephrologist and clinical trialist at Leiden (the Netherlands) University, and his coworkers were pioneers of this one-two punch, in which a two-dose course of rituximab (Rituxan) is given to deplete CD20-positive B-cells, followed by long-term maintenance belimumab (Benlysta) to inhibit repopulation of specific problematic types of B-cells. The rationale for the use of belimumab here lies in the observation that the initial B-cell depletion induced by rituximab triggers a surge in B lymphocyte stimulator (BLyS), which signals the bone marrow to start making more B-cells. And belimumab famously inhibits BLyS, also known as B-cell activating factor, or BAFF.
Dr. Teng presented the 2-year extended results of Synergistic B-cell Immunomodulation in SLE (SYNBIoSe-1), a phase 2a, open-label, single-arm, proof-of-concept study whose 24-week immunologic results have previously been reported (J Autoimmun. 2018 Jul;91:45-54).
Based in part upon the encouraging SYNBIoSe-1 findings as well as the sound mechanistic rationale for this treatment strategy, the combination of rituximab and belimumab is picking up steam in the research world as a potentially important treatment advance in SLE. Currently underway in patients with nonrenal SLE is the phase 3, GlaxoSmithKline-sponsored, global BLISS-BELIEVE trial, as well as the phase 2 BEAT-LUPUS study, a University College London–based randomized trial of rituximab plus either placebo or belimumab. Also, Dr. Teng and his coworkers are now conducting SYNBIoSe-2, in which patients with lupus nephritis are being randomized to standard therapy with glucocorticoids and mycophenolate or to rituximab, belimumab, and mycophenolate.
SYNBIoSe-2 is a further exploration of the encouraging signal of efficacy for lupus nephritis noted in SYNBIoSe-1. Of the 12 participants in SYNBIoSe-1 who had baseline active lupus nephritis, 8 had a positive renal response to the rituximab/belimumab combo, including 6 patients who achieved a prolonged complete renal response through 104 weeks of follow-up.
SYNBIoSe-1 included 15 patients, all with severe refractory SLE as shown by a median 11-year disease duration and a baseline SLE Disease Activity Index score of 18. Two-thirds of patients achieved sustained low-level disease activity, interrupted in one case by a single major disease flare. Two patients stopped treatment because of a lack of response. Several others left the study because they were doing so well on treatment that they decided the time was right to become pregnant.
Immunologically, patients showed an 84% reduction in B-cell repopulation over the course of 2 years. Particularly striking was the long-term inhibition of double-negative B-cells and IgD-positive naive B-cells, which Dr. Teng described as “very trigger happy” in that they readily become transformed into activated antibody-producing cells.
Sustained specific reductions in anti-double-stranded DNA autoantibodies and other pathogenic antinuclear antibodies were also documented through 104 weeks.
SYNBIoSe-1 results at odds with CALIBRATE trial results
The favorable impact of the rituximab/belimumab combo on lupus nephritis seen in SYNBIoSe-1 is at odds with the results of CALIBRATE, a U.S. study in which 43 patients with active lupus nephritis despite conventional treatment were randomized open label to induction therapy with two doses of rituximab on top of standard background therapy, followed by either belimumab and prednisone or prednisone alone. In CALIBRATE, the anti-BLyS biologic didn’t improve clinical outcomes. Dr. Teng said he believes he knows why.
“There was an important difference in background immunosuppression in the two studies. We used mycophenolate in SYNBIoSe-1, while they used cyclophosphamide in CALIBRATE,” he noted. “Other investigators have shown that mycophenolate mostly depletes plasma cells, whereas cyclophosphamide is very much depleting proliferating cells, predominantly the B-cell population and to a lesser extent the plasma cell population. I think this phenomenon might explain why adding BLyS inhibition to patients treated with CellCept [mycophenolate] might be of more added value than adding it to cyclophosphamide therapy.”
Dr. Teng reported having no financial conflicts regarding the SYNBIoSe-1 study, which was funded by research grants from the Dutch Kidney Foundation and the Netherlands Organization for Health Research and Development.
REPORTING FROM LUPUS 2019
Hydroxychloroquine adherence in SLE: worse than you thought
SAN FRANCISCO – Routine office measurement of hydroxychloroquine blood levels in systemic lupus erythematosus (SLE) patients accomplishes two major objectives, Nathalie Costedoat-Chalumeau, MD, asserted at an international congress on systemic lupus erythematosus.
First, measuring hydroxychloroquine levels identifies the surprisingly large number of individuals who are severely nonadherent to this cornerstone of lupus therapy despite its excellent benefit/risk ratio. Also, serial measurements coupled with brief counseling have been shown to boost poor adherence rates, noted Dr. Costedoat-Chalumeau, professor of rheumatology at Paris Descartes University.
Numerous studies have documented startlingly low adherence to hydroxychloroquine among SLE patients. Some of the same studies show prescribing physicians are often clueless as to their patients’ adherence or lack thereof.
Just how bad is the adherence problem? A recent study of 10,406 Medicaid patients with SLE who started on hydroxychloroquine showed that 85% of them were nonadherent as defined by pharmacy refill data, indicating insufficient medication on hand to cover a minimum of 80% of days during at least 1 year of follow-up.
In a novel finding, the investigators also broke down the Medicaid data month by month and identified four broad patterns of adherence/nonadherence. A total of 17% of patients were persistently adherent throughout the first year after the drug was dispensed. Another 36% were persistent nonadherers right from the get-go. A further 24% remained partially adherent, dropping down to a plateau of 30%-40% monthly adherence after the first couple of months and staying there. And 23% dropped steadily from roughly 50% adherence at month 3 to nearly total nonadherence from month 9 onward. Overall, adherence in the Medicaid cohort declined over the course of the first year (Semin Arthritis Rheum. 2018 Oct;48[2]:205-13).
Dr. Costedoat-Chalumeau was the lead investigator in a large French multicenter clinical trial known as the PLUS Study, which established that increasing the hydroxychloroquine daily dose to raise blood levels to a target of at least 1,000 ng/mL didn’t reduce the risk of flares (Ann Rheum Dis. 2013;72[11]:1786-92).
“So there is no reason to use blood drug measurements to adjust hydroxychloroquine daily dose or blood levels to prevent SLE flares. But drug levels teach us something regarding adherence,” she said.
Why routinely measuring hydroxychloroquine levels matters
Dr. Costedoat-Chalumeau and other investigators have shown that whole blood drug levels below 200 ng/mL indicate a patient is severely nonadherent. In various studies, that’s 7%-29% of SLE patients who are supposedly on hydroxychloroquine.
Also, investigators at Johns Hopkins University, Baltimore, have analyzed prospective data from the Hopkins Lupus Cohort and determined that at the first clinic visit after going on a maximum of 400 mg/day of hydroxychloroquine, only 44% of participants had a blood drug level above the 500-ng/mL threshold indicative of adherence.
Importantly, however, the Hopkins researchers also demonstrated that with repeated brief counseling of nonadherent patients as to why hydroxychloroquine is the most important medication they take for their SLE, adherence climbed in stepwise fashion with each visit in which the drug blood level was assessed: With no prior measurement, adherence was 56%; with one prior measurement, it jumped to 69%; with two, 77% of patients were adherent to hydroxychloroquine; and with three or more prior blood level checks, adherence rose to 80% (J Rheumatol. 2015 Nov;42[11]:2092-7).
It is well established that hydroxychloroquine prevents SLE flares, protects against thrombotic events, diabetes, dyslipidemia, and lupus-induced organ damage, and improves survival. Dr. Costedoat-Chalumeau’s final words on hydroxychloroquine adherence: ”Drugs don’t work in people who don’t take them.”
She reported having no financial conflicts regarding her presentation.
SAN FRANCISCO – Routine office measurement of hydroxychloroquine blood levels in systemic lupus erythematosus (SLE) patients accomplishes two major objectives, Nathalie Costedoat-Chalumeau, MD, asserted at an international congress on systemic lupus erythematosus.
First, measuring hydroxychloroquine levels identifies the surprisingly large number of individuals who are severely nonadherent to this cornerstone of lupus therapy despite its excellent benefit/risk ratio. Also, serial measurements coupled with brief counseling have been shown to boost poor adherence rates, noted Dr. Costedoat-Chalumeau, professor of rheumatology at Paris Descartes University.
Numerous studies have documented startlingly low adherence to hydroxychloroquine among SLE patients. Some of the same studies show prescribing physicians are often clueless as to their patients’ adherence or lack thereof.
Just how bad is the adherence problem? A recent study of 10,406 Medicaid patients with SLE who started on hydroxychloroquine showed that 85% of them were nonadherent as defined by pharmacy refill data, indicating insufficient medication on hand to cover a minimum of 80% of days during at least 1 year of follow-up.
In a novel finding, the investigators also broke down the Medicaid data month by month and identified four broad patterns of adherence/nonadherence. A total of 17% of patients were persistently adherent throughout the first year after the drug was dispensed. Another 36% were persistent nonadherers right from the get-go. A further 24% remained partially adherent, dropping down to a plateau of 30%-40% monthly adherence after the first couple of months and staying there. And 23% dropped steadily from roughly 50% adherence at month 3 to nearly total nonadherence from month 9 onward. Overall, adherence in the Medicaid cohort declined over the course of the first year (Semin Arthritis Rheum. 2018 Oct;48[2]:205-13).
Dr. Costedoat-Chalumeau was the lead investigator in a large French multicenter clinical trial known as the PLUS Study, which established that increasing the hydroxychloroquine daily dose to raise blood levels to a target of at least 1,000 ng/mL didn’t reduce the risk of flares (Ann Rheum Dis. 2013;72[11]:1786-92).
“So there is no reason to use blood drug measurements to adjust hydroxychloroquine daily dose or blood levels to prevent SLE flares. But drug levels teach us something regarding adherence,” she said.
Why routinely measuring hydroxychloroquine levels matters
Dr. Costedoat-Chalumeau and other investigators have shown that whole blood drug levels below 200 ng/mL indicate a patient is severely nonadherent. In various studies, that’s 7%-29% of SLE patients who are supposedly on hydroxychloroquine.
Also, investigators at Johns Hopkins University, Baltimore, have analyzed prospective data from the Hopkins Lupus Cohort and determined that at the first clinic visit after going on a maximum of 400 mg/day of hydroxychloroquine, only 44% of participants had a blood drug level above the 500-ng/mL threshold indicative of adherence.
Importantly, however, the Hopkins researchers also demonstrated that with repeated brief counseling of nonadherent patients as to why hydroxychloroquine is the most important medication they take for their SLE, adherence climbed in stepwise fashion with each visit in which the drug blood level was assessed: With no prior measurement, adherence was 56%; with one prior measurement, it jumped to 69%; with two, 77% of patients were adherent to hydroxychloroquine; and with three or more prior blood level checks, adherence rose to 80% (J Rheumatol. 2015 Nov;42[11]:2092-7).
It is well established that hydroxychloroquine prevents SLE flares, protects against thrombotic events, diabetes, dyslipidemia, and lupus-induced organ damage, and improves survival. Dr. Costedoat-Chalumeau’s final words on hydroxychloroquine adherence: ”Drugs don’t work in people who don’t take them.”
She reported having no financial conflicts regarding her presentation.
SAN FRANCISCO – Routine office measurement of hydroxychloroquine blood levels in systemic lupus erythematosus (SLE) patients accomplishes two major objectives, Nathalie Costedoat-Chalumeau, MD, asserted at an international congress on systemic lupus erythematosus.
First, measuring hydroxychloroquine levels identifies the surprisingly large number of individuals who are severely nonadherent to this cornerstone of lupus therapy despite its excellent benefit/risk ratio. Also, serial measurements coupled with brief counseling have been shown to boost poor adherence rates, noted Dr. Costedoat-Chalumeau, professor of rheumatology at Paris Descartes University.
Numerous studies have documented startlingly low adherence to hydroxychloroquine among SLE patients. Some of the same studies show prescribing physicians are often clueless as to their patients’ adherence or lack thereof.
Just how bad is the adherence problem? A recent study of 10,406 Medicaid patients with SLE who started on hydroxychloroquine showed that 85% of them were nonadherent as defined by pharmacy refill data, indicating insufficient medication on hand to cover a minimum of 80% of days during at least 1 year of follow-up.
In a novel finding, the investigators also broke down the Medicaid data month by month and identified four broad patterns of adherence/nonadherence. A total of 17% of patients were persistently adherent throughout the first year after the drug was dispensed. Another 36% were persistent nonadherers right from the get-go. A further 24% remained partially adherent, dropping down to a plateau of 30%-40% monthly adherence after the first couple of months and staying there. And 23% dropped steadily from roughly 50% adherence at month 3 to nearly total nonadherence from month 9 onward. Overall, adherence in the Medicaid cohort declined over the course of the first year (Semin Arthritis Rheum. 2018 Oct;48[2]:205-13).
Dr. Costedoat-Chalumeau was the lead investigator in a large French multicenter clinical trial known as the PLUS Study, which established that increasing the hydroxychloroquine daily dose to raise blood levels to a target of at least 1,000 ng/mL didn’t reduce the risk of flares (Ann Rheum Dis. 2013;72[11]:1786-92).
“So there is no reason to use blood drug measurements to adjust hydroxychloroquine daily dose or blood levels to prevent SLE flares. But drug levels teach us something regarding adherence,” she said.
Why routinely measuring hydroxychloroquine levels matters
Dr. Costedoat-Chalumeau and other investigators have shown that whole blood drug levels below 200 ng/mL indicate a patient is severely nonadherent. In various studies, that’s 7%-29% of SLE patients who are supposedly on hydroxychloroquine.
Also, investigators at Johns Hopkins University, Baltimore, have analyzed prospective data from the Hopkins Lupus Cohort and determined that at the first clinic visit after going on a maximum of 400 mg/day of hydroxychloroquine, only 44% of participants had a blood drug level above the 500-ng/mL threshold indicative of adherence.
Importantly, however, the Hopkins researchers also demonstrated that with repeated brief counseling of nonadherent patients as to why hydroxychloroquine is the most important medication they take for their SLE, adherence climbed in stepwise fashion with each visit in which the drug blood level was assessed: With no prior measurement, adherence was 56%; with one prior measurement, it jumped to 69%; with two, 77% of patients were adherent to hydroxychloroquine; and with three or more prior blood level checks, adherence rose to 80% (J Rheumatol. 2015 Nov;42[11]:2092-7).
It is well established that hydroxychloroquine prevents SLE flares, protects against thrombotic events, diabetes, dyslipidemia, and lupus-induced organ damage, and improves survival. Dr. Costedoat-Chalumeau’s final words on hydroxychloroquine adherence: ”Drugs don’t work in people who don’t take them.”
She reported having no financial conflicts regarding her presentation.
REPORTING FROM LUPUS 2019
‘Type II’ SLE assessment catches what matters to patients
SAN FRANCISCO – For almost a year, lupus patients at Duke University in Durham, N.C., have been getting two physician global assessments, the usual one for classic “type I” disease, and a new one for nonspecific “type II” symptoms: fatigue, widespread pain, depression, sleep disturbance, and cognitive dysfunction.
It’s often the type II problems that affect patients the most, and what they are most concerned about; formally assessing them with the type II physician global assessment (PGA) – a 0- to 3-point visual analog scale – ensures they aren’t overlooked, said Jennifer Rogers, MD, assistant professor of rheumatology at Duke.
It “forces us to address these symptoms,” she said, and the approach seems to be working, according to a study Dr. Rogers presented at an international congress on systemic lupus erythematosus.
In the 5 months leading up to implementation of the PGA II in late spring 2018, type II problems had treatment recommendations in patients’ charts just 53% of the time; the number rose to 89% of the time during the PGA II’s first 5 months (P = .03). Type II PGA scores correlated strongly with patient-reported fibromyalgia and depression symptoms, but did not correlate with PGA scores for type I symptoms, such as nephritis and arthritis.
Type II problems are common in lupus. Patients’ joints might be fine, and their kidney disease in remission, but they can still feel miserable, and will often blame it on a lupus flare. Physicians who disagree end up at odds with their patients, Dr. Rogers explained.
“We decided to rethink how we address these patients, and came up with this new type I, type II categorization.” Now, when paints complain of brain fog, for example, “I say ‘yes, this is your lupus. I believe you,’ but we don’t need to give you more steroids or very expensive immunosuppressives for this. What you need to do is take your Cymbalta, work on your exercise, and maybe see your therapist,” she said.
It validates what people are going through, and builds trust. “Patients like it; they feel heard, and I walk out of the room, and I feel better,” she said.
During its first 5 months, 197 patients had PGAs for type II symptoms, along with type I PGAs. The average age of the patients was 46 years, and 92% were women.
Patients with predominately type II symptoms were more likely than were those with predominately type I disease to be depressed (84% versus 39%), and they reported higher lupus activity, greater symptom severity, and more severe fibromyalgia. The differences were statistically significant.
Type II treatments included medications in 60% of cases, exercise or physical therapy in almost 60% of cases, sleep studies or help with sleep hygiene in about 35%, and psychiatric or psychological referral in almost 20%. Less than 5% of patients were referred to a pain clinic.
There was no external funding for the study, and Dr. Rogers didn’t have any disclosures.
SOURCE: Rogers J et al. Lupus Sci Med. 2019;6[suppl 1]: Abstract 102. doi: 10.1136/lupus-2019-lsm.102
SAN FRANCISCO – For almost a year, lupus patients at Duke University in Durham, N.C., have been getting two physician global assessments, the usual one for classic “type I” disease, and a new one for nonspecific “type II” symptoms: fatigue, widespread pain, depression, sleep disturbance, and cognitive dysfunction.
It’s often the type II problems that affect patients the most, and what they are most concerned about; formally assessing them with the type II physician global assessment (PGA) – a 0- to 3-point visual analog scale – ensures they aren’t overlooked, said Jennifer Rogers, MD, assistant professor of rheumatology at Duke.
It “forces us to address these symptoms,” she said, and the approach seems to be working, according to a study Dr. Rogers presented at an international congress on systemic lupus erythematosus.
In the 5 months leading up to implementation of the PGA II in late spring 2018, type II problems had treatment recommendations in patients’ charts just 53% of the time; the number rose to 89% of the time during the PGA II’s first 5 months (P = .03). Type II PGA scores correlated strongly with patient-reported fibromyalgia and depression symptoms, but did not correlate with PGA scores for type I symptoms, such as nephritis and arthritis.
Type II problems are common in lupus. Patients’ joints might be fine, and their kidney disease in remission, but they can still feel miserable, and will often blame it on a lupus flare. Physicians who disagree end up at odds with their patients, Dr. Rogers explained.
“We decided to rethink how we address these patients, and came up with this new type I, type II categorization.” Now, when paints complain of brain fog, for example, “I say ‘yes, this is your lupus. I believe you,’ but we don’t need to give you more steroids or very expensive immunosuppressives for this. What you need to do is take your Cymbalta, work on your exercise, and maybe see your therapist,” she said.
It validates what people are going through, and builds trust. “Patients like it; they feel heard, and I walk out of the room, and I feel better,” she said.
During its first 5 months, 197 patients had PGAs for type II symptoms, along with type I PGAs. The average age of the patients was 46 years, and 92% were women.
Patients with predominately type II symptoms were more likely than were those with predominately type I disease to be depressed (84% versus 39%), and they reported higher lupus activity, greater symptom severity, and more severe fibromyalgia. The differences were statistically significant.
Type II treatments included medications in 60% of cases, exercise or physical therapy in almost 60% of cases, sleep studies or help with sleep hygiene in about 35%, and psychiatric or psychological referral in almost 20%. Less than 5% of patients were referred to a pain clinic.
There was no external funding for the study, and Dr. Rogers didn’t have any disclosures.
SOURCE: Rogers J et al. Lupus Sci Med. 2019;6[suppl 1]: Abstract 102. doi: 10.1136/lupus-2019-lsm.102
SAN FRANCISCO – For almost a year, lupus patients at Duke University in Durham, N.C., have been getting two physician global assessments, the usual one for classic “type I” disease, and a new one for nonspecific “type II” symptoms: fatigue, widespread pain, depression, sleep disturbance, and cognitive dysfunction.
It’s often the type II problems that affect patients the most, and what they are most concerned about; formally assessing them with the type II physician global assessment (PGA) – a 0- to 3-point visual analog scale – ensures they aren’t overlooked, said Jennifer Rogers, MD, assistant professor of rheumatology at Duke.
It “forces us to address these symptoms,” she said, and the approach seems to be working, according to a study Dr. Rogers presented at an international congress on systemic lupus erythematosus.
In the 5 months leading up to implementation of the PGA II in late spring 2018, type II problems had treatment recommendations in patients’ charts just 53% of the time; the number rose to 89% of the time during the PGA II’s first 5 months (P = .03). Type II PGA scores correlated strongly with patient-reported fibromyalgia and depression symptoms, but did not correlate with PGA scores for type I symptoms, such as nephritis and arthritis.
Type II problems are common in lupus. Patients’ joints might be fine, and their kidney disease in remission, but they can still feel miserable, and will often blame it on a lupus flare. Physicians who disagree end up at odds with their patients, Dr. Rogers explained.
“We decided to rethink how we address these patients, and came up with this new type I, type II categorization.” Now, when paints complain of brain fog, for example, “I say ‘yes, this is your lupus. I believe you,’ but we don’t need to give you more steroids or very expensive immunosuppressives for this. What you need to do is take your Cymbalta, work on your exercise, and maybe see your therapist,” she said.
It validates what people are going through, and builds trust. “Patients like it; they feel heard, and I walk out of the room, and I feel better,” she said.
During its first 5 months, 197 patients had PGAs for type II symptoms, along with type I PGAs. The average age of the patients was 46 years, and 92% were women.
Patients with predominately type II symptoms were more likely than were those with predominately type I disease to be depressed (84% versus 39%), and they reported higher lupus activity, greater symptom severity, and more severe fibromyalgia. The differences were statistically significant.
Type II treatments included medications in 60% of cases, exercise or physical therapy in almost 60% of cases, sleep studies or help with sleep hygiene in about 35%, and psychiatric or psychological referral in almost 20%. Less than 5% of patients were referred to a pain clinic.
There was no external funding for the study, and Dr. Rogers didn’t have any disclosures.
SOURCE: Rogers J et al. Lupus Sci Med. 2019;6[suppl 1]: Abstract 102. doi: 10.1136/lupus-2019-lsm.102
AT LUPUS 2019
Low-dose IL-2 found effective in SLE
SAN FRANCISCO – , according to the first randomized, double-blind, placebo-controlled clinical trial of the novel therapy.
Of note, more than half of the study participants with lupus nephritis experienced complete remission of their renal impairment, and another quarter had partial remission, Jing He, MD, PhD, reported at an international congress on systemic lupus erythematosus.
The mechanism of benefit appears to be the same as previously shown for low-dose interleukin-2 in patients with chronic graft versus host disease refractory to glucocorticoids (N Engl J Med. 2011 Dec 1;365[22]:2055-66): expansion of the deficient population of T regulatory cells, which is a hallmark of both inflammatory diseases.
“Low-dose IL-2 can reinstate the imbalance of T regulatory/T effector cells and improve immune homeostasis, which is critical in clinical remission of SLE,” said Dr. He of Peking University People’s Hospital in Beijing.
For nearly 20 years it has been known that SLE is characterized by very low levels of endogenous IL-2. Dr. He was lead author of the first proof-of-concept study, which showed low-dose subcutaneous IL-2 therapy resulted in markedly reduced SLE disease activity accompanied by expansion of the T regulatory cell population and suppression of follicular helper T cells and IL-17–producing helper T cells (Nat Med. 2016 Sep;22[9]:991-3). However, that was a small, single-center, uncontrolled study, so she and her coworkers have now carried out a 60-patient, double-blind, placebo-controlled randomized trial. In addition to hydroxychloroquine and other standard background medications, the patients in the active treatment arm received 1 million IU of IL-2 every other day for 2 weeks, followed by a 2-week hiatus, for a total of three courses.
At week 24 – 12 weeks after the last injection – the IL-2 recipients showed significantly greater improvement on numerous endpoints.
For example, the median SLE Disease Activity Index (SLEDAI) in the IL-2 group improved from 12 at baseline to 6 at week 12 and to 4 at week 24.
The marked improvement in renal impairment in the IL-2 recipients with lupus nephritis at baseline was accompanied by a significant increase in serum albumin and reduced 24-hour urinary protein, compared with controls.
The treatment was safe, with no increase in infections, severe or otherwise, and indeed with no serious adverse events of any kind, although nine patients in the IL-2 group experienced mild injection site reactions and three developed flu-like symptoms.
Dr. He reported having no financial conflicts regarding her study.
SAN FRANCISCO – , according to the first randomized, double-blind, placebo-controlled clinical trial of the novel therapy.
Of note, more than half of the study participants with lupus nephritis experienced complete remission of their renal impairment, and another quarter had partial remission, Jing He, MD, PhD, reported at an international congress on systemic lupus erythematosus.
The mechanism of benefit appears to be the same as previously shown for low-dose interleukin-2 in patients with chronic graft versus host disease refractory to glucocorticoids (N Engl J Med. 2011 Dec 1;365[22]:2055-66): expansion of the deficient population of T regulatory cells, which is a hallmark of both inflammatory diseases.
“Low-dose IL-2 can reinstate the imbalance of T regulatory/T effector cells and improve immune homeostasis, which is critical in clinical remission of SLE,” said Dr. He of Peking University People’s Hospital in Beijing.
For nearly 20 years it has been known that SLE is characterized by very low levels of endogenous IL-2. Dr. He was lead author of the first proof-of-concept study, which showed low-dose subcutaneous IL-2 therapy resulted in markedly reduced SLE disease activity accompanied by expansion of the T regulatory cell population and suppression of follicular helper T cells and IL-17–producing helper T cells (Nat Med. 2016 Sep;22[9]:991-3). However, that was a small, single-center, uncontrolled study, so she and her coworkers have now carried out a 60-patient, double-blind, placebo-controlled randomized trial. In addition to hydroxychloroquine and other standard background medications, the patients in the active treatment arm received 1 million IU of IL-2 every other day for 2 weeks, followed by a 2-week hiatus, for a total of three courses.
At week 24 – 12 weeks after the last injection – the IL-2 recipients showed significantly greater improvement on numerous endpoints.
For example, the median SLE Disease Activity Index (SLEDAI) in the IL-2 group improved from 12 at baseline to 6 at week 12 and to 4 at week 24.
The marked improvement in renal impairment in the IL-2 recipients with lupus nephritis at baseline was accompanied by a significant increase in serum albumin and reduced 24-hour urinary protein, compared with controls.
The treatment was safe, with no increase in infections, severe or otherwise, and indeed with no serious adverse events of any kind, although nine patients in the IL-2 group experienced mild injection site reactions and three developed flu-like symptoms.
Dr. He reported having no financial conflicts regarding her study.
SAN FRANCISCO – , according to the first randomized, double-blind, placebo-controlled clinical trial of the novel therapy.
Of note, more than half of the study participants with lupus nephritis experienced complete remission of their renal impairment, and another quarter had partial remission, Jing He, MD, PhD, reported at an international congress on systemic lupus erythematosus.
The mechanism of benefit appears to be the same as previously shown for low-dose interleukin-2 in patients with chronic graft versus host disease refractory to glucocorticoids (N Engl J Med. 2011 Dec 1;365[22]:2055-66): expansion of the deficient population of T regulatory cells, which is a hallmark of both inflammatory diseases.
“Low-dose IL-2 can reinstate the imbalance of T regulatory/T effector cells and improve immune homeostasis, which is critical in clinical remission of SLE,” said Dr. He of Peking University People’s Hospital in Beijing.
For nearly 20 years it has been known that SLE is characterized by very low levels of endogenous IL-2. Dr. He was lead author of the first proof-of-concept study, which showed low-dose subcutaneous IL-2 therapy resulted in markedly reduced SLE disease activity accompanied by expansion of the T regulatory cell population and suppression of follicular helper T cells and IL-17–producing helper T cells (Nat Med. 2016 Sep;22[9]:991-3). However, that was a small, single-center, uncontrolled study, so she and her coworkers have now carried out a 60-patient, double-blind, placebo-controlled randomized trial. In addition to hydroxychloroquine and other standard background medications, the patients in the active treatment arm received 1 million IU of IL-2 every other day for 2 weeks, followed by a 2-week hiatus, for a total of three courses.
At week 24 – 12 weeks after the last injection – the IL-2 recipients showed significantly greater improvement on numerous endpoints.
For example, the median SLE Disease Activity Index (SLEDAI) in the IL-2 group improved from 12 at baseline to 6 at week 12 and to 4 at week 24.
The marked improvement in renal impairment in the IL-2 recipients with lupus nephritis at baseline was accompanied by a significant increase in serum albumin and reduced 24-hour urinary protein, compared with controls.
The treatment was safe, with no increase in infections, severe or otherwise, and indeed with no serious adverse events of any kind, although nine patients in the IL-2 group experienced mild injection site reactions and three developed flu-like symptoms.
Dr. He reported having no financial conflicts regarding her study.
REPORTING FROM LUPUS 2019
LUPUS 2019 Congress: Top takeaways
Join us at #MDedgeChats on Tuesday, April 23, 2019, at 7:00 pm EST, for a Twitter discussion in Rheumatology on some of the top studies reported at the LUPUS 2019 Congress in San Francisco, April 5-8. Our special guests are two rheumatologists with expertise in lupus who attended the congress, Jinoos Yazdany, MD, and Gabriela Schmajuk, MD, both with the University of California, San Francisco. They will discuss the ins and outs of the study results presented.
We hope you can join us and invite a colleague, too.
We will discuss the results of the EMBRACE trial, which looks at the efficacy and safety of belimumab (Benlysta) in black patients with systemic lupus erythematosus (SLE); these patients have a higher prevalence of SLE and often higher disease severity but have been poorly represented in past belimumab studies.
We will also chat about the results of a phase 2 trial of baricitinib (Olumiant) in SLE patients.
Finally, we will look at the clinical utility of monitoring hydroxychloroquine levels in SLE patients and how well levels of the drug correlate with disease activity through the results of a meta-analysis of studies that examined these questions.
Topics of conversation
Q1: How does the methodology of the EMBRACE trial differ from past phase 3 belimumab trials?
Q2: How does the EMBRACE trial affect the way you prescribe belimumab?
Q3: Does the hydroxychloroquine level meta-analysis provide persuasive enough evidence to begin measuring it?
Q4: What kinds of interventions show the best evidence for improving hydroxychloroquine adherence?
Q5: Were concerns about the safety of baricitinib in SLE patients reduced by the trial results?
Resources
EMBRACE trial: Efficacy and Safety of Belimumab in Black Race Patients with Systemic Lupus Erythematosus.
LUPUS 2019 abstract | ClinicalTrials.gov listing
Phase 2 trial of baricitinib in SLE.
LUPUS 2019 abstract | ClinicalTrials.gov listing
Meta-analysis examining the clinical significance of monitoring of hydroxychloroquine levels in SLE.
LUPUS 2019 abstract
From LUPUS 2019:
Belimumab a bust for black SLE patients.
Here’s a top strategy for immunosuppressant discontinuation in SLE.
From EULAR 2018:
Baricitinib shows potential as lupus treatment.
About Dr. Yazdany
Dr. Yazdany is an associate professor in the division of rheumatology, department of medicine at UCSF (@UCSFMedicine). She is a rheumatologist and clinical researcher with expertise in systemic lupus erythematosus and health care quality measurement and improvement. Her clinical activities include seeing patients in the UCSF Lupus Clinic, where she serves as codirector, as well as at San Francisco General Hospital. Dr. Yazdany codirects the Quality and Informatics Lab (quil.ucsf.edu), which uses data to drive improvements in health care delivery and outcomes for people with rheumatic diseases. She also leads ongoing, longitudinal studies of lupus that are investigating health disparities and outcomes in the condition.
About Dr. Schmajuk
Dr. Schmajuk is an Associate Professor in the Division of Rheumatology, Department of Medicine at UCSF (@UCSFMedicine) and the San Francisco VA Medical Center. She is a rheumatologist and clinical researcher with expertise in systemic #lupus erythematosus, quality of care, and patient safety. Dr. Schmajuk also co-directs the Quality and Informatics Lab (quil.ucsf.edu), which uses data to drive improvements in health care delivery and outcomes for people with rheumatic diseases. She leads studies to develop patient-facing disease dashboards with the goal of improving patient-provider communication for patients with RA and SLE.
Are you new to Twitter chats? We have included simple steps below to help you join and participate in the conversation.
Join us at #MDedgeChats on Tuesday, April 23, 2019, at 7:00 pm EST, for a Twitter discussion in Rheumatology on some of the top studies reported at the LUPUS 2019 Congress in San Francisco, April 5-8. Our special guests are two rheumatologists with expertise in lupus who attended the congress, Jinoos Yazdany, MD, and Gabriela Schmajuk, MD, both with the University of California, San Francisco. They will discuss the ins and outs of the study results presented.
We hope you can join us and invite a colleague, too.
We will discuss the results of the EMBRACE trial, which looks at the efficacy and safety of belimumab (Benlysta) in black patients with systemic lupus erythematosus (SLE); these patients have a higher prevalence of SLE and often higher disease severity but have been poorly represented in past belimumab studies.
We will also chat about the results of a phase 2 trial of baricitinib (Olumiant) in SLE patients.
Finally, we will look at the clinical utility of monitoring hydroxychloroquine levels in SLE patients and how well levels of the drug correlate with disease activity through the results of a meta-analysis of studies that examined these questions.
Topics of conversation
Q1: How does the methodology of the EMBRACE trial differ from past phase 3 belimumab trials?
Q2: How does the EMBRACE trial affect the way you prescribe belimumab?
Q3: Does the hydroxychloroquine level meta-analysis provide persuasive enough evidence to begin measuring it?
Q4: What kinds of interventions show the best evidence for improving hydroxychloroquine adherence?
Q5: Were concerns about the safety of baricitinib in SLE patients reduced by the trial results?
Resources
EMBRACE trial: Efficacy and Safety of Belimumab in Black Race Patients with Systemic Lupus Erythematosus.
LUPUS 2019 abstract | ClinicalTrials.gov listing
Phase 2 trial of baricitinib in SLE.
LUPUS 2019 abstract | ClinicalTrials.gov listing
Meta-analysis examining the clinical significance of monitoring of hydroxychloroquine levels in SLE.
LUPUS 2019 abstract
From LUPUS 2019:
Belimumab a bust for black SLE patients.
Here’s a top strategy for immunosuppressant discontinuation in SLE.
From EULAR 2018:
Baricitinib shows potential as lupus treatment.
About Dr. Yazdany
Dr. Yazdany is an associate professor in the division of rheumatology, department of medicine at UCSF (@UCSFMedicine). She is a rheumatologist and clinical researcher with expertise in systemic lupus erythematosus and health care quality measurement and improvement. Her clinical activities include seeing patients in the UCSF Lupus Clinic, where she serves as codirector, as well as at San Francisco General Hospital. Dr. Yazdany codirects the Quality and Informatics Lab (quil.ucsf.edu), which uses data to drive improvements in health care delivery and outcomes for people with rheumatic diseases. She also leads ongoing, longitudinal studies of lupus that are investigating health disparities and outcomes in the condition.
About Dr. Schmajuk
Dr. Schmajuk is an Associate Professor in the Division of Rheumatology, Department of Medicine at UCSF (@UCSFMedicine) and the San Francisco VA Medical Center. She is a rheumatologist and clinical researcher with expertise in systemic #lupus erythematosus, quality of care, and patient safety. Dr. Schmajuk also co-directs the Quality and Informatics Lab (quil.ucsf.edu), which uses data to drive improvements in health care delivery and outcomes for people with rheumatic diseases. She leads studies to develop patient-facing disease dashboards with the goal of improving patient-provider communication for patients with RA and SLE.
Are you new to Twitter chats? We have included simple steps below to help you join and participate in the conversation.
Join us at #MDedgeChats on Tuesday, April 23, 2019, at 7:00 pm EST, for a Twitter discussion in Rheumatology on some of the top studies reported at the LUPUS 2019 Congress in San Francisco, April 5-8. Our special guests are two rheumatologists with expertise in lupus who attended the congress, Jinoos Yazdany, MD, and Gabriela Schmajuk, MD, both with the University of California, San Francisco. They will discuss the ins and outs of the study results presented.
We hope you can join us and invite a colleague, too.
We will discuss the results of the EMBRACE trial, which looks at the efficacy and safety of belimumab (Benlysta) in black patients with systemic lupus erythematosus (SLE); these patients have a higher prevalence of SLE and often higher disease severity but have been poorly represented in past belimumab studies.
We will also chat about the results of a phase 2 trial of baricitinib (Olumiant) in SLE patients.
Finally, we will look at the clinical utility of monitoring hydroxychloroquine levels in SLE patients and how well levels of the drug correlate with disease activity through the results of a meta-analysis of studies that examined these questions.
Topics of conversation
Q1: How does the methodology of the EMBRACE trial differ from past phase 3 belimumab trials?
Q2: How does the EMBRACE trial affect the way you prescribe belimumab?
Q3: Does the hydroxychloroquine level meta-analysis provide persuasive enough evidence to begin measuring it?
Q4: What kinds of interventions show the best evidence for improving hydroxychloroquine adherence?
Q5: Were concerns about the safety of baricitinib in SLE patients reduced by the trial results?
Resources
EMBRACE trial: Efficacy and Safety of Belimumab in Black Race Patients with Systemic Lupus Erythematosus.
LUPUS 2019 abstract | ClinicalTrials.gov listing
Phase 2 trial of baricitinib in SLE.
LUPUS 2019 abstract | ClinicalTrials.gov listing
Meta-analysis examining the clinical significance of monitoring of hydroxychloroquine levels in SLE.
LUPUS 2019 abstract
From LUPUS 2019:
Belimumab a bust for black SLE patients.
Here’s a top strategy for immunosuppressant discontinuation in SLE.
From EULAR 2018:
Baricitinib shows potential as lupus treatment.
About Dr. Yazdany
Dr. Yazdany is an associate professor in the division of rheumatology, department of medicine at UCSF (@UCSFMedicine). She is a rheumatologist and clinical researcher with expertise in systemic lupus erythematosus and health care quality measurement and improvement. Her clinical activities include seeing patients in the UCSF Lupus Clinic, where she serves as codirector, as well as at San Francisco General Hospital. Dr. Yazdany codirects the Quality and Informatics Lab (quil.ucsf.edu), which uses data to drive improvements in health care delivery and outcomes for people with rheumatic diseases. She also leads ongoing, longitudinal studies of lupus that are investigating health disparities and outcomes in the condition.
About Dr. Schmajuk
Dr. Schmajuk is an Associate Professor in the Division of Rheumatology, Department of Medicine at UCSF (@UCSFMedicine) and the San Francisco VA Medical Center. She is a rheumatologist and clinical researcher with expertise in systemic #lupus erythematosus, quality of care, and patient safety. Dr. Schmajuk also co-directs the Quality and Informatics Lab (quil.ucsf.edu), which uses data to drive improvements in health care delivery and outcomes for people with rheumatic diseases. She leads studies to develop patient-facing disease dashboards with the goal of improving patient-provider communication for patients with RA and SLE.
Are you new to Twitter chats? We have included simple steps below to help you join and participate in the conversation.
Belimumab a bust for black SLE patients
SAN FRANCISCO – ordered by the Food and Drug Administration.
Numerically, the outcome trends in the EMBRACE study consistently favored belimumab (Benlysta) over placebo. And not just for all three components of the primary endpoint, but for each of the three major prespecified secondary endpoints as well. Yet not a single one of those six favorable trends attained statistical significance, Jim C. Oates, MD, reported at an international congress on systemic lupus erythematosus.
“The study did not achieve its primary endpoint, although there was a numeric advantage for patients on belimumab, with a 40% increase in the chance of response,” observed Dr. Oates, professor of medicine, director of the division of rheumatology and immunology, and vice chair for research at the Medical University of South Carolina, Charleston.
EMBRACE was a 52-week, double-blind trial in which 503 black systemic lupus erythematosus (SLE) patients were randomized 2:1 to 48 weeks of IV belimumab at the approved dose of 10 mg/kg or to placebo infusions on top of standard care background therapies. The postmarketing study was required by the FDA as a condition for the agency’s 2011 marketing approval of belimumab, a human monoclonal antibody that inhibits B-cell activating factor, also known as a B-lymphocyte stimulator. The agency request came because the three premarketing phase 3 intravenous trials, as well as the phase 3 subcutaneous belimumab trial, included only small numbers of black patients, and the results in that population were conflicting.
The EMBRACE results are particularly disappointing in light of the increased prevalence, severity, and mortality of SLE in black patients. However, the final word on EMBRACE isn’t in, as the data from the recently completed open-label extension phase beyond 52 weeks have not yet been analyzed.
Roughly three-quarters of EMBRACE enrollees completed the full 52 weeks of study. Withdrawal for adverse events or lack of efficacy occurred in 6.7% and 5.4%, respectively, of placebo-treated controls, and in a respective 5.4% and 4.7% of patients in the belimumab arm.
The primary study outcome at 52 weeks was the SLE Responder Index (SRI) response rate with the modified SLE Disease Activity Index (SLEDAI)–2000 scoring for proteinuria (SRI-S2K). This required at least a 4-point reduction from baseline in the Safety of Estrogens in Lupus Erythematosus – National Assessment (SELENA)-SLEDAI, no worsening in the Physician Global Assessment, as well as no new British Isles Lupus Assessment Group (BILAG) A or two new BILAG B organ domain scores. This outcome was achieved in 48.7% of the belimumab group and 41.6% of controls, for 40% greater likelihood in the active treatment arm in a logistic regression analysis, which didn’t achieve statistical significance. While the between-group difference was significant in favor of belimumab during the monthly assessments at weeks 32-44, the belimumab and placebo response rates converged thereafter.
The belimumab safety profile contained no surprises. Of note, rates of opportunistic infections, depression, and suicide or self-injury, which had been deemed adverse events of special interest based upon previous studies, were numerically lower than in controls.
The deflating EMBRACE results are sure to come under close scrutiny, since black patients with SLE have been identified as a population with a major unmet need for improved therapies. Of note, 44% of study participants were from the United States and Canada, and they had a longer disease duration, lower damage scores, and less serologically active disease than subjects from the rest of the world.
Because the results of prior phase 3 studies showed increased belimumab response rates in patients with serologically more active disease, prespecified subgroup analyses of the composite endpoint were conducted. These analyses parsed out several subgroups who were significantly more likely to achieve the primary endpoint with belimumab than with placebo. Black patients with a baseline SELENA-SLEDAI-S2K score of 10 or greater had a 52.5% response rate to belimumab, compared with 40.9% with placebo, for a 76% relative increase. Patients with a low baseline C3 and/or C4 were 200% more likely to respond to the biologic agent than placebo, by a margin of 47.2% versus 24.6%. And patients from outside North America were 80% more likely to respond to belimumab, with a 57.5% response rate, compared with 44.0% on placebo.
One audience member noted there is evidence that the use of mycophenolate appears to be advantageous in African American SLE patients and wondered if the EMBRACE subgroup on belimumab plus background mycophenolate fared significantly better than with placebo. Dr. Oates replied that, although it’s an important question, the subset analysis isn’t available yet.
The EMBRACE trial was sponsored by GlaxoSmithKline. Dr. Oates reported receiving research funding from that pharmaceutical company and several others, the National Institutes of Health, and the Department of Veterans Affairs.
SOURCE: Oates JC et al. Lupus Sci Med. 2019;6[suppl 1], Abstract 200.
SAN FRANCISCO – ordered by the Food and Drug Administration.
Numerically, the outcome trends in the EMBRACE study consistently favored belimumab (Benlysta) over placebo. And not just for all three components of the primary endpoint, but for each of the three major prespecified secondary endpoints as well. Yet not a single one of those six favorable trends attained statistical significance, Jim C. Oates, MD, reported at an international congress on systemic lupus erythematosus.
“The study did not achieve its primary endpoint, although there was a numeric advantage for patients on belimumab, with a 40% increase in the chance of response,” observed Dr. Oates, professor of medicine, director of the division of rheumatology and immunology, and vice chair for research at the Medical University of South Carolina, Charleston.
EMBRACE was a 52-week, double-blind trial in which 503 black systemic lupus erythematosus (SLE) patients were randomized 2:1 to 48 weeks of IV belimumab at the approved dose of 10 mg/kg or to placebo infusions on top of standard care background therapies. The postmarketing study was required by the FDA as a condition for the agency’s 2011 marketing approval of belimumab, a human monoclonal antibody that inhibits B-cell activating factor, also known as a B-lymphocyte stimulator. The agency request came because the three premarketing phase 3 intravenous trials, as well as the phase 3 subcutaneous belimumab trial, included only small numbers of black patients, and the results in that population were conflicting.
The EMBRACE results are particularly disappointing in light of the increased prevalence, severity, and mortality of SLE in black patients. However, the final word on EMBRACE isn’t in, as the data from the recently completed open-label extension phase beyond 52 weeks have not yet been analyzed.
Roughly three-quarters of EMBRACE enrollees completed the full 52 weeks of study. Withdrawal for adverse events or lack of efficacy occurred in 6.7% and 5.4%, respectively, of placebo-treated controls, and in a respective 5.4% and 4.7% of patients in the belimumab arm.
The primary study outcome at 52 weeks was the SLE Responder Index (SRI) response rate with the modified SLE Disease Activity Index (SLEDAI)–2000 scoring for proteinuria (SRI-S2K). This required at least a 4-point reduction from baseline in the Safety of Estrogens in Lupus Erythematosus – National Assessment (SELENA)-SLEDAI, no worsening in the Physician Global Assessment, as well as no new British Isles Lupus Assessment Group (BILAG) A or two new BILAG B organ domain scores. This outcome was achieved in 48.7% of the belimumab group and 41.6% of controls, for 40% greater likelihood in the active treatment arm in a logistic regression analysis, which didn’t achieve statistical significance. While the between-group difference was significant in favor of belimumab during the monthly assessments at weeks 32-44, the belimumab and placebo response rates converged thereafter.
The belimumab safety profile contained no surprises. Of note, rates of opportunistic infections, depression, and suicide or self-injury, which had been deemed adverse events of special interest based upon previous studies, were numerically lower than in controls.
The deflating EMBRACE results are sure to come under close scrutiny, since black patients with SLE have been identified as a population with a major unmet need for improved therapies. Of note, 44% of study participants were from the United States and Canada, and they had a longer disease duration, lower damage scores, and less serologically active disease than subjects from the rest of the world.
Because the results of prior phase 3 studies showed increased belimumab response rates in patients with serologically more active disease, prespecified subgroup analyses of the composite endpoint were conducted. These analyses parsed out several subgroups who were significantly more likely to achieve the primary endpoint with belimumab than with placebo. Black patients with a baseline SELENA-SLEDAI-S2K score of 10 or greater had a 52.5% response rate to belimumab, compared with 40.9% with placebo, for a 76% relative increase. Patients with a low baseline C3 and/or C4 were 200% more likely to respond to the biologic agent than placebo, by a margin of 47.2% versus 24.6%. And patients from outside North America were 80% more likely to respond to belimumab, with a 57.5% response rate, compared with 44.0% on placebo.
One audience member noted there is evidence that the use of mycophenolate appears to be advantageous in African American SLE patients and wondered if the EMBRACE subgroup on belimumab plus background mycophenolate fared significantly better than with placebo. Dr. Oates replied that, although it’s an important question, the subset analysis isn’t available yet.
The EMBRACE trial was sponsored by GlaxoSmithKline. Dr. Oates reported receiving research funding from that pharmaceutical company and several others, the National Institutes of Health, and the Department of Veterans Affairs.
SOURCE: Oates JC et al. Lupus Sci Med. 2019;6[suppl 1], Abstract 200.
SAN FRANCISCO – ordered by the Food and Drug Administration.
Numerically, the outcome trends in the EMBRACE study consistently favored belimumab (Benlysta) over placebo. And not just for all three components of the primary endpoint, but for each of the three major prespecified secondary endpoints as well. Yet not a single one of those six favorable trends attained statistical significance, Jim C. Oates, MD, reported at an international congress on systemic lupus erythematosus.
“The study did not achieve its primary endpoint, although there was a numeric advantage for patients on belimumab, with a 40% increase in the chance of response,” observed Dr. Oates, professor of medicine, director of the division of rheumatology and immunology, and vice chair for research at the Medical University of South Carolina, Charleston.
EMBRACE was a 52-week, double-blind trial in which 503 black systemic lupus erythematosus (SLE) patients were randomized 2:1 to 48 weeks of IV belimumab at the approved dose of 10 mg/kg or to placebo infusions on top of standard care background therapies. The postmarketing study was required by the FDA as a condition for the agency’s 2011 marketing approval of belimumab, a human monoclonal antibody that inhibits B-cell activating factor, also known as a B-lymphocyte stimulator. The agency request came because the three premarketing phase 3 intravenous trials, as well as the phase 3 subcutaneous belimumab trial, included only small numbers of black patients, and the results in that population were conflicting.
The EMBRACE results are particularly disappointing in light of the increased prevalence, severity, and mortality of SLE in black patients. However, the final word on EMBRACE isn’t in, as the data from the recently completed open-label extension phase beyond 52 weeks have not yet been analyzed.
Roughly three-quarters of EMBRACE enrollees completed the full 52 weeks of study. Withdrawal for adverse events or lack of efficacy occurred in 6.7% and 5.4%, respectively, of placebo-treated controls, and in a respective 5.4% and 4.7% of patients in the belimumab arm.
The primary study outcome at 52 weeks was the SLE Responder Index (SRI) response rate with the modified SLE Disease Activity Index (SLEDAI)–2000 scoring for proteinuria (SRI-S2K). This required at least a 4-point reduction from baseline in the Safety of Estrogens in Lupus Erythematosus – National Assessment (SELENA)-SLEDAI, no worsening in the Physician Global Assessment, as well as no new British Isles Lupus Assessment Group (BILAG) A or two new BILAG B organ domain scores. This outcome was achieved in 48.7% of the belimumab group and 41.6% of controls, for 40% greater likelihood in the active treatment arm in a logistic regression analysis, which didn’t achieve statistical significance. While the between-group difference was significant in favor of belimumab during the monthly assessments at weeks 32-44, the belimumab and placebo response rates converged thereafter.
The belimumab safety profile contained no surprises. Of note, rates of opportunistic infections, depression, and suicide or self-injury, which had been deemed adverse events of special interest based upon previous studies, were numerically lower than in controls.
The deflating EMBRACE results are sure to come under close scrutiny, since black patients with SLE have been identified as a population with a major unmet need for improved therapies. Of note, 44% of study participants were from the United States and Canada, and they had a longer disease duration, lower damage scores, and less serologically active disease than subjects from the rest of the world.
Because the results of prior phase 3 studies showed increased belimumab response rates in patients with serologically more active disease, prespecified subgroup analyses of the composite endpoint were conducted. These analyses parsed out several subgroups who were significantly more likely to achieve the primary endpoint with belimumab than with placebo. Black patients with a baseline SELENA-SLEDAI-S2K score of 10 or greater had a 52.5% response rate to belimumab, compared with 40.9% with placebo, for a 76% relative increase. Patients with a low baseline C3 and/or C4 were 200% more likely to respond to the biologic agent than placebo, by a margin of 47.2% versus 24.6%. And patients from outside North America were 80% more likely to respond to belimumab, with a 57.5% response rate, compared with 44.0% on placebo.
One audience member noted there is evidence that the use of mycophenolate appears to be advantageous in African American SLE patients and wondered if the EMBRACE subgroup on belimumab plus background mycophenolate fared significantly better than with placebo. Dr. Oates replied that, although it’s an important question, the subset analysis isn’t available yet.
The EMBRACE trial was sponsored by GlaxoSmithKline. Dr. Oates reported receiving research funding from that pharmaceutical company and several others, the National Institutes of Health, and the Department of Veterans Affairs.
SOURCE: Oates JC et al. Lupus Sci Med. 2019;6[suppl 1], Abstract 200.
REPORTING FROM LUPUS 2019
Childhood-onset SLE rate doubles in children born in winter
SAN FRANCISCO – Simone Appenzeller, MD, PhD, reported at an international congress on systemic lupus erythematosus.
She presented a cross-sectional study of 760 consecutive SLE patients seen in a university lupus clinic and 700 healthy controls. Ninety-eight of the lupus patients had childhood-onset disease that began no later than age 16 years, while 662 had adult-onset SLE.
Southeastern Brazil, where the study was conducted, features a mostly subtropical climate with relatively mild winters. Because it is in the southern hemisphere, winter lasts from June 21 to September 21, while spring runs from September 22 to December 20.
Forty-six percent of subjects with childhood-onset SLE were born in winter, 17% in spring, another 17% in summer, and just over 19% in autumn, according to Dr. Appenzeller, a rheumatologist at the University of Campinas (Brazil).
In contrast, the occurrence of adult-onset SLE showed no variation by birth month or season.
The birth disparity between childhood- and adult-onset SLE was greatest in August, the depth of Brazilian winter, when 15.3% of all subjects with childhood-onset SLE were born, compared with 9% of adult-onset SLE patients and 8% of healthy controls.
The explanation for the increased likelihood of patients with childhood-onset SLE to be born in the winter months probably involves a gene-environment interaction, Dr. Appenzeller said. The most likely environmental factors are low seasonal maternal vitamin D levels and/or exposure to winter respiratory infections. The existence of a genetic component to the birth month disparity is suggested by another study by the Brazilian investigators in which they determined that the prevalence of SLE in both the first- and second-degree relatives of individuals with childhood-onset SLE was significantly higher than in patients with adult-onset disease.
Dr. Appenzeller reported having no financial conflicts regarding her study, funded by the Brazilian National Council for Scientific and Technological Development and other noncommercial research organizations.
SAN FRANCISCO – Simone Appenzeller, MD, PhD, reported at an international congress on systemic lupus erythematosus.
She presented a cross-sectional study of 760 consecutive SLE patients seen in a university lupus clinic and 700 healthy controls. Ninety-eight of the lupus patients had childhood-onset disease that began no later than age 16 years, while 662 had adult-onset SLE.
Southeastern Brazil, where the study was conducted, features a mostly subtropical climate with relatively mild winters. Because it is in the southern hemisphere, winter lasts from June 21 to September 21, while spring runs from September 22 to December 20.
Forty-six percent of subjects with childhood-onset SLE were born in winter, 17% in spring, another 17% in summer, and just over 19% in autumn, according to Dr. Appenzeller, a rheumatologist at the University of Campinas (Brazil).
In contrast, the occurrence of adult-onset SLE showed no variation by birth month or season.
The birth disparity between childhood- and adult-onset SLE was greatest in August, the depth of Brazilian winter, when 15.3% of all subjects with childhood-onset SLE were born, compared with 9% of adult-onset SLE patients and 8% of healthy controls.
The explanation for the increased likelihood of patients with childhood-onset SLE to be born in the winter months probably involves a gene-environment interaction, Dr. Appenzeller said. The most likely environmental factors are low seasonal maternal vitamin D levels and/or exposure to winter respiratory infections. The existence of a genetic component to the birth month disparity is suggested by another study by the Brazilian investigators in which they determined that the prevalence of SLE in both the first- and second-degree relatives of individuals with childhood-onset SLE was significantly higher than in patients with adult-onset disease.
Dr. Appenzeller reported having no financial conflicts regarding her study, funded by the Brazilian National Council for Scientific and Technological Development and other noncommercial research organizations.
SAN FRANCISCO – Simone Appenzeller, MD, PhD, reported at an international congress on systemic lupus erythematosus.
She presented a cross-sectional study of 760 consecutive SLE patients seen in a university lupus clinic and 700 healthy controls. Ninety-eight of the lupus patients had childhood-onset disease that began no later than age 16 years, while 662 had adult-onset SLE.
Southeastern Brazil, where the study was conducted, features a mostly subtropical climate with relatively mild winters. Because it is in the southern hemisphere, winter lasts from June 21 to September 21, while spring runs from September 22 to December 20.
Forty-six percent of subjects with childhood-onset SLE were born in winter, 17% in spring, another 17% in summer, and just over 19% in autumn, according to Dr. Appenzeller, a rheumatologist at the University of Campinas (Brazil).
In contrast, the occurrence of adult-onset SLE showed no variation by birth month or season.
The birth disparity between childhood- and adult-onset SLE was greatest in August, the depth of Brazilian winter, when 15.3% of all subjects with childhood-onset SLE were born, compared with 9% of adult-onset SLE patients and 8% of healthy controls.
The explanation for the increased likelihood of patients with childhood-onset SLE to be born in the winter months probably involves a gene-environment interaction, Dr. Appenzeller said. The most likely environmental factors are low seasonal maternal vitamin D levels and/or exposure to winter respiratory infections. The existence of a genetic component to the birth month disparity is suggested by another study by the Brazilian investigators in which they determined that the prevalence of SLE in both the first- and second-degree relatives of individuals with childhood-onset SLE was significantly higher than in patients with adult-onset disease.
Dr. Appenzeller reported having no financial conflicts regarding her study, funded by the Brazilian National Council for Scientific and Technological Development and other noncommercial research organizations.
REPORTING FROM LUPUS 2019
Think ‘fall prevention’ in SLE patients
SAN FRANCISCO – in a Dutch prospective longitudinal study, Irene E.M. Bultink, MD, PhD, reported at an international congress on systemic lupus erythematosus.
“I think we should focus on fall risk and fall events in lupus. I think that’s a neglected area,” according to Dr. Bultink, a rheumatologist at the University of Amsterdam.
Contrary to the conventional wisdom, in her study, cumulative corticosteroid dose, average daily dosage, and bone loss were not significantly related to fracture risk in these SLE patients. That’s because Dr. Bultink and her fellow rheumatologists took steps to mitigate steroid-induced bone loss.
“We know steroids are very important for bone loss in lupus, but we demonstrated in our long-term follow-up study that it’s very dose dependent. If you use steroids below 7.5 mg daily and you protect your patient with calcium and vitamin D and, if possible, with bisphosphonates, the bone loss is restricted. I think fracture risk in lupus is more related to fall risk and fall incidence than to bone loss and steroid use. That’s what we demonstrated in our study,” she said in an interview.
“Unfortunately, until now, no studies on fall risk and fall events in lupus have been published. It’s not investigated very well. I think that fall risk in lupus patients might be greatly increased, compared to healthy controls,” Dr. Bultink added.
The study included 145 Dutch SLE patients with a mean age of 41 years at baseline. Ninety percent were women; 69% were white. Bone mineral density measurements by dual x-ray bone densitometry and x-rays of the lumbar and thoracic spine were obtained at entry and again after a median of 5 years.
Forty-two incident fractures occurred during a median of 7.2 years of follow-up. This equated to an incidence rate of 2.2 peripheral and 2.0 vertebral fractures per 100 person-years, rates double those in the Dutch general population.
In a logistic regression analysis, white ethnicity was independently associated with a 13.2-fold increased risk of fractures overall. Postmenopausal status conferred a fourfold increased risk. Older age was another important determinant. And patients with a prior stroke were at 15.5-fold greater risk of peripheral fractures.
“The prior stroke subgroup is especially vulnerable. In an earlier population-based study using data from the U.K. we also demonstrated that fractures happened more frequently in SLE patients who had already suffered a stroke (Osteoporos Int. 2014 Apr;25[4]:1275-83). So those are patients who are at very high risk for falling and fractures. But I think there are many reasons why patients with SLE would have an elevated fall risk. They have fatigue. They have muscle weakness, which might be due to vitamin D deficiency or prednisone use or inactivity. And they often have balance problems due to neuropathy or medication,” the rheumatologist observed.
She reported having no financial conflicts regarding her study, carried out free of commercial support.
SAN FRANCISCO – in a Dutch prospective longitudinal study, Irene E.M. Bultink, MD, PhD, reported at an international congress on systemic lupus erythematosus.
“I think we should focus on fall risk and fall events in lupus. I think that’s a neglected area,” according to Dr. Bultink, a rheumatologist at the University of Amsterdam.
Contrary to the conventional wisdom, in her study, cumulative corticosteroid dose, average daily dosage, and bone loss were not significantly related to fracture risk in these SLE patients. That’s because Dr. Bultink and her fellow rheumatologists took steps to mitigate steroid-induced bone loss.
“We know steroids are very important for bone loss in lupus, but we demonstrated in our long-term follow-up study that it’s very dose dependent. If you use steroids below 7.5 mg daily and you protect your patient with calcium and vitamin D and, if possible, with bisphosphonates, the bone loss is restricted. I think fracture risk in lupus is more related to fall risk and fall incidence than to bone loss and steroid use. That’s what we demonstrated in our study,” she said in an interview.
“Unfortunately, until now, no studies on fall risk and fall events in lupus have been published. It’s not investigated very well. I think that fall risk in lupus patients might be greatly increased, compared to healthy controls,” Dr. Bultink added.
The study included 145 Dutch SLE patients with a mean age of 41 years at baseline. Ninety percent were women; 69% were white. Bone mineral density measurements by dual x-ray bone densitometry and x-rays of the lumbar and thoracic spine were obtained at entry and again after a median of 5 years.
Forty-two incident fractures occurred during a median of 7.2 years of follow-up. This equated to an incidence rate of 2.2 peripheral and 2.0 vertebral fractures per 100 person-years, rates double those in the Dutch general population.
In a logistic regression analysis, white ethnicity was independently associated with a 13.2-fold increased risk of fractures overall. Postmenopausal status conferred a fourfold increased risk. Older age was another important determinant. And patients with a prior stroke were at 15.5-fold greater risk of peripheral fractures.
“The prior stroke subgroup is especially vulnerable. In an earlier population-based study using data from the U.K. we also demonstrated that fractures happened more frequently in SLE patients who had already suffered a stroke (Osteoporos Int. 2014 Apr;25[4]:1275-83). So those are patients who are at very high risk for falling and fractures. But I think there are many reasons why patients with SLE would have an elevated fall risk. They have fatigue. They have muscle weakness, which might be due to vitamin D deficiency or prednisone use or inactivity. And they often have balance problems due to neuropathy or medication,” the rheumatologist observed.
She reported having no financial conflicts regarding her study, carried out free of commercial support.
SAN FRANCISCO – in a Dutch prospective longitudinal study, Irene E.M. Bultink, MD, PhD, reported at an international congress on systemic lupus erythematosus.
“I think we should focus on fall risk and fall events in lupus. I think that’s a neglected area,” according to Dr. Bultink, a rheumatologist at the University of Amsterdam.
Contrary to the conventional wisdom, in her study, cumulative corticosteroid dose, average daily dosage, and bone loss were not significantly related to fracture risk in these SLE patients. That’s because Dr. Bultink and her fellow rheumatologists took steps to mitigate steroid-induced bone loss.
“We know steroids are very important for bone loss in lupus, but we demonstrated in our long-term follow-up study that it’s very dose dependent. If you use steroids below 7.5 mg daily and you protect your patient with calcium and vitamin D and, if possible, with bisphosphonates, the bone loss is restricted. I think fracture risk in lupus is more related to fall risk and fall incidence than to bone loss and steroid use. That’s what we demonstrated in our study,” she said in an interview.
“Unfortunately, until now, no studies on fall risk and fall events in lupus have been published. It’s not investigated very well. I think that fall risk in lupus patients might be greatly increased, compared to healthy controls,” Dr. Bultink added.
The study included 145 Dutch SLE patients with a mean age of 41 years at baseline. Ninety percent were women; 69% were white. Bone mineral density measurements by dual x-ray bone densitometry and x-rays of the lumbar and thoracic spine were obtained at entry and again after a median of 5 years.
Forty-two incident fractures occurred during a median of 7.2 years of follow-up. This equated to an incidence rate of 2.2 peripheral and 2.0 vertebral fractures per 100 person-years, rates double those in the Dutch general population.
In a logistic regression analysis, white ethnicity was independently associated with a 13.2-fold increased risk of fractures overall. Postmenopausal status conferred a fourfold increased risk. Older age was another important determinant. And patients with a prior stroke were at 15.5-fold greater risk of peripheral fractures.
“The prior stroke subgroup is especially vulnerable. In an earlier population-based study using data from the U.K. we also demonstrated that fractures happened more frequently in SLE patients who had already suffered a stroke (Osteoporos Int. 2014 Apr;25[4]:1275-83). So those are patients who are at very high risk for falling and fractures. But I think there are many reasons why patients with SLE would have an elevated fall risk. They have fatigue. They have muscle weakness, which might be due to vitamin D deficiency or prednisone use or inactivity. And they often have balance problems due to neuropathy or medication,” the rheumatologist observed.
She reported having no financial conflicts regarding her study, carried out free of commercial support.
REPORTING FROM LUPUS 2019
Young lupus patients need more than medications
SAN FRANCISCO – – and therein lies the importance of introducing interventions beyond simply prescribing appropriate medications, Hermine I. Brunner, MD, asserted at an international congress on systemic lupus erythematosus.
Pilot studies conducted by her research group as well as others suggest that brief cognitive-behavioral interventions, web-based patient and caregiver education, and social media interactions significantly improve the fatigue and depression, poor quality of life, and lack of adherence to medication that are pervasive in young patients with SLE, according to Dr. Brunner, director of the division of rheumatology and professor of pediatrics at the University of Cincinnati and scientific director of the Pediatric Rheumatology Collaborative Study Group.
“Don’t misunderstand: I don’t think we can treat lupus simply with a psychological intervention at the bedside. However, I think doctors would be well advised to offer both psychological interventions and medication when they see young lupus patients, because without the psychological intervention the patients may not feel sufficiently at ease to take their medication. They will not get the benefit of the medications you’ve prescribed,” she said.
Patients with SLE take an average of eight medications daily. Their medication adherence rate is comparable to that of patients with diabetes or many other chronic diseases: that is to say, lousy. When investigators at the University of Texas MD Anderson Cancer Center, Houston, utilized an electronic monitoring system to chart adherence to prescribed oral medications in adults with SLE, they found that over the course of 2 years of follow-up only one-fourth of them had an adherence rate of 80% or better, which is the standard definition of adherence (Lupus. 2012 Oct;21[11]:1158-65).
Treatment adherence is particularly problematic in adolescents and young adults with SLE. They often have great difficulty in mastering the self-management skills required to stay on top of their disease when they have so much else going on during what is a vulnerable and challenging period of development, even for healthy youths.
The texting intervention
Dr. Brunner and her colleagues at Cincinnati Children’s Hospital Medical Center recognized the scope of the nonadherence problem early on. Years ago they started sending text messaging reminders of pending clinic visits to their patients who had a poor track record of showing up for appointments.
“We texted patients 2 weeks before their scheduled visit, 1 week before, and then again the day before the visit,” she explained.
This simple intervention resulted in a 47% reduction in missed appointments, compared with a control group. Also, text recipients were more likely to cancel appointments instead of simply not showing up, an important benefit from a practice management and scheduling standpoint (J Rheumatol. 2012 Jan;39[1]:174-9). Disappointingly, however, the text messaging intervention had no impact on adherence to prescribed use of hydroxychloroquine. This led the investigators to conduct a deeper dive into the roots of the nonadherence problem in childhood-onset lupus.
Disease control, quality of life
Dr. Brunner and her coworkers conducted an in-depth assessment of health-related quality of life in 50 patients with childhood-onset SLE over the course of 6 months. The results were surprising.
“When we looked at the correlation between disease control and quality of life, actually there was none,” according to the pediatric rheumatologist.
Instead, the investigators found that young patients with persistently low quality of life despite objectively measured good disease control scored high for fatigue and depressive symptoms (Lupus. 2018 Jan;27[1]:124-33). This led Dr. Brunner and her coinvestigators to consider developing a practical behavioral intervention to address these potentially modifiable predictors of impaired health-related quality of life in their patient population.
The need for novel approaches was highlighted in focus groups conducted by the investigators, in which patients and their primary caregivers emphasized that current therapeutic strategies don’t adequately address key problems of living with lupus, especially the prominent fatigue, pain, and depressed mood that hamper daily function and personal relationships. Patients said they don’t feel an immediate benefit from taking their medications, so why bother? And parents expressed frustration about how difficult it is to get their teenagers to understand the consequences of nonadherence when they’re at an age when they don’t yet even grasp the concept of their own mortality (Lupus. 2019 Mar. doi: 10.1177/0961203319839478. These observations spurred the Cincinnati investigators to develop a modified cognitive-behavioral therapy (CBT) protocol, known as TEACH, which they believe is the first CBT intervention to specifically target psychological problems in young people with childhood-onset SLE.
The TEACH program
TEACH (Treatment and Education Approach for Childhood-Onset Lupus) is a six-session program that teaches patients and caregivers self-advocacy, relaxation techniques, how to improve sleep hygiene, the importance of engaging in planned pleasant activities, and why taking medications matters. The program content differs depending upon whether the patient is an adolescent or young adult.
Results of a recently published small feasibility study were highly encouraging, showing that 83% of people who enrolled in the program completed it. Posttreatment assessment showed that patients had a marked decrease in depressive symptoms as measured by both the Children’s Depression Inventory and the Beck Depression Inventory. They also showed a significant reduction in fatigue. However, while favorable trends in terms of reduced pain and anxiety symptoms were noted, they didn’t achieve statistical significance (Pediatr Rheumatol Online J. 2019 Feb 18. doi: 10.1186/s12969-019-0307-8). The next step in this project is a planned controlled randomized trial.
A web-based medication adherence program
Researchers at Pennsylvania State University took a different approach. They created a publicly available educational website, www.facinglupustogether.com, aimed at improving self-management skills – and especially medication adherence – in teens and young adults with SLE.
The website contains eight modules: Making the transition and taking charge of my medications, Learning about lupus, Learning about lupus medications, Managing symptoms of lupus, How do I handle lupus and my family, How do I handle lupus and my friends, Lupus and stress, and My personal goals and how I will achieve them. Each takes about 10 minutes to complete.
In a pilot study, 37 patients tackled one module per week and were randomized to respond to questions about the weekly topic either in a journal or by discussing the key points in an online social media forum with other young people with SLE. The idea was to create an intervention that capitalizes on the excellent social media skills possessed by today’s youth. And indeed, incorporation of social media proved to be a winning strategy. Medication adherence for hydroxychloroquine in the group randomized to social media participation jumped from 50% in the 3 months prior to starting the program to 92% in the first 3 months post completion, whereas medication adherence didn’t change significantly in the other study arm. The social media group also experienced significant improvements in self-efficacy, sense of community, acceptance of illness, optimism and control over the future, and other measures of empowerment. The control group did not show significant change in any of these domains (Pediatr Rheumatol Online J. 2018 Mar 14. doi: 10.1186/s12969-018-0232-2).
The TEACH study was sponsored by the National Institutes of Health. The web-based medication adherence program pilot study was supported by the Lupus Foundation of America. What the two approaches share in common is a conviction that, when it comes to addressing pain, fatigue, diminished quality of life, and poor medication adherence in young patients with SLE: “Our medication prescription alone doesn’t do it,” Dr. Brunner said.
She reported having no financial conflicts regarding her presentation.
SAN FRANCISCO – – and therein lies the importance of introducing interventions beyond simply prescribing appropriate medications, Hermine I. Brunner, MD, asserted at an international congress on systemic lupus erythematosus.
Pilot studies conducted by her research group as well as others suggest that brief cognitive-behavioral interventions, web-based patient and caregiver education, and social media interactions significantly improve the fatigue and depression, poor quality of life, and lack of adherence to medication that are pervasive in young patients with SLE, according to Dr. Brunner, director of the division of rheumatology and professor of pediatrics at the University of Cincinnati and scientific director of the Pediatric Rheumatology Collaborative Study Group.
“Don’t misunderstand: I don’t think we can treat lupus simply with a psychological intervention at the bedside. However, I think doctors would be well advised to offer both psychological interventions and medication when they see young lupus patients, because without the psychological intervention the patients may not feel sufficiently at ease to take their medication. They will not get the benefit of the medications you’ve prescribed,” she said.
Patients with SLE take an average of eight medications daily. Their medication adherence rate is comparable to that of patients with diabetes or many other chronic diseases: that is to say, lousy. When investigators at the University of Texas MD Anderson Cancer Center, Houston, utilized an electronic monitoring system to chart adherence to prescribed oral medications in adults with SLE, they found that over the course of 2 years of follow-up only one-fourth of them had an adherence rate of 80% or better, which is the standard definition of adherence (Lupus. 2012 Oct;21[11]:1158-65).
Treatment adherence is particularly problematic in adolescents and young adults with SLE. They often have great difficulty in mastering the self-management skills required to stay on top of their disease when they have so much else going on during what is a vulnerable and challenging period of development, even for healthy youths.
The texting intervention
Dr. Brunner and her colleagues at Cincinnati Children’s Hospital Medical Center recognized the scope of the nonadherence problem early on. Years ago they started sending text messaging reminders of pending clinic visits to their patients who had a poor track record of showing up for appointments.
“We texted patients 2 weeks before their scheduled visit, 1 week before, and then again the day before the visit,” she explained.
This simple intervention resulted in a 47% reduction in missed appointments, compared with a control group. Also, text recipients were more likely to cancel appointments instead of simply not showing up, an important benefit from a practice management and scheduling standpoint (J Rheumatol. 2012 Jan;39[1]:174-9). Disappointingly, however, the text messaging intervention had no impact on adherence to prescribed use of hydroxychloroquine. This led the investigators to conduct a deeper dive into the roots of the nonadherence problem in childhood-onset lupus.
Disease control, quality of life
Dr. Brunner and her coworkers conducted an in-depth assessment of health-related quality of life in 50 patients with childhood-onset SLE over the course of 6 months. The results were surprising.
“When we looked at the correlation between disease control and quality of life, actually there was none,” according to the pediatric rheumatologist.
Instead, the investigators found that young patients with persistently low quality of life despite objectively measured good disease control scored high for fatigue and depressive symptoms (Lupus. 2018 Jan;27[1]:124-33). This led Dr. Brunner and her coinvestigators to consider developing a practical behavioral intervention to address these potentially modifiable predictors of impaired health-related quality of life in their patient population.
The need for novel approaches was highlighted in focus groups conducted by the investigators, in which patients and their primary caregivers emphasized that current therapeutic strategies don’t adequately address key problems of living with lupus, especially the prominent fatigue, pain, and depressed mood that hamper daily function and personal relationships. Patients said they don’t feel an immediate benefit from taking their medications, so why bother? And parents expressed frustration about how difficult it is to get their teenagers to understand the consequences of nonadherence when they’re at an age when they don’t yet even grasp the concept of their own mortality (Lupus. 2019 Mar. doi: 10.1177/0961203319839478. These observations spurred the Cincinnati investigators to develop a modified cognitive-behavioral therapy (CBT) protocol, known as TEACH, which they believe is the first CBT intervention to specifically target psychological problems in young people with childhood-onset SLE.
The TEACH program
TEACH (Treatment and Education Approach for Childhood-Onset Lupus) is a six-session program that teaches patients and caregivers self-advocacy, relaxation techniques, how to improve sleep hygiene, the importance of engaging in planned pleasant activities, and why taking medications matters. The program content differs depending upon whether the patient is an adolescent or young adult.
Results of a recently published small feasibility study were highly encouraging, showing that 83% of people who enrolled in the program completed it. Posttreatment assessment showed that patients had a marked decrease in depressive symptoms as measured by both the Children’s Depression Inventory and the Beck Depression Inventory. They also showed a significant reduction in fatigue. However, while favorable trends in terms of reduced pain and anxiety symptoms were noted, they didn’t achieve statistical significance (Pediatr Rheumatol Online J. 2019 Feb 18. doi: 10.1186/s12969-019-0307-8). The next step in this project is a planned controlled randomized trial.
A web-based medication adherence program
Researchers at Pennsylvania State University took a different approach. They created a publicly available educational website, www.facinglupustogether.com, aimed at improving self-management skills – and especially medication adherence – in teens and young adults with SLE.
The website contains eight modules: Making the transition and taking charge of my medications, Learning about lupus, Learning about lupus medications, Managing symptoms of lupus, How do I handle lupus and my family, How do I handle lupus and my friends, Lupus and stress, and My personal goals and how I will achieve them. Each takes about 10 minutes to complete.
In a pilot study, 37 patients tackled one module per week and were randomized to respond to questions about the weekly topic either in a journal or by discussing the key points in an online social media forum with other young people with SLE. The idea was to create an intervention that capitalizes on the excellent social media skills possessed by today’s youth. And indeed, incorporation of social media proved to be a winning strategy. Medication adherence for hydroxychloroquine in the group randomized to social media participation jumped from 50% in the 3 months prior to starting the program to 92% in the first 3 months post completion, whereas medication adherence didn’t change significantly in the other study arm. The social media group also experienced significant improvements in self-efficacy, sense of community, acceptance of illness, optimism and control over the future, and other measures of empowerment. The control group did not show significant change in any of these domains (Pediatr Rheumatol Online J. 2018 Mar 14. doi: 10.1186/s12969-018-0232-2).
The TEACH study was sponsored by the National Institutes of Health. The web-based medication adherence program pilot study was supported by the Lupus Foundation of America. What the two approaches share in common is a conviction that, when it comes to addressing pain, fatigue, diminished quality of life, and poor medication adherence in young patients with SLE: “Our medication prescription alone doesn’t do it,” Dr. Brunner said.
She reported having no financial conflicts regarding her presentation.
SAN FRANCISCO – – and therein lies the importance of introducing interventions beyond simply prescribing appropriate medications, Hermine I. Brunner, MD, asserted at an international congress on systemic lupus erythematosus.
Pilot studies conducted by her research group as well as others suggest that brief cognitive-behavioral interventions, web-based patient and caregiver education, and social media interactions significantly improve the fatigue and depression, poor quality of life, and lack of adherence to medication that are pervasive in young patients with SLE, according to Dr. Brunner, director of the division of rheumatology and professor of pediatrics at the University of Cincinnati and scientific director of the Pediatric Rheumatology Collaborative Study Group.
“Don’t misunderstand: I don’t think we can treat lupus simply with a psychological intervention at the bedside. However, I think doctors would be well advised to offer both psychological interventions and medication when they see young lupus patients, because without the psychological intervention the patients may not feel sufficiently at ease to take their medication. They will not get the benefit of the medications you’ve prescribed,” she said.
Patients with SLE take an average of eight medications daily. Their medication adherence rate is comparable to that of patients with diabetes or many other chronic diseases: that is to say, lousy. When investigators at the University of Texas MD Anderson Cancer Center, Houston, utilized an electronic monitoring system to chart adherence to prescribed oral medications in adults with SLE, they found that over the course of 2 years of follow-up only one-fourth of them had an adherence rate of 80% or better, which is the standard definition of adherence (Lupus. 2012 Oct;21[11]:1158-65).
Treatment adherence is particularly problematic in adolescents and young adults with SLE. They often have great difficulty in mastering the self-management skills required to stay on top of their disease when they have so much else going on during what is a vulnerable and challenging period of development, even for healthy youths.
The texting intervention
Dr. Brunner and her colleagues at Cincinnati Children’s Hospital Medical Center recognized the scope of the nonadherence problem early on. Years ago they started sending text messaging reminders of pending clinic visits to their patients who had a poor track record of showing up for appointments.
“We texted patients 2 weeks before their scheduled visit, 1 week before, and then again the day before the visit,” she explained.
This simple intervention resulted in a 47% reduction in missed appointments, compared with a control group. Also, text recipients were more likely to cancel appointments instead of simply not showing up, an important benefit from a practice management and scheduling standpoint (J Rheumatol. 2012 Jan;39[1]:174-9). Disappointingly, however, the text messaging intervention had no impact on adherence to prescribed use of hydroxychloroquine. This led the investigators to conduct a deeper dive into the roots of the nonadherence problem in childhood-onset lupus.
Disease control, quality of life
Dr. Brunner and her coworkers conducted an in-depth assessment of health-related quality of life in 50 patients with childhood-onset SLE over the course of 6 months. The results were surprising.
“When we looked at the correlation between disease control and quality of life, actually there was none,” according to the pediatric rheumatologist.
Instead, the investigators found that young patients with persistently low quality of life despite objectively measured good disease control scored high for fatigue and depressive symptoms (Lupus. 2018 Jan;27[1]:124-33). This led Dr. Brunner and her coinvestigators to consider developing a practical behavioral intervention to address these potentially modifiable predictors of impaired health-related quality of life in their patient population.
The need for novel approaches was highlighted in focus groups conducted by the investigators, in which patients and their primary caregivers emphasized that current therapeutic strategies don’t adequately address key problems of living with lupus, especially the prominent fatigue, pain, and depressed mood that hamper daily function and personal relationships. Patients said they don’t feel an immediate benefit from taking their medications, so why bother? And parents expressed frustration about how difficult it is to get their teenagers to understand the consequences of nonadherence when they’re at an age when they don’t yet even grasp the concept of their own mortality (Lupus. 2019 Mar. doi: 10.1177/0961203319839478. These observations spurred the Cincinnati investigators to develop a modified cognitive-behavioral therapy (CBT) protocol, known as TEACH, which they believe is the first CBT intervention to specifically target psychological problems in young people with childhood-onset SLE.
The TEACH program
TEACH (Treatment and Education Approach for Childhood-Onset Lupus) is a six-session program that teaches patients and caregivers self-advocacy, relaxation techniques, how to improve sleep hygiene, the importance of engaging in planned pleasant activities, and why taking medications matters. The program content differs depending upon whether the patient is an adolescent or young adult.
Results of a recently published small feasibility study were highly encouraging, showing that 83% of people who enrolled in the program completed it. Posttreatment assessment showed that patients had a marked decrease in depressive symptoms as measured by both the Children’s Depression Inventory and the Beck Depression Inventory. They also showed a significant reduction in fatigue. However, while favorable trends in terms of reduced pain and anxiety symptoms were noted, they didn’t achieve statistical significance (Pediatr Rheumatol Online J. 2019 Feb 18. doi: 10.1186/s12969-019-0307-8). The next step in this project is a planned controlled randomized trial.
A web-based medication adherence program
Researchers at Pennsylvania State University took a different approach. They created a publicly available educational website, www.facinglupustogether.com, aimed at improving self-management skills – and especially medication adherence – in teens and young adults with SLE.
The website contains eight modules: Making the transition and taking charge of my medications, Learning about lupus, Learning about lupus medications, Managing symptoms of lupus, How do I handle lupus and my family, How do I handle lupus and my friends, Lupus and stress, and My personal goals and how I will achieve them. Each takes about 10 minutes to complete.
In a pilot study, 37 patients tackled one module per week and were randomized to respond to questions about the weekly topic either in a journal or by discussing the key points in an online social media forum with other young people with SLE. The idea was to create an intervention that capitalizes on the excellent social media skills possessed by today’s youth. And indeed, incorporation of social media proved to be a winning strategy. Medication adherence for hydroxychloroquine in the group randomized to social media participation jumped from 50% in the 3 months prior to starting the program to 92% in the first 3 months post completion, whereas medication adherence didn’t change significantly in the other study arm. The social media group also experienced significant improvements in self-efficacy, sense of community, acceptance of illness, optimism and control over the future, and other measures of empowerment. The control group did not show significant change in any of these domains (Pediatr Rheumatol Online J. 2018 Mar 14. doi: 10.1186/s12969-018-0232-2).
The TEACH study was sponsored by the National Institutes of Health. The web-based medication adherence program pilot study was supported by the Lupus Foundation of America. What the two approaches share in common is a conviction that, when it comes to addressing pain, fatigue, diminished quality of life, and poor medication adherence in young patients with SLE: “Our medication prescription alone doesn’t do it,” Dr. Brunner said.
She reported having no financial conflicts regarding her presentation.
REPORTING FROM LUPUS 2019