The Food and Drug Administration has approved elagolix (Orilissa) for oral treatment of moderate to severe pain associated with endometriosis, announced AbbVie and Neurocrine Biosciences; this approval makes it the first such treatment in more than a decade. It is expected to be available in the United States in early August.

Elagolix is a gonadotropin-releasing hormone (GnRH) antagonist and the first and only one developed specifically for managing this kind of pain.

The approval is based on two 6-month, randomized, double-blind, placebo-controlled phase 3 trials that compared a total of 952 adult women treated with either elagolix with 734 treated with placebo. All of the women experienced moderate to severe endometriosis pain; their ages ranged from 18 to 49 years.

Of the women in the treatment group, 475 were treated with a 150-mg daily dose, and 477 were treated with a 200-mg twice-daily dose. Both treatment groups showed significantly greater mean reductions in pain – both daily menstrual and nonmenstrual pelvic pain – at 6 months. Furthermore, women in the 200-mg twice-daily group also showed statistically significant greater reductions in pain with sex at 3 months, compared with placebo. Altogether, these represent the three most common kinds of endometriosis pain.

The most concerning adverse event associated with elagolix is dose-dependent decreases in bone mineral density; this effect limits treatment to either 150 mg daily for up to 24 months or 200 mg twice daily for up to 6 months. Bone mineral density loss might not be completely reversible, even with treatment cessation. Common adverse events (occurring in at least 5%) included hot flush/night sweats, headache, and nausea. Elagolix is not recommended for women who are or may be pregnant, have osteoporosis, have severe liver disease, or take strong OATP1B1 inhibitors.

Full prescribing information, as well as further details on the approval, can be found on the AbbVie website.
 

[email protected]

The Food and Drug Administration has approved elagolix (Orilissa) for oral treatment of moderate to severe pain associated with endometriosis, announced AbbVie and Neurocrine Biosciences; this approval makes it the first such treatment in more than a decade. It is expected to be available in the United States in early August.

Elagolix is a gonadotropin-releasing hormone (GnRH) antagonist and the first and only one developed specifically for managing this kind of pain.

The approval is based on two 6-month, randomized, double-blind, placebo-controlled phase 3 trials that compared a total of 952 adult women treated with either elagolix with 734 treated with placebo. All of the women experienced moderate to severe endometriosis pain; their ages ranged from 18 to 49 years.

Of the women in the treatment group, 475 were treated with a 150-mg daily dose, and 477 were treated with a 200-mg twice-daily dose. Both treatment groups showed significantly greater mean reductions in pain – both daily menstrual and nonmenstrual pelvic pain – at 6 months. Furthermore, women in the 200-mg twice-daily group also showed statistically significant greater reductions in pain with sex at 3 months, compared with placebo. Altogether, these represent the three most common kinds of endometriosis pain.

The most concerning adverse event associated with elagolix is dose-dependent decreases in bone mineral density; this effect limits treatment to either 150 mg daily for up to 24 months or 200 mg twice daily for up to 6 months. Bone mineral density loss might not be completely reversible, even with treatment cessation. Common adverse events (occurring in at least 5%) included hot flush/night sweats, headache, and nausea. Elagolix is not recommended for women who are or may be pregnant, have osteoporosis, have severe liver disease, or take strong OATP1B1 inhibitors.

Full prescribing information, as well as further details on the approval, can be found on the AbbVie website.
 

[email protected]

The Food and Drug Administration has approved elagolix (Orilissa) for oral treatment of moderate to severe pain associated with endometriosis, announced AbbVie and Neurocrine Biosciences; this approval makes it the first such treatment in more than a decade. It is expected to be available in the United States in early August.

Elagolix is a gonadotropin-releasing hormone (GnRH) antagonist and the first and only one developed specifically for managing this kind of pain.

The approval is based on two 6-month, randomized, double-blind, placebo-controlled phase 3 trials that compared a total of 952 adult women treated with either elagolix with 734 treated with placebo. All of the women experienced moderate to severe endometriosis pain; their ages ranged from 18 to 49 years.

Of the women in the treatment group, 475 were treated with a 150-mg daily dose, and 477 were treated with a 200-mg twice-daily dose. Both treatment groups showed significantly greater mean reductions in pain – both daily menstrual and nonmenstrual pelvic pain – at 6 months. Furthermore, women in the 200-mg twice-daily group also showed statistically significant greater reductions in pain with sex at 3 months, compared with placebo. Altogether, these represent the three most common kinds of endometriosis pain.

The most concerning adverse event associated with elagolix is dose-dependent decreases in bone mineral density; this effect limits treatment to either 150 mg daily for up to 24 months or 200 mg twice daily for up to 6 months. Bone mineral density loss might not be completely reversible, even with treatment cessation. Common adverse events (occurring in at least 5%) included hot flush/night sweats, headache, and nausea. Elagolix is not recommended for women who are or may be pregnant, have osteoporosis, have severe liver disease, or take strong OATP1B1 inhibitors.

Full prescribing information, as well as further details on the approval, can be found on the AbbVie website.
 

[email protected]

Prevalence of depression in fathers was similar to that of mothers screened at well-child visits, according to a research letter published in JAMA Pediatrics.

An analysis of data obtained from the Child Health Improvement through Computer Automation (CHICA) pediatric health surveillance system found that 4.4% of fathers who attended the well-child visit and completed a prescreening form scored positive for depression, comparable with the rate in mothers (5%). Overall, fathers composed 11.7% of parents who screened positive for depression, reported Erika R. Cheng, PhD, of Indiana University, Indianapolis, and her colleagues.

Dr. Cheng and her colleagues estimated prevalence of paternal depression using CHICA data from parents of children aged 15 months and younger from five community health centers in Indianapolis between August 1, 2016, and December 31, 2017. CHICA is a 20-question prescreen of pediatric health conditions based on the patient’s existing data.

Maternal postpartum depression was assessed using a modified version of the Edinburgh Postnatal Depression Scale, administered every 90 days during the child’s first 15 months of life, Dr. Cheng and her colleagues wrote.

Fathers were present at 30.8% of well-child visits (2,946 of 9,572) and completed the prescreening at 806 visits (8.4% of total visits). A total of 36 (4.4%) fathers screened positive for depression, compared with 273 (5%) mothers. However, since CHICA assesses depression for only one parent, some cases of paternal depression may have been missed, the investigators added.

“Pediatric clinics are thus promising settings in which to address depression in both parents as part of a family-centered approach to care,” Dr. Cheng and her coauthors concluded. “Addressing these gaps could improve detection and treatment rates of postnatal depression in both mothers and fathers.”

Two of the authors coinvented the CHICA system, and one is a co-owner of Digital Health Solutions, which licensed the system. No other disclosures were reported.

SOURCE: Cheng ER et al. JAMA Pediatr. 2018 Jul 23. doi:10.1001/jamapediatrics.2018.1505.

Prevalence of depression in fathers was similar to that of mothers screened at well-child visits, according to a research letter published in JAMA Pediatrics.

An analysis of data obtained from the Child Health Improvement through Computer Automation (CHICA) pediatric health surveillance system found that 4.4% of fathers who attended the well-child visit and completed a prescreening form scored positive for depression, comparable with the rate in mothers (5%). Overall, fathers composed 11.7% of parents who screened positive for depression, reported Erika R. Cheng, PhD, of Indiana University, Indianapolis, and her colleagues.

Dr. Cheng and her colleagues estimated prevalence of paternal depression using CHICA data from parents of children aged 15 months and younger from five community health centers in Indianapolis between August 1, 2016, and December 31, 2017. CHICA is a 20-question prescreen of pediatric health conditions based on the patient’s existing data.

Maternal postpartum depression was assessed using a modified version of the Edinburgh Postnatal Depression Scale, administered every 90 days during the child’s first 15 months of life, Dr. Cheng and her colleagues wrote.

Fathers were present at 30.8% of well-child visits (2,946 of 9,572) and completed the prescreening at 806 visits (8.4% of total visits). A total of 36 (4.4%) fathers screened positive for depression, compared with 273 (5%) mothers. However, since CHICA assesses depression for only one parent, some cases of paternal depression may have been missed, the investigators added.

“Pediatric clinics are thus promising settings in which to address depression in both parents as part of a family-centered approach to care,” Dr. Cheng and her coauthors concluded. “Addressing these gaps could improve detection and treatment rates of postnatal depression in both mothers and fathers.”

Two of the authors coinvented the CHICA system, and one is a co-owner of Digital Health Solutions, which licensed the system. No other disclosures were reported.

SOURCE: Cheng ER et al. JAMA Pediatr. 2018 Jul 23. doi:10.1001/jamapediatrics.2018.1505.

Prevalence of depression in fathers was similar to that of mothers screened at well-child visits, according to a research letter published in JAMA Pediatrics.

An analysis of data obtained from the Child Health Improvement through Computer Automation (CHICA) pediatric health surveillance system found that 4.4% of fathers who attended the well-child visit and completed a prescreening form scored positive for depression, comparable with the rate in mothers (5%). Overall, fathers composed 11.7% of parents who screened positive for depression, reported Erika R. Cheng, PhD, of Indiana University, Indianapolis, and her colleagues.

Dr. Cheng and her colleagues estimated prevalence of paternal depression using CHICA data from parents of children aged 15 months and younger from five community health centers in Indianapolis between August 1, 2016, and December 31, 2017. CHICA is a 20-question prescreen of pediatric health conditions based on the patient’s existing data.

Maternal postpartum depression was assessed using a modified version of the Edinburgh Postnatal Depression Scale, administered every 90 days during the child’s first 15 months of life, Dr. Cheng and her colleagues wrote.

Fathers were present at 30.8% of well-child visits (2,946 of 9,572) and completed the prescreening at 806 visits (8.4% of total visits). A total of 36 (4.4%) fathers screened positive for depression, compared with 273 (5%) mothers. However, since CHICA assesses depression for only one parent, some cases of paternal depression may have been missed, the investigators added.

“Pediatric clinics are thus promising settings in which to address depression in both parents as part of a family-centered approach to care,” Dr. Cheng and her coauthors concluded. “Addressing these gaps could improve detection and treatment rates of postnatal depression in both mothers and fathers.”

Two of the authors coinvented the CHICA system, and one is a co-owner of Digital Health Solutions, which licensed the system. No other disclosures were reported.

SOURCE: Cheng ER et al. JAMA Pediatr. 2018 Jul 23. doi:10.1001/jamapediatrics.2018.1505.

A bundle of blood cultures, broad-spectrum antibiotics, and intravenous fluid replacement reduces risk of in-hospital mortality among children with sepsis if all three forms of management are initiated within an hour, according to a cohort study published in JAMA.

invisioner/Thinkstock

Although published guidelines already recommend prompt initiation of these three elements of care, a mandate created in New York in 2013 called for these interventions to be initiated in children within 1 hour of sepsis recognition. The newly published cohort study shows a mortality benefit when this is done.

In the study, which evaluated the impact of the bundle as well as each of the components in 1,179 pediatric patients with sepsis treated at 54 hospitals, the risk-adjusted odds ratio of in-hospital mortality was 0.59 (P = .02) among patients receiving the mandated protocol, compared with those who did not.

When provided within 1 hour, none of the individual components of the bundles were associated with a significant reduction of risk-adjusted, in-hospital mortality by themselves. However, there were trends for benefit with blood cultures (OR, 0.73; P = .1) and broad-spectrum antibiotics (OR, 0.78; P = .18). There was no trend for administration of intravenous fluids (OR, 0.88; P = .56), for which the mandate specified 20 mL/kg.

Although 46.5% of patients received intravenous fluids, 62.8% received broad-spectrum antibiotics, and blood cultures were obtained in 67.7% of the children within 1 hour, only 24.9% were managed with the entire sepsis bundle. Across hospitals, the proportion of children completing the bundle ranged from 7.3% to 46.1%.

Bundle completion was more common in hospitals already treating a relatively high volume of pediatric patients and in those with pediatric specialty services, but the study authors noted that this was not a linear relationship. Rather, they called this association “hypothesis generating” and speculated that other factors might also be important.

The children in this cohort ranged in age from under 1 month to 17 years. Slightly more than half were aged 6 years or older and nearly one-third were older than 12 years. Nearly 45% had no comorbidities. Slightly more than one-third had a malignancy or were immunosuppressed.

None of the study authors reported any relevant financial relationships with industry.

SOURCE: Evans IVR et al. JAMA. 2018 Jul 24. doi:10.1001/jama.2018.9071.

A bundle of blood cultures, broad-spectrum antibiotics, and intravenous fluid replacement reduces risk of in-hospital mortality among children with sepsis if all three forms of management are initiated within an hour, according to a cohort study published in JAMA.

invisioner/Thinkstock

Although published guidelines already recommend prompt initiation of these three elements of care, a mandate created in New York in 2013 called for these interventions to be initiated in children within 1 hour of sepsis recognition. The newly published cohort study shows a mortality benefit when this is done.

In the study, which evaluated the impact of the bundle as well as each of the components in 1,179 pediatric patients with sepsis treated at 54 hospitals, the risk-adjusted odds ratio of in-hospital mortality was 0.59 (P = .02) among patients receiving the mandated protocol, compared with those who did not.

When provided within 1 hour, none of the individual components of the bundles were associated with a significant reduction of risk-adjusted, in-hospital mortality by themselves. However, there were trends for benefit with blood cultures (OR, 0.73; P = .1) and broad-spectrum antibiotics (OR, 0.78; P = .18). There was no trend for administration of intravenous fluids (OR, 0.88; P = .56), for which the mandate specified 20 mL/kg.

Although 46.5% of patients received intravenous fluids, 62.8% received broad-spectrum antibiotics, and blood cultures were obtained in 67.7% of the children within 1 hour, only 24.9% were managed with the entire sepsis bundle. Across hospitals, the proportion of children completing the bundle ranged from 7.3% to 46.1%.

Bundle completion was more common in hospitals already treating a relatively high volume of pediatric patients and in those with pediatric specialty services, but the study authors noted that this was not a linear relationship. Rather, they called this association “hypothesis generating” and speculated that other factors might also be important.

The children in this cohort ranged in age from under 1 month to 17 years. Slightly more than half were aged 6 years or older and nearly one-third were older than 12 years. Nearly 45% had no comorbidities. Slightly more than one-third had a malignancy or were immunosuppressed.

None of the study authors reported any relevant financial relationships with industry.

SOURCE: Evans IVR et al. JAMA. 2018 Jul 24. doi:10.1001/jama.2018.9071.

A bundle of blood cultures, broad-spectrum antibiotics, and intravenous fluid replacement reduces risk of in-hospital mortality among children with sepsis if all three forms of management are initiated within an hour, according to a cohort study published in JAMA.

invisioner/Thinkstock

Although published guidelines already recommend prompt initiation of these three elements of care, a mandate created in New York in 2013 called for these interventions to be initiated in children within 1 hour of sepsis recognition. The newly published cohort study shows a mortality benefit when this is done.

In the study, which evaluated the impact of the bundle as well as each of the components in 1,179 pediatric patients with sepsis treated at 54 hospitals, the risk-adjusted odds ratio of in-hospital mortality was 0.59 (P = .02) among patients receiving the mandated protocol, compared with those who did not.

When provided within 1 hour, none of the individual components of the bundles were associated with a significant reduction of risk-adjusted, in-hospital mortality by themselves. However, there were trends for benefit with blood cultures (OR, 0.73; P = .1) and broad-spectrum antibiotics (OR, 0.78; P = .18). There was no trend for administration of intravenous fluids (OR, 0.88; P = .56), for which the mandate specified 20 mL/kg.

Although 46.5% of patients received intravenous fluids, 62.8% received broad-spectrum antibiotics, and blood cultures were obtained in 67.7% of the children within 1 hour, only 24.9% were managed with the entire sepsis bundle. Across hospitals, the proportion of children completing the bundle ranged from 7.3% to 46.1%.

Bundle completion was more common in hospitals already treating a relatively high volume of pediatric patients and in those with pediatric specialty services, but the study authors noted that this was not a linear relationship. Rather, they called this association “hypothesis generating” and speculated that other factors might also be important.

The children in this cohort ranged in age from under 1 month to 17 years. Slightly more than half were aged 6 years or older and nearly one-third were older than 12 years. Nearly 45% had no comorbidities. Slightly more than one-third had a malignancy or were immunosuppressed.

None of the study authors reported any relevant financial relationships with industry.

SOURCE: Evans IVR et al. JAMA. 2018 Jul 24. doi:10.1001/jama.2018.9071.

For adult patients with HIV, earlier treatment results in faster and more likely virologic suppression along with greater linkage to care, according to the 2018 Recommendations of the International Antiviral Society-USA (IAS-USA).

The updated treatment and prevention guidelines also have outlined drug selection, including three-drug therapy (usually as a single-tablet combination) and two-drug switch therapy, as well as discouragement of cash incentives for treatment. The guidelines, written by Michael S. Saag, MD, of the University of Alabama at Birmingham and his coauthors, were published in JAMA.

Since the previous IAS-USA guidelines were published in 2016 (JAMA. 2016;316(2):191-210), multiple studies have investigated the importance of timely antiretroviral therapy (ART). In one study, patients with HIV began ART within 24 hours of diagnosis. These patients achieved virologic suppression (fewer than 200 HIV RNA copies/mL) quicker than patients treated according to previous guidelines (medians, 1.8 months vs. 4.3 months; P = .0001). Another study found that patients who began ART immediately were more likely to achieve viral suppression at 12 months (50% vs. 34%; P = .007) and become linked to care at 3 months (68% vs. 43%). As such, the updated guidelines recommended that ART should be started as soon as possible (even without supporting laboratory results). Exceptions were maintained for patients not ready to start therapy and those at risk for immune reconstitution syndrome.

With regard to initial treatment selection, three-drug therapy is recommended, incorporating an integrase single-strand transfer inhibitor (InSTI) with 2 nucleoside reverse transcriptase inhibitors.

Single-tablet formulations are effective, well tolerated, and promote medication adherence. Dolutegravir is not recommended in women who are pregnant or may become pregnant because it may increase the risk of neural tube defects. It is unclear whether other InSTIs pose similar risks. Although two-drug regimens are not recommended for initial therapy, they may be considered as switch therapy to reduce cost and complications.

The 2018 guidelines have discouraged cash incentives for ART adherence because such programs have proven ineffective. Conversely, noncash incentives are likely to be beneficial. Further recommendations to improve outcomes were wide ranging and included identification of patients subject to food scarcity or psychiatric disorders. For the latter, chronic depression has been associated with worse outcomes – including a two-fold mortality risk – and so appropriate treatment is recommended.

The researchers concluded with a brief review of future directions for HIV treatment and prevention. Long-acting injectable and oral antiretrovirals are under investigation, along with implantable and nanoparticle therapies.

“Clinicians who care for patients with HIV have a major role in advocating for programs and their patients at the local, national, and international levels,” the authors wrote. “Advocacy should go beyond access to ART and include access to mental health and substance abuse services, as well as efforts to end policies such as HIV criminalization that impede the ability to provide evidence-based care and prevention services.”

The authors reported support from Gilead, ViiV, Merck, and other sources. The current guidelines were funded by IAS-USA.

SOURCE: Saag MS et al. JAMA. 2018;320[4]:379-96.

For adult patients with HIV, earlier treatment results in faster and more likely virologic suppression along with greater linkage to care, according to the 2018 Recommendations of the International Antiviral Society-USA (IAS-USA).

The updated treatment and prevention guidelines also have outlined drug selection, including three-drug therapy (usually as a single-tablet combination) and two-drug switch therapy, as well as discouragement of cash incentives for treatment. The guidelines, written by Michael S. Saag, MD, of the University of Alabama at Birmingham and his coauthors, were published in JAMA.

Since the previous IAS-USA guidelines were published in 2016 (JAMA. 2016;316(2):191-210), multiple studies have investigated the importance of timely antiretroviral therapy (ART). In one study, patients with HIV began ART within 24 hours of diagnosis. These patients achieved virologic suppression (fewer than 200 HIV RNA copies/mL) quicker than patients treated according to previous guidelines (medians, 1.8 months vs. 4.3 months; P = .0001). Another study found that patients who began ART immediately were more likely to achieve viral suppression at 12 months (50% vs. 34%; P = .007) and become linked to care at 3 months (68% vs. 43%). As such, the updated guidelines recommended that ART should be started as soon as possible (even without supporting laboratory results). Exceptions were maintained for patients not ready to start therapy and those at risk for immune reconstitution syndrome.

With regard to initial treatment selection, three-drug therapy is recommended, incorporating an integrase single-strand transfer inhibitor (InSTI) with 2 nucleoside reverse transcriptase inhibitors.

Single-tablet formulations are effective, well tolerated, and promote medication adherence. Dolutegravir is not recommended in women who are pregnant or may become pregnant because it may increase the risk of neural tube defects. It is unclear whether other InSTIs pose similar risks. Although two-drug regimens are not recommended for initial therapy, they may be considered as switch therapy to reduce cost and complications.

The 2018 guidelines have discouraged cash incentives for ART adherence because such programs have proven ineffective. Conversely, noncash incentives are likely to be beneficial. Further recommendations to improve outcomes were wide ranging and included identification of patients subject to food scarcity or psychiatric disorders. For the latter, chronic depression has been associated with worse outcomes – including a two-fold mortality risk – and so appropriate treatment is recommended.

The researchers concluded with a brief review of future directions for HIV treatment and prevention. Long-acting injectable and oral antiretrovirals are under investigation, along with implantable and nanoparticle therapies.

“Clinicians who care for patients with HIV have a major role in advocating for programs and their patients at the local, national, and international levels,” the authors wrote. “Advocacy should go beyond access to ART and include access to mental health and substance abuse services, as well as efforts to end policies such as HIV criminalization that impede the ability to provide evidence-based care and prevention services.”

The authors reported support from Gilead, ViiV, Merck, and other sources. The current guidelines were funded by IAS-USA.

SOURCE: Saag MS et al. JAMA. 2018;320[4]:379-96.

For adult patients with HIV, earlier treatment results in faster and more likely virologic suppression along with greater linkage to care, according to the 2018 Recommendations of the International Antiviral Society-USA (IAS-USA).

The updated treatment and prevention guidelines also have outlined drug selection, including three-drug therapy (usually as a single-tablet combination) and two-drug switch therapy, as well as discouragement of cash incentives for treatment. The guidelines, written by Michael S. Saag, MD, of the University of Alabama at Birmingham and his coauthors, were published in JAMA.

Since the previous IAS-USA guidelines were published in 2016 (JAMA. 2016;316(2):191-210), multiple studies have investigated the importance of timely antiretroviral therapy (ART). In one study, patients with HIV began ART within 24 hours of diagnosis. These patients achieved virologic suppression (fewer than 200 HIV RNA copies/mL) quicker than patients treated according to previous guidelines (medians, 1.8 months vs. 4.3 months; P = .0001). Another study found that patients who began ART immediately were more likely to achieve viral suppression at 12 months (50% vs. 34%; P = .007) and become linked to care at 3 months (68% vs. 43%). As such, the updated guidelines recommended that ART should be started as soon as possible (even without supporting laboratory results). Exceptions were maintained for patients not ready to start therapy and those at risk for immune reconstitution syndrome.

With regard to initial treatment selection, three-drug therapy is recommended, incorporating an integrase single-strand transfer inhibitor (InSTI) with 2 nucleoside reverse transcriptase inhibitors.

Single-tablet formulations are effective, well tolerated, and promote medication adherence. Dolutegravir is not recommended in women who are pregnant or may become pregnant because it may increase the risk of neural tube defects. It is unclear whether other InSTIs pose similar risks. Although two-drug regimens are not recommended for initial therapy, they may be considered as switch therapy to reduce cost and complications.

The 2018 guidelines have discouraged cash incentives for ART adherence because such programs have proven ineffective. Conversely, noncash incentives are likely to be beneficial. Further recommendations to improve outcomes were wide ranging and included identification of patients subject to food scarcity or psychiatric disorders. For the latter, chronic depression has been associated with worse outcomes – including a two-fold mortality risk – and so appropriate treatment is recommended.

The researchers concluded with a brief review of future directions for HIV treatment and prevention. Long-acting injectable and oral antiretrovirals are under investigation, along with implantable and nanoparticle therapies.

“Clinicians who care for patients with HIV have a major role in advocating for programs and their patients at the local, national, and international levels,” the authors wrote. “Advocacy should go beyond access to ART and include access to mental health and substance abuse services, as well as efforts to end policies such as HIV criminalization that impede the ability to provide evidence-based care and prevention services.”

The authors reported support from Gilead, ViiV, Merck, and other sources. The current guidelines were funded by IAS-USA.

SOURCE: Saag MS et al. JAMA. 2018;320[4]:379-96.

SAN FRANCISCO – Now that erenumab has won approval as the first-in-class calcitonin gene-related peptide inhibitor for prevention of episodic and chronic migraine, a flurry of new studies shedding light on how the drug might best be used in clinical practice emerged as a highlight of the annual meeting of the American Headache Society.

Erenumab (Aimovig) is a fully human monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor. It was approved by the Food and Drug Administration at 140 and 70 mg monthly by subcutaneous injection on the strength of the required 12-week, double-blind, placebo-controlled clinical trial data. Among the fresh data presented at the headache meeting was reassuring evidence of the monoclonal antibody’s continued high degree of safety and tolerability for episodic migraine after more than 3 years of therapy, as well as a suggestion that the biologic’s efficacy for chronic migraine was not only sustained but actually increased over the course of a 1-year study.

Also, erenumab appears to be a novel treatment option for patients who have previously failed adequate trials of two to four standard preventive therapies. In addition, it has now demonstrated efficacy in reducing overuse of acute migraine drugs such as triptans, ergots, and opioids.

Here are the highlights:
 

One-year safety and efficacy for chronic migraine

Stewart J. Tepper, MD, presented results of a 1-year, open-label extension study that began after participants completed a pivotal 12-week, placebo-controlled, double-blind, randomized trial whose findings have been published (Lancet Neurol. 2017 Jun;16[6]:425-34). At the end of the 12-week, double-blind period, the mean number of monthly migraine days (MMD) in the erenumab group had dropped by 6.6 days from 18.1 at baseline. Subsequently, after 52 weeks of open-label erenumab at 140 mg monthly, that figure had further improved to 10.5 fewer MMDs than at baseline.

Bruce Jancin/MDedge News

“That’s encouraging for our patients in that we will be able to tell them that if you’re a responder, you’re likely to show some continued improvement over time,” observed Dr. Tepper, professor of neurology and director of the headache clinic at Dartmouth University in Hanover, N.H.

During 527 patient-years of open-label therapy, at least a 50% reduction in MMDs was achieved by 67% of patients in the 140-mg group and 53% in the 70-mg group.

“I think it’s also important to look at the rate of 75% or greater reduction in MMDs, which is the responder rate most closely linked to a drop in disability. That rate at 52 weeks was 42% at 140 mg and 27% at 70 mg,” the neurologist continued.

At week 52, 12.7% of patients on erenumab at 140 mg monthly had no migraines at all during the previous month.

The mean number of acute migraine-specific medication days per month decreased by about 4 days in the erenumab group during the 12-week, double-blind trial and continued to fall during the open-label extension study, with a mean reduction from baseline of 6.7 days at week 52.

“That’s clearly sustained efficacy, and it looks like some accumulating efficacy,” Dr. Tepper said.

Safety and tolerability continued to be excellent, as in the parent 12-week study.

“One of the very interesting findings we saw which differentiates erenumab from, say, onabotulinumtoxinA, is that if you looked at the patients who were on placebo during the 12 weeks of the double-blind study and then looked at the first month they went on erenumab, they caught up immediately to the patients who’d been receiving the monoclonal antibody from the beginning. That’s unlike onabotulinumtoxinA in the regulatory trials, where the patients who initially received placebo never quite caught up to those who received active therapy from the beginning,” he said.

Dr. Tepper emphasized that a clear-eyed view of an open-label study needs to recognize that only responders would have stayed in the erenumab study for a full 52 weeks, so the results paint an overly rosy picture of overall efficacy. Even so, he found the results impressive. Of 609 patients who enrolled in the study, 74% completed it.

“It’s a very encouraging 1-year study for erenumab,” he concluded.

Safety and tolerability for episodic migraine at 3-plus years

Among 383 episodic migraine patients who enrolled in an ongoing 5-year, open-label extension study of erenumab after completing a 12-week, placebo-controlled, double-blind clinical trial, there have been no new safety signals at a mean 3.2 years of follow-up. The incidence rates and types of adverse events remain indistinguishable from placebo as noted in the parent 12-week double-blind trial, with the exception of an increased rate of mild injection site reactions, reported Daniel D. Mikol, MD, PhD, executive medical director for global neuroscience development at Amgen in Thousand Oaks, Calif.

Bruce Jancin/MDedge News

Erenumab proves effective in patients who have failed multiple preventive therapies

Jan Klatt, MD, presented the results of the 12-week, double-blind portion of the phase 3b LIBERTY study, the first clinical trial specifically designed to assess the effects of CGRP-directed therapy in patients who have previously failed to respond to and/or tolerate two to four currently available preventive medications at adequate doses for at least 2-3 months.

Bruce Jancin/MDedge News

The rationale for the trial was straightforward: “There is a particularly high unmet need in patients who have failed currently available preventive therapies, and who are usually considered difficult to treat,” explained Dr. Klatt of Novartis in Basel, Switzerland.

LIBERTY included 246 such patients with episodic migraine who were randomized to 12 weeks of erenumab at 140 mg monthly or placebo. The primary endpoint – the proportion of patients with at least a 50% reduction in MMDs during weeks 9-12 from the baseline of 9.3 – occurred in 30.3% of the erenumab group, significantly better than the 13.7% rate with placebo, with an adjusted odds ratio of 2.73 for success with erenumab. An open-label extension study is ongoing.

A clear separation was already evident at week 4 of the randomized trial, a prespecified secondary endpoint. A 50% or greater reduction in MMDs was seen at that point in 23.5% of the erenumab group versus 4.8% in placebo-treated controls, for a response odds ratio of 6.16. A 75% or greater reduction in MMDs during weeks 9-12 occurred in 11.8% of the erenumab group and 4% of controls. A 100% response rate – that is, no migraines during weeks 9-12 – occurred in 5.9% of the active treatment arm and none of the controls. Outcomes on two novel patient-reported outcomes – the Migraine Physical Function Impact Diary–physical impairment and –everyday activities subscales – were also significantly better in the active treatment arm.

Treatment outcomes with erenumab were similar regardless of which drug classes patients had previously failed on, the three most common of which were beta-blockers, topiramate, and amitriptyline, which is approved for migraine prevention in Europe, where the LIBERTY trial was conducted.

One audience member observed that the 13.7% primary endpoint placebo response rate was far lower than typically seen in double-blind migraine trials.

“This is something we see quite consistently,” Dr. Klatt replied. “Once you proceed to this kind of more difficult-to-treat population, your placebo response rates drop to really low levels. It’s probably due to the fact that those patients have low expectations for any new therapy.”

Erenumab quells acute migraine medication overuse

Dr. Tepper presented a separate analysis of the 52-week, open-label extension study of erenumab, this time comparing outcomes in 252 chronic migraine patients who met criteria for acute medication overuse (AMO) at baseline and 357 who did not. Overuse was defined via International Headache Society criteria: The use of triptans, ergots, or combination analgesics on 10 or more days per month, or simple analgesics on at least 15 days monthly. Combination analgesics feature a simple analgesic plus opiates or butalbital.

“The bottom line here is that the drug worked about the same and in a very encouraging way in the AMO and nonoveruse patients,” he said. “This is obviously something that’s very, very important to us because we’d like to take our patients who are overusing acute migraine medications and use the monoclonal antibody as a way of getting them off overuse and into episodic migraine.”

After 52 weeks of open-label erenumab, 61% of the non-AMO group and 56% of those with baseline AMO had at least a 50% reduction from baseline in MMDs. The use of acute migraine-specific medications fell by 3.7 days in the non-AMO group and by 6.7 days in those with AMO at baseline.
 

Safety in patients with stable angina

Although no signal of any cardiovascular issues arose in four randomized, double-blind clinical trials or in the long-term extension studies, it was appropriate to take a more focused look at erenumab’s effects in a high-risk population with stable angina and proven ischemic coronary artery disease. That’s because CGRP is a neuropeptide that not only affects migraine, it also acts as a cytoprotective mediator released by cardiac nerve fibers during myocardial ischemia. Thus, erenumab posed a theoretic cardiovascular risk, explained Christophe Depre, MD, PhD, of Amgen.

He presented a 12-week, randomized, double-blind study in which 89 patients with stable angina were assigned to a single IV infusion of 140 mg of erenumab or placebo followed by an exercise treadmill test. Reassuringly, the CGRP inhibitor had no adverse effect on exercise time, time to onset of at least 1 mm of ST segment depression. Nor did it affect heart rate or blood pressure during or after exercise.

Dr. Tepper reported serving as a consultant to numerous pharmaceutical and medical device companies, including Amgen and Novartis, which sponsored the erenumab studies. Dr. Depre and Dr. Mikol are Amgen employees, while Dr. Klatt is employed by Novartis.

[email protected]

SAN FRANCISCO – Now that erenumab has won approval as the first-in-class calcitonin gene-related peptide inhibitor for prevention of episodic and chronic migraine, a flurry of new studies shedding light on how the drug might best be used in clinical practice emerged as a highlight of the annual meeting of the American Headache Society.

Erenumab (Aimovig) is a fully human monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor. It was approved by the Food and Drug Administration at 140 and 70 mg monthly by subcutaneous injection on the strength of the required 12-week, double-blind, placebo-controlled clinical trial data. Among the fresh data presented at the headache meeting was reassuring evidence of the monoclonal antibody’s continued high degree of safety and tolerability for episodic migraine after more than 3 years of therapy, as well as a suggestion that the biologic’s efficacy for chronic migraine was not only sustained but actually increased over the course of a 1-year study.

Also, erenumab appears to be a novel treatment option for patients who have previously failed adequate trials of two to four standard preventive therapies. In addition, it has now demonstrated efficacy in reducing overuse of acute migraine drugs such as triptans, ergots, and opioids.

Here are the highlights:
 

One-year safety and efficacy for chronic migraine

Stewart J. Tepper, MD, presented results of a 1-year, open-label extension study that began after participants completed a pivotal 12-week, placebo-controlled, double-blind, randomized trial whose findings have been published (Lancet Neurol. 2017 Jun;16[6]:425-34). At the end of the 12-week, double-blind period, the mean number of monthly migraine days (MMD) in the erenumab group had dropped by 6.6 days from 18.1 at baseline. Subsequently, after 52 weeks of open-label erenumab at 140 mg monthly, that figure had further improved to 10.5 fewer MMDs than at baseline.

Bruce Jancin/MDedge News

“That’s encouraging for our patients in that we will be able to tell them that if you’re a responder, you’re likely to show some continued improvement over time,” observed Dr. Tepper, professor of neurology and director of the headache clinic at Dartmouth University in Hanover, N.H.

During 527 patient-years of open-label therapy, at least a 50% reduction in MMDs was achieved by 67% of patients in the 140-mg group and 53% in the 70-mg group.

“I think it’s also important to look at the rate of 75% or greater reduction in MMDs, which is the responder rate most closely linked to a drop in disability. That rate at 52 weeks was 42% at 140 mg and 27% at 70 mg,” the neurologist continued.

At week 52, 12.7% of patients on erenumab at 140 mg monthly had no migraines at all during the previous month.

The mean number of acute migraine-specific medication days per month decreased by about 4 days in the erenumab group during the 12-week, double-blind trial and continued to fall during the open-label extension study, with a mean reduction from baseline of 6.7 days at week 52.

“That’s clearly sustained efficacy, and it looks like some accumulating efficacy,” Dr. Tepper said.

Safety and tolerability continued to be excellent, as in the parent 12-week study.

“One of the very interesting findings we saw which differentiates erenumab from, say, onabotulinumtoxinA, is that if you looked at the patients who were on placebo during the 12 weeks of the double-blind study and then looked at the first month they went on erenumab, they caught up immediately to the patients who’d been receiving the monoclonal antibody from the beginning. That’s unlike onabotulinumtoxinA in the regulatory trials, where the patients who initially received placebo never quite caught up to those who received active therapy from the beginning,” he said.

Dr. Tepper emphasized that a clear-eyed view of an open-label study needs to recognize that only responders would have stayed in the erenumab study for a full 52 weeks, so the results paint an overly rosy picture of overall efficacy. Even so, he found the results impressive. Of 609 patients who enrolled in the study, 74% completed it.

“It’s a very encouraging 1-year study for erenumab,” he concluded.

Safety and tolerability for episodic migraine at 3-plus years

Among 383 episodic migraine patients who enrolled in an ongoing 5-year, open-label extension study of erenumab after completing a 12-week, placebo-controlled, double-blind clinical trial, there have been no new safety signals at a mean 3.2 years of follow-up. The incidence rates and types of adverse events remain indistinguishable from placebo as noted in the parent 12-week double-blind trial, with the exception of an increased rate of mild injection site reactions, reported Daniel D. Mikol, MD, PhD, executive medical director for global neuroscience development at Amgen in Thousand Oaks, Calif.

Bruce Jancin/MDedge News

Erenumab proves effective in patients who have failed multiple preventive therapies

Jan Klatt, MD, presented the results of the 12-week, double-blind portion of the phase 3b LIBERTY study, the first clinical trial specifically designed to assess the effects of CGRP-directed therapy in patients who have previously failed to respond to and/or tolerate two to four currently available preventive medications at adequate doses for at least 2-3 months.

Bruce Jancin/MDedge News

The rationale for the trial was straightforward: “There is a particularly high unmet need in patients who have failed currently available preventive therapies, and who are usually considered difficult to treat,” explained Dr. Klatt of Novartis in Basel, Switzerland.

LIBERTY included 246 such patients with episodic migraine who were randomized to 12 weeks of erenumab at 140 mg monthly or placebo. The primary endpoint – the proportion of patients with at least a 50% reduction in MMDs during weeks 9-12 from the baseline of 9.3 – occurred in 30.3% of the erenumab group, significantly better than the 13.7% rate with placebo, with an adjusted odds ratio of 2.73 for success with erenumab. An open-label extension study is ongoing.

A clear separation was already evident at week 4 of the randomized trial, a prespecified secondary endpoint. A 50% or greater reduction in MMDs was seen at that point in 23.5% of the erenumab group versus 4.8% in placebo-treated controls, for a response odds ratio of 6.16. A 75% or greater reduction in MMDs during weeks 9-12 occurred in 11.8% of the erenumab group and 4% of controls. A 100% response rate – that is, no migraines during weeks 9-12 – occurred in 5.9% of the active treatment arm and none of the controls. Outcomes on two novel patient-reported outcomes – the Migraine Physical Function Impact Diary–physical impairment and –everyday activities subscales – were also significantly better in the active treatment arm.

Treatment outcomes with erenumab were similar regardless of which drug classes patients had previously failed on, the three most common of which were beta-blockers, topiramate, and amitriptyline, which is approved for migraine prevention in Europe, where the LIBERTY trial was conducted.

One audience member observed that the 13.7% primary endpoint placebo response rate was far lower than typically seen in double-blind migraine trials.

“This is something we see quite consistently,” Dr. Klatt replied. “Once you proceed to this kind of more difficult-to-treat population, your placebo response rates drop to really low levels. It’s probably due to the fact that those patients have low expectations for any new therapy.”

Erenumab quells acute migraine medication overuse

Dr. Tepper presented a separate analysis of the 52-week, open-label extension study of erenumab, this time comparing outcomes in 252 chronic migraine patients who met criteria for acute medication overuse (AMO) at baseline and 357 who did not. Overuse was defined via International Headache Society criteria: The use of triptans, ergots, or combination analgesics on 10 or more days per month, or simple analgesics on at least 15 days monthly. Combination analgesics feature a simple analgesic plus opiates or butalbital.

“The bottom line here is that the drug worked about the same and in a very encouraging way in the AMO and nonoveruse patients,” he said. “This is obviously something that’s very, very important to us because we’d like to take our patients who are overusing acute migraine medications and use the monoclonal antibody as a way of getting them off overuse and into episodic migraine.”

After 52 weeks of open-label erenumab, 61% of the non-AMO group and 56% of those with baseline AMO had at least a 50% reduction from baseline in MMDs. The use of acute migraine-specific medications fell by 3.7 days in the non-AMO group and by 6.7 days in those with AMO at baseline.
 

Safety in patients with stable angina

Although no signal of any cardiovascular issues arose in four randomized, double-blind clinical trials or in the long-term extension studies, it was appropriate to take a more focused look at erenumab’s effects in a high-risk population with stable angina and proven ischemic coronary artery disease. That’s because CGRP is a neuropeptide that not only affects migraine, it also acts as a cytoprotective mediator released by cardiac nerve fibers during myocardial ischemia. Thus, erenumab posed a theoretic cardiovascular risk, explained Christophe Depre, MD, PhD, of Amgen.

He presented a 12-week, randomized, double-blind study in which 89 patients with stable angina were assigned to a single IV infusion of 140 mg of erenumab or placebo followed by an exercise treadmill test. Reassuringly, the CGRP inhibitor had no adverse effect on exercise time, time to onset of at least 1 mm of ST segment depression. Nor did it affect heart rate or blood pressure during or after exercise.

Dr. Tepper reported serving as a consultant to numerous pharmaceutical and medical device companies, including Amgen and Novartis, which sponsored the erenumab studies. Dr. Depre and Dr. Mikol are Amgen employees, while Dr. Klatt is employed by Novartis.

[email protected]

SAN FRANCISCO – Now that erenumab has won approval as the first-in-class calcitonin gene-related peptide inhibitor for prevention of episodic and chronic migraine, a flurry of new studies shedding light on how the drug might best be used in clinical practice emerged as a highlight of the annual meeting of the American Headache Society.

Erenumab (Aimovig) is a fully human monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor. It was approved by the Food and Drug Administration at 140 and 70 mg monthly by subcutaneous injection on the strength of the required 12-week, double-blind, placebo-controlled clinical trial data. Among the fresh data presented at the headache meeting was reassuring evidence of the monoclonal antibody’s continued high degree of safety and tolerability for episodic migraine after more than 3 years of therapy, as well as a suggestion that the biologic’s efficacy for chronic migraine was not only sustained but actually increased over the course of a 1-year study.

Also, erenumab appears to be a novel treatment option for patients who have previously failed adequate trials of two to four standard preventive therapies. In addition, it has now demonstrated efficacy in reducing overuse of acute migraine drugs such as triptans, ergots, and opioids.

Here are the highlights:
 

One-year safety and efficacy for chronic migraine

Stewart J. Tepper, MD, presented results of a 1-year, open-label extension study that began after participants completed a pivotal 12-week, placebo-controlled, double-blind, randomized trial whose findings have been published (Lancet Neurol. 2017 Jun;16[6]:425-34). At the end of the 12-week, double-blind period, the mean number of monthly migraine days (MMD) in the erenumab group had dropped by 6.6 days from 18.1 at baseline. Subsequently, after 52 weeks of open-label erenumab at 140 mg monthly, that figure had further improved to 10.5 fewer MMDs than at baseline.

Bruce Jancin/MDedge News

“That’s encouraging for our patients in that we will be able to tell them that if you’re a responder, you’re likely to show some continued improvement over time,” observed Dr. Tepper, professor of neurology and director of the headache clinic at Dartmouth University in Hanover, N.H.

During 527 patient-years of open-label therapy, at least a 50% reduction in MMDs was achieved by 67% of patients in the 140-mg group and 53% in the 70-mg group.

“I think it’s also important to look at the rate of 75% or greater reduction in MMDs, which is the responder rate most closely linked to a drop in disability. That rate at 52 weeks was 42% at 140 mg and 27% at 70 mg,” the neurologist continued.

At week 52, 12.7% of patients on erenumab at 140 mg monthly had no migraines at all during the previous month.

The mean number of acute migraine-specific medication days per month decreased by about 4 days in the erenumab group during the 12-week, double-blind trial and continued to fall during the open-label extension study, with a mean reduction from baseline of 6.7 days at week 52.

“That’s clearly sustained efficacy, and it looks like some accumulating efficacy,” Dr. Tepper said.

Safety and tolerability continued to be excellent, as in the parent 12-week study.

“One of the very interesting findings we saw which differentiates erenumab from, say, onabotulinumtoxinA, is that if you looked at the patients who were on placebo during the 12 weeks of the double-blind study and then looked at the first month they went on erenumab, they caught up immediately to the patients who’d been receiving the monoclonal antibody from the beginning. That’s unlike onabotulinumtoxinA in the regulatory trials, where the patients who initially received placebo never quite caught up to those who received active therapy from the beginning,” he said.

Dr. Tepper emphasized that a clear-eyed view of an open-label study needs to recognize that only responders would have stayed in the erenumab study for a full 52 weeks, so the results paint an overly rosy picture of overall efficacy. Even so, he found the results impressive. Of 609 patients who enrolled in the study, 74% completed it.

“It’s a very encouraging 1-year study for erenumab,” he concluded.

Safety and tolerability for episodic migraine at 3-plus years

Among 383 episodic migraine patients who enrolled in an ongoing 5-year, open-label extension study of erenumab after completing a 12-week, placebo-controlled, double-blind clinical trial, there have been no new safety signals at a mean 3.2 years of follow-up. The incidence rates and types of adverse events remain indistinguishable from placebo as noted in the parent 12-week double-blind trial, with the exception of an increased rate of mild injection site reactions, reported Daniel D. Mikol, MD, PhD, executive medical director for global neuroscience development at Amgen in Thousand Oaks, Calif.

Bruce Jancin/MDedge News

Erenumab proves effective in patients who have failed multiple preventive therapies

Jan Klatt, MD, presented the results of the 12-week, double-blind portion of the phase 3b LIBERTY study, the first clinical trial specifically designed to assess the effects of CGRP-directed therapy in patients who have previously failed to respond to and/or tolerate two to four currently available preventive medications at adequate doses for at least 2-3 months.

Bruce Jancin/MDedge News

The rationale for the trial was straightforward: “There is a particularly high unmet need in patients who have failed currently available preventive therapies, and who are usually considered difficult to treat,” explained Dr. Klatt of Novartis in Basel, Switzerland.

LIBERTY included 246 such patients with episodic migraine who were randomized to 12 weeks of erenumab at 140 mg monthly or placebo. The primary endpoint – the proportion of patients with at least a 50% reduction in MMDs during weeks 9-12 from the baseline of 9.3 – occurred in 30.3% of the erenumab group, significantly better than the 13.7% rate with placebo, with an adjusted odds ratio of 2.73 for success with erenumab. An open-label extension study is ongoing.

A clear separation was already evident at week 4 of the randomized trial, a prespecified secondary endpoint. A 50% or greater reduction in MMDs was seen at that point in 23.5% of the erenumab group versus 4.8% in placebo-treated controls, for a response odds ratio of 6.16. A 75% or greater reduction in MMDs during weeks 9-12 occurred in 11.8% of the erenumab group and 4% of controls. A 100% response rate – that is, no migraines during weeks 9-12 – occurred in 5.9% of the active treatment arm and none of the controls. Outcomes on two novel patient-reported outcomes – the Migraine Physical Function Impact Diary–physical impairment and –everyday activities subscales – were also significantly better in the active treatment arm.

Treatment outcomes with erenumab were similar regardless of which drug classes patients had previously failed on, the three most common of which were beta-blockers, topiramate, and amitriptyline, which is approved for migraine prevention in Europe, where the LIBERTY trial was conducted.

One audience member observed that the 13.7% primary endpoint placebo response rate was far lower than typically seen in double-blind migraine trials.

“This is something we see quite consistently,” Dr. Klatt replied. “Once you proceed to this kind of more difficult-to-treat population, your placebo response rates drop to really low levels. It’s probably due to the fact that those patients have low expectations for any new therapy.”

Erenumab quells acute migraine medication overuse

Dr. Tepper presented a separate analysis of the 52-week, open-label extension study of erenumab, this time comparing outcomes in 252 chronic migraine patients who met criteria for acute medication overuse (AMO) at baseline and 357 who did not. Overuse was defined via International Headache Society criteria: The use of triptans, ergots, or combination analgesics on 10 or more days per month, or simple analgesics on at least 15 days monthly. Combination analgesics feature a simple analgesic plus opiates or butalbital.

“The bottom line here is that the drug worked about the same and in a very encouraging way in the AMO and nonoveruse patients,” he said. “This is obviously something that’s very, very important to us because we’d like to take our patients who are overusing acute migraine medications and use the monoclonal antibody as a way of getting them off overuse and into episodic migraine.”

After 52 weeks of open-label erenumab, 61% of the non-AMO group and 56% of those with baseline AMO had at least a 50% reduction from baseline in MMDs. The use of acute migraine-specific medications fell by 3.7 days in the non-AMO group and by 6.7 days in those with AMO at baseline.
 

Safety in patients with stable angina

Although no signal of any cardiovascular issues arose in four randomized, double-blind clinical trials or in the long-term extension studies, it was appropriate to take a more focused look at erenumab’s effects in a high-risk population with stable angina and proven ischemic coronary artery disease. That’s because CGRP is a neuropeptide that not only affects migraine, it also acts as a cytoprotective mediator released by cardiac nerve fibers during myocardial ischemia. Thus, erenumab posed a theoretic cardiovascular risk, explained Christophe Depre, MD, PhD, of Amgen.

He presented a 12-week, randomized, double-blind study in which 89 patients with stable angina were assigned to a single IV infusion of 140 mg of erenumab or placebo followed by an exercise treadmill test. Reassuringly, the CGRP inhibitor had no adverse effect on exercise time, time to onset of at least 1 mm of ST segment depression. Nor did it affect heart rate or blood pressure during or after exercise.

Dr. Tepper reported serving as a consultant to numerous pharmaceutical and medical device companies, including Amgen and Novartis, which sponsored the erenumab studies. Dr. Depre and Dr. Mikol are Amgen employees, while Dr. Klatt is employed by Novartis.

[email protected]

MALMO, SWEDEN – When American physicians think about health care in Europe, what typically comes to mind are government-funded, single-payer national health services with cradle-to-grave coverage of essential services, a strong public health bent, and perhaps some queuing.

Bruce Jancin/MDedge News

The U.S. approach

The current U.S. policy, implemented in 2010, is to recommend an annual flu shot for all persons older than 6 months of age.

Bruce Jancin/MDedge News

The FluMist experience

The FluMist episode is viewed by many European pediatric infectious disease experts as a debacle. Europeans eager to develop a pan-European strategy for seasonal immunization against influenza in children and adolescents viewed the U.S. FluMist episode with dismay. For the 2016-2017 and 2017-2018 flu seasons, the ACIP recommended against FluMist, a previously approved intranasally administered quadrivalent live attenuated virus vaccine, on the basis of a single study showing subpar effectiveness against influenza A H1NI. Then at its October 2017 meeting, ACIP reversed itself and reinstated FluMist for the 2018-2019 season after viewing data from Finland and several other countries demonstrating that, in countries where it hadn’t been taken off the market, the vaccine had performed as well as injectable inactivated influenza vaccines in the 2016-2017 flu season.

“I think from the European side, it’s been a bit of a sorry spectacle,” commented Dr. Osterhaus, referring to the ACIP’s waffling. After all, authorities in Canada and European countries where FluMist was available had looked at the same data that caused ACIP to derecommend the vaccine but hadn’t found it convincing.

“We’re very happy to see ACIP has reinstated the vaccine,” Dr. Nohynek said.

Dr. Abramson declined to defend the ACIP decision to drop FluMist.

“From my standpoint, knowing that influenza B kills more children than A does, if I had been on the ACIP committee – and I’m not anymore – that would not have been my vote,” he said. “Whatever you want to say about the live attenuated influenza vaccine, about how good it is against some A strains or not, it’s better than other vaccines against influenza B. And the death rate is higher from B than A in children, although that is not true in adults.”

Plus, FluMist was an important option for people avoiding immunization because they dislike shots.

“The vast majority of deaths due to flu in children in 2010-2016 have been in kids who didn’t get vaccinated,” he noted.

Dr. Nohynek said the Finnish real-world experience recorded in comprehensive national registries for the 2017-2018 flu season – a bad year for vaccine/virus mismatch in Europe – confirmed Dr. Abramson’s comments about the superiority of quadrivalent live attenuated influenza vaccine against influenza B. Among 54,611 Finnish children aged 24-35 months, the laboratory-confirmed vaccine effectiveness of trivalent inactivated virus vaccine, with 9% coverage, was 4.5% for influenza A and 12.2% for influenza B. In contrast, the vaccine effectiveness for the intranasal quadrivalent live attenuated influenza vaccine was 32% for A and a whopping 80% for B.

“It’s quite amazing, at least to me, to see figures like this in real world data,” she commented.

Session cochair Adam Finn, MD, PhD, said he has found it instructive to take a closer look at the U.K. data for the past several flu seasons.

“We’ve seen greater control of the epidemic in Scotland and Northern Ireland, where coverage in primary school kids was higher, in the 60%-70% area, and lower in England and Wales, where it was more like 50%. So we’re beginning to think that’s the kind of level of annual coverage in children we might need to suppress an epidemic. I think that’s a really important message that people should understand: We’re not looking for 95% coverage,” observed Dr. Finn, aprofessor of pediatrics at the University of Bristol (England).
 

Vaccine effectiveness will improve

Dr. Osterhaus predicted better times are coming in terms of vaccine effectiveness. Vaccine production times will become shorter as recombinant technologies replace the traditional lengthy chicken egg-based vaccine production; as a result, there will be less drift-associated mismatch. Improved surveillance, including the ability to follow strain mobility patterns and population-based antibody landscapes, are another important advance.

“We’ve always been looking at one side of the coin: the virus. Once or twice a year eminent gray people sitting together in Geneva at WHO decide which strains should be selected for the next vaccine. But if you know what antibodies are present in the population, this can be quite important information as well,” he said.

Dr. Nohynek reported receiving research funding from GlaxoSmithKline and Pfizer. The other speakers reported having no relevant financial conflicts of interest.

[email protected]

MALMO, SWEDEN – When American physicians think about health care in Europe, what typically comes to mind are government-funded, single-payer national health services with cradle-to-grave coverage of essential services, a strong public health bent, and perhaps some queuing.

Bruce Jancin/MDedge News

The U.S. approach

The current U.S. policy, implemented in 2010, is to recommend an annual flu shot for all persons older than 6 months of age.

Bruce Jancin/MDedge News

The FluMist experience

The FluMist episode is viewed by many European pediatric infectious disease experts as a debacle. Europeans eager to develop a pan-European strategy for seasonal immunization against influenza in children and adolescents viewed the U.S. FluMist episode with dismay. For the 2016-2017 and 2017-2018 flu seasons, the ACIP recommended against FluMist, a previously approved intranasally administered quadrivalent live attenuated virus vaccine, on the basis of a single study showing subpar effectiveness against influenza A H1NI. Then at its October 2017 meeting, ACIP reversed itself and reinstated FluMist for the 2018-2019 season after viewing data from Finland and several other countries demonstrating that, in countries where it hadn’t been taken off the market, the vaccine had performed as well as injectable inactivated influenza vaccines in the 2016-2017 flu season.

“I think from the European side, it’s been a bit of a sorry spectacle,” commented Dr. Osterhaus, referring to the ACIP’s waffling. After all, authorities in Canada and European countries where FluMist was available had looked at the same data that caused ACIP to derecommend the vaccine but hadn’t found it convincing.

“We’re very happy to see ACIP has reinstated the vaccine,” Dr. Nohynek said.

Dr. Abramson declined to defend the ACIP decision to drop FluMist.

“From my standpoint, knowing that influenza B kills more children than A does, if I had been on the ACIP committee – and I’m not anymore – that would not have been my vote,” he said. “Whatever you want to say about the live attenuated influenza vaccine, about how good it is against some A strains or not, it’s better than other vaccines against influenza B. And the death rate is higher from B than A in children, although that is not true in adults.”

Plus, FluMist was an important option for people avoiding immunization because they dislike shots.

“The vast majority of deaths due to flu in children in 2010-2016 have been in kids who didn’t get vaccinated,” he noted.

Dr. Nohynek said the Finnish real-world experience recorded in comprehensive national registries for the 2017-2018 flu season – a bad year for vaccine/virus mismatch in Europe – confirmed Dr. Abramson’s comments about the superiority of quadrivalent live attenuated influenza vaccine against influenza B. Among 54,611 Finnish children aged 24-35 months, the laboratory-confirmed vaccine effectiveness of trivalent inactivated virus vaccine, with 9% coverage, was 4.5% for influenza A and 12.2% for influenza B. In contrast, the vaccine effectiveness for the intranasal quadrivalent live attenuated influenza vaccine was 32% for A and a whopping 80% for B.

“It’s quite amazing, at least to me, to see figures like this in real world data,” she commented.

Session cochair Adam Finn, MD, PhD, said he has found it instructive to take a closer look at the U.K. data for the past several flu seasons.

“We’ve seen greater control of the epidemic in Scotland and Northern Ireland, where coverage in primary school kids was higher, in the 60%-70% area, and lower in England and Wales, where it was more like 50%. So we’re beginning to think that’s the kind of level of annual coverage in children we might need to suppress an epidemic. I think that’s a really important message that people should understand: We’re not looking for 95% coverage,” observed Dr. Finn, aprofessor of pediatrics at the University of Bristol (England).
 

Vaccine effectiveness will improve

Dr. Osterhaus predicted better times are coming in terms of vaccine effectiveness. Vaccine production times will become shorter as recombinant technologies replace the traditional lengthy chicken egg-based vaccine production; as a result, there will be less drift-associated mismatch. Improved surveillance, including the ability to follow strain mobility patterns and population-based antibody landscapes, are another important advance.

“We’ve always been looking at one side of the coin: the virus. Once or twice a year eminent gray people sitting together in Geneva at WHO decide which strains should be selected for the next vaccine. But if you know what antibodies are present in the population, this can be quite important information as well,” he said.

Dr. Nohynek reported receiving research funding from GlaxoSmithKline and Pfizer. The other speakers reported having no relevant financial conflicts of interest.

[email protected]

MALMO, SWEDEN – When American physicians think about health care in Europe, what typically comes to mind are government-funded, single-payer national health services with cradle-to-grave coverage of essential services, a strong public health bent, and perhaps some queuing.

Bruce Jancin/MDedge News

The U.S. approach

The current U.S. policy, implemented in 2010, is to recommend an annual flu shot for all persons older than 6 months of age.

Bruce Jancin/MDedge News

The FluMist experience

The FluMist episode is viewed by many European pediatric infectious disease experts as a debacle. Europeans eager to develop a pan-European strategy for seasonal immunization against influenza in children and adolescents viewed the U.S. FluMist episode with dismay. For the 2016-2017 and 2017-2018 flu seasons, the ACIP recommended against FluMist, a previously approved intranasally administered quadrivalent live attenuated virus vaccine, on the basis of a single study showing subpar effectiveness against influenza A H1NI. Then at its October 2017 meeting, ACIP reversed itself and reinstated FluMist for the 2018-2019 season after viewing data from Finland and several other countries demonstrating that, in countries where it hadn’t been taken off the market, the vaccine had performed as well as injectable inactivated influenza vaccines in the 2016-2017 flu season.

“I think from the European side, it’s been a bit of a sorry spectacle,” commented Dr. Osterhaus, referring to the ACIP’s waffling. After all, authorities in Canada and European countries where FluMist was available had looked at the same data that caused ACIP to derecommend the vaccine but hadn’t found it convincing.

“We’re very happy to see ACIP has reinstated the vaccine,” Dr. Nohynek said.

Dr. Abramson declined to defend the ACIP decision to drop FluMist.

“From my standpoint, knowing that influenza B kills more children than A does, if I had been on the ACIP committee – and I’m not anymore – that would not have been my vote,” he said. “Whatever you want to say about the live attenuated influenza vaccine, about how good it is against some A strains or not, it’s better than other vaccines against influenza B. And the death rate is higher from B than A in children, although that is not true in adults.”

Plus, FluMist was an important option for people avoiding immunization because they dislike shots.

“The vast majority of deaths due to flu in children in 2010-2016 have been in kids who didn’t get vaccinated,” he noted.

Dr. Nohynek said the Finnish real-world experience recorded in comprehensive national registries for the 2017-2018 flu season – a bad year for vaccine/virus mismatch in Europe – confirmed Dr. Abramson’s comments about the superiority of quadrivalent live attenuated influenza vaccine against influenza B. Among 54,611 Finnish children aged 24-35 months, the laboratory-confirmed vaccine effectiveness of trivalent inactivated virus vaccine, with 9% coverage, was 4.5% for influenza A and 12.2% for influenza B. In contrast, the vaccine effectiveness for the intranasal quadrivalent live attenuated influenza vaccine was 32% for A and a whopping 80% for B.

“It’s quite amazing, at least to me, to see figures like this in real world data,” she commented.

Session cochair Adam Finn, MD, PhD, said he has found it instructive to take a closer look at the U.K. data for the past several flu seasons.

“We’ve seen greater control of the epidemic in Scotland and Northern Ireland, where coverage in primary school kids was higher, in the 60%-70% area, and lower in England and Wales, where it was more like 50%. So we’re beginning to think that’s the kind of level of annual coverage in children we might need to suppress an epidemic. I think that’s a really important message that people should understand: We’re not looking for 95% coverage,” observed Dr. Finn, aprofessor of pediatrics at the University of Bristol (England).
 

Vaccine effectiveness will improve

Dr. Osterhaus predicted better times are coming in terms of vaccine effectiveness. Vaccine production times will become shorter as recombinant technologies replace the traditional lengthy chicken egg-based vaccine production; as a result, there will be less drift-associated mismatch. Improved surveillance, including the ability to follow strain mobility patterns and population-based antibody landscapes, are another important advance.

“We’ve always been looking at one side of the coin: the virus. Once or twice a year eminent gray people sitting together in Geneva at WHO decide which strains should be selected for the next vaccine. But if you know what antibodies are present in the population, this can be quite important information as well,” he said.

Dr. Nohynek reported receiving research funding from GlaxoSmithKline and Pfizer. The other speakers reported having no relevant financial conflicts of interest.

[email protected]

In 2012, the CDC launched the “Tips from Former Smokers” campaign. It was memorable and emotionally forceful—one woman who had oral and throat cancer delivered her ad through an artificial voicebox—but did it have an impact on actual quitting rates?

No study had been done to assess the campaign’s combined, multiyear impact until CDC researchers looked at sustained (6 month) cigarette abstinence during the first 4 years of the campaign (2012-2015).

They found that the Tips campaign led to about 9.15 million total quit attempts. Based on an assumed 5.7% abstinence rate for people attempting to quit, this amounts to approximately 522,000 sustained quits.

The researchers say their findings indicate that the comprehensive approach combining evidence-based messages with the promotion of cessation resources was highly successful. Their finding of more than half-million sustained quits underscores the critical role of national tobacco education campaigns as a “counterpoint” to the substantial pro-tobacco advertising and promotion.

In 2012, the CDC launched the “Tips from Former Smokers” campaign. It was memorable and emotionally forceful—one woman who had oral and throat cancer delivered her ad through an artificial voicebox—but did it have an impact on actual quitting rates?

No study had been done to assess the campaign’s combined, multiyear impact until CDC researchers looked at sustained (6 month) cigarette abstinence during the first 4 years of the campaign (2012-2015).

They found that the Tips campaign led to about 9.15 million total quit attempts. Based on an assumed 5.7% abstinence rate for people attempting to quit, this amounts to approximately 522,000 sustained quits.

The researchers say their findings indicate that the comprehensive approach combining evidence-based messages with the promotion of cessation resources was highly successful. Their finding of more than half-million sustained quits underscores the critical role of national tobacco education campaigns as a “counterpoint” to the substantial pro-tobacco advertising and promotion.

In 2012, the CDC launched the “Tips from Former Smokers” campaign. It was memorable and emotionally forceful—one woman who had oral and throat cancer delivered her ad through an artificial voicebox—but did it have an impact on actual quitting rates?

No study had been done to assess the campaign’s combined, multiyear impact until CDC researchers looked at sustained (6 month) cigarette abstinence during the first 4 years of the campaign (2012-2015).

They found that the Tips campaign led to about 9.15 million total quit attempts. Based on an assumed 5.7% abstinence rate for people attempting to quit, this amounts to approximately 522,000 sustained quits.

The researchers say their findings indicate that the comprehensive approach combining evidence-based messages with the promotion of cessation resources was highly successful. Their finding of more than half-million sustained quits underscores the critical role of national tobacco education campaigns as a “counterpoint” to the substantial pro-tobacco advertising and promotion.

When telemental health care (TMH) works, it works well, the research agrees. For rural patients who often do not have easy access to health care TMH can be a lifesaver. The VA uses TMH to deliver care to veterans in rural VA medical centers, community-based outpatient clinics, and residential areas.  However, TMH is still relatively new in many rural communities, say researchers from University of Mississippi in Oxford and Augusta University in Georgia, and few studies have examined the delivery tool from an administrative standpoint. The literature suggests TMH will save money—the exploratory study, however, suggests otherwise.

The researchers interviewed 6 providers selected from the 15 community mental health (MH) centers (CMHCs) in rural Mississippi as well as an independent MH counselor who develops policy for the Mississippi Counselors Association. They asked respondents about the feasibility of TMH in the Mississippi Delta; in particular, the benefits, the costs, and the role of the state in facilitating the service. The researchers also collected data from a grant-funded pilot project conducted in the Mississippi Delta region by the Delta Health Alliance, a nonprofit organization in partnership with the University of Mississippi Medical Center, which ran from 2008 to 2011. Telepsychiatry sessions are not currently being used in the region, but before the project ended, it was responsible for > 1,000 videoconferencing clinical sessions.

The initial counseling sessions were “awkward” for some patients, the interviewees said, and some clients felt the consultation was “less personal.” Getting used to the technology may take some time. Once clients acclimated the feedback was positive.

The health care providers were concerned by not being able to observe in-person nonverbal clues, such as poor hygiene, that would normally help them evaluate the client’s health. The nurse at the CMHC helped fill a gap, the researchers say, created by technology.

The researchers determined that the benefit side was weighty: For instance, patients had better access to well-trained MH professionals and to the state hospital, and family could visit inpatients via videoconferencing. Staff had better access to professional development and training.

However, cost issues were a definite concern. The project would not have been feasible without grant funding, the researchers say. Medicaid reimburses for TMH services but not for technology setup costs and maintenance. Moreover, the interviews with administrators, the researchers say, indicated that TMH did not save the organization money. Costs for the equipment, installation, rent, and other supplies were prohibitive.

Although start-up costs are high, overall systematic costs go down, with savings on travel-related costs, including fewer missed appointments. Broadband technology, videoconferencing software, webcams, and education all take money. “If policymakers are serious” about TMH, the researchers conclude, they should allocate appropriate funding and resources.

Source:
Holland J, Hatcher W, Meares WL. J Health Hum Serv Adm. 2018;41(1):52-86.

When telemental health care (TMH) works, it works well, the research agrees. For rural patients who often do not have easy access to health care TMH can be a lifesaver. The VA uses TMH to deliver care to veterans in rural VA medical centers, community-based outpatient clinics, and residential areas.  However, TMH is still relatively new in many rural communities, say researchers from University of Mississippi in Oxford and Augusta University in Georgia, and few studies have examined the delivery tool from an administrative standpoint. The literature suggests TMH will save money—the exploratory study, however, suggests otherwise.

The researchers interviewed 6 providers selected from the 15 community mental health (MH) centers (CMHCs) in rural Mississippi as well as an independent MH counselor who develops policy for the Mississippi Counselors Association. They asked respondents about the feasibility of TMH in the Mississippi Delta; in particular, the benefits, the costs, and the role of the state in facilitating the service. The researchers also collected data from a grant-funded pilot project conducted in the Mississippi Delta region by the Delta Health Alliance, a nonprofit organization in partnership with the University of Mississippi Medical Center, which ran from 2008 to 2011. Telepsychiatry sessions are not currently being used in the region, but before the project ended, it was responsible for > 1,000 videoconferencing clinical sessions.

The initial counseling sessions were “awkward” for some patients, the interviewees said, and some clients felt the consultation was “less personal.” Getting used to the technology may take some time. Once clients acclimated the feedback was positive.

The health care providers were concerned by not being able to observe in-person nonverbal clues, such as poor hygiene, that would normally help them evaluate the client’s health. The nurse at the CMHC helped fill a gap, the researchers say, created by technology.

The researchers determined that the benefit side was weighty: For instance, patients had better access to well-trained MH professionals and to the state hospital, and family could visit inpatients via videoconferencing. Staff had better access to professional development and training.

However, cost issues were a definite concern. The project would not have been feasible without grant funding, the researchers say. Medicaid reimburses for TMH services but not for technology setup costs and maintenance. Moreover, the interviews with administrators, the researchers say, indicated that TMH did not save the organization money. Costs for the equipment, installation, rent, and other supplies were prohibitive.

Although start-up costs are high, overall systematic costs go down, with savings on travel-related costs, including fewer missed appointments. Broadband technology, videoconferencing software, webcams, and education all take money. “If policymakers are serious” about TMH, the researchers conclude, they should allocate appropriate funding and resources.

Source:
Holland J, Hatcher W, Meares WL. J Health Hum Serv Adm. 2018;41(1):52-86.

When telemental health care (TMH) works, it works well, the research agrees. For rural patients who often do not have easy access to health care TMH can be a lifesaver. The VA uses TMH to deliver care to veterans in rural VA medical centers, community-based outpatient clinics, and residential areas.  However, TMH is still relatively new in many rural communities, say researchers from University of Mississippi in Oxford and Augusta University in Georgia, and few studies have examined the delivery tool from an administrative standpoint. The literature suggests TMH will save money—the exploratory study, however, suggests otherwise.

The researchers interviewed 6 providers selected from the 15 community mental health (MH) centers (CMHCs) in rural Mississippi as well as an independent MH counselor who develops policy for the Mississippi Counselors Association. They asked respondents about the feasibility of TMH in the Mississippi Delta; in particular, the benefits, the costs, and the role of the state in facilitating the service. The researchers also collected data from a grant-funded pilot project conducted in the Mississippi Delta region by the Delta Health Alliance, a nonprofit organization in partnership with the University of Mississippi Medical Center, which ran from 2008 to 2011. Telepsychiatry sessions are not currently being used in the region, but before the project ended, it was responsible for > 1,000 videoconferencing clinical sessions.

The initial counseling sessions were “awkward” for some patients, the interviewees said, and some clients felt the consultation was “less personal.” Getting used to the technology may take some time. Once clients acclimated the feedback was positive.

The health care providers were concerned by not being able to observe in-person nonverbal clues, such as poor hygiene, that would normally help them evaluate the client’s health. The nurse at the CMHC helped fill a gap, the researchers say, created by technology.

The researchers determined that the benefit side was weighty: For instance, patients had better access to well-trained MH professionals and to the state hospital, and family could visit inpatients via videoconferencing. Staff had better access to professional development and training.

However, cost issues were a definite concern. The project would not have been feasible without grant funding, the researchers say. Medicaid reimburses for TMH services but not for technology setup costs and maintenance. Moreover, the interviews with administrators, the researchers say, indicated that TMH did not save the organization money. Costs for the equipment, installation, rent, and other supplies were prohibitive.

Although start-up costs are high, overall systematic costs go down, with savings on travel-related costs, including fewer missed appointments. Broadband technology, videoconferencing software, webcams, and education all take money. “If policymakers are serious” about TMH, the researchers conclude, they should allocate appropriate funding and resources.

Source:
Holland J, Hatcher W, Meares WL. J Health Hum Serv Adm. 2018;41(1):52-86.

Image by Mae Melvin

The US Food and Drug Administration (FDA) has approved tafenoquine (Krintafel) for the radical cure of Plasmodium vivax malaria.

Tafenoquine is a single-dose medicine that is now approved to prevent relapse of P vivax malaria in patients age 16 and older who are receiving appropriate antimalarial therapy for acute P vivax infection.

Tafenoquine is the first new treatment approved for P vivax malaria in more than 60 years.

Tafenoquine is an 8-aminoquinoline derivative with activity against all stages of the P vivax lifecycle, including hypnozoites. The product was first synthesized by scientists at the Walter Reed Army Institute of Research in 1978.

GSK began developing tafenoquine as a potential medicine for malaria more than 20 years ago. In 2008, GSK entered into a collaboration with Medicines for Malaria Venture to develop tafenoquine as an anti-relapse medicine for patients infected with P vivax.

The primary evidence for the clinical efficacy and safety of the 300 mg, single dose of tafenoquine was provided by a pair of phase 3 studies—DETECTIVE (NCT01376167, TAF112582) and GATHER (NCT02216123, TAF116564).

Results from these studies were presented at the 6th International Conference on Plasmodium vivax Research (ICPVR) in 2017 (abstract 63245 and abstract 63246).

DETECTIVE trial

In this double-blind, double-dummy study, researchers evaluated the efficacy, safety, and tolerability of tafenoquine. The trial included 522 patients with P vivax malaria who were randomized to receive one of the following:

• A single dose (1 day) of tafenoquine (300 mg)
• A 14-day course of primaquine (15 mg)
• Placebo.

All patients also received a 3-day course of chloroquine to treat the acute blood stage of the infection.

A significantly greater proportion of patients remained relapse-free over the 6-month follow-up period if they were treated with tafenoquine rather than placebo—60% and 26%, respectively—with an odds ratio for risk of relapse of 0.24 (P<0.001).

Likewise, a significantly greater proportion of patients were relapse-free when treated with primaquine rather than placebo—64% and 26%, respectively—with an odds ratio of 0.20 (P<0.001).

The frequency of adverse events (AEs) was 63% for the tafenoquine group, 59% for the primaquine group, and 65% for the placebo group. The frequency of serious AEs was 8%, 3%, and 5%, respectively.

GATHER trial

This study enrolled 251 patients, ages 16 and older, with microscopy-confirmed parasitemia.

Researchers compared how a single dose of tafenoquine (300 mg) and a 14-day course of primaquine (15 mg) affected hemoglobin levels in these patients. All patients also received a standard 3-day course of chloroquine.

The incidence of decline in hemoglobin (the primary endpoint) was similar between the 2 treatment groups—2.4% in the tafenoquine arm and 1.2% in the primaquine arm. The difference in proportion was 1.23% (95% CI, -4.16%, 4.98%).

None of the patients in this study required a blood transfusion.

The frequency of AEs was 72% for the tafenoquine group and 75% for the primaquine group. The frequency of serious AEs was 4% and 1%, respectively.

Image by Mae Melvin

The US Food and Drug Administration (FDA) has approved tafenoquine (Krintafel) for the radical cure of Plasmodium vivax malaria.

Tafenoquine is a single-dose medicine that is now approved to prevent relapse of P vivax malaria in patients age 16 and older who are receiving appropriate antimalarial therapy for acute P vivax infection.

Tafenoquine is the first new treatment approved for P vivax malaria in more than 60 years.

Tafenoquine is an 8-aminoquinoline derivative with activity against all stages of the P vivax lifecycle, including hypnozoites. The product was first synthesized by scientists at the Walter Reed Army Institute of Research in 1978.

GSK began developing tafenoquine as a potential medicine for malaria more than 20 years ago. In 2008, GSK entered into a collaboration with Medicines for Malaria Venture to develop tafenoquine as an anti-relapse medicine for patients infected with P vivax.

The primary evidence for the clinical efficacy and safety of the 300 mg, single dose of tafenoquine was provided by a pair of phase 3 studies—DETECTIVE (NCT01376167, TAF112582) and GATHER (NCT02216123, TAF116564).

Results from these studies were presented at the 6th International Conference on Plasmodium vivax Research (ICPVR) in 2017 (abstract 63245 and abstract 63246).

DETECTIVE trial

In this double-blind, double-dummy study, researchers evaluated the efficacy, safety, and tolerability of tafenoquine. The trial included 522 patients with P vivax malaria who were randomized to receive one of the following:

• A single dose (1 day) of tafenoquine (300 mg)
• A 14-day course of primaquine (15 mg)
• Placebo.

All patients also received a 3-day course of chloroquine to treat the acute blood stage of the infection.

A significantly greater proportion of patients remained relapse-free over the 6-month follow-up period if they were treated with tafenoquine rather than placebo—60% and 26%, respectively—with an odds ratio for risk of relapse of 0.24 (P<0.001).

Likewise, a significantly greater proportion of patients were relapse-free when treated with primaquine rather than placebo—64% and 26%, respectively—with an odds ratio of 0.20 (P<0.001).

The frequency of adverse events (AEs) was 63% for the tafenoquine group, 59% for the primaquine group, and 65% for the placebo group. The frequency of serious AEs was 8%, 3%, and 5%, respectively.

GATHER trial

This study enrolled 251 patients, ages 16 and older, with microscopy-confirmed parasitemia.

Researchers compared how a single dose of tafenoquine (300 mg) and a 14-day course of primaquine (15 mg) affected hemoglobin levels in these patients. All patients also received a standard 3-day course of chloroquine.

The incidence of decline in hemoglobin (the primary endpoint) was similar between the 2 treatment groups—2.4% in the tafenoquine arm and 1.2% in the primaquine arm. The difference in proportion was 1.23% (95% CI, -4.16%, 4.98%).

None of the patients in this study required a blood transfusion.

The frequency of AEs was 72% for the tafenoquine group and 75% for the primaquine group. The frequency of serious AEs was 4% and 1%, respectively.

Image by Mae Melvin

The US Food and Drug Administration (FDA) has approved tafenoquine (Krintafel) for the radical cure of Plasmodium vivax malaria.

Tafenoquine is a single-dose medicine that is now approved to prevent relapse of P vivax malaria in patients age 16 and older who are receiving appropriate antimalarial therapy for acute P vivax infection.

Tafenoquine is the first new treatment approved for P vivax malaria in more than 60 years.

Tafenoquine is an 8-aminoquinoline derivative with activity against all stages of the P vivax lifecycle, including hypnozoites. The product was first synthesized by scientists at the Walter Reed Army Institute of Research in 1978.

GSK began developing tafenoquine as a potential medicine for malaria more than 20 years ago. In 2008, GSK entered into a collaboration with Medicines for Malaria Venture to develop tafenoquine as an anti-relapse medicine for patients infected with P vivax.

The primary evidence for the clinical efficacy and safety of the 300 mg, single dose of tafenoquine was provided by a pair of phase 3 studies—DETECTIVE (NCT01376167, TAF112582) and GATHER (NCT02216123, TAF116564).

Results from these studies were presented at the 6th International Conference on Plasmodium vivax Research (ICPVR) in 2017 (abstract 63245 and abstract 63246).

DETECTIVE trial

In this double-blind, double-dummy study, researchers evaluated the efficacy, safety, and tolerability of tafenoquine. The trial included 522 patients with P vivax malaria who were randomized to receive one of the following:

• A single dose (1 day) of tafenoquine (300 mg)
• A 14-day course of primaquine (15 mg)
• Placebo.

All patients also received a 3-day course of chloroquine to treat the acute blood stage of the infection.

A significantly greater proportion of patients remained relapse-free over the 6-month follow-up period if they were treated with tafenoquine rather than placebo—60% and 26%, respectively—with an odds ratio for risk of relapse of 0.24 (P<0.001).

Likewise, a significantly greater proportion of patients were relapse-free when treated with primaquine rather than placebo—64% and 26%, respectively—with an odds ratio of 0.20 (P<0.001).

The frequency of adverse events (AEs) was 63% for the tafenoquine group, 59% for the primaquine group, and 65% for the placebo group. The frequency of serious AEs was 8%, 3%, and 5%, respectively.

GATHER trial

This study enrolled 251 patients, ages 16 and older, with microscopy-confirmed parasitemia.

Researchers compared how a single dose of tafenoquine (300 mg) and a 14-day course of primaquine (15 mg) affected hemoglobin levels in these patients. All patients also received a standard 3-day course of chloroquine.

The incidence of decline in hemoglobin (the primary endpoint) was similar between the 2 treatment groups—2.4% in the tafenoquine arm and 1.2% in the primaquine arm. The difference in proportion was 1.23% (95% CI, -4.16%, 4.98%).

None of the patients in this study required a blood transfusion.

The frequency of AEs was 72% for the tafenoquine group and 75% for the primaquine group. The frequency of serious AEs was 4% and 1%, respectively.

Lab mouse

Researchers have found the NOTCH1 pathway “hijacks” heat shock transcription factor 1 (HSF1) signaling in T-cell acute lymphoblastic leukemia (T-ALL).

Therefore, blocking one or more genes in the HSF1 pathway could represent a new approach to treating T-ALL.

An experimental drug, PU-H71, is already in development against one of these targets, heat shock protein 90 (HSP90).

The researchers found that PU-H71 was active against T-ALL in vitro and in vivo.

The team recounted these findings in Nature Medicine.

“Our study shows how the NOTCH1 pathway hijacks the heat shock transcription factor 1 pathway to promote tumor growth,” said study author Iannis Aifantis, PhD, of NYU School of Medicine in New York, New York.

“The cancer cells are sending into overdrive a system that helps healthy cells respond to stress.”

Dr Aifantis and his colleagues found that HSF1 is involved in the pathogenesis of T-ALL. When they knocked down HSF1 in T-ALL cell lines, the researchers observed an increase in apoptosis, defective proteostasis, and a decrease in the growth of leukemic cells.

Similarly, HSF1 was deemed necessary for disease progression in mouse models of T-ALL. When the researchers deleted HSF1, mice experienced “striking” reductions in leukemic burden and “dramatic” improvements in survival. However, HSF1 deletion did not affect normal hematopoiesis.

Dr Aifantis and his colleagues also showed that NOTCH1 regulates the epichaperome in T-ALL. The team said previous studies have shown that, in the presence of oncogenic stress, heat shock proteins participate in a network nucleated by HSP90 and HSP70 chaperones—the epichaperome.

The researchers found that an intact epichaperome was critical for T-ALL by showing that pharmacologic inhibition of HSP90 and HSP70 significantly hindered the growth of human T-ALL in vitro. The team also found the HSP90 inhibitor PU-H71 reduced leukemic burden and extended survival in a NOTCH1-inducible T-ALL mouse model.

Then, the researchers found NOTCH1 levels could predict response to HSP90 inhibition in vitro. T-ALL patient samples expressing high levels of nuclear NOTCH1 and high levels of epichaperome were significantly more sensitive to treatment with PU-H71.

PU-H71 is already in early clinical trials of patients with breast cancer. If further testing proves successful, PU-H71 could be quickly adapted for trials in T-ALL patients, according to Dr Aifantis.

In the meantime, he and his colleagues plan to evaluate the effects of another 8 proteins produced by genes active in the HSF1 pathway to see if any show promising anticancer activity in T-ALL.

Lab mouse

Researchers have found the NOTCH1 pathway “hijacks” heat shock transcription factor 1 (HSF1) signaling in T-cell acute lymphoblastic leukemia (T-ALL).

Therefore, blocking one or more genes in the HSF1 pathway could represent a new approach to treating T-ALL.

An experimental drug, PU-H71, is already in development against one of these targets, heat shock protein 90 (HSP90).

The researchers found that PU-H71 was active against T-ALL in vitro and in vivo.

The team recounted these findings in Nature Medicine.

“Our study shows how the NOTCH1 pathway hijacks the heat shock transcription factor 1 pathway to promote tumor growth,” said study author Iannis Aifantis, PhD, of NYU School of Medicine in New York, New York.

“The cancer cells are sending into overdrive a system that helps healthy cells respond to stress.”

Dr Aifantis and his colleagues found that HSF1 is involved in the pathogenesis of T-ALL. When they knocked down HSF1 in T-ALL cell lines, the researchers observed an increase in apoptosis, defective proteostasis, and a decrease in the growth of leukemic cells.

Similarly, HSF1 was deemed necessary for disease progression in mouse models of T-ALL. When the researchers deleted HSF1, mice experienced “striking” reductions in leukemic burden and “dramatic” improvements in survival. However, HSF1 deletion did not affect normal hematopoiesis.

Dr Aifantis and his colleagues also showed that NOTCH1 regulates the epichaperome in T-ALL. The team said previous studies have shown that, in the presence of oncogenic stress, heat shock proteins participate in a network nucleated by HSP90 and HSP70 chaperones—the epichaperome.

The researchers found that an intact epichaperome was critical for T-ALL by showing that pharmacologic inhibition of HSP90 and HSP70 significantly hindered the growth of human T-ALL in vitro. The team also found the HSP90 inhibitor PU-H71 reduced leukemic burden and extended survival in a NOTCH1-inducible T-ALL mouse model.

Then, the researchers found NOTCH1 levels could predict response to HSP90 inhibition in vitro. T-ALL patient samples expressing high levels of nuclear NOTCH1 and high levels of epichaperome were significantly more sensitive to treatment with PU-H71.

PU-H71 is already in early clinical trials of patients with breast cancer. If further testing proves successful, PU-H71 could be quickly adapted for trials in T-ALL patients, according to Dr Aifantis.

In the meantime, he and his colleagues plan to evaluate the effects of another 8 proteins produced by genes active in the HSF1 pathway to see if any show promising anticancer activity in T-ALL.

Lab mouse

Researchers have found the NOTCH1 pathway “hijacks” heat shock transcription factor 1 (HSF1) signaling in T-cell acute lymphoblastic leukemia (T-ALL).

Therefore, blocking one or more genes in the HSF1 pathway could represent a new approach to treating T-ALL.

An experimental drug, PU-H71, is already in development against one of these targets, heat shock protein 90 (HSP90).

The researchers found that PU-H71 was active against T-ALL in vitro and in vivo.

The team recounted these findings in Nature Medicine.

“Our study shows how the NOTCH1 pathway hijacks the heat shock transcription factor 1 pathway to promote tumor growth,” said study author Iannis Aifantis, PhD, of NYU School of Medicine in New York, New York.

“The cancer cells are sending into overdrive a system that helps healthy cells respond to stress.”

Dr Aifantis and his colleagues found that HSF1 is involved in the pathogenesis of T-ALL. When they knocked down HSF1 in T-ALL cell lines, the researchers observed an increase in apoptosis, defective proteostasis, and a decrease in the growth of leukemic cells.

Similarly, HSF1 was deemed necessary for disease progression in mouse models of T-ALL. When the researchers deleted HSF1, mice experienced “striking” reductions in leukemic burden and “dramatic” improvements in survival. However, HSF1 deletion did not affect normal hematopoiesis.

Dr Aifantis and his colleagues also showed that NOTCH1 regulates the epichaperome in T-ALL. The team said previous studies have shown that, in the presence of oncogenic stress, heat shock proteins participate in a network nucleated by HSP90 and HSP70 chaperones—the epichaperome.

The researchers found that an intact epichaperome was critical for T-ALL by showing that pharmacologic inhibition of HSP90 and HSP70 significantly hindered the growth of human T-ALL in vitro. The team also found the HSP90 inhibitor PU-H71 reduced leukemic burden and extended survival in a NOTCH1-inducible T-ALL mouse model.

Then, the researchers found NOTCH1 levels could predict response to HSP90 inhibition in vitro. T-ALL patient samples expressing high levels of nuclear NOTCH1 and high levels of epichaperome were significantly more sensitive to treatment with PU-H71.

PU-H71 is already in early clinical trials of patients with breast cancer. If further testing proves successful, PU-H71 could be quickly adapted for trials in T-ALL patients, according to Dr Aifantis.

In the meantime, he and his colleagues plan to evaluate the effects of another 8 proteins produced by genes active in the HSF1 pathway to see if any show promising anticancer activity in T-ALL.