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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
New quadrivalent meningococcal vaccine joins VFC arsenal
No changes to the current meningococcal vaccination recommendations were made. The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) voted 14-0 to include MenACWY-TT as an option for vaccination against meningococcal serogroups A, C, W, and Y in the VFC program. The vote took place in a virtual meeting held on June 24.
The currently available MenACWY vaccines in the United States are MenACWY-D (Menactra), MenACWY-CRW (Menveo), and MenACWY-TT (MedQuadfi), with MenACWY-TT approved by the Food and Drug Administration in April 2020.
Meningococcal vaccination is currently recommended for adolescents, with one dose at age 11 or 12 years and a booster at age 16 years, as well as individuals aged 2 months and older at increased risk for meningococcal disease, according to Lucy McNamara, PhD, of the CDC’s National Center for Immunization and Respiratory Diseases.
Dr. McNamara presented considerations from the Meningococcal Work Group, which determined that the inclusion of MenACWY-TT “is of public health importance given recent vaccine licensure and to support security of vaccine supply.”
The Work Group reviewed 10 studies (phase 2 or 3) of MenACWY-TT that included data on short-term immune response, persistence of immune response, immune interference because of coadministration with other routine adolescent vaccines, and incidence of serious adverse events. Overall, the data showed noninferiority of MenACWY-TT, compared with other available products, in terms of response rates, as well as higher levels of immune response in some studies. Serious adverse events were similar, and none determined to be associated with the vaccines.
ACIP member Paul Hunter, MD, of the University of Milwaukee, Wisc., expressed some concerns about pain or side effects for the new vaccine and Tdap when given together. However, a study of coadministration of MedACWY-TT and Tdap, compared with Tdap alone, showed no impact on geometric mean titer ratios.
Overall, the Work Group concluded that “desirable effects outweigh undesirable effects” and that the data favor the inclusion of MenACWY-TT as an option for meningococcal vaccination.
The committee members and Dr. McNamara had no relevant financial conflicts to disclose.
No changes to the current meningococcal vaccination recommendations were made. The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) voted 14-0 to include MenACWY-TT as an option for vaccination against meningococcal serogroups A, C, W, and Y in the VFC program. The vote took place in a virtual meeting held on June 24.
The currently available MenACWY vaccines in the United States are MenACWY-D (Menactra), MenACWY-CRW (Menveo), and MenACWY-TT (MedQuadfi), with MenACWY-TT approved by the Food and Drug Administration in April 2020.
Meningococcal vaccination is currently recommended for adolescents, with one dose at age 11 or 12 years and a booster at age 16 years, as well as individuals aged 2 months and older at increased risk for meningococcal disease, according to Lucy McNamara, PhD, of the CDC’s National Center for Immunization and Respiratory Diseases.
Dr. McNamara presented considerations from the Meningococcal Work Group, which determined that the inclusion of MenACWY-TT “is of public health importance given recent vaccine licensure and to support security of vaccine supply.”
The Work Group reviewed 10 studies (phase 2 or 3) of MenACWY-TT that included data on short-term immune response, persistence of immune response, immune interference because of coadministration with other routine adolescent vaccines, and incidence of serious adverse events. Overall, the data showed noninferiority of MenACWY-TT, compared with other available products, in terms of response rates, as well as higher levels of immune response in some studies. Serious adverse events were similar, and none determined to be associated with the vaccines.
ACIP member Paul Hunter, MD, of the University of Milwaukee, Wisc., expressed some concerns about pain or side effects for the new vaccine and Tdap when given together. However, a study of coadministration of MedACWY-TT and Tdap, compared with Tdap alone, showed no impact on geometric mean titer ratios.
Overall, the Work Group concluded that “desirable effects outweigh undesirable effects” and that the data favor the inclusion of MenACWY-TT as an option for meningococcal vaccination.
The committee members and Dr. McNamara had no relevant financial conflicts to disclose.
No changes to the current meningococcal vaccination recommendations were made. The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) voted 14-0 to include MenACWY-TT as an option for vaccination against meningococcal serogroups A, C, W, and Y in the VFC program. The vote took place in a virtual meeting held on June 24.
The currently available MenACWY vaccines in the United States are MenACWY-D (Menactra), MenACWY-CRW (Menveo), and MenACWY-TT (MedQuadfi), with MenACWY-TT approved by the Food and Drug Administration in April 2020.
Meningococcal vaccination is currently recommended for adolescents, with one dose at age 11 or 12 years and a booster at age 16 years, as well as individuals aged 2 months and older at increased risk for meningococcal disease, according to Lucy McNamara, PhD, of the CDC’s National Center for Immunization and Respiratory Diseases.
Dr. McNamara presented considerations from the Meningococcal Work Group, which determined that the inclusion of MenACWY-TT “is of public health importance given recent vaccine licensure and to support security of vaccine supply.”
The Work Group reviewed 10 studies (phase 2 or 3) of MenACWY-TT that included data on short-term immune response, persistence of immune response, immune interference because of coadministration with other routine adolescent vaccines, and incidence of serious adverse events. Overall, the data showed noninferiority of MenACWY-TT, compared with other available products, in terms of response rates, as well as higher levels of immune response in some studies. Serious adverse events were similar, and none determined to be associated with the vaccines.
ACIP member Paul Hunter, MD, of the University of Milwaukee, Wisc., expressed some concerns about pain or side effects for the new vaccine and Tdap when given together. However, a study of coadministration of MedACWY-TT and Tdap, compared with Tdap alone, showed no impact on geometric mean titer ratios.
Overall, the Work Group concluded that “desirable effects outweigh undesirable effects” and that the data favor the inclusion of MenACWY-TT as an option for meningococcal vaccination.
The committee members and Dr. McNamara had no relevant financial conflicts to disclose.
HSCT may be best option for therapy-related ALL
Therapy-related acute lymphoblastic leukemia (tALL) is less common and less well known than therapy-related acute myeloid leukemia, but tALL also appears to be associated with poor-prognosis features, compared with de novo ALL, investigators said.
“Currently, this condition is not fully recognized by the [World Health Organization] classification, but it has emerged as a relevant and increasingly common form of ALL. There is no standardized therapy for tALL at this time due to the rarity of the condition. Therefore, more information regarding characteristics, prognosis, and treatment is needed,” wrote Brayan Merchán, MD, and colleagues at Princess Margaret Hospital in Toronto.
At their center, the median overall survival (OS) among 58 patients with tALL who received front line induction therapy was 13 months, although patients who were able to undergo hematopoietic stem cell transplant had a 400% longer OS than patients who did not receive HSCT, they reported in an electronic poster presented as part of the virtual annual congress of the European Hematology Association.
A hematologist-oncologist who has studied tALL agreed that it appears to be a distinct clinical entity from de novo ALL.
“It is distinct from the other ALL because the age [at diagnosis] is different, the cytogenetic and molecular profiles are different, and while responses are the same, it seems that survival is lower in cases who don’t go through bone marrow transplant as consolidation,” said Ibrahim Aldoss, MD, from City of Hope Medical Center in Duarte, Calif.
Dr. Aldoss, who was not involved in the study, was the lead author of a study published in 2018 which found that, “[a]lthough survival of therapy-related acute lymphoblastic leukemia was inferior to de novo cases, allogeneic hematopoietic cell transplantation outcomes were comparable for the two entities” (Haematologica. 2018 Oct; 103[10]:1662-8).
He noted that induction regimen options for patients with tALL may be limited because some patients may had previous exposures to cytotoxic chemotherapy agents – such as anthracyclines used in standard regimens for breast cancer – that have cumulative toxicities and lifetime dose limits.
In addition, “these patients tend to be older, because they went through another cancer and then developed therapy-related ALL, and usually they’re not eligible for pediatric-inspired regimens that we use more frequently in younger patients,” he said.
Retrospective study
Dr. Merchán and colleagues conducted a retrospective study of all consecutive adults with ALL treated at their center from 1999 to 2019 and followed until January 2020. Of this group, they identified 59 patients who had been exposed to chemotherapy or radiation for other diseases prior to their ALL diagnosis.
The mean age of the 59 patients (31 women and 28 men) was 54.7 years. In all, 34 had solid cancers and 25 had hematologic malignancies before their ALL diagnosis. The most common diagnosis was breast cancer in 15 patients, followed by multiple myeloma in 11, lymphoma in 7, and AML in 5. Other prior diagnoses were not specified.
Prior therapies included chemotherapy alone in 18 patients, radiotherapy alone in 19, and 20 had both treatment modalities (information about 2 remaining patients was not presented).
For the overall population the median time to tALL diagnosis was 5 years, but for 9 patients with the poor-prognosis MLL gene rearrangement the median time to tALL was just 21 months. The disease latency period was 21 months for patients who received chemotherapy, compared with 117 months for patients treated with radiotherapy.
The majority of patients (53) had B-phenotype ALL. Of the 49 for whom cytogenetic data were available, 41 had cytogenetic abnormalities, including the MLL rearrangement in 9, and complex karyotype in 7. Of all 59 patients, 12 had translocation t(9;22).
One patient did not undergo induction therapy for ALL because of poor performance status. All of the other patients received induction therapy, either a Dana-Farber Cancer Institute protocol in 44 patients, hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) in 5, or blinatumomab in 3.
A complete response was seen in 41 patients (70%); 7 patients died during induction from causes attributed to therapy.
The mean follow-up for all patients was 27 months, and median overall survival was 13 months.
Median overall survival was 98 months for patients who underwent allogeneic HSCT versus a median of 19 months for patients who did not undergo transplant. This difference was not statistically significant, however, likely because of the small sample size.
Causes of death in 11 patients after transplant included relapse in 4 and graft-versus-host disease in 2 (other causes were not specified). Among the 34 patients who did not undergo HSCT following induction, 15 died from disease progression.
“From our results, tALL patients who were able to receive HSCT had better OS. Our data also supports the notion that tALL may be distinct entity with poor prognosis features compared to de novo ALL,” the investigators concluded.
The authors did not disclose a funding source. Dr. Merchán and Dr. Aldoss reported no relevant disclosures.
SOURCE: Merchán B et al. EHA25, Abstract EP391.
Therapy-related acute lymphoblastic leukemia (tALL) is less common and less well known than therapy-related acute myeloid leukemia, but tALL also appears to be associated with poor-prognosis features, compared with de novo ALL, investigators said.
“Currently, this condition is not fully recognized by the [World Health Organization] classification, but it has emerged as a relevant and increasingly common form of ALL. There is no standardized therapy for tALL at this time due to the rarity of the condition. Therefore, more information regarding characteristics, prognosis, and treatment is needed,” wrote Brayan Merchán, MD, and colleagues at Princess Margaret Hospital in Toronto.
At their center, the median overall survival (OS) among 58 patients with tALL who received front line induction therapy was 13 months, although patients who were able to undergo hematopoietic stem cell transplant had a 400% longer OS than patients who did not receive HSCT, they reported in an electronic poster presented as part of the virtual annual congress of the European Hematology Association.
A hematologist-oncologist who has studied tALL agreed that it appears to be a distinct clinical entity from de novo ALL.
“It is distinct from the other ALL because the age [at diagnosis] is different, the cytogenetic and molecular profiles are different, and while responses are the same, it seems that survival is lower in cases who don’t go through bone marrow transplant as consolidation,” said Ibrahim Aldoss, MD, from City of Hope Medical Center in Duarte, Calif.
Dr. Aldoss, who was not involved in the study, was the lead author of a study published in 2018 which found that, “[a]lthough survival of therapy-related acute lymphoblastic leukemia was inferior to de novo cases, allogeneic hematopoietic cell transplantation outcomes were comparable for the two entities” (Haematologica. 2018 Oct; 103[10]:1662-8).
He noted that induction regimen options for patients with tALL may be limited because some patients may had previous exposures to cytotoxic chemotherapy agents – such as anthracyclines used in standard regimens for breast cancer – that have cumulative toxicities and lifetime dose limits.
In addition, “these patients tend to be older, because they went through another cancer and then developed therapy-related ALL, and usually they’re not eligible for pediatric-inspired regimens that we use more frequently in younger patients,” he said.
Retrospective study
Dr. Merchán and colleagues conducted a retrospective study of all consecutive adults with ALL treated at their center from 1999 to 2019 and followed until January 2020. Of this group, they identified 59 patients who had been exposed to chemotherapy or radiation for other diseases prior to their ALL diagnosis.
The mean age of the 59 patients (31 women and 28 men) was 54.7 years. In all, 34 had solid cancers and 25 had hematologic malignancies before their ALL diagnosis. The most common diagnosis was breast cancer in 15 patients, followed by multiple myeloma in 11, lymphoma in 7, and AML in 5. Other prior diagnoses were not specified.
Prior therapies included chemotherapy alone in 18 patients, radiotherapy alone in 19, and 20 had both treatment modalities (information about 2 remaining patients was not presented).
For the overall population the median time to tALL diagnosis was 5 years, but for 9 patients with the poor-prognosis MLL gene rearrangement the median time to tALL was just 21 months. The disease latency period was 21 months for patients who received chemotherapy, compared with 117 months for patients treated with radiotherapy.
The majority of patients (53) had B-phenotype ALL. Of the 49 for whom cytogenetic data were available, 41 had cytogenetic abnormalities, including the MLL rearrangement in 9, and complex karyotype in 7. Of all 59 patients, 12 had translocation t(9;22).
One patient did not undergo induction therapy for ALL because of poor performance status. All of the other patients received induction therapy, either a Dana-Farber Cancer Institute protocol in 44 patients, hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) in 5, or blinatumomab in 3.
A complete response was seen in 41 patients (70%); 7 patients died during induction from causes attributed to therapy.
The mean follow-up for all patients was 27 months, and median overall survival was 13 months.
Median overall survival was 98 months for patients who underwent allogeneic HSCT versus a median of 19 months for patients who did not undergo transplant. This difference was not statistically significant, however, likely because of the small sample size.
Causes of death in 11 patients after transplant included relapse in 4 and graft-versus-host disease in 2 (other causes were not specified). Among the 34 patients who did not undergo HSCT following induction, 15 died from disease progression.
“From our results, tALL patients who were able to receive HSCT had better OS. Our data also supports the notion that tALL may be distinct entity with poor prognosis features compared to de novo ALL,” the investigators concluded.
The authors did not disclose a funding source. Dr. Merchán and Dr. Aldoss reported no relevant disclosures.
SOURCE: Merchán B et al. EHA25, Abstract EP391.
Therapy-related acute lymphoblastic leukemia (tALL) is less common and less well known than therapy-related acute myeloid leukemia, but tALL also appears to be associated with poor-prognosis features, compared with de novo ALL, investigators said.
“Currently, this condition is not fully recognized by the [World Health Organization] classification, but it has emerged as a relevant and increasingly common form of ALL. There is no standardized therapy for tALL at this time due to the rarity of the condition. Therefore, more information regarding characteristics, prognosis, and treatment is needed,” wrote Brayan Merchán, MD, and colleagues at Princess Margaret Hospital in Toronto.
At their center, the median overall survival (OS) among 58 patients with tALL who received front line induction therapy was 13 months, although patients who were able to undergo hematopoietic stem cell transplant had a 400% longer OS than patients who did not receive HSCT, they reported in an electronic poster presented as part of the virtual annual congress of the European Hematology Association.
A hematologist-oncologist who has studied tALL agreed that it appears to be a distinct clinical entity from de novo ALL.
“It is distinct from the other ALL because the age [at diagnosis] is different, the cytogenetic and molecular profiles are different, and while responses are the same, it seems that survival is lower in cases who don’t go through bone marrow transplant as consolidation,” said Ibrahim Aldoss, MD, from City of Hope Medical Center in Duarte, Calif.
Dr. Aldoss, who was not involved in the study, was the lead author of a study published in 2018 which found that, “[a]lthough survival of therapy-related acute lymphoblastic leukemia was inferior to de novo cases, allogeneic hematopoietic cell transplantation outcomes were comparable for the two entities” (Haematologica. 2018 Oct; 103[10]:1662-8).
He noted that induction regimen options for patients with tALL may be limited because some patients may had previous exposures to cytotoxic chemotherapy agents – such as anthracyclines used in standard regimens for breast cancer – that have cumulative toxicities and lifetime dose limits.
In addition, “these patients tend to be older, because they went through another cancer and then developed therapy-related ALL, and usually they’re not eligible for pediatric-inspired regimens that we use more frequently in younger patients,” he said.
Retrospective study
Dr. Merchán and colleagues conducted a retrospective study of all consecutive adults with ALL treated at their center from 1999 to 2019 and followed until January 2020. Of this group, they identified 59 patients who had been exposed to chemotherapy or radiation for other diseases prior to their ALL diagnosis.
The mean age of the 59 patients (31 women and 28 men) was 54.7 years. In all, 34 had solid cancers and 25 had hematologic malignancies before their ALL diagnosis. The most common diagnosis was breast cancer in 15 patients, followed by multiple myeloma in 11, lymphoma in 7, and AML in 5. Other prior diagnoses were not specified.
Prior therapies included chemotherapy alone in 18 patients, radiotherapy alone in 19, and 20 had both treatment modalities (information about 2 remaining patients was not presented).
For the overall population the median time to tALL diagnosis was 5 years, but for 9 patients with the poor-prognosis MLL gene rearrangement the median time to tALL was just 21 months. The disease latency period was 21 months for patients who received chemotherapy, compared with 117 months for patients treated with radiotherapy.
The majority of patients (53) had B-phenotype ALL. Of the 49 for whom cytogenetic data were available, 41 had cytogenetic abnormalities, including the MLL rearrangement in 9, and complex karyotype in 7. Of all 59 patients, 12 had translocation t(9;22).
One patient did not undergo induction therapy for ALL because of poor performance status. All of the other patients received induction therapy, either a Dana-Farber Cancer Institute protocol in 44 patients, hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) in 5, or blinatumomab in 3.
A complete response was seen in 41 patients (70%); 7 patients died during induction from causes attributed to therapy.
The mean follow-up for all patients was 27 months, and median overall survival was 13 months.
Median overall survival was 98 months for patients who underwent allogeneic HSCT versus a median of 19 months for patients who did not undergo transplant. This difference was not statistically significant, however, likely because of the small sample size.
Causes of death in 11 patients after transplant included relapse in 4 and graft-versus-host disease in 2 (other causes were not specified). Among the 34 patients who did not undergo HSCT following induction, 15 died from disease progression.
“From our results, tALL patients who were able to receive HSCT had better OS. Our data also supports the notion that tALL may be distinct entity with poor prognosis features compared to de novo ALL,” the investigators concluded.
The authors did not disclose a funding source. Dr. Merchán and Dr. Aldoss reported no relevant disclosures.
SOURCE: Merchán B et al. EHA25, Abstract EP391.
FROM EHA CONGRESS
Marijuana for migraine? Some tentative evidence
according to results from a small study conducted at the Jefferson Headache Center at Thomas Jefferson University. The researchers found general satisfaction with medical marijuana, more frequent use as an abortive medication rather than a preventative, and more than two-thirds using the inhaled form rather than oral.
Many patients ask about medical marijuana, but there is relatively little data on its effects on headache. Studies are generally retrospective, and often focus on marijuana use for general pain, with subset analyses looking at headache, according to coauthor Claire Ceriani, MD, who is a headache fellow at Jefferson. “A lot of patients are interested in medical marijuana but don’t know how to integrate it into the therapy plan they already have – whether it should be just to treat bad headaches when they happen, or is it meant to be a preventive medicine they use every day? We have some data out there that it can be helpful, but not a lot of specific information to guide your recommendations,” said Dr. Ceriani in an interview.
Although the research is far from a final word on the subject, it did have some take-home messages, said Dr. Ceriani. “Most people seem to find it effective as an abortive medication that might be able to take the place of some of the prescription medications that they were previously using,” she said.
The study was part of the virtual annual meeting of the American Headache Society.
An effective abortive therapy?
The study began shortly after the Jefferson Headache Center became certified to offer medical marijuana around the beginning of 2019. “We wanted to start keeping track of these patients from the get-go so we’d be able to learn as much as possible from them and help guide the recommendations we give to patients in the future,” said Dr. Ceriani.
The study included 48 patients with migraine or other types of chronic headache who received medical marijuana treatment between January and September 2019. After collecting baseline information from medical records and questionnaires filled out at marijuana treatment initiation, the researchers followed up periodically with telephone questionnaires to assess treatment response and side effects. About half of the participants (56.3%) reported daily headache. 14.6% had posttraumatic headache, 10.4% new daily persistent headache, and 4.2% tension-type headache. Additional symptoms were common, including anxiety (72.9%) and insomnia (62.5%).
A total of 28 subjects completed a follow-up questionnaire over the phone. Out of the 28 participants , 3 had stopped using marijuana. Of 25 subjects who continued use, 71.4% used it two or more times per week, and 25.0% used it every day. Among participants, 50% used a THC-dominant strain of marijuana. Overall, 71.4% used an inhaled form.
Side effects included dry mouth/throat (46.4%), dry/red eyes (35.7%), fatigue/lethargy (35.7%), and increased appetite (35.7%).
Before starting on marijuana, 46.4% of the subjects used abortive medications at least 10 days per month. After starting marijuana treatment, the rate dropped to 25.0%. Marijuana use was associated with improvements in anxiety: 57.1% who had anxiety reported improvement with marijuana use, as did 78.6% with insomnia. On a scale of 10, the average rating of marijuana’s usefulness was 5.9, and 17.9% rated it as 10.
Several concerns
The study has numerous limitations. It has a small sample size, it is from a single center, and the patient population had relatively severe symptoms. Such studies are “fraught with possible bias,” said Andrew Charles, MD, professor of neurology and director of the UCLA Goldberg Migraine Program, when asked to comment.
He pointed out that one key concern for marijuana is concerns over worsening of the condition or refractoriness caused by medication overuse. The cannabinoid receptors it acts on bear some similarity to opioid receptors, and opioid overuse headache is well known. The recent changes in marijuana laws makes it an important issue, one that patients often asked about. But prospective clinical trials face a range of roadblocks: Marijuana remains a controlled substance, it would be difficult to create a placebo control, and no large companies are likely to sponsor such a trial.
“But I think it’s important to keep talking about and developing evidence as much as we can and addressing not just the benefits but also being keenly aware of the possible adverse effects, especially medication overuse,” said Dr. Charles.
The authors also acknowledged the study’s limitations, “but I think there is value, because there are definitely specific patterns we were able to find in terms of what’s helpful for patients, and we also found that a lot of patients also have other disorders in addition to headache, like anxiety and insomnia. And we found that those patients in particular seemed to have more benefit than most with medical marijuana,” said coauthor Angela Hou, MD, who is also a headache fellow at Jefferson.
Dr. Hou and Dr. Ceriani cautioned against use of marijuana in any patient with a substance use disorder, as well as the inhaled form in patients with chronic lung conditions.
The study received no funding. Dr. Ceriani and Dr. Hou had no relevant financial disclosures. Dr. Charles has consulted for Amgen, Biohaven, Eli Lilly, Novartis, and Lundbeck.
SOURCE: Marmura MJ et al. AHS 2020, Abstract 842679.
according to results from a small study conducted at the Jefferson Headache Center at Thomas Jefferson University. The researchers found general satisfaction with medical marijuana, more frequent use as an abortive medication rather than a preventative, and more than two-thirds using the inhaled form rather than oral.
Many patients ask about medical marijuana, but there is relatively little data on its effects on headache. Studies are generally retrospective, and often focus on marijuana use for general pain, with subset analyses looking at headache, according to coauthor Claire Ceriani, MD, who is a headache fellow at Jefferson. “A lot of patients are interested in medical marijuana but don’t know how to integrate it into the therapy plan they already have – whether it should be just to treat bad headaches when they happen, or is it meant to be a preventive medicine they use every day? We have some data out there that it can be helpful, but not a lot of specific information to guide your recommendations,” said Dr. Ceriani in an interview.
Although the research is far from a final word on the subject, it did have some take-home messages, said Dr. Ceriani. “Most people seem to find it effective as an abortive medication that might be able to take the place of some of the prescription medications that they were previously using,” she said.
The study was part of the virtual annual meeting of the American Headache Society.
An effective abortive therapy?
The study began shortly after the Jefferson Headache Center became certified to offer medical marijuana around the beginning of 2019. “We wanted to start keeping track of these patients from the get-go so we’d be able to learn as much as possible from them and help guide the recommendations we give to patients in the future,” said Dr. Ceriani.
The study included 48 patients with migraine or other types of chronic headache who received medical marijuana treatment between January and September 2019. After collecting baseline information from medical records and questionnaires filled out at marijuana treatment initiation, the researchers followed up periodically with telephone questionnaires to assess treatment response and side effects. About half of the participants (56.3%) reported daily headache. 14.6% had posttraumatic headache, 10.4% new daily persistent headache, and 4.2% tension-type headache. Additional symptoms were common, including anxiety (72.9%) and insomnia (62.5%).
A total of 28 subjects completed a follow-up questionnaire over the phone. Out of the 28 participants , 3 had stopped using marijuana. Of 25 subjects who continued use, 71.4% used it two or more times per week, and 25.0% used it every day. Among participants, 50% used a THC-dominant strain of marijuana. Overall, 71.4% used an inhaled form.
Side effects included dry mouth/throat (46.4%), dry/red eyes (35.7%), fatigue/lethargy (35.7%), and increased appetite (35.7%).
Before starting on marijuana, 46.4% of the subjects used abortive medications at least 10 days per month. After starting marijuana treatment, the rate dropped to 25.0%. Marijuana use was associated with improvements in anxiety: 57.1% who had anxiety reported improvement with marijuana use, as did 78.6% with insomnia. On a scale of 10, the average rating of marijuana’s usefulness was 5.9, and 17.9% rated it as 10.
Several concerns
The study has numerous limitations. It has a small sample size, it is from a single center, and the patient population had relatively severe symptoms. Such studies are “fraught with possible bias,” said Andrew Charles, MD, professor of neurology and director of the UCLA Goldberg Migraine Program, when asked to comment.
He pointed out that one key concern for marijuana is concerns over worsening of the condition or refractoriness caused by medication overuse. The cannabinoid receptors it acts on bear some similarity to opioid receptors, and opioid overuse headache is well known. The recent changes in marijuana laws makes it an important issue, one that patients often asked about. But prospective clinical trials face a range of roadblocks: Marijuana remains a controlled substance, it would be difficult to create a placebo control, and no large companies are likely to sponsor such a trial.
“But I think it’s important to keep talking about and developing evidence as much as we can and addressing not just the benefits but also being keenly aware of the possible adverse effects, especially medication overuse,” said Dr. Charles.
The authors also acknowledged the study’s limitations, “but I think there is value, because there are definitely specific patterns we were able to find in terms of what’s helpful for patients, and we also found that a lot of patients also have other disorders in addition to headache, like anxiety and insomnia. And we found that those patients in particular seemed to have more benefit than most with medical marijuana,” said coauthor Angela Hou, MD, who is also a headache fellow at Jefferson.
Dr. Hou and Dr. Ceriani cautioned against use of marijuana in any patient with a substance use disorder, as well as the inhaled form in patients with chronic lung conditions.
The study received no funding. Dr. Ceriani and Dr. Hou had no relevant financial disclosures. Dr. Charles has consulted for Amgen, Biohaven, Eli Lilly, Novartis, and Lundbeck.
SOURCE: Marmura MJ et al. AHS 2020, Abstract 842679.
according to results from a small study conducted at the Jefferson Headache Center at Thomas Jefferson University. The researchers found general satisfaction with medical marijuana, more frequent use as an abortive medication rather than a preventative, and more than two-thirds using the inhaled form rather than oral.
Many patients ask about medical marijuana, but there is relatively little data on its effects on headache. Studies are generally retrospective, and often focus on marijuana use for general pain, with subset analyses looking at headache, according to coauthor Claire Ceriani, MD, who is a headache fellow at Jefferson. “A lot of patients are interested in medical marijuana but don’t know how to integrate it into the therapy plan they already have – whether it should be just to treat bad headaches when they happen, or is it meant to be a preventive medicine they use every day? We have some data out there that it can be helpful, but not a lot of specific information to guide your recommendations,” said Dr. Ceriani in an interview.
Although the research is far from a final word on the subject, it did have some take-home messages, said Dr. Ceriani. “Most people seem to find it effective as an abortive medication that might be able to take the place of some of the prescription medications that they were previously using,” she said.
The study was part of the virtual annual meeting of the American Headache Society.
An effective abortive therapy?
The study began shortly after the Jefferson Headache Center became certified to offer medical marijuana around the beginning of 2019. “We wanted to start keeping track of these patients from the get-go so we’d be able to learn as much as possible from them and help guide the recommendations we give to patients in the future,” said Dr. Ceriani.
The study included 48 patients with migraine or other types of chronic headache who received medical marijuana treatment between January and September 2019. After collecting baseline information from medical records and questionnaires filled out at marijuana treatment initiation, the researchers followed up periodically with telephone questionnaires to assess treatment response and side effects. About half of the participants (56.3%) reported daily headache. 14.6% had posttraumatic headache, 10.4% new daily persistent headache, and 4.2% tension-type headache. Additional symptoms were common, including anxiety (72.9%) and insomnia (62.5%).
A total of 28 subjects completed a follow-up questionnaire over the phone. Out of the 28 participants , 3 had stopped using marijuana. Of 25 subjects who continued use, 71.4% used it two or more times per week, and 25.0% used it every day. Among participants, 50% used a THC-dominant strain of marijuana. Overall, 71.4% used an inhaled form.
Side effects included dry mouth/throat (46.4%), dry/red eyes (35.7%), fatigue/lethargy (35.7%), and increased appetite (35.7%).
Before starting on marijuana, 46.4% of the subjects used abortive medications at least 10 days per month. After starting marijuana treatment, the rate dropped to 25.0%. Marijuana use was associated with improvements in anxiety: 57.1% who had anxiety reported improvement with marijuana use, as did 78.6% with insomnia. On a scale of 10, the average rating of marijuana’s usefulness was 5.9, and 17.9% rated it as 10.
Several concerns
The study has numerous limitations. It has a small sample size, it is from a single center, and the patient population had relatively severe symptoms. Such studies are “fraught with possible bias,” said Andrew Charles, MD, professor of neurology and director of the UCLA Goldberg Migraine Program, when asked to comment.
He pointed out that one key concern for marijuana is concerns over worsening of the condition or refractoriness caused by medication overuse. The cannabinoid receptors it acts on bear some similarity to opioid receptors, and opioid overuse headache is well known. The recent changes in marijuana laws makes it an important issue, one that patients often asked about. But prospective clinical trials face a range of roadblocks: Marijuana remains a controlled substance, it would be difficult to create a placebo control, and no large companies are likely to sponsor such a trial.
“But I think it’s important to keep talking about and developing evidence as much as we can and addressing not just the benefits but also being keenly aware of the possible adverse effects, especially medication overuse,” said Dr. Charles.
The authors also acknowledged the study’s limitations, “but I think there is value, because there are definitely specific patterns we were able to find in terms of what’s helpful for patients, and we also found that a lot of patients also have other disorders in addition to headache, like anxiety and insomnia. And we found that those patients in particular seemed to have more benefit than most with medical marijuana,” said coauthor Angela Hou, MD, who is also a headache fellow at Jefferson.
Dr. Hou and Dr. Ceriani cautioned against use of marijuana in any patient with a substance use disorder, as well as the inhaled form in patients with chronic lung conditions.
The study received no funding. Dr. Ceriani and Dr. Hou had no relevant financial disclosures. Dr. Charles has consulted for Amgen, Biohaven, Eli Lilly, Novartis, and Lundbeck.
SOURCE: Marmura MJ et al. AHS 2020, Abstract 842679.
FROM AHS 2020
Surge in colonoscopies postponed by COVID-19 expected
An expected surge in the number of people seeking colonoscopy after the peak of the COVID-19 pandemic passes could cause physicians to rethink patient prioritization, could create a strain on endoscopy capacity, and might raise the specter of detecting colorectal cancer in more patients at a later stage of disease.
Furthermore, months of delay in diagnosis of colorectal cancer (CRC) could shorten survival, although more data is needed, according to expert analysis from a gastroenterologist, a medical oncologist, and a colorectal surgeon.
“It has been a big decrease in the number of colonoscopies performed at our hospital in Alicante, Spain,” Rodrigo Jover Martinez, MD, PhD, said during a COVID-19 and Digestive Health webinar presented by United European Gastroenterology (UEG). He estimated colonoscopy procedures are down 60%-90%, and the number of CRC surgeries has dropped by 60%. “As you know, the COVID-19 pandemic is hitting Europe hard.”
When patients do return, “the backlog will be huge ... in already exhausted endoscopy units,” predicted Dr. Martinez, a gastroenterologist at Hospital General Universitario in Alicante.
Multiple risks
Not knowing which patients with CRC will develop severe COVID-19 infection is another challenge, Bartomeu Massuti, MD, of the medical oncology service at the Hospital General Universitario de Alicante, said during the webinar.
Caution is warranted because “we know cancer patients have an increased risk of infection.” However, he added, most evidence supports an elevated risk for bacterial infections, not viral infections.
Therefore, physicians must continue to balance the risks associated with potential COVID-19 exposure against the risks associated with postponed treatment, Dr. Massuti said. “The goal of oncology care is to try to maintain the preplanned treatment and follow-up. We need mainly to avoid stopping or delaying treatment ... because we will lose efficacy in oncology disease outcomes.”
Imran Aslam, MD, PhD, a colorectal surgeon who moderated and presented during the webinar, agreed: “By delaying the treatment, we might do harm to our patients.”
Dr. Aslam cited data about clinical costs of delaying CRC surgery. A 2019 population-based study in PLOS ONE evaluated different times from diagnosis to treatment. The researchers found a delay of more than 150 days “significantly reduced survival, even during stage I, II, and III disease,” he said. The stage I hazard ratio was 2.66, compared with a reference HR of 1.00 for 90 days or fewer. They also reported elevated risk for people with stage II CRC (HR, 2.80), stage III CRC (HR, 2.70), and stage IV CRC (HR, 1.36).
“This could become more and more abysmal if the pandemic continues,” added Dr. Aslam, consultant colorectal surgeon at University Hospitals of Coventry and Warwickshire, England.
Prioritizing patients
Restarting endoscopy with prioritization strategies and increasing patient capacity are possible solutions. Dr. Martinez suggested a four-quadrant matrix in which physicians place patients into “now,” “next,” “delayed,” or “never” categories based on clinical indicators. The priority 1 “now” patients, for example, will be those with suspected CRC based on physical examination, imaging results, and/or an abnormal fecal immunochemical test result.
He suggested, furthermore, that more widespread CRC screening can resume once “endoscopy units have been alleviated of priority 1, symptomatic patients.”
Dr. Massuti concurred with Dr. Martinez’s call to prioritize patients carefully. He suggested a green, yellow, and red classification system based on treatment priority recommendations from the European Society for Medical Oncology. The green group, for example, should receive priority for intervention based on a condition that is immediately clinically unstable or life threatening.
“The main goal is to preserve the continuum of care,” he added.
Another concern – although data are limited – is that treatment might also increase risk of mortality among cancer patients with COVID-19, according to a cohort study of nearly 1,000 such patients reported May 2020 in The Lancet. Dr. Massuti, who was not affiliated with the research, noted that 12% of the patients had GI tumors. In addition to increased risk associated with male sex (odds ratio, 1.63), cytotoxic cancer treatment in the prior 4 weeks increased risk (OR, 1.47), as did surgery in the same time frame (OR, 1.52).
“This means patients on treatment have an increased risk of mortality,” Dr. Massuti said.
Moving forward
Implementing telehealth information and communication technologies will continue to grow in importance, Dr. Massuti said. Dr. Aslam noted that video consultation with patients before surgery is already replacing face-to-face interaction, and most follow-up care at his hospital is now done by telephone.
Postoperative care is just as essential in the COVID-19 era, if not more so. “We need to be very vigilant to manage postoperative complications – any symptoms of pyrexia or sepsis, or any sign of COVID,” Dr. Aslam said, including postoperative fever. “If there is any doubt, do a chest CT scan.”
Dr. Aslam predicted the time to perform endoscopy or surgery for each patient will be longer, “so the number of patients done in 1 day will be less than 4 months ago.” In addition, elective surgery patients at his institution undergo COVID-19 testing twice, 3 days apart, prior to intervention.
“This disease will continue in the community for a while, so we have to continue what we’ve done well, like social distancing,” Dr. Aslam said. “We’ve gone through a storm and we are awaiting a tsunami. That tsunami of patients will overwhelm us in the coming months.”
Dr. Martinez, Dr. Massuti, and Dr. Aslam had no relevant disclosures.
Medical issues, deferred or neglected during the pandemic, can result in adverse outcomes, and this applies to colorectal cancer (CRC) screening and surveillance. There is a real risk of increased rates of CRC and discovery of CRC at an advanced stage if individuals go unscreened. While colonoscopy remains an important screening option, capacity has been limited during the pandemic. I believe it is important to offer patients screening choices like fecal immunochemical test, and then prioritize patients with positive fecal immunochemical test results for colonoscopy since these patients have a higher risk of CRC, compared with those with negative tests. Patients with a prior history of high-risk adenomas should be prioritized for surveillance colonoscopy.
David Lieberman, MD, past president of the American Gastroenterological Association, professor of medicine and chief of division of gastroenterology and hepatology at Oregon Health and Science University, Portland. He has no conflicts.
Medical issues, deferred or neglected during the pandemic, can result in adverse outcomes, and this applies to colorectal cancer (CRC) screening and surveillance. There is a real risk of increased rates of CRC and discovery of CRC at an advanced stage if individuals go unscreened. While colonoscopy remains an important screening option, capacity has been limited during the pandemic. I believe it is important to offer patients screening choices like fecal immunochemical test, and then prioritize patients with positive fecal immunochemical test results for colonoscopy since these patients have a higher risk of CRC, compared with those with negative tests. Patients with a prior history of high-risk adenomas should be prioritized for surveillance colonoscopy.
David Lieberman, MD, past president of the American Gastroenterological Association, professor of medicine and chief of division of gastroenterology and hepatology at Oregon Health and Science University, Portland. He has no conflicts.
Medical issues, deferred or neglected during the pandemic, can result in adverse outcomes, and this applies to colorectal cancer (CRC) screening and surveillance. There is a real risk of increased rates of CRC and discovery of CRC at an advanced stage if individuals go unscreened. While colonoscopy remains an important screening option, capacity has been limited during the pandemic. I believe it is important to offer patients screening choices like fecal immunochemical test, and then prioritize patients with positive fecal immunochemical test results for colonoscopy since these patients have a higher risk of CRC, compared with those with negative tests. Patients with a prior history of high-risk adenomas should be prioritized for surveillance colonoscopy.
David Lieberman, MD, past president of the American Gastroenterological Association, professor of medicine and chief of division of gastroenterology and hepatology at Oregon Health and Science University, Portland. He has no conflicts.
An expected surge in the number of people seeking colonoscopy after the peak of the COVID-19 pandemic passes could cause physicians to rethink patient prioritization, could create a strain on endoscopy capacity, and might raise the specter of detecting colorectal cancer in more patients at a later stage of disease.
Furthermore, months of delay in diagnosis of colorectal cancer (CRC) could shorten survival, although more data is needed, according to expert analysis from a gastroenterologist, a medical oncologist, and a colorectal surgeon.
“It has been a big decrease in the number of colonoscopies performed at our hospital in Alicante, Spain,” Rodrigo Jover Martinez, MD, PhD, said during a COVID-19 and Digestive Health webinar presented by United European Gastroenterology (UEG). He estimated colonoscopy procedures are down 60%-90%, and the number of CRC surgeries has dropped by 60%. “As you know, the COVID-19 pandemic is hitting Europe hard.”
When patients do return, “the backlog will be huge ... in already exhausted endoscopy units,” predicted Dr. Martinez, a gastroenterologist at Hospital General Universitario in Alicante.
Multiple risks
Not knowing which patients with CRC will develop severe COVID-19 infection is another challenge, Bartomeu Massuti, MD, of the medical oncology service at the Hospital General Universitario de Alicante, said during the webinar.
Caution is warranted because “we know cancer patients have an increased risk of infection.” However, he added, most evidence supports an elevated risk for bacterial infections, not viral infections.
Therefore, physicians must continue to balance the risks associated with potential COVID-19 exposure against the risks associated with postponed treatment, Dr. Massuti said. “The goal of oncology care is to try to maintain the preplanned treatment and follow-up. We need mainly to avoid stopping or delaying treatment ... because we will lose efficacy in oncology disease outcomes.”
Imran Aslam, MD, PhD, a colorectal surgeon who moderated and presented during the webinar, agreed: “By delaying the treatment, we might do harm to our patients.”
Dr. Aslam cited data about clinical costs of delaying CRC surgery. A 2019 population-based study in PLOS ONE evaluated different times from diagnosis to treatment. The researchers found a delay of more than 150 days “significantly reduced survival, even during stage I, II, and III disease,” he said. The stage I hazard ratio was 2.66, compared with a reference HR of 1.00 for 90 days or fewer. They also reported elevated risk for people with stage II CRC (HR, 2.80), stage III CRC (HR, 2.70), and stage IV CRC (HR, 1.36).
“This could become more and more abysmal if the pandemic continues,” added Dr. Aslam, consultant colorectal surgeon at University Hospitals of Coventry and Warwickshire, England.
Prioritizing patients
Restarting endoscopy with prioritization strategies and increasing patient capacity are possible solutions. Dr. Martinez suggested a four-quadrant matrix in which physicians place patients into “now,” “next,” “delayed,” or “never” categories based on clinical indicators. The priority 1 “now” patients, for example, will be those with suspected CRC based on physical examination, imaging results, and/or an abnormal fecal immunochemical test result.
He suggested, furthermore, that more widespread CRC screening can resume once “endoscopy units have been alleviated of priority 1, symptomatic patients.”
Dr. Massuti concurred with Dr. Martinez’s call to prioritize patients carefully. He suggested a green, yellow, and red classification system based on treatment priority recommendations from the European Society for Medical Oncology. The green group, for example, should receive priority for intervention based on a condition that is immediately clinically unstable or life threatening.
“The main goal is to preserve the continuum of care,” he added.
Another concern – although data are limited – is that treatment might also increase risk of mortality among cancer patients with COVID-19, according to a cohort study of nearly 1,000 such patients reported May 2020 in The Lancet. Dr. Massuti, who was not affiliated with the research, noted that 12% of the patients had GI tumors. In addition to increased risk associated with male sex (odds ratio, 1.63), cytotoxic cancer treatment in the prior 4 weeks increased risk (OR, 1.47), as did surgery in the same time frame (OR, 1.52).
“This means patients on treatment have an increased risk of mortality,” Dr. Massuti said.
Moving forward
Implementing telehealth information and communication technologies will continue to grow in importance, Dr. Massuti said. Dr. Aslam noted that video consultation with patients before surgery is already replacing face-to-face interaction, and most follow-up care at his hospital is now done by telephone.
Postoperative care is just as essential in the COVID-19 era, if not more so. “We need to be very vigilant to manage postoperative complications – any symptoms of pyrexia or sepsis, or any sign of COVID,” Dr. Aslam said, including postoperative fever. “If there is any doubt, do a chest CT scan.”
Dr. Aslam predicted the time to perform endoscopy or surgery for each patient will be longer, “so the number of patients done in 1 day will be less than 4 months ago.” In addition, elective surgery patients at his institution undergo COVID-19 testing twice, 3 days apart, prior to intervention.
“This disease will continue in the community for a while, so we have to continue what we’ve done well, like social distancing,” Dr. Aslam said. “We’ve gone through a storm and we are awaiting a tsunami. That tsunami of patients will overwhelm us in the coming months.”
Dr. Martinez, Dr. Massuti, and Dr. Aslam had no relevant disclosures.
An expected surge in the number of people seeking colonoscopy after the peak of the COVID-19 pandemic passes could cause physicians to rethink patient prioritization, could create a strain on endoscopy capacity, and might raise the specter of detecting colorectal cancer in more patients at a later stage of disease.
Furthermore, months of delay in diagnosis of colorectal cancer (CRC) could shorten survival, although more data is needed, according to expert analysis from a gastroenterologist, a medical oncologist, and a colorectal surgeon.
“It has been a big decrease in the number of colonoscopies performed at our hospital in Alicante, Spain,” Rodrigo Jover Martinez, MD, PhD, said during a COVID-19 and Digestive Health webinar presented by United European Gastroenterology (UEG). He estimated colonoscopy procedures are down 60%-90%, and the number of CRC surgeries has dropped by 60%. “As you know, the COVID-19 pandemic is hitting Europe hard.”
When patients do return, “the backlog will be huge ... in already exhausted endoscopy units,” predicted Dr. Martinez, a gastroenterologist at Hospital General Universitario in Alicante.
Multiple risks
Not knowing which patients with CRC will develop severe COVID-19 infection is another challenge, Bartomeu Massuti, MD, of the medical oncology service at the Hospital General Universitario de Alicante, said during the webinar.
Caution is warranted because “we know cancer patients have an increased risk of infection.” However, he added, most evidence supports an elevated risk for bacterial infections, not viral infections.
Therefore, physicians must continue to balance the risks associated with potential COVID-19 exposure against the risks associated with postponed treatment, Dr. Massuti said. “The goal of oncology care is to try to maintain the preplanned treatment and follow-up. We need mainly to avoid stopping or delaying treatment ... because we will lose efficacy in oncology disease outcomes.”
Imran Aslam, MD, PhD, a colorectal surgeon who moderated and presented during the webinar, agreed: “By delaying the treatment, we might do harm to our patients.”
Dr. Aslam cited data about clinical costs of delaying CRC surgery. A 2019 population-based study in PLOS ONE evaluated different times from diagnosis to treatment. The researchers found a delay of more than 150 days “significantly reduced survival, even during stage I, II, and III disease,” he said. The stage I hazard ratio was 2.66, compared with a reference HR of 1.00 for 90 days or fewer. They also reported elevated risk for people with stage II CRC (HR, 2.80), stage III CRC (HR, 2.70), and stage IV CRC (HR, 1.36).
“This could become more and more abysmal if the pandemic continues,” added Dr. Aslam, consultant colorectal surgeon at University Hospitals of Coventry and Warwickshire, England.
Prioritizing patients
Restarting endoscopy with prioritization strategies and increasing patient capacity are possible solutions. Dr. Martinez suggested a four-quadrant matrix in which physicians place patients into “now,” “next,” “delayed,” or “never” categories based on clinical indicators. The priority 1 “now” patients, for example, will be those with suspected CRC based on physical examination, imaging results, and/or an abnormal fecal immunochemical test result.
He suggested, furthermore, that more widespread CRC screening can resume once “endoscopy units have been alleviated of priority 1, symptomatic patients.”
Dr. Massuti concurred with Dr. Martinez’s call to prioritize patients carefully. He suggested a green, yellow, and red classification system based on treatment priority recommendations from the European Society for Medical Oncology. The green group, for example, should receive priority for intervention based on a condition that is immediately clinically unstable or life threatening.
“The main goal is to preserve the continuum of care,” he added.
Another concern – although data are limited – is that treatment might also increase risk of mortality among cancer patients with COVID-19, according to a cohort study of nearly 1,000 such patients reported May 2020 in The Lancet. Dr. Massuti, who was not affiliated with the research, noted that 12% of the patients had GI tumors. In addition to increased risk associated with male sex (odds ratio, 1.63), cytotoxic cancer treatment in the prior 4 weeks increased risk (OR, 1.47), as did surgery in the same time frame (OR, 1.52).
“This means patients on treatment have an increased risk of mortality,” Dr. Massuti said.
Moving forward
Implementing telehealth information and communication technologies will continue to grow in importance, Dr. Massuti said. Dr. Aslam noted that video consultation with patients before surgery is already replacing face-to-face interaction, and most follow-up care at his hospital is now done by telephone.
Postoperative care is just as essential in the COVID-19 era, if not more so. “We need to be very vigilant to manage postoperative complications – any symptoms of pyrexia or sepsis, or any sign of COVID,” Dr. Aslam said, including postoperative fever. “If there is any doubt, do a chest CT scan.”
Dr. Aslam predicted the time to perform endoscopy or surgery for each patient will be longer, “so the number of patients done in 1 day will be less than 4 months ago.” In addition, elective surgery patients at his institution undergo COVID-19 testing twice, 3 days apart, prior to intervention.
“This disease will continue in the community for a while, so we have to continue what we’ve done well, like social distancing,” Dr. Aslam said. “We’ve gone through a storm and we are awaiting a tsunami. That tsunami of patients will overwhelm us in the coming months.”
Dr. Martinez, Dr. Massuti, and Dr. Aslam had no relevant disclosures.
Isa-Kd improves PFS in relapsed/refractory multiple myeloma
The risk of progression or death for patients with relapsed or refractory multiple myeloma was nearly halved with the addition of isatuximab to carfilzomib and dexamethasone, according to an interim analysis of the phase 3 IKEMA trial (NCT03275285).
After a median follow-up of 20.7 months, the median progression-free survival had not been reached for 179 patients treated with isatuximab (Sarclisa), carfilzomib (Kyprolis), and dexamethasone (together, known as Isa-Kd), compared with 19.5 months for 123 patients treated with carfilzomib and dexamethasone alone (Kd). The hazard ratio for progression free survival with the triple combination was 0.531 (P = .0007), reported coprincipal investigator Phillipe Moreau, MD, from the University Hospital Hôtel-Dieu in Nantes, France.
“The benefit of the triplet combination was observed across subgroups, including patients difficult to treat, such as [those with] high-risk cytogenetics or elderly patients,” he said in a late-breaking abstract presentation during the virtual annual congress of the European Hematology Association.
Isatuximab is an immunoglobulin G1 monoclonal antibody targeting a CD38 transmembrane glycoprotein on multiple myeloma cells, with a mechanism of action similar to that of another anti-CD38 antibody, daratumumab (Darzalex). Isatuximab is approved in the United States and Europe in combination with pomalidomide and dexamethasone for patients with relapsed/refractory multiple myeloma after at least two prior lines of therapy.
A ‘me too’ agent?
It’s unclear, however, whether isatuximab offers any additional benefit over daratumumab, an agent approved for use both in front line therapy combinations and for patients with relapsed/refractory disease, said Brea C. Lipe, MD, a multiple myeloma specialist at the University of Rochester (N.Y.) Wilmot Cancer Institute, who was not involved in the study.
“Every time we get a new drug it’s nice to have another option, but it doesn’t really add anything different from daratumumab at this point,” she said in an interview.
Dr. Lipe noted the IKEMA results are similar to those seen in the phase 3 CANDOR trial, comparing carfilzomib, dexamethasone, and daratumumab to carfilzomib/dexamethasone alone in patients with relapsed/refractory myeloma. In addition, it’s unknown whether patients with disease that is refractory to daratumumab could benefit from isatuximab, she said.
Although isatuximab has been touted as offering more rapid and more convenient dosing than daratumumab, the introduction of rapid infusion and subcutaneous administration of daratumumab has negated any theoretical advantage of the newcomer, Dr. Lipe added.
Study details
In the IKEMA trial, 302 patients with relapsed/refractory multiple myeloma who’d received one to three prior lines of therapy were stratified by the number of prior lines and by revised Multiple Myeloma International Staging System (R-ISS) and were then randomized on a 3:2 basis to treatment with carfilzomib 20 mg/m2 on days 1, 2, 8, 9, 15, and 16 of cycle 1 and 56 mg/m2 on the corresponding days of each subsequent cycle plus dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle, with or without isatuximab. The antibody was dosed 10 mg/kg on days 1, 8, 15, and 22 in cycle 1 then every 2 weeks thereafter.
Treatments were continued until disease progression, unacceptable toxicity, or patient choice intervened.
At a prespecified interim analysis, the trial met its primary endpoint of a minimum 41% risk reduction in the hazard rate for progression free survival (PFS), with an actual risk reduction of 47%.
An analysis of PFS by subgroup showed significant benefits with the triple combination for patients aged 65 years and older, those with baseline estimated glomerular filtration rates below 60 mL/min per 1.73 m2, those with more than one prior line of therapy, those who had not previously received a proteasome inhibitor (e.g., bortezomib) or immunomodulatory agent (e.g., lenalidomide), those with high-risk cytogenetic status, and those with R-ISS stage II at study entry.
Overall response rates were similar between the study arms, at 86.6% with Isa-Kd and 82.9% with Kd, but the rate of very good partial responses or better was significantly higher with the triplet, at 72.6% versus 56.1% (P = .0011). The rate of minimal residual disease negativity was also significantly lower with Isa-Kd in the intent-to-treat population, at 29.6% versus 13%, respectively (P = .0004).
Overall survival data were not mature at the time of data cutoff and will be reported later, Dr. Moreau said.
Grade 3 or greater treatment-emergent adverse events (TEAEs) occurred in 76.8% of patients on the triplet and 67.2% of those on Kd. The incidences of death, serious TEAEs, or adverse events leading to discontinuation of therapy did not differ markedly between the treatment arms, however. Grade 3 or greater cardiac failure occurred in seven patients treated with the triplet (4%) and five treated with Kd (4.1%); respective rates of grade 3 or greater hematologic abnormalities included anemia in 22% and 19.7%, neutropenia in 19.2% and 7.4%, and thrombocytopenia in 29.9% and 23.8%.
The primary completion date for the trial is estimated to occur in November 2020, with final results in November 2023.
The study was sponsored by Sanofi. Dr. Moreau disclosed honoraria and a consulting or advisory role with several companies, not including Sanofi. Dr. Lipe disclosed impending advisory board activity for Janssen.
SOURCE: Moreau P et al. EHA Congress, Abstract LB2603.
The risk of progression or death for patients with relapsed or refractory multiple myeloma was nearly halved with the addition of isatuximab to carfilzomib and dexamethasone, according to an interim analysis of the phase 3 IKEMA trial (NCT03275285).
After a median follow-up of 20.7 months, the median progression-free survival had not been reached for 179 patients treated with isatuximab (Sarclisa), carfilzomib (Kyprolis), and dexamethasone (together, known as Isa-Kd), compared with 19.5 months for 123 patients treated with carfilzomib and dexamethasone alone (Kd). The hazard ratio for progression free survival with the triple combination was 0.531 (P = .0007), reported coprincipal investigator Phillipe Moreau, MD, from the University Hospital Hôtel-Dieu in Nantes, France.
“The benefit of the triplet combination was observed across subgroups, including patients difficult to treat, such as [those with] high-risk cytogenetics or elderly patients,” he said in a late-breaking abstract presentation during the virtual annual congress of the European Hematology Association.
Isatuximab is an immunoglobulin G1 monoclonal antibody targeting a CD38 transmembrane glycoprotein on multiple myeloma cells, with a mechanism of action similar to that of another anti-CD38 antibody, daratumumab (Darzalex). Isatuximab is approved in the United States and Europe in combination with pomalidomide and dexamethasone for patients with relapsed/refractory multiple myeloma after at least two prior lines of therapy.
A ‘me too’ agent?
It’s unclear, however, whether isatuximab offers any additional benefit over daratumumab, an agent approved for use both in front line therapy combinations and for patients with relapsed/refractory disease, said Brea C. Lipe, MD, a multiple myeloma specialist at the University of Rochester (N.Y.) Wilmot Cancer Institute, who was not involved in the study.
“Every time we get a new drug it’s nice to have another option, but it doesn’t really add anything different from daratumumab at this point,” she said in an interview.
Dr. Lipe noted the IKEMA results are similar to those seen in the phase 3 CANDOR trial, comparing carfilzomib, dexamethasone, and daratumumab to carfilzomib/dexamethasone alone in patients with relapsed/refractory myeloma. In addition, it’s unknown whether patients with disease that is refractory to daratumumab could benefit from isatuximab, she said.
Although isatuximab has been touted as offering more rapid and more convenient dosing than daratumumab, the introduction of rapid infusion and subcutaneous administration of daratumumab has negated any theoretical advantage of the newcomer, Dr. Lipe added.
Study details
In the IKEMA trial, 302 patients with relapsed/refractory multiple myeloma who’d received one to three prior lines of therapy were stratified by the number of prior lines and by revised Multiple Myeloma International Staging System (R-ISS) and were then randomized on a 3:2 basis to treatment with carfilzomib 20 mg/m2 on days 1, 2, 8, 9, 15, and 16 of cycle 1 and 56 mg/m2 on the corresponding days of each subsequent cycle plus dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle, with or without isatuximab. The antibody was dosed 10 mg/kg on days 1, 8, 15, and 22 in cycle 1 then every 2 weeks thereafter.
Treatments were continued until disease progression, unacceptable toxicity, or patient choice intervened.
At a prespecified interim analysis, the trial met its primary endpoint of a minimum 41% risk reduction in the hazard rate for progression free survival (PFS), with an actual risk reduction of 47%.
An analysis of PFS by subgroup showed significant benefits with the triple combination for patients aged 65 years and older, those with baseline estimated glomerular filtration rates below 60 mL/min per 1.73 m2, those with more than one prior line of therapy, those who had not previously received a proteasome inhibitor (e.g., bortezomib) or immunomodulatory agent (e.g., lenalidomide), those with high-risk cytogenetic status, and those with R-ISS stage II at study entry.
Overall response rates were similar between the study arms, at 86.6% with Isa-Kd and 82.9% with Kd, but the rate of very good partial responses or better was significantly higher with the triplet, at 72.6% versus 56.1% (P = .0011). The rate of minimal residual disease negativity was also significantly lower with Isa-Kd in the intent-to-treat population, at 29.6% versus 13%, respectively (P = .0004).
Overall survival data were not mature at the time of data cutoff and will be reported later, Dr. Moreau said.
Grade 3 or greater treatment-emergent adverse events (TEAEs) occurred in 76.8% of patients on the triplet and 67.2% of those on Kd. The incidences of death, serious TEAEs, or adverse events leading to discontinuation of therapy did not differ markedly between the treatment arms, however. Grade 3 or greater cardiac failure occurred in seven patients treated with the triplet (4%) and five treated with Kd (4.1%); respective rates of grade 3 or greater hematologic abnormalities included anemia in 22% and 19.7%, neutropenia in 19.2% and 7.4%, and thrombocytopenia in 29.9% and 23.8%.
The primary completion date for the trial is estimated to occur in November 2020, with final results in November 2023.
The study was sponsored by Sanofi. Dr. Moreau disclosed honoraria and a consulting or advisory role with several companies, not including Sanofi. Dr. Lipe disclosed impending advisory board activity for Janssen.
SOURCE: Moreau P et al. EHA Congress, Abstract LB2603.
The risk of progression or death for patients with relapsed or refractory multiple myeloma was nearly halved with the addition of isatuximab to carfilzomib and dexamethasone, according to an interim analysis of the phase 3 IKEMA trial (NCT03275285).
After a median follow-up of 20.7 months, the median progression-free survival had not been reached for 179 patients treated with isatuximab (Sarclisa), carfilzomib (Kyprolis), and dexamethasone (together, known as Isa-Kd), compared with 19.5 months for 123 patients treated with carfilzomib and dexamethasone alone (Kd). The hazard ratio for progression free survival with the triple combination was 0.531 (P = .0007), reported coprincipal investigator Phillipe Moreau, MD, from the University Hospital Hôtel-Dieu in Nantes, France.
“The benefit of the triplet combination was observed across subgroups, including patients difficult to treat, such as [those with] high-risk cytogenetics or elderly patients,” he said in a late-breaking abstract presentation during the virtual annual congress of the European Hematology Association.
Isatuximab is an immunoglobulin G1 monoclonal antibody targeting a CD38 transmembrane glycoprotein on multiple myeloma cells, with a mechanism of action similar to that of another anti-CD38 antibody, daratumumab (Darzalex). Isatuximab is approved in the United States and Europe in combination with pomalidomide and dexamethasone for patients with relapsed/refractory multiple myeloma after at least two prior lines of therapy.
A ‘me too’ agent?
It’s unclear, however, whether isatuximab offers any additional benefit over daratumumab, an agent approved for use both in front line therapy combinations and for patients with relapsed/refractory disease, said Brea C. Lipe, MD, a multiple myeloma specialist at the University of Rochester (N.Y.) Wilmot Cancer Institute, who was not involved in the study.
“Every time we get a new drug it’s nice to have another option, but it doesn’t really add anything different from daratumumab at this point,” she said in an interview.
Dr. Lipe noted the IKEMA results are similar to those seen in the phase 3 CANDOR trial, comparing carfilzomib, dexamethasone, and daratumumab to carfilzomib/dexamethasone alone in patients with relapsed/refractory myeloma. In addition, it’s unknown whether patients with disease that is refractory to daratumumab could benefit from isatuximab, she said.
Although isatuximab has been touted as offering more rapid and more convenient dosing than daratumumab, the introduction of rapid infusion and subcutaneous administration of daratumumab has negated any theoretical advantage of the newcomer, Dr. Lipe added.
Study details
In the IKEMA trial, 302 patients with relapsed/refractory multiple myeloma who’d received one to three prior lines of therapy were stratified by the number of prior lines and by revised Multiple Myeloma International Staging System (R-ISS) and were then randomized on a 3:2 basis to treatment with carfilzomib 20 mg/m2 on days 1, 2, 8, 9, 15, and 16 of cycle 1 and 56 mg/m2 on the corresponding days of each subsequent cycle plus dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle, with or without isatuximab. The antibody was dosed 10 mg/kg on days 1, 8, 15, and 22 in cycle 1 then every 2 weeks thereafter.
Treatments were continued until disease progression, unacceptable toxicity, or patient choice intervened.
At a prespecified interim analysis, the trial met its primary endpoint of a minimum 41% risk reduction in the hazard rate for progression free survival (PFS), with an actual risk reduction of 47%.
An analysis of PFS by subgroup showed significant benefits with the triple combination for patients aged 65 years and older, those with baseline estimated glomerular filtration rates below 60 mL/min per 1.73 m2, those with more than one prior line of therapy, those who had not previously received a proteasome inhibitor (e.g., bortezomib) or immunomodulatory agent (e.g., lenalidomide), those with high-risk cytogenetic status, and those with R-ISS stage II at study entry.
Overall response rates were similar between the study arms, at 86.6% with Isa-Kd and 82.9% with Kd, but the rate of very good partial responses or better was significantly higher with the triplet, at 72.6% versus 56.1% (P = .0011). The rate of minimal residual disease negativity was also significantly lower with Isa-Kd in the intent-to-treat population, at 29.6% versus 13%, respectively (P = .0004).
Overall survival data were not mature at the time of data cutoff and will be reported later, Dr. Moreau said.
Grade 3 or greater treatment-emergent adverse events (TEAEs) occurred in 76.8% of patients on the triplet and 67.2% of those on Kd. The incidences of death, serious TEAEs, or adverse events leading to discontinuation of therapy did not differ markedly between the treatment arms, however. Grade 3 or greater cardiac failure occurred in seven patients treated with the triplet (4%) and five treated with Kd (4.1%); respective rates of grade 3 or greater hematologic abnormalities included anemia in 22% and 19.7%, neutropenia in 19.2% and 7.4%, and thrombocytopenia in 29.9% and 23.8%.
The primary completion date for the trial is estimated to occur in November 2020, with final results in November 2023.
The study was sponsored by Sanofi. Dr. Moreau disclosed honoraria and a consulting or advisory role with several companies, not including Sanofi. Dr. Lipe disclosed impending advisory board activity for Janssen.
SOURCE: Moreau P et al. EHA Congress, Abstract LB2603.
FROM EHA CONGRESS
Microneedling plus 10% TCA peels bests CO2 laser alone for infraorbital dark circles
In a study of patients with mild to moderate infraorbital dark circles, treatment with carbon dioxide laser resurfacing did not produce a significant improvement in infraorbital hyperpigmentation. However, the combination of microneedling and 10% trichloroacetic acid peels did.
The finding comes from what is believed to be the first head-to-head comparison of the two procedures for infraorbital dark circles, which are a common cosmetic concern with increased age.
During a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology, lead study author Banu Farabi, MD, said that dark circles seen in the periorbital area are defined as bilateral, round homogeneous pigmented macules whose etiology is thought to be multifactorial. Available treatments include bleaching creams, topical retinoids, chemical peels, lasers, autologous fat transplantation, injectable fillers, and blepharoplasty.
“Microneedling has been recently suggested as an effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi said. “This technique is based on creating microchannels that can stimulate the production of subcutaneous collagen and elastin. It also enhances the revascularization and fibroblast activity, which increases the skin thickness and gives a shiny appearance to the skin. The fractional CO2 has also been introduced as an effective procedure to remove infraorbital dark circles. However, there are some potential complications with that therapy.”
For the current study, Dr. Farabi, of the department of dermatology at Ankara (Turkey) University, and Mohamad Goldust, MD, of University Hospital Basel (Switzerland), They used the handheld Automatic Microneedle Therapy System-Handhold from MCure. After creating microchannels, the investigators topically applied 10% trichloroacetic acid peels to each infraorbital area and waited for 5 minutes.
In the carbon dioxide laser group, a Lutronic CO2 laser was used with a pulse energy of 10 J/cm2, a 100-microsecond pulse rate, 30 W of power, and a pulse width of 4 mm. The treatment outcome was assessed with the patient’s satisfaction and the physician’s judgment, which were no response, partial response, and complete response. Patients in both study groups were followed up for blinded-investigator assessment of infraorbital hyperpigmentation, adverse events, and improvement, compared with baseline.
The mean age of patients was 40 years, with a range between 27 and 58 years. About one-third of patients in each group had Fitzpatrick skin types II, III, and IV, respectively. In the blinded investigator assessment, the laser-resurfacing procedure did not demonstrate a significant improvement in infraorbital hyperpigmentation at day 90 (P = .24). However, the combination of microneedling and 10% trichloroacetic acid peels significantly improved infraorbital hyperpigmentation by day 90, with improvement maintained through day 180 (P = .012 and .002, respectively).
Adverse events were mild and temporary in both groups. In the laser-resurfacing group, 7 of the patients (22.5%) developed transient infraorbital hyperpigmentation postoperatively that lasted 4 weeks. In the combination treatment group, 18 patients (58%) developed transient erythema that lasted for up to 1 week.
“We suggest using microneedling plus 10% [trichloroacetic acid] as a cost-effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi concluded.
The researchers reported having no financial disclosures.
In a study of patients with mild to moderate infraorbital dark circles, treatment with carbon dioxide laser resurfacing did not produce a significant improvement in infraorbital hyperpigmentation. However, the combination of microneedling and 10% trichloroacetic acid peels did.
The finding comes from what is believed to be the first head-to-head comparison of the two procedures for infraorbital dark circles, which are a common cosmetic concern with increased age.
During a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology, lead study author Banu Farabi, MD, said that dark circles seen in the periorbital area are defined as bilateral, round homogeneous pigmented macules whose etiology is thought to be multifactorial. Available treatments include bleaching creams, topical retinoids, chemical peels, lasers, autologous fat transplantation, injectable fillers, and blepharoplasty.
“Microneedling has been recently suggested as an effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi said. “This technique is based on creating microchannels that can stimulate the production of subcutaneous collagen and elastin. It also enhances the revascularization and fibroblast activity, which increases the skin thickness and gives a shiny appearance to the skin. The fractional CO2 has also been introduced as an effective procedure to remove infraorbital dark circles. However, there are some potential complications with that therapy.”
For the current study, Dr. Farabi, of the department of dermatology at Ankara (Turkey) University, and Mohamad Goldust, MD, of University Hospital Basel (Switzerland), They used the handheld Automatic Microneedle Therapy System-Handhold from MCure. After creating microchannels, the investigators topically applied 10% trichloroacetic acid peels to each infraorbital area and waited for 5 minutes.
In the carbon dioxide laser group, a Lutronic CO2 laser was used with a pulse energy of 10 J/cm2, a 100-microsecond pulse rate, 30 W of power, and a pulse width of 4 mm. The treatment outcome was assessed with the patient’s satisfaction and the physician’s judgment, which were no response, partial response, and complete response. Patients in both study groups were followed up for blinded-investigator assessment of infraorbital hyperpigmentation, adverse events, and improvement, compared with baseline.
The mean age of patients was 40 years, with a range between 27 and 58 years. About one-third of patients in each group had Fitzpatrick skin types II, III, and IV, respectively. In the blinded investigator assessment, the laser-resurfacing procedure did not demonstrate a significant improvement in infraorbital hyperpigmentation at day 90 (P = .24). However, the combination of microneedling and 10% trichloroacetic acid peels significantly improved infraorbital hyperpigmentation by day 90, with improvement maintained through day 180 (P = .012 and .002, respectively).
Adverse events were mild and temporary in both groups. In the laser-resurfacing group, 7 of the patients (22.5%) developed transient infraorbital hyperpigmentation postoperatively that lasted 4 weeks. In the combination treatment group, 18 patients (58%) developed transient erythema that lasted for up to 1 week.
“We suggest using microneedling plus 10% [trichloroacetic acid] as a cost-effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi concluded.
The researchers reported having no financial disclosures.
In a study of patients with mild to moderate infraorbital dark circles, treatment with carbon dioxide laser resurfacing did not produce a significant improvement in infraorbital hyperpigmentation. However, the combination of microneedling and 10% trichloroacetic acid peels did.
The finding comes from what is believed to be the first head-to-head comparison of the two procedures for infraorbital dark circles, which are a common cosmetic concern with increased age.
During a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology, lead study author Banu Farabi, MD, said that dark circles seen in the periorbital area are defined as bilateral, round homogeneous pigmented macules whose etiology is thought to be multifactorial. Available treatments include bleaching creams, topical retinoids, chemical peels, lasers, autologous fat transplantation, injectable fillers, and blepharoplasty.
“Microneedling has been recently suggested as an effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi said. “This technique is based on creating microchannels that can stimulate the production of subcutaneous collagen and elastin. It also enhances the revascularization and fibroblast activity, which increases the skin thickness and gives a shiny appearance to the skin. The fractional CO2 has also been introduced as an effective procedure to remove infraorbital dark circles. However, there are some potential complications with that therapy.”
For the current study, Dr. Farabi, of the department of dermatology at Ankara (Turkey) University, and Mohamad Goldust, MD, of University Hospital Basel (Switzerland), They used the handheld Automatic Microneedle Therapy System-Handhold from MCure. After creating microchannels, the investigators topically applied 10% trichloroacetic acid peels to each infraorbital area and waited for 5 minutes.
In the carbon dioxide laser group, a Lutronic CO2 laser was used with a pulse energy of 10 J/cm2, a 100-microsecond pulse rate, 30 W of power, and a pulse width of 4 mm. The treatment outcome was assessed with the patient’s satisfaction and the physician’s judgment, which were no response, partial response, and complete response. Patients in both study groups were followed up for blinded-investigator assessment of infraorbital hyperpigmentation, adverse events, and improvement, compared with baseline.
The mean age of patients was 40 years, with a range between 27 and 58 years. About one-third of patients in each group had Fitzpatrick skin types II, III, and IV, respectively. In the blinded investigator assessment, the laser-resurfacing procedure did not demonstrate a significant improvement in infraorbital hyperpigmentation at day 90 (P = .24). However, the combination of microneedling and 10% trichloroacetic acid peels significantly improved infraorbital hyperpigmentation by day 90, with improvement maintained through day 180 (P = .012 and .002, respectively).
Adverse events were mild and temporary in both groups. In the laser-resurfacing group, 7 of the patients (22.5%) developed transient infraorbital hyperpigmentation postoperatively that lasted 4 weeks. In the combination treatment group, 18 patients (58%) developed transient erythema that lasted for up to 1 week.
“We suggest using microneedling plus 10% [trichloroacetic acid] as a cost-effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi concluded.
The researchers reported having no financial disclosures.
FROM AAD 20
Women thrive on baroreflex activation for heart failure
The striking gains in functional capacity and quality of life conferred by baroreflex activation therapy in patients with heart failure, as shown in the pivotal phase 3 clinical trial for this novel intervention, were at least as great in women as in men, JoAnn Lindenfeld, MD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.
The results of the multicenter, prospective, randomized BeAT-HF trial led to marketing approval of the BaroStim Neo system for improvement in symptoms of heart failure with reduced ejection fraction (HFrEF) by the Food and Drug Administration in August 2019. Dr. Lindenfeld presented a fresh breakdown of the results by gender which showed, intriguingly, that the improvement in all study endpoints was consistently numerically greater in the women – sometimes startlingly so – although these gender differences in response didn’t achieve statistical significance. The 6-month randomized trial was underpowered for drawing definitive conclusions on that score, with a study population of only 53 women and 211 men. So the investigator remained circumspect.
“We think that what this study shows us is that women have at least equivalent improvement as men in this population. I don’t think we can conclude from this study yet that it’s better, but it’s certainly in all these parameters as least as good. And I think this is a population in which we’ve seen that improving symptoms and functional capacity is very important,” said Dr. Lindenfeld, professor of medicine and director of advanced heart failure/cardiac transplantation at Vanderbilt University, Nashville, Tenn.
The FDA approval was restricted to patients like those enrolled in BeAT-HF: that is, individuals with New York Heart Association functional class III heart failure, a left ventricular ejection fraction of 35% or less while on stable optimal medical therapy, and ineligibility for cardiac resynchronization therapy according to current guidelines. Seventy-eight percent of BeAT-HF participants had an implantable cardioverter-defibrillator.
Participants were randomized to baroreflex activation therapy (BAT) plus optimal medical therapy or to optimal medical therapy alone. The three coprimary endpoints were change from baseline to 6 months in 6-minute hall walk distance (6MHW), scores on the Minnesota Living with Heart Failure Questionnaire (MLHF), and N-terminal pro-B-type natriuretic peptide (NT-proBNP).
In the overall study population, 6MHW increased by 60 m in the BAT group and decreased by 8 m in controls; MLHF scores dropped by 14 and 6 points, respectively; and NT-proBNP fell by an average of 25% with BAT while rising by 3% in controls.
Very often, just a 5-point reduction in MLHF score is considered a clinically meaningful improvement in quality of life, the cardiologist noted.
The gender-based analysis is where things got particularly interesting.
The investigators defined a clinically relevant response as a greater than 10% increase from baseline on the 6MHW, at least a one-class improvement in NYHA class, or a reduction of 5 points or more on the MLHF. Among subjects in the BAT group, 70% of women and 60% of men met the clinically relevant response standard in terms of 6MHW, as did 70% of women and 64% of men for improvement in NYHA class, and 78% of women and 66% of men for MLHF score.
Eighty-seven percent of women and 68% of men on BAT had a clinically relevant response on at least one of these endpoints, as did about 28% of controls. Moreover, 31% of women in the BAT group were clinically relevant responders on at least two endpoints, compared with 19% of BAT men and 4% and 9% of controls.
Women dominate super-responder category
In order to be classified as a super responder, a patient had to demonstrate a greater than 20% increase in 6MHW, improvement in NYHA class I status, or at least a 10-point improvement in MLHF score. Ninety-one percent of women on BAT achieved super-responder status for at least one of these endpoints, compared with 76% of men. Forty-three percent of women and 24% of men in the BAT group were super responders in at least two domains, as were 8% and 11% of female and male controls, Dr. Lindenfeld continued.
Discussant Ewa Anita Jankowska, MD, PhD, deemed the BeAT-HF results on the therapeutic benefits of this autonomic modulation strategy “quite convincing.”
“We need to acknowledge that in recent years we have been spoiled a bit by the huge trials in heart failure where the ultimate goal was a reduction in mortality. But I think this is the time when we should think about the patients who want to live – here, now – with a better life. Patients expect symptomatic benefits. There is a substantial group of patients who are symptomatic even though they receive quite extensive neurohormonal blockage and who are not suitable for CRT. This study demonstrates that, for this group of patients, BAT can bring really significant symptomatic benefits,” she said.
“If you think about a treatment that provides patients who are NYHA class III an increase in 6MHW of 60 meters, that’s really something. And 20% of patients went from NYHA class III to class I – that’s really something, too,” added Dr. Jankowska, professor of medicine and head of the laboratory of applied research on the cardiovascular system at Wroclaw (Poland) University.
How baroreflex activation therapy works
The BaroStim system consists of a 2-mm unipolar electrode on a 7-mm backer that is placed over the carotid sinus. It is supported by a small generator with a 4- to 5-year battery life implanted under the collarbone, along with radiofrequency telemetry capability and programming flexibility.
Stimulation of the carotid baroreceptor promotes an integrated autonomic nervous system response which enhances parasympathetic activity and inhibits sympathetic nervous system activity. The result, as shown in numerous earlier proof-of-concept studies, is a reduced heart rate, decreased ventricular remodeling, enhanced diuresis, increased vasodilation, a drop in elevated blood pressure, and decreased renin secretion – all achieved nonpharmacologically.
The study was sponsored by CVRx. Dr. Lindenfeld reported serving as a consultant to CVRx, Abbott, AstraZeneca, Boehringer Ingelheim, Edwards Lifesciences, Impulse Dynamics, and VWave.
The striking gains in functional capacity and quality of life conferred by baroreflex activation therapy in patients with heart failure, as shown in the pivotal phase 3 clinical trial for this novel intervention, were at least as great in women as in men, JoAnn Lindenfeld, MD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.
The results of the multicenter, prospective, randomized BeAT-HF trial led to marketing approval of the BaroStim Neo system for improvement in symptoms of heart failure with reduced ejection fraction (HFrEF) by the Food and Drug Administration in August 2019. Dr. Lindenfeld presented a fresh breakdown of the results by gender which showed, intriguingly, that the improvement in all study endpoints was consistently numerically greater in the women – sometimes startlingly so – although these gender differences in response didn’t achieve statistical significance. The 6-month randomized trial was underpowered for drawing definitive conclusions on that score, with a study population of only 53 women and 211 men. So the investigator remained circumspect.
“We think that what this study shows us is that women have at least equivalent improvement as men in this population. I don’t think we can conclude from this study yet that it’s better, but it’s certainly in all these parameters as least as good. And I think this is a population in which we’ve seen that improving symptoms and functional capacity is very important,” said Dr. Lindenfeld, professor of medicine and director of advanced heart failure/cardiac transplantation at Vanderbilt University, Nashville, Tenn.
The FDA approval was restricted to patients like those enrolled in BeAT-HF: that is, individuals with New York Heart Association functional class III heart failure, a left ventricular ejection fraction of 35% or less while on stable optimal medical therapy, and ineligibility for cardiac resynchronization therapy according to current guidelines. Seventy-eight percent of BeAT-HF participants had an implantable cardioverter-defibrillator.
Participants were randomized to baroreflex activation therapy (BAT) plus optimal medical therapy or to optimal medical therapy alone. The three coprimary endpoints were change from baseline to 6 months in 6-minute hall walk distance (6MHW), scores on the Minnesota Living with Heart Failure Questionnaire (MLHF), and N-terminal pro-B-type natriuretic peptide (NT-proBNP).
In the overall study population, 6MHW increased by 60 m in the BAT group and decreased by 8 m in controls; MLHF scores dropped by 14 and 6 points, respectively; and NT-proBNP fell by an average of 25% with BAT while rising by 3% in controls.
Very often, just a 5-point reduction in MLHF score is considered a clinically meaningful improvement in quality of life, the cardiologist noted.
The gender-based analysis is where things got particularly interesting.
The investigators defined a clinically relevant response as a greater than 10% increase from baseline on the 6MHW, at least a one-class improvement in NYHA class, or a reduction of 5 points or more on the MLHF. Among subjects in the BAT group, 70% of women and 60% of men met the clinically relevant response standard in terms of 6MHW, as did 70% of women and 64% of men for improvement in NYHA class, and 78% of women and 66% of men for MLHF score.
Eighty-seven percent of women and 68% of men on BAT had a clinically relevant response on at least one of these endpoints, as did about 28% of controls. Moreover, 31% of women in the BAT group were clinically relevant responders on at least two endpoints, compared with 19% of BAT men and 4% and 9% of controls.
Women dominate super-responder category
In order to be classified as a super responder, a patient had to demonstrate a greater than 20% increase in 6MHW, improvement in NYHA class I status, or at least a 10-point improvement in MLHF score. Ninety-one percent of women on BAT achieved super-responder status for at least one of these endpoints, compared with 76% of men. Forty-three percent of women and 24% of men in the BAT group were super responders in at least two domains, as were 8% and 11% of female and male controls, Dr. Lindenfeld continued.
Discussant Ewa Anita Jankowska, MD, PhD, deemed the BeAT-HF results on the therapeutic benefits of this autonomic modulation strategy “quite convincing.”
“We need to acknowledge that in recent years we have been spoiled a bit by the huge trials in heart failure where the ultimate goal was a reduction in mortality. But I think this is the time when we should think about the patients who want to live – here, now – with a better life. Patients expect symptomatic benefits. There is a substantial group of patients who are symptomatic even though they receive quite extensive neurohormonal blockage and who are not suitable for CRT. This study demonstrates that, for this group of patients, BAT can bring really significant symptomatic benefits,” she said.
“If you think about a treatment that provides patients who are NYHA class III an increase in 6MHW of 60 meters, that’s really something. And 20% of patients went from NYHA class III to class I – that’s really something, too,” added Dr. Jankowska, professor of medicine and head of the laboratory of applied research on the cardiovascular system at Wroclaw (Poland) University.
How baroreflex activation therapy works
The BaroStim system consists of a 2-mm unipolar electrode on a 7-mm backer that is placed over the carotid sinus. It is supported by a small generator with a 4- to 5-year battery life implanted under the collarbone, along with radiofrequency telemetry capability and programming flexibility.
Stimulation of the carotid baroreceptor promotes an integrated autonomic nervous system response which enhances parasympathetic activity and inhibits sympathetic nervous system activity. The result, as shown in numerous earlier proof-of-concept studies, is a reduced heart rate, decreased ventricular remodeling, enhanced diuresis, increased vasodilation, a drop in elevated blood pressure, and decreased renin secretion – all achieved nonpharmacologically.
The study was sponsored by CVRx. Dr. Lindenfeld reported serving as a consultant to CVRx, Abbott, AstraZeneca, Boehringer Ingelheim, Edwards Lifesciences, Impulse Dynamics, and VWave.
The striking gains in functional capacity and quality of life conferred by baroreflex activation therapy in patients with heart failure, as shown in the pivotal phase 3 clinical trial for this novel intervention, were at least as great in women as in men, JoAnn Lindenfeld, MD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.
The results of the multicenter, prospective, randomized BeAT-HF trial led to marketing approval of the BaroStim Neo system for improvement in symptoms of heart failure with reduced ejection fraction (HFrEF) by the Food and Drug Administration in August 2019. Dr. Lindenfeld presented a fresh breakdown of the results by gender which showed, intriguingly, that the improvement in all study endpoints was consistently numerically greater in the women – sometimes startlingly so – although these gender differences in response didn’t achieve statistical significance. The 6-month randomized trial was underpowered for drawing definitive conclusions on that score, with a study population of only 53 women and 211 men. So the investigator remained circumspect.
“We think that what this study shows us is that women have at least equivalent improvement as men in this population. I don’t think we can conclude from this study yet that it’s better, but it’s certainly in all these parameters as least as good. And I think this is a population in which we’ve seen that improving symptoms and functional capacity is very important,” said Dr. Lindenfeld, professor of medicine and director of advanced heart failure/cardiac transplantation at Vanderbilt University, Nashville, Tenn.
The FDA approval was restricted to patients like those enrolled in BeAT-HF: that is, individuals with New York Heart Association functional class III heart failure, a left ventricular ejection fraction of 35% or less while on stable optimal medical therapy, and ineligibility for cardiac resynchronization therapy according to current guidelines. Seventy-eight percent of BeAT-HF participants had an implantable cardioverter-defibrillator.
Participants were randomized to baroreflex activation therapy (BAT) plus optimal medical therapy or to optimal medical therapy alone. The three coprimary endpoints were change from baseline to 6 months in 6-minute hall walk distance (6MHW), scores on the Minnesota Living with Heart Failure Questionnaire (MLHF), and N-terminal pro-B-type natriuretic peptide (NT-proBNP).
In the overall study population, 6MHW increased by 60 m in the BAT group and decreased by 8 m in controls; MLHF scores dropped by 14 and 6 points, respectively; and NT-proBNP fell by an average of 25% with BAT while rising by 3% in controls.
Very often, just a 5-point reduction in MLHF score is considered a clinically meaningful improvement in quality of life, the cardiologist noted.
The gender-based analysis is where things got particularly interesting.
The investigators defined a clinically relevant response as a greater than 10% increase from baseline on the 6MHW, at least a one-class improvement in NYHA class, or a reduction of 5 points or more on the MLHF. Among subjects in the BAT group, 70% of women and 60% of men met the clinically relevant response standard in terms of 6MHW, as did 70% of women and 64% of men for improvement in NYHA class, and 78% of women and 66% of men for MLHF score.
Eighty-seven percent of women and 68% of men on BAT had a clinically relevant response on at least one of these endpoints, as did about 28% of controls. Moreover, 31% of women in the BAT group were clinically relevant responders on at least two endpoints, compared with 19% of BAT men and 4% and 9% of controls.
Women dominate super-responder category
In order to be classified as a super responder, a patient had to demonstrate a greater than 20% increase in 6MHW, improvement in NYHA class I status, or at least a 10-point improvement in MLHF score. Ninety-one percent of women on BAT achieved super-responder status for at least one of these endpoints, compared with 76% of men. Forty-three percent of women and 24% of men in the BAT group were super responders in at least two domains, as were 8% and 11% of female and male controls, Dr. Lindenfeld continued.
Discussant Ewa Anita Jankowska, MD, PhD, deemed the BeAT-HF results on the therapeutic benefits of this autonomic modulation strategy “quite convincing.”
“We need to acknowledge that in recent years we have been spoiled a bit by the huge trials in heart failure where the ultimate goal was a reduction in mortality. But I think this is the time when we should think about the patients who want to live – here, now – with a better life. Patients expect symptomatic benefits. There is a substantial group of patients who are symptomatic even though they receive quite extensive neurohormonal blockage and who are not suitable for CRT. This study demonstrates that, for this group of patients, BAT can bring really significant symptomatic benefits,” she said.
“If you think about a treatment that provides patients who are NYHA class III an increase in 6MHW of 60 meters, that’s really something. And 20% of patients went from NYHA class III to class I – that’s really something, too,” added Dr. Jankowska, professor of medicine and head of the laboratory of applied research on the cardiovascular system at Wroclaw (Poland) University.
How baroreflex activation therapy works
The BaroStim system consists of a 2-mm unipolar electrode on a 7-mm backer that is placed over the carotid sinus. It is supported by a small generator with a 4- to 5-year battery life implanted under the collarbone, along with radiofrequency telemetry capability and programming flexibility.
Stimulation of the carotid baroreceptor promotes an integrated autonomic nervous system response which enhances parasympathetic activity and inhibits sympathetic nervous system activity. The result, as shown in numerous earlier proof-of-concept studies, is a reduced heart rate, decreased ventricular remodeling, enhanced diuresis, increased vasodilation, a drop in elevated blood pressure, and decreased renin secretion – all achieved nonpharmacologically.
The study was sponsored by CVRx. Dr. Lindenfeld reported serving as a consultant to CVRx, Abbott, AstraZeneca, Boehringer Ingelheim, Edwards Lifesciences, Impulse Dynamics, and VWave.
FROM ESC HEART FAILURE 2020
Could jump in opioid overdoses be linked to COVID?
Early evidence suggests that opioid overdoses and deaths are on the rise this year, the director of the National Institute on Drug Abuse warned colleagues, although it’s not clear whether the coronavirus pandemic is responsible for the trend.
The picture is complicated since COVID-19 could have both positive and negative effects on substance use, Nora D. Volkow, MD, said in a plenary session at the virtual annual meeting of the College on Problems of Drug Dependence. However, she said, one thing is clear: The pandemic marks an opportunity to investigate new strategies and potentially reform treatment.
“We are being faced with an unknown world, and the lack of information curtails our capacity to implement interventions in the most effective way,” Dr. Volkow said. “There’s an urgency to obtain these data. All of you out there in the trenches have an opportunity to help gather this information in a way that can be integrated and deployed rapidly for us to guide practices and treatment.”
It’s too early to know for certain how the pandemic is affecting substance use in the United States, since statistics are sparse and COVID-19 is still relatively new. Still, local news reports have suggested overdose deaths have risen, Dr. Volkow said.
And, she noted, the Office of National Drug Control Policy’s Overdose Detection Mapping Application Program – which tracks overdoses nationwide – issued 191% more “spike alerts” from January to April this year, compared with the same time period in 2019. However, the spike alerts started going up in January, several weeks before mass numbers of COVID-19 cases began to be diagnosed.
Dr. Volkow noted the uncertainty about the numbers but said several factors could cause the pandemic to boost overdoses:
- Stress and isolation. “My first fear was that overdoses are going to go up because the stress is actually extraordinarily difficult,” she said. “Social distancing is making it very difficult for individuals with substance use disorder or opioid use disorder to get the community support that keeps them from relapsing,” such as methadone clinics and syringe exchange programs.
- Unwitnessed opioid overdoses. Social distancing could “lead to overdoses that nobody has observed, so no one can administer naloxone,” she said.
- Treatment decisions affected by stigma. “Our health systems will be overburdened, and they have to make decisions about which patients to treat,” she said. Stigma could play a very important role in interfering with the treatment of individuals with substance use disorders.”
- Drug-related vulnerabilities. On another front, she said, substance users may be especially vulnerable to the pandemic, because the drugs target multiple body systems that worsen COVID-19 outcomes. These include not only the lungs but also the cardiac and metabolic systems, she said.
For example, “if you have a long history of drug use, you’re going to be much more likely to have a pulmonary disease,” she said. “We know that pulmonary disease is a risk factor for getting COVID and for much worse outcomes.”
But the pandemic could also help in the fight against substance use. For one thing, she said, the pandemic could disrupt drug markets and make it harder for users to get illicit products.
In yet another complication, there is an ongoing debate over whether tobacco use could actually be protective against COVID-19. Research into nicotine patches as a treatment is in the works, she said.
What now? Dr. Volkow said one priority going forward should be an evaluation of virtual medicine. “We have virtual technologies that have enabled us to do telemedicine to provide mental health support and hotlines, as well as virtual support meetings,” she said. “These have proliferated and have served to a certain extent to compensate for some of the deficit from the erosion of the community support systems that exist.”
Now, she said, we should evaluate which interventions are effective, which patients they help, and the components that make them work.
There are other opportunities for useful investigations, she said. For example, researchers could examine the effects of COVID-related changes in policy, such as the federal government allowing more methadone users to take doses home and expanded telemedicine policy allowing more remote prescriptions.
“If we can show that the outcomes are as good or better [than before] then we may be able to transform these practices that make it so very difficult for so many patients to get access to treatment and to sustain treatment – but have not been questioned for years and years.”
Dr. Volkow reported no relevant disclosures.
Early evidence suggests that opioid overdoses and deaths are on the rise this year, the director of the National Institute on Drug Abuse warned colleagues, although it’s not clear whether the coronavirus pandemic is responsible for the trend.
The picture is complicated since COVID-19 could have both positive and negative effects on substance use, Nora D. Volkow, MD, said in a plenary session at the virtual annual meeting of the College on Problems of Drug Dependence. However, she said, one thing is clear: The pandemic marks an opportunity to investigate new strategies and potentially reform treatment.
“We are being faced with an unknown world, and the lack of information curtails our capacity to implement interventions in the most effective way,” Dr. Volkow said. “There’s an urgency to obtain these data. All of you out there in the trenches have an opportunity to help gather this information in a way that can be integrated and deployed rapidly for us to guide practices and treatment.”
It’s too early to know for certain how the pandemic is affecting substance use in the United States, since statistics are sparse and COVID-19 is still relatively new. Still, local news reports have suggested overdose deaths have risen, Dr. Volkow said.
And, she noted, the Office of National Drug Control Policy’s Overdose Detection Mapping Application Program – which tracks overdoses nationwide – issued 191% more “spike alerts” from January to April this year, compared with the same time period in 2019. However, the spike alerts started going up in January, several weeks before mass numbers of COVID-19 cases began to be diagnosed.
Dr. Volkow noted the uncertainty about the numbers but said several factors could cause the pandemic to boost overdoses:
- Stress and isolation. “My first fear was that overdoses are going to go up because the stress is actually extraordinarily difficult,” she said. “Social distancing is making it very difficult for individuals with substance use disorder or opioid use disorder to get the community support that keeps them from relapsing,” such as methadone clinics and syringe exchange programs.
- Unwitnessed opioid overdoses. Social distancing could “lead to overdoses that nobody has observed, so no one can administer naloxone,” she said.
- Treatment decisions affected by stigma. “Our health systems will be overburdened, and they have to make decisions about which patients to treat,” she said. Stigma could play a very important role in interfering with the treatment of individuals with substance use disorders.”
- Drug-related vulnerabilities. On another front, she said, substance users may be especially vulnerable to the pandemic, because the drugs target multiple body systems that worsen COVID-19 outcomes. These include not only the lungs but also the cardiac and metabolic systems, she said.
For example, “if you have a long history of drug use, you’re going to be much more likely to have a pulmonary disease,” she said. “We know that pulmonary disease is a risk factor for getting COVID and for much worse outcomes.”
But the pandemic could also help in the fight against substance use. For one thing, she said, the pandemic could disrupt drug markets and make it harder for users to get illicit products.
In yet another complication, there is an ongoing debate over whether tobacco use could actually be protective against COVID-19. Research into nicotine patches as a treatment is in the works, she said.
What now? Dr. Volkow said one priority going forward should be an evaluation of virtual medicine. “We have virtual technologies that have enabled us to do telemedicine to provide mental health support and hotlines, as well as virtual support meetings,” she said. “These have proliferated and have served to a certain extent to compensate for some of the deficit from the erosion of the community support systems that exist.”
Now, she said, we should evaluate which interventions are effective, which patients they help, and the components that make them work.
There are other opportunities for useful investigations, she said. For example, researchers could examine the effects of COVID-related changes in policy, such as the federal government allowing more methadone users to take doses home and expanded telemedicine policy allowing more remote prescriptions.
“If we can show that the outcomes are as good or better [than before] then we may be able to transform these practices that make it so very difficult for so many patients to get access to treatment and to sustain treatment – but have not been questioned for years and years.”
Dr. Volkow reported no relevant disclosures.
Early evidence suggests that opioid overdoses and deaths are on the rise this year, the director of the National Institute on Drug Abuse warned colleagues, although it’s not clear whether the coronavirus pandemic is responsible for the trend.
The picture is complicated since COVID-19 could have both positive and negative effects on substance use, Nora D. Volkow, MD, said in a plenary session at the virtual annual meeting of the College on Problems of Drug Dependence. However, she said, one thing is clear: The pandemic marks an opportunity to investigate new strategies and potentially reform treatment.
“We are being faced with an unknown world, and the lack of information curtails our capacity to implement interventions in the most effective way,” Dr. Volkow said. “There’s an urgency to obtain these data. All of you out there in the trenches have an opportunity to help gather this information in a way that can be integrated and deployed rapidly for us to guide practices and treatment.”
It’s too early to know for certain how the pandemic is affecting substance use in the United States, since statistics are sparse and COVID-19 is still relatively new. Still, local news reports have suggested overdose deaths have risen, Dr. Volkow said.
And, she noted, the Office of National Drug Control Policy’s Overdose Detection Mapping Application Program – which tracks overdoses nationwide – issued 191% more “spike alerts” from January to April this year, compared with the same time period in 2019. However, the spike alerts started going up in January, several weeks before mass numbers of COVID-19 cases began to be diagnosed.
Dr. Volkow noted the uncertainty about the numbers but said several factors could cause the pandemic to boost overdoses:
- Stress and isolation. “My first fear was that overdoses are going to go up because the stress is actually extraordinarily difficult,” she said. “Social distancing is making it very difficult for individuals with substance use disorder or opioid use disorder to get the community support that keeps them from relapsing,” such as methadone clinics and syringe exchange programs.
- Unwitnessed opioid overdoses. Social distancing could “lead to overdoses that nobody has observed, so no one can administer naloxone,” she said.
- Treatment decisions affected by stigma. “Our health systems will be overburdened, and they have to make decisions about which patients to treat,” she said. Stigma could play a very important role in interfering with the treatment of individuals with substance use disorders.”
- Drug-related vulnerabilities. On another front, she said, substance users may be especially vulnerable to the pandemic, because the drugs target multiple body systems that worsen COVID-19 outcomes. These include not only the lungs but also the cardiac and metabolic systems, she said.
For example, “if you have a long history of drug use, you’re going to be much more likely to have a pulmonary disease,” she said. “We know that pulmonary disease is a risk factor for getting COVID and for much worse outcomes.”
But the pandemic could also help in the fight against substance use. For one thing, she said, the pandemic could disrupt drug markets and make it harder for users to get illicit products.
In yet another complication, there is an ongoing debate over whether tobacco use could actually be protective against COVID-19. Research into nicotine patches as a treatment is in the works, she said.
What now? Dr. Volkow said one priority going forward should be an evaluation of virtual medicine. “We have virtual technologies that have enabled us to do telemedicine to provide mental health support and hotlines, as well as virtual support meetings,” she said. “These have proliferated and have served to a certain extent to compensate for some of the deficit from the erosion of the community support systems that exist.”
Now, she said, we should evaluate which interventions are effective, which patients they help, and the components that make them work.
There are other opportunities for useful investigations, she said. For example, researchers could examine the effects of COVID-related changes in policy, such as the federal government allowing more methadone users to take doses home and expanded telemedicine policy allowing more remote prescriptions.
“If we can show that the outcomes are as good or better [than before] then we may be able to transform these practices that make it so very difficult for so many patients to get access to treatment and to sustain treatment – but have not been questioned for years and years.”
Dr. Volkow reported no relevant disclosures.
FROM CPDD 2020
Diabetes-related amputations on the rise in older adults
The recent resurgence in diabetes-related lower-extremity amputations in the United States is not limited to younger adults, according to the author of a recent study that documents similar increases among an older population of Medicare beneficiaries.
While the rate of amputations fell among these older adults from 2000 to 2009, it increased significantly from 2009 to 2017, albeit at a “less severe rate” than recently reported in younger populations, said study investigator Jessica Harding, PhD.
The rate of nontraumatic lower extremity amputation (NLEA) was ticking upward by more than 1% per year over the 2009-2017 period, according to Dr. Harding, assistant professor in the department of surgery at Emory University, Atlanta.
This latest report follows one from last year, published in Diabetes Care, that documented an annual percentage increase approaching 6% between 2009 and 2015, driven by larger increases among adults 18-64 years of age, as well as an increase among men.
It’s not clear why rates of NLEA would be on the rise among younger and older adults in the United States, Dr. Harding said, though factors she said could be implicated include changes in amputation practice, increased comorbidities, higher insulin costs, or shortcomings in early prevention programs.
“We need large-scale studies with granular data to tease out key risk factors that could help identify the drivers of these increases in amputations,” Dr. Harding said in a presentation at the virtual annual scientific sessions of the American Diabetes Association.
“In the interim, increased attention to preventive foot care across the age spectrum could benefit adults with diabetes,” she added.
Devastating complication in older adults
The latest findings from Dr. Harding and coauthors emphasize the importance of a “team approach” to early prevention in older adults with diabetes, said Derek LeRoith, MD, PhD, director of research in the division of endocrinology, diabetes, and bone diseases with Icahn School of Medicine at Mount Sinai, New York.
“If you take a 75-year-old or even an 80-year-old, their life expectancy can still be a good 10 years or more,” Dr. LeRoith said in an interview. “We shouldn’t give up on them – we should be treating them to prevent complications.”
Lower-extremity amputation is a “particularly devastating” complication that can compromise mobility, ability to exercise, and motivation, according to Dr. LeRoith, lead author of a recent Endocrine Society clinical practice guideline that urges referral of older adults with diabetes to a podiatrist, orthopedist, or vascular specialist for preventive care.
“Quite often, treating their glucose or high blood pressure will be much more difficult because of these changes,” he said.
Lower extremity amputation trends upward
Rates of NLEA declined for years, only to rebound by 50%, according to authors of a recent analysis of Nationwide Inpatient Sample (NIS) data reported last year. In their report, the age-standardized diabetes-related NLEA rate per 1,000 adults with diabetes went from 5.30 in 2000, down to 3.07 in 2009/2010, and back up to 4.62 by 2015 (Diabetes Care. 2019 Jan;42:50-4).
The resurgence was fueled mainly by an increased rate of amputations in younger and middle-aged adults and men, and through increases in minor amputations, notably the toe, according to the investigators. “These changes in trend are concerning because of the disabling and costly consequences of NLEAs as well as what they may mean for the direction of efforts to reduce diabetes-related complications,” authors of that report said at the time.
In the current study, Dr. Harding and colleagues included Medicare Parts A and B claims data for beneficiaries enrolled from 2000 to 2017. There were 4.6 million Medicare fee-for-service beneficiaries with diabetes in 2000, increasing to 6.9 million in 2017, she reported at the virtual ADA meeting.
Rates of NLEA followed a trajectory similar to what was seen in the earlier NIS report, falling from 8.5 per 1,000 persons in 2000 to 4.4 in 2009, for an annual percentage change of –7.9 (P < .001), Dr. Harding said. Then rates ticked upward again, to 4.8 in 2017, for an annual percentage change of 1.2 over that later period (P < .001).
While the trend was similar for most subgroups analyzed, the absolute rates were highest among men and black individuals in this older patient population, reported Dr. Harding and coauthors.
Dr. Harding said she and coauthors had no disclosures related to the research, which was performed as a collaboration between Emory University and the Centers for Disease Control and Prevention Division of Diabetes Translation.
SOURCE: Harding J. ADA 2020, Abstract 106-OR.
The recent resurgence in diabetes-related lower-extremity amputations in the United States is not limited to younger adults, according to the author of a recent study that documents similar increases among an older population of Medicare beneficiaries.
While the rate of amputations fell among these older adults from 2000 to 2009, it increased significantly from 2009 to 2017, albeit at a “less severe rate” than recently reported in younger populations, said study investigator Jessica Harding, PhD.
The rate of nontraumatic lower extremity amputation (NLEA) was ticking upward by more than 1% per year over the 2009-2017 period, according to Dr. Harding, assistant professor in the department of surgery at Emory University, Atlanta.
This latest report follows one from last year, published in Diabetes Care, that documented an annual percentage increase approaching 6% between 2009 and 2015, driven by larger increases among adults 18-64 years of age, as well as an increase among men.
It’s not clear why rates of NLEA would be on the rise among younger and older adults in the United States, Dr. Harding said, though factors she said could be implicated include changes in amputation practice, increased comorbidities, higher insulin costs, or shortcomings in early prevention programs.
“We need large-scale studies with granular data to tease out key risk factors that could help identify the drivers of these increases in amputations,” Dr. Harding said in a presentation at the virtual annual scientific sessions of the American Diabetes Association.
“In the interim, increased attention to preventive foot care across the age spectrum could benefit adults with diabetes,” she added.
Devastating complication in older adults
The latest findings from Dr. Harding and coauthors emphasize the importance of a “team approach” to early prevention in older adults with diabetes, said Derek LeRoith, MD, PhD, director of research in the division of endocrinology, diabetes, and bone diseases with Icahn School of Medicine at Mount Sinai, New York.
“If you take a 75-year-old or even an 80-year-old, their life expectancy can still be a good 10 years or more,” Dr. LeRoith said in an interview. “We shouldn’t give up on them – we should be treating them to prevent complications.”
Lower-extremity amputation is a “particularly devastating” complication that can compromise mobility, ability to exercise, and motivation, according to Dr. LeRoith, lead author of a recent Endocrine Society clinical practice guideline that urges referral of older adults with diabetes to a podiatrist, orthopedist, or vascular specialist for preventive care.
“Quite often, treating their glucose or high blood pressure will be much more difficult because of these changes,” he said.
Lower extremity amputation trends upward
Rates of NLEA declined for years, only to rebound by 50%, according to authors of a recent analysis of Nationwide Inpatient Sample (NIS) data reported last year. In their report, the age-standardized diabetes-related NLEA rate per 1,000 adults with diabetes went from 5.30 in 2000, down to 3.07 in 2009/2010, and back up to 4.62 by 2015 (Diabetes Care. 2019 Jan;42:50-4).
The resurgence was fueled mainly by an increased rate of amputations in younger and middle-aged adults and men, and through increases in minor amputations, notably the toe, according to the investigators. “These changes in trend are concerning because of the disabling and costly consequences of NLEAs as well as what they may mean for the direction of efforts to reduce diabetes-related complications,” authors of that report said at the time.
In the current study, Dr. Harding and colleagues included Medicare Parts A and B claims data for beneficiaries enrolled from 2000 to 2017. There were 4.6 million Medicare fee-for-service beneficiaries with diabetes in 2000, increasing to 6.9 million in 2017, she reported at the virtual ADA meeting.
Rates of NLEA followed a trajectory similar to what was seen in the earlier NIS report, falling from 8.5 per 1,000 persons in 2000 to 4.4 in 2009, for an annual percentage change of –7.9 (P < .001), Dr. Harding said. Then rates ticked upward again, to 4.8 in 2017, for an annual percentage change of 1.2 over that later period (P < .001).
While the trend was similar for most subgroups analyzed, the absolute rates were highest among men and black individuals in this older patient population, reported Dr. Harding and coauthors.
Dr. Harding said she and coauthors had no disclosures related to the research, which was performed as a collaboration between Emory University and the Centers for Disease Control and Prevention Division of Diabetes Translation.
SOURCE: Harding J. ADA 2020, Abstract 106-OR.
The recent resurgence in diabetes-related lower-extremity amputations in the United States is not limited to younger adults, according to the author of a recent study that documents similar increases among an older population of Medicare beneficiaries.
While the rate of amputations fell among these older adults from 2000 to 2009, it increased significantly from 2009 to 2017, albeit at a “less severe rate” than recently reported in younger populations, said study investigator Jessica Harding, PhD.
The rate of nontraumatic lower extremity amputation (NLEA) was ticking upward by more than 1% per year over the 2009-2017 period, according to Dr. Harding, assistant professor in the department of surgery at Emory University, Atlanta.
This latest report follows one from last year, published in Diabetes Care, that documented an annual percentage increase approaching 6% between 2009 and 2015, driven by larger increases among adults 18-64 years of age, as well as an increase among men.
It’s not clear why rates of NLEA would be on the rise among younger and older adults in the United States, Dr. Harding said, though factors she said could be implicated include changes in amputation practice, increased comorbidities, higher insulin costs, or shortcomings in early prevention programs.
“We need large-scale studies with granular data to tease out key risk factors that could help identify the drivers of these increases in amputations,” Dr. Harding said in a presentation at the virtual annual scientific sessions of the American Diabetes Association.
“In the interim, increased attention to preventive foot care across the age spectrum could benefit adults with diabetes,” she added.
Devastating complication in older adults
The latest findings from Dr. Harding and coauthors emphasize the importance of a “team approach” to early prevention in older adults with diabetes, said Derek LeRoith, MD, PhD, director of research in the division of endocrinology, diabetes, and bone diseases with Icahn School of Medicine at Mount Sinai, New York.
“If you take a 75-year-old or even an 80-year-old, their life expectancy can still be a good 10 years or more,” Dr. LeRoith said in an interview. “We shouldn’t give up on them – we should be treating them to prevent complications.”
Lower-extremity amputation is a “particularly devastating” complication that can compromise mobility, ability to exercise, and motivation, according to Dr. LeRoith, lead author of a recent Endocrine Society clinical practice guideline that urges referral of older adults with diabetes to a podiatrist, orthopedist, or vascular specialist for preventive care.
“Quite often, treating their glucose or high blood pressure will be much more difficult because of these changes,” he said.
Lower extremity amputation trends upward
Rates of NLEA declined for years, only to rebound by 50%, according to authors of a recent analysis of Nationwide Inpatient Sample (NIS) data reported last year. In their report, the age-standardized diabetes-related NLEA rate per 1,000 adults with diabetes went from 5.30 in 2000, down to 3.07 in 2009/2010, and back up to 4.62 by 2015 (Diabetes Care. 2019 Jan;42:50-4).
The resurgence was fueled mainly by an increased rate of amputations in younger and middle-aged adults and men, and through increases in minor amputations, notably the toe, according to the investigators. “These changes in trend are concerning because of the disabling and costly consequences of NLEAs as well as what they may mean for the direction of efforts to reduce diabetes-related complications,” authors of that report said at the time.
In the current study, Dr. Harding and colleagues included Medicare Parts A and B claims data for beneficiaries enrolled from 2000 to 2017. There were 4.6 million Medicare fee-for-service beneficiaries with diabetes in 2000, increasing to 6.9 million in 2017, she reported at the virtual ADA meeting.
Rates of NLEA followed a trajectory similar to what was seen in the earlier NIS report, falling from 8.5 per 1,000 persons in 2000 to 4.4 in 2009, for an annual percentage change of –7.9 (P < .001), Dr. Harding said. Then rates ticked upward again, to 4.8 in 2017, for an annual percentage change of 1.2 over that later period (P < .001).
While the trend was similar for most subgroups analyzed, the absolute rates were highest among men and black individuals in this older patient population, reported Dr. Harding and coauthors.
Dr. Harding said she and coauthors had no disclosures related to the research, which was performed as a collaboration between Emory University and the Centers for Disease Control and Prevention Division of Diabetes Translation.
SOURCE: Harding J. ADA 2020, Abstract 106-OR.
FROM ADA 2020
Risankizumab compared with secukinumab in 52-week psoriasis trial
.
Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.
In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.
The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.
The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.
The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.
Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.
He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.
.
Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.
In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.
The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.
The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.
The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.
Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.
He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.
.
Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.
In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.
The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.
The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.
The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.
Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.
He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.
FROM AAD 20