Prior antibiotic use may be associated with a reduced treatment response to checkpoint inhibitors, and worse outcomes, in patients with cancer, according to investigators.

In a prospective cohort study, researchers followed 196 patients with cancer who were treated with immune checkpoint inhibitors in routine clinical practice.

A total of 22 patients had been treated with a 7-day or less course of broad-spectrum beta-lactam–based antibiotics in the 30 days prior to starting immune checkpoint inhibitor therapy, and 68 patients were concurrently taking broad-spectrum beta-lactam–based antibiotics with their checkpoint inhibitor therapy.

The analysis revealed that prior antibiotic therapy was associated with nearly a 100% greater likelihood of poor response to checkpoint inhibitor therapy (P less than .001) and significantly worse overall survival (2 vs. 26 months). Patients who had been on prior antibiotic therapy were also more likely to stop checkpoint inhibitor therapy because their disease had progressed, and were more likely to die of progressive disease while on checkpoint inhibitors.

However, concurrent antibiotic use did not appear to affect either treatment response to checkpoint inhibitors or overall survival.

The most common indication for both prior and concurrent antibiotic use was respiratory tract infections. Researchers examined whether cancer type might play a role in contributing to the association; for example, chronic airway disease in lung cancer might mean higher likelihood of antibiotic use but also lower treatment response and survival.

They found that the association between prior antibiotic therapy and overall survival was consistent across the 119 patients with non–small cell lung cancer, the 38 patients with melanoma, and the 39 patients with other tumor types.

The association was also independent of the class of antibiotic used, the patient’s performance status, and their corticosteroid use.

“Broad-spectrum ATB [antibiotic] use can cause prolonged disruption of the gut ecosystem and impair the effectiveness of the cytotoxic T-cell response against cancer, strengthening the biologic plausibility underlying the adverse effect of ATB therapy on immunotherapy outcomes,” wrote Dr. David J. Pinato, from Imperial College London, and coauthors in JAMA Oncology.

Addressing the question of whether comorbidities might be the mediating factor, the authors pointed out that the use of antibiotics during checkpoint inhibitor therapy – which was a potential indicator of patients’ status worsening during treatment – was not associated with reduced response to treatment or lower overall survival.

“Although provision of cATB [concurrent antibiotic] therapy appears to be safe in the context of immunotherapy, clinicians should carefully weigh the pros and cons of prescribing broad-spectrum ATBs prior to ICI [immune checkpoint inhibitor] treatment,” they wrote.

The study was supported by the Imperial College National Institute for Health Research Biomedical Research Centre, the Imperial College Tissue Bank, the Imperial Cancer Research U.K. Centre, the National Institute for Health Research, and the Wellcome Trust Strategic Fund. Two authors reported receiving grant funding and personal fees from the pharmaceutical sector unrelated to the study.

SOURCE: Pinato D et al. JAMA Oncol. 2019 Sep 12. doi: 10.1001/jamaoncol.2019.2785.

Prior antibiotic use may be associated with a reduced treatment response to checkpoint inhibitors, and worse outcomes, in patients with cancer, according to investigators.

In a prospective cohort study, researchers followed 196 patients with cancer who were treated with immune checkpoint inhibitors in routine clinical practice.

A total of 22 patients had been treated with a 7-day or less course of broad-spectrum beta-lactam–based antibiotics in the 30 days prior to starting immune checkpoint inhibitor therapy, and 68 patients were concurrently taking broad-spectrum beta-lactam–based antibiotics with their checkpoint inhibitor therapy.

The analysis revealed that prior antibiotic therapy was associated with nearly a 100% greater likelihood of poor response to checkpoint inhibitor therapy (P less than .001) and significantly worse overall survival (2 vs. 26 months). Patients who had been on prior antibiotic therapy were also more likely to stop checkpoint inhibitor therapy because their disease had progressed, and were more likely to die of progressive disease while on checkpoint inhibitors.

However, concurrent antibiotic use did not appear to affect either treatment response to checkpoint inhibitors or overall survival.

The most common indication for both prior and concurrent antibiotic use was respiratory tract infections. Researchers examined whether cancer type might play a role in contributing to the association; for example, chronic airway disease in lung cancer might mean higher likelihood of antibiotic use but also lower treatment response and survival.

They found that the association between prior antibiotic therapy and overall survival was consistent across the 119 patients with non–small cell lung cancer, the 38 patients with melanoma, and the 39 patients with other tumor types.

The association was also independent of the class of antibiotic used, the patient’s performance status, and their corticosteroid use.

“Broad-spectrum ATB [antibiotic] use can cause prolonged disruption of the gut ecosystem and impair the effectiveness of the cytotoxic T-cell response against cancer, strengthening the biologic plausibility underlying the adverse effect of ATB therapy on immunotherapy outcomes,” wrote Dr. David J. Pinato, from Imperial College London, and coauthors in JAMA Oncology.

Addressing the question of whether comorbidities might be the mediating factor, the authors pointed out that the use of antibiotics during checkpoint inhibitor therapy – which was a potential indicator of patients’ status worsening during treatment – was not associated with reduced response to treatment or lower overall survival.

“Although provision of cATB [concurrent antibiotic] therapy appears to be safe in the context of immunotherapy, clinicians should carefully weigh the pros and cons of prescribing broad-spectrum ATBs prior to ICI [immune checkpoint inhibitor] treatment,” they wrote.

The study was supported by the Imperial College National Institute for Health Research Biomedical Research Centre, the Imperial College Tissue Bank, the Imperial Cancer Research U.K. Centre, the National Institute for Health Research, and the Wellcome Trust Strategic Fund. Two authors reported receiving grant funding and personal fees from the pharmaceutical sector unrelated to the study.

SOURCE: Pinato D et al. JAMA Oncol. 2019 Sep 12. doi: 10.1001/jamaoncol.2019.2785.

Prior antibiotic use may be associated with a reduced treatment response to checkpoint inhibitors, and worse outcomes, in patients with cancer, according to investigators.

In a prospective cohort study, researchers followed 196 patients with cancer who were treated with immune checkpoint inhibitors in routine clinical practice.

A total of 22 patients had been treated with a 7-day or less course of broad-spectrum beta-lactam–based antibiotics in the 30 days prior to starting immune checkpoint inhibitor therapy, and 68 patients were concurrently taking broad-spectrum beta-lactam–based antibiotics with their checkpoint inhibitor therapy.

The analysis revealed that prior antibiotic therapy was associated with nearly a 100% greater likelihood of poor response to checkpoint inhibitor therapy (P less than .001) and significantly worse overall survival (2 vs. 26 months). Patients who had been on prior antibiotic therapy were also more likely to stop checkpoint inhibitor therapy because their disease had progressed, and were more likely to die of progressive disease while on checkpoint inhibitors.

However, concurrent antibiotic use did not appear to affect either treatment response to checkpoint inhibitors or overall survival.

The most common indication for both prior and concurrent antibiotic use was respiratory tract infections. Researchers examined whether cancer type might play a role in contributing to the association; for example, chronic airway disease in lung cancer might mean higher likelihood of antibiotic use but also lower treatment response and survival.

They found that the association between prior antibiotic therapy and overall survival was consistent across the 119 patients with non–small cell lung cancer, the 38 patients with melanoma, and the 39 patients with other tumor types.

The association was also independent of the class of antibiotic used, the patient’s performance status, and their corticosteroid use.

“Broad-spectrum ATB [antibiotic] use can cause prolonged disruption of the gut ecosystem and impair the effectiveness of the cytotoxic T-cell response against cancer, strengthening the biologic plausibility underlying the adverse effect of ATB therapy on immunotherapy outcomes,” wrote Dr. David J. Pinato, from Imperial College London, and coauthors in JAMA Oncology.

Addressing the question of whether comorbidities might be the mediating factor, the authors pointed out that the use of antibiotics during checkpoint inhibitor therapy – which was a potential indicator of patients’ status worsening during treatment – was not associated with reduced response to treatment or lower overall survival.

“Although provision of cATB [concurrent antibiotic] therapy appears to be safe in the context of immunotherapy, clinicians should carefully weigh the pros and cons of prescribing broad-spectrum ATBs prior to ICI [immune checkpoint inhibitor] treatment,” they wrote.

The study was supported by the Imperial College National Institute for Health Research Biomedical Research Centre, the Imperial College Tissue Bank, the Imperial Cancer Research U.K. Centre, the National Institute for Health Research, and the Wellcome Trust Strategic Fund. Two authors reported receiving grant funding and personal fees from the pharmaceutical sector unrelated to the study.

SOURCE: Pinato D et al. JAMA Oncol. 2019 Sep 12. doi: 10.1001/jamaoncol.2019.2785.

STOCKHOLM – Ponesimod reduces annualized relapse rate, compared with teriflunomide, in adults with relapsing multiple sclerosis (MS), according to research presented at ECTRIMS 2019. Ponesimod also reduces fatigue and the number of active lesions, compared with teriflunomide.

Ponesimod selectively modulates the sphingosine-1-phosphate receptor 1 (S1P1). The drug is administered orally and reduces circulating lymphocyte counts by inducing a rapid, dose-dependent, and reversible sequestration of lymphocytes in lymphoid organs. This effect decreases the number of immune cells available for inflammatory attacks in the CNS, said Ludwig Kappos, MD, head of the department of neurology at University Hospital Basel (Switzerland). The drug has no active metabolites, and its effects on the immune system are reversible.

Dr. Kappos and colleagues conducted the OPTIMUM phase 3 study to assess the efficacy and safety of oral ponesimod, compared with those of teriflunomide. They enrolled patients between ages 18 and 55 years with an established diagnosis of MS according to the 2010 McDonald criteria with a relapsing course from onset into the multicenter, randomized, double-blind, superiority study. Eligible patients had an Expanded Disability Status Scale (EDSS) score of 0 to 5.5 inclusive and recent clinical or MRI disease activity. Dr. Kappos and colleagues randomized participants in equal groups to receive ponesimod (20 mg/day) or teriflunomide (14 mg/day) and the respective placebo for 108 weeks. To mitigate the potential effects on heart rate that are associated with S1P1 modulators, patients were titrated gradually from 2 mg/day to the target dose over 14 days.

The trial’s primary endpoint was the annualized relapse rate over 108 weeks. Secondary endpoints were the effect on fatigue-related symptoms, as assessed with Fatigue Symptom and Impact Questionnaire-Relapsing MS (FSIQ-RMS); active lesions on MRI to week 108; and time to 12- and 24-week confirmed disability accumulation to end of study. The investigators also assessed the drugs’ safety and tolerability.

Dr. Kappos and colleagues randomized 1,133 patients at 162 sites in 28 countries. They stratified randomization according to whether participants had received prior disease-modifying treatment in the previous 2 years (39.4% had, and 60.6% had not) and EDSS score at baseline (83.4% had a score of 3.5 or lower, and 16.6% had a score above 3.5). The population’s mean age was 36.7 years, and 65% of participants were female. Most patients were recruited in Europe, and 51% came from E.U. countries. Patients’ mean baseline EDSS score was 2.6, and mean disease duration was 7.6 years. The mean prestudy 12-month relapse rate was 1.3, and 483 (42.7%) patients had one or more gadolinium-enhancing T1 lesions on baseline MRI. The two treatment groups were well balanced. The rate of treatment discontinuation was 16.6% for ponesimod and 16.4% on teriflunomide.

At the end of the study, the annualized relapse rate was 0.202 in the ponesimod group and 0.290 in the teriflunomide group. Compared with teriflunomide, ponesimod significantly reduced the annualized relapse rate by 30.5%. Fatigue remained stable in the ponesimod group, but worsened in the teriflunomide group: The mean difference in FSIQ-RMS score between the arms at week 108 was 3.57, and this result was statistically significant. In addition, ponesimod significantly reduced the number of active lesions by 56%, compared with teriflunomide. The risk for 12- and 24- week confirmed disability were lower with ponesimod, compared with teriflunomide, but the difference was not statistically significant.

The rates of treatment-emergent adverse events were approximately 89% for the ponesimod arm and 88% for teriflunomide. The rates of serious adverse events were about 9% for ponesimod and about 8% for teriflunomide. Respiratory events and laboratory values prompted slightly more study discontinuations in the ponesimod group than in the teriflunomide group.

This research represents the first controlled study to show superior efficacy of oral ponesimod, compared with an approved oral compound, said Dr. Kappos. “The overall profile suggests that [ponesimod] may be a valuable addition to our armamentarium in treating patients with relapsing forms of MS,” he concluded.

The study was supported by Actelion Pharmaceuticals. University Hospital Basel, where Dr. Kappos works, received steering committee, advisory board, and consultancy fees from Actelion and other companies.

egreb@mdedge.com

SOURCE: Kappos L et al. ECTRIMS 2019, Abstract 93.

STOCKHOLM – Ponesimod reduces annualized relapse rate, compared with teriflunomide, in adults with relapsing multiple sclerosis (MS), according to research presented at ECTRIMS 2019. Ponesimod also reduces fatigue and the number of active lesions, compared with teriflunomide.

Ponesimod selectively modulates the sphingosine-1-phosphate receptor 1 (S1P1). The drug is administered orally and reduces circulating lymphocyte counts by inducing a rapid, dose-dependent, and reversible sequestration of lymphocytes in lymphoid organs. This effect decreases the number of immune cells available for inflammatory attacks in the CNS, said Ludwig Kappos, MD, head of the department of neurology at University Hospital Basel (Switzerland). The drug has no active metabolites, and its effects on the immune system are reversible.

Dr. Kappos and colleagues conducted the OPTIMUM phase 3 study to assess the efficacy and safety of oral ponesimod, compared with those of teriflunomide. They enrolled patients between ages 18 and 55 years with an established diagnosis of MS according to the 2010 McDonald criteria with a relapsing course from onset into the multicenter, randomized, double-blind, superiority study. Eligible patients had an Expanded Disability Status Scale (EDSS) score of 0 to 5.5 inclusive and recent clinical or MRI disease activity. Dr. Kappos and colleagues randomized participants in equal groups to receive ponesimod (20 mg/day) or teriflunomide (14 mg/day) and the respective placebo for 108 weeks. To mitigate the potential effects on heart rate that are associated with S1P1 modulators, patients were titrated gradually from 2 mg/day to the target dose over 14 days.

The trial’s primary endpoint was the annualized relapse rate over 108 weeks. Secondary endpoints were the effect on fatigue-related symptoms, as assessed with Fatigue Symptom and Impact Questionnaire-Relapsing MS (FSIQ-RMS); active lesions on MRI to week 108; and time to 12- and 24-week confirmed disability accumulation to end of study. The investigators also assessed the drugs’ safety and tolerability.

Dr. Kappos and colleagues randomized 1,133 patients at 162 sites in 28 countries. They stratified randomization according to whether participants had received prior disease-modifying treatment in the previous 2 years (39.4% had, and 60.6% had not) and EDSS score at baseline (83.4% had a score of 3.5 or lower, and 16.6% had a score above 3.5). The population’s mean age was 36.7 years, and 65% of participants were female. Most patients were recruited in Europe, and 51% came from E.U. countries. Patients’ mean baseline EDSS score was 2.6, and mean disease duration was 7.6 years. The mean prestudy 12-month relapse rate was 1.3, and 483 (42.7%) patients had one or more gadolinium-enhancing T1 lesions on baseline MRI. The two treatment groups were well balanced. The rate of treatment discontinuation was 16.6% for ponesimod and 16.4% on teriflunomide.

At the end of the study, the annualized relapse rate was 0.202 in the ponesimod group and 0.290 in the teriflunomide group. Compared with teriflunomide, ponesimod significantly reduced the annualized relapse rate by 30.5%. Fatigue remained stable in the ponesimod group, but worsened in the teriflunomide group: The mean difference in FSIQ-RMS score between the arms at week 108 was 3.57, and this result was statistically significant. In addition, ponesimod significantly reduced the number of active lesions by 56%, compared with teriflunomide. The risk for 12- and 24- week confirmed disability were lower with ponesimod, compared with teriflunomide, but the difference was not statistically significant.

The rates of treatment-emergent adverse events were approximately 89% for the ponesimod arm and 88% for teriflunomide. The rates of serious adverse events were about 9% for ponesimod and about 8% for teriflunomide. Respiratory events and laboratory values prompted slightly more study discontinuations in the ponesimod group than in the teriflunomide group.

This research represents the first controlled study to show superior efficacy of oral ponesimod, compared with an approved oral compound, said Dr. Kappos. “The overall profile suggests that [ponesimod] may be a valuable addition to our armamentarium in treating patients with relapsing forms of MS,” he concluded.

The study was supported by Actelion Pharmaceuticals. University Hospital Basel, where Dr. Kappos works, received steering committee, advisory board, and consultancy fees from Actelion and other companies.

egreb@mdedge.com

SOURCE: Kappos L et al. ECTRIMS 2019, Abstract 93.

STOCKHOLM – Ponesimod reduces annualized relapse rate, compared with teriflunomide, in adults with relapsing multiple sclerosis (MS), according to research presented at ECTRIMS 2019. Ponesimod also reduces fatigue and the number of active lesions, compared with teriflunomide.

Ponesimod selectively modulates the sphingosine-1-phosphate receptor 1 (S1P1). The drug is administered orally and reduces circulating lymphocyte counts by inducing a rapid, dose-dependent, and reversible sequestration of lymphocytes in lymphoid organs. This effect decreases the number of immune cells available for inflammatory attacks in the CNS, said Ludwig Kappos, MD, head of the department of neurology at University Hospital Basel (Switzerland). The drug has no active metabolites, and its effects on the immune system are reversible.

Dr. Kappos and colleagues conducted the OPTIMUM phase 3 study to assess the efficacy and safety of oral ponesimod, compared with those of teriflunomide. They enrolled patients between ages 18 and 55 years with an established diagnosis of MS according to the 2010 McDonald criteria with a relapsing course from onset into the multicenter, randomized, double-blind, superiority study. Eligible patients had an Expanded Disability Status Scale (EDSS) score of 0 to 5.5 inclusive and recent clinical or MRI disease activity. Dr. Kappos and colleagues randomized participants in equal groups to receive ponesimod (20 mg/day) or teriflunomide (14 mg/day) and the respective placebo for 108 weeks. To mitigate the potential effects on heart rate that are associated with S1P1 modulators, patients were titrated gradually from 2 mg/day to the target dose over 14 days.

The trial’s primary endpoint was the annualized relapse rate over 108 weeks. Secondary endpoints were the effect on fatigue-related symptoms, as assessed with Fatigue Symptom and Impact Questionnaire-Relapsing MS (FSIQ-RMS); active lesions on MRI to week 108; and time to 12- and 24-week confirmed disability accumulation to end of study. The investigators also assessed the drugs’ safety and tolerability.

Dr. Kappos and colleagues randomized 1,133 patients at 162 sites in 28 countries. They stratified randomization according to whether participants had received prior disease-modifying treatment in the previous 2 years (39.4% had, and 60.6% had not) and EDSS score at baseline (83.4% had a score of 3.5 or lower, and 16.6% had a score above 3.5). The population’s mean age was 36.7 years, and 65% of participants were female. Most patients were recruited in Europe, and 51% came from E.U. countries. Patients’ mean baseline EDSS score was 2.6, and mean disease duration was 7.6 years. The mean prestudy 12-month relapse rate was 1.3, and 483 (42.7%) patients had one or more gadolinium-enhancing T1 lesions on baseline MRI. The two treatment groups were well balanced. The rate of treatment discontinuation was 16.6% for ponesimod and 16.4% on teriflunomide.

At the end of the study, the annualized relapse rate was 0.202 in the ponesimod group and 0.290 in the teriflunomide group. Compared with teriflunomide, ponesimod significantly reduced the annualized relapse rate by 30.5%. Fatigue remained stable in the ponesimod group, but worsened in the teriflunomide group: The mean difference in FSIQ-RMS score between the arms at week 108 was 3.57, and this result was statistically significant. In addition, ponesimod significantly reduced the number of active lesions by 56%, compared with teriflunomide. The risk for 12- and 24- week confirmed disability were lower with ponesimod, compared with teriflunomide, but the difference was not statistically significant.

The rates of treatment-emergent adverse events were approximately 89% for the ponesimod arm and 88% for teriflunomide. The rates of serious adverse events were about 9% for ponesimod and about 8% for teriflunomide. Respiratory events and laboratory values prompted slightly more study discontinuations in the ponesimod group than in the teriflunomide group.

This research represents the first controlled study to show superior efficacy of oral ponesimod, compared with an approved oral compound, said Dr. Kappos. “The overall profile suggests that [ponesimod] may be a valuable addition to our armamentarium in treating patients with relapsing forms of MS,” he concluded.

The study was supported by Actelion Pharmaceuticals. University Hospital Basel, where Dr. Kappos works, received steering committee, advisory board, and consultancy fees from Actelion and other companies.

egreb@mdedge.com

SOURCE: Kappos L et al. ECTRIMS 2019, Abstract 93.

STOCKHOLM – Pooled data from several national multiple sclerosis (MS) registries indicate that continuous exposure to disease-modifying therapy (DMT) for more than 10 years reduces the risk of confirmed disability progression (CDP), according to an investigation presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Using several confirmation points for Expanded Disability Status Scale (EDSS) progression (e.g., 12 months and 24 months), researchers detected a clear gradient of treatment effect. Identification of the most reliable outcome definitions will require further investigations, they said.

“The ultimate goal of MS treatment is the prevention of long-term disability accumulation,” said Giuseppe Lucisano, a biostatistician at the Center for Outcomes Research and Clinical Epidemiology in Pescara, Italy. “Continuous DMT exposure can impact long-term disability accumulation in MS, but it has not been definitively demonstrated yet.”

Registries and clinical databases provide the opportunity to collect longitudinal data for treated and untreated patients as a means of investigating questions such as this one, the researchers said. The Danish, Italian, and Swedish national MS registries, MSBase, and the Observatoire of MS (OFSEP) merged their data in the Big Multiple Sclerosis Data (BMSD) Network, which includes approximately 150,000 patients and more than 470,000 EDSS evaluations. The result is a large dataset suitable for long-term longitudinal studies.

egreb@mdedge.com

SOURCE: Laffaldano P et al. ECTRIMS 2019. Abstract: 94.

STOCKHOLM – Pooled data from several national multiple sclerosis (MS) registries indicate that continuous exposure to disease-modifying therapy (DMT) for more than 10 years reduces the risk of confirmed disability progression (CDP), according to an investigation presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Using several confirmation points for Expanded Disability Status Scale (EDSS) progression (e.g., 12 months and 24 months), researchers detected a clear gradient of treatment effect. Identification of the most reliable outcome definitions will require further investigations, they said.

“The ultimate goal of MS treatment is the prevention of long-term disability accumulation,” said Giuseppe Lucisano, a biostatistician at the Center for Outcomes Research and Clinical Epidemiology in Pescara, Italy. “Continuous DMT exposure can impact long-term disability accumulation in MS, but it has not been definitively demonstrated yet.”

Registries and clinical databases provide the opportunity to collect longitudinal data for treated and untreated patients as a means of investigating questions such as this one, the researchers said. The Danish, Italian, and Swedish national MS registries, MSBase, and the Observatoire of MS (OFSEP) merged their data in the Big Multiple Sclerosis Data (BMSD) Network, which includes approximately 150,000 patients and more than 470,000 EDSS evaluations. The result is a large dataset suitable for long-term longitudinal studies.

egreb@mdedge.com

SOURCE: Laffaldano P et al. ECTRIMS 2019. Abstract: 94.

STOCKHOLM – Pooled data from several national multiple sclerosis (MS) registries indicate that continuous exposure to disease-modifying therapy (DMT) for more than 10 years reduces the risk of confirmed disability progression (CDP), according to an investigation presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Using several confirmation points for Expanded Disability Status Scale (EDSS) progression (e.g., 12 months and 24 months), researchers detected a clear gradient of treatment effect. Identification of the most reliable outcome definitions will require further investigations, they said.

“The ultimate goal of MS treatment is the prevention of long-term disability accumulation,” said Giuseppe Lucisano, a biostatistician at the Center for Outcomes Research and Clinical Epidemiology in Pescara, Italy. “Continuous DMT exposure can impact long-term disability accumulation in MS, but it has not been definitively demonstrated yet.”

Registries and clinical databases provide the opportunity to collect longitudinal data for treated and untreated patients as a means of investigating questions such as this one, the researchers said. The Danish, Italian, and Swedish national MS registries, MSBase, and the Observatoire of MS (OFSEP) merged their data in the Big Multiple Sclerosis Data (BMSD) Network, which includes approximately 150,000 patients and more than 470,000 EDSS evaluations. The result is a large dataset suitable for long-term longitudinal studies.

egreb@mdedge.com

SOURCE: Laffaldano P et al. ECTRIMS 2019. Abstract: 94.

Key clinical point: Only one intervention – transcranial direct current stimulation (tDCS) – has been found to counteract cognitive fatigability in a trial with objective outcome measures.

Major finding: Compared with sham stimulation, anodal tDCS increased P300 amplitude and reduced fatigue-related decrements in reaction time in a preliminary study.

Study details: A systematic review of intervention studies that objectively measured cognitive fatigability in adults with neurologic disorders.

Disclosures: The authors had no disclosures.

Citation: Lindsay-Brown A et al. CMSC 2019, Abstract NNN10.

Key clinical point: Only one intervention – transcranial direct current stimulation (tDCS) – has been found to counteract cognitive fatigability in a trial with objective outcome measures.

Major finding: Compared with sham stimulation, anodal tDCS increased P300 amplitude and reduced fatigue-related decrements in reaction time in a preliminary study.

Study details: A systematic review of intervention studies that objectively measured cognitive fatigability in adults with neurologic disorders.

Disclosures: The authors had no disclosures.

Citation: Lindsay-Brown A et al. CMSC 2019, Abstract NNN10.

Key clinical point: Only one intervention – transcranial direct current stimulation (tDCS) – has been found to counteract cognitive fatigability in a trial with objective outcome measures.

Major finding: Compared with sham stimulation, anodal tDCS increased P300 amplitude and reduced fatigue-related decrements in reaction time in a preliminary study.

Study details: A systematic review of intervention studies that objectively measured cognitive fatigability in adults with neurologic disorders.

Disclosures: The authors had no disclosures.

Citation: Lindsay-Brown A et al. CMSC 2019, Abstract NNN10.

Key clinical point: Prices of self-administered disease-modifying therapies for multiple sclerosis increased significantly from 2006 to 2016.

Major finding: Patients’ out-of-pocket costs increased by a factor of 7.2 during this period.

Study details: A cohort study of Medicare claims data from 2006 to 2016.

Disclosures: The Myers Family Foundation and the National Heart, Lung, and Blood Institute funded this research. Several authors are employees of health insurance companies such as the UPMC Health Plan Insurance Services Division and Humana. One author received personal fees from Pfizer that were unrelated to this study.

Citation: San-Juan-Rodriguez A et al. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2711; Hartung DM and Bourdette D. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2445.

Key clinical point: Prices of self-administered disease-modifying therapies for multiple sclerosis increased significantly from 2006 to 2016.

Major finding: Patients’ out-of-pocket costs increased by a factor of 7.2 during this period.

Study details: A cohort study of Medicare claims data from 2006 to 2016.

Disclosures: The Myers Family Foundation and the National Heart, Lung, and Blood Institute funded this research. Several authors are employees of health insurance companies such as the UPMC Health Plan Insurance Services Division and Humana. One author received personal fees from Pfizer that were unrelated to this study.

Citation: San-Juan-Rodriguez A et al. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2711; Hartung DM and Bourdette D. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2445.

Key clinical point: Prices of self-administered disease-modifying therapies for multiple sclerosis increased significantly from 2006 to 2016.

Major finding: Patients’ out-of-pocket costs increased by a factor of 7.2 during this period.

Study details: A cohort study of Medicare claims data from 2006 to 2016.

Disclosures: The Myers Family Foundation and the National Heart, Lung, and Blood Institute funded this research. Several authors are employees of health insurance companies such as the UPMC Health Plan Insurance Services Division and Humana. One author received personal fees from Pfizer that were unrelated to this study.

Citation: San-Juan-Rodriguez A et al. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2711; Hartung DM and Bourdette D. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2445.

STOCKHOLM – Most neurologists are overly conservative when it comes to advising women with multiple sclerosis (MS) about breastfeeding, discouraging this broadly beneficial practice in favor of early resumption of treatment post pregnancy, Kerstin Hellwig, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Bruce Jancin/MDedge News

“We should change our behavior, and I predict we will change it so that more women are breastfeeding while under MS medication within the next couple years. Breastfeeding should not be discouraged in favor of resuming MS medications in most women,” said Dr. Hellwig, senior consultant and MS specialist in the department of neurology at St. Josef Hospital/Ruhr University in Bochum, Germany.

She was a coauthor of a groundbreaking 2012 meta-analysis that concluded that breastfeeding by MS patients is not harmful (J Neurol. 2012 Oct;259[10]:2246-8), a finding since confirmed in multiple additional studies.

“Women with MS who want to breastfeed should be supported in doing so,” Dr. Hellwig said.

In this regard, many neurologists are out of step with their colleagues in rheumatology and gastroenterology, who commonly endorse breastfeeding by their patients while on monoclonal antibodies for other autoimmune diseases, according to Dr. Hellwig.

It is important to recognize that most women of reproductive age with MS have milder forms of the disease, she said. They can safely breastfeed without being on any MS medications at all for the duration.

For women who want to breastfeed and have more-active disease where early treatment resumption is warranted, the key is to select a breastfeeding-compatible medication. The main determinant of whether a drug will enter the mother’s breast milk is the size of the drug molecule, with large molecules being unlikely to make their way into breast milk in anything approaching clinically meaningful amounts. The injectable first-line disease-modifying drugs are good options: For example, interferon-beta is a very large molecule which has been detected in breast milk at 0.0006% of the relative infant dose. That’s reassuring, Dr. Hellwig said, since anything less than a relative infant dose of 10% is generally considered to be safe for a baby. And while glatiramer acetate, another injectable, has not been tested, it is metabolized so rapidly that it is unlikely to be detectable in breast milk, according to Dr. Hellwig.

Monoclonal antibodies are also compatible with breastfeeding. Rituximab has been detected in breast milk at 1/240th of the maternal serum level, and natalizumab at less than 1/200th. These are large molecules with a low likelihood of infant absorption, since they are probably destroyed in the child’s gastrointestinal tract. Ocrelizumab has not been studied in breast milk, but it is an IgG1 monoclonal antibody, as is rituximab, and so should likewise pose “exceedingly low risk,” Dr. Hellwig said.

At last year’s ECTRIMS conference, she presented reassuring 1-year follow-up data on a cohort of infants breastfed by mothers with MS while on interferon-beta. “We do not see any growth disturbances, any severe infections, hospitalizations, excess antibiotic use, or postponed reaching of developmental milestones in babies being breastfed under the injectables,” she said.

Dr. Hellwig has served on scientific advisory board for Bayer, Biogen, Genzyme Sanofi, Teva, Roche, Novartis, and Merck. She has received speaker honoraria and research support from Bayer, Biogen, Merck, Novartis, SanofiGenzyme, and Teva, and has received support for congress participation from Bayer, Biogen, Genzyme, Teva, Roche, and Merck.

bjancin@mdedge.com

STOCKHOLM – Most neurologists are overly conservative when it comes to advising women with multiple sclerosis (MS) about breastfeeding, discouraging this broadly beneficial practice in favor of early resumption of treatment post pregnancy, Kerstin Hellwig, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Bruce Jancin/MDedge News

“We should change our behavior, and I predict we will change it so that more women are breastfeeding while under MS medication within the next couple years. Breastfeeding should not be discouraged in favor of resuming MS medications in most women,” said Dr. Hellwig, senior consultant and MS specialist in the department of neurology at St. Josef Hospital/Ruhr University in Bochum, Germany.

She was a coauthor of a groundbreaking 2012 meta-analysis that concluded that breastfeeding by MS patients is not harmful (J Neurol. 2012 Oct;259[10]:2246-8), a finding since confirmed in multiple additional studies.

“Women with MS who want to breastfeed should be supported in doing so,” Dr. Hellwig said.

In this regard, many neurologists are out of step with their colleagues in rheumatology and gastroenterology, who commonly endorse breastfeeding by their patients while on monoclonal antibodies for other autoimmune diseases, according to Dr. Hellwig.

It is important to recognize that most women of reproductive age with MS have milder forms of the disease, she said. They can safely breastfeed without being on any MS medications at all for the duration.

For women who want to breastfeed and have more-active disease where early treatment resumption is warranted, the key is to select a breastfeeding-compatible medication. The main determinant of whether a drug will enter the mother’s breast milk is the size of the drug molecule, with large molecules being unlikely to make their way into breast milk in anything approaching clinically meaningful amounts. The injectable first-line disease-modifying drugs are good options: For example, interferon-beta is a very large molecule which has been detected in breast milk at 0.0006% of the relative infant dose. That’s reassuring, Dr. Hellwig said, since anything less than a relative infant dose of 10% is generally considered to be safe for a baby. And while glatiramer acetate, another injectable, has not been tested, it is metabolized so rapidly that it is unlikely to be detectable in breast milk, according to Dr. Hellwig.

Monoclonal antibodies are also compatible with breastfeeding. Rituximab has been detected in breast milk at 1/240th of the maternal serum level, and natalizumab at less than 1/200th. These are large molecules with a low likelihood of infant absorption, since they are probably destroyed in the child’s gastrointestinal tract. Ocrelizumab has not been studied in breast milk, but it is an IgG1 monoclonal antibody, as is rituximab, and so should likewise pose “exceedingly low risk,” Dr. Hellwig said.

At last year’s ECTRIMS conference, she presented reassuring 1-year follow-up data on a cohort of infants breastfed by mothers with MS while on interferon-beta. “We do not see any growth disturbances, any severe infections, hospitalizations, excess antibiotic use, or postponed reaching of developmental milestones in babies being breastfed under the injectables,” she said.

Dr. Hellwig has served on scientific advisory board for Bayer, Biogen, Genzyme Sanofi, Teva, Roche, Novartis, and Merck. She has received speaker honoraria and research support from Bayer, Biogen, Merck, Novartis, SanofiGenzyme, and Teva, and has received support for congress participation from Bayer, Biogen, Genzyme, Teva, Roche, and Merck.

bjancin@mdedge.com

STOCKHOLM – Most neurologists are overly conservative when it comes to advising women with multiple sclerosis (MS) about breastfeeding, discouraging this broadly beneficial practice in favor of early resumption of treatment post pregnancy, Kerstin Hellwig, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Bruce Jancin/MDedge News

“We should change our behavior, and I predict we will change it so that more women are breastfeeding while under MS medication within the next couple years. Breastfeeding should not be discouraged in favor of resuming MS medications in most women,” said Dr. Hellwig, senior consultant and MS specialist in the department of neurology at St. Josef Hospital/Ruhr University in Bochum, Germany.

She was a coauthor of a groundbreaking 2012 meta-analysis that concluded that breastfeeding by MS patients is not harmful (J Neurol. 2012 Oct;259[10]:2246-8), a finding since confirmed in multiple additional studies.

“Women with MS who want to breastfeed should be supported in doing so,” Dr. Hellwig said.

In this regard, many neurologists are out of step with their colleagues in rheumatology and gastroenterology, who commonly endorse breastfeeding by their patients while on monoclonal antibodies for other autoimmune diseases, according to Dr. Hellwig.

It is important to recognize that most women of reproductive age with MS have milder forms of the disease, she said. They can safely breastfeed without being on any MS medications at all for the duration.

For women who want to breastfeed and have more-active disease where early treatment resumption is warranted, the key is to select a breastfeeding-compatible medication. The main determinant of whether a drug will enter the mother’s breast milk is the size of the drug molecule, with large molecules being unlikely to make their way into breast milk in anything approaching clinically meaningful amounts. The injectable first-line disease-modifying drugs are good options: For example, interferon-beta is a very large molecule which has been detected in breast milk at 0.0006% of the relative infant dose. That’s reassuring, Dr. Hellwig said, since anything less than a relative infant dose of 10% is generally considered to be safe for a baby. And while glatiramer acetate, another injectable, has not been tested, it is metabolized so rapidly that it is unlikely to be detectable in breast milk, according to Dr. Hellwig.

Monoclonal antibodies are also compatible with breastfeeding. Rituximab has been detected in breast milk at 1/240th of the maternal serum level, and natalizumab at less than 1/200th. These are large molecules with a low likelihood of infant absorption, since they are probably destroyed in the child’s gastrointestinal tract. Ocrelizumab has not been studied in breast milk, but it is an IgG1 monoclonal antibody, as is rituximab, and so should likewise pose “exceedingly low risk,” Dr. Hellwig said.

At last year’s ECTRIMS conference, she presented reassuring 1-year follow-up data on a cohort of infants breastfed by mothers with MS while on interferon-beta. “We do not see any growth disturbances, any severe infections, hospitalizations, excess antibiotic use, or postponed reaching of developmental milestones in babies being breastfed under the injectables,” she said.

Dr. Hellwig has served on scientific advisory board for Bayer, Biogen, Genzyme Sanofi, Teva, Roche, Novartis, and Merck. She has received speaker honoraria and research support from Bayer, Biogen, Merck, Novartis, SanofiGenzyme, and Teva, and has received support for congress participation from Bayer, Biogen, Genzyme, Teva, Roche, and Merck.

bjancin@mdedge.com

Men and women react differently to common drugs used to treat heart failure with reduced ejection fraction (HFrEF), according to findings from a new European study, and women may be able to safely cut their doses in half and get the same level of relief as that provided by larger doses.

“This study ... brings into question what the true optimal medical therapy is for women versus men,” the study authors, led by Bernadet T. Santema, MD, of the University Medical Center Groningen (the Netherlands), wrote in an article published in the Lancet.

Dr. Santema and colleagues noted that current guidelines for the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) and beta-blockers for men and women with heart failure do not differentiate between the genders, despite findings showing that, “with the same dose, the maximum plasma concentrations of ACE inhibitors, ARBs, and beta-blockers were up to 2.5 times higher in women than in men.”

In addition, the researchers wrote, women are much more likely than men to suffer side effects from medications, and the effects tend to be more severe.

HFrEF accounts for an estimated 50% of the 5.7 million patients with heart failure in the United States (Nat Rev Dis Primers. 2017 Aug 24. doi: 10.1038/nrdp.2017.58; Card Fail Rev. 2017;3[1]:7-11.)

For the new study, researchers launched an ad hoc analysis of the findings of a prospective study of HFrEF patients in 11 European countries (1,308 men and 402 women) who took drugs in the three classes. Patients were receiving suboptimal medication doses at the start of the study, and physicians were encouraged to increase their medication. The median follow-up for the primary endpoint was 21 months.

“In men, the lowest hazards of death or hospitalization for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and beta-blockers, but women showed about 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels,” the researchers wrote. “These sex differences were still present after adjusting for clinical covariates, including age and body surface area.”

The researchers analyzed an Asian registry (3,539 men, 961 women) as a comparison and found the identical numbers.

“Our study provides evidence supporting the hypothesis that women with HFrEF might have the best outcomes with lower doses of ACE inhibitors or ARBs and beta-blockers than do men, and lower doses than recommended in international guidelines for heart failure,” they wrote. However, they added that it was not likely that sex-specific studies analyzing doses would be performed.

In an accompanying editorial, Heather P. Whitley, PharmD, and Warren D. Smith, PharmD, noted that clinical research has often failed to take gender differences into account. They wrote that the study – the first of its kind – was well executed and raises important questions, but the analysis did not take into account the prevalence of adverse effects or the serum concentrations of the various medications. Although those limitations weaken the findings, the study still offers evidence that gender-based, drug-dose guidelines deserve consideration, wrote Dr. Whitley, of Auburn (Ala.) University, and Dr. Smith, of Baptist Health System, Montgomery, Ala (Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736[19]31812-4).

The study was funded by the European Commission. Several study authors reported various disclosures. Dr. Whitley and Dr. Smith reported no conflicts of interest.

SOURCE: Santema BT et al. Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736(19)31792-1.

Men and women react differently to common drugs used to treat heart failure with reduced ejection fraction (HFrEF), according to findings from a new European study, and women may be able to safely cut their doses in half and get the same level of relief as that provided by larger doses.

“This study ... brings into question what the true optimal medical therapy is for women versus men,” the study authors, led by Bernadet T. Santema, MD, of the University Medical Center Groningen (the Netherlands), wrote in an article published in the Lancet.

Dr. Santema and colleagues noted that current guidelines for the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) and beta-blockers for men and women with heart failure do not differentiate between the genders, despite findings showing that, “with the same dose, the maximum plasma concentrations of ACE inhibitors, ARBs, and beta-blockers were up to 2.5 times higher in women than in men.”

In addition, the researchers wrote, women are much more likely than men to suffer side effects from medications, and the effects tend to be more severe.

HFrEF accounts for an estimated 50% of the 5.7 million patients with heart failure in the United States (Nat Rev Dis Primers. 2017 Aug 24. doi: 10.1038/nrdp.2017.58; Card Fail Rev. 2017;3[1]:7-11.)

For the new study, researchers launched an ad hoc analysis of the findings of a prospective study of HFrEF patients in 11 European countries (1,308 men and 402 women) who took drugs in the three classes. Patients were receiving suboptimal medication doses at the start of the study, and physicians were encouraged to increase their medication. The median follow-up for the primary endpoint was 21 months.

“In men, the lowest hazards of death or hospitalization for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and beta-blockers, but women showed about 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels,” the researchers wrote. “These sex differences were still present after adjusting for clinical covariates, including age and body surface area.”

The researchers analyzed an Asian registry (3,539 men, 961 women) as a comparison and found the identical numbers.

“Our study provides evidence supporting the hypothesis that women with HFrEF might have the best outcomes with lower doses of ACE inhibitors or ARBs and beta-blockers than do men, and lower doses than recommended in international guidelines for heart failure,” they wrote. However, they added that it was not likely that sex-specific studies analyzing doses would be performed.

In an accompanying editorial, Heather P. Whitley, PharmD, and Warren D. Smith, PharmD, noted that clinical research has often failed to take gender differences into account. They wrote that the study – the first of its kind – was well executed and raises important questions, but the analysis did not take into account the prevalence of adverse effects or the serum concentrations of the various medications. Although those limitations weaken the findings, the study still offers evidence that gender-based, drug-dose guidelines deserve consideration, wrote Dr. Whitley, of Auburn (Ala.) University, and Dr. Smith, of Baptist Health System, Montgomery, Ala (Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736[19]31812-4).

The study was funded by the European Commission. Several study authors reported various disclosures. Dr. Whitley and Dr. Smith reported no conflicts of interest.

SOURCE: Santema BT et al. Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736(19)31792-1.

Men and women react differently to common drugs used to treat heart failure with reduced ejection fraction (HFrEF), according to findings from a new European study, and women may be able to safely cut their doses in half and get the same level of relief as that provided by larger doses.

“This study ... brings into question what the true optimal medical therapy is for women versus men,” the study authors, led by Bernadet T. Santema, MD, of the University Medical Center Groningen (the Netherlands), wrote in an article published in the Lancet.

Dr. Santema and colleagues noted that current guidelines for the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) and beta-blockers for men and women with heart failure do not differentiate between the genders, despite findings showing that, “with the same dose, the maximum plasma concentrations of ACE inhibitors, ARBs, and beta-blockers were up to 2.5 times higher in women than in men.”

In addition, the researchers wrote, women are much more likely than men to suffer side effects from medications, and the effects tend to be more severe.

HFrEF accounts for an estimated 50% of the 5.7 million patients with heart failure in the United States (Nat Rev Dis Primers. 2017 Aug 24. doi: 10.1038/nrdp.2017.58; Card Fail Rev. 2017;3[1]:7-11.)

For the new study, researchers launched an ad hoc analysis of the findings of a prospective study of HFrEF patients in 11 European countries (1,308 men and 402 women) who took drugs in the three classes. Patients were receiving suboptimal medication doses at the start of the study, and physicians were encouraged to increase their medication. The median follow-up for the primary endpoint was 21 months.

“In men, the lowest hazards of death or hospitalization for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and beta-blockers, but women showed about 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels,” the researchers wrote. “These sex differences were still present after adjusting for clinical covariates, including age and body surface area.”

The researchers analyzed an Asian registry (3,539 men, 961 women) as a comparison and found the identical numbers.

“Our study provides evidence supporting the hypothesis that women with HFrEF might have the best outcomes with lower doses of ACE inhibitors or ARBs and beta-blockers than do men, and lower doses than recommended in international guidelines for heart failure,” they wrote. However, they added that it was not likely that sex-specific studies analyzing doses would be performed.

In an accompanying editorial, Heather P. Whitley, PharmD, and Warren D. Smith, PharmD, noted that clinical research has often failed to take gender differences into account. They wrote that the study – the first of its kind – was well executed and raises important questions, but the analysis did not take into account the prevalence of adverse effects or the serum concentrations of the various medications. Although those limitations weaken the findings, the study still offers evidence that gender-based, drug-dose guidelines deserve consideration, wrote Dr. Whitley, of Auburn (Ala.) University, and Dr. Smith, of Baptist Health System, Montgomery, Ala (Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736[19]31812-4).

The study was funded by the European Commission. Several study authors reported various disclosures. Dr. Whitley and Dr. Smith reported no conflicts of interest.

SOURCE: Santema BT et al. Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736(19)31792-1.

Oral administration of vamorolone, a first-in-class investigational steroidal anti-inflammatory drug, may benefit patients with Duchenne muscular dystrophy (DMD), data from an open-label study suggest.

Jonathan Cohen/Binghamton University

Daily treatment with vamorolone at doses of 2.0 mg/kg per day and 6.0 mg/kg per day suggested possible efficacy in a 24-week study, researchers said. The exploratory study included 48 boys who had completed a phase 2a trial.

The treatment was safe and well tolerated, and patients who received 2.0 mg/kg per day had significantly improved muscle function, as assessed by time to stand, compared with natural history controls, according to the results, which were published in Neurology.

In addition, the novel drug may reduce “safety concerns typically seen with traditional glucocorticoids,” wrote Eric P. Hoffman, PhD, and coauthors. Dr. Hoffman is president and CEO of ReveraGen BioPharma in Rockville, Md., which is developing the drug, and associate dean for research in the school of pharmacy and pharmaceutical sciences at Binghamton (N.Y.) University.

In preclinical studies, vamorolone retained anti-inflammatory efficacy while reducing adverse effects, compared with prednisolone, in a manner that is “consistent with vamorolone blocking [nuclear factor-kappa beta]–associated proinflammatory signals as a ligand/receptor monomeric state instead of the traditional molecular models of ligand/receptor dimeric complexes,” the authors said.

jremaly@mdedge.com

SOURCE: Hoffman EP et al. Neurology. 2019 Aug 26. doi: 10.1212/WNL.0000000000008168.

Oral administration of vamorolone, a first-in-class investigational steroidal anti-inflammatory drug, may benefit patients with Duchenne muscular dystrophy (DMD), data from an open-label study suggest.

Jonathan Cohen/Binghamton University

Daily treatment with vamorolone at doses of 2.0 mg/kg per day and 6.0 mg/kg per day suggested possible efficacy in a 24-week study, researchers said. The exploratory study included 48 boys who had completed a phase 2a trial.

The treatment was safe and well tolerated, and patients who received 2.0 mg/kg per day had significantly improved muscle function, as assessed by time to stand, compared with natural history controls, according to the results, which were published in Neurology.

In addition, the novel drug may reduce “safety concerns typically seen with traditional glucocorticoids,” wrote Eric P. Hoffman, PhD, and coauthors. Dr. Hoffman is president and CEO of ReveraGen BioPharma in Rockville, Md., which is developing the drug, and associate dean for research in the school of pharmacy and pharmaceutical sciences at Binghamton (N.Y.) University.

In preclinical studies, vamorolone retained anti-inflammatory efficacy while reducing adverse effects, compared with prednisolone, in a manner that is “consistent with vamorolone blocking [nuclear factor-kappa beta]–associated proinflammatory signals as a ligand/receptor monomeric state instead of the traditional molecular models of ligand/receptor dimeric complexes,” the authors said.

jremaly@mdedge.com

SOURCE: Hoffman EP et al. Neurology. 2019 Aug 26. doi: 10.1212/WNL.0000000000008168.

Oral administration of vamorolone, a first-in-class investigational steroidal anti-inflammatory drug, may benefit patients with Duchenne muscular dystrophy (DMD), data from an open-label study suggest.

Jonathan Cohen/Binghamton University

Daily treatment with vamorolone at doses of 2.0 mg/kg per day and 6.0 mg/kg per day suggested possible efficacy in a 24-week study, researchers said. The exploratory study included 48 boys who had completed a phase 2a trial.

The treatment was safe and well tolerated, and patients who received 2.0 mg/kg per day had significantly improved muscle function, as assessed by time to stand, compared with natural history controls, according to the results, which were published in Neurology.

In addition, the novel drug may reduce “safety concerns typically seen with traditional glucocorticoids,” wrote Eric P. Hoffman, PhD, and coauthors. Dr. Hoffman is president and CEO of ReveraGen BioPharma in Rockville, Md., which is developing the drug, and associate dean for research in the school of pharmacy and pharmaceutical sciences at Binghamton (N.Y.) University.

In preclinical studies, vamorolone retained anti-inflammatory efficacy while reducing adverse effects, compared with prednisolone, in a manner that is “consistent with vamorolone blocking [nuclear factor-kappa beta]–associated proinflammatory signals as a ligand/receptor monomeric state instead of the traditional molecular models of ligand/receptor dimeric complexes,” the authors said.

jremaly@mdedge.com

SOURCE: Hoffman EP et al. Neurology. 2019 Aug 26. doi: 10.1212/WNL.0000000000008168.

Deep surgical-site infections (SSIs) and septic arthritis are not uncommon after the surgeries for periarticular knee fractures, a meta-analysis of existing research found.

National Institute of Allergy and Infectious Diseases

According to an analysis of data on 11,432 patients who underwent surgery for periarticular knee fractures, 5.7% had deep postoperative SSIs. A smaller analysis of 1,567 patients found that 2.4% had septic arthritis. “Surgeons managing periarticular knee fractures should be vigilant when wounds are not pristine,” the investigators recommended.

The report, which appeared in JAMA Network Open, was led by premed student Grayson R. Norris of High Point (N.C.) University.

The researchers noted that there are widely variable statistics regarding SSI after surgery for periarticular knee fractures. A better understanding of the risk would help orthopedic surgeons, given the mortality risk and extra costs associated with postoperative deep SSIs.

For the analysis, the researchers reviewed 117 studies with 11,432 patients who had fractures in the tibial plateau (61% of studies), distal femur (14%), proximal tibia (11%), patella (9%), and multiple sites (6%). More than two-thirds of the studies were retrospective.

Overall, 5.7% of patients suffered deep SSIs, with the highest percentage in the proximal tibia group (6.4%).

A total of 20 studies examined septic arthritis and found that 2.4% of patients in those studies suffered from the condition. Of 182 cases of deep SSIs with bacterial culture results, methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus were the most common bacteria.

“Considering that MRSA was the most common pathogen in our study and that this pathogen is increasing in prevalence, health care practitioners should revisit the use of specific and appropriate prophylactic antibiotics,” the researchers wrote. “Risk factors, such as open fractures, diabetes, smoking, and, most importantly, compartment syndrome, should alert the treating surgeon to an increased risk. Further work is needed to mitigate the association of these conditions with SSI risk in periarticular knee fractures.”

The researchers added that many of the studies in their analysis were of poor quality. “Authors in orthopedic traumatology should strive to conduct higher-quality research, such as randomized clinical trials and case-control or cohort studies,” they noted.

One author reported receiving grants from Zimmer Biomet and DePuy Synthes outside the submitted work. No other disclosures were reported. No study funding was reported.

SOURCE: Norris GR et al. JAMA Netw Open. 2019;2(8):e199951.

Deep surgical-site infections (SSIs) and septic arthritis are not uncommon after the surgeries for periarticular knee fractures, a meta-analysis of existing research found.

National Institute of Allergy and Infectious Diseases

According to an analysis of data on 11,432 patients who underwent surgery for periarticular knee fractures, 5.7% had deep postoperative SSIs. A smaller analysis of 1,567 patients found that 2.4% had septic arthritis. “Surgeons managing periarticular knee fractures should be vigilant when wounds are not pristine,” the investigators recommended.

The report, which appeared in JAMA Network Open, was led by premed student Grayson R. Norris of High Point (N.C.) University.

The researchers noted that there are widely variable statistics regarding SSI after surgery for periarticular knee fractures. A better understanding of the risk would help orthopedic surgeons, given the mortality risk and extra costs associated with postoperative deep SSIs.

For the analysis, the researchers reviewed 117 studies with 11,432 patients who had fractures in the tibial plateau (61% of studies), distal femur (14%), proximal tibia (11%), patella (9%), and multiple sites (6%). More than two-thirds of the studies were retrospective.

Overall, 5.7% of patients suffered deep SSIs, with the highest percentage in the proximal tibia group (6.4%).

A total of 20 studies examined septic arthritis and found that 2.4% of patients in those studies suffered from the condition. Of 182 cases of deep SSIs with bacterial culture results, methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus were the most common bacteria.

“Considering that MRSA was the most common pathogen in our study and that this pathogen is increasing in prevalence, health care practitioners should revisit the use of specific and appropriate prophylactic antibiotics,” the researchers wrote. “Risk factors, such as open fractures, diabetes, smoking, and, most importantly, compartment syndrome, should alert the treating surgeon to an increased risk. Further work is needed to mitigate the association of these conditions with SSI risk in periarticular knee fractures.”

The researchers added that many of the studies in their analysis were of poor quality. “Authors in orthopedic traumatology should strive to conduct higher-quality research, such as randomized clinical trials and case-control or cohort studies,” they noted.

One author reported receiving grants from Zimmer Biomet and DePuy Synthes outside the submitted work. No other disclosures were reported. No study funding was reported.

SOURCE: Norris GR et al. JAMA Netw Open. 2019;2(8):e199951.

Deep surgical-site infections (SSIs) and septic arthritis are not uncommon after the surgeries for periarticular knee fractures, a meta-analysis of existing research found.

National Institute of Allergy and Infectious Diseases

According to an analysis of data on 11,432 patients who underwent surgery for periarticular knee fractures, 5.7% had deep postoperative SSIs. A smaller analysis of 1,567 patients found that 2.4% had septic arthritis. “Surgeons managing periarticular knee fractures should be vigilant when wounds are not pristine,” the investigators recommended.

The report, which appeared in JAMA Network Open, was led by premed student Grayson R. Norris of High Point (N.C.) University.

The researchers noted that there are widely variable statistics regarding SSI after surgery for periarticular knee fractures. A better understanding of the risk would help orthopedic surgeons, given the mortality risk and extra costs associated with postoperative deep SSIs.

For the analysis, the researchers reviewed 117 studies with 11,432 patients who had fractures in the tibial plateau (61% of studies), distal femur (14%), proximal tibia (11%), patella (9%), and multiple sites (6%). More than two-thirds of the studies were retrospective.

Overall, 5.7% of patients suffered deep SSIs, with the highest percentage in the proximal tibia group (6.4%).

A total of 20 studies examined septic arthritis and found that 2.4% of patients in those studies suffered from the condition. Of 182 cases of deep SSIs with bacterial culture results, methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus were the most common bacteria.

“Considering that MRSA was the most common pathogen in our study and that this pathogen is increasing in prevalence, health care practitioners should revisit the use of specific and appropriate prophylactic antibiotics,” the researchers wrote. “Risk factors, such as open fractures, diabetes, smoking, and, most importantly, compartment syndrome, should alert the treating surgeon to an increased risk. Further work is needed to mitigate the association of these conditions with SSI risk in periarticular knee fractures.”

The researchers added that many of the studies in their analysis were of poor quality. “Authors in orthopedic traumatology should strive to conduct higher-quality research, such as randomized clinical trials and case-control or cohort studies,” they noted.

One author reported receiving grants from Zimmer Biomet and DePuy Synthes outside the submitted work. No other disclosures were reported. No study funding was reported.

SOURCE: Norris GR et al. JAMA Netw Open. 2019;2(8):e199951.

Adolescent suicides can be prevented, and clinicians have a key role to play, Joan Asarnow, PhD, said in a webinar presented on World Suicide Prevention Day, Sept. 10, 2019, to raise awareness of the latest research in suicide prevention and risk factors.

AlexRaths/Thinkstock

“Primary care doctors are the most trusted doctors for our teenagers,” Dr. Asarnow said during a question-and-answer session. Primary care can be the first-line screening to identify risk factors for suicide, and a close link with primary care “can make a very big difference in helping kids get through tough times.”

Other studies have shown that when doctors and nurses are able to recognize suicidality and link to behavioral health when needed, suicide attempts and ideation are reduced. Strategies including dialectical behavioral therapy and cognitive-behavior therapy have demonstrated success in reducing self -harm, she noted.

Schools have a role in suicide prevention as well, said Dr. Asarnow of the University of California, Los Angeles, and editor of a special issue of the Journal of Child Psychology and Psychiatry on suicide and self-harm.

She cited data from the Saving and Empowering Young Lives in Europe (SEYLE) study, a longitudinal study of school-based suicide prevention interventions, in which suicide attempts were significantly lower among teens who were exposed to a school-based program (Youth Aware of Mental Health) than they were among controls.

Additional findings from the SEYLE study recently were published in the Journal of Child Psychology and Psychiatry (2019. doi: 10.1111/jcpp.13119).

The authors investigated the interaction of three interventions with a certain model of suicide risk. The three interventions were Youth Aware of Mental Health (YAM); Question, Persuade and Refer (QPR); and ProfScreen. The latter two are established interventions for use by teachers. In the study, 11,110 high school students from 10 countries in the European Union completed questionnaires to assess baseline feelings of being a burden to others and feelings of loneliness and isolation from family and peers. The questionnaires also assessed health risk behaviors, self-injury, suicide ideation, and suicide attempts (SA), which were factors in the model being investigated. The participants were randomized to one of the interventions or to a control group that received educational posters with information about mental health resources.

In a reassessment of 8,972 adolescents 12 months later, the interventions all significantly reduced the association between repeated suicide attempts and the baseline interaction of self-injury and suicide ideation, compared with the control group.

“Among each of the three intervention groups, [suicide ideation] at baseline did not increase the risk of self-injury to be associated with repeated [suicide attempt]” at follow-up, Shira Barzilay, PhD, of Tel Aviv University, and coauthors said.

In addition, the researchers’ model found that “belongingness to parents” predicted lower odds of SI after controlling for depression, anxiety, and internalizing symptoms, and this prediction was similar across the intervention and control groups, although good relations with peers and lack of feeling like a burden on others were not significantly associated with lower odds of SI.

The study findings were limited by several factors including the limits of the model to fully capture the measures of belongingness or burdensomeness, and the use of a 12-month follow-up, which was too long to examine certain patterns of SA, the researchers noted. However, the results suggest that interventions can help reduce risk behaviors or self-harm that could lead to suicide. Areas for further study include examining spikes in risk variables that might have preceded suicide attempts, elevated stress, or interpersonal conflicts.

“The implications for suicide prevention, in both community and clinical settings, are to monitor youth who may be engaged in risky behaviors regardless of [suicide ideation] presentation and provide them with mental health education,” Dr. Barzilay and coauthors concluded.

The ongoing mission, Dr. Asarnow said, is “to send messages of hope, and that there is help out there.”

This is particularly important in the United States and the United Kingdom because, while suicide rates in adolescents have declined in some countries, they have increased in others, notably the two countries aforementioned, Dennis Ougrin, MD, said at the webinar.

Males are more likely to commit suicide than females by a ratio of 3 or 4 to 1 in most Western countries, said Dr. Ougrin, a child and adolescent psychiatrist at South London and Maudsley National Health Service Foundation Trust, leading the Child and Adolescent Mental Health Services Enhanced Treatment Service.

Although hanging is the most common method for suicides in most countries, followed by poisoning, more than 50% of suicides in the United States are caused by firearms, he noted.

Risk factors for completed suicide include male sex, low social status, restricted educational achievement, parental mental disorder, individual mental disorder, family history of suicidal behavior, problems with interpersonal relationships, drug and alcohol misuse, and feelings of hopelessness, said Dr. Ougrin, citing data from a 2012 study published in the Lancet (2012 Jun 23. doi: 10.1016/S0140-6736[12]60322-5).

The webinar was sponsored by Wiley partnership with the World Federation of Science Journalists and the Association of Health Care Journalists. Dr. Asarnow and Dr. Ougrin had no financial conflicts to disclose. The SEYLE project is supported by the European Union through the Seventh Framework Program. Dr. Barzilay and coauthors of the SEYLE study had no financial conflicts to disclose.

Adolescent suicides can be prevented, and clinicians have a key role to play, Joan Asarnow, PhD, said in a webinar presented on World Suicide Prevention Day, Sept. 10, 2019, to raise awareness of the latest research in suicide prevention and risk factors.

AlexRaths/Thinkstock

“Primary care doctors are the most trusted doctors for our teenagers,” Dr. Asarnow said during a question-and-answer session. Primary care can be the first-line screening to identify risk factors for suicide, and a close link with primary care “can make a very big difference in helping kids get through tough times.”

Other studies have shown that when doctors and nurses are able to recognize suicidality and link to behavioral health when needed, suicide attempts and ideation are reduced. Strategies including dialectical behavioral therapy and cognitive-behavior therapy have demonstrated success in reducing self -harm, she noted.

Schools have a role in suicide prevention as well, said Dr. Asarnow of the University of California, Los Angeles, and editor of a special issue of the Journal of Child Psychology and Psychiatry on suicide and self-harm.

She cited data from the Saving and Empowering Young Lives in Europe (SEYLE) study, a longitudinal study of school-based suicide prevention interventions, in which suicide attempts were significantly lower among teens who were exposed to a school-based program (Youth Aware of Mental Health) than they were among controls.

Additional findings from the SEYLE study recently were published in the Journal of Child Psychology and Psychiatry (2019. doi: 10.1111/jcpp.13119).

The authors investigated the interaction of three interventions with a certain model of suicide risk. The three interventions were Youth Aware of Mental Health (YAM); Question, Persuade and Refer (QPR); and ProfScreen. The latter two are established interventions for use by teachers. In the study, 11,110 high school students from 10 countries in the European Union completed questionnaires to assess baseline feelings of being a burden to others and feelings of loneliness and isolation from family and peers. The questionnaires also assessed health risk behaviors, self-injury, suicide ideation, and suicide attempts (SA), which were factors in the model being investigated. The participants were randomized to one of the interventions or to a control group that received educational posters with information about mental health resources.

In a reassessment of 8,972 adolescents 12 months later, the interventions all significantly reduced the association between repeated suicide attempts and the baseline interaction of self-injury and suicide ideation, compared with the control group.

“Among each of the three intervention groups, [suicide ideation] at baseline did not increase the risk of self-injury to be associated with repeated [suicide attempt]” at follow-up, Shira Barzilay, PhD, of Tel Aviv University, and coauthors said.

In addition, the researchers’ model found that “belongingness to parents” predicted lower odds of SI after controlling for depression, anxiety, and internalizing symptoms, and this prediction was similar across the intervention and control groups, although good relations with peers and lack of feeling like a burden on others were not significantly associated with lower odds of SI.

The study findings were limited by several factors including the limits of the model to fully capture the measures of belongingness or burdensomeness, and the use of a 12-month follow-up, which was too long to examine certain patterns of SA, the researchers noted. However, the results suggest that interventions can help reduce risk behaviors or self-harm that could lead to suicide. Areas for further study include examining spikes in risk variables that might have preceded suicide attempts, elevated stress, or interpersonal conflicts.

“The implications for suicide prevention, in both community and clinical settings, are to monitor youth who may be engaged in risky behaviors regardless of [suicide ideation] presentation and provide them with mental health education,” Dr. Barzilay and coauthors concluded.

The ongoing mission, Dr. Asarnow said, is “to send messages of hope, and that there is help out there.”

This is particularly important in the United States and the United Kingdom because, while suicide rates in adolescents have declined in some countries, they have increased in others, notably the two countries aforementioned, Dennis Ougrin, MD, said at the webinar.

Males are more likely to commit suicide than females by a ratio of 3 or 4 to 1 in most Western countries, said Dr. Ougrin, a child and adolescent psychiatrist at South London and Maudsley National Health Service Foundation Trust, leading the Child and Adolescent Mental Health Services Enhanced Treatment Service.

Although hanging is the most common method for suicides in most countries, followed by poisoning, more than 50% of suicides in the United States are caused by firearms, he noted.

Risk factors for completed suicide include male sex, low social status, restricted educational achievement, parental mental disorder, individual mental disorder, family history of suicidal behavior, problems with interpersonal relationships, drug and alcohol misuse, and feelings of hopelessness, said Dr. Ougrin, citing data from a 2012 study published in the Lancet (2012 Jun 23. doi: 10.1016/S0140-6736[12]60322-5).

The webinar was sponsored by Wiley partnership with the World Federation of Science Journalists and the Association of Health Care Journalists. Dr. Asarnow and Dr. Ougrin had no financial conflicts to disclose. The SEYLE project is supported by the European Union through the Seventh Framework Program. Dr. Barzilay and coauthors of the SEYLE study had no financial conflicts to disclose.

Adolescent suicides can be prevented, and clinicians have a key role to play, Joan Asarnow, PhD, said in a webinar presented on World Suicide Prevention Day, Sept. 10, 2019, to raise awareness of the latest research in suicide prevention and risk factors.

AlexRaths/Thinkstock

“Primary care doctors are the most trusted doctors for our teenagers,” Dr. Asarnow said during a question-and-answer session. Primary care can be the first-line screening to identify risk factors for suicide, and a close link with primary care “can make a very big difference in helping kids get through tough times.”

Other studies have shown that when doctors and nurses are able to recognize suicidality and link to behavioral health when needed, suicide attempts and ideation are reduced. Strategies including dialectical behavioral therapy and cognitive-behavior therapy have demonstrated success in reducing self -harm, she noted.

Schools have a role in suicide prevention as well, said Dr. Asarnow of the University of California, Los Angeles, and editor of a special issue of the Journal of Child Psychology and Psychiatry on suicide and self-harm.

She cited data from the Saving and Empowering Young Lives in Europe (SEYLE) study, a longitudinal study of school-based suicide prevention interventions, in which suicide attempts were significantly lower among teens who were exposed to a school-based program (Youth Aware of Mental Health) than they were among controls.

Additional findings from the SEYLE study recently were published in the Journal of Child Psychology and Psychiatry (2019. doi: 10.1111/jcpp.13119).

The authors investigated the interaction of three interventions with a certain model of suicide risk. The three interventions were Youth Aware of Mental Health (YAM); Question, Persuade and Refer (QPR); and ProfScreen. The latter two are established interventions for use by teachers. In the study, 11,110 high school students from 10 countries in the European Union completed questionnaires to assess baseline feelings of being a burden to others and feelings of loneliness and isolation from family and peers. The questionnaires also assessed health risk behaviors, self-injury, suicide ideation, and suicide attempts (SA), which were factors in the model being investigated. The participants were randomized to one of the interventions or to a control group that received educational posters with information about mental health resources.

In a reassessment of 8,972 adolescents 12 months later, the interventions all significantly reduced the association between repeated suicide attempts and the baseline interaction of self-injury and suicide ideation, compared with the control group.

“Among each of the three intervention groups, [suicide ideation] at baseline did not increase the risk of self-injury to be associated with repeated [suicide attempt]” at follow-up, Shira Barzilay, PhD, of Tel Aviv University, and coauthors said.

In addition, the researchers’ model found that “belongingness to parents” predicted lower odds of SI after controlling for depression, anxiety, and internalizing symptoms, and this prediction was similar across the intervention and control groups, although good relations with peers and lack of feeling like a burden on others were not significantly associated with lower odds of SI.

The study findings were limited by several factors including the limits of the model to fully capture the measures of belongingness or burdensomeness, and the use of a 12-month follow-up, which was too long to examine certain patterns of SA, the researchers noted. However, the results suggest that interventions can help reduce risk behaviors or self-harm that could lead to suicide. Areas for further study include examining spikes in risk variables that might have preceded suicide attempts, elevated stress, or interpersonal conflicts.

“The implications for suicide prevention, in both community and clinical settings, are to monitor youth who may be engaged in risky behaviors regardless of [suicide ideation] presentation and provide them with mental health education,” Dr. Barzilay and coauthors concluded.

The ongoing mission, Dr. Asarnow said, is “to send messages of hope, and that there is help out there.”

This is particularly important in the United States and the United Kingdom because, while suicide rates in adolescents have declined in some countries, they have increased in others, notably the two countries aforementioned, Dennis Ougrin, MD, said at the webinar.

Males are more likely to commit suicide than females by a ratio of 3 or 4 to 1 in most Western countries, said Dr. Ougrin, a child and adolescent psychiatrist at South London and Maudsley National Health Service Foundation Trust, leading the Child and Adolescent Mental Health Services Enhanced Treatment Service.

Although hanging is the most common method for suicides in most countries, followed by poisoning, more than 50% of suicides in the United States are caused by firearms, he noted.

Risk factors for completed suicide include male sex, low social status, restricted educational achievement, parental mental disorder, individual mental disorder, family history of suicidal behavior, problems with interpersonal relationships, drug and alcohol misuse, and feelings of hopelessness, said Dr. Ougrin, citing data from a 2012 study published in the Lancet (2012 Jun 23. doi: 10.1016/S0140-6736[12]60322-5).

The webinar was sponsored by Wiley partnership with the World Federation of Science Journalists and the Association of Health Care Journalists. Dr. Asarnow and Dr. Ougrin had no financial conflicts to disclose. The SEYLE project is supported by the European Union through the Seventh Framework Program. Dr. Barzilay and coauthors of the SEYLE study had no financial conflicts to disclose.