User login
New definitions of hypertension reveal new preeclampsia risks
according to results from a large retrospective cohort study.
In a 2017 guideline, the American College of Cardiology and American Heart Association changed clinical definitions of hypertension in adults. People previously deemed to have prehypertension were classed as having elevated blood pressure (systolic BP 120-129 mm Hg and diastolic BP >80 mm Hg) or stage 1 hypertension (systolic 130-139 mm Hg or diastolic 80-89 mm Hg).
And while hypertension as earlier defined (at or above systolic 140 mm Hg or at or above diastolic 90 mm Hg; now called stage 2 hypertension) has been long associated with adverse maternal and fetal effects, it was unclear whether lesser elevations in blood pressure also are linked to the same.
For their research published in Obstetrics & Gynecology, Elizabeth F. Sutton, PhD, of the University of Pittsburgh and colleagues looked at records from 18,162 women who had given birth to a single baby and had two or more prenatal appointments before week 20 of pregnancy. The women in the study were seen at the same institution over a 3-year period ending in 2018. Three-quarters of the cohort had normal blood pressure, while 14% had elevated blood pressure and 5% had stage 1 hypertension before 20 weeks. Another 6% of the cohort had stage 2 hypertension.
The authors found preeclampsia risk increased with increasing blood pressure elevation. Among women with normal blood pressure before 20 weeks’ gestation, 5% had preeclampsia, while 7% of those with elevated blood pressure did, as did with 12% of women with stage 1 hypertension and 30% of women with stage 2 hypertension. The increase in risk of preeclampsia was because of preterm preeclampsia in the women with elevated blood pressure. Both term and preterm preeclampsia were factors in women with stage 1 and stage 2 hypertension, but preterm preeclampsia was associated with a higher risk. Although black race was associated with a higher risk of preeclampsia, the pattern of increasing risk with higher blood pressure category was similar in both black and white women.
Researchers also looked at gestational diabetes, severe maternal morbidity, neonatal morbidity, and placental abruption as secondary outcomes. They found the risk of gestational diabetes increased in a stepwise fashion as blood pressure increased, compared with normotensive women. Higher risk of severe maternal and neonatal morbidities was seen only in women with stage 2 hypertension. Placental abruption was rare in this cohort and the odds were not increased in any group.
The findings “highlight the importance of early pregnancy BP elevations, which may reflect prepregnancy BP status,” and suggest that the new guidelines “can identify women early in pregnancy who may benefit from increased surveillance,” Dr. Sutton and colleagues wrote.
Although randomized trials will be needed to identify the best prevention and management strategies for this patient group, they added, some clinicians may want to consider low-dose aspirin – an intervention shown to safely reduce preeclampsia risk among women with stage 2 hypertension – for women with elevated BP or stage 1 hypertension.
Dr. Sutton and colleagues acknowledged that its retrospective design is among the limitations of their study, and that use of antihypertensive medications could not be captured in their study.
Preeclampsia researcher Mark Santillan, MD, PhD, of the University of Iowa in Iowa City, said in an interview that the results “open the door to considering these new blood pressure categories as a prognosticator” for preeclampsia. “This paper furthers the field by applying these new categories to hypertensive diseases in pregnancy which are not well studied” in comparison to nonpregnant hypertensive states.
“Are these seemingly normal blood pressures associated with poor outcomes, maternal or neonatal? I think that this paper strongly tells us yes,” Dr. Santillan added. “But does that mean we have to do more aggressive blood pressure monitoring, seeing your doctor every month or so? Maybe we should change the way we’re treating people early on in gestation.”
The question of whether aspirin helps reduce preeclampsia risk in women with elevated blood pressure or stage 1 hypertension needs to be resolved in studies, Dr. Santillan said. But because of its favorable risk profile, “if I consider that if a patient has significant risk factors for developing preeclampsia, baby aspirin is fine.”
Postpregnancy blood pressure management is something that should also be reconsidered in light of the findings, Dr. Santillan said. Half of women with preeclampsia will have chronic hypertension after they deliver, increasing their risk of adverse cardiovascular outcomes later in life. But because most are young and otherwise healthy, they often are lost to follow-up.
“I think this paper has helped open up that conversation, that there is probably a link between what we’re doing in pregnancy to what we should be doing in the postpartum period,” he said.
Dr. Sutton and colleagues’ study received funding from the Richard King Mellon Foundation, the American Heart Association; and the National Institutes of Health. None of its authors had relevant disclosures. Dr. Santillan disclosed holding U.S. and international patents for preeclampsia prediction, diagnosis, and treatment.
SOURCE: Sutton et al. Obstet Gynecol. 2020;136:129-39.
according to results from a large retrospective cohort study.
In a 2017 guideline, the American College of Cardiology and American Heart Association changed clinical definitions of hypertension in adults. People previously deemed to have prehypertension were classed as having elevated blood pressure (systolic BP 120-129 mm Hg and diastolic BP >80 mm Hg) or stage 1 hypertension (systolic 130-139 mm Hg or diastolic 80-89 mm Hg).
And while hypertension as earlier defined (at or above systolic 140 mm Hg or at or above diastolic 90 mm Hg; now called stage 2 hypertension) has been long associated with adverse maternal and fetal effects, it was unclear whether lesser elevations in blood pressure also are linked to the same.
For their research published in Obstetrics & Gynecology, Elizabeth F. Sutton, PhD, of the University of Pittsburgh and colleagues looked at records from 18,162 women who had given birth to a single baby and had two or more prenatal appointments before week 20 of pregnancy. The women in the study were seen at the same institution over a 3-year period ending in 2018. Three-quarters of the cohort had normal blood pressure, while 14% had elevated blood pressure and 5% had stage 1 hypertension before 20 weeks. Another 6% of the cohort had stage 2 hypertension.
The authors found preeclampsia risk increased with increasing blood pressure elevation. Among women with normal blood pressure before 20 weeks’ gestation, 5% had preeclampsia, while 7% of those with elevated blood pressure did, as did with 12% of women with stage 1 hypertension and 30% of women with stage 2 hypertension. The increase in risk of preeclampsia was because of preterm preeclampsia in the women with elevated blood pressure. Both term and preterm preeclampsia were factors in women with stage 1 and stage 2 hypertension, but preterm preeclampsia was associated with a higher risk. Although black race was associated with a higher risk of preeclampsia, the pattern of increasing risk with higher blood pressure category was similar in both black and white women.
Researchers also looked at gestational diabetes, severe maternal morbidity, neonatal morbidity, and placental abruption as secondary outcomes. They found the risk of gestational diabetes increased in a stepwise fashion as blood pressure increased, compared with normotensive women. Higher risk of severe maternal and neonatal morbidities was seen only in women with stage 2 hypertension. Placental abruption was rare in this cohort and the odds were not increased in any group.
The findings “highlight the importance of early pregnancy BP elevations, which may reflect prepregnancy BP status,” and suggest that the new guidelines “can identify women early in pregnancy who may benefit from increased surveillance,” Dr. Sutton and colleagues wrote.
Although randomized trials will be needed to identify the best prevention and management strategies for this patient group, they added, some clinicians may want to consider low-dose aspirin – an intervention shown to safely reduce preeclampsia risk among women with stage 2 hypertension – for women with elevated BP or stage 1 hypertension.
Dr. Sutton and colleagues acknowledged that its retrospective design is among the limitations of their study, and that use of antihypertensive medications could not be captured in their study.
Preeclampsia researcher Mark Santillan, MD, PhD, of the University of Iowa in Iowa City, said in an interview that the results “open the door to considering these new blood pressure categories as a prognosticator” for preeclampsia. “This paper furthers the field by applying these new categories to hypertensive diseases in pregnancy which are not well studied” in comparison to nonpregnant hypertensive states.
“Are these seemingly normal blood pressures associated with poor outcomes, maternal or neonatal? I think that this paper strongly tells us yes,” Dr. Santillan added. “But does that mean we have to do more aggressive blood pressure monitoring, seeing your doctor every month or so? Maybe we should change the way we’re treating people early on in gestation.”
The question of whether aspirin helps reduce preeclampsia risk in women with elevated blood pressure or stage 1 hypertension needs to be resolved in studies, Dr. Santillan said. But because of its favorable risk profile, “if I consider that if a patient has significant risk factors for developing preeclampsia, baby aspirin is fine.”
Postpregnancy blood pressure management is something that should also be reconsidered in light of the findings, Dr. Santillan said. Half of women with preeclampsia will have chronic hypertension after they deliver, increasing their risk of adverse cardiovascular outcomes later in life. But because most are young and otherwise healthy, they often are lost to follow-up.
“I think this paper has helped open up that conversation, that there is probably a link between what we’re doing in pregnancy to what we should be doing in the postpartum period,” he said.
Dr. Sutton and colleagues’ study received funding from the Richard King Mellon Foundation, the American Heart Association; and the National Institutes of Health. None of its authors had relevant disclosures. Dr. Santillan disclosed holding U.S. and international patents for preeclampsia prediction, diagnosis, and treatment.
SOURCE: Sutton et al. Obstet Gynecol. 2020;136:129-39.
according to results from a large retrospective cohort study.
In a 2017 guideline, the American College of Cardiology and American Heart Association changed clinical definitions of hypertension in adults. People previously deemed to have prehypertension were classed as having elevated blood pressure (systolic BP 120-129 mm Hg and diastolic BP >80 mm Hg) or stage 1 hypertension (systolic 130-139 mm Hg or diastolic 80-89 mm Hg).
And while hypertension as earlier defined (at or above systolic 140 mm Hg or at or above diastolic 90 mm Hg; now called stage 2 hypertension) has been long associated with adverse maternal and fetal effects, it was unclear whether lesser elevations in blood pressure also are linked to the same.
For their research published in Obstetrics & Gynecology, Elizabeth F. Sutton, PhD, of the University of Pittsburgh and colleagues looked at records from 18,162 women who had given birth to a single baby and had two or more prenatal appointments before week 20 of pregnancy. The women in the study were seen at the same institution over a 3-year period ending in 2018. Three-quarters of the cohort had normal blood pressure, while 14% had elevated blood pressure and 5% had stage 1 hypertension before 20 weeks. Another 6% of the cohort had stage 2 hypertension.
The authors found preeclampsia risk increased with increasing blood pressure elevation. Among women with normal blood pressure before 20 weeks’ gestation, 5% had preeclampsia, while 7% of those with elevated blood pressure did, as did with 12% of women with stage 1 hypertension and 30% of women with stage 2 hypertension. The increase in risk of preeclampsia was because of preterm preeclampsia in the women with elevated blood pressure. Both term and preterm preeclampsia were factors in women with stage 1 and stage 2 hypertension, but preterm preeclampsia was associated with a higher risk. Although black race was associated with a higher risk of preeclampsia, the pattern of increasing risk with higher blood pressure category was similar in both black and white women.
Researchers also looked at gestational diabetes, severe maternal morbidity, neonatal morbidity, and placental abruption as secondary outcomes. They found the risk of gestational diabetes increased in a stepwise fashion as blood pressure increased, compared with normotensive women. Higher risk of severe maternal and neonatal morbidities was seen only in women with stage 2 hypertension. Placental abruption was rare in this cohort and the odds were not increased in any group.
The findings “highlight the importance of early pregnancy BP elevations, which may reflect prepregnancy BP status,” and suggest that the new guidelines “can identify women early in pregnancy who may benefit from increased surveillance,” Dr. Sutton and colleagues wrote.
Although randomized trials will be needed to identify the best prevention and management strategies for this patient group, they added, some clinicians may want to consider low-dose aspirin – an intervention shown to safely reduce preeclampsia risk among women with stage 2 hypertension – for women with elevated BP or stage 1 hypertension.
Dr. Sutton and colleagues acknowledged that its retrospective design is among the limitations of their study, and that use of antihypertensive medications could not be captured in their study.
Preeclampsia researcher Mark Santillan, MD, PhD, of the University of Iowa in Iowa City, said in an interview that the results “open the door to considering these new blood pressure categories as a prognosticator” for preeclampsia. “This paper furthers the field by applying these new categories to hypertensive diseases in pregnancy which are not well studied” in comparison to nonpregnant hypertensive states.
“Are these seemingly normal blood pressures associated with poor outcomes, maternal or neonatal? I think that this paper strongly tells us yes,” Dr. Santillan added. “But does that mean we have to do more aggressive blood pressure monitoring, seeing your doctor every month or so? Maybe we should change the way we’re treating people early on in gestation.”
The question of whether aspirin helps reduce preeclampsia risk in women with elevated blood pressure or stage 1 hypertension needs to be resolved in studies, Dr. Santillan said. But because of its favorable risk profile, “if I consider that if a patient has significant risk factors for developing preeclampsia, baby aspirin is fine.”
Postpregnancy blood pressure management is something that should also be reconsidered in light of the findings, Dr. Santillan said. Half of women with preeclampsia will have chronic hypertension after they deliver, increasing their risk of adverse cardiovascular outcomes later in life. But because most are young and otherwise healthy, they often are lost to follow-up.
“I think this paper has helped open up that conversation, that there is probably a link between what we’re doing in pregnancy to what we should be doing in the postpartum period,” he said.
Dr. Sutton and colleagues’ study received funding from the Richard King Mellon Foundation, the American Heart Association; and the National Institutes of Health. None of its authors had relevant disclosures. Dr. Santillan disclosed holding U.S. and international patents for preeclampsia prediction, diagnosis, and treatment.
SOURCE: Sutton et al. Obstet Gynecol. 2020;136:129-39.
FROM OBSTETRICS & GYNECOLOGY
New registry focuses on rheumatic immune-related AEs of cancer therapy
Its first findings were reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.
“We have limited knowledge on the interrelationships between malignant and rheumatic diseases on both the clinical and molecular level, and we have a large unmet need for management guidelines in the case of the coincidence of both disease entities,” noted lead author Karolina Benesova, MD, of the department of hematology, oncology, and rheumatology at University Hospital Heidelberg (Germany).
The TRheuMa registry – Therapy-Induced Rheumatic Symptoms in Patients with Malignancy – is one of three registries in a multicenter observational project exploring various contexts between malignant and rheumatic diseases. Over its first 22 months, the registry recruited 69 patients having rheumatic symptoms as a result of immune checkpoint inhibitor therapy or other cancer therapies.
Registry findings
The largest shares of patients had non–small cell lung cancer (38%) or melanoma (33%), Dr. Benesova reported. The immune checkpoint inhibitors most commonly received were pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy).
The immune-related adverse events usually presented with symptoms of de novo spondyloarthritis or psoriatic arthritis (42%), late-onset RA (17%), or polymyalgia rheumatica (14%). But 16% of the patients were experiencing a flare of a preexisting rheumatic and musculoskeletal disease.
Laboratory findings differed somewhat from those of classical rheumatic and musculoskeletal diseases, according to Dr. Benesova. Specific findings were rare; in particular, most patients did not have detectable autoantibodies. However, 76% had an elevated C-reactive protein level and 39% had an elevated soluble CD25 level. In addition, nearly all patients (96%) undergoing joint ultrasound had pathologic findings.
“Based on our experiences from interdisciplinary care together with our local oncologists, we have developed a therapeutic algorithm for rheumatic immune-related adverse events,” she reported, noting that the algorithm is consistent with recently published recommendations in this area.
The large majority of patients were adequately treated with prednisone at a dose greater than 10 mg (40%) or at a dose of 10 mg or less with or without an NSAID (40%), while some received NSAID monotherapy (14%).
“We have a growing proportion of patients on conventional or biological [disease-modifying antirheumatic drugs],” Dr. Benesova noted. “These are mostly patients with preexisting rheumatic and musculoskeletal disease or highly suspected de novo classical rheumatic and musculoskeletal disease under checkpoint inhibitor therapy.”
Patients with melanoma having a rheumatic immune-related adverse event had a better response to their therapy than historical counterparts who did not have such events: 39% of the former had a complete response, relative to merely 4% of the latter.
Only a small proportion of patients overall (9%) had to discontinue immune checkpoint inhibitor therapy because of their adverse event, and some of them may be eligible for rechallenge if their cancer progresses, Dr. Benesova noted.
“There is still a lot to be done,” she stated, such as better elucidating the nature of these adverse events [whether transient side effects or a triggering of chronic rheumatic and musculoskeletal diseases], the need for a defensive treatment strategy, and the advisability of closer monitoring of high-risk patients given immune checkpoint inhibitors. “We are aiming at solving these questions in the next few years,” she concluded.
Findings in context
“Registries are important to gain prospective data on patient outcomes,” Sabina Sandigursky, MD, an instructor in the division of rheumatology at the Laura and Isaac Perlmutter Cancer Center at New York University, commented in an interview. “One must be careful, while interpreting these data, especially since they are not randomized, controlled trials.”
Patterns may differ at other centers, too, she pointed out. “The German registry reported a predominance of spondyloarthritis-like disease; however, our patients have a predominance of small-joint involvement. It is unclear what accounts for this difference.”
Individual institutions in North America are similarly collecting data on this patient population, with efforts underway to compile those data to provide a larger picture, according to Dr. Sandigursky.
“Many of the syndromes that we consider to be rheumatic immune-related adverse events have been well described by groups from the U.S., Canada, Australia, and European Union,” she concluded. “From this registry, we can observe how patients are being treated in real time since this information is largely consensus based.”
The study did not receive any specific funding. Dr. Benesova disclosed grant/research support from AbbVie, Novartis, Rheumaliga Baden-Wurttemberg, and the University of Heidelberg, and consultancies, speaker fees, and/or travel reimbursements from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Medac, Merck Sharp & Dohme, Mundipharma, Novartis, Pfizer, Roche, and UCB. Some of her coauthors also disclosed financial relationships with industry. Dr. Sandigursky disclosed having no relevant conflicts of interest.
SOURCE: Benesova K et al. Ann Rheum Dis 2020;79[suppl 1]:168-9, Abstract OP0270.
Its first findings were reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.
“We have limited knowledge on the interrelationships between malignant and rheumatic diseases on both the clinical and molecular level, and we have a large unmet need for management guidelines in the case of the coincidence of both disease entities,” noted lead author Karolina Benesova, MD, of the department of hematology, oncology, and rheumatology at University Hospital Heidelberg (Germany).
The TRheuMa registry – Therapy-Induced Rheumatic Symptoms in Patients with Malignancy – is one of three registries in a multicenter observational project exploring various contexts between malignant and rheumatic diseases. Over its first 22 months, the registry recruited 69 patients having rheumatic symptoms as a result of immune checkpoint inhibitor therapy or other cancer therapies.
Registry findings
The largest shares of patients had non–small cell lung cancer (38%) or melanoma (33%), Dr. Benesova reported. The immune checkpoint inhibitors most commonly received were pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy).
The immune-related adverse events usually presented with symptoms of de novo spondyloarthritis or psoriatic arthritis (42%), late-onset RA (17%), or polymyalgia rheumatica (14%). But 16% of the patients were experiencing a flare of a preexisting rheumatic and musculoskeletal disease.
Laboratory findings differed somewhat from those of classical rheumatic and musculoskeletal diseases, according to Dr. Benesova. Specific findings were rare; in particular, most patients did not have detectable autoantibodies. However, 76% had an elevated C-reactive protein level and 39% had an elevated soluble CD25 level. In addition, nearly all patients (96%) undergoing joint ultrasound had pathologic findings.
“Based on our experiences from interdisciplinary care together with our local oncologists, we have developed a therapeutic algorithm for rheumatic immune-related adverse events,” she reported, noting that the algorithm is consistent with recently published recommendations in this area.
The large majority of patients were adequately treated with prednisone at a dose greater than 10 mg (40%) or at a dose of 10 mg or less with or without an NSAID (40%), while some received NSAID monotherapy (14%).
“We have a growing proportion of patients on conventional or biological [disease-modifying antirheumatic drugs],” Dr. Benesova noted. “These are mostly patients with preexisting rheumatic and musculoskeletal disease or highly suspected de novo classical rheumatic and musculoskeletal disease under checkpoint inhibitor therapy.”
Patients with melanoma having a rheumatic immune-related adverse event had a better response to their therapy than historical counterparts who did not have such events: 39% of the former had a complete response, relative to merely 4% of the latter.
Only a small proportion of patients overall (9%) had to discontinue immune checkpoint inhibitor therapy because of their adverse event, and some of them may be eligible for rechallenge if their cancer progresses, Dr. Benesova noted.
“There is still a lot to be done,” she stated, such as better elucidating the nature of these adverse events [whether transient side effects or a triggering of chronic rheumatic and musculoskeletal diseases], the need for a defensive treatment strategy, and the advisability of closer monitoring of high-risk patients given immune checkpoint inhibitors. “We are aiming at solving these questions in the next few years,” she concluded.
Findings in context
“Registries are important to gain prospective data on patient outcomes,” Sabina Sandigursky, MD, an instructor in the division of rheumatology at the Laura and Isaac Perlmutter Cancer Center at New York University, commented in an interview. “One must be careful, while interpreting these data, especially since they are not randomized, controlled trials.”
Patterns may differ at other centers, too, she pointed out. “The German registry reported a predominance of spondyloarthritis-like disease; however, our patients have a predominance of small-joint involvement. It is unclear what accounts for this difference.”
Individual institutions in North America are similarly collecting data on this patient population, with efforts underway to compile those data to provide a larger picture, according to Dr. Sandigursky.
“Many of the syndromes that we consider to be rheumatic immune-related adverse events have been well described by groups from the U.S., Canada, Australia, and European Union,” she concluded. “From this registry, we can observe how patients are being treated in real time since this information is largely consensus based.”
The study did not receive any specific funding. Dr. Benesova disclosed grant/research support from AbbVie, Novartis, Rheumaliga Baden-Wurttemberg, and the University of Heidelberg, and consultancies, speaker fees, and/or travel reimbursements from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Medac, Merck Sharp & Dohme, Mundipharma, Novartis, Pfizer, Roche, and UCB. Some of her coauthors also disclosed financial relationships with industry. Dr. Sandigursky disclosed having no relevant conflicts of interest.
SOURCE: Benesova K et al. Ann Rheum Dis 2020;79[suppl 1]:168-9, Abstract OP0270.
Its first findings were reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.
“We have limited knowledge on the interrelationships between malignant and rheumatic diseases on both the clinical and molecular level, and we have a large unmet need for management guidelines in the case of the coincidence of both disease entities,” noted lead author Karolina Benesova, MD, of the department of hematology, oncology, and rheumatology at University Hospital Heidelberg (Germany).
The TRheuMa registry – Therapy-Induced Rheumatic Symptoms in Patients with Malignancy – is one of three registries in a multicenter observational project exploring various contexts between malignant and rheumatic diseases. Over its first 22 months, the registry recruited 69 patients having rheumatic symptoms as a result of immune checkpoint inhibitor therapy or other cancer therapies.
Registry findings
The largest shares of patients had non–small cell lung cancer (38%) or melanoma (33%), Dr. Benesova reported. The immune checkpoint inhibitors most commonly received were pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy).
The immune-related adverse events usually presented with symptoms of de novo spondyloarthritis or psoriatic arthritis (42%), late-onset RA (17%), or polymyalgia rheumatica (14%). But 16% of the patients were experiencing a flare of a preexisting rheumatic and musculoskeletal disease.
Laboratory findings differed somewhat from those of classical rheumatic and musculoskeletal diseases, according to Dr. Benesova. Specific findings were rare; in particular, most patients did not have detectable autoantibodies. However, 76% had an elevated C-reactive protein level and 39% had an elevated soluble CD25 level. In addition, nearly all patients (96%) undergoing joint ultrasound had pathologic findings.
“Based on our experiences from interdisciplinary care together with our local oncologists, we have developed a therapeutic algorithm for rheumatic immune-related adverse events,” she reported, noting that the algorithm is consistent with recently published recommendations in this area.
The large majority of patients were adequately treated with prednisone at a dose greater than 10 mg (40%) or at a dose of 10 mg or less with or without an NSAID (40%), while some received NSAID monotherapy (14%).
“We have a growing proportion of patients on conventional or biological [disease-modifying antirheumatic drugs],” Dr. Benesova noted. “These are mostly patients with preexisting rheumatic and musculoskeletal disease or highly suspected de novo classical rheumatic and musculoskeletal disease under checkpoint inhibitor therapy.”
Patients with melanoma having a rheumatic immune-related adverse event had a better response to their therapy than historical counterparts who did not have such events: 39% of the former had a complete response, relative to merely 4% of the latter.
Only a small proportion of patients overall (9%) had to discontinue immune checkpoint inhibitor therapy because of their adverse event, and some of them may be eligible for rechallenge if their cancer progresses, Dr. Benesova noted.
“There is still a lot to be done,” she stated, such as better elucidating the nature of these adverse events [whether transient side effects or a triggering of chronic rheumatic and musculoskeletal diseases], the need for a defensive treatment strategy, and the advisability of closer monitoring of high-risk patients given immune checkpoint inhibitors. “We are aiming at solving these questions in the next few years,” she concluded.
Findings in context
“Registries are important to gain prospective data on patient outcomes,” Sabina Sandigursky, MD, an instructor in the division of rheumatology at the Laura and Isaac Perlmutter Cancer Center at New York University, commented in an interview. “One must be careful, while interpreting these data, especially since they are not randomized, controlled trials.”
Patterns may differ at other centers, too, she pointed out. “The German registry reported a predominance of spondyloarthritis-like disease; however, our patients have a predominance of small-joint involvement. It is unclear what accounts for this difference.”
Individual institutions in North America are similarly collecting data on this patient population, with efforts underway to compile those data to provide a larger picture, according to Dr. Sandigursky.
“Many of the syndromes that we consider to be rheumatic immune-related adverse events have been well described by groups from the U.S., Canada, Australia, and European Union,” she concluded. “From this registry, we can observe how patients are being treated in real time since this information is largely consensus based.”
The study did not receive any specific funding. Dr. Benesova disclosed grant/research support from AbbVie, Novartis, Rheumaliga Baden-Wurttemberg, and the University of Heidelberg, and consultancies, speaker fees, and/or travel reimbursements from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Medac, Merck Sharp & Dohme, Mundipharma, Novartis, Pfizer, Roche, and UCB. Some of her coauthors also disclosed financial relationships with industry. Dr. Sandigursky disclosed having no relevant conflicts of interest.
SOURCE: Benesova K et al. Ann Rheum Dis 2020;79[suppl 1]:168-9, Abstract OP0270.
FROM THE EULAR 2020 E-CONGRESS
Dapagliflozin’s T2D renal protection extends to ‘fast decline’ of eGFR
Treatment of patients with type 2 diabetes with the SGLT2 inhibitor dapagliflozin led to a significant drop in the occurrence of ‘fast decline’ of renal function in more than 15,000 patients enrolled in the drug’s main cardiovascular outcome trial, another example of the potent renal protective effects of agents from this drug class.
Among patients with type 2 diabetes enrolled in the DECLARE-TIMI 58 trial, the incidence of a fast decline in renal function, defined as a drop in estimated glomerular filtration rate (eGFR) of at least 3 mL/min per 1.73 m2, was 27% among patients treated with dapagliflozin and 37% in control patients who received placebo, a statistically significant difference for this post-hoc analysis, Itamar Raz, MD, said at the virtual annual scientific sessions of the American Diabetes Association.
This finding, which adds to a long list of other renal function parameters reported to have been improved by treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors, “emphasizes the value of SGLT2 inhibitors as an important component of both prevention and treatment of chronic kidney disease among patients with type 2 diabetes,” said Dr. Raz, a diabetes researcher and professor of medicine at Hadassah University Hospital in Jerusalem.
The primary, prespecified renal outcomes in DECLARE-TIMI 58 were a cardiorenal composite outcome of sustained decline of at least 40% in eGFR to less than 60 mL/min per 1.73 m2, end-stage renal disease (defined as dialysis for at least 90 days, kidney transplantation, or confirmed sustained eGFR of less than 15 mL/min per 1.73 m2), or death from renal or cardiovascular causes; and a second prespecified renal-specific composite outcome that was the same except for excluding death from cardiovascular causes. The results showed that the cardiorenal outcome dropped by a statistically significant 24% with dapagliflozin treatment relative to control patients, and the renal-specific outcome fell by a statistically significant 47% with dapagliflozin relative to control patients (Lancet Diab Endocrinol. 2019 Aug 1;7[8];606-17).
The new findings on the incidence of fast decline in renal function help to further flesh out the scope of renal benefit exerted by SGLT2 inhibitors like dapagliflozin in patients with type 2 diabetes, said experts. Fast decline is a relatively recently devised measure of a high-risk, precipitous loss of renal function that has been defined as a drop of either 3 or 5 mL/min per 1.73 m2 per year (Kidney Int. 2017 Jun;91[6]:1300-11); for this analysis Dr. Raz and his associates used the less stringent definition.
Finding and treating ‘fast decliners’
The new report from Dr. Raz “confirms the original [renal] findings and looks to expand them to a particularly high risk group: the fast decliners,” commented Robert A. Gabbay, MD, chief science & medical officer of the ADA. “In some ways, the group of patients that we need to find a better treatment for most are those whose GFR declines quickly. We don’t always know who they are until after the fact, and studies have been looking for markers that might prospectively identify them,” he said in an interview.
The new analysis showed that dapagliflozin “was effective in this subgroup of patients. Furthermore, it didn’t matter if they had significant baseline disease or not. Even people with normal kidney function [at baseline] who were still fast decliners fared better with the drug than without it. This suggests that, if it can be confirmed in a prospective study, dapagliflozin might be effective very early in the course of treatment if we can identify who will be the fast decliners.”
Dr. Raz and his associates had the data necessary to calculate the rates of eGFR decline during the full follow-up period for 15,012 of the 17,160 patients enrolled in DECLARE-TIMI 58, and they found that 4,788 (32%) were fast decliners and 10,224 had a slower rate of renal deterioration. The average annual decline in eGFR during the period from 6 months after study entry through 4 years was 6.3 mL/min per 1.73 m2 per year (median of 5.1 mL/min per 1.73 m2 per year) among the fast decliners, and zero (median of 0.6 mL/min per 1.73 m2 per year) among the other patients.
Overcoming dapagliflozin’s initial eGFR reduction
The researchers focused on the 6-month to 4-year period of treatment as more representative of the impact of dapagliflozin because the SGLT2 inhibitors have an established pattern of triggering an initial, moderate decline in eGFR over roughly the first 6 months on the drug, which is similar to what happens to patients who start treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.
“Some patients get as much as a 10% decline in eGFR” when SGLT2 inhibitor treatment starts, but “patients do better over time even with this initial hit,” the same way they do on drugs that act on the renin-angiotensin system, explained Silvio E. Inzucchi, MD, an endocrinologist and professor of medicine at Yale University in New Haven who has extensively studied the SGLT2 inhibitors.
The analyses reported by Dr. Raz showed that the protection against fast decline during the 6-month to 4-year period with dapagliflozin treatment was consistent across a range of patient subgroups regardless of age, duration of their type 2 diabetes, their baseline level of hyperglycemia, and their baseline eGFR. Nearly half the patients enrolled in DECLARE-TIMI 58 had an eGFR at baseline of at least 91 mL/min per 1.73 m2 and in this subgroup the incidence of fast decliners was 23% with dapagliflozin and 31% on placebo. Among the 45% of patients who began with an eGFR of 60-90 mL/min per 1.73 m2 the fast-decliner incidence was 32% and 43% when on or off dapagliflozin. Among the 7% of patients who entered with an eGFR below 60 mL/min per 1.73 m2, the fast-decliner incidence was 25% on dapagliflozin and 36% among controls. All the between-group differences were statistically significant.
The incidence of fast decliners was also lower with dapagliflozin treatment when the analysis included the entire first 4 years on treatment, including the first 6 months when SGLT2s usually spikes a loss of renal function. For the entire 4-year period, fast decline occurred among 34% of patients on dapagliflozin and in 37% of control patients, a statistically significant difference.
The mechanisms behind the consistent renal-protective effects of the SGLT2 inhibitors remain unclear right now, but likely seem related to the “perfect” diuretic action the drugs produce, said Dr. Inzucchi. “They’re not as hugely effective as diuretics, but they’re gentler.” While the SGLT2 inhibitors cause a modest amount of fluid loss ”for some reason they don’t activate the compensatory mechanisms that prevent further reductions in plasma volume,” a property that manifests as little or no change in catecholamines or renin-angiotensin activity, which sets this diuretic action apart from what happens with conventional diuretic drugs, he said in an interview.
In DECLARE-TIMI 58 treatment with dapagliflozin met its primary safety outcome of noninferiority to placebo with respect to major adverse cardiovascular events. The results failed to show statistically significant superiority for one of the primary efficacy endpoints, the rate of major adverse coronary events, but they did show significantly better performance for the second primary efficacy outcome of the rate of cardiovascular death or hospitalization for heart failure, which occurred in 4.9% of patients treated with dapagliflozin and in 5.8% of the control patients during a median follow-up of 4.2 years (N Engl J Med. 2019 Jan 24;380[4]:347-57).
DECLARE-TIMI 58 was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Raz has been an advisor to and speaker on behalf of AstraZeneca as well as several other companies. Dr. Gabbay had no relevant disclosures. Dr. Inzucchi has been a consultant to AstraZeneca, and also to Abbott, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics.
SOURCE: Raz I et al. ADA 2020, Abstract 303-OR.
Treatment of patients with type 2 diabetes with the SGLT2 inhibitor dapagliflozin led to a significant drop in the occurrence of ‘fast decline’ of renal function in more than 15,000 patients enrolled in the drug’s main cardiovascular outcome trial, another example of the potent renal protective effects of agents from this drug class.
Among patients with type 2 diabetes enrolled in the DECLARE-TIMI 58 trial, the incidence of a fast decline in renal function, defined as a drop in estimated glomerular filtration rate (eGFR) of at least 3 mL/min per 1.73 m2, was 27% among patients treated with dapagliflozin and 37% in control patients who received placebo, a statistically significant difference for this post-hoc analysis, Itamar Raz, MD, said at the virtual annual scientific sessions of the American Diabetes Association.
This finding, which adds to a long list of other renal function parameters reported to have been improved by treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors, “emphasizes the value of SGLT2 inhibitors as an important component of both prevention and treatment of chronic kidney disease among patients with type 2 diabetes,” said Dr. Raz, a diabetes researcher and professor of medicine at Hadassah University Hospital in Jerusalem.
The primary, prespecified renal outcomes in DECLARE-TIMI 58 were a cardiorenal composite outcome of sustained decline of at least 40% in eGFR to less than 60 mL/min per 1.73 m2, end-stage renal disease (defined as dialysis for at least 90 days, kidney transplantation, or confirmed sustained eGFR of less than 15 mL/min per 1.73 m2), or death from renal or cardiovascular causes; and a second prespecified renal-specific composite outcome that was the same except for excluding death from cardiovascular causes. The results showed that the cardiorenal outcome dropped by a statistically significant 24% with dapagliflozin treatment relative to control patients, and the renal-specific outcome fell by a statistically significant 47% with dapagliflozin relative to control patients (Lancet Diab Endocrinol. 2019 Aug 1;7[8];606-17).
The new findings on the incidence of fast decline in renal function help to further flesh out the scope of renal benefit exerted by SGLT2 inhibitors like dapagliflozin in patients with type 2 diabetes, said experts. Fast decline is a relatively recently devised measure of a high-risk, precipitous loss of renal function that has been defined as a drop of either 3 or 5 mL/min per 1.73 m2 per year (Kidney Int. 2017 Jun;91[6]:1300-11); for this analysis Dr. Raz and his associates used the less stringent definition.
Finding and treating ‘fast decliners’
The new report from Dr. Raz “confirms the original [renal] findings and looks to expand them to a particularly high risk group: the fast decliners,” commented Robert A. Gabbay, MD, chief science & medical officer of the ADA. “In some ways, the group of patients that we need to find a better treatment for most are those whose GFR declines quickly. We don’t always know who they are until after the fact, and studies have been looking for markers that might prospectively identify them,” he said in an interview.
The new analysis showed that dapagliflozin “was effective in this subgroup of patients. Furthermore, it didn’t matter if they had significant baseline disease or not. Even people with normal kidney function [at baseline] who were still fast decliners fared better with the drug than without it. This suggests that, if it can be confirmed in a prospective study, dapagliflozin might be effective very early in the course of treatment if we can identify who will be the fast decliners.”
Dr. Raz and his associates had the data necessary to calculate the rates of eGFR decline during the full follow-up period for 15,012 of the 17,160 patients enrolled in DECLARE-TIMI 58, and they found that 4,788 (32%) were fast decliners and 10,224 had a slower rate of renal deterioration. The average annual decline in eGFR during the period from 6 months after study entry through 4 years was 6.3 mL/min per 1.73 m2 per year (median of 5.1 mL/min per 1.73 m2 per year) among the fast decliners, and zero (median of 0.6 mL/min per 1.73 m2 per year) among the other patients.
Overcoming dapagliflozin’s initial eGFR reduction
The researchers focused on the 6-month to 4-year period of treatment as more representative of the impact of dapagliflozin because the SGLT2 inhibitors have an established pattern of triggering an initial, moderate decline in eGFR over roughly the first 6 months on the drug, which is similar to what happens to patients who start treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.
“Some patients get as much as a 10% decline in eGFR” when SGLT2 inhibitor treatment starts, but “patients do better over time even with this initial hit,” the same way they do on drugs that act on the renin-angiotensin system, explained Silvio E. Inzucchi, MD, an endocrinologist and professor of medicine at Yale University in New Haven who has extensively studied the SGLT2 inhibitors.
The analyses reported by Dr. Raz showed that the protection against fast decline during the 6-month to 4-year period with dapagliflozin treatment was consistent across a range of patient subgroups regardless of age, duration of their type 2 diabetes, their baseline level of hyperglycemia, and their baseline eGFR. Nearly half the patients enrolled in DECLARE-TIMI 58 had an eGFR at baseline of at least 91 mL/min per 1.73 m2 and in this subgroup the incidence of fast decliners was 23% with dapagliflozin and 31% on placebo. Among the 45% of patients who began with an eGFR of 60-90 mL/min per 1.73 m2 the fast-decliner incidence was 32% and 43% when on or off dapagliflozin. Among the 7% of patients who entered with an eGFR below 60 mL/min per 1.73 m2, the fast-decliner incidence was 25% on dapagliflozin and 36% among controls. All the between-group differences were statistically significant.
The incidence of fast decliners was also lower with dapagliflozin treatment when the analysis included the entire first 4 years on treatment, including the first 6 months when SGLT2s usually spikes a loss of renal function. For the entire 4-year period, fast decline occurred among 34% of patients on dapagliflozin and in 37% of control patients, a statistically significant difference.
The mechanisms behind the consistent renal-protective effects of the SGLT2 inhibitors remain unclear right now, but likely seem related to the “perfect” diuretic action the drugs produce, said Dr. Inzucchi. “They’re not as hugely effective as diuretics, but they’re gentler.” While the SGLT2 inhibitors cause a modest amount of fluid loss ”for some reason they don’t activate the compensatory mechanisms that prevent further reductions in plasma volume,” a property that manifests as little or no change in catecholamines or renin-angiotensin activity, which sets this diuretic action apart from what happens with conventional diuretic drugs, he said in an interview.
In DECLARE-TIMI 58 treatment with dapagliflozin met its primary safety outcome of noninferiority to placebo with respect to major adverse cardiovascular events. The results failed to show statistically significant superiority for one of the primary efficacy endpoints, the rate of major adverse coronary events, but they did show significantly better performance for the second primary efficacy outcome of the rate of cardiovascular death or hospitalization for heart failure, which occurred in 4.9% of patients treated with dapagliflozin and in 5.8% of the control patients during a median follow-up of 4.2 years (N Engl J Med. 2019 Jan 24;380[4]:347-57).
DECLARE-TIMI 58 was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Raz has been an advisor to and speaker on behalf of AstraZeneca as well as several other companies. Dr. Gabbay had no relevant disclosures. Dr. Inzucchi has been a consultant to AstraZeneca, and also to Abbott, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics.
SOURCE: Raz I et al. ADA 2020, Abstract 303-OR.
Treatment of patients with type 2 diabetes with the SGLT2 inhibitor dapagliflozin led to a significant drop in the occurrence of ‘fast decline’ of renal function in more than 15,000 patients enrolled in the drug’s main cardiovascular outcome trial, another example of the potent renal protective effects of agents from this drug class.
Among patients with type 2 diabetes enrolled in the DECLARE-TIMI 58 trial, the incidence of a fast decline in renal function, defined as a drop in estimated glomerular filtration rate (eGFR) of at least 3 mL/min per 1.73 m2, was 27% among patients treated with dapagliflozin and 37% in control patients who received placebo, a statistically significant difference for this post-hoc analysis, Itamar Raz, MD, said at the virtual annual scientific sessions of the American Diabetes Association.
This finding, which adds to a long list of other renal function parameters reported to have been improved by treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors, “emphasizes the value of SGLT2 inhibitors as an important component of both prevention and treatment of chronic kidney disease among patients with type 2 diabetes,” said Dr. Raz, a diabetes researcher and professor of medicine at Hadassah University Hospital in Jerusalem.
The primary, prespecified renal outcomes in DECLARE-TIMI 58 were a cardiorenal composite outcome of sustained decline of at least 40% in eGFR to less than 60 mL/min per 1.73 m2, end-stage renal disease (defined as dialysis for at least 90 days, kidney transplantation, or confirmed sustained eGFR of less than 15 mL/min per 1.73 m2), or death from renal or cardiovascular causes; and a second prespecified renal-specific composite outcome that was the same except for excluding death from cardiovascular causes. The results showed that the cardiorenal outcome dropped by a statistically significant 24% with dapagliflozin treatment relative to control patients, and the renal-specific outcome fell by a statistically significant 47% with dapagliflozin relative to control patients (Lancet Diab Endocrinol. 2019 Aug 1;7[8];606-17).
The new findings on the incidence of fast decline in renal function help to further flesh out the scope of renal benefit exerted by SGLT2 inhibitors like dapagliflozin in patients with type 2 diabetes, said experts. Fast decline is a relatively recently devised measure of a high-risk, precipitous loss of renal function that has been defined as a drop of either 3 or 5 mL/min per 1.73 m2 per year (Kidney Int. 2017 Jun;91[6]:1300-11); for this analysis Dr. Raz and his associates used the less stringent definition.
Finding and treating ‘fast decliners’
The new report from Dr. Raz “confirms the original [renal] findings and looks to expand them to a particularly high risk group: the fast decliners,” commented Robert A. Gabbay, MD, chief science & medical officer of the ADA. “In some ways, the group of patients that we need to find a better treatment for most are those whose GFR declines quickly. We don’t always know who they are until after the fact, and studies have been looking for markers that might prospectively identify them,” he said in an interview.
The new analysis showed that dapagliflozin “was effective in this subgroup of patients. Furthermore, it didn’t matter if they had significant baseline disease or not. Even people with normal kidney function [at baseline] who were still fast decliners fared better with the drug than without it. This suggests that, if it can be confirmed in a prospective study, dapagliflozin might be effective very early in the course of treatment if we can identify who will be the fast decliners.”
Dr. Raz and his associates had the data necessary to calculate the rates of eGFR decline during the full follow-up period for 15,012 of the 17,160 patients enrolled in DECLARE-TIMI 58, and they found that 4,788 (32%) were fast decliners and 10,224 had a slower rate of renal deterioration. The average annual decline in eGFR during the period from 6 months after study entry through 4 years was 6.3 mL/min per 1.73 m2 per year (median of 5.1 mL/min per 1.73 m2 per year) among the fast decliners, and zero (median of 0.6 mL/min per 1.73 m2 per year) among the other patients.
Overcoming dapagliflozin’s initial eGFR reduction
The researchers focused on the 6-month to 4-year period of treatment as more representative of the impact of dapagliflozin because the SGLT2 inhibitors have an established pattern of triggering an initial, moderate decline in eGFR over roughly the first 6 months on the drug, which is similar to what happens to patients who start treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.
“Some patients get as much as a 10% decline in eGFR” when SGLT2 inhibitor treatment starts, but “patients do better over time even with this initial hit,” the same way they do on drugs that act on the renin-angiotensin system, explained Silvio E. Inzucchi, MD, an endocrinologist and professor of medicine at Yale University in New Haven who has extensively studied the SGLT2 inhibitors.
The analyses reported by Dr. Raz showed that the protection against fast decline during the 6-month to 4-year period with dapagliflozin treatment was consistent across a range of patient subgroups regardless of age, duration of their type 2 diabetes, their baseline level of hyperglycemia, and their baseline eGFR. Nearly half the patients enrolled in DECLARE-TIMI 58 had an eGFR at baseline of at least 91 mL/min per 1.73 m2 and in this subgroup the incidence of fast decliners was 23% with dapagliflozin and 31% on placebo. Among the 45% of patients who began with an eGFR of 60-90 mL/min per 1.73 m2 the fast-decliner incidence was 32% and 43% when on or off dapagliflozin. Among the 7% of patients who entered with an eGFR below 60 mL/min per 1.73 m2, the fast-decliner incidence was 25% on dapagliflozin and 36% among controls. All the between-group differences were statistically significant.
The incidence of fast decliners was also lower with dapagliflozin treatment when the analysis included the entire first 4 years on treatment, including the first 6 months when SGLT2s usually spikes a loss of renal function. For the entire 4-year period, fast decline occurred among 34% of patients on dapagliflozin and in 37% of control patients, a statistically significant difference.
The mechanisms behind the consistent renal-protective effects of the SGLT2 inhibitors remain unclear right now, but likely seem related to the “perfect” diuretic action the drugs produce, said Dr. Inzucchi. “They’re not as hugely effective as diuretics, but they’re gentler.” While the SGLT2 inhibitors cause a modest amount of fluid loss ”for some reason they don’t activate the compensatory mechanisms that prevent further reductions in plasma volume,” a property that manifests as little or no change in catecholamines or renin-angiotensin activity, which sets this diuretic action apart from what happens with conventional diuretic drugs, he said in an interview.
In DECLARE-TIMI 58 treatment with dapagliflozin met its primary safety outcome of noninferiority to placebo with respect to major adverse cardiovascular events. The results failed to show statistically significant superiority for one of the primary efficacy endpoints, the rate of major adverse coronary events, but they did show significantly better performance for the second primary efficacy outcome of the rate of cardiovascular death or hospitalization for heart failure, which occurred in 4.9% of patients treated with dapagliflozin and in 5.8% of the control patients during a median follow-up of 4.2 years (N Engl J Med. 2019 Jan 24;380[4]:347-57).
DECLARE-TIMI 58 was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Raz has been an advisor to and speaker on behalf of AstraZeneca as well as several other companies. Dr. Gabbay had no relevant disclosures. Dr. Inzucchi has been a consultant to AstraZeneca, and also to Abbott, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics.
SOURCE: Raz I et al. ADA 2020, Abstract 303-OR.
FROM ADA 2020
Examining bias
I have an automatic preference for white people over black people. This isn’t my opinion; rather, it is my implicit bias test result. I didn’t believe it at first. Trying hard to not be biased, I took the test again and received the same outcome. My reaction – disbelief – is typical for those like me: White people who believe they are good human beings.
We’ve all watched in horror the acts of violence against blacks in the news. I was shocked and disgusted. It was easy to believe, however, that I am in no way complicit in the injustice and racism I was watching. I think I’m fair and without prejudice. I have never intentionally discriminated against someone. Wanting to help, I listened to my black colleagues, staff, and patients. What I learned made me uncomfortable.
Through all this news, I’d said little to my colleagues and friends. I cannot identify with how a black person has felt recently. What if I said the wrong thing or caused offense? The safe option is to say nothing. I learned that this is a common reaction and the least helpful. The advice from one black colleague was simple: “Just ask us.” Instead of ignoring the issue, she advised me to say: “I wonder what this experience has been like for you. Would you like to share?” And, if you mean it, to add, “I stand with you.” The latter should be followed by “What can I do to help?” Or, more powerfully, “What have I done that makes me complicit?”
Some of these conversations will be uncomfortable. If you want to help, then sit with that. Feeling uncomfortable might mean you are beginning to understand.
I also heard about the excellent book “White Fragility,” by Robin DiAngelo, PhD. In it, she argues that it is difficult for white people to talk about racism because of a tendency to react with defensiveness, guilt, and sometimes anger.
Many of the chapters in the book were easy to read because they didn’t apply to me: I don’t get angry in equity, inclusion, and diversity meetings. I don’t resent affirmative action programs. But then Dr. DiAngelo got me: I believed because I’m a good person and I have no intention of being racist, I’m absolved. Her argument was enlightening. Like all white people in the United States, I have benefited from white privilege. Yes, I’ve worked hard, but I also grew up in a white family with a college-educated father. That alone afforded me academic and financial advantages, which pushed me ahead. I’ve benefited from the status quo.
I have also failed to speak up when white friends carried on about how unnecessary affirmative action programs have become. I’ve sat with sealed lips when I’ve heard comments like “As a white male, it’s a lot harder to get into prestigious schools now.” Having no intention to harm doesn’t matter; plenty of harm is done unintentionally.
I also believed that because I have good intentions, I have no racial bias. I was wrong. The test I took online is an excellent tool to combat this blind spot. It was created by Harvard researchers and is available to everyone: Take a Test. It asks you to categorize faces as good or bad and records your tiny reaction times. Based on these and other questions, it provides feedback on your personal biases.
I was surprised that I have an implicit preference for white people over black people. That’s the point. Most of us are unaware of our biases and falsely believe we are free of them. I encourage you to take the test and learn about yourself. If the result makes you uncomfortable, then sit with it. Try not to be defensive, as I was, and accept that, even if you are a good person, you can become a better one.
Based on what I’ve learned and heard in the last few weeks, I’ve committed to a few things: To acknowledge the harm done to my black and brown colleagues and my complicity even by acts of omission. To not avoid uncomfortable feelings or uncomfortable conversations. As a leader, to use my organizational status to advocate. To stand by my partners of color not only in dramatic one-time marches but also against the everyday perpetrators of microaggressions. To create a safe space and invite my colleagues, staff, friends, and patients to share.
Standing up against racism is all our responsibility. As Dr. Martin Luther King Jr. reminds us: “In the end, we will remember not the words of our enemies, but the silence of our friends.”
Dr. Benabio is director of healthcare transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. He has no disclosures related to this column. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
I have an automatic preference for white people over black people. This isn’t my opinion; rather, it is my implicit bias test result. I didn’t believe it at first. Trying hard to not be biased, I took the test again and received the same outcome. My reaction – disbelief – is typical for those like me: White people who believe they are good human beings.
We’ve all watched in horror the acts of violence against blacks in the news. I was shocked and disgusted. It was easy to believe, however, that I am in no way complicit in the injustice and racism I was watching. I think I’m fair and without prejudice. I have never intentionally discriminated against someone. Wanting to help, I listened to my black colleagues, staff, and patients. What I learned made me uncomfortable.
Through all this news, I’d said little to my colleagues and friends. I cannot identify with how a black person has felt recently. What if I said the wrong thing or caused offense? The safe option is to say nothing. I learned that this is a common reaction and the least helpful. The advice from one black colleague was simple: “Just ask us.” Instead of ignoring the issue, she advised me to say: “I wonder what this experience has been like for you. Would you like to share?” And, if you mean it, to add, “I stand with you.” The latter should be followed by “What can I do to help?” Or, more powerfully, “What have I done that makes me complicit?”
Some of these conversations will be uncomfortable. If you want to help, then sit with that. Feeling uncomfortable might mean you are beginning to understand.
I also heard about the excellent book “White Fragility,” by Robin DiAngelo, PhD. In it, she argues that it is difficult for white people to talk about racism because of a tendency to react with defensiveness, guilt, and sometimes anger.
Many of the chapters in the book were easy to read because they didn’t apply to me: I don’t get angry in equity, inclusion, and diversity meetings. I don’t resent affirmative action programs. But then Dr. DiAngelo got me: I believed because I’m a good person and I have no intention of being racist, I’m absolved. Her argument was enlightening. Like all white people in the United States, I have benefited from white privilege. Yes, I’ve worked hard, but I also grew up in a white family with a college-educated father. That alone afforded me academic and financial advantages, which pushed me ahead. I’ve benefited from the status quo.
I have also failed to speak up when white friends carried on about how unnecessary affirmative action programs have become. I’ve sat with sealed lips when I’ve heard comments like “As a white male, it’s a lot harder to get into prestigious schools now.” Having no intention to harm doesn’t matter; plenty of harm is done unintentionally.
I also believed that because I have good intentions, I have no racial bias. I was wrong. The test I took online is an excellent tool to combat this blind spot. It was created by Harvard researchers and is available to everyone: Take a Test. It asks you to categorize faces as good or bad and records your tiny reaction times. Based on these and other questions, it provides feedback on your personal biases.
I was surprised that I have an implicit preference for white people over black people. That’s the point. Most of us are unaware of our biases and falsely believe we are free of them. I encourage you to take the test and learn about yourself. If the result makes you uncomfortable, then sit with it. Try not to be defensive, as I was, and accept that, even if you are a good person, you can become a better one.
Based on what I’ve learned and heard in the last few weeks, I’ve committed to a few things: To acknowledge the harm done to my black and brown colleagues and my complicity even by acts of omission. To not avoid uncomfortable feelings or uncomfortable conversations. As a leader, to use my organizational status to advocate. To stand by my partners of color not only in dramatic one-time marches but also against the everyday perpetrators of microaggressions. To create a safe space and invite my colleagues, staff, friends, and patients to share.
Standing up against racism is all our responsibility. As Dr. Martin Luther King Jr. reminds us: “In the end, we will remember not the words of our enemies, but the silence of our friends.”
Dr. Benabio is director of healthcare transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. He has no disclosures related to this column. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
I have an automatic preference for white people over black people. This isn’t my opinion; rather, it is my implicit bias test result. I didn’t believe it at first. Trying hard to not be biased, I took the test again and received the same outcome. My reaction – disbelief – is typical for those like me: White people who believe they are good human beings.
We’ve all watched in horror the acts of violence against blacks in the news. I was shocked and disgusted. It was easy to believe, however, that I am in no way complicit in the injustice and racism I was watching. I think I’m fair and without prejudice. I have never intentionally discriminated against someone. Wanting to help, I listened to my black colleagues, staff, and patients. What I learned made me uncomfortable.
Through all this news, I’d said little to my colleagues and friends. I cannot identify with how a black person has felt recently. What if I said the wrong thing or caused offense? The safe option is to say nothing. I learned that this is a common reaction and the least helpful. The advice from one black colleague was simple: “Just ask us.” Instead of ignoring the issue, she advised me to say: “I wonder what this experience has been like for you. Would you like to share?” And, if you mean it, to add, “I stand with you.” The latter should be followed by “What can I do to help?” Or, more powerfully, “What have I done that makes me complicit?”
Some of these conversations will be uncomfortable. If you want to help, then sit with that. Feeling uncomfortable might mean you are beginning to understand.
I also heard about the excellent book “White Fragility,” by Robin DiAngelo, PhD. In it, she argues that it is difficult for white people to talk about racism because of a tendency to react with defensiveness, guilt, and sometimes anger.
Many of the chapters in the book were easy to read because they didn’t apply to me: I don’t get angry in equity, inclusion, and diversity meetings. I don’t resent affirmative action programs. But then Dr. DiAngelo got me: I believed because I’m a good person and I have no intention of being racist, I’m absolved. Her argument was enlightening. Like all white people in the United States, I have benefited from white privilege. Yes, I’ve worked hard, but I also grew up in a white family with a college-educated father. That alone afforded me academic and financial advantages, which pushed me ahead. I’ve benefited from the status quo.
I have also failed to speak up when white friends carried on about how unnecessary affirmative action programs have become. I’ve sat with sealed lips when I’ve heard comments like “As a white male, it’s a lot harder to get into prestigious schools now.” Having no intention to harm doesn’t matter; plenty of harm is done unintentionally.
I also believed that because I have good intentions, I have no racial bias. I was wrong. The test I took online is an excellent tool to combat this blind spot. It was created by Harvard researchers and is available to everyone: Take a Test. It asks you to categorize faces as good or bad and records your tiny reaction times. Based on these and other questions, it provides feedback on your personal biases.
I was surprised that I have an implicit preference for white people over black people. That’s the point. Most of us are unaware of our biases and falsely believe we are free of them. I encourage you to take the test and learn about yourself. If the result makes you uncomfortable, then sit with it. Try not to be defensive, as I was, and accept that, even if you are a good person, you can become a better one.
Based on what I’ve learned and heard in the last few weeks, I’ve committed to a few things: To acknowledge the harm done to my black and brown colleagues and my complicity even by acts of omission. To not avoid uncomfortable feelings or uncomfortable conversations. As a leader, to use my organizational status to advocate. To stand by my partners of color not only in dramatic one-time marches but also against the everyday perpetrators of microaggressions. To create a safe space and invite my colleagues, staff, friends, and patients to share.
Standing up against racism is all our responsibility. As Dr. Martin Luther King Jr. reminds us: “In the end, we will remember not the words of our enemies, but the silence of our friends.”
Dr. Benabio is director of healthcare transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. He has no disclosures related to this column. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
First-episode psychosis in the time of COVID-19
Patients may need more than weekly teletherapy
In response to COVID-19, we have seen a rapid transformation to virtually delivered mental health care, essential for the prevention and treatment of various mental health conditions during an isolating and stress-inducing pandemic. Yet teletherapy and virtual medication management alone may not adequately address the needs of some of the populations we serve.
Take Jackson, whose name and details have been changed for privacy. A year ago, Jackson, in his last year of high school, began hearing voices that others could not hear. After becoming increasingly withdrawn, his father sought out treatment for him and learned that Jackson was experiencing his first episode of psychosis.
Psychosis involves disruptions in the way one processes thoughts and feelings or behaves, and includes delusions – or unusual beliefs – and hallucinations, meaning seeing and hearing things that others cannot. “First-episode psychosis” (FEP) simply refers to the first time an individual experiences this. It typically occurs between one’s teenage years and their 20s. Whereas some individuals recover from their first episode and may not experience another, others go on to experience recurrence, and sometimes a waxing and waning illness course.
Jackson enrolled in a comprehensive mental health program that not only includes a psychiatrist, but also therapists who provide case management services, as well as a peer specialist; this is someone with lived experience navigating mental illness. The program also includes an employment and education specialist and family and group therapy sessions. His team helped him identify and work toward his personal recovery goals: graduating from high school, obtaining a job, and maintaining a strong relationship with his father.
One hundred thousand adolescents and young adults like Jackson experience FEP each year, and now, in the wake of COVID-19, they probably have more limited access to the kind of support that can be vital to recovery.
Studies have shown that untreated psychosis can detrimentally affect quality of life in several ways, including by negatively affecting interpersonal relationships, interfering with obtaining or maintaining employment, and increasing the risk for problematic substance use. The psychosocial effects of COVID-19 could compound problems that individuals navigating psychosis already face, such as stigmatization, social isolation, and unemployment. On top of this, individuals who experience additional marginalization and downstream effects of systematic discriminatory practices by virtue of their race or ethnicity, immigration status, or language bear the brunt of some of this pandemic’s worst health inequities.
Early and efficacious treatment is critically important for individuals experiencing psychosis. Evidence shows that engagement in coordinated specialty care (CSC) specifically can improve outcomes, including the likelihood of being engaged in school or work and lower rates of hospitalization. CSC is a team-based approach that utilizes the unique skills of every team member to support an individual in reaching their recovery goals, whether it’s starting or finishing college or building a new relationship.
Unlike traditional treatment goals, which often focus on “symptom reduction,” recovery-oriented care is about supporting an individual in obtaining a sense of satisfaction, meaning, and purpose in life. It also supports navigating such experiences as a job interview or a date. These key, multifaceted components must be made accessible and adapted during these times.
For individuals like Jackson, it is crucial to be able to continue accessing quality CSC, even during our current pandemic. Lisa Dixon, MD, a professor of psychiatry at Columbia University, leads ONTrackNY, a statewide FEP program. She states that “effective, recovery-oriented treatment can make such a huge difference in the lives of these young people who are at a potential inflection point in their lives. Creative, collaborative clinicians can maintain connection and support.”
So how can we adapt CSC during this time? In addition to virtualized medication management and individual therapy, other components of CSC can be creatively adapted for online platforms. Group sessions can be completed virtually, from family to peer-led. Though the unemployment rate continues to rise, we can still help participants with a desire to work find employers that are offering remote work or navigate the risks of potential COVID-19 work exposures if remote options aren’t available. We can also support their developing skills to be used once other employers that pose less risk reopen.
For those in school, virtual education support can provide study skills, ways to cope with transition to an online classroom, or help with obtaining tutoring. Nutritionists can work remotely to provide support and creatively use online platforms for real-time feedback in a participant’s kitchen. Virtual case management is even more essential in the wake of COVID-19, from assistance with applying for unemployment insurance and financial aid to obtaining health insurance or determining eligibility.
For those without access to virtual platforms, individual and group telephone sessions and text check-ins can provide meaningful opportunities for continued engagement. For those who are unstably housed or have limited privacy in housing, teams must generate ideas of where to have remote sessions, such as a nearby park.
In a world now dominated by virtual care, it is critically important that individuals needing to see a clinician in person still be able to do so. Whether it is due to an acute crisis or to administer a long-acting injection medication, it is our responsibility to thoughtfully and judiciously remain available to patients, using appropriate personal protective equipment and precautions.
Jackson is one of many young people in recovery from psychosis. He is not defined by or limited by his experiences, but rather is navigating the possibilities that lie ahead of him, defining for himself who he wants to be in this world as it evolves. In the midst of COVID-19, as we seek to innovate – from how we exercise to how we throw birthday parties – let’s also be innovative in how we provide care and support for individuals experiencing psychosis.
This article first appeared on Medscape.com.
Patients may need more than weekly teletherapy
Patients may need more than weekly teletherapy
In response to COVID-19, we have seen a rapid transformation to virtually delivered mental health care, essential for the prevention and treatment of various mental health conditions during an isolating and stress-inducing pandemic. Yet teletherapy and virtual medication management alone may not adequately address the needs of some of the populations we serve.
Take Jackson, whose name and details have been changed for privacy. A year ago, Jackson, in his last year of high school, began hearing voices that others could not hear. After becoming increasingly withdrawn, his father sought out treatment for him and learned that Jackson was experiencing his first episode of psychosis.
Psychosis involves disruptions in the way one processes thoughts and feelings or behaves, and includes delusions – or unusual beliefs – and hallucinations, meaning seeing and hearing things that others cannot. “First-episode psychosis” (FEP) simply refers to the first time an individual experiences this. It typically occurs between one’s teenage years and their 20s. Whereas some individuals recover from their first episode and may not experience another, others go on to experience recurrence, and sometimes a waxing and waning illness course.
Jackson enrolled in a comprehensive mental health program that not only includes a psychiatrist, but also therapists who provide case management services, as well as a peer specialist; this is someone with lived experience navigating mental illness. The program also includes an employment and education specialist and family and group therapy sessions. His team helped him identify and work toward his personal recovery goals: graduating from high school, obtaining a job, and maintaining a strong relationship with his father.
One hundred thousand adolescents and young adults like Jackson experience FEP each year, and now, in the wake of COVID-19, they probably have more limited access to the kind of support that can be vital to recovery.
Studies have shown that untreated psychosis can detrimentally affect quality of life in several ways, including by negatively affecting interpersonal relationships, interfering with obtaining or maintaining employment, and increasing the risk for problematic substance use. The psychosocial effects of COVID-19 could compound problems that individuals navigating psychosis already face, such as stigmatization, social isolation, and unemployment. On top of this, individuals who experience additional marginalization and downstream effects of systematic discriminatory practices by virtue of their race or ethnicity, immigration status, or language bear the brunt of some of this pandemic’s worst health inequities.
Early and efficacious treatment is critically important for individuals experiencing psychosis. Evidence shows that engagement in coordinated specialty care (CSC) specifically can improve outcomes, including the likelihood of being engaged in school or work and lower rates of hospitalization. CSC is a team-based approach that utilizes the unique skills of every team member to support an individual in reaching their recovery goals, whether it’s starting or finishing college or building a new relationship.
Unlike traditional treatment goals, which often focus on “symptom reduction,” recovery-oriented care is about supporting an individual in obtaining a sense of satisfaction, meaning, and purpose in life. It also supports navigating such experiences as a job interview or a date. These key, multifaceted components must be made accessible and adapted during these times.
For individuals like Jackson, it is crucial to be able to continue accessing quality CSC, even during our current pandemic. Lisa Dixon, MD, a professor of psychiatry at Columbia University, leads ONTrackNY, a statewide FEP program. She states that “effective, recovery-oriented treatment can make such a huge difference in the lives of these young people who are at a potential inflection point in their lives. Creative, collaborative clinicians can maintain connection and support.”
So how can we adapt CSC during this time? In addition to virtualized medication management and individual therapy, other components of CSC can be creatively adapted for online platforms. Group sessions can be completed virtually, from family to peer-led. Though the unemployment rate continues to rise, we can still help participants with a desire to work find employers that are offering remote work or navigate the risks of potential COVID-19 work exposures if remote options aren’t available. We can also support their developing skills to be used once other employers that pose less risk reopen.
For those in school, virtual education support can provide study skills, ways to cope with transition to an online classroom, or help with obtaining tutoring. Nutritionists can work remotely to provide support and creatively use online platforms for real-time feedback in a participant’s kitchen. Virtual case management is even more essential in the wake of COVID-19, from assistance with applying for unemployment insurance and financial aid to obtaining health insurance or determining eligibility.
For those without access to virtual platforms, individual and group telephone sessions and text check-ins can provide meaningful opportunities for continued engagement. For those who are unstably housed or have limited privacy in housing, teams must generate ideas of where to have remote sessions, such as a nearby park.
In a world now dominated by virtual care, it is critically important that individuals needing to see a clinician in person still be able to do so. Whether it is due to an acute crisis or to administer a long-acting injection medication, it is our responsibility to thoughtfully and judiciously remain available to patients, using appropriate personal protective equipment and precautions.
Jackson is one of many young people in recovery from psychosis. He is not defined by or limited by his experiences, but rather is navigating the possibilities that lie ahead of him, defining for himself who he wants to be in this world as it evolves. In the midst of COVID-19, as we seek to innovate – from how we exercise to how we throw birthday parties – let’s also be innovative in how we provide care and support for individuals experiencing psychosis.
This article first appeared on Medscape.com.
In response to COVID-19, we have seen a rapid transformation to virtually delivered mental health care, essential for the prevention and treatment of various mental health conditions during an isolating and stress-inducing pandemic. Yet teletherapy and virtual medication management alone may not adequately address the needs of some of the populations we serve.
Take Jackson, whose name and details have been changed for privacy. A year ago, Jackson, in his last year of high school, began hearing voices that others could not hear. After becoming increasingly withdrawn, his father sought out treatment for him and learned that Jackson was experiencing his first episode of psychosis.
Psychosis involves disruptions in the way one processes thoughts and feelings or behaves, and includes delusions – or unusual beliefs – and hallucinations, meaning seeing and hearing things that others cannot. “First-episode psychosis” (FEP) simply refers to the first time an individual experiences this. It typically occurs between one’s teenage years and their 20s. Whereas some individuals recover from their first episode and may not experience another, others go on to experience recurrence, and sometimes a waxing and waning illness course.
Jackson enrolled in a comprehensive mental health program that not only includes a psychiatrist, but also therapists who provide case management services, as well as a peer specialist; this is someone with lived experience navigating mental illness. The program also includes an employment and education specialist and family and group therapy sessions. His team helped him identify and work toward his personal recovery goals: graduating from high school, obtaining a job, and maintaining a strong relationship with his father.
One hundred thousand adolescents and young adults like Jackson experience FEP each year, and now, in the wake of COVID-19, they probably have more limited access to the kind of support that can be vital to recovery.
Studies have shown that untreated psychosis can detrimentally affect quality of life in several ways, including by negatively affecting interpersonal relationships, interfering with obtaining or maintaining employment, and increasing the risk for problematic substance use. The psychosocial effects of COVID-19 could compound problems that individuals navigating psychosis already face, such as stigmatization, social isolation, and unemployment. On top of this, individuals who experience additional marginalization and downstream effects of systematic discriminatory practices by virtue of their race or ethnicity, immigration status, or language bear the brunt of some of this pandemic’s worst health inequities.
Early and efficacious treatment is critically important for individuals experiencing psychosis. Evidence shows that engagement in coordinated specialty care (CSC) specifically can improve outcomes, including the likelihood of being engaged in school or work and lower rates of hospitalization. CSC is a team-based approach that utilizes the unique skills of every team member to support an individual in reaching their recovery goals, whether it’s starting or finishing college or building a new relationship.
Unlike traditional treatment goals, which often focus on “symptom reduction,” recovery-oriented care is about supporting an individual in obtaining a sense of satisfaction, meaning, and purpose in life. It also supports navigating such experiences as a job interview or a date. These key, multifaceted components must be made accessible and adapted during these times.
For individuals like Jackson, it is crucial to be able to continue accessing quality CSC, even during our current pandemic. Lisa Dixon, MD, a professor of psychiatry at Columbia University, leads ONTrackNY, a statewide FEP program. She states that “effective, recovery-oriented treatment can make such a huge difference in the lives of these young people who are at a potential inflection point in their lives. Creative, collaborative clinicians can maintain connection and support.”
So how can we adapt CSC during this time? In addition to virtualized medication management and individual therapy, other components of CSC can be creatively adapted for online platforms. Group sessions can be completed virtually, from family to peer-led. Though the unemployment rate continues to rise, we can still help participants with a desire to work find employers that are offering remote work or navigate the risks of potential COVID-19 work exposures if remote options aren’t available. We can also support their developing skills to be used once other employers that pose less risk reopen.
For those in school, virtual education support can provide study skills, ways to cope with transition to an online classroom, or help with obtaining tutoring. Nutritionists can work remotely to provide support and creatively use online platforms for real-time feedback in a participant’s kitchen. Virtual case management is even more essential in the wake of COVID-19, from assistance with applying for unemployment insurance and financial aid to obtaining health insurance or determining eligibility.
For those without access to virtual platforms, individual and group telephone sessions and text check-ins can provide meaningful opportunities for continued engagement. For those who are unstably housed or have limited privacy in housing, teams must generate ideas of where to have remote sessions, such as a nearby park.
In a world now dominated by virtual care, it is critically important that individuals needing to see a clinician in person still be able to do so. Whether it is due to an acute crisis or to administer a long-acting injection medication, it is our responsibility to thoughtfully and judiciously remain available to patients, using appropriate personal protective equipment and precautions.
Jackson is one of many young people in recovery from psychosis. He is not defined by or limited by his experiences, but rather is navigating the possibilities that lie ahead of him, defining for himself who he wants to be in this world as it evolves. In the midst of COVID-19, as we seek to innovate – from how we exercise to how we throw birthday parties – let’s also be innovative in how we provide care and support for individuals experiencing psychosis.
This article first appeared on Medscape.com.
NSAID/triptan combination improves treatment-resistant migraine
The combination (AXS-07), in development by Axsome Therapeutics, was also safe and well tolerated, according to Cedric O’Gorman, MD, Axsome senior vice president for clinical development and medical affairs. It was tested in subjects who had inadequately responded to previous treatment and who had an average of 2-8 migraines per month.
The therapy combines 10-mg rizatriptan with 20-mg meloxicam delivered by the company’s MoSEIC technology. “Treatment with AXS-07 resulted in rapid, sustained, substantial, and statistically significant effect as compared with rizatriptan and placebo. The enhanced effect of AXS-07 may be especially relevant for patients with more difficult-to-treat migraine,” said Dr. O’Gorman during a presentation of the study at the virtual annual meeting of the American Headache Society.
Matthew Robbins, MD, said in an interview, “This combination may be particularly useful for patients who want to take an oral medication but still need rapid and sustained pain freedom.” Dr. Robbins is the neurology residency program director at New York Presbyterian Hospital and an associate professor of neurology at Weill Cornell Medicine, New York. He was not involved in the research.
The study randomized 1,594 patients 2:2:2:1 to AXS-07, rizatriptan alone, MoSEIC meloxicam alone, or placebo, which could be administered immediately after a migraine event. Between 35% and 40% of participants across the groups had previously used triptans. The mean migraine treatment optimization questionnaire (mTOQ4) score was 3.6, indicating that the population was made up of people with poor responses to medication. Among patients in the study group, 37%-43% had severe pain intensity, 41%-47% were obese, and 35%-37% had morning migraine.
At 2 hours, more patients in the AXS-07 group than in the placebo group were pain free (19.9% vs. 6.7%; P < 0.001). They were also more likely to experience freedom from the most bothersome symptom at 2 hours (36.9% vs. 24.4%; P = 0.002). Secondary outcome measures favored the AXS-07 group when compared with the rizatriptan-only group, including 1-hour pain relief (44% vs. 37%; P = 0.04), 2- to 24-hour sustained pain relief (53% vs. 44%; P = 0.006), 2- to 48-hour sustained pain relief (47% vs. 37%; P = 0.003), 2- to 24-hour sustained pain freedom (16% vs. 11%; P = 0.038), 2- to 48-hour sustained pain freedom (15% vs. 8.8%; P = 0.003), rescue medication use (23% vs. 35%; P < 0.001), a rating of much or very much improved on the Patient Global Impression of Change (PGI-C) scale (47% vs. 39%; P = 0.022), and functional improvement at 24 hours (64% vs. 56%; P = 0.027).
“The percentage of patients achieving pain relief with AXS-07 was numerically greater than with rizatriptan at every time point measure, starting at 15 minutes, and was statistically significant by 60 minutes. This is significant because rizatriptan is widely recognized as the fastest-acting and one of the most effective oral triptans,” said Dr. O’Gorman.
The frequency of adverse events was 11.0% in the AXS-07, 15.4% in the rizatriptan group, 11.5% in the meloxicam group, and 6.0% in the placebo group.
“The added benefit of this study was the demonstration of efficacy in patients who have previously failed other acute treatments. We know that ineffective acute treatments are a likely risk factor for the progression of episodic migraine to chronic migraine, and the more options that we have for our patients, the better,” Dr. Robbins commented.
He remains concerned about cost and access, however. A limited number of tablets per month for acute treatments prompt clinicians to prescribe the medications individually and advise patients to take them in combination. “Rizatriptan is generally available in 12 monthly tablets by many coverage plans, and I would hope that, if ultimately FDA approved, a similar allotment is made affordable and accessible,” he said.
The study was funded by Axsome Therapeutics. Dr. O’Gorman is an employee of Axsome. Dr. Robbins has no relevant financial disclosures.
SOURCE: O’Gorman C et al. AHS 2020, Abstract 840673.
The combination (AXS-07), in development by Axsome Therapeutics, was also safe and well tolerated, according to Cedric O’Gorman, MD, Axsome senior vice president for clinical development and medical affairs. It was tested in subjects who had inadequately responded to previous treatment and who had an average of 2-8 migraines per month.
The therapy combines 10-mg rizatriptan with 20-mg meloxicam delivered by the company’s MoSEIC technology. “Treatment with AXS-07 resulted in rapid, sustained, substantial, and statistically significant effect as compared with rizatriptan and placebo. The enhanced effect of AXS-07 may be especially relevant for patients with more difficult-to-treat migraine,” said Dr. O’Gorman during a presentation of the study at the virtual annual meeting of the American Headache Society.
Matthew Robbins, MD, said in an interview, “This combination may be particularly useful for patients who want to take an oral medication but still need rapid and sustained pain freedom.” Dr. Robbins is the neurology residency program director at New York Presbyterian Hospital and an associate professor of neurology at Weill Cornell Medicine, New York. He was not involved in the research.
The study randomized 1,594 patients 2:2:2:1 to AXS-07, rizatriptan alone, MoSEIC meloxicam alone, or placebo, which could be administered immediately after a migraine event. Between 35% and 40% of participants across the groups had previously used triptans. The mean migraine treatment optimization questionnaire (mTOQ4) score was 3.6, indicating that the population was made up of people with poor responses to medication. Among patients in the study group, 37%-43% had severe pain intensity, 41%-47% were obese, and 35%-37% had morning migraine.
At 2 hours, more patients in the AXS-07 group than in the placebo group were pain free (19.9% vs. 6.7%; P < 0.001). They were also more likely to experience freedom from the most bothersome symptom at 2 hours (36.9% vs. 24.4%; P = 0.002). Secondary outcome measures favored the AXS-07 group when compared with the rizatriptan-only group, including 1-hour pain relief (44% vs. 37%; P = 0.04), 2- to 24-hour sustained pain relief (53% vs. 44%; P = 0.006), 2- to 48-hour sustained pain relief (47% vs. 37%; P = 0.003), 2- to 24-hour sustained pain freedom (16% vs. 11%; P = 0.038), 2- to 48-hour sustained pain freedom (15% vs. 8.8%; P = 0.003), rescue medication use (23% vs. 35%; P < 0.001), a rating of much or very much improved on the Patient Global Impression of Change (PGI-C) scale (47% vs. 39%; P = 0.022), and functional improvement at 24 hours (64% vs. 56%; P = 0.027).
“The percentage of patients achieving pain relief with AXS-07 was numerically greater than with rizatriptan at every time point measure, starting at 15 minutes, and was statistically significant by 60 minutes. This is significant because rizatriptan is widely recognized as the fastest-acting and one of the most effective oral triptans,” said Dr. O’Gorman.
The frequency of adverse events was 11.0% in the AXS-07, 15.4% in the rizatriptan group, 11.5% in the meloxicam group, and 6.0% in the placebo group.
“The added benefit of this study was the demonstration of efficacy in patients who have previously failed other acute treatments. We know that ineffective acute treatments are a likely risk factor for the progression of episodic migraine to chronic migraine, and the more options that we have for our patients, the better,” Dr. Robbins commented.
He remains concerned about cost and access, however. A limited number of tablets per month for acute treatments prompt clinicians to prescribe the medications individually and advise patients to take them in combination. “Rizatriptan is generally available in 12 monthly tablets by many coverage plans, and I would hope that, if ultimately FDA approved, a similar allotment is made affordable and accessible,” he said.
The study was funded by Axsome Therapeutics. Dr. O’Gorman is an employee of Axsome. Dr. Robbins has no relevant financial disclosures.
SOURCE: O’Gorman C et al. AHS 2020, Abstract 840673.
The combination (AXS-07), in development by Axsome Therapeutics, was also safe and well tolerated, according to Cedric O’Gorman, MD, Axsome senior vice president for clinical development and medical affairs. It was tested in subjects who had inadequately responded to previous treatment and who had an average of 2-8 migraines per month.
The therapy combines 10-mg rizatriptan with 20-mg meloxicam delivered by the company’s MoSEIC technology. “Treatment with AXS-07 resulted in rapid, sustained, substantial, and statistically significant effect as compared with rizatriptan and placebo. The enhanced effect of AXS-07 may be especially relevant for patients with more difficult-to-treat migraine,” said Dr. O’Gorman during a presentation of the study at the virtual annual meeting of the American Headache Society.
Matthew Robbins, MD, said in an interview, “This combination may be particularly useful for patients who want to take an oral medication but still need rapid and sustained pain freedom.” Dr. Robbins is the neurology residency program director at New York Presbyterian Hospital and an associate professor of neurology at Weill Cornell Medicine, New York. He was not involved in the research.
The study randomized 1,594 patients 2:2:2:1 to AXS-07, rizatriptan alone, MoSEIC meloxicam alone, or placebo, which could be administered immediately after a migraine event. Between 35% and 40% of participants across the groups had previously used triptans. The mean migraine treatment optimization questionnaire (mTOQ4) score was 3.6, indicating that the population was made up of people with poor responses to medication. Among patients in the study group, 37%-43% had severe pain intensity, 41%-47% were obese, and 35%-37% had morning migraine.
At 2 hours, more patients in the AXS-07 group than in the placebo group were pain free (19.9% vs. 6.7%; P < 0.001). They were also more likely to experience freedom from the most bothersome symptom at 2 hours (36.9% vs. 24.4%; P = 0.002). Secondary outcome measures favored the AXS-07 group when compared with the rizatriptan-only group, including 1-hour pain relief (44% vs. 37%; P = 0.04), 2- to 24-hour sustained pain relief (53% vs. 44%; P = 0.006), 2- to 48-hour sustained pain relief (47% vs. 37%; P = 0.003), 2- to 24-hour sustained pain freedom (16% vs. 11%; P = 0.038), 2- to 48-hour sustained pain freedom (15% vs. 8.8%; P = 0.003), rescue medication use (23% vs. 35%; P < 0.001), a rating of much or very much improved on the Patient Global Impression of Change (PGI-C) scale (47% vs. 39%; P = 0.022), and functional improvement at 24 hours (64% vs. 56%; P = 0.027).
“The percentage of patients achieving pain relief with AXS-07 was numerically greater than with rizatriptan at every time point measure, starting at 15 minutes, and was statistically significant by 60 minutes. This is significant because rizatriptan is widely recognized as the fastest-acting and one of the most effective oral triptans,” said Dr. O’Gorman.
The frequency of adverse events was 11.0% in the AXS-07, 15.4% in the rizatriptan group, 11.5% in the meloxicam group, and 6.0% in the placebo group.
“The added benefit of this study was the demonstration of efficacy in patients who have previously failed other acute treatments. We know that ineffective acute treatments are a likely risk factor for the progression of episodic migraine to chronic migraine, and the more options that we have for our patients, the better,” Dr. Robbins commented.
He remains concerned about cost and access, however. A limited number of tablets per month for acute treatments prompt clinicians to prescribe the medications individually and advise patients to take them in combination. “Rizatriptan is generally available in 12 monthly tablets by many coverage plans, and I would hope that, if ultimately FDA approved, a similar allotment is made affordable and accessible,” he said.
The study was funded by Axsome Therapeutics. Dr. O’Gorman is an employee of Axsome. Dr. Robbins has no relevant financial disclosures.
SOURCE: O’Gorman C et al. AHS 2020, Abstract 840673.
FROM AHS 2020
Lung ultrasound works well in children with COVID-19
researchers wrote in Pediatrics.
They also noted the benefits that modality provides over other imaging techniques.
Marco Denina, MD, and colleagues from the pediatric infectious diseases unit at Regina Margherita Children’s Hospital in Turin, Italy, performed an observational study of eight children aged 0-17 years who were admitted to the hospital for COVID-19 between March 8 and 26, 2020. In seven of eight patients, the findings were concordant between imaging modalities; in the remaining patient, lung ultrasound (LUS) found an interstitial B-lines pattern that was not seen on radiography. In seven patients with pathologic ultrasound findings at baseline, the improvement or resolution of the subpleural consolidations or interstitial patterns was consistent with concomitant radiologic findings.
The authors cited the benefits of using point-of-care ultrasound instead of other modalities, such as CT. “First, it may reduce the number of radiologic examinations, lowering the radiation exposure of the patients,” they wrote. “Secondly, when performed at the bedside, LUS allows for the reduction of the patient’s movement within the hospital; thus, it lowers the number of health care workers and medical devices exposed to [SARS-CoV-2].”
One limitation of the study is the small sample size; however, the researchers felt the high concordance still suggests LUS is a reasonable method for COVID-19 patients.
There was no external funding for this study and the investigators had no relevant financial disclosures.
SOURCE: Denina M et al. Pediatrics. 2020 Jun. doi: 10.1542/peds.2020-1157.
researchers wrote in Pediatrics.
They also noted the benefits that modality provides over other imaging techniques.
Marco Denina, MD, and colleagues from the pediatric infectious diseases unit at Regina Margherita Children’s Hospital in Turin, Italy, performed an observational study of eight children aged 0-17 years who were admitted to the hospital for COVID-19 between March 8 and 26, 2020. In seven of eight patients, the findings were concordant between imaging modalities; in the remaining patient, lung ultrasound (LUS) found an interstitial B-lines pattern that was not seen on radiography. In seven patients with pathologic ultrasound findings at baseline, the improvement or resolution of the subpleural consolidations or interstitial patterns was consistent with concomitant radiologic findings.
The authors cited the benefits of using point-of-care ultrasound instead of other modalities, such as CT. “First, it may reduce the number of radiologic examinations, lowering the radiation exposure of the patients,” they wrote. “Secondly, when performed at the bedside, LUS allows for the reduction of the patient’s movement within the hospital; thus, it lowers the number of health care workers and medical devices exposed to [SARS-CoV-2].”
One limitation of the study is the small sample size; however, the researchers felt the high concordance still suggests LUS is a reasonable method for COVID-19 patients.
There was no external funding for this study and the investigators had no relevant financial disclosures.
SOURCE: Denina M et al. Pediatrics. 2020 Jun. doi: 10.1542/peds.2020-1157.
researchers wrote in Pediatrics.
They also noted the benefits that modality provides over other imaging techniques.
Marco Denina, MD, and colleagues from the pediatric infectious diseases unit at Regina Margherita Children’s Hospital in Turin, Italy, performed an observational study of eight children aged 0-17 years who were admitted to the hospital for COVID-19 between March 8 and 26, 2020. In seven of eight patients, the findings were concordant between imaging modalities; in the remaining patient, lung ultrasound (LUS) found an interstitial B-lines pattern that was not seen on radiography. In seven patients with pathologic ultrasound findings at baseline, the improvement or resolution of the subpleural consolidations or interstitial patterns was consistent with concomitant radiologic findings.
The authors cited the benefits of using point-of-care ultrasound instead of other modalities, such as CT. “First, it may reduce the number of radiologic examinations, lowering the radiation exposure of the patients,” they wrote. “Secondly, when performed at the bedside, LUS allows for the reduction of the patient’s movement within the hospital; thus, it lowers the number of health care workers and medical devices exposed to [SARS-CoV-2].”
One limitation of the study is the small sample size; however, the researchers felt the high concordance still suggests LUS is a reasonable method for COVID-19 patients.
There was no external funding for this study and the investigators had no relevant financial disclosures.
SOURCE: Denina M et al. Pediatrics. 2020 Jun. doi: 10.1542/peds.2020-1157.
FROM PEDIATRICS
Assessing Spinal Muscular Atrophy Across the Patient Journey
Click here to read.
Supplement Faculty
Perry Shieh, MD, PhD
Professor
Department of Neurology
David Geffen School
of Medicine at UCLA
Ronald Reagan UCLA
Medical Center
Los Angeles, CA
Sally Dunaway Young, PT, DPT
Physical Therapist
and Clinical Research
Evaluator/Manager
Stanford University School
of Medicine
Stanford, CA
Click here to read.
Supplement Faculty
Perry Shieh, MD, PhD
Professor
Department of Neurology
David Geffen School
of Medicine at UCLA
Ronald Reagan UCLA
Medical Center
Los Angeles, CA
Sally Dunaway Young, PT, DPT
Physical Therapist
and Clinical Research
Evaluator/Manager
Stanford University School
of Medicine
Stanford, CA
Click here to read.
Supplement Faculty
Perry Shieh, MD, PhD
Professor
Department of Neurology
David Geffen School
of Medicine at UCLA
Ronald Reagan UCLA
Medical Center
Los Angeles, CA
Sally Dunaway Young, PT, DPT
Physical Therapist
and Clinical Research
Evaluator/Manager
Stanford University School
of Medicine
Stanford, CA
CGRPs in real world: Similar efficacy, more AEs
and has found that patients who fail on one of the treatments are likely to fail again if they’re switched to another.
At the virtual annual meeting of the American Headache Society, Larry Robbins, MD, assistant professor of neurology at Chicago Medical School, North Chicago, reported on the results of his postapproval study of 369 migraine patients taking one of the three approved CGRP mAbs. “If patients do not do well on one mAb, it is sometimes worthwhile to switch, but most patients do not do well from the second or third mAb as well,” Dr. Robbins said in an interview. “In addition, there are numerous adverse effects that were not captured in the official phase 3 studies. Efficacy has held up well, but for a number of reasons, the true adverse event profile is often missed.”
Assessing efficacy and adverse events
In evaluating the efficacy of the three approved CGRP mAbs, Dr. Robbins used measures of degree of relief based on percentage decrease of symptoms versus baseline and the number of migraine days, combined with the number of moderate or severe headache days. Most of the patients kept calendars and were interviewed by two headache specialists. The study also utilized a 10-point visual analog scale and averaged relief over 3 months.
Of the patients on erenumab (n = 220), 10% described 95%-100% relief of symptoms, 24% reported 71%-100% relief, 34% described 31%-70% relief, and 43% experienced 0%-30% relief. Adverse events among this group included constipation (20%), nausea (7%), increased headache and fatigue (5% for each), and joint pain and depression (3% for each). Three patients on erenumab experienced unspecified serious adverse reactions.
In the fremanezumab group (n = 79), 8% described 95%-100% relief, 18% had 71%-100% relief, 33% experienced 31%-70% improvement, and 50% had 30% improvement or less. Adverse events in these patients included nausea, constipation, and depression (6% each); increased headache and muscle pain or cramps (5% each); rash, joint pain, anxiety, fatigue, or weight gain (4% for each ); and injection-site reactions, irritability, or alopecia (3% combined).
Patients taking galcanezumab (n = 70) reported the following outcomes: 3% had 95%-100% relief of symptoms, 14% had 71%-100% relief, 46% with 31%-70% relief, and 40% had 0%-30% relief. This group’s adverse events included constipation (10%); depression and increased headache (6% for each); nausea, fatigue, or injection-site reactions (4% each ); and muscle pain or cramps, rash, anxiety, weight gain, or alopecia (3% each).
Dr. Robbins also assessed switching from one CGRP mAb to another for various reasons. “When the reason for switching was poor efficacy, only 27% of patients did well,” he stated in the presentation. “If the reason was adverse events, 33% did well. When insurance/financial reasons alone were the reason, but efficacy was adequate, 58% did well after switching.”
Overall, postapproval efficacy of the medications “held up well,” Dr. Robbins noted. “Efficacy after 2 months somewhat predicted how patients would do after 6 months.” Among the predictors of poor response his study identified were opioid use and moderate or severe refractory chronic migraine at baseline.
However, the rates of adverse events he reported were significantly greater than those reported in the clinical trials, Dr. Robbins said. He noted four reasons to explain this discrepancy: the trials did not use an 18-item supplemental checklist that he has advocated to identify patients at risk of side effects, the trials weren’t powered for adverse events, patients in the trials tended to be less refractory than those in the clinic, and that adverse events tend to be underreported in trials.
“Adverse events become disaggregated, with the same descriptors used for an adverse event,” Dr. Robbins said. “Examples include fatigue, somnolence, and tiredness; all may be 1%, while different patients are describing the same adverse event. It is possible to reaggregate the adverse events after the study, but this is fraught with error.”
Uncovering shortcomings in clinical trials
Emily Rubenstein Engel, MD, director of the Dalessio Headache Center at the Scripps Clinic in La Jolla, Calif., noted that Dr. Robbins’ findings are significant for two reasons. “Dr. Robbins has uncovered a general flaw in clinical trials, whereby the lack of consistency of adverse event terminology as well as the lack of a standardized questionnaire format for adverse events can result in significant under-reporting of adverse events,” she said.
“Specifically for the CGRPs,” Dr. Engel continued, “he has raised awareness that this new class of medication, however promising from an efficacy standpoint, has side effects that are much more frequent and severe than seen in the initial clinical trials.”
Dr. Robbins reported financial relationships with Allergan, Amgen and Teva. Dr. Engel has no financial relationships to disclose.
and has found that patients who fail on one of the treatments are likely to fail again if they’re switched to another.
At the virtual annual meeting of the American Headache Society, Larry Robbins, MD, assistant professor of neurology at Chicago Medical School, North Chicago, reported on the results of his postapproval study of 369 migraine patients taking one of the three approved CGRP mAbs. “If patients do not do well on one mAb, it is sometimes worthwhile to switch, but most patients do not do well from the second or third mAb as well,” Dr. Robbins said in an interview. “In addition, there are numerous adverse effects that were not captured in the official phase 3 studies. Efficacy has held up well, but for a number of reasons, the true adverse event profile is often missed.”
Assessing efficacy and adverse events
In evaluating the efficacy of the three approved CGRP mAbs, Dr. Robbins used measures of degree of relief based on percentage decrease of symptoms versus baseline and the number of migraine days, combined with the number of moderate or severe headache days. Most of the patients kept calendars and were interviewed by two headache specialists. The study also utilized a 10-point visual analog scale and averaged relief over 3 months.
Of the patients on erenumab (n = 220), 10% described 95%-100% relief of symptoms, 24% reported 71%-100% relief, 34% described 31%-70% relief, and 43% experienced 0%-30% relief. Adverse events among this group included constipation (20%), nausea (7%), increased headache and fatigue (5% for each), and joint pain and depression (3% for each). Three patients on erenumab experienced unspecified serious adverse reactions.
In the fremanezumab group (n = 79), 8% described 95%-100% relief, 18% had 71%-100% relief, 33% experienced 31%-70% improvement, and 50% had 30% improvement or less. Adverse events in these patients included nausea, constipation, and depression (6% each); increased headache and muscle pain or cramps (5% each); rash, joint pain, anxiety, fatigue, or weight gain (4% for each ); and injection-site reactions, irritability, or alopecia (3% combined).
Patients taking galcanezumab (n = 70) reported the following outcomes: 3% had 95%-100% relief of symptoms, 14% had 71%-100% relief, 46% with 31%-70% relief, and 40% had 0%-30% relief. This group’s adverse events included constipation (10%); depression and increased headache (6% for each); nausea, fatigue, or injection-site reactions (4% each ); and muscle pain or cramps, rash, anxiety, weight gain, or alopecia (3% each).
Dr. Robbins also assessed switching from one CGRP mAb to another for various reasons. “When the reason for switching was poor efficacy, only 27% of patients did well,” he stated in the presentation. “If the reason was adverse events, 33% did well. When insurance/financial reasons alone were the reason, but efficacy was adequate, 58% did well after switching.”
Overall, postapproval efficacy of the medications “held up well,” Dr. Robbins noted. “Efficacy after 2 months somewhat predicted how patients would do after 6 months.” Among the predictors of poor response his study identified were opioid use and moderate or severe refractory chronic migraine at baseline.
However, the rates of adverse events he reported were significantly greater than those reported in the clinical trials, Dr. Robbins said. He noted four reasons to explain this discrepancy: the trials did not use an 18-item supplemental checklist that he has advocated to identify patients at risk of side effects, the trials weren’t powered for adverse events, patients in the trials tended to be less refractory than those in the clinic, and that adverse events tend to be underreported in trials.
“Adverse events become disaggregated, with the same descriptors used for an adverse event,” Dr. Robbins said. “Examples include fatigue, somnolence, and tiredness; all may be 1%, while different patients are describing the same adverse event. It is possible to reaggregate the adverse events after the study, but this is fraught with error.”
Uncovering shortcomings in clinical trials
Emily Rubenstein Engel, MD, director of the Dalessio Headache Center at the Scripps Clinic in La Jolla, Calif., noted that Dr. Robbins’ findings are significant for two reasons. “Dr. Robbins has uncovered a general flaw in clinical trials, whereby the lack of consistency of adverse event terminology as well as the lack of a standardized questionnaire format for adverse events can result in significant under-reporting of adverse events,” she said.
“Specifically for the CGRPs,” Dr. Engel continued, “he has raised awareness that this new class of medication, however promising from an efficacy standpoint, has side effects that are much more frequent and severe than seen in the initial clinical trials.”
Dr. Robbins reported financial relationships with Allergan, Amgen and Teva. Dr. Engel has no financial relationships to disclose.
and has found that patients who fail on one of the treatments are likely to fail again if they’re switched to another.
At the virtual annual meeting of the American Headache Society, Larry Robbins, MD, assistant professor of neurology at Chicago Medical School, North Chicago, reported on the results of his postapproval study of 369 migraine patients taking one of the three approved CGRP mAbs. “If patients do not do well on one mAb, it is sometimes worthwhile to switch, but most patients do not do well from the second or third mAb as well,” Dr. Robbins said in an interview. “In addition, there are numerous adverse effects that were not captured in the official phase 3 studies. Efficacy has held up well, but for a number of reasons, the true adverse event profile is often missed.”
Assessing efficacy and adverse events
In evaluating the efficacy of the three approved CGRP mAbs, Dr. Robbins used measures of degree of relief based on percentage decrease of symptoms versus baseline and the number of migraine days, combined with the number of moderate or severe headache days. Most of the patients kept calendars and were interviewed by two headache specialists. The study also utilized a 10-point visual analog scale and averaged relief over 3 months.
Of the patients on erenumab (n = 220), 10% described 95%-100% relief of symptoms, 24% reported 71%-100% relief, 34% described 31%-70% relief, and 43% experienced 0%-30% relief. Adverse events among this group included constipation (20%), nausea (7%), increased headache and fatigue (5% for each), and joint pain and depression (3% for each). Three patients on erenumab experienced unspecified serious adverse reactions.
In the fremanezumab group (n = 79), 8% described 95%-100% relief, 18% had 71%-100% relief, 33% experienced 31%-70% improvement, and 50% had 30% improvement or less. Adverse events in these patients included nausea, constipation, and depression (6% each); increased headache and muscle pain or cramps (5% each); rash, joint pain, anxiety, fatigue, or weight gain (4% for each ); and injection-site reactions, irritability, or alopecia (3% combined).
Patients taking galcanezumab (n = 70) reported the following outcomes: 3% had 95%-100% relief of symptoms, 14% had 71%-100% relief, 46% with 31%-70% relief, and 40% had 0%-30% relief. This group’s adverse events included constipation (10%); depression and increased headache (6% for each); nausea, fatigue, or injection-site reactions (4% each ); and muscle pain or cramps, rash, anxiety, weight gain, or alopecia (3% each).
Dr. Robbins also assessed switching from one CGRP mAb to another for various reasons. “When the reason for switching was poor efficacy, only 27% of patients did well,” he stated in the presentation. “If the reason was adverse events, 33% did well. When insurance/financial reasons alone were the reason, but efficacy was adequate, 58% did well after switching.”
Overall, postapproval efficacy of the medications “held up well,” Dr. Robbins noted. “Efficacy after 2 months somewhat predicted how patients would do after 6 months.” Among the predictors of poor response his study identified were opioid use and moderate or severe refractory chronic migraine at baseline.
However, the rates of adverse events he reported were significantly greater than those reported in the clinical trials, Dr. Robbins said. He noted four reasons to explain this discrepancy: the trials did not use an 18-item supplemental checklist that he has advocated to identify patients at risk of side effects, the trials weren’t powered for adverse events, patients in the trials tended to be less refractory than those in the clinic, and that adverse events tend to be underreported in trials.
“Adverse events become disaggregated, with the same descriptors used for an adverse event,” Dr. Robbins said. “Examples include fatigue, somnolence, and tiredness; all may be 1%, while different patients are describing the same adverse event. It is possible to reaggregate the adverse events after the study, but this is fraught with error.”
Uncovering shortcomings in clinical trials
Emily Rubenstein Engel, MD, director of the Dalessio Headache Center at the Scripps Clinic in La Jolla, Calif., noted that Dr. Robbins’ findings are significant for two reasons. “Dr. Robbins has uncovered a general flaw in clinical trials, whereby the lack of consistency of adverse event terminology as well as the lack of a standardized questionnaire format for adverse events can result in significant under-reporting of adverse events,” she said.
“Specifically for the CGRPs,” Dr. Engel continued, “he has raised awareness that this new class of medication, however promising from an efficacy standpoint, has side effects that are much more frequent and severe than seen in the initial clinical trials.”
Dr. Robbins reported financial relationships with Allergan, Amgen and Teva. Dr. Engel has no financial relationships to disclose.
FROM AHS 2020
‘I can’t breathe’: Health inequity and state-sanctioned violence
One might immediately think of the deaths of Eric Garner, George Floyd, or even the fictional character Radio Raheem from Spike Lee’s critically acclaimed film, “Do the Right Thing,” when they hear the words “I can’t breathe.” These words are a cry for help. The deaths of these unarmed black men is devastating and has led to a state of rage, palpable pain, and protest across the world.
However, in this moment, I am talking about the health inequity exposed by the COVID-19 pandemic. Whether it be acute respiratory distress syndrome (ARDS) secondary to severe COVID-19, or the subsequent hypercoagulable state of COVID-19 that leads to venous thromboembolism, many black people in this country are left breathless. Many black patients who had no employee-based health insurance also had no primary care physician to order a SARS-CoV2 PCR lab test for them. Many of these patients have preexisting conditions, such as asthma from living in redlined communities affected by environmental racism. Many grew up in food deserts, where no fresh-produce store was interested enough to set up shop in their neighborhoods. They have been eating fast food since early childhood, as a fast-food burger is still cheaper than a salad. The result is obesity, an epidemic that can lead to diabetes mellitus, hypertension that can lead to coronary artery disease, stroke, and end-stage renal disease.
Earlier in my career, I once had a colleague gleefully tell me that all black people drank Kool-Aid while in discussion of the effects of high-sugar diets in our patients; this colleague was sure I would agree. Not all black people drink Kool-Aid. Secondary to my fear of the backlash that can come from the discomfort of “white fragility” that Robin DiAngelo describes in her New York Times bestseller by the same name, ”White Fragility: Why It’s So Hard for White People to Talk About Racism,” I refrained from expressing my own hurt, and I did not offer explicit correction. I, instead, took a serious pause. That pause, which lasted only minutes, seemed to last 400 years. It was a brief reflection of the 400 years of systemic racism seeping into everyday life. This included the circumstances that would lead to the health inequities that result in the health disparities from which many black patients suffer. It is that same systemic racism that could create two America’s in which my colleague might not have to know the historic context in which that question could be hurtful. I retorted with modified shock and a chuckle so that I could muster up enough strength to repeat what was said and leave it open for reflection. The goal was for my colleague to realize the obvious implicit bias that lingered, despite intention. The chuckle was also to cover my pain.
Whether we know it or not, we all carry some form of implicit bias, regardless of race, class, gender, ethnicity, sexual preference, or socioeconomic status. In this case, it is the same implicit bias that causes physicians to ignore some black patients when they have said that they are in pain. A groundbreaking April 2016 article in Proceedings of the National Academy of Sciences, “Racial Bias in Pain Assessment and Treatment Recommendations, and False Beliefs about Biological Differences Between Blacks and Whites” (doi: 10.1073/pnas.1516047113), revealed that racial disparities in pain assessment and treatment recommendations can be directly connected to the racial bias of the provider. It could be possible that this phenomenon has affected black patients who have walked into clinics and emergency departments and said, “I’m short of breath. I think that I might have coronavirus and need to be tested.” It may be that same implicit bias that has cut the air supply to a patient encounter. Instead of inquiring further, the patient might be met with minimum questions while their provider obtains their history and physical. Assumptions and blame on behavior and lack of personal responsibility secretly replace questions that could have been asked. Differentials between exacerbations and other etiologies are not explored. Could that patient have been sent home without a SARS-CoV2 polymerase chain reaction test? Well, what if the tests were in short supply? Sometimes they may have been sent home without a chest x-ray. In most cases, there are no funds to send them home with a pulse oximeter.
The act of assuming a person’s story that we consider to be one dimensional is always dangerous – and even more so during this pandemic. That person we can relate to – secondary to a cool pop culture moment, a TikTok song, or a negative stereotype – is not one dimensional. That assumption and that stereotype can make room for implicit bias. That same implicit bias is the knee on a neck of any marginalized patient. Implicit bias is the choke hold that slowly removes the light and life from a person who has a story, who has a family, and who has been an essential worker who can’t work from home. That person is telling us that they can’t breathe, but sometimes the only things seen are comorbidities through a misinformed or biased lens that suggest an assumed lack of personal responsibility. In a May 2020 New England Journal of Medicine perspective, “Racial health disparities and Covid-19” (doi: 10.1056/NEJMp2012910), Merlin Chowkwanyun, PhD, MPH, and Adolph L. Reed Jr., PhD, caution us against creating race-based explanations for presumed behavioral patterns.
Systemic racism has created the myth that the playing field has been leveled since the end of enslavement. It hasn’t. That black man, woman, or nonbinary person is telling you “I can’t breathe. I’m tired. I’m short of breath ... I have a cough ... I’m feeling weak these days, Doc.” However, implicit bias is still that knee that won’t let up. It has not let up. Communities with lower-income black and Hispanic patients have already seen local hospitals and frontline workers fight to save their lives while losing their own to COVID-19. We all witnessed the battle for scarce resources and PPE [personal protective equipment]. In contrast, some wealthy neighborhoods have occupants who most likely have access to a primary care physician and more testing centers.
As we reexamine ourselves and look at these cases of police brutality against unarmed black men, women, and children with the appropriate shame and outrage, let us reflect upon the privileges that we enjoy. Let us find our voice as we speak up for black lives. Let us look deeply into the history of medicine as it relates to black patients by reading “Medical Apartheid: The Dark History of Medical Experimentation on Black Americans from Colonial Times to the Present” by Harriet A. Washington. Let us examine that painful legacy, which, while having moments of good intention, still carries the stain of indifference, racism, neglect, and even experimentation without informed consent.
Why should we do these things? Because some of our black patients have also yelled or whispered, “I can’t breathe,” and we were not always listening either.
Dr. Ajala is a hospitalist and associate site director for education at Grady Memorial Hospital in Atlanta. She is a member of the executive council for SHM’s Care for Vulnerable Populations special interest group.
One might immediately think of the deaths of Eric Garner, George Floyd, or even the fictional character Radio Raheem from Spike Lee’s critically acclaimed film, “Do the Right Thing,” when they hear the words “I can’t breathe.” These words are a cry for help. The deaths of these unarmed black men is devastating and has led to a state of rage, palpable pain, and protest across the world.
However, in this moment, I am talking about the health inequity exposed by the COVID-19 pandemic. Whether it be acute respiratory distress syndrome (ARDS) secondary to severe COVID-19, or the subsequent hypercoagulable state of COVID-19 that leads to venous thromboembolism, many black people in this country are left breathless. Many black patients who had no employee-based health insurance also had no primary care physician to order a SARS-CoV2 PCR lab test for them. Many of these patients have preexisting conditions, such as asthma from living in redlined communities affected by environmental racism. Many grew up in food deserts, where no fresh-produce store was interested enough to set up shop in their neighborhoods. They have been eating fast food since early childhood, as a fast-food burger is still cheaper than a salad. The result is obesity, an epidemic that can lead to diabetes mellitus, hypertension that can lead to coronary artery disease, stroke, and end-stage renal disease.
Earlier in my career, I once had a colleague gleefully tell me that all black people drank Kool-Aid while in discussion of the effects of high-sugar diets in our patients; this colleague was sure I would agree. Not all black people drink Kool-Aid. Secondary to my fear of the backlash that can come from the discomfort of “white fragility” that Robin DiAngelo describes in her New York Times bestseller by the same name, ”White Fragility: Why It’s So Hard for White People to Talk About Racism,” I refrained from expressing my own hurt, and I did not offer explicit correction. I, instead, took a serious pause. That pause, which lasted only minutes, seemed to last 400 years. It was a brief reflection of the 400 years of systemic racism seeping into everyday life. This included the circumstances that would lead to the health inequities that result in the health disparities from which many black patients suffer. It is that same systemic racism that could create two America’s in which my colleague might not have to know the historic context in which that question could be hurtful. I retorted with modified shock and a chuckle so that I could muster up enough strength to repeat what was said and leave it open for reflection. The goal was for my colleague to realize the obvious implicit bias that lingered, despite intention. The chuckle was also to cover my pain.
Whether we know it or not, we all carry some form of implicit bias, regardless of race, class, gender, ethnicity, sexual preference, or socioeconomic status. In this case, it is the same implicit bias that causes physicians to ignore some black patients when they have said that they are in pain. A groundbreaking April 2016 article in Proceedings of the National Academy of Sciences, “Racial Bias in Pain Assessment and Treatment Recommendations, and False Beliefs about Biological Differences Between Blacks and Whites” (doi: 10.1073/pnas.1516047113), revealed that racial disparities in pain assessment and treatment recommendations can be directly connected to the racial bias of the provider. It could be possible that this phenomenon has affected black patients who have walked into clinics and emergency departments and said, “I’m short of breath. I think that I might have coronavirus and need to be tested.” It may be that same implicit bias that has cut the air supply to a patient encounter. Instead of inquiring further, the patient might be met with minimum questions while their provider obtains their history and physical. Assumptions and blame on behavior and lack of personal responsibility secretly replace questions that could have been asked. Differentials between exacerbations and other etiologies are not explored. Could that patient have been sent home without a SARS-CoV2 polymerase chain reaction test? Well, what if the tests were in short supply? Sometimes they may have been sent home without a chest x-ray. In most cases, there are no funds to send them home with a pulse oximeter.
The act of assuming a person’s story that we consider to be one dimensional is always dangerous – and even more so during this pandemic. That person we can relate to – secondary to a cool pop culture moment, a TikTok song, or a negative stereotype – is not one dimensional. That assumption and that stereotype can make room for implicit bias. That same implicit bias is the knee on a neck of any marginalized patient. Implicit bias is the choke hold that slowly removes the light and life from a person who has a story, who has a family, and who has been an essential worker who can’t work from home. That person is telling us that they can’t breathe, but sometimes the only things seen are comorbidities through a misinformed or biased lens that suggest an assumed lack of personal responsibility. In a May 2020 New England Journal of Medicine perspective, “Racial health disparities and Covid-19” (doi: 10.1056/NEJMp2012910), Merlin Chowkwanyun, PhD, MPH, and Adolph L. Reed Jr., PhD, caution us against creating race-based explanations for presumed behavioral patterns.
Systemic racism has created the myth that the playing field has been leveled since the end of enslavement. It hasn’t. That black man, woman, or nonbinary person is telling you “I can’t breathe. I’m tired. I’m short of breath ... I have a cough ... I’m feeling weak these days, Doc.” However, implicit bias is still that knee that won’t let up. It has not let up. Communities with lower-income black and Hispanic patients have already seen local hospitals and frontline workers fight to save their lives while losing their own to COVID-19. We all witnessed the battle for scarce resources and PPE [personal protective equipment]. In contrast, some wealthy neighborhoods have occupants who most likely have access to a primary care physician and more testing centers.
As we reexamine ourselves and look at these cases of police brutality against unarmed black men, women, and children with the appropriate shame and outrage, let us reflect upon the privileges that we enjoy. Let us find our voice as we speak up for black lives. Let us look deeply into the history of medicine as it relates to black patients by reading “Medical Apartheid: The Dark History of Medical Experimentation on Black Americans from Colonial Times to the Present” by Harriet A. Washington. Let us examine that painful legacy, which, while having moments of good intention, still carries the stain of indifference, racism, neglect, and even experimentation without informed consent.
Why should we do these things? Because some of our black patients have also yelled or whispered, “I can’t breathe,” and we were not always listening either.
Dr. Ajala is a hospitalist and associate site director for education at Grady Memorial Hospital in Atlanta. She is a member of the executive council for SHM’s Care for Vulnerable Populations special interest group.
One might immediately think of the deaths of Eric Garner, George Floyd, or even the fictional character Radio Raheem from Spike Lee’s critically acclaimed film, “Do the Right Thing,” when they hear the words “I can’t breathe.” These words are a cry for help. The deaths of these unarmed black men is devastating and has led to a state of rage, palpable pain, and protest across the world.
However, in this moment, I am talking about the health inequity exposed by the COVID-19 pandemic. Whether it be acute respiratory distress syndrome (ARDS) secondary to severe COVID-19, or the subsequent hypercoagulable state of COVID-19 that leads to venous thromboembolism, many black people in this country are left breathless. Many black patients who had no employee-based health insurance also had no primary care physician to order a SARS-CoV2 PCR lab test for them. Many of these patients have preexisting conditions, such as asthma from living in redlined communities affected by environmental racism. Many grew up in food deserts, where no fresh-produce store was interested enough to set up shop in their neighborhoods. They have been eating fast food since early childhood, as a fast-food burger is still cheaper than a salad. The result is obesity, an epidemic that can lead to diabetes mellitus, hypertension that can lead to coronary artery disease, stroke, and end-stage renal disease.
Earlier in my career, I once had a colleague gleefully tell me that all black people drank Kool-Aid while in discussion of the effects of high-sugar diets in our patients; this colleague was sure I would agree. Not all black people drink Kool-Aid. Secondary to my fear of the backlash that can come from the discomfort of “white fragility” that Robin DiAngelo describes in her New York Times bestseller by the same name, ”White Fragility: Why It’s So Hard for White People to Talk About Racism,” I refrained from expressing my own hurt, and I did not offer explicit correction. I, instead, took a serious pause. That pause, which lasted only minutes, seemed to last 400 years. It was a brief reflection of the 400 years of systemic racism seeping into everyday life. This included the circumstances that would lead to the health inequities that result in the health disparities from which many black patients suffer. It is that same systemic racism that could create two America’s in which my colleague might not have to know the historic context in which that question could be hurtful. I retorted with modified shock and a chuckle so that I could muster up enough strength to repeat what was said and leave it open for reflection. The goal was for my colleague to realize the obvious implicit bias that lingered, despite intention. The chuckle was also to cover my pain.
Whether we know it or not, we all carry some form of implicit bias, regardless of race, class, gender, ethnicity, sexual preference, or socioeconomic status. In this case, it is the same implicit bias that causes physicians to ignore some black patients when they have said that they are in pain. A groundbreaking April 2016 article in Proceedings of the National Academy of Sciences, “Racial Bias in Pain Assessment and Treatment Recommendations, and False Beliefs about Biological Differences Between Blacks and Whites” (doi: 10.1073/pnas.1516047113), revealed that racial disparities in pain assessment and treatment recommendations can be directly connected to the racial bias of the provider. It could be possible that this phenomenon has affected black patients who have walked into clinics and emergency departments and said, “I’m short of breath. I think that I might have coronavirus and need to be tested.” It may be that same implicit bias that has cut the air supply to a patient encounter. Instead of inquiring further, the patient might be met with minimum questions while their provider obtains their history and physical. Assumptions and blame on behavior and lack of personal responsibility secretly replace questions that could have been asked. Differentials between exacerbations and other etiologies are not explored. Could that patient have been sent home without a SARS-CoV2 polymerase chain reaction test? Well, what if the tests were in short supply? Sometimes they may have been sent home without a chest x-ray. In most cases, there are no funds to send them home with a pulse oximeter.
The act of assuming a person’s story that we consider to be one dimensional is always dangerous – and even more so during this pandemic. That person we can relate to – secondary to a cool pop culture moment, a TikTok song, or a negative stereotype – is not one dimensional. That assumption and that stereotype can make room for implicit bias. That same implicit bias is the knee on a neck of any marginalized patient. Implicit bias is the choke hold that slowly removes the light and life from a person who has a story, who has a family, and who has been an essential worker who can’t work from home. That person is telling us that they can’t breathe, but sometimes the only things seen are comorbidities through a misinformed or biased lens that suggest an assumed lack of personal responsibility. In a May 2020 New England Journal of Medicine perspective, “Racial health disparities and Covid-19” (doi: 10.1056/NEJMp2012910), Merlin Chowkwanyun, PhD, MPH, and Adolph L. Reed Jr., PhD, caution us against creating race-based explanations for presumed behavioral patterns.
Systemic racism has created the myth that the playing field has been leveled since the end of enslavement. It hasn’t. That black man, woman, or nonbinary person is telling you “I can’t breathe. I’m tired. I’m short of breath ... I have a cough ... I’m feeling weak these days, Doc.” However, implicit bias is still that knee that won’t let up. It has not let up. Communities with lower-income black and Hispanic patients have already seen local hospitals and frontline workers fight to save their lives while losing their own to COVID-19. We all witnessed the battle for scarce resources and PPE [personal protective equipment]. In contrast, some wealthy neighborhoods have occupants who most likely have access to a primary care physician and more testing centers.
As we reexamine ourselves and look at these cases of police brutality against unarmed black men, women, and children with the appropriate shame and outrage, let us reflect upon the privileges that we enjoy. Let us find our voice as we speak up for black lives. Let us look deeply into the history of medicine as it relates to black patients by reading “Medical Apartheid: The Dark History of Medical Experimentation on Black Americans from Colonial Times to the Present” by Harriet A. Washington. Let us examine that painful legacy, which, while having moments of good intention, still carries the stain of indifference, racism, neglect, and even experimentation without informed consent.
Why should we do these things? Because some of our black patients have also yelled or whispered, “I can’t breathe,” and we were not always listening either.
Dr. Ajala is a hospitalist and associate site director for education at Grady Memorial Hospital in Atlanta. She is a member of the executive council for SHM’s Care for Vulnerable Populations special interest group.