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FDA approves corticosteroid-retinoid lotion for plaque psoriasis
The in a lotion formulation, for the treatment of plaque psoriasis in adults, the manufacturer announced on April 25.
A press release from the manufacturer, Ortho Dermatologics, summarized the results of two phase 3 studies that compared treatment with the combination product, in 418 adults with moderate to severe plaque psoriasis. At week 8, the proportion of patients who had achieved treatment success – defined as at least a two-grade improvement in Investigator Global Assessment score and a score of “clear” or “almost clear” – was 36% and 45% in the treatment groups, compared with 7% and 13% of those on vehicle, respectively (P less than .001 for both).
The release also refers to a phase 2 study of 212 patients, which found that the combination treatment was more effective in treating plaque psoriasis than was either component separately (J Drugs Dermatol. 2017 Mar 1;16[1]:197-204). By week 8, 52.5% of patients treated with the combination lotion had shown treatment success – compared with 33.3% of those treated with halobetasol, 18.6% of those treated with tazarotene, and 9.7% of those treated with vehicle (P = .033).
Common treatment-related adverse events included treatment site reactions, such as irritation, pain, itching, and folliculitis. Treatment may cause birth defects if used during pregnancy, so a negative pregnancy test should be obtained before treatment begins and effective birth control should be used during treatment.
It will be marketed under the trade name Duobrii and is priced at $825 for a 100-gram tube, according to the press release.
The in a lotion formulation, for the treatment of plaque psoriasis in adults, the manufacturer announced on April 25.
A press release from the manufacturer, Ortho Dermatologics, summarized the results of two phase 3 studies that compared treatment with the combination product, in 418 adults with moderate to severe plaque psoriasis. At week 8, the proportion of patients who had achieved treatment success – defined as at least a two-grade improvement in Investigator Global Assessment score and a score of “clear” or “almost clear” – was 36% and 45% in the treatment groups, compared with 7% and 13% of those on vehicle, respectively (P less than .001 for both).
The release also refers to a phase 2 study of 212 patients, which found that the combination treatment was more effective in treating plaque psoriasis than was either component separately (J Drugs Dermatol. 2017 Mar 1;16[1]:197-204). By week 8, 52.5% of patients treated with the combination lotion had shown treatment success – compared with 33.3% of those treated with halobetasol, 18.6% of those treated with tazarotene, and 9.7% of those treated with vehicle (P = .033).
Common treatment-related adverse events included treatment site reactions, such as irritation, pain, itching, and folliculitis. Treatment may cause birth defects if used during pregnancy, so a negative pregnancy test should be obtained before treatment begins and effective birth control should be used during treatment.
It will be marketed under the trade name Duobrii and is priced at $825 for a 100-gram tube, according to the press release.
The in a lotion formulation, for the treatment of plaque psoriasis in adults, the manufacturer announced on April 25.
A press release from the manufacturer, Ortho Dermatologics, summarized the results of two phase 3 studies that compared treatment with the combination product, in 418 adults with moderate to severe plaque psoriasis. At week 8, the proportion of patients who had achieved treatment success – defined as at least a two-grade improvement in Investigator Global Assessment score and a score of “clear” or “almost clear” – was 36% and 45% in the treatment groups, compared with 7% and 13% of those on vehicle, respectively (P less than .001 for both).
The release also refers to a phase 2 study of 212 patients, which found that the combination treatment was more effective in treating plaque psoriasis than was either component separately (J Drugs Dermatol. 2017 Mar 1;16[1]:197-204). By week 8, 52.5% of patients treated with the combination lotion had shown treatment success – compared with 33.3% of those treated with halobetasol, 18.6% of those treated with tazarotene, and 9.7% of those treated with vehicle (P = .033).
Common treatment-related adverse events included treatment site reactions, such as irritation, pain, itching, and folliculitis. Treatment may cause birth defects if used during pregnancy, so a negative pregnancy test should be obtained before treatment begins and effective birth control should be used during treatment.
It will be marketed under the trade name Duobrii and is priced at $825 for a 100-gram tube, according to the press release.
Losing a patient to suicide: ‘Never Worry Alone’
Losing a patient to suicide is one of the most difficult and painful experiences a psychiatrist will face. In addition to concern for the patient and his or her family, psychiatrists may experience thoughts of responsibility and what they could have done to prevent the suicide. Although often trained in helping patients address grief, psychiatrists may not be as comfortable processing their own grief after the loss of a patient to suicide.
On April 24, MDedge Psychiatry hosted a conversation on Twitter to help psychiatrists examine some of their own feelings about losing patients in this way. Two psychiatrists – Dinah Miller, MD, and Eric Plakun, MD – responded to questions on this topic.
Dr. Miller is the author of numerous books and articles, including “Committed: The Battle Over Involuntary Care” (Baltimore: Johns Hopkins University Press, 2016), which she wrote with Dr. Annette Hanson, and a piece in the New England Journal of Medicine about her own experience with the death of a patient to suicide. She has a private practice in Baltimore and is affiliated with Johns Hopkins University there. Dr. Plakun is the medical director and CEO of the Austen Riggs Center based in Stockbridge, Mass., a “Top 10” U.S. News and World Report “Best Hospital” in psychiatry. He also serves on the board of trustees of the American Psychiatric Association representing New England and Eastern Canada, and was the founding leader of the APA Psychotherapy Caucus. Dr. Plakun is a board-certified psychiatrist, psychoanalyst, former member of the Harvard Medical School clinical faculty, and author of more than 50 publications.
Some of the conversation focused on the impact of patient suicide on young doctors. “I tell the residents: Never Worry Alone,” Dr. Miller wrote. “When in doubt, get supervision, curbside consult, formal paid supervision, or send the patient for a second opinion. Have friends.”
Dr. Miller also wrote that these kinds of losses are difficult for experienced doctors, but “just awful when you’re just starting out. A young psychiatrist I knew lost two patients early on in her career. Hang in there – sending support.”
Dr. Plakun wrote. “Questioning whether one wants to do such work is not unusual.”
The following is an edited version of the discussion.
Question: Have you ever lost a patient to suicide?
Dr. Plakun: This is an important subject and worth bringing to wider discussion. Thirty-eight percent of clinicians experience a significant reaction to this kind of loss.
Dr. Miller: I spent decades worrying that a patient might die by suicide. The reality was more troubling to me than I imagined. It left me more hesitant, less trusting of both the patients and myself. Not always, just at moments. The work we do is hard.
Dr. Plakun: Not one I was working with, but several after we terminated. And it has happened to patients I admitted to Austen Riggs during 35 years as director of admissions.
Dr. Miller: You know, I was struck by the fact that we have no formal way to approach this ... the APA info is for residents. This was part of why I wrote the NEJM piece, to open the conversation.
Question: How do you think the loss of your patient changed your approach to psychiatry?
Dr. Miller: One of the things I’ve heard is that recovering from this tremendous loss helps doctors/therapists to know that others have had a rough time, and that this isn’t weird or odd, and that they are not alone.
Question: How did the loss change you?
Dr. Miller: I did not feel a sense of “blame.” I imagine that would have made it much more difficult. An internist wrote to me discussing how he’d dismissed a patient’s chest pain and the patient died – there are so many layers of complexity here. So many different stories.
Dr. Plakun: I think the impact on us is great because in suicide the deceased is both victim and perpetrator of murder, while we have tried to empathize with both sides.
Dr. Miller: I imagine everyone feels some distress, some emotional response. It’s hard to imagine that a doctor or therapist would hear a patient under their care died of any cause and would feel nothing.
Closing observations
Dr. Plakun: If you lose a patient to suicide, seek consultation and support from a trusted colleague. Remember that isolation will be part of the problem, not the solution. Remember to call your insurance carrier for consultation regarding risk-management issues.
Dr. Miller: I think this topic is difficult for docs/therapists to listen to. It’s hard to sit with a friend/colleague’s pain.
Dr. Plakun: Meeting with family is an issue. The primary purpose of such meetings is to meet their needs – not your own. Help them deal with a traumatic loss causing powerful and complicated feelings. If it helps you, that’s a bonus rather than the goal of the meeting.
References
Miller D. When a patient dies by suicide –The physician’s silent sorrow. (N Engl J Med. 2019 Jan 24;380:311-3).
Plakun EM. Psychotherapy with suicidal patients, Part 1: Expert consensus recommendations. (J Psychiatr Prac. 2018 Nov;249[6]:420-3).
Plakun EM and Jane G. Tillman. Responding to clinicians after loss of a patient to suicide. Directions in Psychiatry. 2005 Oct.
Connect with Dr. Miller on Twitter at @shrinkrapdinah and with Dr. Plakun at @EricPlakunMD. And look for #MDedgeChats to find the complete conversation on Twitter. Dr. Miller and Dr. Plakun will be joining Lorenzo Norris, MD, and Jane Tillman, PhD, for a discussion of this topic from noon to 1 p.m. on Monday, May 20, at the American Psychiatric Association annual meeting in San Francisco for a live recording of the MDedge Psychcast. Join them at booth 1518!
Also, as in past years, Dr. Plakun will join Dr. Tillman to offer a workshop at the APA meeting called “Responding to the Impact of Suicide on Clinicians.” The workshop (session ID: 1054) will be held on Sunday, May 19, 10 a.m. – 11:30 a.m., in Room 153, upper mezzanine, Moscone South.
Losing a patient to suicide is one of the most difficult and painful experiences a psychiatrist will face. In addition to concern for the patient and his or her family, psychiatrists may experience thoughts of responsibility and what they could have done to prevent the suicide. Although often trained in helping patients address grief, psychiatrists may not be as comfortable processing their own grief after the loss of a patient to suicide.
On April 24, MDedge Psychiatry hosted a conversation on Twitter to help psychiatrists examine some of their own feelings about losing patients in this way. Two psychiatrists – Dinah Miller, MD, and Eric Plakun, MD – responded to questions on this topic.
Dr. Miller is the author of numerous books and articles, including “Committed: The Battle Over Involuntary Care” (Baltimore: Johns Hopkins University Press, 2016), which she wrote with Dr. Annette Hanson, and a piece in the New England Journal of Medicine about her own experience with the death of a patient to suicide. She has a private practice in Baltimore and is affiliated with Johns Hopkins University there. Dr. Plakun is the medical director and CEO of the Austen Riggs Center based in Stockbridge, Mass., a “Top 10” U.S. News and World Report “Best Hospital” in psychiatry. He also serves on the board of trustees of the American Psychiatric Association representing New England and Eastern Canada, and was the founding leader of the APA Psychotherapy Caucus. Dr. Plakun is a board-certified psychiatrist, psychoanalyst, former member of the Harvard Medical School clinical faculty, and author of more than 50 publications.
Some of the conversation focused on the impact of patient suicide on young doctors. “I tell the residents: Never Worry Alone,” Dr. Miller wrote. “When in doubt, get supervision, curbside consult, formal paid supervision, or send the patient for a second opinion. Have friends.”
Dr. Miller also wrote that these kinds of losses are difficult for experienced doctors, but “just awful when you’re just starting out. A young psychiatrist I knew lost two patients early on in her career. Hang in there – sending support.”
Dr. Plakun wrote. “Questioning whether one wants to do such work is not unusual.”
The following is an edited version of the discussion.
Question: Have you ever lost a patient to suicide?
Dr. Plakun: This is an important subject and worth bringing to wider discussion. Thirty-eight percent of clinicians experience a significant reaction to this kind of loss.
Dr. Miller: I spent decades worrying that a patient might die by suicide. The reality was more troubling to me than I imagined. It left me more hesitant, less trusting of both the patients and myself. Not always, just at moments. The work we do is hard.
Dr. Plakun: Not one I was working with, but several after we terminated. And it has happened to patients I admitted to Austen Riggs during 35 years as director of admissions.
Dr. Miller: You know, I was struck by the fact that we have no formal way to approach this ... the APA info is for residents. This was part of why I wrote the NEJM piece, to open the conversation.
Question: How do you think the loss of your patient changed your approach to psychiatry?
Dr. Miller: One of the things I’ve heard is that recovering from this tremendous loss helps doctors/therapists to know that others have had a rough time, and that this isn’t weird or odd, and that they are not alone.
Question: How did the loss change you?
Dr. Miller: I did not feel a sense of “blame.” I imagine that would have made it much more difficult. An internist wrote to me discussing how he’d dismissed a patient’s chest pain and the patient died – there are so many layers of complexity here. So many different stories.
Dr. Plakun: I think the impact on us is great because in suicide the deceased is both victim and perpetrator of murder, while we have tried to empathize with both sides.
Dr. Miller: I imagine everyone feels some distress, some emotional response. It’s hard to imagine that a doctor or therapist would hear a patient under their care died of any cause and would feel nothing.
Closing observations
Dr. Plakun: If you lose a patient to suicide, seek consultation and support from a trusted colleague. Remember that isolation will be part of the problem, not the solution. Remember to call your insurance carrier for consultation regarding risk-management issues.
Dr. Miller: I think this topic is difficult for docs/therapists to listen to. It’s hard to sit with a friend/colleague’s pain.
Dr. Plakun: Meeting with family is an issue. The primary purpose of such meetings is to meet their needs – not your own. Help them deal with a traumatic loss causing powerful and complicated feelings. If it helps you, that’s a bonus rather than the goal of the meeting.
References
Miller D. When a patient dies by suicide –The physician’s silent sorrow. (N Engl J Med. 2019 Jan 24;380:311-3).
Plakun EM. Psychotherapy with suicidal patients, Part 1: Expert consensus recommendations. (J Psychiatr Prac. 2018 Nov;249[6]:420-3).
Plakun EM and Jane G. Tillman. Responding to clinicians after loss of a patient to suicide. Directions in Psychiatry. 2005 Oct.
Connect with Dr. Miller on Twitter at @shrinkrapdinah and with Dr. Plakun at @EricPlakunMD. And look for #MDedgeChats to find the complete conversation on Twitter. Dr. Miller and Dr. Plakun will be joining Lorenzo Norris, MD, and Jane Tillman, PhD, for a discussion of this topic from noon to 1 p.m. on Monday, May 20, at the American Psychiatric Association annual meeting in San Francisco for a live recording of the MDedge Psychcast. Join them at booth 1518!
Also, as in past years, Dr. Plakun will join Dr. Tillman to offer a workshop at the APA meeting called “Responding to the Impact of Suicide on Clinicians.” The workshop (session ID: 1054) will be held on Sunday, May 19, 10 a.m. – 11:30 a.m., in Room 153, upper mezzanine, Moscone South.
Losing a patient to suicide is one of the most difficult and painful experiences a psychiatrist will face. In addition to concern for the patient and his or her family, psychiatrists may experience thoughts of responsibility and what they could have done to prevent the suicide. Although often trained in helping patients address grief, psychiatrists may not be as comfortable processing their own grief after the loss of a patient to suicide.
On April 24, MDedge Psychiatry hosted a conversation on Twitter to help psychiatrists examine some of their own feelings about losing patients in this way. Two psychiatrists – Dinah Miller, MD, and Eric Plakun, MD – responded to questions on this topic.
Dr. Miller is the author of numerous books and articles, including “Committed: The Battle Over Involuntary Care” (Baltimore: Johns Hopkins University Press, 2016), which she wrote with Dr. Annette Hanson, and a piece in the New England Journal of Medicine about her own experience with the death of a patient to suicide. She has a private practice in Baltimore and is affiliated with Johns Hopkins University there. Dr. Plakun is the medical director and CEO of the Austen Riggs Center based in Stockbridge, Mass., a “Top 10” U.S. News and World Report “Best Hospital” in psychiatry. He also serves on the board of trustees of the American Psychiatric Association representing New England and Eastern Canada, and was the founding leader of the APA Psychotherapy Caucus. Dr. Plakun is a board-certified psychiatrist, psychoanalyst, former member of the Harvard Medical School clinical faculty, and author of more than 50 publications.
Some of the conversation focused on the impact of patient suicide on young doctors. “I tell the residents: Never Worry Alone,” Dr. Miller wrote. “When in doubt, get supervision, curbside consult, formal paid supervision, or send the patient for a second opinion. Have friends.”
Dr. Miller also wrote that these kinds of losses are difficult for experienced doctors, but “just awful when you’re just starting out. A young psychiatrist I knew lost two patients early on in her career. Hang in there – sending support.”
Dr. Plakun wrote. “Questioning whether one wants to do such work is not unusual.”
The following is an edited version of the discussion.
Question: Have you ever lost a patient to suicide?
Dr. Plakun: This is an important subject and worth bringing to wider discussion. Thirty-eight percent of clinicians experience a significant reaction to this kind of loss.
Dr. Miller: I spent decades worrying that a patient might die by suicide. The reality was more troubling to me than I imagined. It left me more hesitant, less trusting of both the patients and myself. Not always, just at moments. The work we do is hard.
Dr. Plakun: Not one I was working with, but several after we terminated. And it has happened to patients I admitted to Austen Riggs during 35 years as director of admissions.
Dr. Miller: You know, I was struck by the fact that we have no formal way to approach this ... the APA info is for residents. This was part of why I wrote the NEJM piece, to open the conversation.
Question: How do you think the loss of your patient changed your approach to psychiatry?
Dr. Miller: One of the things I’ve heard is that recovering from this tremendous loss helps doctors/therapists to know that others have had a rough time, and that this isn’t weird or odd, and that they are not alone.
Question: How did the loss change you?
Dr. Miller: I did not feel a sense of “blame.” I imagine that would have made it much more difficult. An internist wrote to me discussing how he’d dismissed a patient’s chest pain and the patient died – there are so many layers of complexity here. So many different stories.
Dr. Plakun: I think the impact on us is great because in suicide the deceased is both victim and perpetrator of murder, while we have tried to empathize with both sides.
Dr. Miller: I imagine everyone feels some distress, some emotional response. It’s hard to imagine that a doctor or therapist would hear a patient under their care died of any cause and would feel nothing.
Closing observations
Dr. Plakun: If you lose a patient to suicide, seek consultation and support from a trusted colleague. Remember that isolation will be part of the problem, not the solution. Remember to call your insurance carrier for consultation regarding risk-management issues.
Dr. Miller: I think this topic is difficult for docs/therapists to listen to. It’s hard to sit with a friend/colleague’s pain.
Dr. Plakun: Meeting with family is an issue. The primary purpose of such meetings is to meet their needs – not your own. Help them deal with a traumatic loss causing powerful and complicated feelings. If it helps you, that’s a bonus rather than the goal of the meeting.
References
Miller D. When a patient dies by suicide –The physician’s silent sorrow. (N Engl J Med. 2019 Jan 24;380:311-3).
Plakun EM. Psychotherapy with suicidal patients, Part 1: Expert consensus recommendations. (J Psychiatr Prac. 2018 Nov;249[6]:420-3).
Plakun EM and Jane G. Tillman. Responding to clinicians after loss of a patient to suicide. Directions in Psychiatry. 2005 Oct.
Connect with Dr. Miller on Twitter at @shrinkrapdinah and with Dr. Plakun at @EricPlakunMD. And look for #MDedgeChats to find the complete conversation on Twitter. Dr. Miller and Dr. Plakun will be joining Lorenzo Norris, MD, and Jane Tillman, PhD, for a discussion of this topic from noon to 1 p.m. on Monday, May 20, at the American Psychiatric Association annual meeting in San Francisco for a live recording of the MDedge Psychcast. Join them at booth 1518!
Also, as in past years, Dr. Plakun will join Dr. Tillman to offer a workshop at the APA meeting called “Responding to the Impact of Suicide on Clinicians.” The workshop (session ID: 1054) will be held on Sunday, May 19, 10 a.m. – 11:30 a.m., in Room 153, upper mezzanine, Moscone South.
Few stroke patients undergo osteoporosis screening, treatment
Although stroke is a risk factor for osteoporosis, falls, and fractures, very few people who have experienced a recent stroke are either screened for osteoporosis or treated, research suggests.
Writing in Stroke, researchers presented an analysis of Ontario registry data from 16,581 patients who were aged 65 years or older and presented with stroke between 2003 and 2013.
Overall, just 5.1% of patients underwent bone mineral density testing. Of the 1,577 patients who had experienced a prior fracture, 71 (4.7%) had bone mineral density testing, and only 2.9% of those who had not had prior bone mineral density testing were tested after their stroke. Bone mineral density testing was more likely in patients who were younger, who were female, and who experienced a low-trauma fracture in the year after their stroke.
In total, 15.5% of patients were prescribed osteoporosis drugs in the first year after their stroke. However, only 7.8% of those who had fractures before the stroke and 14.8% of those with fractures after the stroke received osteoporosis treatment after the stroke. Patients who were female, had prior osteoporosis, had experienced prior fracture, had previously undergone bone mineral density testing, or had experienced a fracture or fall after their stroke were more likely to receive osteoporosis pharmacotherapy.
The authors found that the neither the severity of stroke nor the presence of other comorbidities was associated with an increased likelihood of screening or treatment of osteoporosis after the stroke.
Stroke is associated with up to a fourfold increased risk of osteoporosis and fracture, compared with healthy controls, most probably because of reduced mobility and an increased risk of falls, wrote Eshita Kapoor of the department of medicine at the University of Toronto and her coauthors.
“Screening and treatment may be particularly low poststroke because of under-recognition of osteoporosis as a consequence of stroke, a selective focus on the management of cardiovascular risk and stroke recovery, or factors such as dysphagia precluding use of oral bisphosphonates,” the authors wrote.
While the association is noted in U.S. stroke guidelines, there are few recommendations for treatment aside from fall prevention strategies, which the authors noted was a missed opportunity for prevention.
“Use of a risk prediction score to identify those at particularly high short-term risk of fractures after stroke may help to prioritize patients for osteoporosis testing and treatment,” they suggested.
The study was funded by the Heart and Stroke Foundation of Canada and was supported by ICES (Institute for Clinical Evaluative Sciences) and the Ontario Ministry of Health and Long-Term Care. One author declared consultancies for the pharmaceutical sector. No other conflicts of interest were declared.
SOURCE: Kapoor E et al. Stroke. 2019 April 25. doi: 10.1161/STROKEAHA.118.024685
Although stroke is a risk factor for osteoporosis, falls, and fractures, very few people who have experienced a recent stroke are either screened for osteoporosis or treated, research suggests.
Writing in Stroke, researchers presented an analysis of Ontario registry data from 16,581 patients who were aged 65 years or older and presented with stroke between 2003 and 2013.
Overall, just 5.1% of patients underwent bone mineral density testing. Of the 1,577 patients who had experienced a prior fracture, 71 (4.7%) had bone mineral density testing, and only 2.9% of those who had not had prior bone mineral density testing were tested after their stroke. Bone mineral density testing was more likely in patients who were younger, who were female, and who experienced a low-trauma fracture in the year after their stroke.
In total, 15.5% of patients were prescribed osteoporosis drugs in the first year after their stroke. However, only 7.8% of those who had fractures before the stroke and 14.8% of those with fractures after the stroke received osteoporosis treatment after the stroke. Patients who were female, had prior osteoporosis, had experienced prior fracture, had previously undergone bone mineral density testing, or had experienced a fracture or fall after their stroke were more likely to receive osteoporosis pharmacotherapy.
The authors found that the neither the severity of stroke nor the presence of other comorbidities was associated with an increased likelihood of screening or treatment of osteoporosis after the stroke.
Stroke is associated with up to a fourfold increased risk of osteoporosis and fracture, compared with healthy controls, most probably because of reduced mobility and an increased risk of falls, wrote Eshita Kapoor of the department of medicine at the University of Toronto and her coauthors.
“Screening and treatment may be particularly low poststroke because of under-recognition of osteoporosis as a consequence of stroke, a selective focus on the management of cardiovascular risk and stroke recovery, or factors such as dysphagia precluding use of oral bisphosphonates,” the authors wrote.
While the association is noted in U.S. stroke guidelines, there are few recommendations for treatment aside from fall prevention strategies, which the authors noted was a missed opportunity for prevention.
“Use of a risk prediction score to identify those at particularly high short-term risk of fractures after stroke may help to prioritize patients for osteoporosis testing and treatment,” they suggested.
The study was funded by the Heart and Stroke Foundation of Canada and was supported by ICES (Institute for Clinical Evaluative Sciences) and the Ontario Ministry of Health and Long-Term Care. One author declared consultancies for the pharmaceutical sector. No other conflicts of interest were declared.
SOURCE: Kapoor E et al. Stroke. 2019 April 25. doi: 10.1161/STROKEAHA.118.024685
Although stroke is a risk factor for osteoporosis, falls, and fractures, very few people who have experienced a recent stroke are either screened for osteoporosis or treated, research suggests.
Writing in Stroke, researchers presented an analysis of Ontario registry data from 16,581 patients who were aged 65 years or older and presented with stroke between 2003 and 2013.
Overall, just 5.1% of patients underwent bone mineral density testing. Of the 1,577 patients who had experienced a prior fracture, 71 (4.7%) had bone mineral density testing, and only 2.9% of those who had not had prior bone mineral density testing were tested after their stroke. Bone mineral density testing was more likely in patients who were younger, who were female, and who experienced a low-trauma fracture in the year after their stroke.
In total, 15.5% of patients were prescribed osteoporosis drugs in the first year after their stroke. However, only 7.8% of those who had fractures before the stroke and 14.8% of those with fractures after the stroke received osteoporosis treatment after the stroke. Patients who were female, had prior osteoporosis, had experienced prior fracture, had previously undergone bone mineral density testing, or had experienced a fracture or fall after their stroke were more likely to receive osteoporosis pharmacotherapy.
The authors found that the neither the severity of stroke nor the presence of other comorbidities was associated with an increased likelihood of screening or treatment of osteoporosis after the stroke.
Stroke is associated with up to a fourfold increased risk of osteoporosis and fracture, compared with healthy controls, most probably because of reduced mobility and an increased risk of falls, wrote Eshita Kapoor of the department of medicine at the University of Toronto and her coauthors.
“Screening and treatment may be particularly low poststroke because of under-recognition of osteoporosis as a consequence of stroke, a selective focus on the management of cardiovascular risk and stroke recovery, or factors such as dysphagia precluding use of oral bisphosphonates,” the authors wrote.
While the association is noted in U.S. stroke guidelines, there are few recommendations for treatment aside from fall prevention strategies, which the authors noted was a missed opportunity for prevention.
“Use of a risk prediction score to identify those at particularly high short-term risk of fractures after stroke may help to prioritize patients for osteoporosis testing and treatment,” they suggested.
The study was funded by the Heart and Stroke Foundation of Canada and was supported by ICES (Institute for Clinical Evaluative Sciences) and the Ontario Ministry of Health and Long-Term Care. One author declared consultancies for the pharmaceutical sector. No other conflicts of interest were declared.
SOURCE: Kapoor E et al. Stroke. 2019 April 25. doi: 10.1161/STROKEAHA.118.024685
FROM STROKE
Anxiety, not depression, commonly afflicts euthyroid patients with thyroid disease
LOS ANGELES – results from a cross-sectional study have shown.
“Thyroid disease is often associated with impaired quality of life and psychological well-being,” lead study author Anette Merke, MD, MS, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “In daily practice, anxiety and depression complaints are common in patients with thyroid dysfunctions. While depressive symptoms are often associated with hypothyroidism, anxiety is claimed to be mainly linked to hyperthyroidism. Data on euthyroid patients with thyroid disease are controversial. Some studies point out that autoimmunity itself contributes to psychosomatic malfunctions. Overall, the mechanisms underlying the interaction between thyroid dysfunction and neuropsychiatric processes are still unknown.”
Dr. Merke, of the Thyroid Center Bergstrasse in Bensheim, Germany, and her husband/coauthor Jüergen Merke, MD, PhD, used the self-administered German version of the validated Hospital Anxiety and Depression Scale (HADS-D) to perform a cross-sectional study of 215 euthyroid adults with thyroid disease between January and February of 2019. Of the 14 items on the measure, half relate to anxiety and the other half to depression. Each item on the HADS-D is scored from 0-3, and a score of 10 or higher is considered a positive case of anxiety or depression. Patients completed the HADS-D within 3 months of routine lab testing, and the researchers collected the patients’ demographic data after they had assessed the individual scores.
Of the 215 study participants, most (89%) were women, the mean age was 47 years, and the mean anxiety and depression scores were 6.68 and 4.68, respectively (P = .0001). There was no significant difference in severity with respect to anxiety or depression. Of the 70 patients (33%) with antibody-positive Hashimoto’s thyroiditis, the mean anxiety and depression scores were 7.26 and 4.17.
In patients with HADS-D scores of 10 or greater, 50 (23%) had prominent anxiety scores (mean, 12.4), whereas 22 (10%) had prominent depression scores (mean, 13.18). Among the subset of Hashimoto’s thyroiditis patients, 18 (26%) had a mean anxiety score of 12.6 and 8 (11%) had a mean depression score of 13.18. Overall, significantly more cases were found in those who met criteria for anxiety, compared with those who met criteria for depression (P = .0001), with no significant difference in severity of either condition.
Depressive symptoms are usually more closely associated with thyroid disease, and there are more studies that have examined that relationship, so “we were surprised to find no significant difference in depressive symptoms between our study cohort and the German general population,” Dr. Merke said. “We were also surprised that anxiety had a significantly higher incidence in the cohort.”
The findings suggest that clinicians should focus on signs of anxiety symptoms when dealing with euthyroid patients with thyroid disease who report psychosomatic impairments, she continued, especially when patients complain of not being able to relax and release somatic tension.
“According to HADS, fears and worries are an expression of anxiety, and not of depression,” Dr. Merke said. “With this in mind, doctors [should] actively ask [about] the above-mentioned symptoms and advise patients to learn relaxation techniques to improve their quality of life. Interdisciplinary collaboration is needed between clinicians and psychotherapeutic professionals for the sake of the patients and to evaluate a cause-and-effect relationship and potential risk factors for development of psychosomatic cofactors in thyroid and other chronic somatic diseases. We should all be aware that misinterpretation or even denial of psychosomatic complaints may lead to complications and even a higher mortality of somatic diseases, as shown for chronic heart failure. This could also be true for thyroid disease.”
Dr Merke acknowledged certain limitations of the study, including the fact that neither the duration of thyroid disease nor the use of specific thyroid medications was assessed. In addition, “the definition of euthyroidism in our study is somewhat broad, especially compared with the recommendations of the [American Association of Clinical Endocrinologists],” she said. “Division of the respective thyroid hormone status into quartiles may be helpful to indicate the critical thyroid hormone serum concentration, which may be associated with clinically relevant anxiety symptoms in euthyroid patients.”
Dr. Merke reported having no financial disclosures or conflict of interest.
LOS ANGELES – results from a cross-sectional study have shown.
“Thyroid disease is often associated with impaired quality of life and psychological well-being,” lead study author Anette Merke, MD, MS, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “In daily practice, anxiety and depression complaints are common in patients with thyroid dysfunctions. While depressive symptoms are often associated with hypothyroidism, anxiety is claimed to be mainly linked to hyperthyroidism. Data on euthyroid patients with thyroid disease are controversial. Some studies point out that autoimmunity itself contributes to psychosomatic malfunctions. Overall, the mechanisms underlying the interaction between thyroid dysfunction and neuropsychiatric processes are still unknown.”
Dr. Merke, of the Thyroid Center Bergstrasse in Bensheim, Germany, and her husband/coauthor Jüergen Merke, MD, PhD, used the self-administered German version of the validated Hospital Anxiety and Depression Scale (HADS-D) to perform a cross-sectional study of 215 euthyroid adults with thyroid disease between January and February of 2019. Of the 14 items on the measure, half relate to anxiety and the other half to depression. Each item on the HADS-D is scored from 0-3, and a score of 10 or higher is considered a positive case of anxiety or depression. Patients completed the HADS-D within 3 months of routine lab testing, and the researchers collected the patients’ demographic data after they had assessed the individual scores.
Of the 215 study participants, most (89%) were women, the mean age was 47 years, and the mean anxiety and depression scores were 6.68 and 4.68, respectively (P = .0001). There was no significant difference in severity with respect to anxiety or depression. Of the 70 patients (33%) with antibody-positive Hashimoto’s thyroiditis, the mean anxiety and depression scores were 7.26 and 4.17.
In patients with HADS-D scores of 10 or greater, 50 (23%) had prominent anxiety scores (mean, 12.4), whereas 22 (10%) had prominent depression scores (mean, 13.18). Among the subset of Hashimoto’s thyroiditis patients, 18 (26%) had a mean anxiety score of 12.6 and 8 (11%) had a mean depression score of 13.18. Overall, significantly more cases were found in those who met criteria for anxiety, compared with those who met criteria for depression (P = .0001), with no significant difference in severity of either condition.
Depressive symptoms are usually more closely associated with thyroid disease, and there are more studies that have examined that relationship, so “we were surprised to find no significant difference in depressive symptoms between our study cohort and the German general population,” Dr. Merke said. “We were also surprised that anxiety had a significantly higher incidence in the cohort.”
The findings suggest that clinicians should focus on signs of anxiety symptoms when dealing with euthyroid patients with thyroid disease who report psychosomatic impairments, she continued, especially when patients complain of not being able to relax and release somatic tension.
“According to HADS, fears and worries are an expression of anxiety, and not of depression,” Dr. Merke said. “With this in mind, doctors [should] actively ask [about] the above-mentioned symptoms and advise patients to learn relaxation techniques to improve their quality of life. Interdisciplinary collaboration is needed between clinicians and psychotherapeutic professionals for the sake of the patients and to evaluate a cause-and-effect relationship and potential risk factors for development of psychosomatic cofactors in thyroid and other chronic somatic diseases. We should all be aware that misinterpretation or even denial of psychosomatic complaints may lead to complications and even a higher mortality of somatic diseases, as shown for chronic heart failure. This could also be true for thyroid disease.”
Dr Merke acknowledged certain limitations of the study, including the fact that neither the duration of thyroid disease nor the use of specific thyroid medications was assessed. In addition, “the definition of euthyroidism in our study is somewhat broad, especially compared with the recommendations of the [American Association of Clinical Endocrinologists],” she said. “Division of the respective thyroid hormone status into quartiles may be helpful to indicate the critical thyroid hormone serum concentration, which may be associated with clinically relevant anxiety symptoms in euthyroid patients.”
Dr. Merke reported having no financial disclosures or conflict of interest.
LOS ANGELES – results from a cross-sectional study have shown.
“Thyroid disease is often associated with impaired quality of life and psychological well-being,” lead study author Anette Merke, MD, MS, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “In daily practice, anxiety and depression complaints are common in patients with thyroid dysfunctions. While depressive symptoms are often associated with hypothyroidism, anxiety is claimed to be mainly linked to hyperthyroidism. Data on euthyroid patients with thyroid disease are controversial. Some studies point out that autoimmunity itself contributes to psychosomatic malfunctions. Overall, the mechanisms underlying the interaction between thyroid dysfunction and neuropsychiatric processes are still unknown.”
Dr. Merke, of the Thyroid Center Bergstrasse in Bensheim, Germany, and her husband/coauthor Jüergen Merke, MD, PhD, used the self-administered German version of the validated Hospital Anxiety and Depression Scale (HADS-D) to perform a cross-sectional study of 215 euthyroid adults with thyroid disease between January and February of 2019. Of the 14 items on the measure, half relate to anxiety and the other half to depression. Each item on the HADS-D is scored from 0-3, and a score of 10 or higher is considered a positive case of anxiety or depression. Patients completed the HADS-D within 3 months of routine lab testing, and the researchers collected the patients’ demographic data after they had assessed the individual scores.
Of the 215 study participants, most (89%) were women, the mean age was 47 years, and the mean anxiety and depression scores were 6.68 and 4.68, respectively (P = .0001). There was no significant difference in severity with respect to anxiety or depression. Of the 70 patients (33%) with antibody-positive Hashimoto’s thyroiditis, the mean anxiety and depression scores were 7.26 and 4.17.
In patients with HADS-D scores of 10 or greater, 50 (23%) had prominent anxiety scores (mean, 12.4), whereas 22 (10%) had prominent depression scores (mean, 13.18). Among the subset of Hashimoto’s thyroiditis patients, 18 (26%) had a mean anxiety score of 12.6 and 8 (11%) had a mean depression score of 13.18. Overall, significantly more cases were found in those who met criteria for anxiety, compared with those who met criteria for depression (P = .0001), with no significant difference in severity of either condition.
Depressive symptoms are usually more closely associated with thyroid disease, and there are more studies that have examined that relationship, so “we were surprised to find no significant difference in depressive symptoms between our study cohort and the German general population,” Dr. Merke said. “We were also surprised that anxiety had a significantly higher incidence in the cohort.”
The findings suggest that clinicians should focus on signs of anxiety symptoms when dealing with euthyroid patients with thyroid disease who report psychosomatic impairments, she continued, especially when patients complain of not being able to relax and release somatic tension.
“According to HADS, fears and worries are an expression of anxiety, and not of depression,” Dr. Merke said. “With this in mind, doctors [should] actively ask [about] the above-mentioned symptoms and advise patients to learn relaxation techniques to improve their quality of life. Interdisciplinary collaboration is needed between clinicians and psychotherapeutic professionals for the sake of the patients and to evaluate a cause-and-effect relationship and potential risk factors for development of psychosomatic cofactors in thyroid and other chronic somatic diseases. We should all be aware that misinterpretation or even denial of psychosomatic complaints may lead to complications and even a higher mortality of somatic diseases, as shown for chronic heart failure. This could also be true for thyroid disease.”
Dr Merke acknowledged certain limitations of the study, including the fact that neither the duration of thyroid disease nor the use of specific thyroid medications was assessed. In addition, “the definition of euthyroidism in our study is somewhat broad, especially compared with the recommendations of the [American Association of Clinical Endocrinologists],” she said. “Division of the respective thyroid hormone status into quartiles may be helpful to indicate the critical thyroid hormone serum concentration, which may be associated with clinically relevant anxiety symptoms in euthyroid patients.”
Dr. Merke reported having no financial disclosures or conflict of interest.
REPORTING FROM AACE 2019
Key clinical point: Anxiety in patients with thyroid disease might have a pathological pathway different from depressive disorders.
Major finding: In patients with HADS-D scores of 10 or greater, 50 (23%) had prominent anxiety scores (mean, 12.4) and 22 (10%) had prominent depression scores (mean, 13.18).
Study details: A cross-sectional study of 215 euthyroid patients with thyroid disease.
Disclosures: Dr. Merke reported having no financial disclosures or conflicts of interest.
Best of RIV highlights practical, innovative projects
Delirium, alcohol detox, and med rec
A project to improve how hospitalists address inpatient delirium, which has led to reductions in length of stay and cost, took center stage in the Best of RIV plenary session at HM19 in March.
The project, conducted at the University of California, San Francisco (UCSF), was presented alongside projects on alcohol detox at the Cleveland Veterans Affairs Medical Center and on medication reconciliation at Brigham and Women’s Hospital in Boston.
“The plenary is the top three of the 1,000 that are out there – so, impressive work,” said Benji Mathews, MD, SFHM, the chair of the Research, Innovations and Vignettes competition.
At UCSF, the project was meant to tackle the huge problem of delirium in the hospital, said Catherine Lau, MD, SFHM, associate professor of medicine there. Each year delirium affects more than 7 million people who are hospitalized, and hospital-acquired delirium is linked with prolonged stays and more emergency department visits and hospital readmissions. But research has found that as many as a third of these hospital-acquired cases can be prevented, Dr. Lau said.
New admissions and transfers – a total of more than 2,800 patients – were assessed for delirium risk, and those deemed high risk were entered into a delirium care plan, aimed at prevention with nonpharmacologic steps such as maximizing their mobility and helping them sleep at night.
All patients also were screened on every nursing shift for delirium, and those diagnosed with the disorder were placed in the delirium care plan, with notification of the patient’s team for treatment.
The average length of stay decreased by 0.8 days (P less than .001), with a decrease of 1.9 days in patients with delirium, compared with outcomes for nearly 2,600 patients before the intervention was implemented, Dr. Lau said. Researchers also found a decrease in $850 spent per patient (P less than .001), with a direct savings to the hospital of a total of $997,000, she said. The 30-day readmission rate also fell significantly, from 18.9% to 15.9% (P = .03).
The screening itself seemed to be the most important factor in the project, Dr. Lau said.
“Just the recognition that their patient was at risk for delirium or actually had delirium really raised awareness,” she said.
The project on alcohol detox used careful risk assessments at emergency department discharge, e-consults, protocols to limit benzodiazepine prescribing, and telephone follow-up to reduce hospital admissions and 30-day readmissions, as well as length of stay.
Researchers used scores on CIWA – a 10-question measurement of the severity of someone’s alcohol withdrawal – and history of complicated alcohol-use withdrawal to determine whether ED patients should be admitted to the floor or sent home with or without prescriptions for gabapentin and lorazepam, said Robert Patrick, MD, a hospitalist at the Cleveland VA.
Perhaps the most innovative feature of the program was using systolic blood pressure and heart rate in addition to CIWA to determine whether someone should receive a benzodiazepine, he said. Someone with a CIWA of 9-12, for instance, would be prescribed one of these drugs only if their vitals were elevated, Dr. Patrick said.
He encouraged other hospitalists to try a similar program at their centers.
“You don’t have to be at a VA to do this,” he said. “And most importantly, you don’t have to have a cooperative ED to do this. You can do this just within your hospitalist group.”
In another presentation, Jeffrey Schnipper MD, MPH, FHM, associate professor of medicine at Harvard Medical School, Boston, described the results from a project in which SHM’s MARQUIS program – an evidence-based “toolkit” on medication reconciliation – was implemented at 18 hospitals. The kit offers a plan to get the best possible medication history, give medication counseling on discharge, and identify patients at risk for medication discrepancies. The 18 sites were coached, with areas of improvement identified.
By months 13-18 of the study period, the number of medication discrepancies had fallen to 0.93 per patient for those who’d received at least one form of intervention, compared with 2.69 per patient among those who’d received none.
“The MARQUIS interventions, including the toolkit and mentored implementation,” Dr. Schnipper said, “are associated with a marked reduction in medication discrepancies.”
Delirium, alcohol detox, and med rec
Delirium, alcohol detox, and med rec
A project to improve how hospitalists address inpatient delirium, which has led to reductions in length of stay and cost, took center stage in the Best of RIV plenary session at HM19 in March.
The project, conducted at the University of California, San Francisco (UCSF), was presented alongside projects on alcohol detox at the Cleveland Veterans Affairs Medical Center and on medication reconciliation at Brigham and Women’s Hospital in Boston.
“The plenary is the top three of the 1,000 that are out there – so, impressive work,” said Benji Mathews, MD, SFHM, the chair of the Research, Innovations and Vignettes competition.
At UCSF, the project was meant to tackle the huge problem of delirium in the hospital, said Catherine Lau, MD, SFHM, associate professor of medicine there. Each year delirium affects more than 7 million people who are hospitalized, and hospital-acquired delirium is linked with prolonged stays and more emergency department visits and hospital readmissions. But research has found that as many as a third of these hospital-acquired cases can be prevented, Dr. Lau said.
New admissions and transfers – a total of more than 2,800 patients – were assessed for delirium risk, and those deemed high risk were entered into a delirium care plan, aimed at prevention with nonpharmacologic steps such as maximizing their mobility and helping them sleep at night.
All patients also were screened on every nursing shift for delirium, and those diagnosed with the disorder were placed in the delirium care plan, with notification of the patient’s team for treatment.
The average length of stay decreased by 0.8 days (P less than .001), with a decrease of 1.9 days in patients with delirium, compared with outcomes for nearly 2,600 patients before the intervention was implemented, Dr. Lau said. Researchers also found a decrease in $850 spent per patient (P less than .001), with a direct savings to the hospital of a total of $997,000, she said. The 30-day readmission rate also fell significantly, from 18.9% to 15.9% (P = .03).
The screening itself seemed to be the most important factor in the project, Dr. Lau said.
“Just the recognition that their patient was at risk for delirium or actually had delirium really raised awareness,” she said.
The project on alcohol detox used careful risk assessments at emergency department discharge, e-consults, protocols to limit benzodiazepine prescribing, and telephone follow-up to reduce hospital admissions and 30-day readmissions, as well as length of stay.
Researchers used scores on CIWA – a 10-question measurement of the severity of someone’s alcohol withdrawal – and history of complicated alcohol-use withdrawal to determine whether ED patients should be admitted to the floor or sent home with or without prescriptions for gabapentin and lorazepam, said Robert Patrick, MD, a hospitalist at the Cleveland VA.
Perhaps the most innovative feature of the program was using systolic blood pressure and heart rate in addition to CIWA to determine whether someone should receive a benzodiazepine, he said. Someone with a CIWA of 9-12, for instance, would be prescribed one of these drugs only if their vitals were elevated, Dr. Patrick said.
He encouraged other hospitalists to try a similar program at their centers.
“You don’t have to be at a VA to do this,” he said. “And most importantly, you don’t have to have a cooperative ED to do this. You can do this just within your hospitalist group.”
In another presentation, Jeffrey Schnipper MD, MPH, FHM, associate professor of medicine at Harvard Medical School, Boston, described the results from a project in which SHM’s MARQUIS program – an evidence-based “toolkit” on medication reconciliation – was implemented at 18 hospitals. The kit offers a plan to get the best possible medication history, give medication counseling on discharge, and identify patients at risk for medication discrepancies. The 18 sites were coached, with areas of improvement identified.
By months 13-18 of the study period, the number of medication discrepancies had fallen to 0.93 per patient for those who’d received at least one form of intervention, compared with 2.69 per patient among those who’d received none.
“The MARQUIS interventions, including the toolkit and mentored implementation,” Dr. Schnipper said, “are associated with a marked reduction in medication discrepancies.”
A project to improve how hospitalists address inpatient delirium, which has led to reductions in length of stay and cost, took center stage in the Best of RIV plenary session at HM19 in March.
The project, conducted at the University of California, San Francisco (UCSF), was presented alongside projects on alcohol detox at the Cleveland Veterans Affairs Medical Center and on medication reconciliation at Brigham and Women’s Hospital in Boston.
“The plenary is the top three of the 1,000 that are out there – so, impressive work,” said Benji Mathews, MD, SFHM, the chair of the Research, Innovations and Vignettes competition.
At UCSF, the project was meant to tackle the huge problem of delirium in the hospital, said Catherine Lau, MD, SFHM, associate professor of medicine there. Each year delirium affects more than 7 million people who are hospitalized, and hospital-acquired delirium is linked with prolonged stays and more emergency department visits and hospital readmissions. But research has found that as many as a third of these hospital-acquired cases can be prevented, Dr. Lau said.
New admissions and transfers – a total of more than 2,800 patients – were assessed for delirium risk, and those deemed high risk were entered into a delirium care plan, aimed at prevention with nonpharmacologic steps such as maximizing their mobility and helping them sleep at night.
All patients also were screened on every nursing shift for delirium, and those diagnosed with the disorder were placed in the delirium care plan, with notification of the patient’s team for treatment.
The average length of stay decreased by 0.8 days (P less than .001), with a decrease of 1.9 days in patients with delirium, compared with outcomes for nearly 2,600 patients before the intervention was implemented, Dr. Lau said. Researchers also found a decrease in $850 spent per patient (P less than .001), with a direct savings to the hospital of a total of $997,000, she said. The 30-day readmission rate also fell significantly, from 18.9% to 15.9% (P = .03).
The screening itself seemed to be the most important factor in the project, Dr. Lau said.
“Just the recognition that their patient was at risk for delirium or actually had delirium really raised awareness,” she said.
The project on alcohol detox used careful risk assessments at emergency department discharge, e-consults, protocols to limit benzodiazepine prescribing, and telephone follow-up to reduce hospital admissions and 30-day readmissions, as well as length of stay.
Researchers used scores on CIWA – a 10-question measurement of the severity of someone’s alcohol withdrawal – and history of complicated alcohol-use withdrawal to determine whether ED patients should be admitted to the floor or sent home with or without prescriptions for gabapentin and lorazepam, said Robert Patrick, MD, a hospitalist at the Cleveland VA.
Perhaps the most innovative feature of the program was using systolic blood pressure and heart rate in addition to CIWA to determine whether someone should receive a benzodiazepine, he said. Someone with a CIWA of 9-12, for instance, would be prescribed one of these drugs only if their vitals were elevated, Dr. Patrick said.
He encouraged other hospitalists to try a similar program at their centers.
“You don’t have to be at a VA to do this,” he said. “And most importantly, you don’t have to have a cooperative ED to do this. You can do this just within your hospitalist group.”
In another presentation, Jeffrey Schnipper MD, MPH, FHM, associate professor of medicine at Harvard Medical School, Boston, described the results from a project in which SHM’s MARQUIS program – an evidence-based “toolkit” on medication reconciliation – was implemented at 18 hospitals. The kit offers a plan to get the best possible medication history, give medication counseling on discharge, and identify patients at risk for medication discrepancies. The 18 sites were coached, with areas of improvement identified.
By months 13-18 of the study period, the number of medication discrepancies had fallen to 0.93 per patient for those who’d received at least one form of intervention, compared with 2.69 per patient among those who’d received none.
“The MARQUIS interventions, including the toolkit and mentored implementation,” Dr. Schnipper said, “are associated with a marked reduction in medication discrepancies.”
Patients with higher HbA1c levels face greater risk for diabetic ketoacidosis
LOS ANGELES – results from a registry study have demonstrated.
The findings come from an analysis of the 2016-2017 Type 1 Diabetes Exchange Clinic Registry dataset that researchers, led by Carol Wysham, MD, presented at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists.
“This study is unique in that we have stratified patients based on A1c, and identified factors and patient characteristics associated with a greater risk of DKA as glycemic control diminishes,” Dr. Wysham, an endocrinologist at MultiCare Rockwood Clinic Diabetes & Endocrinology Center in Spokane, Wash., said in advance of the meeting. “Multiple interrelated factors, such as lower levels of education and household income, relationship status, access to private health insurance, being younger, and smoking, all affect a patient’s ability to properly manage insulin dosing and are associated with a higher risk of DKA. Health care providers should continue to monitor and educate all patients on the risk factors associated with developing DKA, and be vigilant in patients with an A1c of more than 9%.”
Dr. Wysham and her colleagues conducted a cross-sectional analysis of 6,242 patients in the registry. They examined associations between patient characteristics and treatment patterns with the occurrence of a DKA event in three categories of HbA1c: 7% to less than 8%, 8% to less than 9%, and 9% or greater. The researchers used chi-square or Fisher exact tests to compare DKA and non-DKA groups for categorical variables and t tests to compare continuous variables.
Of the 6,242 patients, 43% had an HbA1c from 7% to less than 8% (cohort 1), 31% had an HbA1c of 8% to less than 9% (cohort 2), and 30% had an HbA1c of 9% or greater (cohort 3). In all, 269 patients reported a DKA event. In addition, 1.7% of those in cohort 1 had a DKA episode versus 2.3% of those in cohort 2 and 9.5% of those in cohort 3.
In patients in cohort 1, the researchers observed no significant associations between individual patient demographic, socioeconomic, or treatment patterns and DKA incidence. In patients in cohort 2, race, marital status, insurance coverage, and annual household income were significantly associated with DKA incidence (P less than .01). In patients in cohort 3, DKA incidence was significantly associated with the same patterns as those in cohort 2, with the addition of age, type 1 diabetes duration, sex, education level, body mass index, and insulin delivery method (P less than .01).
On adjusted multivariate analysis, the researchers observed no significant associations between the factors studied and DKA in patients in cohort 2. In patients in cohort 3, only household income, smoking status, body mass index, and insulin delivery method (injection) were associated with DKA.
Dr. Wysham said she was surprised to learn that the patient characteristics and socioeconomic factors associated with DKA in patients with an HbA1c of more than 9% start to become less significant risk factors as patients achieved better glycemic control.
“Also, in the past, insulin pump users tended to have higher rates of DKA, compared with patients taking multiple daily insulin injections,” she said. “That phenomenon no longer seems to apply, and in this dataset, patients with an HbA1c of more than 9% and who were taking multiple daily injections had significantly higher risk of DKA than did pump users. Insulin delivery method was not a contributing factor to DKA risk at all in patients with an HbA1c of less than 9%.”
Dr. Wysham acknowledged certain limitations of the analysis, including the fact that the registry data “are collected from patients treated at diabetes centers of excellence and may not reflect the population as a whole. Data could have been collected from medical records and/or self-reported questionnaires from patients. Self-reported data are subjective and are limited to the patient’s own recollections.”
Dr. Wysham disclosed that she has received honoraria for advising, consulting, and/or speaking from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Dexcom, Novo Nordisk, and Sanofi. She also disclosed having received research funding from Mylan and Novo Nordisk that went to her institution.
LOS ANGELES – results from a registry study have demonstrated.
The findings come from an analysis of the 2016-2017 Type 1 Diabetes Exchange Clinic Registry dataset that researchers, led by Carol Wysham, MD, presented at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists.
“This study is unique in that we have stratified patients based on A1c, and identified factors and patient characteristics associated with a greater risk of DKA as glycemic control diminishes,” Dr. Wysham, an endocrinologist at MultiCare Rockwood Clinic Diabetes & Endocrinology Center in Spokane, Wash., said in advance of the meeting. “Multiple interrelated factors, such as lower levels of education and household income, relationship status, access to private health insurance, being younger, and smoking, all affect a patient’s ability to properly manage insulin dosing and are associated with a higher risk of DKA. Health care providers should continue to monitor and educate all patients on the risk factors associated with developing DKA, and be vigilant in patients with an A1c of more than 9%.”
Dr. Wysham and her colleagues conducted a cross-sectional analysis of 6,242 patients in the registry. They examined associations between patient characteristics and treatment patterns with the occurrence of a DKA event in three categories of HbA1c: 7% to less than 8%, 8% to less than 9%, and 9% or greater. The researchers used chi-square or Fisher exact tests to compare DKA and non-DKA groups for categorical variables and t tests to compare continuous variables.
Of the 6,242 patients, 43% had an HbA1c from 7% to less than 8% (cohort 1), 31% had an HbA1c of 8% to less than 9% (cohort 2), and 30% had an HbA1c of 9% or greater (cohort 3). In all, 269 patients reported a DKA event. In addition, 1.7% of those in cohort 1 had a DKA episode versus 2.3% of those in cohort 2 and 9.5% of those in cohort 3.
In patients in cohort 1, the researchers observed no significant associations between individual patient demographic, socioeconomic, or treatment patterns and DKA incidence. In patients in cohort 2, race, marital status, insurance coverage, and annual household income were significantly associated with DKA incidence (P less than .01). In patients in cohort 3, DKA incidence was significantly associated with the same patterns as those in cohort 2, with the addition of age, type 1 diabetes duration, sex, education level, body mass index, and insulin delivery method (P less than .01).
On adjusted multivariate analysis, the researchers observed no significant associations between the factors studied and DKA in patients in cohort 2. In patients in cohort 3, only household income, smoking status, body mass index, and insulin delivery method (injection) were associated with DKA.
Dr. Wysham said she was surprised to learn that the patient characteristics and socioeconomic factors associated with DKA in patients with an HbA1c of more than 9% start to become less significant risk factors as patients achieved better glycemic control.
“Also, in the past, insulin pump users tended to have higher rates of DKA, compared with patients taking multiple daily insulin injections,” she said. “That phenomenon no longer seems to apply, and in this dataset, patients with an HbA1c of more than 9% and who were taking multiple daily injections had significantly higher risk of DKA than did pump users. Insulin delivery method was not a contributing factor to DKA risk at all in patients with an HbA1c of less than 9%.”
Dr. Wysham acknowledged certain limitations of the analysis, including the fact that the registry data “are collected from patients treated at diabetes centers of excellence and may not reflect the population as a whole. Data could have been collected from medical records and/or self-reported questionnaires from patients. Self-reported data are subjective and are limited to the patient’s own recollections.”
Dr. Wysham disclosed that she has received honoraria for advising, consulting, and/or speaking from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Dexcom, Novo Nordisk, and Sanofi. She also disclosed having received research funding from Mylan and Novo Nordisk that went to her institution.
LOS ANGELES – results from a registry study have demonstrated.
The findings come from an analysis of the 2016-2017 Type 1 Diabetes Exchange Clinic Registry dataset that researchers, led by Carol Wysham, MD, presented at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists.
“This study is unique in that we have stratified patients based on A1c, and identified factors and patient characteristics associated with a greater risk of DKA as glycemic control diminishes,” Dr. Wysham, an endocrinologist at MultiCare Rockwood Clinic Diabetes & Endocrinology Center in Spokane, Wash., said in advance of the meeting. “Multiple interrelated factors, such as lower levels of education and household income, relationship status, access to private health insurance, being younger, and smoking, all affect a patient’s ability to properly manage insulin dosing and are associated with a higher risk of DKA. Health care providers should continue to monitor and educate all patients on the risk factors associated with developing DKA, and be vigilant in patients with an A1c of more than 9%.”
Dr. Wysham and her colleagues conducted a cross-sectional analysis of 6,242 patients in the registry. They examined associations between patient characteristics and treatment patterns with the occurrence of a DKA event in three categories of HbA1c: 7% to less than 8%, 8% to less than 9%, and 9% or greater. The researchers used chi-square or Fisher exact tests to compare DKA and non-DKA groups for categorical variables and t tests to compare continuous variables.
Of the 6,242 patients, 43% had an HbA1c from 7% to less than 8% (cohort 1), 31% had an HbA1c of 8% to less than 9% (cohort 2), and 30% had an HbA1c of 9% or greater (cohort 3). In all, 269 patients reported a DKA event. In addition, 1.7% of those in cohort 1 had a DKA episode versus 2.3% of those in cohort 2 and 9.5% of those in cohort 3.
In patients in cohort 1, the researchers observed no significant associations between individual patient demographic, socioeconomic, or treatment patterns and DKA incidence. In patients in cohort 2, race, marital status, insurance coverage, and annual household income were significantly associated with DKA incidence (P less than .01). In patients in cohort 3, DKA incidence was significantly associated with the same patterns as those in cohort 2, with the addition of age, type 1 diabetes duration, sex, education level, body mass index, and insulin delivery method (P less than .01).
On adjusted multivariate analysis, the researchers observed no significant associations between the factors studied and DKA in patients in cohort 2. In patients in cohort 3, only household income, smoking status, body mass index, and insulin delivery method (injection) were associated with DKA.
Dr. Wysham said she was surprised to learn that the patient characteristics and socioeconomic factors associated with DKA in patients with an HbA1c of more than 9% start to become less significant risk factors as patients achieved better glycemic control.
“Also, in the past, insulin pump users tended to have higher rates of DKA, compared with patients taking multiple daily insulin injections,” she said. “That phenomenon no longer seems to apply, and in this dataset, patients with an HbA1c of more than 9% and who were taking multiple daily injections had significantly higher risk of DKA than did pump users. Insulin delivery method was not a contributing factor to DKA risk at all in patients with an HbA1c of less than 9%.”
Dr. Wysham acknowledged certain limitations of the analysis, including the fact that the registry data “are collected from patients treated at diabetes centers of excellence and may not reflect the population as a whole. Data could have been collected from medical records and/or self-reported questionnaires from patients. Self-reported data are subjective and are limited to the patient’s own recollections.”
Dr. Wysham disclosed that she has received honoraria for advising, consulting, and/or speaking from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Dexcom, Novo Nordisk, and Sanofi. She also disclosed having received research funding from Mylan and Novo Nordisk that went to her institution.
REPORTING FROM AACE 2019
Use of levoketoconazole improved several clinical features of Cushing’s disease
LOS ANGELES – including acne, hirsutism, and peripheral edema, as did patient-reported quality of life and symptoms of depression.
The findings come from an analysis of secondary endpoints among patients enrolled in SONICS, an open-label, phase 3 study of levoketoconazole as a treatment for endogenous Cushing’s disease (CD) that enrolled 94 patients at centers in North America, Europe and the Middle East. An investigational cortisol synthesis inhibitor, levoketoconazole is being developed by Strongbridge Biopharma and is not yet approved by the Food and Drug Administration.
“Despite the availability of approved treatments, the medical needs in Cushing’s [disease] remain very high,” the study’s principal investigator, Maria Fleseriu, MD, FACE, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists, where the data were presented. “This study demonstrates that levoketoconazole has the potential to address several clinical features of Cushing’s, owing to its clinically translated novel mechanism of action to suppress both cortisol and androgen syntheses (the latter elevated in many women with CD). Interestingly, there was no evidence of clinically important free-T reduction in men, and more studies are needed to elucidate this mechanism.”
In SONICS, adults with confirmed CD and mean 24-hour urinary free-cortisol (mUFC) value at least 1.5 times the upper limit of normal were treated with levoketoconazole in three phases: 2- to 21-week dose-titration phase (150-600 mg BID, as needed, to target mUFC normalization); 6-month maintenance phase (primary endpoint); and 6-month extended evaluation phase. The end of maintenance phase findings that focused on reductions in mUFC and safety had been previously reported. The current analysis focused on secondary endpoints, including changes from baseline to end of maintenance in investigator-assessed CD clinical signs and symptoms (acne score [range: 0-44]; hirsutism score [women only; range: 0-36]; and peripheral edema score [range: 0-12]), and patient-reported outcomes of quality of life (Cushing QoL questionnaire score [range: 0-100]) and depression (Beck Depression Inventory II score [range: 0-63]). The researchers also assessed hormones including free testosterone levels, and they used paired t-tests to infer statistical significance of the mean changes from baseline to end of maintenance for all measures.
Of the 94 patients enrolled in SONICS, 77 entered the maintenance phase, said Dr. Fleseriu, professor of medicine and neurological surgery and director of the pituitary center at Oregon Health and Science University, Portland. The patients’ mean age was 44 years and mean baseline mUFC was 243.3 mcg/day; 82% of patients were female, and 96% were white. Between baseline and the end of maintenance, the researchers observed significant mean improvements in acne scores (from 2.8 to –1.8, respectively; P = .0063), hirsutism scores (women only, from 7.8 to –2.6; P = .0008), and peripheral edema scores (from 1.0 to –0.4; P = .0295). They also observed significant mean improvements in quality of life and depression scores between baseline and end of maintenance (P less than .0001 and P = .0043, respectively). Mean free-testosterone levels increased nonsignificantly between baseline and end of maintenance in men (from 5.1 to 5.8 ng/dL) yet decreased significantly in women (from 0.3 to 0.1 ng/dL; P less than 0.0001; reference). Overall, 33 patients (35%) discontinued taking levoketoconazole by the end of the maintenance phase. Twelve (13%) discontinued because of adverse events.
“I wasn’t necessarily surprised with any of the data in this poster as I had experience with the drug in clinical trials, but I was definitely pleased to see overall significant improvements in acne score, hirsutism score in women, and peripheral edema score,” Dr. Fleseriu said. “Those are benefits that could potentially increase long-term adherence to treatment and quality-of-life improvements, particularly in women. It’s also exciting to see that quality of life and depression improved in these patients as well.”
These types of patient-reported outcomes are so important to how our patients feel about their disease and should be more of a focus for us physicians; it’s important to look at efficacy, safety and patient reported outcomes when we decide for an individualized treatment for each patient,” she noted.
Dr. Fleseriu reported that she has received research funding for Oregon Health and Science University from Novartis, Millendo, and Strongbridge. She has also received scientific consulting fees from Novartis and Strongbridge.
LOS ANGELES – including acne, hirsutism, and peripheral edema, as did patient-reported quality of life and symptoms of depression.
The findings come from an analysis of secondary endpoints among patients enrolled in SONICS, an open-label, phase 3 study of levoketoconazole as a treatment for endogenous Cushing’s disease (CD) that enrolled 94 patients at centers in North America, Europe and the Middle East. An investigational cortisol synthesis inhibitor, levoketoconazole is being developed by Strongbridge Biopharma and is not yet approved by the Food and Drug Administration.
“Despite the availability of approved treatments, the medical needs in Cushing’s [disease] remain very high,” the study’s principal investigator, Maria Fleseriu, MD, FACE, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists, where the data were presented. “This study demonstrates that levoketoconazole has the potential to address several clinical features of Cushing’s, owing to its clinically translated novel mechanism of action to suppress both cortisol and androgen syntheses (the latter elevated in many women with CD). Interestingly, there was no evidence of clinically important free-T reduction in men, and more studies are needed to elucidate this mechanism.”
In SONICS, adults with confirmed CD and mean 24-hour urinary free-cortisol (mUFC) value at least 1.5 times the upper limit of normal were treated with levoketoconazole in three phases: 2- to 21-week dose-titration phase (150-600 mg BID, as needed, to target mUFC normalization); 6-month maintenance phase (primary endpoint); and 6-month extended evaluation phase. The end of maintenance phase findings that focused on reductions in mUFC and safety had been previously reported. The current analysis focused on secondary endpoints, including changes from baseline to end of maintenance in investigator-assessed CD clinical signs and symptoms (acne score [range: 0-44]; hirsutism score [women only; range: 0-36]; and peripheral edema score [range: 0-12]), and patient-reported outcomes of quality of life (Cushing QoL questionnaire score [range: 0-100]) and depression (Beck Depression Inventory II score [range: 0-63]). The researchers also assessed hormones including free testosterone levels, and they used paired t-tests to infer statistical significance of the mean changes from baseline to end of maintenance for all measures.
Of the 94 patients enrolled in SONICS, 77 entered the maintenance phase, said Dr. Fleseriu, professor of medicine and neurological surgery and director of the pituitary center at Oregon Health and Science University, Portland. The patients’ mean age was 44 years and mean baseline mUFC was 243.3 mcg/day; 82% of patients were female, and 96% were white. Between baseline and the end of maintenance, the researchers observed significant mean improvements in acne scores (from 2.8 to –1.8, respectively; P = .0063), hirsutism scores (women only, from 7.8 to –2.6; P = .0008), and peripheral edema scores (from 1.0 to –0.4; P = .0295). They also observed significant mean improvements in quality of life and depression scores between baseline and end of maintenance (P less than .0001 and P = .0043, respectively). Mean free-testosterone levels increased nonsignificantly between baseline and end of maintenance in men (from 5.1 to 5.8 ng/dL) yet decreased significantly in women (from 0.3 to 0.1 ng/dL; P less than 0.0001; reference). Overall, 33 patients (35%) discontinued taking levoketoconazole by the end of the maintenance phase. Twelve (13%) discontinued because of adverse events.
“I wasn’t necessarily surprised with any of the data in this poster as I had experience with the drug in clinical trials, but I was definitely pleased to see overall significant improvements in acne score, hirsutism score in women, and peripheral edema score,” Dr. Fleseriu said. “Those are benefits that could potentially increase long-term adherence to treatment and quality-of-life improvements, particularly in women. It’s also exciting to see that quality of life and depression improved in these patients as well.”
These types of patient-reported outcomes are so important to how our patients feel about their disease and should be more of a focus for us physicians; it’s important to look at efficacy, safety and patient reported outcomes when we decide for an individualized treatment for each patient,” she noted.
Dr. Fleseriu reported that she has received research funding for Oregon Health and Science University from Novartis, Millendo, and Strongbridge. She has also received scientific consulting fees from Novartis and Strongbridge.
LOS ANGELES – including acne, hirsutism, and peripheral edema, as did patient-reported quality of life and symptoms of depression.
The findings come from an analysis of secondary endpoints among patients enrolled in SONICS, an open-label, phase 3 study of levoketoconazole as a treatment for endogenous Cushing’s disease (CD) that enrolled 94 patients at centers in North America, Europe and the Middle East. An investigational cortisol synthesis inhibitor, levoketoconazole is being developed by Strongbridge Biopharma and is not yet approved by the Food and Drug Administration.
“Despite the availability of approved treatments, the medical needs in Cushing’s [disease] remain very high,” the study’s principal investigator, Maria Fleseriu, MD, FACE, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists, where the data were presented. “This study demonstrates that levoketoconazole has the potential to address several clinical features of Cushing’s, owing to its clinically translated novel mechanism of action to suppress both cortisol and androgen syntheses (the latter elevated in many women with CD). Interestingly, there was no evidence of clinically important free-T reduction in men, and more studies are needed to elucidate this mechanism.”
In SONICS, adults with confirmed CD and mean 24-hour urinary free-cortisol (mUFC) value at least 1.5 times the upper limit of normal were treated with levoketoconazole in three phases: 2- to 21-week dose-titration phase (150-600 mg BID, as needed, to target mUFC normalization); 6-month maintenance phase (primary endpoint); and 6-month extended evaluation phase. The end of maintenance phase findings that focused on reductions in mUFC and safety had been previously reported. The current analysis focused on secondary endpoints, including changes from baseline to end of maintenance in investigator-assessed CD clinical signs and symptoms (acne score [range: 0-44]; hirsutism score [women only; range: 0-36]; and peripheral edema score [range: 0-12]), and patient-reported outcomes of quality of life (Cushing QoL questionnaire score [range: 0-100]) and depression (Beck Depression Inventory II score [range: 0-63]). The researchers also assessed hormones including free testosterone levels, and they used paired t-tests to infer statistical significance of the mean changes from baseline to end of maintenance for all measures.
Of the 94 patients enrolled in SONICS, 77 entered the maintenance phase, said Dr. Fleseriu, professor of medicine and neurological surgery and director of the pituitary center at Oregon Health and Science University, Portland. The patients’ mean age was 44 years and mean baseline mUFC was 243.3 mcg/day; 82% of patients were female, and 96% were white. Between baseline and the end of maintenance, the researchers observed significant mean improvements in acne scores (from 2.8 to –1.8, respectively; P = .0063), hirsutism scores (women only, from 7.8 to –2.6; P = .0008), and peripheral edema scores (from 1.0 to –0.4; P = .0295). They also observed significant mean improvements in quality of life and depression scores between baseline and end of maintenance (P less than .0001 and P = .0043, respectively). Mean free-testosterone levels increased nonsignificantly between baseline and end of maintenance in men (from 5.1 to 5.8 ng/dL) yet decreased significantly in women (from 0.3 to 0.1 ng/dL; P less than 0.0001; reference). Overall, 33 patients (35%) discontinued taking levoketoconazole by the end of the maintenance phase. Twelve (13%) discontinued because of adverse events.
“I wasn’t necessarily surprised with any of the data in this poster as I had experience with the drug in clinical trials, but I was definitely pleased to see overall significant improvements in acne score, hirsutism score in women, and peripheral edema score,” Dr. Fleseriu said. “Those are benefits that could potentially increase long-term adherence to treatment and quality-of-life improvements, particularly in women. It’s also exciting to see that quality of life and depression improved in these patients as well.”
These types of patient-reported outcomes are so important to how our patients feel about their disease and should be more of a focus for us physicians; it’s important to look at efficacy, safety and patient reported outcomes when we decide for an individualized treatment for each patient,” she noted.
Dr. Fleseriu reported that she has received research funding for Oregon Health and Science University from Novartis, Millendo, and Strongbridge. She has also received scientific consulting fees from Novartis and Strongbridge.
REPORTING FROM AACE 2019
Key clinical point: Several clinical features of Cushing’s disease improved following 6 months of treatment with the investigational agent levoketoconazole.
Major finding: Between baseline and the end of maintenance, the researchers observed significant mean improvements in acne scores (from 2.8 to –1.8, respectively; P = .0063), hirsutism scores (women only, from 7.8 to –2.6; P = .0008), and peripheral edema scores (from 1.0 to –0.4; P = .0295).
Study details: An analysis of secondary endpoints among 77 patients enrolled in SONICS.
Disclosures: Dr. Fleseriu reported that she has received research funding for Oregon Health and Science University from Novartis, Millendo, and Strongbridge. She has also received scientific consulting fees from Novartis and Strongbridge.
Twitter chat recap: Take-homes from LUPUS 2019
Despite negative trial findings, belimumab (Benlysta) remains a valid option for black lupus patients, so long as they have high disease activity and positive serology.
That was just one of the many useful messages from a robust question-and-answer session on Twitter April 23, about important findings from the recent LUPUS 2019 Congress in San Francisco. The Twitter chat was hosted by MDedge Rheumatology and led by Jinoos Yazdany, MD, and Gabriela Schmajuk, MD, both associate professors of rheumatology at the University of California, San Francisco (UCSF). The chat included scores of posts from over a dozen participants, most of them rheumatologists, and it’s worth a recap.
The EMBRACE trial
The belimumab EMBRACE trial was the first topic up to bat. The Food and Drug Administration ordered GlaxoSmithKline to conduct the trial as a condition of approval for lupus in 2011; phase 3 trials found no benefit among a small number of black subjects and even a suggestion of harm.
Although lupus is highly prevalent among black people, and outcomes are generally worse, EMBRACE was the first lupus trial to enroll an entirely black population; 345 patients were treated for a year at 10 mg/kg IV every 4 weeks. Inclusion criteria included disease activity scores of at least 8.
Overall, 49% of belimumab patients, and 42% on placebo, had a positive response, which meant a drop of 4 or more disease activity points, among other things. The difference was not statistically significant (P = .11).
However, GSK’s data showed a statistically significant benefit in favor of belimumab among people who entered with a disease activity score of at least 10 (53% vs. 41% for placebo), as well as for those with low complement levels (47% vs. 25%) and both anti–double stranded DNA antibodies and low complement (45% vs. 24%). Response rates were also significantly higher among the 57% of subjects who lived outside of the United States and Canada.
So what to make of the results?
“The EMBRACE efficacy data seems to reinforce what we already know: belimumab doesn’t work in a lot of patients, and it [has] the best chance of working in patients with higher baseline disease activity,” tweeted Dr. Yazdany.
As for prescribing, Sarah Patterson, MD, a postdoctoral fellow in the UCSF Division of Rheumatology, tweeted that the results “support the use of belimumab for black lupus patients with high disease activity” and positive serology.
For those who don’t fit the treatment profile, “we should take care to not over-use it,” said Megan Clowse, MD, an associate professor of rheumatology at Duke University, Durham, N.C., in a tweet.
The HCQ adherence fail
Poor hydroxychloroquine (HCQ) adherence came up next on Twitter. The chat participants agreed it’s a huge problem, but no one knows why. Perhaps it’s because patients don’t feel a therapeutic effect or perhaps because GI problems and other side effects are worse than doctors think. Maybe there’s simply not enough social support to encourage people to stay on the drug, even though it’s the single most important medication in lupus.
A nine-study meta-analysis presented at LUPUS 2019 suggested a solution: blood levels. The odds of nonadherence were three times higher in patients below threshold HCQ levels, and although not statistically significant, the mean lupus disease activity index score was more than 3 points higher.
A rheumatologist on the chat said that he’s already checking them.
“We have been measuring HCQ for the past 12 months” at Washington University, St. Louis, according to Alfred Kim, MD, PhD, an assistant professor of rheumatology at the school. The data are just now coming in, he said, but it seems to be catching people.
That raised another question on the chat, however: What do you do with people who aren’t down with the program? They’ll be out the door and gone with the wrong words.
“I haven’t figured out the proper tone for when I say ‘So, I see that you haven’t picked up your HCQ in 5 months,’ ” tweeted Dr. Clowse. “It is a really uncomfortable phone call.”
Dr. Kim said that “I ‘gotcha’ them all the time. Guess what typically goes up after they get that 1st HCQ test? Their HCQ levels ... But this rise isn’t durable in our short experience. It goes back down later.”
He tweeted that overall “this is an opportunity to educate patients on the benefits of HCQ ... Most actually do not [know] why they are taking this medication, in our experience.” In another tweet, Dr. Kim said “I tell them I care,” and that checking HCQ levels “is one way of demonstrating how I want to improve their outcomes.”
Tiffany from #LupusChat thought that it’s time for doctors to sit down with patient advocates and hash it out. She tweeted that “I truly feel this would be a positive 1st step ... a two-way conversation that’s non-judgmental and focused on improving” outcomes and quality of life.
Baricitinib for lupus?
The final topic was baricitinib (Olumiant).
There were modest indications of benefit at 4 mg/day oral after 6 months in a phase 2 trial with 314 people. There were also serious infections in 6% versus 2% on 2 mg/day and 1% on placebo. One patient in the 4-mg/day arm (1%) developed deep vein thrombosis (DVT), but they were positive for antiphospholipid antibodies, which raise the clot risk.
Baricitinib is FDA approved as second line at 2 mg/day for adult rheumatoid arthritis; there’s a black box warning of malignancies, thrombosis, and serious infections.
“I’m not sure” the risk-benefit is in the right direction for baricitinib in lupus. “There were a significant number of serious infections ... for not a lot of effect on” disease activity, tweeted the Twitter chat coleader, Dr. Schmajuk. In a separate tweet, she said that, even in nonlupus patients, “we are avoiding [Janus kinase inhibitors] in patients with DVT risk factors. If I were a patient, [I’m] not sure I would want to take the risk.”
“Future studies with larger sample size and longer follow up ... are needed to address some of the concerns related to DVT,” said Zahi Touma, MD, an assistant professor of rheumatology at the University of Toronto.
Despite negative trial findings, belimumab (Benlysta) remains a valid option for black lupus patients, so long as they have high disease activity and positive serology.
That was just one of the many useful messages from a robust question-and-answer session on Twitter April 23, about important findings from the recent LUPUS 2019 Congress in San Francisco. The Twitter chat was hosted by MDedge Rheumatology and led by Jinoos Yazdany, MD, and Gabriela Schmajuk, MD, both associate professors of rheumatology at the University of California, San Francisco (UCSF). The chat included scores of posts from over a dozen participants, most of them rheumatologists, and it’s worth a recap.
The EMBRACE trial
The belimumab EMBRACE trial was the first topic up to bat. The Food and Drug Administration ordered GlaxoSmithKline to conduct the trial as a condition of approval for lupus in 2011; phase 3 trials found no benefit among a small number of black subjects and even a suggestion of harm.
Although lupus is highly prevalent among black people, and outcomes are generally worse, EMBRACE was the first lupus trial to enroll an entirely black population; 345 patients were treated for a year at 10 mg/kg IV every 4 weeks. Inclusion criteria included disease activity scores of at least 8.
Overall, 49% of belimumab patients, and 42% on placebo, had a positive response, which meant a drop of 4 or more disease activity points, among other things. The difference was not statistically significant (P = .11).
However, GSK’s data showed a statistically significant benefit in favor of belimumab among people who entered with a disease activity score of at least 10 (53% vs. 41% for placebo), as well as for those with low complement levels (47% vs. 25%) and both anti–double stranded DNA antibodies and low complement (45% vs. 24%). Response rates were also significantly higher among the 57% of subjects who lived outside of the United States and Canada.
So what to make of the results?
“The EMBRACE efficacy data seems to reinforce what we already know: belimumab doesn’t work in a lot of patients, and it [has] the best chance of working in patients with higher baseline disease activity,” tweeted Dr. Yazdany.
As for prescribing, Sarah Patterson, MD, a postdoctoral fellow in the UCSF Division of Rheumatology, tweeted that the results “support the use of belimumab for black lupus patients with high disease activity” and positive serology.
For those who don’t fit the treatment profile, “we should take care to not over-use it,” said Megan Clowse, MD, an associate professor of rheumatology at Duke University, Durham, N.C., in a tweet.
The HCQ adherence fail
Poor hydroxychloroquine (HCQ) adherence came up next on Twitter. The chat participants agreed it’s a huge problem, but no one knows why. Perhaps it’s because patients don’t feel a therapeutic effect or perhaps because GI problems and other side effects are worse than doctors think. Maybe there’s simply not enough social support to encourage people to stay on the drug, even though it’s the single most important medication in lupus.
A nine-study meta-analysis presented at LUPUS 2019 suggested a solution: blood levels. The odds of nonadherence were three times higher in patients below threshold HCQ levels, and although not statistically significant, the mean lupus disease activity index score was more than 3 points higher.
A rheumatologist on the chat said that he’s already checking them.
“We have been measuring HCQ for the past 12 months” at Washington University, St. Louis, according to Alfred Kim, MD, PhD, an assistant professor of rheumatology at the school. The data are just now coming in, he said, but it seems to be catching people.
That raised another question on the chat, however: What do you do with people who aren’t down with the program? They’ll be out the door and gone with the wrong words.
“I haven’t figured out the proper tone for when I say ‘So, I see that you haven’t picked up your HCQ in 5 months,’ ” tweeted Dr. Clowse. “It is a really uncomfortable phone call.”
Dr. Kim said that “I ‘gotcha’ them all the time. Guess what typically goes up after they get that 1st HCQ test? Their HCQ levels ... But this rise isn’t durable in our short experience. It goes back down later.”
He tweeted that overall “this is an opportunity to educate patients on the benefits of HCQ ... Most actually do not [know] why they are taking this medication, in our experience.” In another tweet, Dr. Kim said “I tell them I care,” and that checking HCQ levels “is one way of demonstrating how I want to improve their outcomes.”
Tiffany from #LupusChat thought that it’s time for doctors to sit down with patient advocates and hash it out. She tweeted that “I truly feel this would be a positive 1st step ... a two-way conversation that’s non-judgmental and focused on improving” outcomes and quality of life.
Baricitinib for lupus?
The final topic was baricitinib (Olumiant).
There were modest indications of benefit at 4 mg/day oral after 6 months in a phase 2 trial with 314 people. There were also serious infections in 6% versus 2% on 2 mg/day and 1% on placebo. One patient in the 4-mg/day arm (1%) developed deep vein thrombosis (DVT), but they were positive for antiphospholipid antibodies, which raise the clot risk.
Baricitinib is FDA approved as second line at 2 mg/day for adult rheumatoid arthritis; there’s a black box warning of malignancies, thrombosis, and serious infections.
“I’m not sure” the risk-benefit is in the right direction for baricitinib in lupus. “There were a significant number of serious infections ... for not a lot of effect on” disease activity, tweeted the Twitter chat coleader, Dr. Schmajuk. In a separate tweet, she said that, even in nonlupus patients, “we are avoiding [Janus kinase inhibitors] in patients with DVT risk factors. If I were a patient, [I’m] not sure I would want to take the risk.”
“Future studies with larger sample size and longer follow up ... are needed to address some of the concerns related to DVT,” said Zahi Touma, MD, an assistant professor of rheumatology at the University of Toronto.
Despite negative trial findings, belimumab (Benlysta) remains a valid option for black lupus patients, so long as they have high disease activity and positive serology.
That was just one of the many useful messages from a robust question-and-answer session on Twitter April 23, about important findings from the recent LUPUS 2019 Congress in San Francisco. The Twitter chat was hosted by MDedge Rheumatology and led by Jinoos Yazdany, MD, and Gabriela Schmajuk, MD, both associate professors of rheumatology at the University of California, San Francisco (UCSF). The chat included scores of posts from over a dozen participants, most of them rheumatologists, and it’s worth a recap.
The EMBRACE trial
The belimumab EMBRACE trial was the first topic up to bat. The Food and Drug Administration ordered GlaxoSmithKline to conduct the trial as a condition of approval for lupus in 2011; phase 3 trials found no benefit among a small number of black subjects and even a suggestion of harm.
Although lupus is highly prevalent among black people, and outcomes are generally worse, EMBRACE was the first lupus trial to enroll an entirely black population; 345 patients were treated for a year at 10 mg/kg IV every 4 weeks. Inclusion criteria included disease activity scores of at least 8.
Overall, 49% of belimumab patients, and 42% on placebo, had a positive response, which meant a drop of 4 or more disease activity points, among other things. The difference was not statistically significant (P = .11).
However, GSK’s data showed a statistically significant benefit in favor of belimumab among people who entered with a disease activity score of at least 10 (53% vs. 41% for placebo), as well as for those with low complement levels (47% vs. 25%) and both anti–double stranded DNA antibodies and low complement (45% vs. 24%). Response rates were also significantly higher among the 57% of subjects who lived outside of the United States and Canada.
So what to make of the results?
“The EMBRACE efficacy data seems to reinforce what we already know: belimumab doesn’t work in a lot of patients, and it [has] the best chance of working in patients with higher baseline disease activity,” tweeted Dr. Yazdany.
As for prescribing, Sarah Patterson, MD, a postdoctoral fellow in the UCSF Division of Rheumatology, tweeted that the results “support the use of belimumab for black lupus patients with high disease activity” and positive serology.
For those who don’t fit the treatment profile, “we should take care to not over-use it,” said Megan Clowse, MD, an associate professor of rheumatology at Duke University, Durham, N.C., in a tweet.
The HCQ adherence fail
Poor hydroxychloroquine (HCQ) adherence came up next on Twitter. The chat participants agreed it’s a huge problem, but no one knows why. Perhaps it’s because patients don’t feel a therapeutic effect or perhaps because GI problems and other side effects are worse than doctors think. Maybe there’s simply not enough social support to encourage people to stay on the drug, even though it’s the single most important medication in lupus.
A nine-study meta-analysis presented at LUPUS 2019 suggested a solution: blood levels. The odds of nonadherence were three times higher in patients below threshold HCQ levels, and although not statistically significant, the mean lupus disease activity index score was more than 3 points higher.
A rheumatologist on the chat said that he’s already checking them.
“We have been measuring HCQ for the past 12 months” at Washington University, St. Louis, according to Alfred Kim, MD, PhD, an assistant professor of rheumatology at the school. The data are just now coming in, he said, but it seems to be catching people.
That raised another question on the chat, however: What do you do with people who aren’t down with the program? They’ll be out the door and gone with the wrong words.
“I haven’t figured out the proper tone for when I say ‘So, I see that you haven’t picked up your HCQ in 5 months,’ ” tweeted Dr. Clowse. “It is a really uncomfortable phone call.”
Dr. Kim said that “I ‘gotcha’ them all the time. Guess what typically goes up after they get that 1st HCQ test? Their HCQ levels ... But this rise isn’t durable in our short experience. It goes back down later.”
He tweeted that overall “this is an opportunity to educate patients on the benefits of HCQ ... Most actually do not [know] why they are taking this medication, in our experience.” In another tweet, Dr. Kim said “I tell them I care,” and that checking HCQ levels “is one way of demonstrating how I want to improve their outcomes.”
Tiffany from #LupusChat thought that it’s time for doctors to sit down with patient advocates and hash it out. She tweeted that “I truly feel this would be a positive 1st step ... a two-way conversation that’s non-judgmental and focused on improving” outcomes and quality of life.
Baricitinib for lupus?
The final topic was baricitinib (Olumiant).
There were modest indications of benefit at 4 mg/day oral after 6 months in a phase 2 trial with 314 people. There were also serious infections in 6% versus 2% on 2 mg/day and 1% on placebo. One patient in the 4-mg/day arm (1%) developed deep vein thrombosis (DVT), but they were positive for antiphospholipid antibodies, which raise the clot risk.
Baricitinib is FDA approved as second line at 2 mg/day for adult rheumatoid arthritis; there’s a black box warning of malignancies, thrombosis, and serious infections.
“I’m not sure” the risk-benefit is in the right direction for baricitinib in lupus. “There were a significant number of serious infections ... for not a lot of effect on” disease activity, tweeted the Twitter chat coleader, Dr. Schmajuk. In a separate tweet, she said that, even in nonlupus patients, “we are avoiding [Janus kinase inhibitors] in patients with DVT risk factors. If I were a patient, [I’m] not sure I would want to take the risk.”
“Future studies with larger sample size and longer follow up ... are needed to address some of the concerns related to DVT,” said Zahi Touma, MD, an assistant professor of rheumatology at the University of Toronto.
FROM LUPUS 2019
Three-drug regimen shows promise for refractory primary biliary cholangitis
VIENNA –
In addition to producing drops in levels of alkaline phosphatase and bilirubin, key surrogate markers for ultimate clinical benefit, the addition of bezafibrate also led to reduced pruritis among five of eight patients who had this symptom when they started on bezafibrate, Lena Smets said at the meeting, sponsored by the European Association for the Study of the Liver. Pruritis is a bothersome adverse effect from obeticholic acid (OCA) treatment that also occurs in patients with untreated primary biliary cholangitis (PBC), so the drop in pruritis in patients who started bezafibrate was notable. Overall, the triple regimen of ursodeoxycholic acid (UDCA), OCA, and bezafibrate was “well tolerated,” said Ms. Smets, a researcher at KU Leuven, Belgium.
Bezafibrate is available in Europe as a lipid-lowering treatment, especially for lowering triglycerides, so there might be a temptation to use it off label in routine practice as an add-on to UDCA and OCA in PBC patients who are not fully responsive to this dual therapy, Ms. Smets acknowledged. But she stressed that what’s needed now is a multicenter, randomized trial of bezafibrate as part of triple-therapy regimen with many more than the 10 patients included in her review.
Both UDCA and OCA have Food and Drug Administration approval for U.S. treatment of PBC. Bezafibrate is not approved for U.S. marketing, but the related agent fenofibrate has FDA approval and has shown preliminary evidence of acting like bezafibrate in PBC patients in small pilot studies or case reports, showing that “growing evidence supports the use of fibrates, but their safety has not been firmly established, and caution should be used,” according to a recent review by clinicians from the University of California, Davis (Gastroenterol Hepatol [NY]. 2018 March;14[3]:154-63).
The series of 10 PBC patients who received triple therapy at KU Leuven began as part of a cohort of 16 PBC patients treated at that center with UDCA monotherapy for an average of 6 years before entering the POISE (Phase 3 Study of Obeticholic Acid in Patients With Primary Biliary Cirrhosis) phase 3 trial that ran at KU Leuven and 57 other sites in 13 countries. POISE randomized 216 PBC patients with persistently elevated alkaline phosphatase and bilirubin levels despite UDCA treatment to added treatment with OCA. The results showed incremental benefit to these patients from a tolerable OCA acid regimen (N Engl J Med. 2016 Aug 18;375[7]631-43). The findings helped OCA (Ocaliva) get FDA marketing approval in 2016 for treatment of PBC when added to UDCA in patients not fully responsive to UDCA monotherapy.
The case for bezafibrate as an add-on to UDCA for refractory PBC patients was documented by a 2018 report from the BEZURSO (Phase 3 Study of Bezafibrate in Combination With Ursodeoxycholic Acid in Primary Biliary Cirrhosis) trial. Run at multiple centers in France, the trial randomized 100 patients on UDCA treatment to added bezafibrate or placebo, and showed that bezafibrate produced significant incremental decreases in and normalizations of alkaline phosphatase and bilirubin levels. It also had the expected effect of increasing serum creatinine level by an average of 5% (N Engl J Med. 2018 June 7;378[23]:2171-81).
Among the 16 participants in the POISE trial at KU Leuven, 13 completed that trial and then agreed to start on a triple regimen with bezafibrate added because of persistent elevations in alkaline phosphatase, and 10 patients completed 6 months on triple treatment. After 6 months, alkaline phosphatase levels reached the normal range in 5 of these 10 patients, Ms. Smets reported. Bilirubin levels also decreased in each of the 10 patients, although bilirubin had already been at a normal level in 9 of the 10 patients at the start of bezafibrate treatment, and this rate remained at 9 of 10 after 6 months. Eight of the 10 had pruritis when they started bezafibrate, and five of these eight reported decreased symptoms on treatment. Patients also showed no biochemical evidence of hepatotoxicity on the triple regimen, Ms. Smets said.
Guidelines published in 2017 from the European Association for the Study of the Liver cited evidence from small studies showing possible efficacy of fibrates as an add-on for PBC patients refractory to UDCA monotherapy, but stopped short of any endorsement of their use (J Hepatol. 2017 July;67[1]:145-72). However, guidelines from the American Association for the Study of Liver Diseases, released several months later and after publication of the BEZURSO results, said that “fibrates can be considered as off-label alternatives for patients with PBC and inadequate response to UDCA,” but also warned that “use of OCA and fibrates is discouraged in patients with decompensated liver disease (Child Pugh–Turcotte B or C)” (Hepatology. 2018 Jan;69[1]:394-419).
SOURCE: Smets L et al. J Hepatol. 2019 April;70[1]:e130.
Clinicians in Europe already use this triple therapy in appropriate patients. Bezafibrate is cheap, it has been used since the 1970s to lower triglyceride levels, and it is generally safe. Following the report of results from the BEZURSO trial in 2018, guidelines changed to accept the option of adding a fibrate to ursodeoxycholic acid and obeticholic acid.
Thomas Berg, MD, is professor and head of hepatology at University Hospital in Leipzig, Germany. He has received personal fees and research support from several companies including Intercept, the company that markets obeticholic acid (Ocaliva). He made these comments in an interview.
Clinicians in Europe already use this triple therapy in appropriate patients. Bezafibrate is cheap, it has been used since the 1970s to lower triglyceride levels, and it is generally safe. Following the report of results from the BEZURSO trial in 2018, guidelines changed to accept the option of adding a fibrate to ursodeoxycholic acid and obeticholic acid.
Thomas Berg, MD, is professor and head of hepatology at University Hospital in Leipzig, Germany. He has received personal fees and research support from several companies including Intercept, the company that markets obeticholic acid (Ocaliva). He made these comments in an interview.
Clinicians in Europe already use this triple therapy in appropriate patients. Bezafibrate is cheap, it has been used since the 1970s to lower triglyceride levels, and it is generally safe. Following the report of results from the BEZURSO trial in 2018, guidelines changed to accept the option of adding a fibrate to ursodeoxycholic acid and obeticholic acid.
Thomas Berg, MD, is professor and head of hepatology at University Hospital in Leipzig, Germany. He has received personal fees and research support from several companies including Intercept, the company that markets obeticholic acid (Ocaliva). He made these comments in an interview.
VIENNA –
In addition to producing drops in levels of alkaline phosphatase and bilirubin, key surrogate markers for ultimate clinical benefit, the addition of bezafibrate also led to reduced pruritis among five of eight patients who had this symptom when they started on bezafibrate, Lena Smets said at the meeting, sponsored by the European Association for the Study of the Liver. Pruritis is a bothersome adverse effect from obeticholic acid (OCA) treatment that also occurs in patients with untreated primary biliary cholangitis (PBC), so the drop in pruritis in patients who started bezafibrate was notable. Overall, the triple regimen of ursodeoxycholic acid (UDCA), OCA, and bezafibrate was “well tolerated,” said Ms. Smets, a researcher at KU Leuven, Belgium.
Bezafibrate is available in Europe as a lipid-lowering treatment, especially for lowering triglycerides, so there might be a temptation to use it off label in routine practice as an add-on to UDCA and OCA in PBC patients who are not fully responsive to this dual therapy, Ms. Smets acknowledged. But she stressed that what’s needed now is a multicenter, randomized trial of bezafibrate as part of triple-therapy regimen with many more than the 10 patients included in her review.
Both UDCA and OCA have Food and Drug Administration approval for U.S. treatment of PBC. Bezafibrate is not approved for U.S. marketing, but the related agent fenofibrate has FDA approval and has shown preliminary evidence of acting like bezafibrate in PBC patients in small pilot studies or case reports, showing that “growing evidence supports the use of fibrates, but their safety has not been firmly established, and caution should be used,” according to a recent review by clinicians from the University of California, Davis (Gastroenterol Hepatol [NY]. 2018 March;14[3]:154-63).
The series of 10 PBC patients who received triple therapy at KU Leuven began as part of a cohort of 16 PBC patients treated at that center with UDCA monotherapy for an average of 6 years before entering the POISE (Phase 3 Study of Obeticholic Acid in Patients With Primary Biliary Cirrhosis) phase 3 trial that ran at KU Leuven and 57 other sites in 13 countries. POISE randomized 216 PBC patients with persistently elevated alkaline phosphatase and bilirubin levels despite UDCA treatment to added treatment with OCA. The results showed incremental benefit to these patients from a tolerable OCA acid regimen (N Engl J Med. 2016 Aug 18;375[7]631-43). The findings helped OCA (Ocaliva) get FDA marketing approval in 2016 for treatment of PBC when added to UDCA in patients not fully responsive to UDCA monotherapy.
The case for bezafibrate as an add-on to UDCA for refractory PBC patients was documented by a 2018 report from the BEZURSO (Phase 3 Study of Bezafibrate in Combination With Ursodeoxycholic Acid in Primary Biliary Cirrhosis) trial. Run at multiple centers in France, the trial randomized 100 patients on UDCA treatment to added bezafibrate or placebo, and showed that bezafibrate produced significant incremental decreases in and normalizations of alkaline phosphatase and bilirubin levels. It also had the expected effect of increasing serum creatinine level by an average of 5% (N Engl J Med. 2018 June 7;378[23]:2171-81).
Among the 16 participants in the POISE trial at KU Leuven, 13 completed that trial and then agreed to start on a triple regimen with bezafibrate added because of persistent elevations in alkaline phosphatase, and 10 patients completed 6 months on triple treatment. After 6 months, alkaline phosphatase levels reached the normal range in 5 of these 10 patients, Ms. Smets reported. Bilirubin levels also decreased in each of the 10 patients, although bilirubin had already been at a normal level in 9 of the 10 patients at the start of bezafibrate treatment, and this rate remained at 9 of 10 after 6 months. Eight of the 10 had pruritis when they started bezafibrate, and five of these eight reported decreased symptoms on treatment. Patients also showed no biochemical evidence of hepatotoxicity on the triple regimen, Ms. Smets said.
Guidelines published in 2017 from the European Association for the Study of the Liver cited evidence from small studies showing possible efficacy of fibrates as an add-on for PBC patients refractory to UDCA monotherapy, but stopped short of any endorsement of their use (J Hepatol. 2017 July;67[1]:145-72). However, guidelines from the American Association for the Study of Liver Diseases, released several months later and after publication of the BEZURSO results, said that “fibrates can be considered as off-label alternatives for patients with PBC and inadequate response to UDCA,” but also warned that “use of OCA and fibrates is discouraged in patients with decompensated liver disease (Child Pugh–Turcotte B or C)” (Hepatology. 2018 Jan;69[1]:394-419).
SOURCE: Smets L et al. J Hepatol. 2019 April;70[1]:e130.
VIENNA –
In addition to producing drops in levels of alkaline phosphatase and bilirubin, key surrogate markers for ultimate clinical benefit, the addition of bezafibrate also led to reduced pruritis among five of eight patients who had this symptom when they started on bezafibrate, Lena Smets said at the meeting, sponsored by the European Association for the Study of the Liver. Pruritis is a bothersome adverse effect from obeticholic acid (OCA) treatment that also occurs in patients with untreated primary biliary cholangitis (PBC), so the drop in pruritis in patients who started bezafibrate was notable. Overall, the triple regimen of ursodeoxycholic acid (UDCA), OCA, and bezafibrate was “well tolerated,” said Ms. Smets, a researcher at KU Leuven, Belgium.
Bezafibrate is available in Europe as a lipid-lowering treatment, especially for lowering triglycerides, so there might be a temptation to use it off label in routine practice as an add-on to UDCA and OCA in PBC patients who are not fully responsive to this dual therapy, Ms. Smets acknowledged. But she stressed that what’s needed now is a multicenter, randomized trial of bezafibrate as part of triple-therapy regimen with many more than the 10 patients included in her review.
Both UDCA and OCA have Food and Drug Administration approval for U.S. treatment of PBC. Bezafibrate is not approved for U.S. marketing, but the related agent fenofibrate has FDA approval and has shown preliminary evidence of acting like bezafibrate in PBC patients in small pilot studies or case reports, showing that “growing evidence supports the use of fibrates, but their safety has not been firmly established, and caution should be used,” according to a recent review by clinicians from the University of California, Davis (Gastroenterol Hepatol [NY]. 2018 March;14[3]:154-63).
The series of 10 PBC patients who received triple therapy at KU Leuven began as part of a cohort of 16 PBC patients treated at that center with UDCA monotherapy for an average of 6 years before entering the POISE (Phase 3 Study of Obeticholic Acid in Patients With Primary Biliary Cirrhosis) phase 3 trial that ran at KU Leuven and 57 other sites in 13 countries. POISE randomized 216 PBC patients with persistently elevated alkaline phosphatase and bilirubin levels despite UDCA treatment to added treatment with OCA. The results showed incremental benefit to these patients from a tolerable OCA acid regimen (N Engl J Med. 2016 Aug 18;375[7]631-43). The findings helped OCA (Ocaliva) get FDA marketing approval in 2016 for treatment of PBC when added to UDCA in patients not fully responsive to UDCA monotherapy.
The case for bezafibrate as an add-on to UDCA for refractory PBC patients was documented by a 2018 report from the BEZURSO (Phase 3 Study of Bezafibrate in Combination With Ursodeoxycholic Acid in Primary Biliary Cirrhosis) trial. Run at multiple centers in France, the trial randomized 100 patients on UDCA treatment to added bezafibrate or placebo, and showed that bezafibrate produced significant incremental decreases in and normalizations of alkaline phosphatase and bilirubin levels. It also had the expected effect of increasing serum creatinine level by an average of 5% (N Engl J Med. 2018 June 7;378[23]:2171-81).
Among the 16 participants in the POISE trial at KU Leuven, 13 completed that trial and then agreed to start on a triple regimen with bezafibrate added because of persistent elevations in alkaline phosphatase, and 10 patients completed 6 months on triple treatment. After 6 months, alkaline phosphatase levels reached the normal range in 5 of these 10 patients, Ms. Smets reported. Bilirubin levels also decreased in each of the 10 patients, although bilirubin had already been at a normal level in 9 of the 10 patients at the start of bezafibrate treatment, and this rate remained at 9 of 10 after 6 months. Eight of the 10 had pruritis when they started bezafibrate, and five of these eight reported decreased symptoms on treatment. Patients also showed no biochemical evidence of hepatotoxicity on the triple regimen, Ms. Smets said.
Guidelines published in 2017 from the European Association for the Study of the Liver cited evidence from small studies showing possible efficacy of fibrates as an add-on for PBC patients refractory to UDCA monotherapy, but stopped short of any endorsement of their use (J Hepatol. 2017 July;67[1]:145-72). However, guidelines from the American Association for the Study of Liver Diseases, released several months later and after publication of the BEZURSO results, said that “fibrates can be considered as off-label alternatives for patients with PBC and inadequate response to UDCA,” but also warned that “use of OCA and fibrates is discouraged in patients with decompensated liver disease (Child Pugh–Turcotte B or C)” (Hepatology. 2018 Jan;69[1]:394-419).
SOURCE: Smets L et al. J Hepatol. 2019 April;70[1]:e130.
REPORTING FROM ILC 2019
Association insurance pushes on despite court ruling
When the Trump administration in June 2018 issued rules making it easier for small employers to band together to buy health insurance, “we started looking immediately,” recalled Scott Lyon, a top executive at the Small Business Association of Michigan.
Although he offered traditional small-group health insurance to his association’s employees and members, Mr. Lyon liked adding a new option for both: potentially less expensive coverage through an association health plan, which doesn’t have to meet all the rules of the Affordable Care Act (ACA).
Now, a few months in, “we’ve got 400 companies and a couple of thousand workers signed up,” said Mr. Lyon.
Most of the new enrollees joined through groups like Mr. Lyon’s or local chambers of commerce, farm bureaus, or agriculture-based cooperatives. Such groups see the plans not only as a way to offer insurance, but also as an enticement to boost membership.
In the first legal test, however, U.S. District Judge John Bates at the end of March sided with 11 states and the District of Columbia challenging the law. He invalidated a large chunk of those June rules, saying the administration issued them as an “end-run around the Affordable Care Act.”
So what now?
Unless the government seeks – which it has yet to do – and is granted a stay of the judge’s order, “plans formed under the vacated sections of the rule are illegal,” said Timothy Jost, an emeritus health law professor from Washington and Lee University, Lexington, Va.
Still, that won’t mean anything for existing plans if the states or federal regulators choose not to enforce the ruling, Mr. Jost said.
And that could cause more confusion in the marketplace.
While the states that brought the challenge are expected to enforce the ruling, some other states support broader access to association health plans, said Christopher Condeluci, an attorney who represents several such plans, including the one formed by Mr. Lyon’s group.
“These plans are not an end run around the ACA,” said Mr. Condeluci.
Association health plans already established under the administration’s rules cover “virtually” all the federal law’s essential health benefits, he said, with the exception of dental and vision care for children.
Local chamber of commerce plans are mainly continuing business as usual while watching to see if the government will appeal, said Katie Mahoney, vice president of health policy at the U.S. Chamber of Commerce.
A few, including a plan offered through the Las Vegas chamber, may limit new enrollment for sole proprietors, she said, as the judge sharply questioned whether they qualified as “employers” under federal laws.
Sole proprietors are generally individuals who own and operate their own businesses without any employees.
Judge Bates wrote that, in the regulation, the Department of Labor “stretches the definition of employer” beyond what federal law allows. The rule was designed to increase access to plans that “avoid the most stringent requirements” of the ACA.
The opinion by Judge Bates, who was appointed by President George W. Bush, is widely expected to be appealed, although the government has not yet done so.
The decision affects one pillar of a broader effort by the Trump administration to expand access to less expensive health insurance. Association plans have long been a favorite of Republicans, existing before the ACA. Supporters say they are one way to pool groups of businesses together to get better premium rates.
Still, some plans faced problems in the past, including bankruptcy or complaints that they misled consumers by not fully informing them about what is covered.
After the ACA took effect, enrollment fell, partly because many small businesses were buying new ACA plans and many existing association plans had to comply with ACA rules for small-group coverage anyway. People who ran their own businesses and had no employees qualified only for coverage through the ACA’s individual market.
But the Trump administration in June broadened the definition of those eligible to buy insurance through employer-based associations to include sole proprietors and also made it easier to form associations to offer coverage.
In addition, the changes allowed more association plans to be classified as large-employer coverage, which exempts them from some of the ACA’s requirements. For example, association plans don’t have to include all 10 of the ACA’s “essential” health benefits, such as mental health care and prescription drug coverage.
Also, unlike ACA plans, association insurers can set premium rates based on an employer’s industry, as well as taking into account the age range and gender makeup of their workforce.
In other words, association plans can charge less for companies with workforces that are generally younger and male in occupations that involve mainly desk work than for firms with mostly older workers or companies doing riskier work, such as cutting down trees or roofing.
Still, such plans must abide by other ACA provisions, including accepting people with preexisting medical conditions.
Critics, including the states that sued, say the new rules and other administration-backed changes will weaken the market for ACA plans by drawing out younger and healthier people. The states also argued that the new rules would be costly for them to administer, alleging they would have to devote more resources to preventing consumer fraud.
In Michigan, Mr. Lyon said the association his group formed, called Transcend, offers coverage to small employers and sole proprietors that is just as generous as large-group plans. It is a fully insured plan through the state’s Blue Cross Blue Shield carrier that covers a broad array of benefits, except children’s dental and vision.
“One thing we don’t want to do is sell a bag of air to our members,” said Mr. Lyon.
While some new members have reported large savings by enrolling, Mr. Lyon said association plans are not necessarily less expensive than small-group coverage. It all depends on the demographic and occupational makeup of the small business, he said.
“Our best estimate was association health plans would be the right solution for 30%-35% of the small-group world,” said Mr. Lyon. “It all has to come together. Age matters. Gender matters. It’s so specific to each company.”
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
When the Trump administration in June 2018 issued rules making it easier for small employers to band together to buy health insurance, “we started looking immediately,” recalled Scott Lyon, a top executive at the Small Business Association of Michigan.
Although he offered traditional small-group health insurance to his association’s employees and members, Mr. Lyon liked adding a new option for both: potentially less expensive coverage through an association health plan, which doesn’t have to meet all the rules of the Affordable Care Act (ACA).
Now, a few months in, “we’ve got 400 companies and a couple of thousand workers signed up,” said Mr. Lyon.
Most of the new enrollees joined through groups like Mr. Lyon’s or local chambers of commerce, farm bureaus, or agriculture-based cooperatives. Such groups see the plans not only as a way to offer insurance, but also as an enticement to boost membership.
In the first legal test, however, U.S. District Judge John Bates at the end of March sided with 11 states and the District of Columbia challenging the law. He invalidated a large chunk of those June rules, saying the administration issued them as an “end-run around the Affordable Care Act.”
So what now?
Unless the government seeks – which it has yet to do – and is granted a stay of the judge’s order, “plans formed under the vacated sections of the rule are illegal,” said Timothy Jost, an emeritus health law professor from Washington and Lee University, Lexington, Va.
Still, that won’t mean anything for existing plans if the states or federal regulators choose not to enforce the ruling, Mr. Jost said.
And that could cause more confusion in the marketplace.
While the states that brought the challenge are expected to enforce the ruling, some other states support broader access to association health plans, said Christopher Condeluci, an attorney who represents several such plans, including the one formed by Mr. Lyon’s group.
“These plans are not an end run around the ACA,” said Mr. Condeluci.
Association health plans already established under the administration’s rules cover “virtually” all the federal law’s essential health benefits, he said, with the exception of dental and vision care for children.
Local chamber of commerce plans are mainly continuing business as usual while watching to see if the government will appeal, said Katie Mahoney, vice president of health policy at the U.S. Chamber of Commerce.
A few, including a plan offered through the Las Vegas chamber, may limit new enrollment for sole proprietors, she said, as the judge sharply questioned whether they qualified as “employers” under federal laws.
Sole proprietors are generally individuals who own and operate their own businesses without any employees.
Judge Bates wrote that, in the regulation, the Department of Labor “stretches the definition of employer” beyond what federal law allows. The rule was designed to increase access to plans that “avoid the most stringent requirements” of the ACA.
The opinion by Judge Bates, who was appointed by President George W. Bush, is widely expected to be appealed, although the government has not yet done so.
The decision affects one pillar of a broader effort by the Trump administration to expand access to less expensive health insurance. Association plans have long been a favorite of Republicans, existing before the ACA. Supporters say they are one way to pool groups of businesses together to get better premium rates.
Still, some plans faced problems in the past, including bankruptcy or complaints that they misled consumers by not fully informing them about what is covered.
After the ACA took effect, enrollment fell, partly because many small businesses were buying new ACA plans and many existing association plans had to comply with ACA rules for small-group coverage anyway. People who ran their own businesses and had no employees qualified only for coverage through the ACA’s individual market.
But the Trump administration in June broadened the definition of those eligible to buy insurance through employer-based associations to include sole proprietors and also made it easier to form associations to offer coverage.
In addition, the changes allowed more association plans to be classified as large-employer coverage, which exempts them from some of the ACA’s requirements. For example, association plans don’t have to include all 10 of the ACA’s “essential” health benefits, such as mental health care and prescription drug coverage.
Also, unlike ACA plans, association insurers can set premium rates based on an employer’s industry, as well as taking into account the age range and gender makeup of their workforce.
In other words, association plans can charge less for companies with workforces that are generally younger and male in occupations that involve mainly desk work than for firms with mostly older workers or companies doing riskier work, such as cutting down trees or roofing.
Still, such plans must abide by other ACA provisions, including accepting people with preexisting medical conditions.
Critics, including the states that sued, say the new rules and other administration-backed changes will weaken the market for ACA plans by drawing out younger and healthier people. The states also argued that the new rules would be costly for them to administer, alleging they would have to devote more resources to preventing consumer fraud.
In Michigan, Mr. Lyon said the association his group formed, called Transcend, offers coverage to small employers and sole proprietors that is just as generous as large-group plans. It is a fully insured plan through the state’s Blue Cross Blue Shield carrier that covers a broad array of benefits, except children’s dental and vision.
“One thing we don’t want to do is sell a bag of air to our members,” said Mr. Lyon.
While some new members have reported large savings by enrolling, Mr. Lyon said association plans are not necessarily less expensive than small-group coverage. It all depends on the demographic and occupational makeup of the small business, he said.
“Our best estimate was association health plans would be the right solution for 30%-35% of the small-group world,” said Mr. Lyon. “It all has to come together. Age matters. Gender matters. It’s so specific to each company.”
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
When the Trump administration in June 2018 issued rules making it easier for small employers to band together to buy health insurance, “we started looking immediately,” recalled Scott Lyon, a top executive at the Small Business Association of Michigan.
Although he offered traditional small-group health insurance to his association’s employees and members, Mr. Lyon liked adding a new option for both: potentially less expensive coverage through an association health plan, which doesn’t have to meet all the rules of the Affordable Care Act (ACA).
Now, a few months in, “we’ve got 400 companies and a couple of thousand workers signed up,” said Mr. Lyon.
Most of the new enrollees joined through groups like Mr. Lyon’s or local chambers of commerce, farm bureaus, or agriculture-based cooperatives. Such groups see the plans not only as a way to offer insurance, but also as an enticement to boost membership.
In the first legal test, however, U.S. District Judge John Bates at the end of March sided with 11 states and the District of Columbia challenging the law. He invalidated a large chunk of those June rules, saying the administration issued them as an “end-run around the Affordable Care Act.”
So what now?
Unless the government seeks – which it has yet to do – and is granted a stay of the judge’s order, “plans formed under the vacated sections of the rule are illegal,” said Timothy Jost, an emeritus health law professor from Washington and Lee University, Lexington, Va.
Still, that won’t mean anything for existing plans if the states or federal regulators choose not to enforce the ruling, Mr. Jost said.
And that could cause more confusion in the marketplace.
While the states that brought the challenge are expected to enforce the ruling, some other states support broader access to association health plans, said Christopher Condeluci, an attorney who represents several such plans, including the one formed by Mr. Lyon’s group.
“These plans are not an end run around the ACA,” said Mr. Condeluci.
Association health plans already established under the administration’s rules cover “virtually” all the federal law’s essential health benefits, he said, with the exception of dental and vision care for children.
Local chamber of commerce plans are mainly continuing business as usual while watching to see if the government will appeal, said Katie Mahoney, vice president of health policy at the U.S. Chamber of Commerce.
A few, including a plan offered through the Las Vegas chamber, may limit new enrollment for sole proprietors, she said, as the judge sharply questioned whether they qualified as “employers” under federal laws.
Sole proprietors are generally individuals who own and operate their own businesses without any employees.
Judge Bates wrote that, in the regulation, the Department of Labor “stretches the definition of employer” beyond what federal law allows. The rule was designed to increase access to plans that “avoid the most stringent requirements” of the ACA.
The opinion by Judge Bates, who was appointed by President George W. Bush, is widely expected to be appealed, although the government has not yet done so.
The decision affects one pillar of a broader effort by the Trump administration to expand access to less expensive health insurance. Association plans have long been a favorite of Republicans, existing before the ACA. Supporters say they are one way to pool groups of businesses together to get better premium rates.
Still, some plans faced problems in the past, including bankruptcy or complaints that they misled consumers by not fully informing them about what is covered.
After the ACA took effect, enrollment fell, partly because many small businesses were buying new ACA plans and many existing association plans had to comply with ACA rules for small-group coverage anyway. People who ran their own businesses and had no employees qualified only for coverage through the ACA’s individual market.
But the Trump administration in June broadened the definition of those eligible to buy insurance through employer-based associations to include sole proprietors and also made it easier to form associations to offer coverage.
In addition, the changes allowed more association plans to be classified as large-employer coverage, which exempts them from some of the ACA’s requirements. For example, association plans don’t have to include all 10 of the ACA’s “essential” health benefits, such as mental health care and prescription drug coverage.
Also, unlike ACA plans, association insurers can set premium rates based on an employer’s industry, as well as taking into account the age range and gender makeup of their workforce.
In other words, association plans can charge less for companies with workforces that are generally younger and male in occupations that involve mainly desk work than for firms with mostly older workers or companies doing riskier work, such as cutting down trees or roofing.
Still, such plans must abide by other ACA provisions, including accepting people with preexisting medical conditions.
Critics, including the states that sued, say the new rules and other administration-backed changes will weaken the market for ACA plans by drawing out younger and healthier people. The states also argued that the new rules would be costly for them to administer, alleging they would have to devote more resources to preventing consumer fraud.
In Michigan, Mr. Lyon said the association his group formed, called Transcend, offers coverage to small employers and sole proprietors that is just as generous as large-group plans. It is a fully insured plan through the state’s Blue Cross Blue Shield carrier that covers a broad array of benefits, except children’s dental and vision.
“One thing we don’t want to do is sell a bag of air to our members,” said Mr. Lyon.
While some new members have reported large savings by enrolling, Mr. Lyon said association plans are not necessarily less expensive than small-group coverage. It all depends on the demographic and occupational makeup of the small business, he said.
“Our best estimate was association health plans would be the right solution for 30%-35% of the small-group world,” said Mr. Lyon. “It all has to come together. Age matters. Gender matters. It’s so specific to each company.”
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.