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Triple therapy ups response in refractory mantle cell lymphoma
A combination of ibrutinib, lenalidomide, and rituximab produced an overall response rate of 76% at 17.8 months median follow-up among 50 adults with relapsed or refractory mantle cell lymphoma, according to an open-label, single-arm, phase 2 trial.
There were complete responses in 28 patients (56%) and partial responses in 10 (20%). Median progression-free survival was 16 months and median overall survival was 22 months. Similar proportions of patients, with and without TP53 mutations, had overall and complete responses, suggesting that triple therapy might be particularly useful in patients with high-risk genetic features.
“Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomized controlled trial,” wrote Mats Jerkeman, MD, of Lund University, Sweden, and colleagues. The report was published in The Lancet Haematology.
“Addition of lenalidomide to ibrutinib and rituximab might increase the proportion of patients who have complete remission ... Previous studies reported complete responses in 44% of patients on ibrutinib and rituximab, in 36% of patients on rituximab and lenalidomide, and in 19% of patients on ibrutinib alone,” they wrote.
Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only, given until disease progression or unacceptable toxicity. All the patients had previously been treated with at least one rituximab-containing regimen.
Janssen and Celgene funded the work. Dr. Jerkeman reported ties to Janssen and Celgene, as well as AbbVie and Gilead.
SOURCE: Jerkeman M et al. Lancet Haematol. 2018 Jan 29. doi: 10.1016/S2352-3026(18)30018-8.
A combination of ibrutinib, lenalidomide, and rituximab produced an overall response rate of 76% at 17.8 months median follow-up among 50 adults with relapsed or refractory mantle cell lymphoma, according to an open-label, single-arm, phase 2 trial.
There were complete responses in 28 patients (56%) and partial responses in 10 (20%). Median progression-free survival was 16 months and median overall survival was 22 months. Similar proportions of patients, with and without TP53 mutations, had overall and complete responses, suggesting that triple therapy might be particularly useful in patients with high-risk genetic features.
“Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomized controlled trial,” wrote Mats Jerkeman, MD, of Lund University, Sweden, and colleagues. The report was published in The Lancet Haematology.
“Addition of lenalidomide to ibrutinib and rituximab might increase the proportion of patients who have complete remission ... Previous studies reported complete responses in 44% of patients on ibrutinib and rituximab, in 36% of patients on rituximab and lenalidomide, and in 19% of patients on ibrutinib alone,” they wrote.
Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only, given until disease progression or unacceptable toxicity. All the patients had previously been treated with at least one rituximab-containing regimen.
Janssen and Celgene funded the work. Dr. Jerkeman reported ties to Janssen and Celgene, as well as AbbVie and Gilead.
SOURCE: Jerkeman M et al. Lancet Haematol. 2018 Jan 29. doi: 10.1016/S2352-3026(18)30018-8.
A combination of ibrutinib, lenalidomide, and rituximab produced an overall response rate of 76% at 17.8 months median follow-up among 50 adults with relapsed or refractory mantle cell lymphoma, according to an open-label, single-arm, phase 2 trial.
There were complete responses in 28 patients (56%) and partial responses in 10 (20%). Median progression-free survival was 16 months and median overall survival was 22 months. Similar proportions of patients, with and without TP53 mutations, had overall and complete responses, suggesting that triple therapy might be particularly useful in patients with high-risk genetic features.
“Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomized controlled trial,” wrote Mats Jerkeman, MD, of Lund University, Sweden, and colleagues. The report was published in The Lancet Haematology.
“Addition of lenalidomide to ibrutinib and rituximab might increase the proportion of patients who have complete remission ... Previous studies reported complete responses in 44% of patients on ibrutinib and rituximab, in 36% of patients on rituximab and lenalidomide, and in 19% of patients on ibrutinib alone,” they wrote.
Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only, given until disease progression or unacceptable toxicity. All the patients had previously been treated with at least one rituximab-containing regimen.
Janssen and Celgene funded the work. Dr. Jerkeman reported ties to Janssen and Celgene, as well as AbbVie and Gilead.
SOURCE: Jerkeman M et al. Lancet Haematol. 2018 Jan 29. doi: 10.1016/S2352-3026(18)30018-8.
FROM THE LANCET HAEMATOLOGY
Key clinical point:
Major finding: The overall response from for the combination of the three drugs was 76% at 17.8 months median follow-up.
Study details: An open-label, single-arm, phase 2 trial of 50 adults with relapsed/refractory MCL.
Disclosures: Janssen and Celgene funded the work. Dr. Jerkeman reported ties to Janssen and Celgene, as well as AbbVie and Gilead.
Source: Jerkeman M et al. Lancet Haematol. 2018 Jan 29. doi: 10.1016/S2352-3026(18)30018-8.
MedPAC mulls boost to payments for E&M visits
WASHINGTON – Members of the Medicare Payment Advisory Commission, which advises Congress, are weighing whether to recommend a 10% increase in payments for evaluation and management services.
The boost would be offset by a 4.5% decrease in all other payments on the Medicare physician fee schedule.
“The fee schedule underprices ambulatory [evaluation and management] services relative to other services,” MedPAC staff member Ariel Winter said during a Jan. 12 presentation of a draft proposal.
Payments in the physician fee schedule are based on the relative amount of time and intensity required for each service, she noted. “E&M services are labor intensive,” she said. “A clinician takes the patient’s history, examines the patient, engages in medical decision-making and so forth. These activities do not lend themselves to reductions in the time it takes to provide the visit.”
In contrast, “the time needed for other services, such as procedures, often declines over time due to productivity gains in clinical practice and technology,” Ms. Winter continued. “Ideally, the prices for these services would also be reduced to reflect these efficiency gains.”
Ms. Winter pointed out that the payment reduction that captures the efficiency gains rarely happens, and because of budget neutral requirements, it means that “payment rates for ambulatory E&M services are too low relative to other services.”
MedPAC looked at the fee schedule time estimates across four specialties (cardiology, family medicine, orthopedics, and urology) and found that across the board, the fee schedule assumed it took the specialist more time than what was actually needed.
“However, the discrepancy was much greater for the practices that focus on procedures, which suggests that the services they provide may be based on inflated time estimates,” Ms. Winter said. “For example, the hours assumed in the fee schedule were 24% higher than actual hours worked for family medicine, but 64% higher in cardiology and 92% higher in orthopedics.”
To account for this, and psychiatric services, regardless of specialty, resulting in an increase of $2.7 billion in spending on these codes. That would force a reduction of 4.5% in payments for everything else in the fee schedule under budget neutrality requirements.
Based on this change, licensed clinical social workers would see the full 10% increase to their physician fee schedule payments and clinical psychologists would see an 8% increase, based on 2016 Medicare claims. Endocrinology would see a 6.5% increase, family practice a 5.7% increase, and rheumatology a 5.4% increase.
Of the specialties displayed on a presentation slide that showed an increase, internal medicine fared the worst, with a 2% increase. “That is because this specialty performs a lot of services other than ambulatory E&M” and the 4.5% reduction in those other services would have an offsetting effect, Ms. Winter said.
Ms. Winter noted that a number of specialties would see a reduction in their physician fee schedule payments greater than 4% “because they provide very few E&M or psychiatric services, and these include radiology, pathology, physical therapy, and occupational therapy.”
Another option presented to the MedPAC commissioners was offering a special incentive payment equal to a 10% increase to clinicians who bill 60% of their claims for E&M services. That idea, which is similar to the now-expired primary care incentive payment program, would require a 1.7% reduction in other services to maintain budget neutrality.
But MedPAC commissioners questioned the overall aim of this type of payment rebalancing.
“Are we hoping that enhancing payments for primary care will actually improve coordination of care and management of patients?” asked Commissioner Kathy Buto, former vice president of global health policy at Johnson & Johnson. “I don’t think either of these options really does that. So that leads me to ask the question, ‘should we be thinking more about that issue?’”
Commissioner David Nerenz, PhD, director of the Center for Health Policy and Health Services Research at the Henry Ford Health System in Detroit, pointed out that a 10% uptick is not going to solve the problem of payment disparities. “And that doesn’t mean it should not be done. It just means that other things have to be considered and addressed at the same time if ultimately we are talking about people’s choice, for example, to go under primary care.”
Dr. Nerenz also noted that providers such as physical therapists and occupational therapists have to spend their time in face-to-face settings in the same way E&M visits are structured, but because it is billed as a procedure, they would get penalized under the draft proposal.
“I have the same concern about a procedure like colonoscopy,” he added. “You know, for the appropriate people, it’s a lifesaving procedure. Should that payment go down 4.5%? I don’t know.”
Commissioner Rita Redberg, MD, of the University of California San Francisco, suggested that some of these issues would go away on their own as physicians move into advanced alternative payment models in the Quality Payment Program, something MedPAC hopes will happen if their repeal and replacement of the Merit-based Incentive Payment System portion of the Quality Payment Program is adopted.
Commissioner Dana Gelb Safran, ScD, of Blue Cross Blue Shield of Massachusetts, looked at payment adequacy from three perspectives: better equity, better access, and better alignment with value. “I guess on all three counts, I am finding both of these approaches coming up short,” Dr. Safran said. “It maybe helps the most with equity, but then there’s the challenge about how payment actually gets shaped by the organizations providers are a part of,” she said, referring to whether employed physicians would see any benefit trickle down to them in the form of increased salary and benefits. “So I struggle with whether it even accomplished that, but maybe it’s not a bad idea for that.”
MedPAC is in the early stages of developing a recommendation on this subject and more discussions are expected at upcoming meetings. The next scheduled meeting is in March 2018.
WASHINGTON – Members of the Medicare Payment Advisory Commission, which advises Congress, are weighing whether to recommend a 10% increase in payments for evaluation and management services.
The boost would be offset by a 4.5% decrease in all other payments on the Medicare physician fee schedule.
“The fee schedule underprices ambulatory [evaluation and management] services relative to other services,” MedPAC staff member Ariel Winter said during a Jan. 12 presentation of a draft proposal.
Payments in the physician fee schedule are based on the relative amount of time and intensity required for each service, she noted. “E&M services are labor intensive,” she said. “A clinician takes the patient’s history, examines the patient, engages in medical decision-making and so forth. These activities do not lend themselves to reductions in the time it takes to provide the visit.”
In contrast, “the time needed for other services, such as procedures, often declines over time due to productivity gains in clinical practice and technology,” Ms. Winter continued. “Ideally, the prices for these services would also be reduced to reflect these efficiency gains.”
Ms. Winter pointed out that the payment reduction that captures the efficiency gains rarely happens, and because of budget neutral requirements, it means that “payment rates for ambulatory E&M services are too low relative to other services.”
MedPAC looked at the fee schedule time estimates across four specialties (cardiology, family medicine, orthopedics, and urology) and found that across the board, the fee schedule assumed it took the specialist more time than what was actually needed.
“However, the discrepancy was much greater for the practices that focus on procedures, which suggests that the services they provide may be based on inflated time estimates,” Ms. Winter said. “For example, the hours assumed in the fee schedule were 24% higher than actual hours worked for family medicine, but 64% higher in cardiology and 92% higher in orthopedics.”
To account for this, and psychiatric services, regardless of specialty, resulting in an increase of $2.7 billion in spending on these codes. That would force a reduction of 4.5% in payments for everything else in the fee schedule under budget neutrality requirements.
Based on this change, licensed clinical social workers would see the full 10% increase to their physician fee schedule payments and clinical psychologists would see an 8% increase, based on 2016 Medicare claims. Endocrinology would see a 6.5% increase, family practice a 5.7% increase, and rheumatology a 5.4% increase.
Of the specialties displayed on a presentation slide that showed an increase, internal medicine fared the worst, with a 2% increase. “That is because this specialty performs a lot of services other than ambulatory E&M” and the 4.5% reduction in those other services would have an offsetting effect, Ms. Winter said.
Ms. Winter noted that a number of specialties would see a reduction in their physician fee schedule payments greater than 4% “because they provide very few E&M or psychiatric services, and these include radiology, pathology, physical therapy, and occupational therapy.”
Another option presented to the MedPAC commissioners was offering a special incentive payment equal to a 10% increase to clinicians who bill 60% of their claims for E&M services. That idea, which is similar to the now-expired primary care incentive payment program, would require a 1.7% reduction in other services to maintain budget neutrality.
But MedPAC commissioners questioned the overall aim of this type of payment rebalancing.
“Are we hoping that enhancing payments for primary care will actually improve coordination of care and management of patients?” asked Commissioner Kathy Buto, former vice president of global health policy at Johnson & Johnson. “I don’t think either of these options really does that. So that leads me to ask the question, ‘should we be thinking more about that issue?’”
Commissioner David Nerenz, PhD, director of the Center for Health Policy and Health Services Research at the Henry Ford Health System in Detroit, pointed out that a 10% uptick is not going to solve the problem of payment disparities. “And that doesn’t mean it should not be done. It just means that other things have to be considered and addressed at the same time if ultimately we are talking about people’s choice, for example, to go under primary care.”
Dr. Nerenz also noted that providers such as physical therapists and occupational therapists have to spend their time in face-to-face settings in the same way E&M visits are structured, but because it is billed as a procedure, they would get penalized under the draft proposal.
“I have the same concern about a procedure like colonoscopy,” he added. “You know, for the appropriate people, it’s a lifesaving procedure. Should that payment go down 4.5%? I don’t know.”
Commissioner Rita Redberg, MD, of the University of California San Francisco, suggested that some of these issues would go away on their own as physicians move into advanced alternative payment models in the Quality Payment Program, something MedPAC hopes will happen if their repeal and replacement of the Merit-based Incentive Payment System portion of the Quality Payment Program is adopted.
Commissioner Dana Gelb Safran, ScD, of Blue Cross Blue Shield of Massachusetts, looked at payment adequacy from three perspectives: better equity, better access, and better alignment with value. “I guess on all three counts, I am finding both of these approaches coming up short,” Dr. Safran said. “It maybe helps the most with equity, but then there’s the challenge about how payment actually gets shaped by the organizations providers are a part of,” she said, referring to whether employed physicians would see any benefit trickle down to them in the form of increased salary and benefits. “So I struggle with whether it even accomplished that, but maybe it’s not a bad idea for that.”
MedPAC is in the early stages of developing a recommendation on this subject and more discussions are expected at upcoming meetings. The next scheduled meeting is in March 2018.
WASHINGTON – Members of the Medicare Payment Advisory Commission, which advises Congress, are weighing whether to recommend a 10% increase in payments for evaluation and management services.
The boost would be offset by a 4.5% decrease in all other payments on the Medicare physician fee schedule.
“The fee schedule underprices ambulatory [evaluation and management] services relative to other services,” MedPAC staff member Ariel Winter said during a Jan. 12 presentation of a draft proposal.
Payments in the physician fee schedule are based on the relative amount of time and intensity required for each service, she noted. “E&M services are labor intensive,” she said. “A clinician takes the patient’s history, examines the patient, engages in medical decision-making and so forth. These activities do not lend themselves to reductions in the time it takes to provide the visit.”
In contrast, “the time needed for other services, such as procedures, often declines over time due to productivity gains in clinical practice and technology,” Ms. Winter continued. “Ideally, the prices for these services would also be reduced to reflect these efficiency gains.”
Ms. Winter pointed out that the payment reduction that captures the efficiency gains rarely happens, and because of budget neutral requirements, it means that “payment rates for ambulatory E&M services are too low relative to other services.”
MedPAC looked at the fee schedule time estimates across four specialties (cardiology, family medicine, orthopedics, and urology) and found that across the board, the fee schedule assumed it took the specialist more time than what was actually needed.
“However, the discrepancy was much greater for the practices that focus on procedures, which suggests that the services they provide may be based on inflated time estimates,” Ms. Winter said. “For example, the hours assumed in the fee schedule were 24% higher than actual hours worked for family medicine, but 64% higher in cardiology and 92% higher in orthopedics.”
To account for this, and psychiatric services, regardless of specialty, resulting in an increase of $2.7 billion in spending on these codes. That would force a reduction of 4.5% in payments for everything else in the fee schedule under budget neutrality requirements.
Based on this change, licensed clinical social workers would see the full 10% increase to their physician fee schedule payments and clinical psychologists would see an 8% increase, based on 2016 Medicare claims. Endocrinology would see a 6.5% increase, family practice a 5.7% increase, and rheumatology a 5.4% increase.
Of the specialties displayed on a presentation slide that showed an increase, internal medicine fared the worst, with a 2% increase. “That is because this specialty performs a lot of services other than ambulatory E&M” and the 4.5% reduction in those other services would have an offsetting effect, Ms. Winter said.
Ms. Winter noted that a number of specialties would see a reduction in their physician fee schedule payments greater than 4% “because they provide very few E&M or psychiatric services, and these include radiology, pathology, physical therapy, and occupational therapy.”
Another option presented to the MedPAC commissioners was offering a special incentive payment equal to a 10% increase to clinicians who bill 60% of their claims for E&M services. That idea, which is similar to the now-expired primary care incentive payment program, would require a 1.7% reduction in other services to maintain budget neutrality.
But MedPAC commissioners questioned the overall aim of this type of payment rebalancing.
“Are we hoping that enhancing payments for primary care will actually improve coordination of care and management of patients?” asked Commissioner Kathy Buto, former vice president of global health policy at Johnson & Johnson. “I don’t think either of these options really does that. So that leads me to ask the question, ‘should we be thinking more about that issue?’”
Commissioner David Nerenz, PhD, director of the Center for Health Policy and Health Services Research at the Henry Ford Health System in Detroit, pointed out that a 10% uptick is not going to solve the problem of payment disparities. “And that doesn’t mean it should not be done. It just means that other things have to be considered and addressed at the same time if ultimately we are talking about people’s choice, for example, to go under primary care.”
Dr. Nerenz also noted that providers such as physical therapists and occupational therapists have to spend their time in face-to-face settings in the same way E&M visits are structured, but because it is billed as a procedure, they would get penalized under the draft proposal.
“I have the same concern about a procedure like colonoscopy,” he added. “You know, for the appropriate people, it’s a lifesaving procedure. Should that payment go down 4.5%? I don’t know.”
Commissioner Rita Redberg, MD, of the University of California San Francisco, suggested that some of these issues would go away on their own as physicians move into advanced alternative payment models in the Quality Payment Program, something MedPAC hopes will happen if their repeal and replacement of the Merit-based Incentive Payment System portion of the Quality Payment Program is adopted.
Commissioner Dana Gelb Safran, ScD, of Blue Cross Blue Shield of Massachusetts, looked at payment adequacy from three perspectives: better equity, better access, and better alignment with value. “I guess on all three counts, I am finding both of these approaches coming up short,” Dr. Safran said. “It maybe helps the most with equity, but then there’s the challenge about how payment actually gets shaped by the organizations providers are a part of,” she said, referring to whether employed physicians would see any benefit trickle down to them in the form of increased salary and benefits. “So I struggle with whether it even accomplished that, but maybe it’s not a bad idea for that.”
MedPAC is in the early stages of developing a recommendation on this subject and more discussions are expected at upcoming meetings. The next scheduled meeting is in March 2018.
REPORTING FROM A MEDPAC MEETING
Latest PANS trials suggest cause may be treatable
NEW YORK – New controlled trials in the treatment of pediatric acute neuropsychiatric syndrome (PANS) support the hypothesis that the cause may, in fact, be treatable, an expert said at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
PANS and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are controversial diagnoses. But ongoing research has expanded the body of literature describing symptoms and evaluating treatments, according to an overview from Barbara J. Coffey, MD, division chief in child and adolescent psychiatry at the University of Miami.
PANS and PANDAS, which are clinical diagnoses of exclusion, are characterized by an abrupt onset of one or more neuropsychiatric symptoms in children that can include signs of obsessive-compulsive disorder (OCD), tics, anxiety, irritability, and behavioral changes. Despite more than 15 years of clinical and experimental studies, almost all aspects of PANS and PANDAS remain controversial, Dr. Coffey said.
“Many pediatricians I work with do not want to see these kids, because they really do not know what to do,” she reported.
This prevailing conception has led to treatment trials with antibiotics for the underlying infection and, most recently, with intravenous immunoglobulins (IVIG) to prevent cross-reactive antibodies induced by infection. Dr. Coffey, reviewing several recently published studies, noted that there have been signals of activity suggesting “there may be something there.” However, she cautioned that the data are inconclusive.
Of recent studies, a trial with azithromycin in children with PANS generated somewhat positive findings (J Child Adolesc Psychopharmacol. 2017;27[7]:640-51). In this study, 31 children aged 4-14 years were randomized to receive azithromycin or placebo for 4 weeks. They were evaluated via the Children’s Yale–Brown Obsessive Compulsive Scale (CY-BOCS) and the OCD Clinical Global Impression Severity (CGI-S OCD) scale.
The study associated azithromycin with a significant reduction in symptoms as measured with CGI-S OCD (41.2% vs. 7.1%; P = .045), but no difference was found in response as measured with the CY-BOCS, which Dr. Coffey described as the more conservative measure. Even when measured with the CGI-S OCD scale, symptom improvements were modest. But the authors concluded that azithromycin “may be helpful” for the control of neuropsychiatric symptoms.
In a trial with IVIG, 35 children with PANDAS were randomized to IVIG or placebo (J Am Acad Child Adolesc Psychiatry. 2016;55[10]:860-7). The primary outcome was at least a 30% reduction in CY-BOCS at 12 weeks. Nonresponders at 12 weeks were permitted 12 more weeks of treatment with open-label IVIG.
Twice as many patients receiving IVIG, compared with those on placebo, reached the primary outcome (24% vs. 12%), but the study was small and the difference did not reach significance. However, the authors reported that the mean CY-BOCS improvement from baseline on IVIG, which was well tolerated, was 55% at week 12 and 62% at week 24. The authors suggested that larger trials are warranted.
“One critique of this study is that all of the patients were placed on prophylactic antibiotics, which may have attenuated the response,” Dr. Coffey said. In outlining these results, she emphasized: “This is not something I am recommending. I just want to acquaint you with what is going on out there.”
None of the most recent trials provide conclusive support for therapy targeted at infection or an autoimmune process in PANS or PANDAS, but Dr. Coffey indicated that . One of the most recent sets of data come from a recently published Scandinavian cohort study with 17 years of follow-up (JAMA Psychiatry. 2017;74[7]:740-6). That study associated pediatric infections of any kind, not just streptococcal infections, with an elevated risk of mental disorders – particularly OCD and tics.
Overall, the evidence base is growing to suggest “antibiotics and immune therapy may be beneficial, but the jury is not in yet for which patients, how much, and how long,” Dr. Coffey said. She is aware of clinicians who are now using antibiotics empirically to control neuropsychiatric symptoms in PANDAS but cautioned that more investigation is needed.
Dr. Coffey reports financial relationships with Genco Sciences, Neurocrine Biosciences, Shire, and Teva/Nuvelution.
NEW YORK – New controlled trials in the treatment of pediatric acute neuropsychiatric syndrome (PANS) support the hypothesis that the cause may, in fact, be treatable, an expert said at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
PANS and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are controversial diagnoses. But ongoing research has expanded the body of literature describing symptoms and evaluating treatments, according to an overview from Barbara J. Coffey, MD, division chief in child and adolescent psychiatry at the University of Miami.
PANS and PANDAS, which are clinical diagnoses of exclusion, are characterized by an abrupt onset of one or more neuropsychiatric symptoms in children that can include signs of obsessive-compulsive disorder (OCD), tics, anxiety, irritability, and behavioral changes. Despite more than 15 years of clinical and experimental studies, almost all aspects of PANS and PANDAS remain controversial, Dr. Coffey said.
“Many pediatricians I work with do not want to see these kids, because they really do not know what to do,” she reported.
This prevailing conception has led to treatment trials with antibiotics for the underlying infection and, most recently, with intravenous immunoglobulins (IVIG) to prevent cross-reactive antibodies induced by infection. Dr. Coffey, reviewing several recently published studies, noted that there have been signals of activity suggesting “there may be something there.” However, she cautioned that the data are inconclusive.
Of recent studies, a trial with azithromycin in children with PANS generated somewhat positive findings (J Child Adolesc Psychopharmacol. 2017;27[7]:640-51). In this study, 31 children aged 4-14 years were randomized to receive azithromycin or placebo for 4 weeks. They were evaluated via the Children’s Yale–Brown Obsessive Compulsive Scale (CY-BOCS) and the OCD Clinical Global Impression Severity (CGI-S OCD) scale.
The study associated azithromycin with a significant reduction in symptoms as measured with CGI-S OCD (41.2% vs. 7.1%; P = .045), but no difference was found in response as measured with the CY-BOCS, which Dr. Coffey described as the more conservative measure. Even when measured with the CGI-S OCD scale, symptom improvements were modest. But the authors concluded that azithromycin “may be helpful” for the control of neuropsychiatric symptoms.
In a trial with IVIG, 35 children with PANDAS were randomized to IVIG or placebo (J Am Acad Child Adolesc Psychiatry. 2016;55[10]:860-7). The primary outcome was at least a 30% reduction in CY-BOCS at 12 weeks. Nonresponders at 12 weeks were permitted 12 more weeks of treatment with open-label IVIG.
Twice as many patients receiving IVIG, compared with those on placebo, reached the primary outcome (24% vs. 12%), but the study was small and the difference did not reach significance. However, the authors reported that the mean CY-BOCS improvement from baseline on IVIG, which was well tolerated, was 55% at week 12 and 62% at week 24. The authors suggested that larger trials are warranted.
“One critique of this study is that all of the patients were placed on prophylactic antibiotics, which may have attenuated the response,” Dr. Coffey said. In outlining these results, she emphasized: “This is not something I am recommending. I just want to acquaint you with what is going on out there.”
None of the most recent trials provide conclusive support for therapy targeted at infection or an autoimmune process in PANS or PANDAS, but Dr. Coffey indicated that . One of the most recent sets of data come from a recently published Scandinavian cohort study with 17 years of follow-up (JAMA Psychiatry. 2017;74[7]:740-6). That study associated pediatric infections of any kind, not just streptococcal infections, with an elevated risk of mental disorders – particularly OCD and tics.
Overall, the evidence base is growing to suggest “antibiotics and immune therapy may be beneficial, but the jury is not in yet for which patients, how much, and how long,” Dr. Coffey said. She is aware of clinicians who are now using antibiotics empirically to control neuropsychiatric symptoms in PANDAS but cautioned that more investigation is needed.
Dr. Coffey reports financial relationships with Genco Sciences, Neurocrine Biosciences, Shire, and Teva/Nuvelution.
NEW YORK – New controlled trials in the treatment of pediatric acute neuropsychiatric syndrome (PANS) support the hypothesis that the cause may, in fact, be treatable, an expert said at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
PANS and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are controversial diagnoses. But ongoing research has expanded the body of literature describing symptoms and evaluating treatments, according to an overview from Barbara J. Coffey, MD, division chief in child and adolescent psychiatry at the University of Miami.
PANS and PANDAS, which are clinical diagnoses of exclusion, are characterized by an abrupt onset of one or more neuropsychiatric symptoms in children that can include signs of obsessive-compulsive disorder (OCD), tics, anxiety, irritability, and behavioral changes. Despite more than 15 years of clinical and experimental studies, almost all aspects of PANS and PANDAS remain controversial, Dr. Coffey said.
“Many pediatricians I work with do not want to see these kids, because they really do not know what to do,” she reported.
This prevailing conception has led to treatment trials with antibiotics for the underlying infection and, most recently, with intravenous immunoglobulins (IVIG) to prevent cross-reactive antibodies induced by infection. Dr. Coffey, reviewing several recently published studies, noted that there have been signals of activity suggesting “there may be something there.” However, she cautioned that the data are inconclusive.
Of recent studies, a trial with azithromycin in children with PANS generated somewhat positive findings (J Child Adolesc Psychopharmacol. 2017;27[7]:640-51). In this study, 31 children aged 4-14 years were randomized to receive azithromycin or placebo for 4 weeks. They were evaluated via the Children’s Yale–Brown Obsessive Compulsive Scale (CY-BOCS) and the OCD Clinical Global Impression Severity (CGI-S OCD) scale.
The study associated azithromycin with a significant reduction in symptoms as measured with CGI-S OCD (41.2% vs. 7.1%; P = .045), but no difference was found in response as measured with the CY-BOCS, which Dr. Coffey described as the more conservative measure. Even when measured with the CGI-S OCD scale, symptom improvements were modest. But the authors concluded that azithromycin “may be helpful” for the control of neuropsychiatric symptoms.
In a trial with IVIG, 35 children with PANDAS were randomized to IVIG or placebo (J Am Acad Child Adolesc Psychiatry. 2016;55[10]:860-7). The primary outcome was at least a 30% reduction in CY-BOCS at 12 weeks. Nonresponders at 12 weeks were permitted 12 more weeks of treatment with open-label IVIG.
Twice as many patients receiving IVIG, compared with those on placebo, reached the primary outcome (24% vs. 12%), but the study was small and the difference did not reach significance. However, the authors reported that the mean CY-BOCS improvement from baseline on IVIG, which was well tolerated, was 55% at week 12 and 62% at week 24. The authors suggested that larger trials are warranted.
“One critique of this study is that all of the patients were placed on prophylactic antibiotics, which may have attenuated the response,” Dr. Coffey said. In outlining these results, she emphasized: “This is not something I am recommending. I just want to acquaint you with what is going on out there.”
None of the most recent trials provide conclusive support for therapy targeted at infection or an autoimmune process in PANS or PANDAS, but Dr. Coffey indicated that . One of the most recent sets of data come from a recently published Scandinavian cohort study with 17 years of follow-up (JAMA Psychiatry. 2017;74[7]:740-6). That study associated pediatric infections of any kind, not just streptococcal infections, with an elevated risk of mental disorders – particularly OCD and tics.
Overall, the evidence base is growing to suggest “antibiotics and immune therapy may be beneficial, but the jury is not in yet for which patients, how much, and how long,” Dr. Coffey said. She is aware of clinicians who are now using antibiotics empirically to control neuropsychiatric symptoms in PANDAS but cautioned that more investigation is needed.
Dr. Coffey reports financial relationships with Genco Sciences, Neurocrine Biosciences, Shire, and Teva/Nuvelution.
REPORTING FROM THE PSYCHOPHARMACOLOGY UPDATE INSTITUTE
Insights revealed into rheumatologist-patient discussions about biologics
A small study of the discussions of biologic treatment options between rheumatoid arthritis patients and their rheumatologists suggests they are limited in scope and may be influenced by clinicians’ preconceived notions about patient preferences.
In an analysis of video footage from office visits of 48 rheumatoid arthritis (RA) patients initiating biologics with 16 rheumatologists, only 5.6 minutes out of visits with an average duration of 15 minutes were spent discussing biologic therapy options. Postvisit interviews with patients highlighted problems in rheumatologists’ awareness of patients’ familiarity with biologic treatment options, particularly a lack of knowledge about intravenous (IV) options, according to findings from the ethnographic, observational study conducted by Nicholas Kottak, PhD, of Ethnographic Solutions LLC, and his colleagues and published in Arthritis Care & Research.
Of the 48 visits, the researchers found that subcutaneous (SC) therapy options were discussed in 45 visits and IV options were discussed in 35. In 27 of the 35 visits in which IV options were mentioned, the rheumatologists did not define or describe IV administration.
In postvisit interviews, all patients said they were previously aware that biologic therapy was available subcutaneously, but 22 entered their visit with no previous knowledge of IV options, 19 of whom remained unfamiliar after their visit.
According to the researchers, some patients said that they would prefer to receive IV biologic treatment and some would prefer SC delivery. However, all 16 participating rheumatologists thought that IV therapy would be less convenient for the patient than SC therapy, but only 22 of 48 patients said inconvenience was the main barrier to IV therapy. A total of 23 patients thought SC therapy would be easier, 17 thought IV therapy would be easier, 4 thought they would be the same, and 4 were unsure.
The way in which mode of biologic administration is discussed may also have financial implications, particularly for Medicare patients. “During 26 visits with Medicare patients, IV and SC therapies were mentioned during 22 and 23 visits, respectively. This is noteworthy as Medicare with supplemental insurance may preferably cover IV over SC therapy, since IV therapy qualifies as a medical benefit (Part B) and SC therapy falls under pharmacy benefits (Part D),” Dr. Kottak and his associates wrote.
• Preparing patients for biologic therapy at an earlier disease stage.
• Providing educational tools such as pamphlets and flyers.
• Increasing time spent with the patient and/or including nurse practitioners and physician assistants in the follow-up portion of the patient visit.
• Creating a treatment alliance with a patient to make the process more collaborative.
• Allowing patients to choose which biologic medication they start with while emphasizing the potential for positive outcomes and relative safety.
• Researching shared decision making between patients and physicians in a randomized, outcomes-based setting.
Janssen provided funding for the study as well as the writing of the report. Ethnographic Solutions received financial compensation from Janssen. Three of the six authors are employees of Janssen. The other researchers reported various financial disclosures, including, but not limited to, stock ownership, speaking fees, and advisory board positions.
SOURCE: Kottak N et al. Arthritis Care Res. 2018 Feb 5. doi: 10/1002/acr.23527
A small study of the discussions of biologic treatment options between rheumatoid arthritis patients and their rheumatologists suggests they are limited in scope and may be influenced by clinicians’ preconceived notions about patient preferences.
In an analysis of video footage from office visits of 48 rheumatoid arthritis (RA) patients initiating biologics with 16 rheumatologists, only 5.6 minutes out of visits with an average duration of 15 minutes were spent discussing biologic therapy options. Postvisit interviews with patients highlighted problems in rheumatologists’ awareness of patients’ familiarity with biologic treatment options, particularly a lack of knowledge about intravenous (IV) options, according to findings from the ethnographic, observational study conducted by Nicholas Kottak, PhD, of Ethnographic Solutions LLC, and his colleagues and published in Arthritis Care & Research.
Of the 48 visits, the researchers found that subcutaneous (SC) therapy options were discussed in 45 visits and IV options were discussed in 35. In 27 of the 35 visits in which IV options were mentioned, the rheumatologists did not define or describe IV administration.
In postvisit interviews, all patients said they were previously aware that biologic therapy was available subcutaneously, but 22 entered their visit with no previous knowledge of IV options, 19 of whom remained unfamiliar after their visit.
According to the researchers, some patients said that they would prefer to receive IV biologic treatment and some would prefer SC delivery. However, all 16 participating rheumatologists thought that IV therapy would be less convenient for the patient than SC therapy, but only 22 of 48 patients said inconvenience was the main barrier to IV therapy. A total of 23 patients thought SC therapy would be easier, 17 thought IV therapy would be easier, 4 thought they would be the same, and 4 were unsure.
The way in which mode of biologic administration is discussed may also have financial implications, particularly for Medicare patients. “During 26 visits with Medicare patients, IV and SC therapies were mentioned during 22 and 23 visits, respectively. This is noteworthy as Medicare with supplemental insurance may preferably cover IV over SC therapy, since IV therapy qualifies as a medical benefit (Part B) and SC therapy falls under pharmacy benefits (Part D),” Dr. Kottak and his associates wrote.
• Preparing patients for biologic therapy at an earlier disease stage.
• Providing educational tools such as pamphlets and flyers.
• Increasing time spent with the patient and/or including nurse practitioners and physician assistants in the follow-up portion of the patient visit.
• Creating a treatment alliance with a patient to make the process more collaborative.
• Allowing patients to choose which biologic medication they start with while emphasizing the potential for positive outcomes and relative safety.
• Researching shared decision making between patients and physicians in a randomized, outcomes-based setting.
Janssen provided funding for the study as well as the writing of the report. Ethnographic Solutions received financial compensation from Janssen. Three of the six authors are employees of Janssen. The other researchers reported various financial disclosures, including, but not limited to, stock ownership, speaking fees, and advisory board positions.
SOURCE: Kottak N et al. Arthritis Care Res. 2018 Feb 5. doi: 10/1002/acr.23527
A small study of the discussions of biologic treatment options between rheumatoid arthritis patients and their rheumatologists suggests they are limited in scope and may be influenced by clinicians’ preconceived notions about patient preferences.
In an analysis of video footage from office visits of 48 rheumatoid arthritis (RA) patients initiating biologics with 16 rheumatologists, only 5.6 minutes out of visits with an average duration of 15 minutes were spent discussing biologic therapy options. Postvisit interviews with patients highlighted problems in rheumatologists’ awareness of patients’ familiarity with biologic treatment options, particularly a lack of knowledge about intravenous (IV) options, according to findings from the ethnographic, observational study conducted by Nicholas Kottak, PhD, of Ethnographic Solutions LLC, and his colleagues and published in Arthritis Care & Research.
Of the 48 visits, the researchers found that subcutaneous (SC) therapy options were discussed in 45 visits and IV options were discussed in 35. In 27 of the 35 visits in which IV options were mentioned, the rheumatologists did not define or describe IV administration.
In postvisit interviews, all patients said they were previously aware that biologic therapy was available subcutaneously, but 22 entered their visit with no previous knowledge of IV options, 19 of whom remained unfamiliar after their visit.
According to the researchers, some patients said that they would prefer to receive IV biologic treatment and some would prefer SC delivery. However, all 16 participating rheumatologists thought that IV therapy would be less convenient for the patient than SC therapy, but only 22 of 48 patients said inconvenience was the main barrier to IV therapy. A total of 23 patients thought SC therapy would be easier, 17 thought IV therapy would be easier, 4 thought they would be the same, and 4 were unsure.
The way in which mode of biologic administration is discussed may also have financial implications, particularly for Medicare patients. “During 26 visits with Medicare patients, IV and SC therapies were mentioned during 22 and 23 visits, respectively. This is noteworthy as Medicare with supplemental insurance may preferably cover IV over SC therapy, since IV therapy qualifies as a medical benefit (Part B) and SC therapy falls under pharmacy benefits (Part D),” Dr. Kottak and his associates wrote.
• Preparing patients for biologic therapy at an earlier disease stage.
• Providing educational tools such as pamphlets and flyers.
• Increasing time spent with the patient and/or including nurse practitioners and physician assistants in the follow-up portion of the patient visit.
• Creating a treatment alliance with a patient to make the process more collaborative.
• Allowing patients to choose which biologic medication they start with while emphasizing the potential for positive outcomes and relative safety.
• Researching shared decision making between patients and physicians in a randomized, outcomes-based setting.
Janssen provided funding for the study as well as the writing of the report. Ethnographic Solutions received financial compensation from Janssen. Three of the six authors are employees of Janssen. The other researchers reported various financial disclosures, including, but not limited to, stock ownership, speaking fees, and advisory board positions.
SOURCE: Kottak N et al. Arthritis Care Res. 2018 Feb 5. doi: 10/1002/acr.23527
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Provide educational resources about biologics and don’t assume that subcutaneous therapy is more convenient or that patients understand IV therapy terminology and procedures.
Major finding: All 16 participating rheumatologists thought that intravenous therapy would be less convenient for the patient than subcutaneous therapy, but only 22 of 48 patients said inconvenience was the main barrier to IV therapy.
Study details: An ethnographic, observational study of 48 patients and 16 rheumatologists.
Disclosures: Janssen Pharmaceuticals funded the research. Dr. Kottak is president of Ethnographic Solutions LLC, which received compensation from Janssen Pharmaceuticals for this project.
Source: Kottak N et al. Arthritis Care Res. 2018 Feb 5. doi: 10/1002/acr.23527
Drug combo indicated for bacterial pneumonia
(Avycaz) to include hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults.
Specifically, the approved indication is for infections caused by certain Gram-negative bacteria – some of which are increasingly resistant to available antibiotics – including, Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae.
There have not been new treatment options for HABP/VABP caused by Gram-negative bacteria in more than 15 years, according to Allergan, the drug’s manufacturer.
This is the third approved indication for ceftazidime/avibactam; the other two indications are for complicated intra-abdominal infections (in combination with metronidazole) and for complicated urinary tract infections.
(Avycaz) to include hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults.
Specifically, the approved indication is for infections caused by certain Gram-negative bacteria – some of which are increasingly resistant to available antibiotics – including, Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae.
There have not been new treatment options for HABP/VABP caused by Gram-negative bacteria in more than 15 years, according to Allergan, the drug’s manufacturer.
This is the third approved indication for ceftazidime/avibactam; the other two indications are for complicated intra-abdominal infections (in combination with metronidazole) and for complicated urinary tract infections.
(Avycaz) to include hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults.
Specifically, the approved indication is for infections caused by certain Gram-negative bacteria – some of which are increasingly resistant to available antibiotics – including, Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae.
There have not been new treatment options for HABP/VABP caused by Gram-negative bacteria in more than 15 years, according to Allergan, the drug’s manufacturer.
This is the third approved indication for ceftazidime/avibactam; the other two indications are for complicated intra-abdominal infections (in combination with metronidazole) and for complicated urinary tract infections.
Socioeconomic deprivation tied to survival in ALL
Socioeconomic deprivation may decrease survival in adults with acute lymphoblastic leukemia (ALL), according to research published in BMC Cancer.
Researchers found that ALL patients living in more deprived areas of England had a 16% to 21% greater risk of dying than patients living in the least deprived areas.
The researchers also observed a 33% higher risk of mortality in patients who were treated at hospitals that manage few ALL patients.
“The findings are likely to have significant implications for the organization of NHS [National Health Service] services for the treatment of adults with this rare but serious condition,” said study author Ravi Maheswaran, MD, of the University of Sheffield in Sheffield, UK.
To conduct this study, Dr Maheswaran and Nick Morley, MBBS, of Royal Hallamshire Hospital in Sheffield, analyzed anonymized NHS data on hospital admissions.
The researchers identified 2921 adults (age 18 and older) who were diagnosed with ALL from 2001 to 2012 and assessed follow-up data on survival rates up to 2013.
There were 1870 deaths during follow-up, and the 5-year survival rate was 32%.
As expected, survival decreased with age but increased over time. The mortality hazard ratio (HR) was 1.38 for patients ages 30 to 39, 3.72 for patients ages 60 to 69, and 9.02 for patients age 80 and older.
The HR was 0.98 for patients diagnosed from 2005 to 2008 and 0.70 for patients diagnosed from 2009 to 2012, compared to 1.00 for patients diagnosed from 2001 to 2004.
Patients living in areas of socioeconomic deprivation had a greater risk of death, but it did not seem to matter whether the patients lived in rural or urban areas.
The mortality HR was 1.16 for patients living in the most deprived areas and 1.21 for patients in intermediate areas (with the least deprived areas as the reference, 1.00). The HR was 1.00 for both rural and urban areas.
The risk of death was higher for patients treated at hospitals with low volumes of adults with ALL. The mortality HR was 1.33 for low-volume hospitals, which were defined as hospitals with 15 or fewer ALL patients admitted over a 3-year time period for which data were available.
“These results, although concerning, are from a single study, and further work is needed to confirm our findings,” Dr Maheswaran said.
“If the association between high deprivation and poorer survival is confirmed, more investigation will be needed to understand why adults with this type of leukemia living in deprived areas have poorer survival and what can be done to address this inequality.”
“Confirmation that hospitals treating few patients with this rare condition have worse outcomes would mean that the NHS should seriously consider if treatment services for adults with acute lymphoblastic leukemia should mainly be provided by specialist centers in order to improve survival.” 
Socioeconomic deprivation may decrease survival in adults with acute lymphoblastic leukemia (ALL), according to research published in BMC Cancer.
Researchers found that ALL patients living in more deprived areas of England had a 16% to 21% greater risk of dying than patients living in the least deprived areas.
The researchers also observed a 33% higher risk of mortality in patients who were treated at hospitals that manage few ALL patients.
“The findings are likely to have significant implications for the organization of NHS [National Health Service] services for the treatment of adults with this rare but serious condition,” said study author Ravi Maheswaran, MD, of the University of Sheffield in Sheffield, UK.
To conduct this study, Dr Maheswaran and Nick Morley, MBBS, of Royal Hallamshire Hospital in Sheffield, analyzed anonymized NHS data on hospital admissions.
The researchers identified 2921 adults (age 18 and older) who were diagnosed with ALL from 2001 to 2012 and assessed follow-up data on survival rates up to 2013.
There were 1870 deaths during follow-up, and the 5-year survival rate was 32%.
As expected, survival decreased with age but increased over time. The mortality hazard ratio (HR) was 1.38 for patients ages 30 to 39, 3.72 for patients ages 60 to 69, and 9.02 for patients age 80 and older.
The HR was 0.98 for patients diagnosed from 2005 to 2008 and 0.70 for patients diagnosed from 2009 to 2012, compared to 1.00 for patients diagnosed from 2001 to 2004.
Patients living in areas of socioeconomic deprivation had a greater risk of death, but it did not seem to matter whether the patients lived in rural or urban areas.
The mortality HR was 1.16 for patients living in the most deprived areas and 1.21 for patients in intermediate areas (with the least deprived areas as the reference, 1.00). The HR was 1.00 for both rural and urban areas.
The risk of death was higher for patients treated at hospitals with low volumes of adults with ALL. The mortality HR was 1.33 for low-volume hospitals, which were defined as hospitals with 15 or fewer ALL patients admitted over a 3-year time period for which data were available.
“These results, although concerning, are from a single study, and further work is needed to confirm our findings,” Dr Maheswaran said.
“If the association between high deprivation and poorer survival is confirmed, more investigation will be needed to understand why adults with this type of leukemia living in deprived areas have poorer survival and what can be done to address this inequality.”
“Confirmation that hospitals treating few patients with this rare condition have worse outcomes would mean that the NHS should seriously consider if treatment services for adults with acute lymphoblastic leukemia should mainly be provided by specialist centers in order to improve survival.”
Socioeconomic deprivation may decrease survival in adults with acute lymphoblastic leukemia (ALL), according to research published in BMC Cancer.
Researchers found that ALL patients living in more deprived areas of England had a 16% to 21% greater risk of dying than patients living in the least deprived areas.
The researchers also observed a 33% higher risk of mortality in patients who were treated at hospitals that manage few ALL patients.
“The findings are likely to have significant implications for the organization of NHS [National Health Service] services for the treatment of adults with this rare but serious condition,” said study author Ravi Maheswaran, MD, of the University of Sheffield in Sheffield, UK.
To conduct this study, Dr Maheswaran and Nick Morley, MBBS, of Royal Hallamshire Hospital in Sheffield, analyzed anonymized NHS data on hospital admissions.
The researchers identified 2921 adults (age 18 and older) who were diagnosed with ALL from 2001 to 2012 and assessed follow-up data on survival rates up to 2013.
There were 1870 deaths during follow-up, and the 5-year survival rate was 32%.
As expected, survival decreased with age but increased over time. The mortality hazard ratio (HR) was 1.38 for patients ages 30 to 39, 3.72 for patients ages 60 to 69, and 9.02 for patients age 80 and older.
The HR was 0.98 for patients diagnosed from 2005 to 2008 and 0.70 for patients diagnosed from 2009 to 2012, compared to 1.00 for patients diagnosed from 2001 to 2004.
Patients living in areas of socioeconomic deprivation had a greater risk of death, but it did not seem to matter whether the patients lived in rural or urban areas.
The mortality HR was 1.16 for patients living in the most deprived areas and 1.21 for patients in intermediate areas (with the least deprived areas as the reference, 1.00). The HR was 1.00 for both rural and urban areas.
The risk of death was higher for patients treated at hospitals with low volumes of adults with ALL. The mortality HR was 1.33 for low-volume hospitals, which were defined as hospitals with 15 or fewer ALL patients admitted over a 3-year time period for which data were available.
“These results, although concerning, are from a single study, and further work is needed to confirm our findings,” Dr Maheswaran said.
“If the association between high deprivation and poorer survival is confirmed, more investigation will be needed to understand why adults with this type of leukemia living in deprived areas have poorer survival and what can be done to address this inequality.”
“Confirmation that hospitals treating few patients with this rare condition have worse outcomes would mean that the NHS should seriously consider if treatment services for adults with acute lymphoblastic leukemia should mainly be provided by specialist centers in order to improve survival.”
VIDEO: Managing the alemtuzumab paradox
SAN DIEGO – A paradox of treating people with the monoclonal antibody alemtuzumab is that the agent can be an effective therapy for many people living with multiple sclerosis, but in some patients is associated with the development of other autoimmune diseases.
“I counsel patients with multiple sclerosis that this is a high risk, high gain drug,” Alasdair Coles, MD, of the University of Cambridge (England), said at the meeting, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Patients can make it safer through strict compliance with the drug’s risk monitoring program. But without patient compliance, alemtuzumab becomes a dangerous drug, he said in a video interview.
Knowing in advance which patients are at an elevated risk for subsequent autoimmune diseases has been difficult to predict. But researchers are getting closer, Dr. Coles said. In the future, measuring a serum factor, potentially interleukin 21, could produce a pretreatment risk assessment for each individual.
SAN DIEGO – A paradox of treating people with the monoclonal antibody alemtuzumab is that the agent can be an effective therapy for many people living with multiple sclerosis, but in some patients is associated with the development of other autoimmune diseases.
“I counsel patients with multiple sclerosis that this is a high risk, high gain drug,” Alasdair Coles, MD, of the University of Cambridge (England), said at the meeting, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Patients can make it safer through strict compliance with the drug’s risk monitoring program. But without patient compliance, alemtuzumab becomes a dangerous drug, he said in a video interview.
Knowing in advance which patients are at an elevated risk for subsequent autoimmune diseases has been difficult to predict. But researchers are getting closer, Dr. Coles said. In the future, measuring a serum factor, potentially interleukin 21, could produce a pretreatment risk assessment for each individual.
SAN DIEGO – A paradox of treating people with the monoclonal antibody alemtuzumab is that the agent can be an effective therapy for many people living with multiple sclerosis, but in some patients is associated with the development of other autoimmune diseases.
“I counsel patients with multiple sclerosis that this is a high risk, high gain drug,” Alasdair Coles, MD, of the University of Cambridge (England), said at the meeting, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Patients can make it safer through strict compliance with the drug’s risk monitoring program. But without patient compliance, alemtuzumab becomes a dangerous drug, he said in a video interview.
Knowing in advance which patients are at an elevated risk for subsequent autoimmune diseases has been difficult to predict. But researchers are getting closer, Dr. Coles said. In the future, measuring a serum factor, potentially interleukin 21, could produce a pretreatment risk assessment for each individual.
REPORTING FROM ACTRIMS FORUM 2018
Ibuprofen appears safe with preeclampsia, study says
DALLAS – Compared to acetaminophen, ibuprofen does not prolong the time needed to control postpartum hypertension in women who experience preeclampsia with severe features, Nathan Blue MD, reported at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.
Ibuprofen did not exacerbate postpartum hypertension, as some studies have suggested, and women randomized to it for postpartum pain control reached their target blood pressure at a mean of 35 hours after delivery, similar to the 38 hours needed among women receiving acetaminophen.
Dr. Blue’s findings contradict the recommendation by the American College of Obstetricians and Gynecologists to avoid the use of ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) for pain control in women who experience preeclampsia or other hypertensive disorders of pregnancy.
“While our study was not meant to answer all questions about the potential problems of nonsteroidal anti-inflammatories [in this population], I would conclude from these results that providers and patients can make a decision together and feel good about the use of NSAIDs,” in the presence of postpartum hypertension, said Dr. Blue, a fellow at the University of New Mexico, Albuquerque.
These concerns led ACOG to issue its recommendation in 2013 against the use of NSAIDs in pregnant women with hypertension.
“This is problematic, because NSAIDs are particularly well-suited to address obstetric pain,” Dr. Blue said at the meeting. “They have been shown to be better than acetaminophen for perineal injury and they are associated with a reduced use of opioids after cesarean section.”
To investigate the effect of ibuprofen on postpartum hypertension, Dr. Blue and his colleagues conducted a double-blind randomized controlled trial of 100 women with preeclampsia with severe features. The study population also included women who had chronic hypertension complicated by preeclampsia with severe features, and women with HELLP syndrome – a constellation of hemolysis, elevated liver enzymes, and low platelet count.
Women were randomized to either 600 mg ibuprofen or 650 mg acetaminophen every 6 hours, around the clock, with the first dose delivered within 6 hours of delivery. All patients received at least eight doses of their assigned medication. The primary endpoint was the time required to achieve blood pressure control. “We defined blood pressure control as the number of hours from delivery to the last reading of at least 160/110 mm Hg before discharge,” Dr. Blue said. “Our rationale here was that persistence of a blood pressure of that level would require a delay in discharge of at least 24 hours.”
The study had a number of secondary outcomes, including time from delivery to last blood pressure reading of at least 150/100 mm Hg; postpartum mean arterial pressure; any blood pressure reading of 160/110 mm Hg or higher; need for antihypertensive drugs at discharge; prolongation of hospital stay due to hypertension; and the need for postpartum opioids.
There was a 6-week follow-up assessment, at which time women reported any continued antihypertensive or opioid use, obstetrical triage visits after discharge, and hospital readmission.
The study cohort was well-balanced at baseline. Women were a mean of 30 years old; about a third were nulliparous, and half had a vaginal delivery. Chronic hypertension requiring medication was present in about 15%. The maximum blood pressure before delivery was about 180/107.
There was no significant difference between the ibuprofen group and the acetaminophen group in the primary endpoint of time to blood pressure of 160/110 mm Hg or below (35.3 vs. 38 hours). Nor were there significant differences in any of the secondary endpoints, including time to achieve a blood pressure of less than 150/100 mm Hg (58 vs. 57 hours), postpartum mean arterial pressure, maximum systolic and diastolic blood pressures, or the number of women who needed a short-acting antihypertensive (30 vs. 26) and who went home on an antihypertensive (33 vs. 31).
There were also no significant between-group differences in opioid use, either on postpartum days 0, 1, or 2. The total morphine equivalent dose for each group was likewise not significantly different (77 vs. 88 mg).
Dr. Blue was able to contact 77 women at 6 weeks’ postpartum. He found that 6-week outcomes were also similar. There were no significant differences in the number who required continuing antihypertensive or opioids, no difference in obstetric triage visits, and no difference in hospital readmission.
“Our study does not support the hypothesis that NSAIDs adversely affect blood pressure control in patients with preeclampsia,” he said. “Not only did we not find a difference in the primary outcome, we found not even a suggestion of difference in any measure of blood pressure control.”
The University of New Mexico sponsored the study. Dr. Blue reported having no financial disclosures.
SOURCE: Blue et al. The Pregnancy Meeting 2018 Abstract LB04.
DALLAS – Compared to acetaminophen, ibuprofen does not prolong the time needed to control postpartum hypertension in women who experience preeclampsia with severe features, Nathan Blue MD, reported at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.
Ibuprofen did not exacerbate postpartum hypertension, as some studies have suggested, and women randomized to it for postpartum pain control reached their target blood pressure at a mean of 35 hours after delivery, similar to the 38 hours needed among women receiving acetaminophen.
Dr. Blue’s findings contradict the recommendation by the American College of Obstetricians and Gynecologists to avoid the use of ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) for pain control in women who experience preeclampsia or other hypertensive disorders of pregnancy.
“While our study was not meant to answer all questions about the potential problems of nonsteroidal anti-inflammatories [in this population], I would conclude from these results that providers and patients can make a decision together and feel good about the use of NSAIDs,” in the presence of postpartum hypertension, said Dr. Blue, a fellow at the University of New Mexico, Albuquerque.
These concerns led ACOG to issue its recommendation in 2013 against the use of NSAIDs in pregnant women with hypertension.
“This is problematic, because NSAIDs are particularly well-suited to address obstetric pain,” Dr. Blue said at the meeting. “They have been shown to be better than acetaminophen for perineal injury and they are associated with a reduced use of opioids after cesarean section.”
To investigate the effect of ibuprofen on postpartum hypertension, Dr. Blue and his colleagues conducted a double-blind randomized controlled trial of 100 women with preeclampsia with severe features. The study population also included women who had chronic hypertension complicated by preeclampsia with severe features, and women with HELLP syndrome – a constellation of hemolysis, elevated liver enzymes, and low platelet count.
Women were randomized to either 600 mg ibuprofen or 650 mg acetaminophen every 6 hours, around the clock, with the first dose delivered within 6 hours of delivery. All patients received at least eight doses of their assigned medication. The primary endpoint was the time required to achieve blood pressure control. “We defined blood pressure control as the number of hours from delivery to the last reading of at least 160/110 mm Hg before discharge,” Dr. Blue said. “Our rationale here was that persistence of a blood pressure of that level would require a delay in discharge of at least 24 hours.”
The study had a number of secondary outcomes, including time from delivery to last blood pressure reading of at least 150/100 mm Hg; postpartum mean arterial pressure; any blood pressure reading of 160/110 mm Hg or higher; need for antihypertensive drugs at discharge; prolongation of hospital stay due to hypertension; and the need for postpartum opioids.
There was a 6-week follow-up assessment, at which time women reported any continued antihypertensive or opioid use, obstetrical triage visits after discharge, and hospital readmission.
The study cohort was well-balanced at baseline. Women were a mean of 30 years old; about a third were nulliparous, and half had a vaginal delivery. Chronic hypertension requiring medication was present in about 15%. The maximum blood pressure before delivery was about 180/107.
There was no significant difference between the ibuprofen group and the acetaminophen group in the primary endpoint of time to blood pressure of 160/110 mm Hg or below (35.3 vs. 38 hours). Nor were there significant differences in any of the secondary endpoints, including time to achieve a blood pressure of less than 150/100 mm Hg (58 vs. 57 hours), postpartum mean arterial pressure, maximum systolic and diastolic blood pressures, or the number of women who needed a short-acting antihypertensive (30 vs. 26) and who went home on an antihypertensive (33 vs. 31).
There were also no significant between-group differences in opioid use, either on postpartum days 0, 1, or 2. The total morphine equivalent dose for each group was likewise not significantly different (77 vs. 88 mg).
Dr. Blue was able to contact 77 women at 6 weeks’ postpartum. He found that 6-week outcomes were also similar. There were no significant differences in the number who required continuing antihypertensive or opioids, no difference in obstetric triage visits, and no difference in hospital readmission.
“Our study does not support the hypothesis that NSAIDs adversely affect blood pressure control in patients with preeclampsia,” he said. “Not only did we not find a difference in the primary outcome, we found not even a suggestion of difference in any measure of blood pressure control.”
The University of New Mexico sponsored the study. Dr. Blue reported having no financial disclosures.
SOURCE: Blue et al. The Pregnancy Meeting 2018 Abstract LB04.
DALLAS – Compared to acetaminophen, ibuprofen does not prolong the time needed to control postpartum hypertension in women who experience preeclampsia with severe features, Nathan Blue MD, reported at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.
Ibuprofen did not exacerbate postpartum hypertension, as some studies have suggested, and women randomized to it for postpartum pain control reached their target blood pressure at a mean of 35 hours after delivery, similar to the 38 hours needed among women receiving acetaminophen.
Dr. Blue’s findings contradict the recommendation by the American College of Obstetricians and Gynecologists to avoid the use of ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) for pain control in women who experience preeclampsia or other hypertensive disorders of pregnancy.
“While our study was not meant to answer all questions about the potential problems of nonsteroidal anti-inflammatories [in this population], I would conclude from these results that providers and patients can make a decision together and feel good about the use of NSAIDs,” in the presence of postpartum hypertension, said Dr. Blue, a fellow at the University of New Mexico, Albuquerque.
These concerns led ACOG to issue its recommendation in 2013 against the use of NSAIDs in pregnant women with hypertension.
“This is problematic, because NSAIDs are particularly well-suited to address obstetric pain,” Dr. Blue said at the meeting. “They have been shown to be better than acetaminophen for perineal injury and they are associated with a reduced use of opioids after cesarean section.”
To investigate the effect of ibuprofen on postpartum hypertension, Dr. Blue and his colleagues conducted a double-blind randomized controlled trial of 100 women with preeclampsia with severe features. The study population also included women who had chronic hypertension complicated by preeclampsia with severe features, and women with HELLP syndrome – a constellation of hemolysis, elevated liver enzymes, and low platelet count.
Women were randomized to either 600 mg ibuprofen or 650 mg acetaminophen every 6 hours, around the clock, with the first dose delivered within 6 hours of delivery. All patients received at least eight doses of their assigned medication. The primary endpoint was the time required to achieve blood pressure control. “We defined blood pressure control as the number of hours from delivery to the last reading of at least 160/110 mm Hg before discharge,” Dr. Blue said. “Our rationale here was that persistence of a blood pressure of that level would require a delay in discharge of at least 24 hours.”
The study had a number of secondary outcomes, including time from delivery to last blood pressure reading of at least 150/100 mm Hg; postpartum mean arterial pressure; any blood pressure reading of 160/110 mm Hg or higher; need for antihypertensive drugs at discharge; prolongation of hospital stay due to hypertension; and the need for postpartum opioids.
There was a 6-week follow-up assessment, at which time women reported any continued antihypertensive or opioid use, obstetrical triage visits after discharge, and hospital readmission.
The study cohort was well-balanced at baseline. Women were a mean of 30 years old; about a third were nulliparous, and half had a vaginal delivery. Chronic hypertension requiring medication was present in about 15%. The maximum blood pressure before delivery was about 180/107.
There was no significant difference between the ibuprofen group and the acetaminophen group in the primary endpoint of time to blood pressure of 160/110 mm Hg or below (35.3 vs. 38 hours). Nor were there significant differences in any of the secondary endpoints, including time to achieve a blood pressure of less than 150/100 mm Hg (58 vs. 57 hours), postpartum mean arterial pressure, maximum systolic and diastolic blood pressures, or the number of women who needed a short-acting antihypertensive (30 vs. 26) and who went home on an antihypertensive (33 vs. 31).
There were also no significant between-group differences in opioid use, either on postpartum days 0, 1, or 2. The total morphine equivalent dose for each group was likewise not significantly different (77 vs. 88 mg).
Dr. Blue was able to contact 77 women at 6 weeks’ postpartum. He found that 6-week outcomes were also similar. There were no significant differences in the number who required continuing antihypertensive or opioids, no difference in obstetric triage visits, and no difference in hospital readmission.
“Our study does not support the hypothesis that NSAIDs adversely affect blood pressure control in patients with preeclampsia,” he said. “Not only did we not find a difference in the primary outcome, we found not even a suggestion of difference in any measure of blood pressure control.”
The University of New Mexico sponsored the study. Dr. Blue reported having no financial disclosures.
SOURCE: Blue et al. The Pregnancy Meeting 2018 Abstract LB04.
REPORTING FROM THE PREGNANCY MEETING
Key clinical point:
Major finding: The mean time to achieve postpartum blood pressure control was 35 hours in the ibuprofen group and 38 hours in the acetaminophen group.
Study details: The randomized study comprised 100 women.
Disclosures: The University of New Mexico sponsored the study. Dr. Blue reported having no financial disclosures.
Source: Blue N et al. The Pregnancy Meeting 2018 Abstract LB04.
Third course of alemtuzumab can improve MS outcomes
SAN DIEGO – Approximately 30% of people with active multiple sclerosis who initially responded well to two courses of alemtuzumab in the CARE-MS II trial experience relapse or MRI activity over time. But investigators set out to determine whether retreatment with a subsequent course of alemtuzumab is worthwhile.
“What we found is, after the third course, they continued to do well again – at this point for an average of another 3-4 years,” Ann D. Bass, MD, said in an interview at the meeting, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“The take-home message is if they do need to be retreated after those two courses, it doesn’t [necessarily] mean they are a treatment failure. Give them another chance and see if they will do well with a third course, which is what they did,” said Dr. Bass, of the Neurology Center of San Antonio.
Through year 6 of an extension study with 393 of the original CARE-MS II trial participants, 45% received one or more additional courses of alemtuzumab. Participants were required to wait 12 months or more after completion of the two initial courses of therapy. This figure includes 30% who received a third course of alemtuzumab, 12% who received a fourth course, and 2% and 1% who received a fifth or sixth course, respectively.
“The average time until they needed a third course was 2.5 years after the second course; so they didn’t need it right away,” Dr. Bass said. “The majority, even at 6 years, did not need to have a third course.”
When patients did require a subsequent course, “about half needed it because of clinical relapse; one-quarter needed it because of MRI relapse; and about one-quarter needed it because of both,” Dr. Bass said during a poster presentation.
In terms of effectiveness, the annual relapse rate significantly decreased following a third course of alemtuzumab, from 0.85 in the 12 months prior to the third course to 0.20 in the 12 months after (P less than .0001). In these patients, the annual relapse rate remained low, at 0.17, up to 3 years later.
Investigators also tracked disability using the Expanded Disability Status Scale. They found that more than two-thirds, 68%, maintained stable or had improved scores after administration of a third alemtuzumab course. In addition, the percentage of patients with confirmed disability improvement increased from 4.4% in the 12 months prior to a third course to 14.4% in the year following pretreatment.
Retreatment was at the patient’s discretion. “The patients have the right to say ‘No, I’m doing great. I don’t want to be retreated’ or ‘I want to explore other options’ for whatever reason,” Dr. Bass said. “That’s rare though; most patients actually say yes.”
To qualify for retreatment based on MRI findings, patients had to have at least two lesions – one enlarging and one enhancing, two enlarging, or two new.
Only patients who opted for a subsequent course of alemtuzumab were included in the current analysis; those who chose a different disease-modifying therapy were excluded.
“Many achieve clinical and MRI remission. I never say cure – you don’t want to say that word,” Dr. Bass said.
Sanofi and Bayer HealthCare Pharmaceuticals supported the study. Dr. Bass reported that she is a principal investigator, speaker, and member of the advisory board for Sanofi Genzyme.
SOURCE: Bass A et al. ACTRIMS Forum 2018 Poster P035.
SAN DIEGO – Approximately 30% of people with active multiple sclerosis who initially responded well to two courses of alemtuzumab in the CARE-MS II trial experience relapse or MRI activity over time. But investigators set out to determine whether retreatment with a subsequent course of alemtuzumab is worthwhile.
“What we found is, after the third course, they continued to do well again – at this point for an average of another 3-4 years,” Ann D. Bass, MD, said in an interview at the meeting, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“The take-home message is if they do need to be retreated after those two courses, it doesn’t [necessarily] mean they are a treatment failure. Give them another chance and see if they will do well with a third course, which is what they did,” said Dr. Bass, of the Neurology Center of San Antonio.
Through year 6 of an extension study with 393 of the original CARE-MS II trial participants, 45% received one or more additional courses of alemtuzumab. Participants were required to wait 12 months or more after completion of the two initial courses of therapy. This figure includes 30% who received a third course of alemtuzumab, 12% who received a fourth course, and 2% and 1% who received a fifth or sixth course, respectively.
“The average time until they needed a third course was 2.5 years after the second course; so they didn’t need it right away,” Dr. Bass said. “The majority, even at 6 years, did not need to have a third course.”
When patients did require a subsequent course, “about half needed it because of clinical relapse; one-quarter needed it because of MRI relapse; and about one-quarter needed it because of both,” Dr. Bass said during a poster presentation.
In terms of effectiveness, the annual relapse rate significantly decreased following a third course of alemtuzumab, from 0.85 in the 12 months prior to the third course to 0.20 in the 12 months after (P less than .0001). In these patients, the annual relapse rate remained low, at 0.17, up to 3 years later.
Investigators also tracked disability using the Expanded Disability Status Scale. They found that more than two-thirds, 68%, maintained stable or had improved scores after administration of a third alemtuzumab course. In addition, the percentage of patients with confirmed disability improvement increased from 4.4% in the 12 months prior to a third course to 14.4% in the year following pretreatment.
Retreatment was at the patient’s discretion. “The patients have the right to say ‘No, I’m doing great. I don’t want to be retreated’ or ‘I want to explore other options’ for whatever reason,” Dr. Bass said. “That’s rare though; most patients actually say yes.”
To qualify for retreatment based on MRI findings, patients had to have at least two lesions – one enlarging and one enhancing, two enlarging, or two new.
Only patients who opted for a subsequent course of alemtuzumab were included in the current analysis; those who chose a different disease-modifying therapy were excluded.
“Many achieve clinical and MRI remission. I never say cure – you don’t want to say that word,” Dr. Bass said.
Sanofi and Bayer HealthCare Pharmaceuticals supported the study. Dr. Bass reported that she is a principal investigator, speaker, and member of the advisory board for Sanofi Genzyme.
SOURCE: Bass A et al. ACTRIMS Forum 2018 Poster P035.
SAN DIEGO – Approximately 30% of people with active multiple sclerosis who initially responded well to two courses of alemtuzumab in the CARE-MS II trial experience relapse or MRI activity over time. But investigators set out to determine whether retreatment with a subsequent course of alemtuzumab is worthwhile.
“What we found is, after the third course, they continued to do well again – at this point for an average of another 3-4 years,” Ann D. Bass, MD, said in an interview at the meeting, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“The take-home message is if they do need to be retreated after those two courses, it doesn’t [necessarily] mean they are a treatment failure. Give them another chance and see if they will do well with a third course, which is what they did,” said Dr. Bass, of the Neurology Center of San Antonio.
Through year 6 of an extension study with 393 of the original CARE-MS II trial participants, 45% received one or more additional courses of alemtuzumab. Participants were required to wait 12 months or more after completion of the two initial courses of therapy. This figure includes 30% who received a third course of alemtuzumab, 12% who received a fourth course, and 2% and 1% who received a fifth or sixth course, respectively.
“The average time until they needed a third course was 2.5 years after the second course; so they didn’t need it right away,” Dr. Bass said. “The majority, even at 6 years, did not need to have a third course.”
When patients did require a subsequent course, “about half needed it because of clinical relapse; one-quarter needed it because of MRI relapse; and about one-quarter needed it because of both,” Dr. Bass said during a poster presentation.
In terms of effectiveness, the annual relapse rate significantly decreased following a third course of alemtuzumab, from 0.85 in the 12 months prior to the third course to 0.20 in the 12 months after (P less than .0001). In these patients, the annual relapse rate remained low, at 0.17, up to 3 years later.
Investigators also tracked disability using the Expanded Disability Status Scale. They found that more than two-thirds, 68%, maintained stable or had improved scores after administration of a third alemtuzumab course. In addition, the percentage of patients with confirmed disability improvement increased from 4.4% in the 12 months prior to a third course to 14.4% in the year following pretreatment.
Retreatment was at the patient’s discretion. “The patients have the right to say ‘No, I’m doing great. I don’t want to be retreated’ or ‘I want to explore other options’ for whatever reason,” Dr. Bass said. “That’s rare though; most patients actually say yes.”
To qualify for retreatment based on MRI findings, patients had to have at least two lesions – one enlarging and one enhancing, two enlarging, or two new.
Only patients who opted for a subsequent course of alemtuzumab were included in the current analysis; those who chose a different disease-modifying therapy were excluded.
“Many achieve clinical and MRI remission. I never say cure – you don’t want to say that word,” Dr. Bass said.
Sanofi and Bayer HealthCare Pharmaceuticals supported the study. Dr. Bass reported that she is a principal investigator, speaker, and member of the advisory board for Sanofi Genzyme.
SOURCE: Bass A et al. ACTRIMS Forum 2018 Poster P035.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point:
Major finding: The annual relapse rate significantly decreased following a third course of alemtuzumab, from 0.85 in the 12 months prior to the third course to 0.20 in the 12 months after (P less than .0001).
Study details: An extension study of the CARE-MS II trial involving 393 of the original study participants.
Disclosures: Sanofi and Bayer HealthCare Pharmaceuticals supported the study. Dr. Bass reported that she is a principal investigator, speaker, and member of the advisory board for Sanofi Genzyme.
Source: Bass A et al. ACTRIMS Forum 2018 Poster P035.
Switching RRMS patients to daclizumab beta appears safe
SAN DIEGO – Switching relapsing-remitting multiple sclerosis patients from glatiramer acetate to daclizumab beta resulted in no increase in the adverse event profile and was associated with superior efficacy, a post hoc analysis of data from the DECIDE study showed.
“There is always a challenge in transitioning patients from one therapeutic agent to another, with concerns for adequate efficacy to justify the switch, and heightened risks of toxicity or adverse events,” lead study author Stanley L. Cohan, MD, PhD, said in an interview prior to the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “Daclizumab is not a first-line or platform therapeutic agent, but has clearly superior efficacy to first-line medication, and, based upon the current data presented, safety and efficacy are not adversely influenced by prior treatment history with a first-line agent.”
In the phase 3 DECIDE trial, daclizumab beta 150 mg demonstrated greater efficacy versus intramuscular (IM) interferon (IFN) beta-1a 30 mcg on several clinical, radiographic, and patient-centered outcomes in patients with relapsing-remitting multiple sclerosis (N Engl J Med 2015; 373:1418-28). The purpose of the current study was to examine the efficacy and safety of daclizumab beta vs. IM IFN beta-1a in the subgroup of RRMS patients treated with glatiramer acetate (GA) as their only previous disease-modifying therapy (DMT) before entering DECIDE.
Dr. Cohan, a neurologist who directs the Providence MS Center at the Providence Brain and Spine Institute in Portland, Ore., and his associates reported data from 42 of 922 (5%) IM IFN beta-1a and 50 of 919 (5%) daclizumab beta patients who had received treatment with GA only prior to DECIDE. Baseline characteristics were balanced between treatment groups, including duration of prior treatment with GA, reasons for discontinuing GA, and time between GA discontinuation and start of treatment in DECIDE. The annualized relapse rate was 42% lower in patients treated with daclizumab beta vs. IM IFN beta-1a (rate ratio of 0.58). Daclizumab beta also reduced risk of relapse by 53% (hazard ratio of 0.47; P = .048) and the mean number of new or newly-enlarging T2-hyperintense lesions at week 96 by 58% (lesion mean ratio, 0.42; P = .021) vs. IM IFN beta-1a.
In patients treated with GA only before DECIDE, 98% of IM IFN beta-1a patients and 94% of daclizumab beta patients reported any adverse event (AE). In all, 2% of IM IFN beta-1a patients and 16% of daclizumab beta patients had a serious AE (excluding MS relapse), and 10% of IM IFN beta-1a and 12% of daclizumab beta patients discontinued treatment because of an AE (excluding MS relapse).
The incidence of elevations of alanine aminotransferase or aspartate aminotransferase three times the upper limit of normal or greater was 10% in the IM IFN beta-1a group and 8% in the daclizumab beta, while the ALT and AST elevations were greater than five times the ULN in 0% and 4% of patients, respectively.
Serious adverse events were reported in eight participants in the daclizumab beta group (including abortion induced, ankle fracture, anal fistula, anxiety, appendicitis perforated, convulsion, pelvic abscess, inguinal hernia, abnormal cervix smear), and one participant in the IM IFN beta-1a group (ligament rupture).
“This post hoc analysis demonstrates that in switching from glatiramer to daclizumab there was no unanticipated or increase in the AE profile, and that a switch from glatiramer to daclizumab was associated with superior efficacy, again in line with overall efficacy observed for daclizumab in this study,” Dr. Cohan said.
He acknowledged certain limitations of the study, including the post hoc nature of the analysis. “The small glatiramer cohort size, and the large percentage of former glatiramer patients who entered DECIDE because of lack of glatiramer efficacy may have introduced a selection bias which would magnify the seeming efficacy of daclizumab, and interferon-beta,” he added.
Dr. Cohan reported that he receives research support from Biogen, Novartis, Roche, Sanofi, and Mallinckrodt, and speaking honoraria from Acorda, Biogen, Roche, and Sanofi. He has served on advisory boards for Biogen, Sanofi, and Novartis.
SOURCE: Cohan et al. ACTRIMS Forum 2018, Poster 42.
SAN DIEGO – Switching relapsing-remitting multiple sclerosis patients from glatiramer acetate to daclizumab beta resulted in no increase in the adverse event profile and was associated with superior efficacy, a post hoc analysis of data from the DECIDE study showed.
“There is always a challenge in transitioning patients from one therapeutic agent to another, with concerns for adequate efficacy to justify the switch, and heightened risks of toxicity or adverse events,” lead study author Stanley L. Cohan, MD, PhD, said in an interview prior to the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “Daclizumab is not a first-line or platform therapeutic agent, but has clearly superior efficacy to first-line medication, and, based upon the current data presented, safety and efficacy are not adversely influenced by prior treatment history with a first-line agent.”
In the phase 3 DECIDE trial, daclizumab beta 150 mg demonstrated greater efficacy versus intramuscular (IM) interferon (IFN) beta-1a 30 mcg on several clinical, radiographic, and patient-centered outcomes in patients with relapsing-remitting multiple sclerosis (N Engl J Med 2015; 373:1418-28). The purpose of the current study was to examine the efficacy and safety of daclizumab beta vs. IM IFN beta-1a in the subgroup of RRMS patients treated with glatiramer acetate (GA) as their only previous disease-modifying therapy (DMT) before entering DECIDE.
Dr. Cohan, a neurologist who directs the Providence MS Center at the Providence Brain and Spine Institute in Portland, Ore., and his associates reported data from 42 of 922 (5%) IM IFN beta-1a and 50 of 919 (5%) daclizumab beta patients who had received treatment with GA only prior to DECIDE. Baseline characteristics were balanced between treatment groups, including duration of prior treatment with GA, reasons for discontinuing GA, and time between GA discontinuation and start of treatment in DECIDE. The annualized relapse rate was 42% lower in patients treated with daclizumab beta vs. IM IFN beta-1a (rate ratio of 0.58). Daclizumab beta also reduced risk of relapse by 53% (hazard ratio of 0.47; P = .048) and the mean number of new or newly-enlarging T2-hyperintense lesions at week 96 by 58% (lesion mean ratio, 0.42; P = .021) vs. IM IFN beta-1a.
In patients treated with GA only before DECIDE, 98% of IM IFN beta-1a patients and 94% of daclizumab beta patients reported any adverse event (AE). In all, 2% of IM IFN beta-1a patients and 16% of daclizumab beta patients had a serious AE (excluding MS relapse), and 10% of IM IFN beta-1a and 12% of daclizumab beta patients discontinued treatment because of an AE (excluding MS relapse).
The incidence of elevations of alanine aminotransferase or aspartate aminotransferase three times the upper limit of normal or greater was 10% in the IM IFN beta-1a group and 8% in the daclizumab beta, while the ALT and AST elevations were greater than five times the ULN in 0% and 4% of patients, respectively.
Serious adverse events were reported in eight participants in the daclizumab beta group (including abortion induced, ankle fracture, anal fistula, anxiety, appendicitis perforated, convulsion, pelvic abscess, inguinal hernia, abnormal cervix smear), and one participant in the IM IFN beta-1a group (ligament rupture).
“This post hoc analysis demonstrates that in switching from glatiramer to daclizumab there was no unanticipated or increase in the AE profile, and that a switch from glatiramer to daclizumab was associated with superior efficacy, again in line with overall efficacy observed for daclizumab in this study,” Dr. Cohan said.
He acknowledged certain limitations of the study, including the post hoc nature of the analysis. “The small glatiramer cohort size, and the large percentage of former glatiramer patients who entered DECIDE because of lack of glatiramer efficacy may have introduced a selection bias which would magnify the seeming efficacy of daclizumab, and interferon-beta,” he added.
Dr. Cohan reported that he receives research support from Biogen, Novartis, Roche, Sanofi, and Mallinckrodt, and speaking honoraria from Acorda, Biogen, Roche, and Sanofi. He has served on advisory boards for Biogen, Sanofi, and Novartis.
SOURCE: Cohan et al. ACTRIMS Forum 2018, Poster 42.
SAN DIEGO – Switching relapsing-remitting multiple sclerosis patients from glatiramer acetate to daclizumab beta resulted in no increase in the adverse event profile and was associated with superior efficacy, a post hoc analysis of data from the DECIDE study showed.
“There is always a challenge in transitioning patients from one therapeutic agent to another, with concerns for adequate efficacy to justify the switch, and heightened risks of toxicity or adverse events,” lead study author Stanley L. Cohan, MD, PhD, said in an interview prior to the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “Daclizumab is not a first-line or platform therapeutic agent, but has clearly superior efficacy to first-line medication, and, based upon the current data presented, safety and efficacy are not adversely influenced by prior treatment history with a first-line agent.”
In the phase 3 DECIDE trial, daclizumab beta 150 mg demonstrated greater efficacy versus intramuscular (IM) interferon (IFN) beta-1a 30 mcg on several clinical, radiographic, and patient-centered outcomes in patients with relapsing-remitting multiple sclerosis (N Engl J Med 2015; 373:1418-28). The purpose of the current study was to examine the efficacy and safety of daclizumab beta vs. IM IFN beta-1a in the subgroup of RRMS patients treated with glatiramer acetate (GA) as their only previous disease-modifying therapy (DMT) before entering DECIDE.
Dr. Cohan, a neurologist who directs the Providence MS Center at the Providence Brain and Spine Institute in Portland, Ore., and his associates reported data from 42 of 922 (5%) IM IFN beta-1a and 50 of 919 (5%) daclizumab beta patients who had received treatment with GA only prior to DECIDE. Baseline characteristics were balanced between treatment groups, including duration of prior treatment with GA, reasons for discontinuing GA, and time between GA discontinuation and start of treatment in DECIDE. The annualized relapse rate was 42% lower in patients treated with daclizumab beta vs. IM IFN beta-1a (rate ratio of 0.58). Daclizumab beta also reduced risk of relapse by 53% (hazard ratio of 0.47; P = .048) and the mean number of new or newly-enlarging T2-hyperintense lesions at week 96 by 58% (lesion mean ratio, 0.42; P = .021) vs. IM IFN beta-1a.
In patients treated with GA only before DECIDE, 98% of IM IFN beta-1a patients and 94% of daclizumab beta patients reported any adverse event (AE). In all, 2% of IM IFN beta-1a patients and 16% of daclizumab beta patients had a serious AE (excluding MS relapse), and 10% of IM IFN beta-1a and 12% of daclizumab beta patients discontinued treatment because of an AE (excluding MS relapse).
The incidence of elevations of alanine aminotransferase or aspartate aminotransferase three times the upper limit of normal or greater was 10% in the IM IFN beta-1a group and 8% in the daclizumab beta, while the ALT and AST elevations were greater than five times the ULN in 0% and 4% of patients, respectively.
Serious adverse events were reported in eight participants in the daclizumab beta group (including abortion induced, ankle fracture, anal fistula, anxiety, appendicitis perforated, convulsion, pelvic abscess, inguinal hernia, abnormal cervix smear), and one participant in the IM IFN beta-1a group (ligament rupture).
“This post hoc analysis demonstrates that in switching from glatiramer to daclizumab there was no unanticipated or increase in the AE profile, and that a switch from glatiramer to daclizumab was associated with superior efficacy, again in line with overall efficacy observed for daclizumab in this study,” Dr. Cohan said.
He acknowledged certain limitations of the study, including the post hoc nature of the analysis. “The small glatiramer cohort size, and the large percentage of former glatiramer patients who entered DECIDE because of lack of glatiramer efficacy may have introduced a selection bias which would magnify the seeming efficacy of daclizumab, and interferon-beta,” he added.
Dr. Cohan reported that he receives research support from Biogen, Novartis, Roche, Sanofi, and Mallinckrodt, and speaking honoraria from Acorda, Biogen, Roche, and Sanofi. He has served on advisory boards for Biogen, Sanofi, and Novartis.
SOURCE: Cohan et al. ACTRIMS Forum 2018, Poster 42.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point:
Major finding: The annualized relapse rate was 42% lower in patients treated with daclizumab beta vs. IM IFN beta-1a (rate ratio of 0.58).
Study details: A post hoc analysis of 42 of 922 (5%) IM IFN beta-1a and 50 of 919 (5%) daclizumab beta patients who had received treatment with glatiramer acetate only prior to the DECIDE trial.
Disclosures: Dr. Cohan reported that he receives research support from Biogen, Novartis, Roche, Sanofi, and Mallinckrodt, and speaking honoraria from Acorda, Biogen, Roche, and Sanofi. He has served on advisory boards for Biogen, Sanofi, and Novartis.
Source: Cohan S et al. ACTRIMS Forum 2018 Poster 42.