In a large, nationally representative retrospective cohort study, migraine admission with aura was independently associated with transient ischemic attack (TIA) readmission, and status migrainosus was independently associated with subarachnoid hemorrhage. The Nationwide Readmissions Database was designed to analyze readmissions for all payers and uninsured, with data on more than 14 million US admissions in 2013. Researchers identified index migraine admissions with and without aura or status migrainosus, and readmissions for cerebrovascular events. Cox proportional hazards regression was performed for each outcome with aura and status migrainosus as main predictors, adjusting for age and vascular risk factors. They found:

• Out of 12,448 index admissions for migraine, 9972 (80.1%) were women, mean age was 45.5 ± 14.8 years, aura was present in 3038 (24.41%), and status migrainosus in 1798 (14.44%).
• The 30‐day readmission rate (per 100,000 index admissions) was 154 for ischemic stroke, 86 for TIA, 42 for subarachnoid hemorrhage, and 17 for intracranial hemorrhage.
• In unadjusted models, aura was significantly associated with TIA (hazard ratio 2.43), but not acute ischemic stroke (1.26), intracranial hemorrhage (1.86), or subarachnoid hemorrhage (1.85).

Velickovic Osotjic L, Liang JW, Sheikh HU, Dhamoon MS. Impact of aura and status migrainosus on readmissions for vascular events after migraine admission. [Published online ahead of print June 22, 2018]. Headache. doi:10.1111/head.13347.

In a large, nationally representative retrospective cohort study, migraine admission with aura was independently associated with transient ischemic attack (TIA) readmission, and status migrainosus was independently associated with subarachnoid hemorrhage. The Nationwide Readmissions Database was designed to analyze readmissions for all payers and uninsured, with data on more than 14 million US admissions in 2013. Researchers identified index migraine admissions with and without aura or status migrainosus, and readmissions for cerebrovascular events. Cox proportional hazards regression was performed for each outcome with aura and status migrainosus as main predictors, adjusting for age and vascular risk factors. They found:

• Out of 12,448 index admissions for migraine, 9972 (80.1%) were women, mean age was 45.5 ± 14.8 years, aura was present in 3038 (24.41%), and status migrainosus in 1798 (14.44%).
• The 30‐day readmission rate (per 100,000 index admissions) was 154 for ischemic stroke, 86 for TIA, 42 for subarachnoid hemorrhage, and 17 for intracranial hemorrhage.
• In unadjusted models, aura was significantly associated with TIA (hazard ratio 2.43), but not acute ischemic stroke (1.26), intracranial hemorrhage (1.86), or subarachnoid hemorrhage (1.85).

Velickovic Osotjic L, Liang JW, Sheikh HU, Dhamoon MS. Impact of aura and status migrainosus on readmissions for vascular events after migraine admission. [Published online ahead of print June 22, 2018]. Headache. doi:10.1111/head.13347.

In a large, nationally representative retrospective cohort study, migraine admission with aura was independently associated with transient ischemic attack (TIA) readmission, and status migrainosus was independently associated with subarachnoid hemorrhage. The Nationwide Readmissions Database was designed to analyze readmissions for all payers and uninsured, with data on more than 14 million US admissions in 2013. Researchers identified index migraine admissions with and without aura or status migrainosus, and readmissions for cerebrovascular events. Cox proportional hazards regression was performed for each outcome with aura and status migrainosus as main predictors, adjusting for age and vascular risk factors. They found:

• Out of 12,448 index admissions for migraine, 9972 (80.1%) were women, mean age was 45.5 ± 14.8 years, aura was present in 3038 (24.41%), and status migrainosus in 1798 (14.44%).
• The 30‐day readmission rate (per 100,000 index admissions) was 154 for ischemic stroke, 86 for TIA, 42 for subarachnoid hemorrhage, and 17 for intracranial hemorrhage.
• In unadjusted models, aura was significantly associated with TIA (hazard ratio 2.43), but not acute ischemic stroke (1.26), intracranial hemorrhage (1.86), or subarachnoid hemorrhage (1.85).

Velickovic Osotjic L, Liang JW, Sheikh HU, Dhamoon MS. Impact of aura and status migrainosus on readmissions for vascular events after migraine admission. [Published online ahead of print June 22, 2018]. Headache. doi:10.1111/head.13347.

Headache smartphone applications (apps) shared information with third parties, posing privacy risks partly because there are few legal protections against the sale or disclosure of data from medical apps to third parties. This is according to a recent study that sought to assess whether there are privacy issues surrounding apps and the potential privacy implications of how the app companies (and other third parties) might use that information. Researchers conducted a systematic search of the most popular “headache” and “migraine” apps and developed a database of the types of data the apps requested for input by the user, and whether the apps had clear privacy policies. They also examined the content of the privacy policies and found:

• Twenty-nine apps were examined (14 diary apps, 15 relaxation apps).
• Of the diary applications, 79% (11/14) had visible privacy policies.
• Of the diary apps with privacy policies, all (11/11) stated whether or not the app collects and stores information remotely.
• A total of 55% (6/11) stated that some user data were used to serve targeted advertisements.
• A total of 11/15 (73%) of the relaxation apps had privacy policies.

Minen MT, Stieglitz EJ, Sciortino R, Torous J. Privacy issues in smartphone applications: An analysis of headache/migraine applications. [Published online ahead of print July 4, 2018]. Headache. doi:10.1111/head.13341.

Headache smartphone applications (apps) shared information with third parties, posing privacy risks partly because there are few legal protections against the sale or disclosure of data from medical apps to third parties. This is according to a recent study that sought to assess whether there are privacy issues surrounding apps and the potential privacy implications of how the app companies (and other third parties) might use that information. Researchers conducted a systematic search of the most popular “headache” and “migraine” apps and developed a database of the types of data the apps requested for input by the user, and whether the apps had clear privacy policies. They also examined the content of the privacy policies and found:

• Twenty-nine apps were examined (14 diary apps, 15 relaxation apps).
• Of the diary applications, 79% (11/14) had visible privacy policies.
• Of the diary apps with privacy policies, all (11/11) stated whether or not the app collects and stores information remotely.
• A total of 55% (6/11) stated that some user data were used to serve targeted advertisements.
• A total of 11/15 (73%) of the relaxation apps had privacy policies.

Minen MT, Stieglitz EJ, Sciortino R, Torous J. Privacy issues in smartphone applications: An analysis of headache/migraine applications. [Published online ahead of print July 4, 2018]. Headache. doi:10.1111/head.13341.

Headache smartphone applications (apps) shared information with third parties, posing privacy risks partly because there are few legal protections against the sale or disclosure of data from medical apps to third parties. This is according to a recent study that sought to assess whether there are privacy issues surrounding apps and the potential privacy implications of how the app companies (and other third parties) might use that information. Researchers conducted a systematic search of the most popular “headache” and “migraine” apps and developed a database of the types of data the apps requested for input by the user, and whether the apps had clear privacy policies. They also examined the content of the privacy policies and found:

• Twenty-nine apps were examined (14 diary apps, 15 relaxation apps).
• Of the diary applications, 79% (11/14) had visible privacy policies.
• Of the diary apps with privacy policies, all (11/11) stated whether or not the app collects and stores information remotely.
• A total of 55% (6/11) stated that some user data were used to serve targeted advertisements.
• A total of 11/15 (73%) of the relaxation apps had privacy policies.

Minen MT, Stieglitz EJ, Sciortino R, Torous J. Privacy issues in smartphone applications: An analysis of headache/migraine applications. [Published online ahead of print July 4, 2018]. Headache. doi:10.1111/head.13341.

Patients with migraine undergoing surgery are at increased risk of 30-day hospital readmission due to pain, a recent study found. This hospital registry study examined 150,710 patients, aged 18 years or older, who underwent surgery with general anesthesia and mechanical ventilation between 2007 and 2015 at a tertiary care center and 2 affiliated community hospitals in Massachusetts. Researchers found:

• Migraine was associated with an increased risk of 30-day pain-related readmission after surgery (adjusted odds ratio [OR] 1.42).
• The association was stronger for migraine with aura (compared to migraine without aura: adjusted OR 1.69; compared to no migraine: adjusted OR 2.20).
• The predicted adjusted risk of pain-related 30-day readmissions was 9.1 in 1000 surgical patients with migraine with aura and 5.4 in 1,000 patients with migraine without aura, compared to 4.2 in 1000 patients with no migraine.
• Furthermore, migraine was associated with an increased risk of postsurgical 30-day readmission due to a priori defined migraine-related pain (headache or abdominal pain) (adjusted OR 1.55).

Platzbecker K, Zhang MB, Kurth T, et al. The association between migraine and hospital readmission due to pain after surgery: A hospital registry study. [Published online ahead of print July 8, 2018]. Cephalalgia. doi:10.1177/0333102418786457.

Patients with migraine undergoing surgery are at increased risk of 30-day hospital readmission due to pain, a recent study found. This hospital registry study examined 150,710 patients, aged 18 years or older, who underwent surgery with general anesthesia and mechanical ventilation between 2007 and 2015 at a tertiary care center and 2 affiliated community hospitals in Massachusetts. Researchers found:

• Migraine was associated with an increased risk of 30-day pain-related readmission after surgery (adjusted odds ratio [OR] 1.42).
• The association was stronger for migraine with aura (compared to migraine without aura: adjusted OR 1.69; compared to no migraine: adjusted OR 2.20).
• The predicted adjusted risk of pain-related 30-day readmissions was 9.1 in 1000 surgical patients with migraine with aura and 5.4 in 1,000 patients with migraine without aura, compared to 4.2 in 1000 patients with no migraine.
• Furthermore, migraine was associated with an increased risk of postsurgical 30-day readmission due to a priori defined migraine-related pain (headache or abdominal pain) (adjusted OR 1.55).

Platzbecker K, Zhang MB, Kurth T, et al. The association between migraine and hospital readmission due to pain after surgery: A hospital registry study. [Published online ahead of print July 8, 2018]. Cephalalgia. doi:10.1177/0333102418786457.

Patients with migraine undergoing surgery are at increased risk of 30-day hospital readmission due to pain, a recent study found. This hospital registry study examined 150,710 patients, aged 18 years or older, who underwent surgery with general anesthesia and mechanical ventilation between 2007 and 2015 at a tertiary care center and 2 affiliated community hospitals in Massachusetts. Researchers found:

• Migraine was associated with an increased risk of 30-day pain-related readmission after surgery (adjusted odds ratio [OR] 1.42).
• The association was stronger for migraine with aura (compared to migraine without aura: adjusted OR 1.69; compared to no migraine: adjusted OR 2.20).
• The predicted adjusted risk of pain-related 30-day readmissions was 9.1 in 1000 surgical patients with migraine with aura and 5.4 in 1,000 patients with migraine without aura, compared to 4.2 in 1000 patients with no migraine.
• Furthermore, migraine was associated with an increased risk of postsurgical 30-day readmission due to a priori defined migraine-related pain (headache or abdominal pain) (adjusted OR 1.55).

Platzbecker K, Zhang MB, Kurth T, et al. The association between migraine and hospital readmission due to pain after surgery: A hospital registry study. [Published online ahead of print July 8, 2018]. Cephalalgia. doi:10.1177/0333102418786457.

AMSTERDAM – Greater increases in bone strength were achieved with denosumab (Prolia) than with risedronate in patients receiving glucocorticoid treatment in a phase 3 trial, suggesting it may prove to be an effective means of preventing osteoporosis in this at-risk population of patients.

At 2 years, the percentage change in bone mineral density (BMD) from baseline with denosumab compared to risedronate in patients initiating steroid treatment was significantly higher (all P values less than .001) at the lumbar spine (6% vs. 2%), total hip (3% vs. 0%), and the femoral neck (1.5% vs. –1%). Similar results were seen in patients who were continuing steroid treatment when they entered the randomized, multicenter, double blind trial.

These data build on the 1-year data that have just been published (Lancet Diabetes Endocrinol. 2018;6[6]:445-54), Willem F. Lems, MD, the presenting study investigator, said at the European Congress of Rheumatology.

“Denosumab continued to increased BMD significantly more then risedronate through 24 months,” said Dr. Lems of VU University Medical Center, Amsterdam. He added that “the treatment differences at all skeletal sites were larger at 24 months than as 12 months.”

The Food and Drug Administration approved an additional indication in May of 2018 for denosumab to treat glucocorticoid-induced osteoporosis in adults at high risk of fracture. The biologic, a monoclonal antibody that targets the RANK ligand, was already approved to treat postmenopausal women with osteoporosis at high fracture risk, to increase bone mass in men with osteoporosis at high fracture risk, and to increase bone mass in women receiving adjuvant aromatase inhibitor therapy for breast cancer and in men receiving androgen deprivation therapy for nonmetastatic prostate cancer.

Secondary osteoporosis is a well known downside of glucocorticoid treatment, and despite there being approved therapies, many patients do not receive such treatment, Dr. Lems noted.

“This 24-month study assessed the safety and efficacy of denosumab versus risedronate in glucocorticoid-treated individuals, in whom guidelines advocate treatment,” Dr. Lems said.

Sara Freeman/MDedge News

SOURCE: Saag KG et al. Ann Rheum Dis. 2018;77(Suppl 2):218. Abstract OP0345.

AMSTERDAM – Greater increases in bone strength were achieved with denosumab (Prolia) than with risedronate in patients receiving glucocorticoid treatment in a phase 3 trial, suggesting it may prove to be an effective means of preventing osteoporosis in this at-risk population of patients.

At 2 years, the percentage change in bone mineral density (BMD) from baseline with denosumab compared to risedronate in patients initiating steroid treatment was significantly higher (all P values less than .001) at the lumbar spine (6% vs. 2%), total hip (3% vs. 0%), and the femoral neck (1.5% vs. –1%). Similar results were seen in patients who were continuing steroid treatment when they entered the randomized, multicenter, double blind trial.

These data build on the 1-year data that have just been published (Lancet Diabetes Endocrinol. 2018;6[6]:445-54), Willem F. Lems, MD, the presenting study investigator, said at the European Congress of Rheumatology.

“Denosumab continued to increased BMD significantly more then risedronate through 24 months,” said Dr. Lems of VU University Medical Center, Amsterdam. He added that “the treatment differences at all skeletal sites were larger at 24 months than as 12 months.”

The Food and Drug Administration approved an additional indication in May of 2018 for denosumab to treat glucocorticoid-induced osteoporosis in adults at high risk of fracture. The biologic, a monoclonal antibody that targets the RANK ligand, was already approved to treat postmenopausal women with osteoporosis at high fracture risk, to increase bone mass in men with osteoporosis at high fracture risk, and to increase bone mass in women receiving adjuvant aromatase inhibitor therapy for breast cancer and in men receiving androgen deprivation therapy for nonmetastatic prostate cancer.

Secondary osteoporosis is a well known downside of glucocorticoid treatment, and despite there being approved therapies, many patients do not receive such treatment, Dr. Lems noted.

“This 24-month study assessed the safety and efficacy of denosumab versus risedronate in glucocorticoid-treated individuals, in whom guidelines advocate treatment,” Dr. Lems said.

Sara Freeman/MDedge News

SOURCE: Saag KG et al. Ann Rheum Dis. 2018;77(Suppl 2):218. Abstract OP0345.

AMSTERDAM – Greater increases in bone strength were achieved with denosumab (Prolia) than with risedronate in patients receiving glucocorticoid treatment in a phase 3 trial, suggesting it may prove to be an effective means of preventing osteoporosis in this at-risk population of patients.

At 2 years, the percentage change in bone mineral density (BMD) from baseline with denosumab compared to risedronate in patients initiating steroid treatment was significantly higher (all P values less than .001) at the lumbar spine (6% vs. 2%), total hip (3% vs. 0%), and the femoral neck (1.5% vs. –1%). Similar results were seen in patients who were continuing steroid treatment when they entered the randomized, multicenter, double blind trial.

These data build on the 1-year data that have just been published (Lancet Diabetes Endocrinol. 2018;6[6]:445-54), Willem F. Lems, MD, the presenting study investigator, said at the European Congress of Rheumatology.

“Denosumab continued to increased BMD significantly more then risedronate through 24 months,” said Dr. Lems of VU University Medical Center, Amsterdam. He added that “the treatment differences at all skeletal sites were larger at 24 months than as 12 months.”

The Food and Drug Administration approved an additional indication in May of 2018 for denosumab to treat glucocorticoid-induced osteoporosis in adults at high risk of fracture. The biologic, a monoclonal antibody that targets the RANK ligand, was already approved to treat postmenopausal women with osteoporosis at high fracture risk, to increase bone mass in men with osteoporosis at high fracture risk, and to increase bone mass in women receiving adjuvant aromatase inhibitor therapy for breast cancer and in men receiving androgen deprivation therapy for nonmetastatic prostate cancer.

Secondary osteoporosis is a well known downside of glucocorticoid treatment, and despite there being approved therapies, many patients do not receive such treatment, Dr. Lems noted.

“This 24-month study assessed the safety and efficacy of denosumab versus risedronate in glucocorticoid-treated individuals, in whom guidelines advocate treatment,” Dr. Lems said.

Sara Freeman/MDedge News

SOURCE: Saag KG et al. Ann Rheum Dis. 2018;77(Suppl 2):218. Abstract OP0345.

The Department of Defense has received emergency use authorization from the Food and Drug Administration to use pathogen-reduced, leukocyte-depleted, freeze-dried plasma for the emergency treatment of hemorrhage and coagulopathy in combat situations.

Hemorrhage and coagulopathy are the leading causes of preventable deaths among combat trauma casualties. While plasma contains proteins that help clot blood and thus can treat these conditions, it isn’t feasible to keep it on hand for combat emergencies in the field because of logistical and operational requirements, such as refrigeration or thawing periods. This freeze-dried plasma product, on the other hand, can be easily reconstituted in situations in which refrigeration isn’t possible.

The FDA authorization allows for the use of a French-made, powdered, freeze-dried product. This emergency use authorization came about in part because of a joint program established between the FDA and the Department of Defense in January 2018.

“Earlier this year, we reaffirmed our commitment to the Department of Defense and to the dedicated men and women protecting our country, by expediting the development and availability of safe and effective, priority medical products that are essential to the health of our military service members,” said FDA commissioner Scott Gottlieb, MD. “This is especially true when it comes to products used to treat injuries in a potential battlefield setting.”

More information about this emergency use authorization can be found in the FDA’s full press announcement.

[email protected]

The Department of Defense has received emergency use authorization from the Food and Drug Administration to use pathogen-reduced, leukocyte-depleted, freeze-dried plasma for the emergency treatment of hemorrhage and coagulopathy in combat situations.

Hemorrhage and coagulopathy are the leading causes of preventable deaths among combat trauma casualties. While plasma contains proteins that help clot blood and thus can treat these conditions, it isn’t feasible to keep it on hand for combat emergencies in the field because of logistical and operational requirements, such as refrigeration or thawing periods. This freeze-dried plasma product, on the other hand, can be easily reconstituted in situations in which refrigeration isn’t possible.

The FDA authorization allows for the use of a French-made, powdered, freeze-dried product. This emergency use authorization came about in part because of a joint program established between the FDA and the Department of Defense in January 2018.

“Earlier this year, we reaffirmed our commitment to the Department of Defense and to the dedicated men and women protecting our country, by expediting the development and availability of safe and effective, priority medical products that are essential to the health of our military service members,” said FDA commissioner Scott Gottlieb, MD. “This is especially true when it comes to products used to treat injuries in a potential battlefield setting.”

More information about this emergency use authorization can be found in the FDA’s full press announcement.

[email protected]

The Department of Defense has received emergency use authorization from the Food and Drug Administration to use pathogen-reduced, leukocyte-depleted, freeze-dried plasma for the emergency treatment of hemorrhage and coagulopathy in combat situations.

Hemorrhage and coagulopathy are the leading causes of preventable deaths among combat trauma casualties. While plasma contains proteins that help clot blood and thus can treat these conditions, it isn’t feasible to keep it on hand for combat emergencies in the field because of logistical and operational requirements, such as refrigeration or thawing periods. This freeze-dried plasma product, on the other hand, can be easily reconstituted in situations in which refrigeration isn’t possible.

The FDA authorization allows for the use of a French-made, powdered, freeze-dried product. This emergency use authorization came about in part because of a joint program established between the FDA and the Department of Defense in January 2018.

“Earlier this year, we reaffirmed our commitment to the Department of Defense and to the dedicated men and women protecting our country, by expediting the development and availability of safe and effective, priority medical products that are essential to the health of our military service members,” said FDA commissioner Scott Gottlieb, MD. “This is especially true when it comes to products used to treat injuries in a potential battlefield setting.”

More information about this emergency use authorization can be found in the FDA’s full press announcement.

[email protected]

Transcutaneous electrical nerve stimulation (TENS) was effective at treating chronic vulvar pain at the vestibule in combination with vaginal diazepam and with placebo in a randomized, double-blind, placebo-controlled trial.

In the TENS/diazepam and TENS/placebo groups, participants reported significant improvements from baseline in pain and sexual functioning by questionnaire and visual analog scale. They also improved in measurements of pelvic floor muscle tone and vestibular nerve fiber current perception threshold.

The study had two groups of 21 women each, all aged 18 years or older and diagnosed (by physical exam) with moderate or severe pelvic floor hypertonic dysfunction. The diazepam was a tablet inserted vaginally daily before bed.

The TENS therapy was also self-administered (after six or seven supervised trial sessions), a recommended three times per week. The device is a 20-mm diameter plastic vaginal probe with gold metallic transversal rings as electrodes, inserted 20 mm, with 30 minutes of electrical stimulation increased slowly until sensation “reached a level described as the maximum tolerable without experiencing pain.” Vulvar pain was assessed on a on a 10-cm visual analog scale and dyspareunia on the Marinoff dyspareunia scale.

At the primary endpoint, the mean change from baseline to 60 days, the diazepam combination improved from 7.5 on the visual scale to 4.7, while the placebo combination improved from 7.2 to 4.3 (P not significant between the groups). Marinoff dyspareunia scores, however, improved from 2.5 to 1.6 and from 2.0 to 1.3, respectively (P less than .01).

Though “very few statistically significant differences in outcomes between the two groups were observed ... our results indicate that diazepam is able to positively change the functions of the pelvic floor muscle often highlighted” in women with vestibulodynia, reported Filippo Murina, MD, of the University of Milan and his coauthors. This conclusion followed from the Marinoff scores and from vaginal surface electromyography. In the latter measure, the diazepam group showed a significantly greater ability to relax the pelvic floor muscle after contraction (3.8 vs. 2.4 microvolts; P = .01), compared with the placebo group.

“We also observed that TENS itself is essential in reducing vulvar pain and the action of diazepam is useful but not decisive. ... It is possible that vaginal diazepam alone is insufficient to resolve the symptoms related to pelvic floor muscle dysfunction, while vaginal diazepam and TENS together provide a synergistic benefit in vestibulodynia patients,” wrote Dr. Murina and his coauthors.

This study was supported by the Associazione Italiana Vulvodinia. The authors declared no conflicts of interest.

[email protected]

SOURCE: Murina F et al. Eur J Obstet Gynecol Reprod Biol. 2018 Jun;228:148-53.

Transcutaneous electrical nerve stimulation (TENS) was effective at treating chronic vulvar pain at the vestibule in combination with vaginal diazepam and with placebo in a randomized, double-blind, placebo-controlled trial.

In the TENS/diazepam and TENS/placebo groups, participants reported significant improvements from baseline in pain and sexual functioning by questionnaire and visual analog scale. They also improved in measurements of pelvic floor muscle tone and vestibular nerve fiber current perception threshold.

The study had two groups of 21 women each, all aged 18 years or older and diagnosed (by physical exam) with moderate or severe pelvic floor hypertonic dysfunction. The diazepam was a tablet inserted vaginally daily before bed.

The TENS therapy was also self-administered (after six or seven supervised trial sessions), a recommended three times per week. The device is a 20-mm diameter plastic vaginal probe with gold metallic transversal rings as electrodes, inserted 20 mm, with 30 minutes of electrical stimulation increased slowly until sensation “reached a level described as the maximum tolerable without experiencing pain.” Vulvar pain was assessed on a on a 10-cm visual analog scale and dyspareunia on the Marinoff dyspareunia scale.

At the primary endpoint, the mean change from baseline to 60 days, the diazepam combination improved from 7.5 on the visual scale to 4.7, while the placebo combination improved from 7.2 to 4.3 (P not significant between the groups). Marinoff dyspareunia scores, however, improved from 2.5 to 1.6 and from 2.0 to 1.3, respectively (P less than .01).

Though “very few statistically significant differences in outcomes between the two groups were observed ... our results indicate that diazepam is able to positively change the functions of the pelvic floor muscle often highlighted” in women with vestibulodynia, reported Filippo Murina, MD, of the University of Milan and his coauthors. This conclusion followed from the Marinoff scores and from vaginal surface electromyography. In the latter measure, the diazepam group showed a significantly greater ability to relax the pelvic floor muscle after contraction (3.8 vs. 2.4 microvolts; P = .01), compared with the placebo group.

“We also observed that TENS itself is essential in reducing vulvar pain and the action of diazepam is useful but not decisive. ... It is possible that vaginal diazepam alone is insufficient to resolve the symptoms related to pelvic floor muscle dysfunction, while vaginal diazepam and TENS together provide a synergistic benefit in vestibulodynia patients,” wrote Dr. Murina and his coauthors.

This study was supported by the Associazione Italiana Vulvodinia. The authors declared no conflicts of interest.

[email protected]

SOURCE: Murina F et al. Eur J Obstet Gynecol Reprod Biol. 2018 Jun;228:148-53.

Transcutaneous electrical nerve stimulation (TENS) was effective at treating chronic vulvar pain at the vestibule in combination with vaginal diazepam and with placebo in a randomized, double-blind, placebo-controlled trial.

In the TENS/diazepam and TENS/placebo groups, participants reported significant improvements from baseline in pain and sexual functioning by questionnaire and visual analog scale. They also improved in measurements of pelvic floor muscle tone and vestibular nerve fiber current perception threshold.

The study had two groups of 21 women each, all aged 18 years or older and diagnosed (by physical exam) with moderate or severe pelvic floor hypertonic dysfunction. The diazepam was a tablet inserted vaginally daily before bed.

The TENS therapy was also self-administered (after six or seven supervised trial sessions), a recommended three times per week. The device is a 20-mm diameter plastic vaginal probe with gold metallic transversal rings as electrodes, inserted 20 mm, with 30 minutes of electrical stimulation increased slowly until sensation “reached a level described as the maximum tolerable without experiencing pain.” Vulvar pain was assessed on a on a 10-cm visual analog scale and dyspareunia on the Marinoff dyspareunia scale.

At the primary endpoint, the mean change from baseline to 60 days, the diazepam combination improved from 7.5 on the visual scale to 4.7, while the placebo combination improved from 7.2 to 4.3 (P not significant between the groups). Marinoff dyspareunia scores, however, improved from 2.5 to 1.6 and from 2.0 to 1.3, respectively (P less than .01).

Though “very few statistically significant differences in outcomes between the two groups were observed ... our results indicate that diazepam is able to positively change the functions of the pelvic floor muscle often highlighted” in women with vestibulodynia, reported Filippo Murina, MD, of the University of Milan and his coauthors. This conclusion followed from the Marinoff scores and from vaginal surface electromyography. In the latter measure, the diazepam group showed a significantly greater ability to relax the pelvic floor muscle after contraction (3.8 vs. 2.4 microvolts; P = .01), compared with the placebo group.

“We also observed that TENS itself is essential in reducing vulvar pain and the action of diazepam is useful but not decisive. ... It is possible that vaginal diazepam alone is insufficient to resolve the symptoms related to pelvic floor muscle dysfunction, while vaginal diazepam and TENS together provide a synergistic benefit in vestibulodynia patients,” wrote Dr. Murina and his coauthors.

This study was supported by the Associazione Italiana Vulvodinia. The authors declared no conflicts of interest.

[email protected]

SOURCE: Murina F et al. Eur J Obstet Gynecol Reprod Biol. 2018 Jun;228:148-53.

After a successful and invigorating 2018 AGA Tech Summit, we can confidently say that innovation continues to be alive and well in the GI space. As you’ll see in the pages of this comprehensive AGA Tech Summit report, there is no shortage of novel ideas or potentially disruptive technologies poised to improve how we care for our patients.

What’s most special about the AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology, is the camaraderie and shared commitment to innovation from physicians, innovators, industry, regulators, and investors. By coming together for this important dialogue, we can continue to move the pendulum forward and work toward new innovations that ultimately will improve patient outcomes. As the chair and vice chair of the center, we’re committed to continuing the conversations from the AGA Tech Summit year-round to help bring promising new technologies to our practices.

In this report, you’ll find summaries of select AGA Tech Summit presentations and key takeaways that will help you as a practicing gastroenterologist. Our recap of the annual AGA Tech Summit Shark Tank will give you insight into five new technologies making a splash in GI – flip to page 9 to see which device won this year’s Shark Tank. We also discuss physician barriers to incorporating new technologies, with tips for overcoming these challenges. You’ll also find articles on areas ripe for innovation in GI, including digital health, tissue resection techniques, and obesity treatment. Finally, for our physician innovators, we have advice and guidance throughout on how to take your idea from concept to product.

We’re looking ahead to the 2019 AGA Tech Summit, taking place April 10-12 at the Mark Hopkins Intercontinental in San Francisco, CA. This will be our 10th annual meeting of stakeholders in GI innovation – it’s amazing to reflect on all we’ve accomplished in the last 10 years. If you read this report with great interest, we hope you’ll join us for this unique and lively dialogue on advancing innovation in GI.

If you’d like to connect with us about innovation in GI – send us an email at [email protected] or visit www.gastro.org/CGIT.

Sincerely,

V. Raman Muthusamy, MD, AGAF, FACG, FASGE
Chair, AGA Center for GI Innovation and Technology

Sri Komanduri, MD, AGAF
Vice Chair, AGA Center for GI Innovation and Technology

After a successful and invigorating 2018 AGA Tech Summit, we can confidently say that innovation continues to be alive and well in the GI space. As you’ll see in the pages of this comprehensive AGA Tech Summit report, there is no shortage of novel ideas or potentially disruptive technologies poised to improve how we care for our patients.

What’s most special about the AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology, is the camaraderie and shared commitment to innovation from physicians, innovators, industry, regulators, and investors. By coming together for this important dialogue, we can continue to move the pendulum forward and work toward new innovations that ultimately will improve patient outcomes. As the chair and vice chair of the center, we’re committed to continuing the conversations from the AGA Tech Summit year-round to help bring promising new technologies to our practices.

In this report, you’ll find summaries of select AGA Tech Summit presentations and key takeaways that will help you as a practicing gastroenterologist. Our recap of the annual AGA Tech Summit Shark Tank will give you insight into five new technologies making a splash in GI – flip to page 9 to see which device won this year’s Shark Tank. We also discuss physician barriers to incorporating new technologies, with tips for overcoming these challenges. You’ll also find articles on areas ripe for innovation in GI, including digital health, tissue resection techniques, and obesity treatment. Finally, for our physician innovators, we have advice and guidance throughout on how to take your idea from concept to product.

We’re looking ahead to the 2019 AGA Tech Summit, taking place April 10-12 at the Mark Hopkins Intercontinental in San Francisco, CA. This will be our 10th annual meeting of stakeholders in GI innovation – it’s amazing to reflect on all we’ve accomplished in the last 10 years. If you read this report with great interest, we hope you’ll join us for this unique and lively dialogue on advancing innovation in GI.

If you’d like to connect with us about innovation in GI – send us an email at [email protected] or visit www.gastro.org/CGIT.

Sincerely,

V. Raman Muthusamy, MD, AGAF, FACG, FASGE
Chair, AGA Center for GI Innovation and Technology

Sri Komanduri, MD, AGAF
Vice Chair, AGA Center for GI Innovation and Technology

After a successful and invigorating 2018 AGA Tech Summit, we can confidently say that innovation continues to be alive and well in the GI space. As you’ll see in the pages of this comprehensive AGA Tech Summit report, there is no shortage of novel ideas or potentially disruptive technologies poised to improve how we care for our patients.

What’s most special about the AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology, is the camaraderie and shared commitment to innovation from physicians, innovators, industry, regulators, and investors. By coming together for this important dialogue, we can continue to move the pendulum forward and work toward new innovations that ultimately will improve patient outcomes. As the chair and vice chair of the center, we’re committed to continuing the conversations from the AGA Tech Summit year-round to help bring promising new technologies to our practices.

In this report, you’ll find summaries of select AGA Tech Summit presentations and key takeaways that will help you as a practicing gastroenterologist. Our recap of the annual AGA Tech Summit Shark Tank will give you insight into five new technologies making a splash in GI – flip to page 9 to see which device won this year’s Shark Tank. We also discuss physician barriers to incorporating new technologies, with tips for overcoming these challenges. You’ll also find articles on areas ripe for innovation in GI, including digital health, tissue resection techniques, and obesity treatment. Finally, for our physician innovators, we have advice and guidance throughout on how to take your idea from concept to product.

We’re looking ahead to the 2019 AGA Tech Summit, taking place April 10-12 at the Mark Hopkins Intercontinental in San Francisco, CA. This will be our 10th annual meeting of stakeholders in GI innovation – it’s amazing to reflect on all we’ve accomplished in the last 10 years. If you read this report with great interest, we hope you’ll join us for this unique and lively dialogue on advancing innovation in GI.

If you’d like to connect with us about innovation in GI – send us an email at [email protected] or visit www.gastro.org/CGIT.

Sincerely,

V. Raman Muthusamy, MD, AGAF, FACG, FASGE
Chair, AGA Center for GI Innovation and Technology

Sri Komanduri, MD, AGAF
Vice Chair, AGA Center for GI Innovation and Technology

AMSTERDAM – A new way to assess clinically meaningful, multiorgan changes in patients receiving treatment for systemic sclerosis has transformed the way new drugs for this disease are judged.

The Combined Response Index for Systemic Sclerosis (CRISS) “will change how we look at drugs” for systemic sclerosis, Daniel E. Furst, MD, said at the European Congress of Rheumatology.

Mitchel L. Zoler/MDedge News

• A new scleroderma renal crisis.
• A decline in forced vital capacity of 15% or more of predicted.
• A new decline of left ventricular ejection fraction to 45% or less.
• New onset of pulmonary arterial hypertension that requires treatment.

If none of these apply, the next step is to assess treatment response by measuring changes in five parameters and then integrating them into a single number using a mathematical formula. The five elements in the equation are:

• Modified Rodnan skin score.
• Percent of predicted forced vital capacity.
• Health Assessment Questionnaire-Disability Index.
• Patient’s global assessment.
• Physician’s global assessment.

When factored together, changes in these five measures determine the probability that the patient responded to the intervention.

One limitation of the CRISS is that it only measures change from baseline, which makes it similar to the ACR 20, Dr. Furst noted. Another useful score would be one that reflects the status of a patient with systemic sclerosis at a specific point in time, a type of disease activity score. Dr. Furst said that he and others active in the systemic sclerosis field would like to develop a method that provides this type of patient assessment. Another addition would be to develop a “minimally clinically important change” in the score, which would make the CRISS more intuitive to understand.

Dr. Furst has received research support from Amgen, Bristol-Myers Squibb, Celgene, Corbus, Genentech-Roche, GlaxoSmithKline, Pfizer, and Novartis.

[email protected]

SOURCE: Furst DE. EULAR 2018. Abstract SP0012.

AMSTERDAM – A new way to assess clinically meaningful, multiorgan changes in patients receiving treatment for systemic sclerosis has transformed the way new drugs for this disease are judged.

The Combined Response Index for Systemic Sclerosis (CRISS) “will change how we look at drugs” for systemic sclerosis, Daniel E. Furst, MD, said at the European Congress of Rheumatology.

Mitchel L. Zoler/MDedge News

• A new scleroderma renal crisis.
• A decline in forced vital capacity of 15% or more of predicted.
• A new decline of left ventricular ejection fraction to 45% or less.
• New onset of pulmonary arterial hypertension that requires treatment.

If none of these apply, the next step is to assess treatment response by measuring changes in five parameters and then integrating them into a single number using a mathematical formula. The five elements in the equation are:

• Modified Rodnan skin score.
• Percent of predicted forced vital capacity.
• Health Assessment Questionnaire-Disability Index.
• Patient’s global assessment.
• Physician’s global assessment.

When factored together, changes in these five measures determine the probability that the patient responded to the intervention.

One limitation of the CRISS is that it only measures change from baseline, which makes it similar to the ACR 20, Dr. Furst noted. Another useful score would be one that reflects the status of a patient with systemic sclerosis at a specific point in time, a type of disease activity score. Dr. Furst said that he and others active in the systemic sclerosis field would like to develop a method that provides this type of patient assessment. Another addition would be to develop a “minimally clinically important change” in the score, which would make the CRISS more intuitive to understand.

Dr. Furst has received research support from Amgen, Bristol-Myers Squibb, Celgene, Corbus, Genentech-Roche, GlaxoSmithKline, Pfizer, and Novartis.

[email protected]

SOURCE: Furst DE. EULAR 2018. Abstract SP0012.

AMSTERDAM – A new way to assess clinically meaningful, multiorgan changes in patients receiving treatment for systemic sclerosis has transformed the way new drugs for this disease are judged.

The Combined Response Index for Systemic Sclerosis (CRISS) “will change how we look at drugs” for systemic sclerosis, Daniel E. Furst, MD, said at the European Congress of Rheumatology.

Mitchel L. Zoler/MDedge News

• A new scleroderma renal crisis.
• A decline in forced vital capacity of 15% or more of predicted.
• A new decline of left ventricular ejection fraction to 45% or less.
• New onset of pulmonary arterial hypertension that requires treatment.

If none of these apply, the next step is to assess treatment response by measuring changes in five parameters and then integrating them into a single number using a mathematical formula. The five elements in the equation are:

• Modified Rodnan skin score.
• Percent of predicted forced vital capacity.
• Health Assessment Questionnaire-Disability Index.
• Patient’s global assessment.
• Physician’s global assessment.

When factored together, changes in these five measures determine the probability that the patient responded to the intervention.

One limitation of the CRISS is that it only measures change from baseline, which makes it similar to the ACR 20, Dr. Furst noted. Another useful score would be one that reflects the status of a patient with systemic sclerosis at a specific point in time, a type of disease activity score. Dr. Furst said that he and others active in the systemic sclerosis field would like to develop a method that provides this type of patient assessment. Another addition would be to develop a “minimally clinically important change” in the score, which would make the CRISS more intuitive to understand.

Dr. Furst has received research support from Amgen, Bristol-Myers Squibb, Celgene, Corbus, Genentech-Roche, GlaxoSmithKline, Pfizer, and Novartis.

[email protected]

SOURCE: Furst DE. EULAR 2018. Abstract SP0012.

ORLANDO – Canagliflozin is generally well tolerated for up to 6.5 years in patients with type 2 diabetes and high cardiovascular risk, according to the latest safety data from the CANVAS (Canagliflozin Cardiovascular Assessment Study) program.

CANVAS included two studies (CANVAS and CANVAS-R) involving a total of 10,142 patients, which established the superiority of canagliflozin (Invokana) over placebo for reducing the risk of a three-point major adverse cardiac event endpoint, including cardiovascular death, nonfatal MI, and nonfatal stroke. The sodium-glucose cotransporter-2 (SGLT2) inhibitor also improved other cardiovascular outcomes.

For the current analysis, outcomes in the CANVAS participants were compared with those from a general population of 8,114 patients with type 2 diabetes mellitus (T2DM) who participated in 12 non-CANVAS studies of canagliflozin. As previously reported, the risks for fracture or amputation were novel safety findings associated with canagliflozin in the CANVAS program and, in the current analysis, the incidence of fractures per 1,000 patient-years in CANVAS was 15.4 vs. 11.9 with treatment vs. placebo, whereas no significant difference was seen in the non-CANVAS studies (incidence rate of 11.8 vs. 10.8 per 1,000 patient-years for treatment vs. placebo), Priscilla Hollander, MD, reported at the annual meeting of the American Diabetes Association.

Of note, when the CANVAS and CANVAS-R studies were compared, the imbalance was seen only in CANVAS (incidence rates of 16.9 vs. 10.9 for treatment vs. placebo [hazard ratio, 1.55], compared with incidence rates of 11.3 and 13.2 , respectively, in CANVAS-R [HR, 0.86]), said Dr. Hollander, Baylor Scott & White Endocrine Center in Dallas.

“Ongoing analyses are trying to determine why there is a difference between the two studies,” she noted.

For the novel safety finding of increased amputation risk with canagliflozin, an excess of three events per 1,000 patient years was seen in both CANVAS (incidence of 6.3 vs. 3.4; HR, 1.97) and CANVAS-R (incidence of 5.9 vs. 2.8; HR, 2.12). No difference in risk was seen among the non-CANVAS population (incidence of 0.5 and 2.2 with treatment vs. placebo; HR, 0.23).

“Amputations were primarily at the level of the toe or the metatarsal. Patients with a history of amputation or peripheral vascular disease had the highest risk of amputation,” she said, adding that this was true in both treatment and placebo groups.

“Again, ongoing analyses are being done to look at the mechanism in this regard,” she said.

For safety outcomes known to be related to the mechanism of SGLT2 inhibition, including osmotic diuresis, volume depletion, and genital mycotic infection (GMI), similar differences between canagliflozin and placebo groups were seen in the CANVAS and non-CANVAS studies at 6.5 years, Dr. Hollander said.

Hazard ratios in the canagliflozin vs. placebo groups for the CANVAS and non-CANVAS studies, respectively, were 2.80 and 2.66 for osmotic diuresis, 1.44 and 1.35 for volume depletion, 4.37 and 4.32 for female GMI, and 3.76 and 6.26 for male GMI.

No imbalances were observed in other AEs of interest – including hypoglycemia, urinary tract infections, or hypersensitivity reactions – in either the CANVAS or the non-CANVAS studies.

“The point estimate for [diabetic ketoacidosis] was 2.3, but with very wide confidence intervals due to a very low number of events, so it really did not reach significance,” Dr. Hollander noted. “Again, due to the mechanism of action of canagliflozin, and the warning for acute kidney injury on the label, renal adverse events were also of interest, but there was no imbalance observed in the renal-related AEs between the CANVAS program and the non-CANVAS program.”

A closer look at renal-related adverse events (AEs) of interest in the CANVAS program only (not in comparison with the non-CANVAS findings) also showed no significant difference with canagliflozin vs. placebo in blood creatinine increase, blood urea increase, glomerular filtration rate decrease, acute kidney injury, renal impairment, renal failure, oliguria, acute prerenal failure, hypercreatininemia, nephritis, or prerenal failure, she said.

Furthermore, although hyperkalemia is noted as a risk with canagliflozin in patients with moderate renal impairment who are taking medications that interfere with potassium excretion, no significant differences were observed between the treatment and placebo groups over 6.5 years in the CANVAS program, she added, noting that “this was also supported by the lack of imbalance between the laboratory changes for serum potassium in the two groups.”

There also were no differences seen between the treatment and placebo groups in the rates of all serious AEs or in the rates of AEs leading to discontinuation, she said.

Canagliflozin has been generally well tolerated in both placebo-controlled trials and trials in which the SGLT2 inhibitor was compared with other active treatments. The non-CANVAS studies used for comparison in the current analysis included phase 3/4 canagliflozin clinical development program studies lasting up to 104 weeks and involving a general T2DM patient population, Dr. Hollander noted.

The CANVAS program, which was launched in 2009, included patients with T2DM and established cardiovascular disease or high cardiovascular disease risk who received a 2-week placebo run-in followed by placebo or either 100- or 300-mg doses of canagliflozin. CANVAS participants had hemoglobin A_1c of 7%-10.5%; estimated glomerular filtration rate of 30 mL/min per 1.72m2 or greater; age of 30 years or greater plus a history of a prior cardiovascular event, or age of 50 years or greater with at least 2 cardiovascular risk factors, including diabetes for 10 years or more; systolic blood pressure greater than 140 mm Hg on at least one medication; current smoking status; micro- or macroalbuminuria; and an HDL cholesterol level less than 1 mmol/L.

The current analysis provides the longest-term safety data to date for the program, Dr. Hollander said.

The CANVAS Program is sponsored by Janssen Research & Development. Dr. Hollander is an advisory panel member for Eli Lilly, Merck, and Novo Nordisk.

[email protected]

SOURCE: Hollander P et al. ADA 2018, Abstract 259-OR.

ORLANDO – Canagliflozin is generally well tolerated for up to 6.5 years in patients with type 2 diabetes and high cardiovascular risk, according to the latest safety data from the CANVAS (Canagliflozin Cardiovascular Assessment Study) program.

CANVAS included two studies (CANVAS and CANVAS-R) involving a total of 10,142 patients, which established the superiority of canagliflozin (Invokana) over placebo for reducing the risk of a three-point major adverse cardiac event endpoint, including cardiovascular death, nonfatal MI, and nonfatal stroke. The sodium-glucose cotransporter-2 (SGLT2) inhibitor also improved other cardiovascular outcomes.

For the current analysis, outcomes in the CANVAS participants were compared with those from a general population of 8,114 patients with type 2 diabetes mellitus (T2DM) who participated in 12 non-CANVAS studies of canagliflozin. As previously reported, the risks for fracture or amputation were novel safety findings associated with canagliflozin in the CANVAS program and, in the current analysis, the incidence of fractures per 1,000 patient-years in CANVAS was 15.4 vs. 11.9 with treatment vs. placebo, whereas no significant difference was seen in the non-CANVAS studies (incidence rate of 11.8 vs. 10.8 per 1,000 patient-years for treatment vs. placebo), Priscilla Hollander, MD, reported at the annual meeting of the American Diabetes Association.

Of note, when the CANVAS and CANVAS-R studies were compared, the imbalance was seen only in CANVAS (incidence rates of 16.9 vs. 10.9 for treatment vs. placebo [hazard ratio, 1.55], compared with incidence rates of 11.3 and 13.2 , respectively, in CANVAS-R [HR, 0.86]), said Dr. Hollander, Baylor Scott & White Endocrine Center in Dallas.

“Ongoing analyses are trying to determine why there is a difference between the two studies,” she noted.

For the novel safety finding of increased amputation risk with canagliflozin, an excess of three events per 1,000 patient years was seen in both CANVAS (incidence of 6.3 vs. 3.4; HR, 1.97) and CANVAS-R (incidence of 5.9 vs. 2.8; HR, 2.12). No difference in risk was seen among the non-CANVAS population (incidence of 0.5 and 2.2 with treatment vs. placebo; HR, 0.23).

“Amputations were primarily at the level of the toe or the metatarsal. Patients with a history of amputation or peripheral vascular disease had the highest risk of amputation,” she said, adding that this was true in both treatment and placebo groups.

“Again, ongoing analyses are being done to look at the mechanism in this regard,” she said.

For safety outcomes known to be related to the mechanism of SGLT2 inhibition, including osmotic diuresis, volume depletion, and genital mycotic infection (GMI), similar differences between canagliflozin and placebo groups were seen in the CANVAS and non-CANVAS studies at 6.5 years, Dr. Hollander said.

Hazard ratios in the canagliflozin vs. placebo groups for the CANVAS and non-CANVAS studies, respectively, were 2.80 and 2.66 for osmotic diuresis, 1.44 and 1.35 for volume depletion, 4.37 and 4.32 for female GMI, and 3.76 and 6.26 for male GMI.

No imbalances were observed in other AEs of interest – including hypoglycemia, urinary tract infections, or hypersensitivity reactions – in either the CANVAS or the non-CANVAS studies.

“The point estimate for [diabetic ketoacidosis] was 2.3, but with very wide confidence intervals due to a very low number of events, so it really did not reach significance,” Dr. Hollander noted. “Again, due to the mechanism of action of canagliflozin, and the warning for acute kidney injury on the label, renal adverse events were also of interest, but there was no imbalance observed in the renal-related AEs between the CANVAS program and the non-CANVAS program.”

A closer look at renal-related adverse events (AEs) of interest in the CANVAS program only (not in comparison with the non-CANVAS findings) also showed no significant difference with canagliflozin vs. placebo in blood creatinine increase, blood urea increase, glomerular filtration rate decrease, acute kidney injury, renal impairment, renal failure, oliguria, acute prerenal failure, hypercreatininemia, nephritis, or prerenal failure, she said.

Furthermore, although hyperkalemia is noted as a risk with canagliflozin in patients with moderate renal impairment who are taking medications that interfere with potassium excretion, no significant differences were observed between the treatment and placebo groups over 6.5 years in the CANVAS program, she added, noting that “this was also supported by the lack of imbalance between the laboratory changes for serum potassium in the two groups.”

There also were no differences seen between the treatment and placebo groups in the rates of all serious AEs or in the rates of AEs leading to discontinuation, she said.

Canagliflozin has been generally well tolerated in both placebo-controlled trials and trials in which the SGLT2 inhibitor was compared with other active treatments. The non-CANVAS studies used for comparison in the current analysis included phase 3/4 canagliflozin clinical development program studies lasting up to 104 weeks and involving a general T2DM patient population, Dr. Hollander noted.

The CANVAS program, which was launched in 2009, included patients with T2DM and established cardiovascular disease or high cardiovascular disease risk who received a 2-week placebo run-in followed by placebo or either 100- or 300-mg doses of canagliflozin. CANVAS participants had hemoglobin A_1c of 7%-10.5%; estimated glomerular filtration rate of 30 mL/min per 1.72m2 or greater; age of 30 years or greater plus a history of a prior cardiovascular event, or age of 50 years or greater with at least 2 cardiovascular risk factors, including diabetes for 10 years or more; systolic blood pressure greater than 140 mm Hg on at least one medication; current smoking status; micro- or macroalbuminuria; and an HDL cholesterol level less than 1 mmol/L.

The current analysis provides the longest-term safety data to date for the program, Dr. Hollander said.

The CANVAS Program is sponsored by Janssen Research & Development. Dr. Hollander is an advisory panel member for Eli Lilly, Merck, and Novo Nordisk.

[email protected]

SOURCE: Hollander P et al. ADA 2018, Abstract 259-OR.

ORLANDO – Canagliflozin is generally well tolerated for up to 6.5 years in patients with type 2 diabetes and high cardiovascular risk, according to the latest safety data from the CANVAS (Canagliflozin Cardiovascular Assessment Study) program.

CANVAS included two studies (CANVAS and CANVAS-R) involving a total of 10,142 patients, which established the superiority of canagliflozin (Invokana) over placebo for reducing the risk of a three-point major adverse cardiac event endpoint, including cardiovascular death, nonfatal MI, and nonfatal stroke. The sodium-glucose cotransporter-2 (SGLT2) inhibitor also improved other cardiovascular outcomes.

For the current analysis, outcomes in the CANVAS participants were compared with those from a general population of 8,114 patients with type 2 diabetes mellitus (T2DM) who participated in 12 non-CANVAS studies of canagliflozin. As previously reported, the risks for fracture or amputation were novel safety findings associated with canagliflozin in the CANVAS program and, in the current analysis, the incidence of fractures per 1,000 patient-years in CANVAS was 15.4 vs. 11.9 with treatment vs. placebo, whereas no significant difference was seen in the non-CANVAS studies (incidence rate of 11.8 vs. 10.8 per 1,000 patient-years for treatment vs. placebo), Priscilla Hollander, MD, reported at the annual meeting of the American Diabetes Association.

Of note, when the CANVAS and CANVAS-R studies were compared, the imbalance was seen only in CANVAS (incidence rates of 16.9 vs. 10.9 for treatment vs. placebo [hazard ratio, 1.55], compared with incidence rates of 11.3 and 13.2 , respectively, in CANVAS-R [HR, 0.86]), said Dr. Hollander, Baylor Scott & White Endocrine Center in Dallas.

“Ongoing analyses are trying to determine why there is a difference between the two studies,” she noted.

For the novel safety finding of increased amputation risk with canagliflozin, an excess of three events per 1,000 patient years was seen in both CANVAS (incidence of 6.3 vs. 3.4; HR, 1.97) and CANVAS-R (incidence of 5.9 vs. 2.8; HR, 2.12). No difference in risk was seen among the non-CANVAS population (incidence of 0.5 and 2.2 with treatment vs. placebo; HR, 0.23).

“Amputations were primarily at the level of the toe or the metatarsal. Patients with a history of amputation or peripheral vascular disease had the highest risk of amputation,” she said, adding that this was true in both treatment and placebo groups.

“Again, ongoing analyses are being done to look at the mechanism in this regard,” she said.

For safety outcomes known to be related to the mechanism of SGLT2 inhibition, including osmotic diuresis, volume depletion, and genital mycotic infection (GMI), similar differences between canagliflozin and placebo groups were seen in the CANVAS and non-CANVAS studies at 6.5 years, Dr. Hollander said.

Hazard ratios in the canagliflozin vs. placebo groups for the CANVAS and non-CANVAS studies, respectively, were 2.80 and 2.66 for osmotic diuresis, 1.44 and 1.35 for volume depletion, 4.37 and 4.32 for female GMI, and 3.76 and 6.26 for male GMI.

No imbalances were observed in other AEs of interest – including hypoglycemia, urinary tract infections, or hypersensitivity reactions – in either the CANVAS or the non-CANVAS studies.

“The point estimate for [diabetic ketoacidosis] was 2.3, but with very wide confidence intervals due to a very low number of events, so it really did not reach significance,” Dr. Hollander noted. “Again, due to the mechanism of action of canagliflozin, and the warning for acute kidney injury on the label, renal adverse events were also of interest, but there was no imbalance observed in the renal-related AEs between the CANVAS program and the non-CANVAS program.”

A closer look at renal-related adverse events (AEs) of interest in the CANVAS program only (not in comparison with the non-CANVAS findings) also showed no significant difference with canagliflozin vs. placebo in blood creatinine increase, blood urea increase, glomerular filtration rate decrease, acute kidney injury, renal impairment, renal failure, oliguria, acute prerenal failure, hypercreatininemia, nephritis, or prerenal failure, she said.

Furthermore, although hyperkalemia is noted as a risk with canagliflozin in patients with moderate renal impairment who are taking medications that interfere with potassium excretion, no significant differences were observed between the treatment and placebo groups over 6.5 years in the CANVAS program, she added, noting that “this was also supported by the lack of imbalance between the laboratory changes for serum potassium in the two groups.”

There also were no differences seen between the treatment and placebo groups in the rates of all serious AEs or in the rates of AEs leading to discontinuation, she said.

Canagliflozin has been generally well tolerated in both placebo-controlled trials and trials in which the SGLT2 inhibitor was compared with other active treatments. The non-CANVAS studies used for comparison in the current analysis included phase 3/4 canagliflozin clinical development program studies lasting up to 104 weeks and involving a general T2DM patient population, Dr. Hollander noted.

The CANVAS program, which was launched in 2009, included patients with T2DM and established cardiovascular disease or high cardiovascular disease risk who received a 2-week placebo run-in followed by placebo or either 100- or 300-mg doses of canagliflozin. CANVAS participants had hemoglobin A_1c of 7%-10.5%; estimated glomerular filtration rate of 30 mL/min per 1.72m2 or greater; age of 30 years or greater plus a history of a prior cardiovascular event, or age of 50 years or greater with at least 2 cardiovascular risk factors, including diabetes for 10 years or more; systolic blood pressure greater than 140 mm Hg on at least one medication; current smoking status; micro- or macroalbuminuria; and an HDL cholesterol level less than 1 mmol/L.

The current analysis provides the longest-term safety data to date for the program, Dr. Hollander said.

The CANVAS Program is sponsored by Janssen Research & Development. Dr. Hollander is an advisory panel member for Eli Lilly, Merck, and Novo Nordisk.

[email protected]

SOURCE: Hollander P et al. ADA 2018, Abstract 259-OR.

SAN FRANCISCO – The odds of at least a 50% reduction in headache days per month in chronic migraine patients 32 weeks after randomization to onabotulinumtoxinA for prophylaxis were 394% greater than with topiramate in the multicenter, open-label FORWARD trial, Andrew M. Blumenfeld, MD, reported at the annual meeting of the American Headache Society.

Bruce Jancin/MDedge News

A reduction in HIT-6 scores of more than 2.5 points is considered to represent clinically significant improvement in migraine-related disability. At week 6, the HIT-6 score had fallen by an average of 4.0 points from baseline in the onabotulinumtoxinA group, compared with –2.2 points with topiramate. At week 18, the margin of improvement was –5.1 versus –1.6 points, while at week 36 the average improvement was –5.6 points in the onabotulinumtoxinA group, compared with –1.4 points in the topiramate arm in a last-observation-carried-forward analysis.

Mean baseline scores on the WPAI-SHP were 4.8 in the onabotulinumtoxinA group and 5.1 in those on topiramate. At week 12, the scores had improved to 3.3 and 4.4, respectively, and at week 36, to 3.5 and 4.4, respectively, a significant and clinically meaningful difference.

Mean baseline scores on the FIMQ were 59.8 and 53.9 in the onabotulinumtoxinA and topiramate groups. By week 30, the scores were 37.1 and 47.5, respectively.

The main reasons half of the topiramate patients discontinued were the adverse events classically associated with the drug: paresthesia, cognitive impairment, nausea, and fatigue. None of these were reported by more than 0.5% of onabotulinumtoxinA recipients.

This is not the first study to show superior outcomes with neurotoxin therapy for the prevention of chronic migraine.

“There is a disconnect between the published data and what happens in the community,” Dr. Blumenfeld observed. “In clinical practice, topiramate is listed as first-line therapy for chronic migraine, while onabotulinumtoxinA is third or fourth line.”

Insurers normally balk at covering neurotoxin therapy because it is relatively expensive. But in an era when PROs have taken on new weight with regulatory agencies and payers, the ground may be soon be shifting.

One audience member noted that in the relatively small subgroup of patients who could tolerate topiramate sufficiently to stay on the drug, the outcomes were quite good. Dr. Blumenfeld concurred.

“It’s something that we all see in clinical practice: Those patients who can stay on topiramate, who can tolerate it, do very well. So for the 17 of 25 who stayed on it and had a 50% reduction in headache days, that 68% is a good number, and I think it matches our clinical experience,” he said. “But the key message of this study – and I think this is a different way of looking at the way we assess medications – is to look at efficacy, but also at tolerability and long-term adherence. And the problem with topiramate-treated patients, particularly in chronic migraine, is they have a difficult time staying on the medication long enough to see that good effect.”

The FORWARD trial was sponsored by Allergan. Dr. Blumenfeld serves as a consultant to that company and a half-dozen others.

[email protected]

SOURCE: Blumenfeld AM et al. Headache. 2018 Jun;58(52):75. Abstract IOR06.

SAN FRANCISCO – The odds of at least a 50% reduction in headache days per month in chronic migraine patients 32 weeks after randomization to onabotulinumtoxinA for prophylaxis were 394% greater than with topiramate in the multicenter, open-label FORWARD trial, Andrew M. Blumenfeld, MD, reported at the annual meeting of the American Headache Society.

Bruce Jancin/MDedge News

A reduction in HIT-6 scores of more than 2.5 points is considered to represent clinically significant improvement in migraine-related disability. At week 6, the HIT-6 score had fallen by an average of 4.0 points from baseline in the onabotulinumtoxinA group, compared with –2.2 points with topiramate. At week 18, the margin of improvement was –5.1 versus –1.6 points, while at week 36 the average improvement was –5.6 points in the onabotulinumtoxinA group, compared with –1.4 points in the topiramate arm in a last-observation-carried-forward analysis.

Mean baseline scores on the WPAI-SHP were 4.8 in the onabotulinumtoxinA group and 5.1 in those on topiramate. At week 12, the scores had improved to 3.3 and 4.4, respectively, and at week 36, to 3.5 and 4.4, respectively, a significant and clinically meaningful difference.

Mean baseline scores on the FIMQ were 59.8 and 53.9 in the onabotulinumtoxinA and topiramate groups. By week 30, the scores were 37.1 and 47.5, respectively.

The main reasons half of the topiramate patients discontinued were the adverse events classically associated with the drug: paresthesia, cognitive impairment, nausea, and fatigue. None of these were reported by more than 0.5% of onabotulinumtoxinA recipients.

This is not the first study to show superior outcomes with neurotoxin therapy for the prevention of chronic migraine.

“There is a disconnect between the published data and what happens in the community,” Dr. Blumenfeld observed. “In clinical practice, topiramate is listed as first-line therapy for chronic migraine, while onabotulinumtoxinA is third or fourth line.”

Insurers normally balk at covering neurotoxin therapy because it is relatively expensive. But in an era when PROs have taken on new weight with regulatory agencies and payers, the ground may be soon be shifting.

One audience member noted that in the relatively small subgroup of patients who could tolerate topiramate sufficiently to stay on the drug, the outcomes were quite good. Dr. Blumenfeld concurred.

“It’s something that we all see in clinical practice: Those patients who can stay on topiramate, who can tolerate it, do very well. So for the 17 of 25 who stayed on it and had a 50% reduction in headache days, that 68% is a good number, and I think it matches our clinical experience,” he said. “But the key message of this study – and I think this is a different way of looking at the way we assess medications – is to look at efficacy, but also at tolerability and long-term adherence. And the problem with topiramate-treated patients, particularly in chronic migraine, is they have a difficult time staying on the medication long enough to see that good effect.”

The FORWARD trial was sponsored by Allergan. Dr. Blumenfeld serves as a consultant to that company and a half-dozen others.

[email protected]

SOURCE: Blumenfeld AM et al. Headache. 2018 Jun;58(52):75. Abstract IOR06.

SAN FRANCISCO – The odds of at least a 50% reduction in headache days per month in chronic migraine patients 32 weeks after randomization to onabotulinumtoxinA for prophylaxis were 394% greater than with topiramate in the multicenter, open-label FORWARD trial, Andrew M. Blumenfeld, MD, reported at the annual meeting of the American Headache Society.

Bruce Jancin/MDedge News

A reduction in HIT-6 scores of more than 2.5 points is considered to represent clinically significant improvement in migraine-related disability. At week 6, the HIT-6 score had fallen by an average of 4.0 points from baseline in the onabotulinumtoxinA group, compared with –2.2 points with topiramate. At week 18, the margin of improvement was –5.1 versus –1.6 points, while at week 36 the average improvement was –5.6 points in the onabotulinumtoxinA group, compared with –1.4 points in the topiramate arm in a last-observation-carried-forward analysis.

Mean baseline scores on the WPAI-SHP were 4.8 in the onabotulinumtoxinA group and 5.1 in those on topiramate. At week 12, the scores had improved to 3.3 and 4.4, respectively, and at week 36, to 3.5 and 4.4, respectively, a significant and clinically meaningful difference.

Mean baseline scores on the FIMQ were 59.8 and 53.9 in the onabotulinumtoxinA and topiramate groups. By week 30, the scores were 37.1 and 47.5, respectively.

The main reasons half of the topiramate patients discontinued were the adverse events classically associated with the drug: paresthesia, cognitive impairment, nausea, and fatigue. None of these were reported by more than 0.5% of onabotulinumtoxinA recipients.

This is not the first study to show superior outcomes with neurotoxin therapy for the prevention of chronic migraine.

“There is a disconnect between the published data and what happens in the community,” Dr. Blumenfeld observed. “In clinical practice, topiramate is listed as first-line therapy for chronic migraine, while onabotulinumtoxinA is third or fourth line.”

Insurers normally balk at covering neurotoxin therapy because it is relatively expensive. But in an era when PROs have taken on new weight with regulatory agencies and payers, the ground may be soon be shifting.

One audience member noted that in the relatively small subgroup of patients who could tolerate topiramate sufficiently to stay on the drug, the outcomes were quite good. Dr. Blumenfeld concurred.

“It’s something that we all see in clinical practice: Those patients who can stay on topiramate, who can tolerate it, do very well. So for the 17 of 25 who stayed on it and had a 50% reduction in headache days, that 68% is a good number, and I think it matches our clinical experience,” he said. “But the key message of this study – and I think this is a different way of looking at the way we assess medications – is to look at efficacy, but also at tolerability and long-term adherence. And the problem with topiramate-treated patients, particularly in chronic migraine, is they have a difficult time staying on the medication long enough to see that good effect.”

The FORWARD trial was sponsored by Allergan. Dr. Blumenfeld serves as a consultant to that company and a half-dozen others.

[email protected]

SOURCE: Blumenfeld AM et al. Headache. 2018 Jun;58(52):75. Abstract IOR06.