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Once-daily oral JAK inhibitor for atopic dermatitis effective in phase 3 study
MADRID – (AD) on the strength of its knockout performance in the pivotal phase 3 JADE MONO-1 trial, presented at the annual congress of the European Academy of Dermatology and Venereology.
“The IGA [Investigator Global Assessment] and EASI [Eczema Area and Severity Index]-75 responses for both doses of abrocitinib were significantly greater than placebo as early as week 2 and continued to increase until week 12 with no plateau. This study stopped at week 12. I would have liked to see what happened at 16 weeks or further. I don’t know where this is going to end up maxing out,” commented principal investigator Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland.
JADE MONO-1 (JAK1 Atopic Dermatitis Efficacy and Safety Monotherapy–1) was a 12-week, double-blind, multicenter study which included 387 adolescents and adults with moderate or severe AD randomized 2:2:1 to abrocitinib at 200 mg or 100 mg once daily, or to placebo. Overall, this was a fairly severely affected population, with a mean baseline EASI (Eczema Area and Severity Index) score of about 30, a peak pruritus numeric rating scale score of 7 out of 10, and a mean Dermatology Quality Life Index score greater than 14. Nonetheless, this was a rigorous abrocitinib monotherapy trial, as participants were not allowed to take even a single dose of topical corticosteroids.
The coprimary endpoints in JADE MONO-1 were achievement of an IGA score of 0 or 1 – that is, clear or almost clear – at week 12 plus at least a 2-point improvement, compared with baseline on the 0-4 scale, and an EASI-75 response as defined by a 75% or greater improvement from baseline.
A clear-cut dose response was evident: the IGA response rate was 43.8% in the group on abrocitinib at 200 mg/day, 23.7% with 100 mg, and 7.9% with placebo. The EASI-75 response rates were 62.7%, 39.7%, and 11.8%, respectively, with a statistically significant separation from placebo by week 2.
Key secondary endpoints included the rigorous EASI-90 response rate: 38.6% with the higher dose of abrocitinib, 18.6% at 100 mg per day, and 5.3% with placebo. And again, that’s without resort to topical steroids, Dr. Simpson noted.
Another important secondary endpoint was the proportion of patients who achieved at least a 4-point improvement in itch on the pruritus self-rating scale by week 12: 57.2%, 37.7%, and 15.3%. The rapidity of the improvement was notable: By week 2, this endpoint was achieved in 45.6% of patients on abrocitinib on the 200-mg dose, 20.4% on the 100-mg dose, and 2.7% of placebo-treated controls.
“By day 2, 1 day after taking the first pill, you can see really nice reductions in itch at both doses, compared with placebo,” the dermatologist said.
Study dropout rates were low despite the inability to utilize topical steroids: 11% in the higher-dose abrocitinib group and 13.5% with abrocitinib at 100 mg/day, both of which were lower than in controls.
Turning to safety results, Dr. Simpson noted that the 9.1% rate of discontinuations because of adverse events in the placebo group was significantly higher than the 5.8% rates in each of the active treatment arms. The serious adverse event rate was 3.2% in each of the abrocitinib groups and 1.9% with placebo. Among the serious adverse events in abrocitinib-treated patients Dr. Simpson considered worthy of special mention were a single case of inflammatory bowel disease, which resolved after halting treatment; one case of peritonsillitis; and a case of pancreatitis in an alcoholic patient. No deaths, major adverse cardiovascular events, or malignancies occurred in this brief 12-week trial. Nor were there any cases of deep vein thrombosis or pulmonary embolism, which has been an issue with some other JAK inhibitors.
“We need long-term safety data, of course,” he said.
Laboratory findings were generally unremarkable, with no clinically significant changes. Platelet counts dropped to a nadir at about 4 weeks while staying within normal range, then came back up. Mean LDL cholesterol levels rose by about 10%, an unwelcome event that was counterbalanced by a favorable 20% rise in HDL cholesterol.
Asked about the efficacy rates in the 20%-plus adolescent study participants, compared with the adults, Dr. Simpson replied that a detailed analysis is planned, adding: “I can say that things are looking pretty similar.”
Abrocitinib is selective for inhibition of JAK1, with resultant modulation of interleukins-4, -13, and -31, as well as interferon-gamma, all of which are cytokines involved in the pathophysiology of AD.
Of note, Pfizer, the drug’s developer, has announced positive results from the sister pivotal phase 3 trial, JADE MONO-2, with full details forthcoming in early 2020. Results of a phase 2b study of abrocitinib were also recently published (JAMA Dermatol. 2019 Oct 2. doi: 10.1001/jamadermatol.2019.2855).
Dr. Simpson reported receiving research grants from and serving as a consultant to Pfizer, the study sponsor. He has similar financial relationships with close to a dozen other pharmaceutical companies.
MADRID – (AD) on the strength of its knockout performance in the pivotal phase 3 JADE MONO-1 trial, presented at the annual congress of the European Academy of Dermatology and Venereology.
“The IGA [Investigator Global Assessment] and EASI [Eczema Area and Severity Index]-75 responses for both doses of abrocitinib were significantly greater than placebo as early as week 2 and continued to increase until week 12 with no plateau. This study stopped at week 12. I would have liked to see what happened at 16 weeks or further. I don’t know where this is going to end up maxing out,” commented principal investigator Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland.
JADE MONO-1 (JAK1 Atopic Dermatitis Efficacy and Safety Monotherapy–1) was a 12-week, double-blind, multicenter study which included 387 adolescents and adults with moderate or severe AD randomized 2:2:1 to abrocitinib at 200 mg or 100 mg once daily, or to placebo. Overall, this was a fairly severely affected population, with a mean baseline EASI (Eczema Area and Severity Index) score of about 30, a peak pruritus numeric rating scale score of 7 out of 10, and a mean Dermatology Quality Life Index score greater than 14. Nonetheless, this was a rigorous abrocitinib monotherapy trial, as participants were not allowed to take even a single dose of topical corticosteroids.
The coprimary endpoints in JADE MONO-1 were achievement of an IGA score of 0 or 1 – that is, clear or almost clear – at week 12 plus at least a 2-point improvement, compared with baseline on the 0-4 scale, and an EASI-75 response as defined by a 75% or greater improvement from baseline.
A clear-cut dose response was evident: the IGA response rate was 43.8% in the group on abrocitinib at 200 mg/day, 23.7% with 100 mg, and 7.9% with placebo. The EASI-75 response rates were 62.7%, 39.7%, and 11.8%, respectively, with a statistically significant separation from placebo by week 2.
Key secondary endpoints included the rigorous EASI-90 response rate: 38.6% with the higher dose of abrocitinib, 18.6% at 100 mg per day, and 5.3% with placebo. And again, that’s without resort to topical steroids, Dr. Simpson noted.
Another important secondary endpoint was the proportion of patients who achieved at least a 4-point improvement in itch on the pruritus self-rating scale by week 12: 57.2%, 37.7%, and 15.3%. The rapidity of the improvement was notable: By week 2, this endpoint was achieved in 45.6% of patients on abrocitinib on the 200-mg dose, 20.4% on the 100-mg dose, and 2.7% of placebo-treated controls.
“By day 2, 1 day after taking the first pill, you can see really nice reductions in itch at both doses, compared with placebo,” the dermatologist said.
Study dropout rates were low despite the inability to utilize topical steroids: 11% in the higher-dose abrocitinib group and 13.5% with abrocitinib at 100 mg/day, both of which were lower than in controls.
Turning to safety results, Dr. Simpson noted that the 9.1% rate of discontinuations because of adverse events in the placebo group was significantly higher than the 5.8% rates in each of the active treatment arms. The serious adverse event rate was 3.2% in each of the abrocitinib groups and 1.9% with placebo. Among the serious adverse events in abrocitinib-treated patients Dr. Simpson considered worthy of special mention were a single case of inflammatory bowel disease, which resolved after halting treatment; one case of peritonsillitis; and a case of pancreatitis in an alcoholic patient. No deaths, major adverse cardiovascular events, or malignancies occurred in this brief 12-week trial. Nor were there any cases of deep vein thrombosis or pulmonary embolism, which has been an issue with some other JAK inhibitors.
“We need long-term safety data, of course,” he said.
Laboratory findings were generally unremarkable, with no clinically significant changes. Platelet counts dropped to a nadir at about 4 weeks while staying within normal range, then came back up. Mean LDL cholesterol levels rose by about 10%, an unwelcome event that was counterbalanced by a favorable 20% rise in HDL cholesterol.
Asked about the efficacy rates in the 20%-plus adolescent study participants, compared with the adults, Dr. Simpson replied that a detailed analysis is planned, adding: “I can say that things are looking pretty similar.”
Abrocitinib is selective for inhibition of JAK1, with resultant modulation of interleukins-4, -13, and -31, as well as interferon-gamma, all of which are cytokines involved in the pathophysiology of AD.
Of note, Pfizer, the drug’s developer, has announced positive results from the sister pivotal phase 3 trial, JADE MONO-2, with full details forthcoming in early 2020. Results of a phase 2b study of abrocitinib were also recently published (JAMA Dermatol. 2019 Oct 2. doi: 10.1001/jamadermatol.2019.2855).
Dr. Simpson reported receiving research grants from and serving as a consultant to Pfizer, the study sponsor. He has similar financial relationships with close to a dozen other pharmaceutical companies.
MADRID – (AD) on the strength of its knockout performance in the pivotal phase 3 JADE MONO-1 trial, presented at the annual congress of the European Academy of Dermatology and Venereology.
“The IGA [Investigator Global Assessment] and EASI [Eczema Area and Severity Index]-75 responses for both doses of abrocitinib were significantly greater than placebo as early as week 2 and continued to increase until week 12 with no plateau. This study stopped at week 12. I would have liked to see what happened at 16 weeks or further. I don’t know where this is going to end up maxing out,” commented principal investigator Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland.
JADE MONO-1 (JAK1 Atopic Dermatitis Efficacy and Safety Monotherapy–1) was a 12-week, double-blind, multicenter study which included 387 adolescents and adults with moderate or severe AD randomized 2:2:1 to abrocitinib at 200 mg or 100 mg once daily, or to placebo. Overall, this was a fairly severely affected population, with a mean baseline EASI (Eczema Area and Severity Index) score of about 30, a peak pruritus numeric rating scale score of 7 out of 10, and a mean Dermatology Quality Life Index score greater than 14. Nonetheless, this was a rigorous abrocitinib monotherapy trial, as participants were not allowed to take even a single dose of topical corticosteroids.
The coprimary endpoints in JADE MONO-1 were achievement of an IGA score of 0 or 1 – that is, clear or almost clear – at week 12 plus at least a 2-point improvement, compared with baseline on the 0-4 scale, and an EASI-75 response as defined by a 75% or greater improvement from baseline.
A clear-cut dose response was evident: the IGA response rate was 43.8% in the group on abrocitinib at 200 mg/day, 23.7% with 100 mg, and 7.9% with placebo. The EASI-75 response rates were 62.7%, 39.7%, and 11.8%, respectively, with a statistically significant separation from placebo by week 2.
Key secondary endpoints included the rigorous EASI-90 response rate: 38.6% with the higher dose of abrocitinib, 18.6% at 100 mg per day, and 5.3% with placebo. And again, that’s without resort to topical steroids, Dr. Simpson noted.
Another important secondary endpoint was the proportion of patients who achieved at least a 4-point improvement in itch on the pruritus self-rating scale by week 12: 57.2%, 37.7%, and 15.3%. The rapidity of the improvement was notable: By week 2, this endpoint was achieved in 45.6% of patients on abrocitinib on the 200-mg dose, 20.4% on the 100-mg dose, and 2.7% of placebo-treated controls.
“By day 2, 1 day after taking the first pill, you can see really nice reductions in itch at both doses, compared with placebo,” the dermatologist said.
Study dropout rates were low despite the inability to utilize topical steroids: 11% in the higher-dose abrocitinib group and 13.5% with abrocitinib at 100 mg/day, both of which were lower than in controls.
Turning to safety results, Dr. Simpson noted that the 9.1% rate of discontinuations because of adverse events in the placebo group was significantly higher than the 5.8% rates in each of the active treatment arms. The serious adverse event rate was 3.2% in each of the abrocitinib groups and 1.9% with placebo. Among the serious adverse events in abrocitinib-treated patients Dr. Simpson considered worthy of special mention were a single case of inflammatory bowel disease, which resolved after halting treatment; one case of peritonsillitis; and a case of pancreatitis in an alcoholic patient. No deaths, major adverse cardiovascular events, or malignancies occurred in this brief 12-week trial. Nor were there any cases of deep vein thrombosis or pulmonary embolism, which has been an issue with some other JAK inhibitors.
“We need long-term safety data, of course,” he said.
Laboratory findings were generally unremarkable, with no clinically significant changes. Platelet counts dropped to a nadir at about 4 weeks while staying within normal range, then came back up. Mean LDL cholesterol levels rose by about 10%, an unwelcome event that was counterbalanced by a favorable 20% rise in HDL cholesterol.
Asked about the efficacy rates in the 20%-plus adolescent study participants, compared with the adults, Dr. Simpson replied that a detailed analysis is planned, adding: “I can say that things are looking pretty similar.”
Abrocitinib is selective for inhibition of JAK1, with resultant modulation of interleukins-4, -13, and -31, as well as interferon-gamma, all of which are cytokines involved in the pathophysiology of AD.
Of note, Pfizer, the drug’s developer, has announced positive results from the sister pivotal phase 3 trial, JADE MONO-2, with full details forthcoming in early 2020. Results of a phase 2b study of abrocitinib were also recently published (JAMA Dermatol. 2019 Oct 2. doi: 10.1001/jamadermatol.2019.2855).
Dr. Simpson reported receiving research grants from and serving as a consultant to Pfizer, the study sponsor. He has similar financial relationships with close to a dozen other pharmaceutical companies.
REPORTING FROM THE EADV CONGRESS
Child Neurology Society 2019
"The Child Neurology Society Annual Meeting is the meeting of choice for child neurologists and professionals in other fields of study related to neurologic and neurodevelopmental disorders in children and adolescents,” according to the society. Check back later this month for top news from the 48th conference in Charlotte, NC.
"The Child Neurology Society Annual Meeting is the meeting of choice for child neurologists and professionals in other fields of study related to neurologic and neurodevelopmental disorders in children and adolescents,” according to the society. Check back later this month for top news from the 48th conference in Charlotte, NC.
"The Child Neurology Society Annual Meeting is the meeting of choice for child neurologists and professionals in other fields of study related to neurologic and neurodevelopmental disorders in children and adolescents,” according to the society. Check back later this month for top news from the 48th conference in Charlotte, NC.
SPARTAN: Apalutamide delays second progression in nonmetastatic CRPC
BARCELONA – The androgen receptor inhibitor apalutamide was associated with a 45% improvement in time to second progression in patients with nonmetastatic, castration-resistant prostate cancer as well as an overall survival edge, although the latter fell just short of statistical significance in an interim analysis of results from the SPARTAN trial.
Among 1,207 men with nonmetastatic castration-resistant prostate cancer (CRPC), those randomly assigned to apalutamide had significantly longer second progression-free survival (PFS2), an exploratory endpoint defined as the time of study entry to progression on subsequent treatment.
In all, 69% of patients on placebo and 40% of those on apalutamide went on to another life-prolonging therapy, usually abiraterone acetate (Zytiga) plus prednisone. The respective median PFS2s were 43.8 and 55.6 months, translating into a hazard ratio for second progression in the apalutamide group of 0.55 (P less than .0001).
Overall survival (OS) also trended toward a benefit for apalutamide, but the difference did not reach the prespecified boundary for significance in this planned interim analysis, reported Matthew R. Smith, MD, PhD, from the Massachusetts General Hospital Cancer Center in Boston.
Among men randomly assigned in the phase 3 trial to receive apalutamide (Erleada), the 4-year OS rate was 72.1%, compared with 64.7% for patients assigned to placebo.
“This OS benefit for apalutamide was observed despite crossover of placebo patients to apalutamide, and higher rates of subsequent life-prolonging therapy in the placebo group,” he said at the European Society for Medical Oncology Congress.
Apalutamide was approved by the Food and Drug Administration in 2018 for treatment of patients with nonmetastatic CRPC who were on androgen deprivation therapy with a rapidly rising prostate-specific antigen level and no detectable distant metastases on conventional imaging.
That approval was based on the primary results from SPARTAN, which showed a median metastasis-free survival for patients taking apalutamide of 40.5 months, compared with 16.2 months for patients taking placebo.
The drug also recently received FDA approval for treatment of men with metastatic CRPC, based on results of the TITAN trial.
Overall survival
At the time of the primary analysis of SPARTAN for metastasis-free survival, the OS data were immature, with only 104 of 427 events required for the prespecified analysis.
At ESMO 2019, Dr. Smith presented results of the second interim survival analysis looking at the effects of apalutamide on OS, as well as time to chemotherapy, PFS2, and safety.
In the trial, men with nonmetastatic CRPC were randomized on a 2:1 basis to receive either apalutamide 240 mg daily (806 patients) or placebo (401) plus androgen deprivation therapy, either with gonadotropin-releasing hormone analogue therapy or with surgical castration.
At a median follow-up of 41 months, median OS was not reached in either arm. As noted before, the 4-year OS rate was higher in the apalutamide group, translating into a HR for death of 0.75. However, the P value of .0197 was higher than the prespecified O’Brien-Fleming boundary of 0.0121, which means that the study follow-up will continue per protocol, with the final analysis for overall survival planned after 427 deaths have occurred, Dr. Smith said.
The survival benefit with apalutamide either trended toward significance across all subgroups, with notable benefits in patients aged younger than 65 years, those with good performance status, prostate-specific antigen doubling time longer than 6 months, and those with locoregional disease status of N1 versus N0.
The secondary endpoint of time to chemotherapy initiation was not formally tested because OS did not reach statistical significance, but proportionally fewer patients on apalutamide had started cytotoxic chemotherapy at the time of the interim analysis (14% vs. 20% of patients on placebo). The median time to initiation of chemotherapy has not been reached in either trial arm, however.
The safety profile of the androgen receptor inhibitor was consistent with that seen in the primary PFS analysis, with any adverse event seen in 97.3% of patients versus 93.7% of patients on placebo, grade 3-4 adverse events in 53.1% versus 36.7%, any serious adverse event in 33.5% versus 24.9%, events leading to treatment discontinuation in 13.8% versus 7.3%, and fatal adverse events in 2.1 versus .5%.
“Of some note, discontinuation due to disease progression was 34% in the apalutamide group, compared to 74% in the placebo group,” Dr. Smith said.
“These results further support apalutamide as a standard-of-care option for men with high-risk, nonmetastatic CRPC,” he concluded.
PFS2 data ‘important’
Invited discussant Karim Fizazi, MD, PhD, from the Institut Gustave Roussy in Villejuif, France, acknowledged it’s too early to draw conclusions about OS, but added that the PFS2 data are important.
The 45% reduction in risk of progression “is particularly important in this trial because abiraterone was provided as a potential salvage treatment in both arms. So in other words, in that trial they were almost truly comparing early AR [androgen receptor] targeting versus deferred AR targeting, at least in some patients, and it seems that [apalutamide] is making a difference in terms of second progression,” he said.
An unanswered question about the trial, however, is how active abiraterone was post apalutamide in the experimental, because there are data suggesting minimal efficacy in sequential therapy of AR-targeted agents, he added.
The SPARTAN trial was funded by Janssen. Dr. Smith disclosed an advisory role, research funding, and travel reimbursement for Janssen and others. Dr. Fizazi disclosed consulting for Janssen and others.
SOURCE: Smith MR et al. ESMO 2019, Abstract 843O
BARCELONA – The androgen receptor inhibitor apalutamide was associated with a 45% improvement in time to second progression in patients with nonmetastatic, castration-resistant prostate cancer as well as an overall survival edge, although the latter fell just short of statistical significance in an interim analysis of results from the SPARTAN trial.
Among 1,207 men with nonmetastatic castration-resistant prostate cancer (CRPC), those randomly assigned to apalutamide had significantly longer second progression-free survival (PFS2), an exploratory endpoint defined as the time of study entry to progression on subsequent treatment.
In all, 69% of patients on placebo and 40% of those on apalutamide went on to another life-prolonging therapy, usually abiraterone acetate (Zytiga) plus prednisone. The respective median PFS2s were 43.8 and 55.6 months, translating into a hazard ratio for second progression in the apalutamide group of 0.55 (P less than .0001).
Overall survival (OS) also trended toward a benefit for apalutamide, but the difference did not reach the prespecified boundary for significance in this planned interim analysis, reported Matthew R. Smith, MD, PhD, from the Massachusetts General Hospital Cancer Center in Boston.
Among men randomly assigned in the phase 3 trial to receive apalutamide (Erleada), the 4-year OS rate was 72.1%, compared with 64.7% for patients assigned to placebo.
“This OS benefit for apalutamide was observed despite crossover of placebo patients to apalutamide, and higher rates of subsequent life-prolonging therapy in the placebo group,” he said at the European Society for Medical Oncology Congress.
Apalutamide was approved by the Food and Drug Administration in 2018 for treatment of patients with nonmetastatic CRPC who were on androgen deprivation therapy with a rapidly rising prostate-specific antigen level and no detectable distant metastases on conventional imaging.
That approval was based on the primary results from SPARTAN, which showed a median metastasis-free survival for patients taking apalutamide of 40.5 months, compared with 16.2 months for patients taking placebo.
The drug also recently received FDA approval for treatment of men with metastatic CRPC, based on results of the TITAN trial.
Overall survival
At the time of the primary analysis of SPARTAN for metastasis-free survival, the OS data were immature, with only 104 of 427 events required for the prespecified analysis.
At ESMO 2019, Dr. Smith presented results of the second interim survival analysis looking at the effects of apalutamide on OS, as well as time to chemotherapy, PFS2, and safety.
In the trial, men with nonmetastatic CRPC were randomized on a 2:1 basis to receive either apalutamide 240 mg daily (806 patients) or placebo (401) plus androgen deprivation therapy, either with gonadotropin-releasing hormone analogue therapy or with surgical castration.
At a median follow-up of 41 months, median OS was not reached in either arm. As noted before, the 4-year OS rate was higher in the apalutamide group, translating into a HR for death of 0.75. However, the P value of .0197 was higher than the prespecified O’Brien-Fleming boundary of 0.0121, which means that the study follow-up will continue per protocol, with the final analysis for overall survival planned after 427 deaths have occurred, Dr. Smith said.
The survival benefit with apalutamide either trended toward significance across all subgroups, with notable benefits in patients aged younger than 65 years, those with good performance status, prostate-specific antigen doubling time longer than 6 months, and those with locoregional disease status of N1 versus N0.
The secondary endpoint of time to chemotherapy initiation was not formally tested because OS did not reach statistical significance, but proportionally fewer patients on apalutamide had started cytotoxic chemotherapy at the time of the interim analysis (14% vs. 20% of patients on placebo). The median time to initiation of chemotherapy has not been reached in either trial arm, however.
The safety profile of the androgen receptor inhibitor was consistent with that seen in the primary PFS analysis, with any adverse event seen in 97.3% of patients versus 93.7% of patients on placebo, grade 3-4 adverse events in 53.1% versus 36.7%, any serious adverse event in 33.5% versus 24.9%, events leading to treatment discontinuation in 13.8% versus 7.3%, and fatal adverse events in 2.1 versus .5%.
“Of some note, discontinuation due to disease progression was 34% in the apalutamide group, compared to 74% in the placebo group,” Dr. Smith said.
“These results further support apalutamide as a standard-of-care option for men with high-risk, nonmetastatic CRPC,” he concluded.
PFS2 data ‘important’
Invited discussant Karim Fizazi, MD, PhD, from the Institut Gustave Roussy in Villejuif, France, acknowledged it’s too early to draw conclusions about OS, but added that the PFS2 data are important.
The 45% reduction in risk of progression “is particularly important in this trial because abiraterone was provided as a potential salvage treatment in both arms. So in other words, in that trial they were almost truly comparing early AR [androgen receptor] targeting versus deferred AR targeting, at least in some patients, and it seems that [apalutamide] is making a difference in terms of second progression,” he said.
An unanswered question about the trial, however, is how active abiraterone was post apalutamide in the experimental, because there are data suggesting minimal efficacy in sequential therapy of AR-targeted agents, he added.
The SPARTAN trial was funded by Janssen. Dr. Smith disclosed an advisory role, research funding, and travel reimbursement for Janssen and others. Dr. Fizazi disclosed consulting for Janssen and others.
SOURCE: Smith MR et al. ESMO 2019, Abstract 843O
BARCELONA – The androgen receptor inhibitor apalutamide was associated with a 45% improvement in time to second progression in patients with nonmetastatic, castration-resistant prostate cancer as well as an overall survival edge, although the latter fell just short of statistical significance in an interim analysis of results from the SPARTAN trial.
Among 1,207 men with nonmetastatic castration-resistant prostate cancer (CRPC), those randomly assigned to apalutamide had significantly longer second progression-free survival (PFS2), an exploratory endpoint defined as the time of study entry to progression on subsequent treatment.
In all, 69% of patients on placebo and 40% of those on apalutamide went on to another life-prolonging therapy, usually abiraterone acetate (Zytiga) plus prednisone. The respective median PFS2s were 43.8 and 55.6 months, translating into a hazard ratio for second progression in the apalutamide group of 0.55 (P less than .0001).
Overall survival (OS) also trended toward a benefit for apalutamide, but the difference did not reach the prespecified boundary for significance in this planned interim analysis, reported Matthew R. Smith, MD, PhD, from the Massachusetts General Hospital Cancer Center in Boston.
Among men randomly assigned in the phase 3 trial to receive apalutamide (Erleada), the 4-year OS rate was 72.1%, compared with 64.7% for patients assigned to placebo.
“This OS benefit for apalutamide was observed despite crossover of placebo patients to apalutamide, and higher rates of subsequent life-prolonging therapy in the placebo group,” he said at the European Society for Medical Oncology Congress.
Apalutamide was approved by the Food and Drug Administration in 2018 for treatment of patients with nonmetastatic CRPC who were on androgen deprivation therapy with a rapidly rising prostate-specific antigen level and no detectable distant metastases on conventional imaging.
That approval was based on the primary results from SPARTAN, which showed a median metastasis-free survival for patients taking apalutamide of 40.5 months, compared with 16.2 months for patients taking placebo.
The drug also recently received FDA approval for treatment of men with metastatic CRPC, based on results of the TITAN trial.
Overall survival
At the time of the primary analysis of SPARTAN for metastasis-free survival, the OS data were immature, with only 104 of 427 events required for the prespecified analysis.
At ESMO 2019, Dr. Smith presented results of the second interim survival analysis looking at the effects of apalutamide on OS, as well as time to chemotherapy, PFS2, and safety.
In the trial, men with nonmetastatic CRPC were randomized on a 2:1 basis to receive either apalutamide 240 mg daily (806 patients) or placebo (401) plus androgen deprivation therapy, either with gonadotropin-releasing hormone analogue therapy or with surgical castration.
At a median follow-up of 41 months, median OS was not reached in either arm. As noted before, the 4-year OS rate was higher in the apalutamide group, translating into a HR for death of 0.75. However, the P value of .0197 was higher than the prespecified O’Brien-Fleming boundary of 0.0121, which means that the study follow-up will continue per protocol, with the final analysis for overall survival planned after 427 deaths have occurred, Dr. Smith said.
The survival benefit with apalutamide either trended toward significance across all subgroups, with notable benefits in patients aged younger than 65 years, those with good performance status, prostate-specific antigen doubling time longer than 6 months, and those with locoregional disease status of N1 versus N0.
The secondary endpoint of time to chemotherapy initiation was not formally tested because OS did not reach statistical significance, but proportionally fewer patients on apalutamide had started cytotoxic chemotherapy at the time of the interim analysis (14% vs. 20% of patients on placebo). The median time to initiation of chemotherapy has not been reached in either trial arm, however.
The safety profile of the androgen receptor inhibitor was consistent with that seen in the primary PFS analysis, with any adverse event seen in 97.3% of patients versus 93.7% of patients on placebo, grade 3-4 adverse events in 53.1% versus 36.7%, any serious adverse event in 33.5% versus 24.9%, events leading to treatment discontinuation in 13.8% versus 7.3%, and fatal adverse events in 2.1 versus .5%.
“Of some note, discontinuation due to disease progression was 34% in the apalutamide group, compared to 74% in the placebo group,” Dr. Smith said.
“These results further support apalutamide as a standard-of-care option for men with high-risk, nonmetastatic CRPC,” he concluded.
PFS2 data ‘important’
Invited discussant Karim Fizazi, MD, PhD, from the Institut Gustave Roussy in Villejuif, France, acknowledged it’s too early to draw conclusions about OS, but added that the PFS2 data are important.
The 45% reduction in risk of progression “is particularly important in this trial because abiraterone was provided as a potential salvage treatment in both arms. So in other words, in that trial they were almost truly comparing early AR [androgen receptor] targeting versus deferred AR targeting, at least in some patients, and it seems that [apalutamide] is making a difference in terms of second progression,” he said.
An unanswered question about the trial, however, is how active abiraterone was post apalutamide in the experimental, because there are data suggesting minimal efficacy in sequential therapy of AR-targeted agents, he added.
The SPARTAN trial was funded by Janssen. Dr. Smith disclosed an advisory role, research funding, and travel reimbursement for Janssen and others. Dr. Fizazi disclosed consulting for Janssen and others.
SOURCE: Smith MR et al. ESMO 2019, Abstract 843O
REPORTING FROM ESMO 2019
FDA gives nod to earlier use of Nplate in adults with ITP
Romiplostim (Nplate) earned a new indication from the Food and Drug Administration, allowing for earlier usage in adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
The new indication is for newly diagnosed and persistent adult patients.
Romiplostim is already approved for the treatment of pediatric patients aged 1 year and older who have had ITP for at least 6 months and had an insufficient response to other treatments, as well as for adults patients with chronic ITP who had insufficient response to other therapies.
The latest approval is based on positive results from a single-arm, phase 2 trial in adults with ITP who had an insufficient response to first-line treatment. The study met its primary endpoint – platelet response (50 x 109/L or greater). The median number of months with platelet response was 11 months during a 12-month treatment period. The median time to first platelet response was just over 2 weeks.
Adverse events of at least 5% incidence in patients taking romiplostim with an ITP duration up to 12 months included bronchitis, sinusitis, vomiting, arthralgia, myalgia, headache, dizziness, diarrhea, upper respiratory tract infection, cough, nausea, and oropharyngeal pain. There was a 2% incidence of thrombocytosis among adults with an ITP duration up to 12 months.
Romiplostim (Nplate) earned a new indication from the Food and Drug Administration, allowing for earlier usage in adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
The new indication is for newly diagnosed and persistent adult patients.
Romiplostim is already approved for the treatment of pediatric patients aged 1 year and older who have had ITP for at least 6 months and had an insufficient response to other treatments, as well as for adults patients with chronic ITP who had insufficient response to other therapies.
The latest approval is based on positive results from a single-arm, phase 2 trial in adults with ITP who had an insufficient response to first-line treatment. The study met its primary endpoint – platelet response (50 x 109/L or greater). The median number of months with platelet response was 11 months during a 12-month treatment period. The median time to first platelet response was just over 2 weeks.
Adverse events of at least 5% incidence in patients taking romiplostim with an ITP duration up to 12 months included bronchitis, sinusitis, vomiting, arthralgia, myalgia, headache, dizziness, diarrhea, upper respiratory tract infection, cough, nausea, and oropharyngeal pain. There was a 2% incidence of thrombocytosis among adults with an ITP duration up to 12 months.
Romiplostim (Nplate) earned a new indication from the Food and Drug Administration, allowing for earlier usage in adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
The new indication is for newly diagnosed and persistent adult patients.
Romiplostim is already approved for the treatment of pediatric patients aged 1 year and older who have had ITP for at least 6 months and had an insufficient response to other treatments, as well as for adults patients with chronic ITP who had insufficient response to other therapies.
The latest approval is based on positive results from a single-arm, phase 2 trial in adults with ITP who had an insufficient response to first-line treatment. The study met its primary endpoint – platelet response (50 x 109/L or greater). The median number of months with platelet response was 11 months during a 12-month treatment period. The median time to first platelet response was just over 2 weeks.
Adverse events of at least 5% incidence in patients taking romiplostim with an ITP duration up to 12 months included bronchitis, sinusitis, vomiting, arthralgia, myalgia, headache, dizziness, diarrhea, upper respiratory tract infection, cough, nausea, and oropharyngeal pain. There was a 2% incidence of thrombocytosis among adults with an ITP duration up to 12 months.
Balloon pulmonary angioplasty beats riociguat in randomized CTEPH trial
MADRID – according to a multicenter trial presented at the annual congress of the European Respiratory Congress.
Both therapies are widely used in the treatment of CTEPH, but this is the first controlled trial in which they were directly compared, according to Xavier Jaïs, MD, of the Pulmonology Service, Kremlin-Bicêtre Hospital, University of Paris-Sud.
In this randomized trial, called RACE, newly diagnosed and previously untreated patients with nonoperable CTEPH were enrolled. The key eligibility criteria included PVR greater than 320 dynes/sec per cm–5 and a pulmonary capillary wedge pressure of 15 mm Hg or less.
The patients were randomized to BPA or riociguat and followed for 26 weeks. The primary endpoint was relative change in PVR from baseline. The 6-minute walk distance, change in functional class, time to clinical worsening and safety were among secondary endpoints.
As calculated by geometric mean from baseline, PVR was reduced by nearly 60% in the BPA group and by 32% in the riociguat group, providing a 40% (P less than .0001) relative advantage of BPA.
Although there was a small relative advantage in the 6-minute walk distance for the BPA group at the end of the study, it did not reach statistical significant. However, 88% of those randomized to BPA versus 49% of those treated with riociguat (P less than .0001) improved by at least one WHO class by the end of the study.
Clinical worsening events over the course of the trial were uncommon. All three of these events occurred in the riociguat group, but the difference was not significant.
The end-of-study reduction in brain natriuretic peptide, which was another secondary endpoint, was 67% greater in the BPA group (P less than .0001).
There was a safety cost for the greater efficacy of BPA. This included a higher proportion of patients in the BPA group with at least one serious adverse event (50% vs. 26%) and at least one serious treatment-related adverse event (14% vs. 9%). No patient in either arm discontinued therapy because of treatment-related adverse events, and there were no deaths over the course of the study in either arm.
The study has included a 6-month extension to allow patients symptomatic on their originally assigned therapy to switch to the opposite treatment. Results of the extension are not yet available, but Dr. Jaïs said that these data might provide insight about which therapy to start first.
“It was very important to do this trial,” according to the ERS-invited discussant, Martin Kolb, MD, of the Firestone Institute of Respiratory Health, McMaster University, Hamilton, Ont. The most recent World Symposium on Pulmonary Hypertension identified BPA and medical therapy as reasonable choices in inoperable CTEPH, but Dr. Kolb said there has been an unmet need for comparative data.
“This was a very strong study that demonstrated a powerful impact for both interventions on pulmonary vascular resistance,” Dr. Kolb said, adding that, although BPA proved to be more effective, clinicians consider the greater risk of adverse events. He believes further work needs to be done in identifying the best candidates for each and to explore hybrid approaches.
“What do you think about doing these sequentially so that you lower the pressure first with medical therapy and then go in with the balloon?” Dr. Kolb asked Dr. Jaïs during a discussion that followed presentation of the RACE results.
Dr. Jaïs conceded this point, noting that the treatments have different targets and might be complementary.
“We plan to do a study like this in the future,” Dr. Jaïs said.
Dr. Jaïs reported no potential conflicts of interest.
MADRID – according to a multicenter trial presented at the annual congress of the European Respiratory Congress.
Both therapies are widely used in the treatment of CTEPH, but this is the first controlled trial in which they were directly compared, according to Xavier Jaïs, MD, of the Pulmonology Service, Kremlin-Bicêtre Hospital, University of Paris-Sud.
In this randomized trial, called RACE, newly diagnosed and previously untreated patients with nonoperable CTEPH were enrolled. The key eligibility criteria included PVR greater than 320 dynes/sec per cm–5 and a pulmonary capillary wedge pressure of 15 mm Hg or less.
The patients were randomized to BPA or riociguat and followed for 26 weeks. The primary endpoint was relative change in PVR from baseline. The 6-minute walk distance, change in functional class, time to clinical worsening and safety were among secondary endpoints.
As calculated by geometric mean from baseline, PVR was reduced by nearly 60% in the BPA group and by 32% in the riociguat group, providing a 40% (P less than .0001) relative advantage of BPA.
Although there was a small relative advantage in the 6-minute walk distance for the BPA group at the end of the study, it did not reach statistical significant. However, 88% of those randomized to BPA versus 49% of those treated with riociguat (P less than .0001) improved by at least one WHO class by the end of the study.
Clinical worsening events over the course of the trial were uncommon. All three of these events occurred in the riociguat group, but the difference was not significant.
The end-of-study reduction in brain natriuretic peptide, which was another secondary endpoint, was 67% greater in the BPA group (P less than .0001).
There was a safety cost for the greater efficacy of BPA. This included a higher proportion of patients in the BPA group with at least one serious adverse event (50% vs. 26%) and at least one serious treatment-related adverse event (14% vs. 9%). No patient in either arm discontinued therapy because of treatment-related adverse events, and there were no deaths over the course of the study in either arm.
The study has included a 6-month extension to allow patients symptomatic on their originally assigned therapy to switch to the opposite treatment. Results of the extension are not yet available, but Dr. Jaïs said that these data might provide insight about which therapy to start first.
“It was very important to do this trial,” according to the ERS-invited discussant, Martin Kolb, MD, of the Firestone Institute of Respiratory Health, McMaster University, Hamilton, Ont. The most recent World Symposium on Pulmonary Hypertension identified BPA and medical therapy as reasonable choices in inoperable CTEPH, but Dr. Kolb said there has been an unmet need for comparative data.
“This was a very strong study that demonstrated a powerful impact for both interventions on pulmonary vascular resistance,” Dr. Kolb said, adding that, although BPA proved to be more effective, clinicians consider the greater risk of adverse events. He believes further work needs to be done in identifying the best candidates for each and to explore hybrid approaches.
“What do you think about doing these sequentially so that you lower the pressure first with medical therapy and then go in with the balloon?” Dr. Kolb asked Dr. Jaïs during a discussion that followed presentation of the RACE results.
Dr. Jaïs conceded this point, noting that the treatments have different targets and might be complementary.
“We plan to do a study like this in the future,” Dr. Jaïs said.
Dr. Jaïs reported no potential conflicts of interest.
MADRID – according to a multicenter trial presented at the annual congress of the European Respiratory Congress.
Both therapies are widely used in the treatment of CTEPH, but this is the first controlled trial in which they were directly compared, according to Xavier Jaïs, MD, of the Pulmonology Service, Kremlin-Bicêtre Hospital, University of Paris-Sud.
In this randomized trial, called RACE, newly diagnosed and previously untreated patients with nonoperable CTEPH were enrolled. The key eligibility criteria included PVR greater than 320 dynes/sec per cm–5 and a pulmonary capillary wedge pressure of 15 mm Hg or less.
The patients were randomized to BPA or riociguat and followed for 26 weeks. The primary endpoint was relative change in PVR from baseline. The 6-minute walk distance, change in functional class, time to clinical worsening and safety were among secondary endpoints.
As calculated by geometric mean from baseline, PVR was reduced by nearly 60% in the BPA group and by 32% in the riociguat group, providing a 40% (P less than .0001) relative advantage of BPA.
Although there was a small relative advantage in the 6-minute walk distance for the BPA group at the end of the study, it did not reach statistical significant. However, 88% of those randomized to BPA versus 49% of those treated with riociguat (P less than .0001) improved by at least one WHO class by the end of the study.
Clinical worsening events over the course of the trial were uncommon. All three of these events occurred in the riociguat group, but the difference was not significant.
The end-of-study reduction in brain natriuretic peptide, which was another secondary endpoint, was 67% greater in the BPA group (P less than .0001).
There was a safety cost for the greater efficacy of BPA. This included a higher proportion of patients in the BPA group with at least one serious adverse event (50% vs. 26%) and at least one serious treatment-related adverse event (14% vs. 9%). No patient in either arm discontinued therapy because of treatment-related adverse events, and there were no deaths over the course of the study in either arm.
The study has included a 6-month extension to allow patients symptomatic on their originally assigned therapy to switch to the opposite treatment. Results of the extension are not yet available, but Dr. Jaïs said that these data might provide insight about which therapy to start first.
“It was very important to do this trial,” according to the ERS-invited discussant, Martin Kolb, MD, of the Firestone Institute of Respiratory Health, McMaster University, Hamilton, Ont. The most recent World Symposium on Pulmonary Hypertension identified BPA and medical therapy as reasonable choices in inoperable CTEPH, but Dr. Kolb said there has been an unmet need for comparative data.
“This was a very strong study that demonstrated a powerful impact for both interventions on pulmonary vascular resistance,” Dr. Kolb said, adding that, although BPA proved to be more effective, clinicians consider the greater risk of adverse events. He believes further work needs to be done in identifying the best candidates for each and to explore hybrid approaches.
“What do you think about doing these sequentially so that you lower the pressure first with medical therapy and then go in with the balloon?” Dr. Kolb asked Dr. Jaïs during a discussion that followed presentation of the RACE results.
Dr. Jaïs conceded this point, noting that the treatments have different targets and might be complementary.
“We plan to do a study like this in the future,” Dr. Jaïs said.
Dr. Jaïs reported no potential conflicts of interest.
REPORTING FROM ERS 2019
Obesity ups type 2 diabetes risk far more than lifestyle, genetics
BARCELONA – Obesity, more so than having a poor lifestyle, significantly raised the odds of developing type 2 diabetes, independent of individuals’ genetic susceptibility, according to data from a Danish population-based, case-cohort study.
In fact, having a body mass index (BMI) of more than 30 kg/m2 was linked with a 480% risk of incident type 2 diabetes, compared with being of normal weight (BMI, 18.5-24.9 kg/m2). The 95% confidence interval was 5.16-6.55. Being overweight (BMI, 25-29.9 kg/m2) also carried a 100% increased risk of type 2 diabetes (hazard ratio, 2.37; 95% CI, 2.15-2.62).
Having an unfavorable lifestyle – which was defined as having no or only one of several healthy-living characteristics, from not smoking and moderating alcohol use to eating a well-balanced, nutritious diet and exercising regularly – increased the risk of diabetes by 18%, compared with having a favorable lifestyle (HR, 1.18; 95% CI, 1.06-1.30).
Individuals with a high genetic risk score (GRS) had a 100% increased risk of developing the disease versus those with a low GRS (HR, 2.0; 95% CI, 1.1-1.3).
“High genetic risk, obesity, and [an] unfavorable lifestyle increase the individual-level risk of incident type 2 diabetes,” Hermina Jakupovic and associates reported in a poster presentation at the annual meeting of the European Association for the Study of Diabetes. Their results suggest that “the effect of obesity on type 2 diabetes risk is dominant over other risk factors, highlighting the importance of weight management in type 2 diabetes prevention.”
Ms. Jakupovic, a PhD student at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, and coauthors examined data on 9,555 participants of the Diet, Cancer, and Health cohort, a large, prospective study that has been running since the early 1990s.
Around half of the study sample were women and the mean age was 52 years. Just over one-fifth (22.8%) were obese, 43% were overweight, and the remaining 35.2% were of normal weight. A quarter (25.4%) had an unfavorable lifestyle, 40% a favorable lifestyle, and the remainder an “intermediate” lifestyle. Over a follow-up of almost 15 years, nearly half (49.5%) developed type 2 diabetes.
Genetic risk was assessed by a GRS comprising 193 genetic variants known to be strongly associated with type 2 diabetes, Ms. Jakupovic explained, adding that, using the GRS, patients were categorized into being at low (the lowest 20%), intermediate (middle 60%) and high risk (top 20%) of type 2 diabetes.
Considering individuals’ GRS and lifestyle score together showed an increasing risk of developing type 2 diabetes from the low GRS/favorable-lifestyle category (HR, 1.0; reference) upward to the high GRS/unfavorable lifestyle (HR, 2.22; 95% CI, 1.76-2.81).
The Diet, Cancer, and Health cohort is supported by the Danish Cancer Society. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation. Ms. Jakupovic and associates are funded either directly or indirectly by the Novo Nordisk Foundation.
SOURCE: Jakupovic H et al. EASD 2019, Abstract 376.
BARCELONA – Obesity, more so than having a poor lifestyle, significantly raised the odds of developing type 2 diabetes, independent of individuals’ genetic susceptibility, according to data from a Danish population-based, case-cohort study.
In fact, having a body mass index (BMI) of more than 30 kg/m2 was linked with a 480% risk of incident type 2 diabetes, compared with being of normal weight (BMI, 18.5-24.9 kg/m2). The 95% confidence interval was 5.16-6.55. Being overweight (BMI, 25-29.9 kg/m2) also carried a 100% increased risk of type 2 diabetes (hazard ratio, 2.37; 95% CI, 2.15-2.62).
Having an unfavorable lifestyle – which was defined as having no or only one of several healthy-living characteristics, from not smoking and moderating alcohol use to eating a well-balanced, nutritious diet and exercising regularly – increased the risk of diabetes by 18%, compared with having a favorable lifestyle (HR, 1.18; 95% CI, 1.06-1.30).
Individuals with a high genetic risk score (GRS) had a 100% increased risk of developing the disease versus those with a low GRS (HR, 2.0; 95% CI, 1.1-1.3).
“High genetic risk, obesity, and [an] unfavorable lifestyle increase the individual-level risk of incident type 2 diabetes,” Hermina Jakupovic and associates reported in a poster presentation at the annual meeting of the European Association for the Study of Diabetes. Their results suggest that “the effect of obesity on type 2 diabetes risk is dominant over other risk factors, highlighting the importance of weight management in type 2 diabetes prevention.”
Ms. Jakupovic, a PhD student at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, and coauthors examined data on 9,555 participants of the Diet, Cancer, and Health cohort, a large, prospective study that has been running since the early 1990s.
Around half of the study sample were women and the mean age was 52 years. Just over one-fifth (22.8%) were obese, 43% were overweight, and the remaining 35.2% were of normal weight. A quarter (25.4%) had an unfavorable lifestyle, 40% a favorable lifestyle, and the remainder an “intermediate” lifestyle. Over a follow-up of almost 15 years, nearly half (49.5%) developed type 2 diabetes.
Genetic risk was assessed by a GRS comprising 193 genetic variants known to be strongly associated with type 2 diabetes, Ms. Jakupovic explained, adding that, using the GRS, patients were categorized into being at low (the lowest 20%), intermediate (middle 60%) and high risk (top 20%) of type 2 diabetes.
Considering individuals’ GRS and lifestyle score together showed an increasing risk of developing type 2 diabetes from the low GRS/favorable-lifestyle category (HR, 1.0; reference) upward to the high GRS/unfavorable lifestyle (HR, 2.22; 95% CI, 1.76-2.81).
The Diet, Cancer, and Health cohort is supported by the Danish Cancer Society. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation. Ms. Jakupovic and associates are funded either directly or indirectly by the Novo Nordisk Foundation.
SOURCE: Jakupovic H et al. EASD 2019, Abstract 376.
BARCELONA – Obesity, more so than having a poor lifestyle, significantly raised the odds of developing type 2 diabetes, independent of individuals’ genetic susceptibility, according to data from a Danish population-based, case-cohort study.
In fact, having a body mass index (BMI) of more than 30 kg/m2 was linked with a 480% risk of incident type 2 diabetes, compared with being of normal weight (BMI, 18.5-24.9 kg/m2). The 95% confidence interval was 5.16-6.55. Being overweight (BMI, 25-29.9 kg/m2) also carried a 100% increased risk of type 2 diabetes (hazard ratio, 2.37; 95% CI, 2.15-2.62).
Having an unfavorable lifestyle – which was defined as having no or only one of several healthy-living characteristics, from not smoking and moderating alcohol use to eating a well-balanced, nutritious diet and exercising regularly – increased the risk of diabetes by 18%, compared with having a favorable lifestyle (HR, 1.18; 95% CI, 1.06-1.30).
Individuals with a high genetic risk score (GRS) had a 100% increased risk of developing the disease versus those with a low GRS (HR, 2.0; 95% CI, 1.1-1.3).
“High genetic risk, obesity, and [an] unfavorable lifestyle increase the individual-level risk of incident type 2 diabetes,” Hermina Jakupovic and associates reported in a poster presentation at the annual meeting of the European Association for the Study of Diabetes. Their results suggest that “the effect of obesity on type 2 diabetes risk is dominant over other risk factors, highlighting the importance of weight management in type 2 diabetes prevention.”
Ms. Jakupovic, a PhD student at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, and coauthors examined data on 9,555 participants of the Diet, Cancer, and Health cohort, a large, prospective study that has been running since the early 1990s.
Around half of the study sample were women and the mean age was 52 years. Just over one-fifth (22.8%) were obese, 43% were overweight, and the remaining 35.2% were of normal weight. A quarter (25.4%) had an unfavorable lifestyle, 40% a favorable lifestyle, and the remainder an “intermediate” lifestyle. Over a follow-up of almost 15 years, nearly half (49.5%) developed type 2 diabetes.
Genetic risk was assessed by a GRS comprising 193 genetic variants known to be strongly associated with type 2 diabetes, Ms. Jakupovic explained, adding that, using the GRS, patients were categorized into being at low (the lowest 20%), intermediate (middle 60%) and high risk (top 20%) of type 2 diabetes.
Considering individuals’ GRS and lifestyle score together showed an increasing risk of developing type 2 diabetes from the low GRS/favorable-lifestyle category (HR, 1.0; reference) upward to the high GRS/unfavorable lifestyle (HR, 2.22; 95% CI, 1.76-2.81).
The Diet, Cancer, and Health cohort is supported by the Danish Cancer Society. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation. Ms. Jakupovic and associates are funded either directly or indirectly by the Novo Nordisk Foundation.
SOURCE: Jakupovic H et al. EASD 2019, Abstract 376.
REPORTING FROM EASD 2019
Closed-loop delivery system increases time in target glucose range
Patients with type 1 diabetes who used a closed-loop insulin delivery system spent a greater percentage of time in their target blood glucose range, compared with patients using a sensor-augmented insulin pump.
The significant, between-group, mean-adjusted difference of 11 percentage points between the two groups translated into the closed-loop patients spending an additional 2.6 hr/day in the target range of 70-180 mg/dL, Susan A. Brown, MD, and colleagues wrote in the New England Journal of Medicine.
Most of the benefit occurred in the early morning hours, at 5 am, when 89% of patients using the closed-loop system remained in the target range, compared with 62% of those using the pump system, said Dr. Brown of the University of Virginia, Charlottesville, and colleagues.
The randomized study comprised 168 patients with a mean age of 33 years, although the age range was wide (14-71 years). The patients had a mean disease duration of 16 years. Their baseline glycated hemoglobin level ranged between 5.4% and 10.6%. At enrollment, 79% of patients used insulin pumps, and 21% used multiple daily insulin injections; 70% were using continuous glucose monitoring, of whom 86% were using pumps. Patients in both groups had follow-up visits at 2, 6, 13, and 26 weeks.
There were no dropouts in this study – 100% of clinical and telephone follow-ups were completed.
During the 6-month trial, the mean percentage of time spent in the glucose target range rose from 61% at baseline to 71% in the closed-loop group, but remained unchanged at 59% in the pump group. The difference became apparent very early in the study and remained consistent over its course.
“The mean percentage of time that the glucose level was in the target range was 70% in the closed-loop group and 59% in the control [pump] group during the daytime (6 a.m. to midnight) and 76% and 59%, respectively, during the nighttime (midnight to 6 am) ... and the greatest differences in the mean glucose level occurred at 5 a.m. and 6 a.m. [139 mg/dL in the closed-loop group vs. 166 mg/dL in the control group at both time points]. This diurnal pattern is a result of the increased aggressiveness of the algorithm to meet a lower glucose target during the second half of the night,” the authors noted.
The closed-loop system was also better than the pump system on all secondary endpoints, including the following:
- Glycated hemoglobin at 26 weeks: mean difference, –0.33 percentage points.
- Percentage of time with glucose higher than 180 mg/dL: mean difference, –10 percentage points (a difference of 2.4 hr/day).
- Percentage of time with glucose less than 70 mg/dL: mean difference, –0.88 percentage points (a difference of 13 min/day).
The other secondary endpoints – mean glucose level and mean glycated hemoglobin level – were also significantly better in those using the closed-loop system.
The benefits “consistently favored the closed-loop system across a broad range of baseline characteristics, including age, sex, body mass index, income, educational level, insulin pump or infection use, previous use of continuous glucose monitor, and glycated hemoglobin,” the authors said.
There were 17 adverse events in 16 patients in the closed-loop group, and 2 events in 2 patients in the pump group, but no incidents of severe hypoglycemia. One person in the closed-loop system experienced ketoacidosis because of a failure in the pump infusion set. There were 13 hyperglycemic or ketosis episodes in 12 patients in the closed-loop group, and 2 in 2 patients the pump group, but none of them met the criteria for diabetic ketoacidosis. All of these episodes were deemed related to infusion set failures.
There were three serious adverse events in the closed-loop group, and none related to the device. Blood ketones exceeding 1 mmol/L occurred in 11 closed-loop patients and 8 pump patients.
The results should be interpreted with consideration of potential group bias, the authors noted. “In our trial, 70% of the patients were using a continuous glucose monitor, and 79% were using an insulin pump at the time of enrollment, percentages that are substantially higher than the reported usage in the general population of type 1 diabetes. These data may reflect an interest in and willingness to use a closed-loop system among patients who were already using devices as part of diabetes management.”
Dr. Brown reported receiving grant support from Tandem Diabetes Care, Dexcom, and Roche Diagnostics. Other authors reported a range of support from numerous pharmaceutical and medical technology companies. Several reported patents on diabetes-related devices.
SOURCE: Brown SA et al. New Engl J Med. 2019 Oct 16. doi: 10.1056/NEJMoa1907863.
Patients with type 1 diabetes who used a closed-loop insulin delivery system spent a greater percentage of time in their target blood glucose range, compared with patients using a sensor-augmented insulin pump.
The significant, between-group, mean-adjusted difference of 11 percentage points between the two groups translated into the closed-loop patients spending an additional 2.6 hr/day in the target range of 70-180 mg/dL, Susan A. Brown, MD, and colleagues wrote in the New England Journal of Medicine.
Most of the benefit occurred in the early morning hours, at 5 am, when 89% of patients using the closed-loop system remained in the target range, compared with 62% of those using the pump system, said Dr. Brown of the University of Virginia, Charlottesville, and colleagues.
The randomized study comprised 168 patients with a mean age of 33 years, although the age range was wide (14-71 years). The patients had a mean disease duration of 16 years. Their baseline glycated hemoglobin level ranged between 5.4% and 10.6%. At enrollment, 79% of patients used insulin pumps, and 21% used multiple daily insulin injections; 70% were using continuous glucose monitoring, of whom 86% were using pumps. Patients in both groups had follow-up visits at 2, 6, 13, and 26 weeks.
There were no dropouts in this study – 100% of clinical and telephone follow-ups were completed.
During the 6-month trial, the mean percentage of time spent in the glucose target range rose from 61% at baseline to 71% in the closed-loop group, but remained unchanged at 59% in the pump group. The difference became apparent very early in the study and remained consistent over its course.
“The mean percentage of time that the glucose level was in the target range was 70% in the closed-loop group and 59% in the control [pump] group during the daytime (6 a.m. to midnight) and 76% and 59%, respectively, during the nighttime (midnight to 6 am) ... and the greatest differences in the mean glucose level occurred at 5 a.m. and 6 a.m. [139 mg/dL in the closed-loop group vs. 166 mg/dL in the control group at both time points]. This diurnal pattern is a result of the increased aggressiveness of the algorithm to meet a lower glucose target during the second half of the night,” the authors noted.
The closed-loop system was also better than the pump system on all secondary endpoints, including the following:
- Glycated hemoglobin at 26 weeks: mean difference, –0.33 percentage points.
- Percentage of time with glucose higher than 180 mg/dL: mean difference, –10 percentage points (a difference of 2.4 hr/day).
- Percentage of time with glucose less than 70 mg/dL: mean difference, –0.88 percentage points (a difference of 13 min/day).
The other secondary endpoints – mean glucose level and mean glycated hemoglobin level – were also significantly better in those using the closed-loop system.
The benefits “consistently favored the closed-loop system across a broad range of baseline characteristics, including age, sex, body mass index, income, educational level, insulin pump or infection use, previous use of continuous glucose monitor, and glycated hemoglobin,” the authors said.
There were 17 adverse events in 16 patients in the closed-loop group, and 2 events in 2 patients in the pump group, but no incidents of severe hypoglycemia. One person in the closed-loop system experienced ketoacidosis because of a failure in the pump infusion set. There were 13 hyperglycemic or ketosis episodes in 12 patients in the closed-loop group, and 2 in 2 patients the pump group, but none of them met the criteria for diabetic ketoacidosis. All of these episodes were deemed related to infusion set failures.
There were three serious adverse events in the closed-loop group, and none related to the device. Blood ketones exceeding 1 mmol/L occurred in 11 closed-loop patients and 8 pump patients.
The results should be interpreted with consideration of potential group bias, the authors noted. “In our trial, 70% of the patients were using a continuous glucose monitor, and 79% were using an insulin pump at the time of enrollment, percentages that are substantially higher than the reported usage in the general population of type 1 diabetes. These data may reflect an interest in and willingness to use a closed-loop system among patients who were already using devices as part of diabetes management.”
Dr. Brown reported receiving grant support from Tandem Diabetes Care, Dexcom, and Roche Diagnostics. Other authors reported a range of support from numerous pharmaceutical and medical technology companies. Several reported patents on diabetes-related devices.
SOURCE: Brown SA et al. New Engl J Med. 2019 Oct 16. doi: 10.1056/NEJMoa1907863.
Patients with type 1 diabetes who used a closed-loop insulin delivery system spent a greater percentage of time in their target blood glucose range, compared with patients using a sensor-augmented insulin pump.
The significant, between-group, mean-adjusted difference of 11 percentage points between the two groups translated into the closed-loop patients spending an additional 2.6 hr/day in the target range of 70-180 mg/dL, Susan A. Brown, MD, and colleagues wrote in the New England Journal of Medicine.
Most of the benefit occurred in the early morning hours, at 5 am, when 89% of patients using the closed-loop system remained in the target range, compared with 62% of those using the pump system, said Dr. Brown of the University of Virginia, Charlottesville, and colleagues.
The randomized study comprised 168 patients with a mean age of 33 years, although the age range was wide (14-71 years). The patients had a mean disease duration of 16 years. Their baseline glycated hemoglobin level ranged between 5.4% and 10.6%. At enrollment, 79% of patients used insulin pumps, and 21% used multiple daily insulin injections; 70% were using continuous glucose monitoring, of whom 86% were using pumps. Patients in both groups had follow-up visits at 2, 6, 13, and 26 weeks.
There were no dropouts in this study – 100% of clinical and telephone follow-ups were completed.
During the 6-month trial, the mean percentage of time spent in the glucose target range rose from 61% at baseline to 71% in the closed-loop group, but remained unchanged at 59% in the pump group. The difference became apparent very early in the study and remained consistent over its course.
“The mean percentage of time that the glucose level was in the target range was 70% in the closed-loop group and 59% in the control [pump] group during the daytime (6 a.m. to midnight) and 76% and 59%, respectively, during the nighttime (midnight to 6 am) ... and the greatest differences in the mean glucose level occurred at 5 a.m. and 6 a.m. [139 mg/dL in the closed-loop group vs. 166 mg/dL in the control group at both time points]. This diurnal pattern is a result of the increased aggressiveness of the algorithm to meet a lower glucose target during the second half of the night,” the authors noted.
The closed-loop system was also better than the pump system on all secondary endpoints, including the following:
- Glycated hemoglobin at 26 weeks: mean difference, –0.33 percentage points.
- Percentage of time with glucose higher than 180 mg/dL: mean difference, –10 percentage points (a difference of 2.4 hr/day).
- Percentage of time with glucose less than 70 mg/dL: mean difference, –0.88 percentage points (a difference of 13 min/day).
The other secondary endpoints – mean glucose level and mean glycated hemoglobin level – were also significantly better in those using the closed-loop system.
The benefits “consistently favored the closed-loop system across a broad range of baseline characteristics, including age, sex, body mass index, income, educational level, insulin pump or infection use, previous use of continuous glucose monitor, and glycated hemoglobin,” the authors said.
There were 17 adverse events in 16 patients in the closed-loop group, and 2 events in 2 patients in the pump group, but no incidents of severe hypoglycemia. One person in the closed-loop system experienced ketoacidosis because of a failure in the pump infusion set. There were 13 hyperglycemic or ketosis episodes in 12 patients in the closed-loop group, and 2 in 2 patients the pump group, but none of them met the criteria for diabetic ketoacidosis. All of these episodes were deemed related to infusion set failures.
There were three serious adverse events in the closed-loop group, and none related to the device. Blood ketones exceeding 1 mmol/L occurred in 11 closed-loop patients and 8 pump patients.
The results should be interpreted with consideration of potential group bias, the authors noted. “In our trial, 70% of the patients were using a continuous glucose monitor, and 79% were using an insulin pump at the time of enrollment, percentages that are substantially higher than the reported usage in the general population of type 1 diabetes. These data may reflect an interest in and willingness to use a closed-loop system among patients who were already using devices as part of diabetes management.”
Dr. Brown reported receiving grant support from Tandem Diabetes Care, Dexcom, and Roche Diagnostics. Other authors reported a range of support from numerous pharmaceutical and medical technology companies. Several reported patents on diabetes-related devices.
SOURCE: Brown SA et al. New Engl J Med. 2019 Oct 16. doi: 10.1056/NEJMoa1907863.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Which patients are most likely to have a positive RNS test for myasthenia gravis?
AUSTIN, TEX. – , according to research presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine.
Low-frequency RNS is a common test that neurologists perform to evaluate a patient for myasthenia gravis. The effects of various clinical factors on the diagnostic yield of this test are unknown, however.
Myasthenia gravis is “mostly a clinical diagnosis,” study first author Tingting Hua, a medical student at the University of Missouri in Columbia, said in an interview. “RNS is just one of the helpful diagnostic tests for it. If we can find out in what kind of populations of patients this test is more helpful, maybe that would help cut down unnecessary tests in patients for whom it’s not necessarily helpful.”
Ms. Hua and her colleagues conducted research to assess the effects of clinical, serologic, and demographic factors on the diagnostic yield of RNS. They retrospectively analyzed patients with an established diagnosis of myasthenia gravis and at least 1 year of follow-up. The variables that the investigators examined were demographic characteristics, MGFA class, RNS study results, antibody test results, thymoma status, and treatments received.
Ms. Hua and her colleagues included 65 patients in their analysis. Thirty-one patients were female. Fifty-five patients were white, eight were black, and two were categorized as “unknown.” Of this population, 32 patients (49.2%) were in MGFA Class I, 14 (21.5%) were in MGFA Class IIa, 13 (20.0%) were in MGFA Class IIb, and the remaining 6 (9.2%) were in MGFA Classes IIIa through V. Twenty-seven patients (42%) had positive RNS studies. Twenty-one patients (32%) were seropositive for myasthenia gravis antibodies.
Eleven patients underwent RNS in an inpatient setting, and 54 were tested in an outpatient setting. Acetylcholine receptor (AChR) binding antibody titer ranged from 0.12 nmol/L to 118 nmol/L. The RNS results were significantly more likely to be positive for seropositive patients, compared with seronegative patients. Patients with MGFA Class III or higher also had higher likelihood of positive RNS results, compared with patients in lower classes. Finally, the diagnostic yield was highest for patients with MGFA Class III or higher who were tested in an inpatient setting.
The study was supported by a Missouri School of Medicine Summer Research Fellowship.
SOURCE: Hua T et al. AANEM 2019, Abstract 9.
AUSTIN, TEX. – , according to research presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine.
Low-frequency RNS is a common test that neurologists perform to evaluate a patient for myasthenia gravis. The effects of various clinical factors on the diagnostic yield of this test are unknown, however.
Myasthenia gravis is “mostly a clinical diagnosis,” study first author Tingting Hua, a medical student at the University of Missouri in Columbia, said in an interview. “RNS is just one of the helpful diagnostic tests for it. If we can find out in what kind of populations of patients this test is more helpful, maybe that would help cut down unnecessary tests in patients for whom it’s not necessarily helpful.”
Ms. Hua and her colleagues conducted research to assess the effects of clinical, serologic, and demographic factors on the diagnostic yield of RNS. They retrospectively analyzed patients with an established diagnosis of myasthenia gravis and at least 1 year of follow-up. The variables that the investigators examined were demographic characteristics, MGFA class, RNS study results, antibody test results, thymoma status, and treatments received.
Ms. Hua and her colleagues included 65 patients in their analysis. Thirty-one patients were female. Fifty-five patients were white, eight were black, and two were categorized as “unknown.” Of this population, 32 patients (49.2%) were in MGFA Class I, 14 (21.5%) were in MGFA Class IIa, 13 (20.0%) were in MGFA Class IIb, and the remaining 6 (9.2%) were in MGFA Classes IIIa through V. Twenty-seven patients (42%) had positive RNS studies. Twenty-one patients (32%) were seropositive for myasthenia gravis antibodies.
Eleven patients underwent RNS in an inpatient setting, and 54 were tested in an outpatient setting. Acetylcholine receptor (AChR) binding antibody titer ranged from 0.12 nmol/L to 118 nmol/L. The RNS results were significantly more likely to be positive for seropositive patients, compared with seronegative patients. Patients with MGFA Class III or higher also had higher likelihood of positive RNS results, compared with patients in lower classes. Finally, the diagnostic yield was highest for patients with MGFA Class III or higher who were tested in an inpatient setting.
The study was supported by a Missouri School of Medicine Summer Research Fellowship.
SOURCE: Hua T et al. AANEM 2019, Abstract 9.
AUSTIN, TEX. – , according to research presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine.
Low-frequency RNS is a common test that neurologists perform to evaluate a patient for myasthenia gravis. The effects of various clinical factors on the diagnostic yield of this test are unknown, however.
Myasthenia gravis is “mostly a clinical diagnosis,” study first author Tingting Hua, a medical student at the University of Missouri in Columbia, said in an interview. “RNS is just one of the helpful diagnostic tests for it. If we can find out in what kind of populations of patients this test is more helpful, maybe that would help cut down unnecessary tests in patients for whom it’s not necessarily helpful.”
Ms. Hua and her colleagues conducted research to assess the effects of clinical, serologic, and demographic factors on the diagnostic yield of RNS. They retrospectively analyzed patients with an established diagnosis of myasthenia gravis and at least 1 year of follow-up. The variables that the investigators examined were demographic characteristics, MGFA class, RNS study results, antibody test results, thymoma status, and treatments received.
Ms. Hua and her colleagues included 65 patients in their analysis. Thirty-one patients were female. Fifty-five patients were white, eight were black, and two were categorized as “unknown.” Of this population, 32 patients (49.2%) were in MGFA Class I, 14 (21.5%) were in MGFA Class IIa, 13 (20.0%) were in MGFA Class IIb, and the remaining 6 (9.2%) were in MGFA Classes IIIa through V. Twenty-seven patients (42%) had positive RNS studies. Twenty-one patients (32%) were seropositive for myasthenia gravis antibodies.
Eleven patients underwent RNS in an inpatient setting, and 54 were tested in an outpatient setting. Acetylcholine receptor (AChR) binding antibody titer ranged from 0.12 nmol/L to 118 nmol/L. The RNS results were significantly more likely to be positive for seropositive patients, compared with seronegative patients. Patients with MGFA Class III or higher also had higher likelihood of positive RNS results, compared with patients in lower classes. Finally, the diagnostic yield was highest for patients with MGFA Class III or higher who were tested in an inpatient setting.
The study was supported by a Missouri School of Medicine Summer Research Fellowship.
SOURCE: Hua T et al. AANEM 2019, Abstract 9.
REPORTING FROM AANEM 2019
Study examines utility of repeat outpatient electrodiagnostic testing
AUSTIN, TEX. – During a 3-year period, 5.7% of patients referred to an electromyography laboratory returned for at least one additional electrodiagnostic study, according to research presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine. A preliminary analysis suggests that repeat testing for the same indication does not change symptom or disease management in about one-third of cases.
Physicians may request repeat electrodiagnostic studies to monitor previous, new, or progressing symptoms in the same or different body segments. “While the utility of [electrodiagnostic] studies for clinical care has been established, testing is associated with some patient risk, time, and cost,” the researchers wrote. “To date, there have been no known studies investigating the utility of repeat [electrodiagnostic] testing in the outpatient setting.”
To study referral patterns and outcomes following repeat electrodiagnostic testing, Aimee K. Boegle, MD, PhD, an instructor in neurology at Beth Israel Deaconess Medical Center in Boston, and colleagues examined all outpatient electromyography and nerve conduction studies performed between 2015 and 2017 in the neurology department at their institution. The investigators excluded patients who underwent inpatient electrodiagnostic studies from their analysis.
Approximately 4,800 patients underwent electrodiagnostic testing, 276 of whom underwent testing more than once.
Among patients who underwent two studies, 55% were referred by a different physician for the second study. Median neuropathy was the most common referring and final diagnosis among patients who underwent repeat electrodiagnostic testing, Dr. Boegle said. This finding was not surprising because carpal tunnel syndrome is among the most common reasons for referral overall.
Median neuropathy was the referring diagnosis in 31% and the final diagnosis in 30%, cervical radiculopathy in 15% and 14%, ulnar neuropathy in 14% and 17%, lumbosacral radiculopathy in 12% and 10%, and polyneuropathy in 8% and 10%.
The neurology and orthopedics departments made the most referrals for repeat electrodiagnostic studies (49.4% and 29.3%, respectively), followed by primary care physicians/internal medicine (13%).
About 24% of the returning patients underwent testing for the same indication as their initial referral.
A preliminary analysis of 26 patients who underwent a repeat study for the same indication found no change in treatment in 34%. When a study prompted intervention, a conservative course of management such as a splint or physical therapy was used in 42%. About 8% received a pharmacologic intervention, such as a medication change or steroid injections. Another 8% received a surgical intervention and about 8% received further work-up.
The researchers had no relevant disclosures.
SOURCE: Boegle AK et al. AANEM 2019, Abstract 85.
AUSTIN, TEX. – During a 3-year period, 5.7% of patients referred to an electromyography laboratory returned for at least one additional electrodiagnostic study, according to research presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine. A preliminary analysis suggests that repeat testing for the same indication does not change symptom or disease management in about one-third of cases.
Physicians may request repeat electrodiagnostic studies to monitor previous, new, or progressing symptoms in the same or different body segments. “While the utility of [electrodiagnostic] studies for clinical care has been established, testing is associated with some patient risk, time, and cost,” the researchers wrote. “To date, there have been no known studies investigating the utility of repeat [electrodiagnostic] testing in the outpatient setting.”
To study referral patterns and outcomes following repeat electrodiagnostic testing, Aimee K. Boegle, MD, PhD, an instructor in neurology at Beth Israel Deaconess Medical Center in Boston, and colleagues examined all outpatient electromyography and nerve conduction studies performed between 2015 and 2017 in the neurology department at their institution. The investigators excluded patients who underwent inpatient electrodiagnostic studies from their analysis.
Approximately 4,800 patients underwent electrodiagnostic testing, 276 of whom underwent testing more than once.
Among patients who underwent two studies, 55% were referred by a different physician for the second study. Median neuropathy was the most common referring and final diagnosis among patients who underwent repeat electrodiagnostic testing, Dr. Boegle said. This finding was not surprising because carpal tunnel syndrome is among the most common reasons for referral overall.
Median neuropathy was the referring diagnosis in 31% and the final diagnosis in 30%, cervical radiculopathy in 15% and 14%, ulnar neuropathy in 14% and 17%, lumbosacral radiculopathy in 12% and 10%, and polyneuropathy in 8% and 10%.
The neurology and orthopedics departments made the most referrals for repeat electrodiagnostic studies (49.4% and 29.3%, respectively), followed by primary care physicians/internal medicine (13%).
About 24% of the returning patients underwent testing for the same indication as their initial referral.
A preliminary analysis of 26 patients who underwent a repeat study for the same indication found no change in treatment in 34%. When a study prompted intervention, a conservative course of management such as a splint or physical therapy was used in 42%. About 8% received a pharmacologic intervention, such as a medication change or steroid injections. Another 8% received a surgical intervention and about 8% received further work-up.
The researchers had no relevant disclosures.
SOURCE: Boegle AK et al. AANEM 2019, Abstract 85.
AUSTIN, TEX. – During a 3-year period, 5.7% of patients referred to an electromyography laboratory returned for at least one additional electrodiagnostic study, according to research presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine. A preliminary analysis suggests that repeat testing for the same indication does not change symptom or disease management in about one-third of cases.
Physicians may request repeat electrodiagnostic studies to monitor previous, new, or progressing symptoms in the same or different body segments. “While the utility of [electrodiagnostic] studies for clinical care has been established, testing is associated with some patient risk, time, and cost,” the researchers wrote. “To date, there have been no known studies investigating the utility of repeat [electrodiagnostic] testing in the outpatient setting.”
To study referral patterns and outcomes following repeat electrodiagnostic testing, Aimee K. Boegle, MD, PhD, an instructor in neurology at Beth Israel Deaconess Medical Center in Boston, and colleagues examined all outpatient electromyography and nerve conduction studies performed between 2015 and 2017 in the neurology department at their institution. The investigators excluded patients who underwent inpatient electrodiagnostic studies from their analysis.
Approximately 4,800 patients underwent electrodiagnostic testing, 276 of whom underwent testing more than once.
Among patients who underwent two studies, 55% were referred by a different physician for the second study. Median neuropathy was the most common referring and final diagnosis among patients who underwent repeat electrodiagnostic testing, Dr. Boegle said. This finding was not surprising because carpal tunnel syndrome is among the most common reasons for referral overall.
Median neuropathy was the referring diagnosis in 31% and the final diagnosis in 30%, cervical radiculopathy in 15% and 14%, ulnar neuropathy in 14% and 17%, lumbosacral radiculopathy in 12% and 10%, and polyneuropathy in 8% and 10%.
The neurology and orthopedics departments made the most referrals for repeat electrodiagnostic studies (49.4% and 29.3%, respectively), followed by primary care physicians/internal medicine (13%).
About 24% of the returning patients underwent testing for the same indication as their initial referral.
A preliminary analysis of 26 patients who underwent a repeat study for the same indication found no change in treatment in 34%. When a study prompted intervention, a conservative course of management such as a splint or physical therapy was used in 42%. About 8% received a pharmacologic intervention, such as a medication change or steroid injections. Another 8% received a surgical intervention and about 8% received further work-up.
The researchers had no relevant disclosures.
SOURCE: Boegle AK et al. AANEM 2019, Abstract 85.
REPORTING FROM AANEM 2019
Amoxicillin/clavulanate emerges as best antibiotic for childhood bronchiectasis
MADRID – A placebo-controlled trial has confirmed that amoxicillin/clavulanate is beneficial for resolution of acute exacerbations in nonsevere bronchiectasis while also demonstrating a greater relative effect than azithromycin, based on data presented at the annual congress of the European Respiratory Society.
“We now have robust data with which to support our guidelines,” reported Vikas Goyal, MD, of the Children’s Health Clinical Unit, University of Queensland, Brisbane, Australia.
The study addresses a knowledge gap. Antibiotics are already recommended by many guidelines for treatment of acute exacerbations in children with bronchiectasis, but Dr. Goyal said that no controlled trials have ever been performed in this age group to confirm superiority to placebo.
In this multicenter study, called BEST-1, 197 children with bronchiectasis were randomized at the start of an exacerbation to placebo, 45 mg/kg per day of amoxicillin/clavulanate, or 5 mg/kg per day of azithromycin. To maintain blinding, patients in the active treatment groups received a dummy for the opposite antibiotic while patients on placebo received dummies for both active agents.
For the primary outcome, 65% of children randomized to amoxicillin/clavulanate had resolution of their exacerbation by day 14 versus 61% of those randomized to azithromycin and 43% of those randomized to placebo. On the basis of relative risk for reaching this end point, the outcome was superior to placebo for amoxicillin/clavulanate (RR, 1.5; P = .015).
Although the relative risk for azithromycin (RR, 1.4; P = .042) was only slightly lower, it did not reach a prespecified level of significance set at P = .025. Dr. Goyal did report that the resolution rate at 14 days in the placebo group was “higher than expected.”
In this trial, 53% of the 154 children who were tested for respiratory viruses with nasal swabs on day 1 of the exacerbation were found to have respiratory viruses. Of these viruses, rhinovirus was the most common, according to Dr. Goyal, whose data were published just prior to his presentation (Lancet Respir Med. 2019;7:791-801).
The median durations of the exacerbations were 7 days, 8 days, and 10 days for those treated with amoxicillin/clavulanate, azithromycin, and placebo, respectively. The difference between amoxicillin/clavulanate and placebo, but not that between azithromycin and placebo, reached statistical significance, Dr. Goyal said.
There were no between group differences in the time to next exacerbation.
In discussing limitations of this study, Dr. Goyal pointed out that the optimal doses of amoxicillin/clavulanate or azithromycin have never been established for the treatment of exacerbations in children with bronchiectasis. He noted that some infectious disease specialists have advocated higher doses of both than those employed in this trial, but dose-ranging studies have never been conducted in this age group.
In this study, adverse events were less common on azithromycin than amoxicillin/clavulanate (21% vs. 30%), but none were severe, according to Dr. Goyal. He said treatment with azithromycin was associated with increased macrolide-resistant bacteria.
On the basis of these data, Dr. Goyal concluded that amoxicillin/clavulanate should remain, as already specified in some guidelines, the standard first-line therapy for nonsevere exacerbations in nonhospitalized children with bronchiectasis. He recommended reserving azithromycin as an alternative therapy.
Dr. Goyal reports no potential conflicts of interest.
SOURCE: Goyal V et al. Lancet Respir Med. 2019;7:791-801.
MADRID – A placebo-controlled trial has confirmed that amoxicillin/clavulanate is beneficial for resolution of acute exacerbations in nonsevere bronchiectasis while also demonstrating a greater relative effect than azithromycin, based on data presented at the annual congress of the European Respiratory Society.
“We now have robust data with which to support our guidelines,” reported Vikas Goyal, MD, of the Children’s Health Clinical Unit, University of Queensland, Brisbane, Australia.
The study addresses a knowledge gap. Antibiotics are already recommended by many guidelines for treatment of acute exacerbations in children with bronchiectasis, but Dr. Goyal said that no controlled trials have ever been performed in this age group to confirm superiority to placebo.
In this multicenter study, called BEST-1, 197 children with bronchiectasis were randomized at the start of an exacerbation to placebo, 45 mg/kg per day of amoxicillin/clavulanate, or 5 mg/kg per day of azithromycin. To maintain blinding, patients in the active treatment groups received a dummy for the opposite antibiotic while patients on placebo received dummies for both active agents.
For the primary outcome, 65% of children randomized to amoxicillin/clavulanate had resolution of their exacerbation by day 14 versus 61% of those randomized to azithromycin and 43% of those randomized to placebo. On the basis of relative risk for reaching this end point, the outcome was superior to placebo for amoxicillin/clavulanate (RR, 1.5; P = .015).
Although the relative risk for azithromycin (RR, 1.4; P = .042) was only slightly lower, it did not reach a prespecified level of significance set at P = .025. Dr. Goyal did report that the resolution rate at 14 days in the placebo group was “higher than expected.”
In this trial, 53% of the 154 children who were tested for respiratory viruses with nasal swabs on day 1 of the exacerbation were found to have respiratory viruses. Of these viruses, rhinovirus was the most common, according to Dr. Goyal, whose data were published just prior to his presentation (Lancet Respir Med. 2019;7:791-801).
The median durations of the exacerbations were 7 days, 8 days, and 10 days for those treated with amoxicillin/clavulanate, azithromycin, and placebo, respectively. The difference between amoxicillin/clavulanate and placebo, but not that between azithromycin and placebo, reached statistical significance, Dr. Goyal said.
There were no between group differences in the time to next exacerbation.
In discussing limitations of this study, Dr. Goyal pointed out that the optimal doses of amoxicillin/clavulanate or azithromycin have never been established for the treatment of exacerbations in children with bronchiectasis. He noted that some infectious disease specialists have advocated higher doses of both than those employed in this trial, but dose-ranging studies have never been conducted in this age group.
In this study, adverse events were less common on azithromycin than amoxicillin/clavulanate (21% vs. 30%), but none were severe, according to Dr. Goyal. He said treatment with azithromycin was associated with increased macrolide-resistant bacteria.
On the basis of these data, Dr. Goyal concluded that amoxicillin/clavulanate should remain, as already specified in some guidelines, the standard first-line therapy for nonsevere exacerbations in nonhospitalized children with bronchiectasis. He recommended reserving azithromycin as an alternative therapy.
Dr. Goyal reports no potential conflicts of interest.
SOURCE: Goyal V et al. Lancet Respir Med. 2019;7:791-801.
MADRID – A placebo-controlled trial has confirmed that amoxicillin/clavulanate is beneficial for resolution of acute exacerbations in nonsevere bronchiectasis while also demonstrating a greater relative effect than azithromycin, based on data presented at the annual congress of the European Respiratory Society.
“We now have robust data with which to support our guidelines,” reported Vikas Goyal, MD, of the Children’s Health Clinical Unit, University of Queensland, Brisbane, Australia.
The study addresses a knowledge gap. Antibiotics are already recommended by many guidelines for treatment of acute exacerbations in children with bronchiectasis, but Dr. Goyal said that no controlled trials have ever been performed in this age group to confirm superiority to placebo.
In this multicenter study, called BEST-1, 197 children with bronchiectasis were randomized at the start of an exacerbation to placebo, 45 mg/kg per day of amoxicillin/clavulanate, or 5 mg/kg per day of azithromycin. To maintain blinding, patients in the active treatment groups received a dummy for the opposite antibiotic while patients on placebo received dummies for both active agents.
For the primary outcome, 65% of children randomized to amoxicillin/clavulanate had resolution of their exacerbation by day 14 versus 61% of those randomized to azithromycin and 43% of those randomized to placebo. On the basis of relative risk for reaching this end point, the outcome was superior to placebo for amoxicillin/clavulanate (RR, 1.5; P = .015).
Although the relative risk for azithromycin (RR, 1.4; P = .042) was only slightly lower, it did not reach a prespecified level of significance set at P = .025. Dr. Goyal did report that the resolution rate at 14 days in the placebo group was “higher than expected.”
In this trial, 53% of the 154 children who were tested for respiratory viruses with nasal swabs on day 1 of the exacerbation were found to have respiratory viruses. Of these viruses, rhinovirus was the most common, according to Dr. Goyal, whose data were published just prior to his presentation (Lancet Respir Med. 2019;7:791-801).
The median durations of the exacerbations were 7 days, 8 days, and 10 days for those treated with amoxicillin/clavulanate, azithromycin, and placebo, respectively. The difference between amoxicillin/clavulanate and placebo, but not that between azithromycin and placebo, reached statistical significance, Dr. Goyal said.
There were no between group differences in the time to next exacerbation.
In discussing limitations of this study, Dr. Goyal pointed out that the optimal doses of amoxicillin/clavulanate or azithromycin have never been established for the treatment of exacerbations in children with bronchiectasis. He noted that some infectious disease specialists have advocated higher doses of both than those employed in this trial, but dose-ranging studies have never been conducted in this age group.
In this study, adverse events were less common on azithromycin than amoxicillin/clavulanate (21% vs. 30%), but none were severe, according to Dr. Goyal. He said treatment with azithromycin was associated with increased macrolide-resistant bacteria.
On the basis of these data, Dr. Goyal concluded that amoxicillin/clavulanate should remain, as already specified in some guidelines, the standard first-line therapy for nonsevere exacerbations in nonhospitalized children with bronchiectasis. He recommended reserving azithromycin as an alternative therapy.
Dr. Goyal reports no potential conflicts of interest.
SOURCE: Goyal V et al. Lancet Respir Med. 2019;7:791-801.
REPORTING FROM ERS 2019