The Food and Drug Administration has approved Ajovy (fremanezumab-vfrm) for the preventive treatment of migraines in adults.

Fremanezumab-vfrm is an injectable anti–calcitonin gene-related peptide monoclonal antibody, the first ever approved by the FDA. It can be administered at a 225-mg dose every month or at a 675-mg dose every 3 months, according to a press release from Teva, the drug’s manufacturer.

FDA approval was based on results from two, phase 3 trials in patients with disabling migraines, one of which involved fremanezumab-vfrm alone, with the other involving the injection in tandem with an oral treatment.

In both trials, patients experienced a reduction of monthly migraine days over a 12-week period. The most common adverse event in both trials was injection site reactions.

“Migraine is a disabling neurological disease that affects more than 36 million people in the United States. About 40 percent of people living with migraine may be appropriate candidates for preventive treatment, yet the majority of them are untreated. I am pleased to have another treatment option that may allow my patients to experience fewer monthly migraine days,” Stephen Silberstein, MD, director of the Jefferson Headache Center at Thomas Jefferson University Hospital in Philadelphia, said in the Teva press release.

[email protected]

The Food and Drug Administration has approved Ajovy (fremanezumab-vfrm) for the preventive treatment of migraines in adults.

Fremanezumab-vfrm is an injectable anti–calcitonin gene-related peptide monoclonal antibody, the first ever approved by the FDA. It can be administered at a 225-mg dose every month or at a 675-mg dose every 3 months, according to a press release from Teva, the drug’s manufacturer.

FDA approval was based on results from two, phase 3 trials in patients with disabling migraines, one of which involved fremanezumab-vfrm alone, with the other involving the injection in tandem with an oral treatment.

In both trials, patients experienced a reduction of monthly migraine days over a 12-week period. The most common adverse event in both trials was injection site reactions.

“Migraine is a disabling neurological disease that affects more than 36 million people in the United States. About 40 percent of people living with migraine may be appropriate candidates for preventive treatment, yet the majority of them are untreated. I am pleased to have another treatment option that may allow my patients to experience fewer monthly migraine days,” Stephen Silberstein, MD, director of the Jefferson Headache Center at Thomas Jefferson University Hospital in Philadelphia, said in the Teva press release.

[email protected]

The Food and Drug Administration has approved Ajovy (fremanezumab-vfrm) for the preventive treatment of migraines in adults.

Fremanezumab-vfrm is an injectable anti–calcitonin gene-related peptide monoclonal antibody, the first ever approved by the FDA. It can be administered at a 225-mg dose every month or at a 675-mg dose every 3 months, according to a press release from Teva, the drug’s manufacturer.

FDA approval was based on results from two, phase 3 trials in patients with disabling migraines, one of which involved fremanezumab-vfrm alone, with the other involving the injection in tandem with an oral treatment.

In both trials, patients experienced a reduction of monthly migraine days over a 12-week period. The most common adverse event in both trials was injection site reactions.

“Migraine is a disabling neurological disease that affects more than 36 million people in the United States. About 40 percent of people living with migraine may be appropriate candidates for preventive treatment, yet the majority of them are untreated. I am pleased to have another treatment option that may allow my patients to experience fewer monthly migraine days,” Stephen Silberstein, MD, director of the Jefferson Headache Center at Thomas Jefferson University Hospital in Philadelphia, said in the Teva press release.

[email protected]

The European Commission has granted Shire marketing authorization for vonicog alfa (Veyvondi), a recombinant von Willebrand factor (rVWF) product.

The European Commission (EC) approved vonicog alfa for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults with von Willebrand disease (VWD) when desmopressin treatment alone is ineffective or not indicated.

The product was approved in the United States in 2015 for on-demand treatment and control of bleeding episodes in adults.

The approval means Shire is authorized to market vonicog alfa in the European Union as well as in Iceland, Lichtenstein, and Norway.

The EC’s approval of vonicog alfa was based on outcomes from three clinical trials. This includes a phase 1 study and a pair of phase 3 trials – one in a surgical setting and one in a nonsurgical setting.

Data from these studies are available in the Summary of Product Characteristics for vonicog alfa.The phase 1 trial (NCT00816660) enrolled patients with type 3 or severe type 1 VWD.

The goal was to assess the safety and pharmacokinetics of vonicog alfa combined at a fixed ratio with recombinant factor VIII – referred to as “rVWF-rFVIII.” The researchers compared rVWF-rFVIII with plasma-derived (pd) VWF combined with pdFVIII (pdVWF-pdFVIII).

[email protected]

The European Commission has granted Shire marketing authorization for vonicog alfa (Veyvondi), a recombinant von Willebrand factor (rVWF) product.

The European Commission (EC) approved vonicog alfa for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults with von Willebrand disease (VWD) when desmopressin treatment alone is ineffective or not indicated.

The product was approved in the United States in 2015 for on-demand treatment and control of bleeding episodes in adults.

The approval means Shire is authorized to market vonicog alfa in the European Union as well as in Iceland, Lichtenstein, and Norway.

The EC’s approval of vonicog alfa was based on outcomes from three clinical trials. This includes a phase 1 study and a pair of phase 3 trials – one in a surgical setting and one in a nonsurgical setting.

Data from these studies are available in the Summary of Product Characteristics for vonicog alfa.The phase 1 trial (NCT00816660) enrolled patients with type 3 or severe type 1 VWD.

The goal was to assess the safety and pharmacokinetics of vonicog alfa combined at a fixed ratio with recombinant factor VIII – referred to as “rVWF-rFVIII.” The researchers compared rVWF-rFVIII with plasma-derived (pd) VWF combined with pdFVIII (pdVWF-pdFVIII).

[email protected]

The European Commission has granted Shire marketing authorization for vonicog alfa (Veyvondi), a recombinant von Willebrand factor (rVWF) product.

The European Commission (EC) approved vonicog alfa for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults with von Willebrand disease (VWD) when desmopressin treatment alone is ineffective or not indicated.

The product was approved in the United States in 2015 for on-demand treatment and control of bleeding episodes in adults.

The approval means Shire is authorized to market vonicog alfa in the European Union as well as in Iceland, Lichtenstein, and Norway.

The EC’s approval of vonicog alfa was based on outcomes from three clinical trials. This includes a phase 1 study and a pair of phase 3 trials – one in a surgical setting and one in a nonsurgical setting.

Data from these studies are available in the Summary of Product Characteristics for vonicog alfa.The phase 1 trial (NCT00816660) enrolled patients with type 3 or severe type 1 VWD.

The goal was to assess the safety and pharmacokinetics of vonicog alfa combined at a fixed ratio with recombinant factor VIII – referred to as “rVWF-rFVIII.” The researchers compared rVWF-rFVIII with plasma-derived (pd) VWF combined with pdFVIII (pdVWF-pdFVIII).

[email protected]

ORLANDO – Most patients with type 2 diabetes mellitus stop taking their medication within a year, and nearly one-third stop within the first 3 months, a retrospective analysis of claims data for more than 324,000 patients suggests.

Boarding1Now/Thinkstock

The findings in this population of commercially insured adults are startling and highlight a need for interventions to improve treatment persistence, according to Lisa Latts, MD, deputy chief health officer for IBM Watson Health in Cambridge, Mass.

Dr. Latts and her colleagues reviewed medication claims data for 324,136 patients with at least one diagnosis for type 2 diabetes mellitus and one outpatient pharmacy claim for a type 2 diabetes medication after at least 12 prior months without such a claim.

Of those patients, 58% discontinued treatment within 12 months, 31% discontinued within the first 3 months, and 44% discontinued within 6 months, Dr. Latts reported at the annual scientific sessions of the American Diabetes Association.

“Less than half of those patients who discontinued had a restart within the following year. So what we’re seeing here is a huge percentage of individuals who had a diagnosis of type 2 diabetes, were prescribed a medication, and then did not continue the medication,” she said.

Of those who discontinued within the 12-month follow-up, 27% restarted therapy within 60 days and 39% restarted therapy anytime during the 12-month follow-up (mean treatment gap, 107 days). Of those who discontinued by 3 months, 45% restarted within a year (mean treatment gap, 112 days), and of those who discontinued by 6 months, 44% restarted within a year (mean treatment gap, 119 days).

Patients included in the review, which was a collaborative effort of IBM Watson Health and the ADA, had at least 12 months of continuous enrollment in the Truven Health MarketScan Commercial and Medicare Supplemental Databases between 2013 and 2017, before and after the therapy initiation date.

[email protected]

SOURCE: Latts L et al. ADA 2018, Abstract 135-OR.

ORLANDO – Most patients with type 2 diabetes mellitus stop taking their medication within a year, and nearly one-third stop within the first 3 months, a retrospective analysis of claims data for more than 324,000 patients suggests.

Boarding1Now/Thinkstock

The findings in this population of commercially insured adults are startling and highlight a need for interventions to improve treatment persistence, according to Lisa Latts, MD, deputy chief health officer for IBM Watson Health in Cambridge, Mass.

Dr. Latts and her colleagues reviewed medication claims data for 324,136 patients with at least one diagnosis for type 2 diabetes mellitus and one outpatient pharmacy claim for a type 2 diabetes medication after at least 12 prior months without such a claim.

Of those patients, 58% discontinued treatment within 12 months, 31% discontinued within the first 3 months, and 44% discontinued within 6 months, Dr. Latts reported at the annual scientific sessions of the American Diabetes Association.

“Less than half of those patients who discontinued had a restart within the following year. So what we’re seeing here is a huge percentage of individuals who had a diagnosis of type 2 diabetes, were prescribed a medication, and then did not continue the medication,” she said.

Of those who discontinued within the 12-month follow-up, 27% restarted therapy within 60 days and 39% restarted therapy anytime during the 12-month follow-up (mean treatment gap, 107 days). Of those who discontinued by 3 months, 45% restarted within a year (mean treatment gap, 112 days), and of those who discontinued by 6 months, 44% restarted within a year (mean treatment gap, 119 days).

Patients included in the review, which was a collaborative effort of IBM Watson Health and the ADA, had at least 12 months of continuous enrollment in the Truven Health MarketScan Commercial and Medicare Supplemental Databases between 2013 and 2017, before and after the therapy initiation date.

[email protected]

SOURCE: Latts L et al. ADA 2018, Abstract 135-OR.

ORLANDO – Most patients with type 2 diabetes mellitus stop taking their medication within a year, and nearly one-third stop within the first 3 months, a retrospective analysis of claims data for more than 324,000 patients suggests.

Boarding1Now/Thinkstock

The findings in this population of commercially insured adults are startling and highlight a need for interventions to improve treatment persistence, according to Lisa Latts, MD, deputy chief health officer for IBM Watson Health in Cambridge, Mass.

Dr. Latts and her colleagues reviewed medication claims data for 324,136 patients with at least one diagnosis for type 2 diabetes mellitus and one outpatient pharmacy claim for a type 2 diabetes medication after at least 12 prior months without such a claim.

Of those patients, 58% discontinued treatment within 12 months, 31% discontinued within the first 3 months, and 44% discontinued within 6 months, Dr. Latts reported at the annual scientific sessions of the American Diabetes Association.

“Less than half of those patients who discontinued had a restart within the following year. So what we’re seeing here is a huge percentage of individuals who had a diagnosis of type 2 diabetes, were prescribed a medication, and then did not continue the medication,” she said.

Of those who discontinued within the 12-month follow-up, 27% restarted therapy within 60 days and 39% restarted therapy anytime during the 12-month follow-up (mean treatment gap, 107 days). Of those who discontinued by 3 months, 45% restarted within a year (mean treatment gap, 112 days), and of those who discontinued by 6 months, 44% restarted within a year (mean treatment gap, 119 days).

Patients included in the review, which was a collaborative effort of IBM Watson Health and the ADA, had at least 12 months of continuous enrollment in the Truven Health MarketScan Commercial and Medicare Supplemental Databases between 2013 and 2017, before and after the therapy initiation date.

[email protected]

SOURCE: Latts L et al. ADA 2018, Abstract 135-OR.

multiple myeloma

BOSTON—Early results from a phase 1 trial suggest the chimeric antigen receptor (CAR) T-cell therapy P-BCMA-101 can produce responses in patients with relapsed/refractory multiple myeloma (MM).

All 11 patients treated have experienced some clinical response, with 8 patients achieving a partial response (PR) or better.

The most common adverse events were neutropenia and thrombocytopenia. One patient was suspected to have cytokine release syndrome, but the condition resolved without use of tociluzimab or steroids.

These results were presented at the 2018 CAR-TCR Summit by Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics Inc., the company developing P-BCMA-101.

Dr. Ostertag presented data on 11 patients with heavily pretreated MM. They had a median of six prior therapies. Their median age was 60, and 73% were considered high risk.

Prior to receiving P-BCMA-101, patients received conditioning with fludarabine (30 mg/m²) and cyclophosphamide (300 mg/m²) for 3 days.

Patients were then treated across three dose groups with average CAR T-cell doses of 51×10⁶ (n=3), 152×10⁶ (n=7), and 430×10⁶ (n=1).

As of August 10, 2018, all 11 patients were still on study.

There were no dose-limiting toxicities. Eight patients developed neutropenia, and 5 had thrombocytopenia.

Researchers suspected cytokine release syndrome in one patient, but the condition resolved without tociluzimab or steroid treatment. There was no neurotoxicity reported, and none of the patients required admission to an intensive care unit.

All patients showed improvement in biomarkers following treatment.

Ten patients were evaluable for response by International Myeloma Working Group criteria. Seven of these patients achieved at least a PR, including very good partial responses (VGPRs) and stringent complete response (CR).

The eleventh patient also responded to treatment, but this patient has oligosecretory disease and was only evaluable by PET. The patient had a near-CR by PET.

Poseida Therapeutics would not disclose additional details regarding how many patients achieved a PR, VGPR, or CR, but the company plans to release more information on response at an upcoming meeting.

“The latest data results show that P-BCMA-101 induces deep responses in a heavily pretreated population with relapsed/refractory multiple myeloma, with some patients reaching VGPR and even stringent CR at early efficacy assessments,” Dr. Ostertag said.

“We believe our advantages of a purified product, where all cells express the CAR molecule, and a product with high levels of stem cell memory T cells, producing a more gradual and prolonged immune response against tumor cells, provide a significantly better therapeutic index when compared with other CAR-T therapeutics. We are also encouraged that P-BCMA-101 is demonstrating significant efficacy even at doses that have been ineffective for other anti-BCMA CAR-T therapies and that our response rates continue to improve as the dose increases.”

This study (NCT03288493) is funded by the California Institute for Regenerative Medicine and Poseida Therapeutics.

multiple myeloma

BOSTON—Early results from a phase 1 trial suggest the chimeric antigen receptor (CAR) T-cell therapy P-BCMA-101 can produce responses in patients with relapsed/refractory multiple myeloma (MM).

All 11 patients treated have experienced some clinical response, with 8 patients achieving a partial response (PR) or better.

The most common adverse events were neutropenia and thrombocytopenia. One patient was suspected to have cytokine release syndrome, but the condition resolved without use of tociluzimab or steroids.

These results were presented at the 2018 CAR-TCR Summit by Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics Inc., the company developing P-BCMA-101.

Dr. Ostertag presented data on 11 patients with heavily pretreated MM. They had a median of six prior therapies. Their median age was 60, and 73% were considered high risk.

Prior to receiving P-BCMA-101, patients received conditioning with fludarabine (30 mg/m²) and cyclophosphamide (300 mg/m²) for 3 days.

Patients were then treated across three dose groups with average CAR T-cell doses of 51×10⁶ (n=3), 152×10⁶ (n=7), and 430×10⁶ (n=1).

As of August 10, 2018, all 11 patients were still on study.

There were no dose-limiting toxicities. Eight patients developed neutropenia, and 5 had thrombocytopenia.

Researchers suspected cytokine release syndrome in one patient, but the condition resolved without tociluzimab or steroid treatment. There was no neurotoxicity reported, and none of the patients required admission to an intensive care unit.

All patients showed improvement in biomarkers following treatment.

Ten patients were evaluable for response by International Myeloma Working Group criteria. Seven of these patients achieved at least a PR, including very good partial responses (VGPRs) and stringent complete response (CR).

The eleventh patient also responded to treatment, but this patient has oligosecretory disease and was only evaluable by PET. The patient had a near-CR by PET.

Poseida Therapeutics would not disclose additional details regarding how many patients achieved a PR, VGPR, or CR, but the company plans to release more information on response at an upcoming meeting.

“The latest data results show that P-BCMA-101 induces deep responses in a heavily pretreated population with relapsed/refractory multiple myeloma, with some patients reaching VGPR and even stringent CR at early efficacy assessments,” Dr. Ostertag said.

“We believe our advantages of a purified product, where all cells express the CAR molecule, and a product with high levels of stem cell memory T cells, producing a more gradual and prolonged immune response against tumor cells, provide a significantly better therapeutic index when compared with other CAR-T therapeutics. We are also encouraged that P-BCMA-101 is demonstrating significant efficacy even at doses that have been ineffective for other anti-BCMA CAR-T therapies and that our response rates continue to improve as the dose increases.”

This study (NCT03288493) is funded by the California Institute for Regenerative Medicine and Poseida Therapeutics.

multiple myeloma

BOSTON—Early results from a phase 1 trial suggest the chimeric antigen receptor (CAR) T-cell therapy P-BCMA-101 can produce responses in patients with relapsed/refractory multiple myeloma (MM).

All 11 patients treated have experienced some clinical response, with 8 patients achieving a partial response (PR) or better.

The most common adverse events were neutropenia and thrombocytopenia. One patient was suspected to have cytokine release syndrome, but the condition resolved without use of tociluzimab or steroids.

These results were presented at the 2018 CAR-TCR Summit by Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics Inc., the company developing P-BCMA-101.

Dr. Ostertag presented data on 11 patients with heavily pretreated MM. They had a median of six prior therapies. Their median age was 60, and 73% were considered high risk.

Prior to receiving P-BCMA-101, patients received conditioning with fludarabine (30 mg/m²) and cyclophosphamide (300 mg/m²) for 3 days.

Patients were then treated across three dose groups with average CAR T-cell doses of 51×10⁶ (n=3), 152×10⁶ (n=7), and 430×10⁶ (n=1).

As of August 10, 2018, all 11 patients were still on study.

There were no dose-limiting toxicities. Eight patients developed neutropenia, and 5 had thrombocytopenia.

Researchers suspected cytokine release syndrome in one patient, but the condition resolved without tociluzimab or steroid treatment. There was no neurotoxicity reported, and none of the patients required admission to an intensive care unit.

All patients showed improvement in biomarkers following treatment.

Ten patients were evaluable for response by International Myeloma Working Group criteria. Seven of these patients achieved at least a PR, including very good partial responses (VGPRs) and stringent complete response (CR).

The eleventh patient also responded to treatment, but this patient has oligosecretory disease and was only evaluable by PET. The patient had a near-CR by PET.

Poseida Therapeutics would not disclose additional details regarding how many patients achieved a PR, VGPR, or CR, but the company plans to release more information on response at an upcoming meeting.

“The latest data results show that P-BCMA-101 induces deep responses in a heavily pretreated population with relapsed/refractory multiple myeloma, with some patients reaching VGPR and even stringent CR at early efficacy assessments,” Dr. Ostertag said.

“We believe our advantages of a purified product, where all cells express the CAR molecule, and a product with high levels of stem cell memory T cells, producing a more gradual and prolonged immune response against tumor cells, provide a significantly better therapeutic index when compared with other CAR-T therapeutics. We are also encouraged that P-BCMA-101 is demonstrating significant efficacy even at doses that have been ineffective for other anti-BCMA CAR-T therapies and that our response rates continue to improve as the dose increases.”

This study (NCT03288493) is funded by the California Institute for Regenerative Medicine and Poseida Therapeutics.

Predictive risk factors for cardiac events (CEs) after general and vascular surgery differed significantly, according to a large retrospective study. However, there was no significant difference seen in the overall incidence of CEs between the two types of surgery, reported Derrick Acheampong, MD, and his colleagues at the Icahn School of Medicine at Mount Sinai, New York.

©Thinkstock

They performed a retrospective data analysis of 8,441 adult patients at their large urban teaching hospital; these patients had undergone general or vascular surgery during 2013-2016 and, in the analysis, were grouped by whether they experienced postoperative CEs.

Univariate and multivariate analyses identified predictors of postoperative CE and the association of CEs with adverse postoperative outcomes. CEs were defined as myocardial infarction or cardiac arrest within the 30-day postoperative period.

A total of 157 patients (1.9%) experienced CEs after major general and vascular surgery, with no significant difference in incidence between the two types of surgery (P = .44), according to their report, published online in the Annals of Medicine and Surgery. CE-associated mortality among this group was high, at 55.4%.

The occurrence of a CE following surgery in both groups was significantly associated with increased mortality, as well as pulmonary, renal, and neurological complications, in addition to systemic sepsis, postoperative red blood cell transfusion, unplanned return to the operating room, and prolonged hospitalization, according to the researchers.

However, predictors of CEs risk between vascular and general surgery were significantly different.

For general surgery, American Society of Anesthesiologists (ASA) status greater than 3, dependent functional status, acute renal failure or dialysis, weight loss, creatinine greater than 1.2 mg/dL, international normalized ratio (INR) greater than 1.5, and partial thromboplastin time (PTT) less than 35 seconds were all unique independent predictors of postoperative CEs.

For vascular surgery, the unique significant predictors of postoperative CEs were age greater than 65 years, emergency surgery, diabetes, congestive heart failure, systemic sepsis, and operative time greater than 240 minutes.

The only common predictive risk factors for postoperative CEs for the two forms of surgery were hematocrit less than 34% and ventilator dependence.

“The present study corroborates reported studies that recommend separate predictive CE risk indices and risk stratification among different surgical specialties. Predictors for CE greatly differed between general and vascular surgery patients in our patient population,” the authors stated.

They concluded with the hope that their study “provides useful information to surgeons and allows for the necessary resources to be focused on identified at-risk patients to improve surgical outcomes.”

Dr. Acheampong and his colleagues reported having no disclosures.

[email protected]

SOURCE: Acheampong D et al. Ann Med Surg. 2018. doi: 10.1016/j.amsu.2018.08.001.

Predictive risk factors for cardiac events (CEs) after general and vascular surgery differed significantly, according to a large retrospective study. However, there was no significant difference seen in the overall incidence of CEs between the two types of surgery, reported Derrick Acheampong, MD, and his colleagues at the Icahn School of Medicine at Mount Sinai, New York.

©Thinkstock

They performed a retrospective data analysis of 8,441 adult patients at their large urban teaching hospital; these patients had undergone general or vascular surgery during 2013-2016 and, in the analysis, were grouped by whether they experienced postoperative CEs.

Univariate and multivariate analyses identified predictors of postoperative CE and the association of CEs with adverse postoperative outcomes. CEs were defined as myocardial infarction or cardiac arrest within the 30-day postoperative period.

A total of 157 patients (1.9%) experienced CEs after major general and vascular surgery, with no significant difference in incidence between the two types of surgery (P = .44), according to their report, published online in the Annals of Medicine and Surgery. CE-associated mortality among this group was high, at 55.4%.

The occurrence of a CE following surgery in both groups was significantly associated with increased mortality, as well as pulmonary, renal, and neurological complications, in addition to systemic sepsis, postoperative red blood cell transfusion, unplanned return to the operating room, and prolonged hospitalization, according to the researchers.

However, predictors of CEs risk between vascular and general surgery were significantly different.

For general surgery, American Society of Anesthesiologists (ASA) status greater than 3, dependent functional status, acute renal failure or dialysis, weight loss, creatinine greater than 1.2 mg/dL, international normalized ratio (INR) greater than 1.5, and partial thromboplastin time (PTT) less than 35 seconds were all unique independent predictors of postoperative CEs.

For vascular surgery, the unique significant predictors of postoperative CEs were age greater than 65 years, emergency surgery, diabetes, congestive heart failure, systemic sepsis, and operative time greater than 240 minutes.

The only common predictive risk factors for postoperative CEs for the two forms of surgery were hematocrit less than 34% and ventilator dependence.

“The present study corroborates reported studies that recommend separate predictive CE risk indices and risk stratification among different surgical specialties. Predictors for CE greatly differed between general and vascular surgery patients in our patient population,” the authors stated.

They concluded with the hope that their study “provides useful information to surgeons and allows for the necessary resources to be focused on identified at-risk patients to improve surgical outcomes.”

Dr. Acheampong and his colleagues reported having no disclosures.

[email protected]

SOURCE: Acheampong D et al. Ann Med Surg. 2018. doi: 10.1016/j.amsu.2018.08.001.

Predictive risk factors for cardiac events (CEs) after general and vascular surgery differed significantly, according to a large retrospective study. However, there was no significant difference seen in the overall incidence of CEs between the two types of surgery, reported Derrick Acheampong, MD, and his colleagues at the Icahn School of Medicine at Mount Sinai, New York.

©Thinkstock

They performed a retrospective data analysis of 8,441 adult patients at their large urban teaching hospital; these patients had undergone general or vascular surgery during 2013-2016 and, in the analysis, were grouped by whether they experienced postoperative CEs.

Univariate and multivariate analyses identified predictors of postoperative CE and the association of CEs with adverse postoperative outcomes. CEs were defined as myocardial infarction or cardiac arrest within the 30-day postoperative period.

A total of 157 patients (1.9%) experienced CEs after major general and vascular surgery, with no significant difference in incidence between the two types of surgery (P = .44), according to their report, published online in the Annals of Medicine and Surgery. CE-associated mortality among this group was high, at 55.4%.

The occurrence of a CE following surgery in both groups was significantly associated with increased mortality, as well as pulmonary, renal, and neurological complications, in addition to systemic sepsis, postoperative red blood cell transfusion, unplanned return to the operating room, and prolonged hospitalization, according to the researchers.

However, predictors of CEs risk between vascular and general surgery were significantly different.

For general surgery, American Society of Anesthesiologists (ASA) status greater than 3, dependent functional status, acute renal failure or dialysis, weight loss, creatinine greater than 1.2 mg/dL, international normalized ratio (INR) greater than 1.5, and partial thromboplastin time (PTT) less than 35 seconds were all unique independent predictors of postoperative CEs.

For vascular surgery, the unique significant predictors of postoperative CEs were age greater than 65 years, emergency surgery, diabetes, congestive heart failure, systemic sepsis, and operative time greater than 240 minutes.

The only common predictive risk factors for postoperative CEs for the two forms of surgery were hematocrit less than 34% and ventilator dependence.

“The present study corroborates reported studies that recommend separate predictive CE risk indices and risk stratification among different surgical specialties. Predictors for CE greatly differed between general and vascular surgery patients in our patient population,” the authors stated.

They concluded with the hope that their study “provides useful information to surgeons and allows for the necessary resources to be focused on identified at-risk patients to improve surgical outcomes.”

Dr. Acheampong and his colleagues reported having no disclosures.

[email protected]

SOURCE: Acheampong D et al. Ann Med Surg. 2018. doi: 10.1016/j.amsu.2018.08.001.

PARIS – Adjunctive oral pantothenic acid prolonged the beneficial effects of oral antibiotic therapy for moderate to severe acne vulgaris in a randomized, double-blind, placebo-controlled trial, Maria A. Santos, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The beauty of this treatment strategy is that it enables acne patients to obtain the therapeutic benefits of oral antibiotic therapy while minimizing exposure in accord with the current push to curb the growing problem of antibiotic resistance. Indeed, adjunctive oral pantothenic acid (also known as vitamin B₅) appears to offer a solution to the high rate of clinical deterioration that often follows antibiotic discontinuation, observed Dr. Santos, a dermatologist at University of Santo Tomas Hospital in Manila.

“The use of pantothenic acid as an adjunct may enhance acne therapy and possibly prolong control despite antibiotic discontinuation,” she said.

Dr. Santos reported on 40 patients aged 16-45 years with moderate to severe acne who were randomized to 2 g/day of pantothenic acid or placebo for 16 weeks on top of 6 weeks of oral doxycycline at 100 mg once daily, plus ongoing topical adapalene and benzoyl peroxide gel.

After 8 weeks – that is, 2 weeks after everyone completed 6 weeks on doxycycline – the mean reduction in noninflammatory and total lesion counts was virtually identical in the two groups. For example, there was a 57.7% decrease in total lesion count compared with baseline in the pantothenic acid group and a 55% reduction in placebo-treated controls. Thereafter, however, the response curves diverged. Backsliding occurred in the control group such that their mean reduction in total lesions was 48.4% at 14 weeks and 40.4% at 16 weeks, compared with baseline. In contrast, patients on daily pantothenic acid had a 78.7% reduction in total lesion count at 14 weeks and an 80% decrease from baseline at 16 weeks.

Similarly, at 16 weeks, the mean reduction in noninflammatory lesions was 49% in the pantothenic acid group versus 19.2% in controls, compared with 34%-36% reductions at 10 weeks, even though all patients remained on topical adapalene and benzoyl peroxide throughout.

Mean reduction in inflammatory lesions followed the same trend; however, the numeric advantage in the pantothenic acid group didn’t achieve statistical significance.

Median Dermatology Life Quality Index scores improved over the course of the study in both groups, although significantly more patients in the pantothenic acid group achieved at least a 4-point improvement over baseline, which is considered the minimum clinically important difference. Moreover, while modified Global Severity Scores and subjective self-assessment scores improved in both groups, from week 12 onwards, the improvements were significantly greater in the pantothenic acid group.

Receiving adjunctive pantothenic acid for 10 weeks was safe. Adverse events were the same in both study arms, consisting chiefly of mild erythema, scaling, dryness, and nausea during the initial weeks on doxycycline.

Pantothenic acid is a water-soluble essential nutrient. Dr. Santos said that while the precise mechanism of the benefit seen in this randomized trial isn’t known, other investigators have generated evidence suggestive of enhanced epidermal barrier function through normalization of keratinocyte proliferation and differentiation in acne patients, coupled with antioxidant and anti-inflammatory effects.

Dr. Santos reported having no financial conflicts regarding her study, conducted free of commercial support.
 

[email protected]

PARIS – Adjunctive oral pantothenic acid prolonged the beneficial effects of oral antibiotic therapy for moderate to severe acne vulgaris in a randomized, double-blind, placebo-controlled trial, Maria A. Santos, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The beauty of this treatment strategy is that it enables acne patients to obtain the therapeutic benefits of oral antibiotic therapy while minimizing exposure in accord with the current push to curb the growing problem of antibiotic resistance. Indeed, adjunctive oral pantothenic acid (also known as vitamin B₅) appears to offer a solution to the high rate of clinical deterioration that often follows antibiotic discontinuation, observed Dr. Santos, a dermatologist at University of Santo Tomas Hospital in Manila.

“The use of pantothenic acid as an adjunct may enhance acne therapy and possibly prolong control despite antibiotic discontinuation,” she said.

Dr. Santos reported on 40 patients aged 16-45 years with moderate to severe acne who were randomized to 2 g/day of pantothenic acid or placebo for 16 weeks on top of 6 weeks of oral doxycycline at 100 mg once daily, plus ongoing topical adapalene and benzoyl peroxide gel.

After 8 weeks – that is, 2 weeks after everyone completed 6 weeks on doxycycline – the mean reduction in noninflammatory and total lesion counts was virtually identical in the two groups. For example, there was a 57.7% decrease in total lesion count compared with baseline in the pantothenic acid group and a 55% reduction in placebo-treated controls. Thereafter, however, the response curves diverged. Backsliding occurred in the control group such that their mean reduction in total lesions was 48.4% at 14 weeks and 40.4% at 16 weeks, compared with baseline. In contrast, patients on daily pantothenic acid had a 78.7% reduction in total lesion count at 14 weeks and an 80% decrease from baseline at 16 weeks.

Similarly, at 16 weeks, the mean reduction in noninflammatory lesions was 49% in the pantothenic acid group versus 19.2% in controls, compared with 34%-36% reductions at 10 weeks, even though all patients remained on topical adapalene and benzoyl peroxide throughout.

Mean reduction in inflammatory lesions followed the same trend; however, the numeric advantage in the pantothenic acid group didn’t achieve statistical significance.

Median Dermatology Life Quality Index scores improved over the course of the study in both groups, although significantly more patients in the pantothenic acid group achieved at least a 4-point improvement over baseline, which is considered the minimum clinically important difference. Moreover, while modified Global Severity Scores and subjective self-assessment scores improved in both groups, from week 12 onwards, the improvements were significantly greater in the pantothenic acid group.

Receiving adjunctive pantothenic acid for 10 weeks was safe. Adverse events were the same in both study arms, consisting chiefly of mild erythema, scaling, dryness, and nausea during the initial weeks on doxycycline.

Pantothenic acid is a water-soluble essential nutrient. Dr. Santos said that while the precise mechanism of the benefit seen in this randomized trial isn’t known, other investigators have generated evidence suggestive of enhanced epidermal barrier function through normalization of keratinocyte proliferation and differentiation in acne patients, coupled with antioxidant and anti-inflammatory effects.

Dr. Santos reported having no financial conflicts regarding her study, conducted free of commercial support.
 

[email protected]

PARIS – Adjunctive oral pantothenic acid prolonged the beneficial effects of oral antibiotic therapy for moderate to severe acne vulgaris in a randomized, double-blind, placebo-controlled trial, Maria A. Santos, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The beauty of this treatment strategy is that it enables acne patients to obtain the therapeutic benefits of oral antibiotic therapy while minimizing exposure in accord with the current push to curb the growing problem of antibiotic resistance. Indeed, adjunctive oral pantothenic acid (also known as vitamin B₅) appears to offer a solution to the high rate of clinical deterioration that often follows antibiotic discontinuation, observed Dr. Santos, a dermatologist at University of Santo Tomas Hospital in Manila.

“The use of pantothenic acid as an adjunct may enhance acne therapy and possibly prolong control despite antibiotic discontinuation,” she said.

Dr. Santos reported on 40 patients aged 16-45 years with moderate to severe acne who were randomized to 2 g/day of pantothenic acid or placebo for 16 weeks on top of 6 weeks of oral doxycycline at 100 mg once daily, plus ongoing topical adapalene and benzoyl peroxide gel.

After 8 weeks – that is, 2 weeks after everyone completed 6 weeks on doxycycline – the mean reduction in noninflammatory and total lesion counts was virtually identical in the two groups. For example, there was a 57.7% decrease in total lesion count compared with baseline in the pantothenic acid group and a 55% reduction in placebo-treated controls. Thereafter, however, the response curves diverged. Backsliding occurred in the control group such that their mean reduction in total lesions was 48.4% at 14 weeks and 40.4% at 16 weeks, compared with baseline. In contrast, patients on daily pantothenic acid had a 78.7% reduction in total lesion count at 14 weeks and an 80% decrease from baseline at 16 weeks.

Similarly, at 16 weeks, the mean reduction in noninflammatory lesions was 49% in the pantothenic acid group versus 19.2% in controls, compared with 34%-36% reductions at 10 weeks, even though all patients remained on topical adapalene and benzoyl peroxide throughout.

Mean reduction in inflammatory lesions followed the same trend; however, the numeric advantage in the pantothenic acid group didn’t achieve statistical significance.

Median Dermatology Life Quality Index scores improved over the course of the study in both groups, although significantly more patients in the pantothenic acid group achieved at least a 4-point improvement over baseline, which is considered the minimum clinically important difference. Moreover, while modified Global Severity Scores and subjective self-assessment scores improved in both groups, from week 12 onwards, the improvements were significantly greater in the pantothenic acid group.

Receiving adjunctive pantothenic acid for 10 weeks was safe. Adverse events were the same in both study arms, consisting chiefly of mild erythema, scaling, dryness, and nausea during the initial weeks on doxycycline.

Pantothenic acid is a water-soluble essential nutrient. Dr. Santos said that while the precise mechanism of the benefit seen in this randomized trial isn’t known, other investigators have generated evidence suggestive of enhanced epidermal barrier function through normalization of keratinocyte proliferation and differentiation in acne patients, coupled with antioxidant and anti-inflammatory effects.

Dr. Santos reported having no financial conflicts regarding her study, conducted free of commercial support.
 

[email protected]

WASHINGTON – A strategy combining stewardship and science is needed to help combat antimicrobial resistance, and updated plans from the U.S. Food and Drug Administration include four key components to address all aspects of product development and use, FDA commissioner Scott Gottlieb, MD, said in a press briefing in Washington on Sept. 14. 

“The FDA plays a unique role in advancing human and animal health” that provides a unique vantage point for coordinating all aspects of product development and application, he said. 

The FDA’s comprehensive approach to the challenge of antimicrobial resistance (AMR) includes:

• Facilitating product development.
• Promoting antimicrobial stewardship.
• Supporting the development of new tools for surveillance.
• Advancing scientific initiatives, including research for the development of alternative treatments.

The FDA’s product development plan to combat AMR includes the creation of incentives for companies to develop new antibiotic products and create a robust pipeline, which is a challenge because of the lack of immediate economic gain, Dr. Gottlieb said.
“It necessary to change the perception that the costs and risks of antibiotic innovation are too high relative to their expected gains,” he emphasized. 

Strategies to incentivize companies include fast track designation, priority review, and breakthrough therapy designation. In addition, the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) is designed to promote development of antimicrobial drugs for limited and underserved populations, Dr. Gottlieb said. The FDA plan also calls for pursuing reimbursement options with the Centers for Medicare & Medicaid Services. 

Promoting antimicrobial stewardship remains an ongoing element of the FDA’s plan to reduce AMR. In conjunction with the release of the FDA’s updated approach to AMR, the FDA’s Center for Veterinary Medicine CVM released a 5-year action plan to promote and support antimicrobial stewardship in not only the agricultural arena, but in companion animals as well. 

The FDA plans to bring all antimicrobials of medical importance that are approved for use in animals under the oversight of CVM, which will pursue the improve labeling on antimicrobial drugs used in the feed and water of food-producing animals, including defining durations of use, Dr. Gottlieb noted.

Supporting the development and improvement of surveillance tools is “essential to understanding the drivers of resistance in human and veterinary settings and formulating appropriate responses” to outbreaks, Dr. Gottlieb said.

To help meet this goal, the FDA will expand sampling via the National Antimicrobial Resistance Monitoring System (NARMS) database, he said. Other surveillance goals include supporting genomics research and expanding AMR monitoring to include pathogens associated with animal feed and companion animals, he added. 

As part of the final component of the FDA’s AMR strategy to advance scientific initiatives, the FDA has released a new Request for Information “to obtain additional, external input on how best to develop an annual list of regulatory science initiatives specific for antimicrobial products,” Dr. Gottlieb announced. The FDA intends to use the information gained from clinicians and others in its creation of guidance documents and recommendations to streamline the antibiotic development process. He also cited the FDA’s ongoing support of partnerships with public and private organizations such as the Clinical Trials Transformation Initiative, which focuses on drug development for severe bacterial infections with current unmet medical need.

“We need to harness science and policy to help our public health systems and researchers become nimbler in the battle against drug-resistant pathogens,” Dr. Gottlieb concluded. 

In a panel discussion following the briefing, several experts offered perspective on the FDA’s goals and on the challenges of AMR. 

William Flynn, DVM, deputy director of science policy for the Center of Veterinary Medicine, noted some goals for reducing the use of antibiotics in the veterinary arena. 

“We are trying to focus on the driver: What are the disease conditions that drive use of the product,” he said. Ideally, better management of disease conditions can reduce reliance on antibiotics, he added. 

Also in the panel discussion, Steven Gitterman, MD, deputy director of the division of microbiology devices at the Center for Devices and Radiological Health, emphasized the value of sustainable trial databases so AMR research can continue on an ongoing basis. Finally, Carolyn Wilson, PhD, associate director of research at the Center for Biologics Evaluation and Research, noted that the FDA’s research and development efforts include antibiotic alternatives, including live biotherapeutic products, fecal microbiota transplantation, and bacteriophage therapy.

Visit www.fda.gov for a transcript of Dr. Gottlieb’s talk, and for the updated FDA website page with more details on the agency’s plans to combat antimicrobial resistance. 

Dr. Gottlieb and the panelists had no financial conflicts to disclose.

WASHINGTON – A strategy combining stewardship and science is needed to help combat antimicrobial resistance, and updated plans from the U.S. Food and Drug Administration include four key components to address all aspects of product development and use, FDA commissioner Scott Gottlieb, MD, said in a press briefing in Washington on Sept. 14. 

“The FDA plays a unique role in advancing human and animal health” that provides a unique vantage point for coordinating all aspects of product development and application, he said. 

The FDA’s comprehensive approach to the challenge of antimicrobial resistance (AMR) includes:

• Facilitating product development.
• Promoting antimicrobial stewardship.
• Supporting the development of new tools for surveillance.
• Advancing scientific initiatives, including research for the development of alternative treatments.

The FDA’s product development plan to combat AMR includes the creation of incentives for companies to develop new antibiotic products and create a robust pipeline, which is a challenge because of the lack of immediate economic gain, Dr. Gottlieb said.
“It necessary to change the perception that the costs and risks of antibiotic innovation are too high relative to their expected gains,” he emphasized. 

Strategies to incentivize companies include fast track designation, priority review, and breakthrough therapy designation. In addition, the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) is designed to promote development of antimicrobial drugs for limited and underserved populations, Dr. Gottlieb said. The FDA plan also calls for pursuing reimbursement options with the Centers for Medicare & Medicaid Services. 

Promoting antimicrobial stewardship remains an ongoing element of the FDA’s plan to reduce AMR. In conjunction with the release of the FDA’s updated approach to AMR, the FDA’s Center for Veterinary Medicine CVM released a 5-year action plan to promote and support antimicrobial stewardship in not only the agricultural arena, but in companion animals as well. 

The FDA plans to bring all antimicrobials of medical importance that are approved for use in animals under the oversight of CVM, which will pursue the improve labeling on antimicrobial drugs used in the feed and water of food-producing animals, including defining durations of use, Dr. Gottlieb noted.

Supporting the development and improvement of surveillance tools is “essential to understanding the drivers of resistance in human and veterinary settings and formulating appropriate responses” to outbreaks, Dr. Gottlieb said.

To help meet this goal, the FDA will expand sampling via the National Antimicrobial Resistance Monitoring System (NARMS) database, he said. Other surveillance goals include supporting genomics research and expanding AMR monitoring to include pathogens associated with animal feed and companion animals, he added. 

As part of the final component of the FDA’s AMR strategy to advance scientific initiatives, the FDA has released a new Request for Information “to obtain additional, external input on how best to develop an annual list of regulatory science initiatives specific for antimicrobial products,” Dr. Gottlieb announced. The FDA intends to use the information gained from clinicians and others in its creation of guidance documents and recommendations to streamline the antibiotic development process. He also cited the FDA’s ongoing support of partnerships with public and private organizations such as the Clinical Trials Transformation Initiative, which focuses on drug development for severe bacterial infections with current unmet medical need.

“We need to harness science and policy to help our public health systems and researchers become nimbler in the battle against drug-resistant pathogens,” Dr. Gottlieb concluded. 

In a panel discussion following the briefing, several experts offered perspective on the FDA’s goals and on the challenges of AMR. 

William Flynn, DVM, deputy director of science policy for the Center of Veterinary Medicine, noted some goals for reducing the use of antibiotics in the veterinary arena. 

“We are trying to focus on the driver: What are the disease conditions that drive use of the product,” he said. Ideally, better management of disease conditions can reduce reliance on antibiotics, he added. 

Also in the panel discussion, Steven Gitterman, MD, deputy director of the division of microbiology devices at the Center for Devices and Radiological Health, emphasized the value of sustainable trial databases so AMR research can continue on an ongoing basis. Finally, Carolyn Wilson, PhD, associate director of research at the Center for Biologics Evaluation and Research, noted that the FDA’s research and development efforts include antibiotic alternatives, including live biotherapeutic products, fecal microbiota transplantation, and bacteriophage therapy.

Visit www.fda.gov for a transcript of Dr. Gottlieb’s talk, and for the updated FDA website page with more details on the agency’s plans to combat antimicrobial resistance. 

Dr. Gottlieb and the panelists had no financial conflicts to disclose.

WASHINGTON – A strategy combining stewardship and science is needed to help combat antimicrobial resistance, and updated plans from the U.S. Food and Drug Administration include four key components to address all aspects of product development and use, FDA commissioner Scott Gottlieb, MD, said in a press briefing in Washington on Sept. 14. 

“The FDA plays a unique role in advancing human and animal health” that provides a unique vantage point for coordinating all aspects of product development and application, he said. 

The FDA’s comprehensive approach to the challenge of antimicrobial resistance (AMR) includes:

• Facilitating product development.
• Promoting antimicrobial stewardship.
• Supporting the development of new tools for surveillance.
• Advancing scientific initiatives, including research for the development of alternative treatments.

The FDA’s product development plan to combat AMR includes the creation of incentives for companies to develop new antibiotic products and create a robust pipeline, which is a challenge because of the lack of immediate economic gain, Dr. Gottlieb said.
“It necessary to change the perception that the costs and risks of antibiotic innovation are too high relative to their expected gains,” he emphasized. 

Strategies to incentivize companies include fast track designation, priority review, and breakthrough therapy designation. In addition, the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) is designed to promote development of antimicrobial drugs for limited and underserved populations, Dr. Gottlieb said. The FDA plan also calls for pursuing reimbursement options with the Centers for Medicare & Medicaid Services. 

Promoting antimicrobial stewardship remains an ongoing element of the FDA’s plan to reduce AMR. In conjunction with the release of the FDA’s updated approach to AMR, the FDA’s Center for Veterinary Medicine CVM released a 5-year action plan to promote and support antimicrobial stewardship in not only the agricultural arena, but in companion animals as well. 

The FDA plans to bring all antimicrobials of medical importance that are approved for use in animals under the oversight of CVM, which will pursue the improve labeling on antimicrobial drugs used in the feed and water of food-producing animals, including defining durations of use, Dr. Gottlieb noted.

Supporting the development and improvement of surveillance tools is “essential to understanding the drivers of resistance in human and veterinary settings and formulating appropriate responses” to outbreaks, Dr. Gottlieb said.

To help meet this goal, the FDA will expand sampling via the National Antimicrobial Resistance Monitoring System (NARMS) database, he said. Other surveillance goals include supporting genomics research and expanding AMR monitoring to include pathogens associated with animal feed and companion animals, he added. 

As part of the final component of the FDA’s AMR strategy to advance scientific initiatives, the FDA has released a new Request for Information “to obtain additional, external input on how best to develop an annual list of regulatory science initiatives specific for antimicrobial products,” Dr. Gottlieb announced. The FDA intends to use the information gained from clinicians and others in its creation of guidance documents and recommendations to streamline the antibiotic development process. He also cited the FDA’s ongoing support of partnerships with public and private organizations such as the Clinical Trials Transformation Initiative, which focuses on drug development for severe bacterial infections with current unmet medical need.

“We need to harness science and policy to help our public health systems and researchers become nimbler in the battle against drug-resistant pathogens,” Dr. Gottlieb concluded. 

In a panel discussion following the briefing, several experts offered perspective on the FDA’s goals and on the challenges of AMR. 

William Flynn, DVM, deputy director of science policy for the Center of Veterinary Medicine, noted some goals for reducing the use of antibiotics in the veterinary arena. 

“We are trying to focus on the driver: What are the disease conditions that drive use of the product,” he said. Ideally, better management of disease conditions can reduce reliance on antibiotics, he added. 

Also in the panel discussion, Steven Gitterman, MD, deputy director of the division of microbiology devices at the Center for Devices and Radiological Health, emphasized the value of sustainable trial databases so AMR research can continue on an ongoing basis. Finally, Carolyn Wilson, PhD, associate director of research at the Center for Biologics Evaluation and Research, noted that the FDA’s research and development efforts include antibiotic alternatives, including live biotherapeutic products, fecal microbiota transplantation, and bacteriophage therapy.

Visit www.fda.gov for a transcript of Dr. Gottlieb’s talk, and for the updated FDA website page with more details on the agency’s plans to combat antimicrobial resistance. 

Dr. Gottlieb and the panelists had no financial conflicts to disclose.

Posttraumatic stress disorder (PTSD) develops after exposure to a traumatic event, which can involve witnessing the traumatic event or directly experiencing the trauma.¹ The prevalence of PTSD in the general population is approximately 7% to 8%.¹ However, not everyone who experiences trauma develops PTSD since the majority of men and women experience at least 1 traumatic event in their lifetimes but do not develop PTSD.¹

In order to be diagnosed with PTSD, a patient must meet several criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).² The patient is required to have exposure to trauma, begin having a certain number of prespecified symptoms, and these symptoms must persist for at least a month.² Symptoms of PTSD include re-experiencing the traumatic event, avoidance of stimuli associated with the trauma, negative cognitions and mood, and hyperarousal.^3,4 The hyperarousal that is associated with PTSD has been theorized to be either a result of the trauma experienced or exacerbation of a pre-existing tendency.⁵ This can manifest in various ways, such as hypervigilance, exaggerated startle response, trouble sleeping, problems concentrating, or irritability.^3,5 These symptoms can cause individuals with PTSD to have elevated levels of stress and to experience difficulties with completing everyday tasks.⁶

PTSD and Inflimmation-Related Medical Conditions

Posttraumatic stress disorder has been linked to various physical health problems. Studies have found that PTSD is often comorbid with cardiovascular, autoimmune, musculoskeletal, digestive, chronic pain and respiratory disorders.^3,7-11 Inflammation may be a contributing factor in the associations between PTSD and these conditions.^12-16 Studies have found that increases in pro-inflammatory cytokines and interferons are associated with PTSD, as well as changes in immune-related blood cells.^12-16

Considering that PTSD has been linked to many medical conditions that have inflammatory components, especially cardiovascular disease, inflammatory markers may be early indicators of PTSD.^12-16 Additionally, inflammatory markers such as cytokines and interferons can be targeted through medications, and potentially influence symptoms.¹³ However, the relation between PTSD and inflammation remains unclear. Associations between PTSD and inflammation-related medical conditions may be due to confounding variables, such as sociodemographic characteristics and health behaviors. Moreover, the list of inflammation-related medical conditions is long and there is no universal agreement of what conditions are related to inflammation.

We recently conducted an epidemiological study using a representative sample of residents living in New York City and found significant associations between PTSD and some inflammation-related medical conditions.⁸ We found that participants who had PTSD were more than 4 times more likely to report having had a heart attack or emphysema than were those without PTSD. In addition, participants with PTSD were 2 times more likely to report having hypercholesterolemia, insulin resistance, and angina than were those without PTSD. However, we also found that participants who had PTSD were less likely to develop other inflammation-related conditions like hypertension, type 1 diabetes mellitus, asthma, coronary heart disease, stroke, osteoporosis, and failing kidney.

Together, these associations suggest there is a strong link between PTSD and certain medical conditions, but the link may not be solely based on inflammation.⁸ Moreover, positive associations between PTSD and hypertension, asthma, and coronary heart disease disappeared when depression was controlled for. This finding points to depression as a major factor, consistent with previous findings that depression is associated with the development of various medical conditions and may be a stronger factor than PTSD.⁸

Nonetheless, findings concerning the increased risk for heart problems among adults with PTSD are striking and important given that heart disease is one of the main causes of death in the United States.⁹ Specifically, well over half a million people in the United States die of heart disease annually as the leading cause of death.¹⁷ Heart disease has been one of the top 2 leading causes of death for Americans since 1975.¹⁸  

In the veteran population, heart disease has also been found to be a leading cause of death, accounting for 20 percent of all deaths in veterans from 1993 to 2002.¹⁹ Posttraumatic stress disorder has been linked to a 55% increase in the chance of developing heart disease or dying from a heart-related medical problem.⁹ For example, data from the World Trade Center Registry showed that on average adults who developed PTSD from the 9/11 terrorist attack had a heightened risk for heart disease for 3 years after the event.⁹ Other studies of the U.S. veteran population have shown that veterans with PTSD are more likely to experience heart failure, myocardial infarction, and cardiac arrhythmia than other veterans.^10,20

Veteran-Specific Issues

In the US veteran population, there is a higher prevalence of PTSD and physical health conditions when compared with the general population.^21,21 The prevalence of combat-related PTSD in veterans ranges from 2% to 17%, compared with a 7% to 8% prevalence of PTSD in the general population.^1,22 In a study of veterans who were seen in patient-aligned care teams (PACTs) > 1 year, 9.3% were diagnosed with PTSD and many of those with PTSD also had other medical conditions.²¹ It was found that 43% of veterans seen by PACTs with chronic pain had PTSD, 33% with hypertension had PTSD, and 32% with diabetes mellitus had PTSD.²¹ In another study of combat veterans it was found that those who were trauma-exposed had more physical health problems, regardless of the amount of time spent in combat.¹⁹ Consequentially, veterans with PTSD have been found to make more frequent visits to primary care and specialty medical care clinics. ²¹

Integrated healthcare has been a main service model for the Department of Veteran Affairs (VA) and several programs have been created to integrate mental health and primary care. For example, the VA primary care-mental health integration (PCMHI) program places mental health services within primary care services.²¹ Assessments of this program have demonstrated that it improves the screening of psychological disorders and preventive care of patients who have psychological disorders.²¹ Specifically, it has been found that contact with PCMHI diminishes risks for poor outcomes among psychiatric patients.²¹ Another program called SCAN-ECHO, provides specialized training for VA general practitioners on treating specific health conditions through a specialty care team and video conferencing.²³ This VA program allows for patients in more remote locations to receive specialty care from generalists.²³ While there has not yet been a focus in SCAN-ECHO on PTSD, this may be considered in the future as a way to better train primary care and mental health providers about PTSD and common comorbid medical conditions.

Through their professional experiences, VA practitioners have knowledge of the link between PTSD and various medical conditions. The VA has already implemented screening for PTSD in primary care clinics, but it is important for mental health providers and medical practitioners to continue educating themselves about medical comorbidities and the possible exacerbation of medical conditions due to PTSD.²¹ Some physical manifestations of PTSD symptoms, such as sleep disturbances, avoidance of crowds, or hypervigilance, can affect overall health. Hypervigilance can result in over-activation of stress pathways, which puts patients with PTSD at a heighted risk for medical conditions.¹¹ Additionally, some of the cognitive symptoms of PTSD, such as sleep problems, may worsen current health problems. Therefore, further collaboration between primary care physicians and mental health providers is beneficial in treating clients that have PTSD.

Conclusion

Posttraumatic stress disorder is a prevalent condition among veterans that is often comorbid with other medical conditions, which may have important implications for VA healthcare teams.³ It can manifest both psychologically and physiologically, and can greatly affect a patient’s quality of life.³ Veterans with PTSD may be at increased risk for certain medical conditions, such as cardiovascular disease.^9,10,20  However, preventive screenings for medical conditions linked to PTSD and regular health assessments may reduce these risks.²¹ The VA’s infrastructure of integrated medical and mental healthcare can help provide comprehensive care to the many veterans who have both PTSD and serious medical conditions.²¹ While the relation between PTSD and inflammation remains unclear, it is clear that many people with PTSD have medical conditions that may be affected by PTSD symptoms.

Posttraumatic stress disorder (PTSD) develops after exposure to a traumatic event, which can involve witnessing the traumatic event or directly experiencing the trauma.¹ The prevalence of PTSD in the general population is approximately 7% to 8%.¹ However, not everyone who experiences trauma develops PTSD since the majority of men and women experience at least 1 traumatic event in their lifetimes but do not develop PTSD.¹

In order to be diagnosed with PTSD, a patient must meet several criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).² The patient is required to have exposure to trauma, begin having a certain number of prespecified symptoms, and these symptoms must persist for at least a month.² Symptoms of PTSD include re-experiencing the traumatic event, avoidance of stimuli associated with the trauma, negative cognitions and mood, and hyperarousal.^3,4 The hyperarousal that is associated with PTSD has been theorized to be either a result of the trauma experienced or exacerbation of a pre-existing tendency.⁵ This can manifest in various ways, such as hypervigilance, exaggerated startle response, trouble sleeping, problems concentrating, or irritability.^3,5 These symptoms can cause individuals with PTSD to have elevated levels of stress and to experience difficulties with completing everyday tasks.⁶

PTSD and Inflimmation-Related Medical Conditions

Posttraumatic stress disorder has been linked to various physical health problems. Studies have found that PTSD is often comorbid with cardiovascular, autoimmune, musculoskeletal, digestive, chronic pain and respiratory disorders.^3,7-11 Inflammation may be a contributing factor in the associations between PTSD and these conditions.^12-16 Studies have found that increases in pro-inflammatory cytokines and interferons are associated with PTSD, as well as changes in immune-related blood cells.^12-16

Considering that PTSD has been linked to many medical conditions that have inflammatory components, especially cardiovascular disease, inflammatory markers may be early indicators of PTSD.^12-16 Additionally, inflammatory markers such as cytokines and interferons can be targeted through medications, and potentially influence symptoms.¹³ However, the relation between PTSD and inflammation remains unclear. Associations between PTSD and inflammation-related medical conditions may be due to confounding variables, such as sociodemographic characteristics and health behaviors. Moreover, the list of inflammation-related medical conditions is long and there is no universal agreement of what conditions are related to inflammation.

We recently conducted an epidemiological study using a representative sample of residents living in New York City and found significant associations between PTSD and some inflammation-related medical conditions.⁸ We found that participants who had PTSD were more than 4 times more likely to report having had a heart attack or emphysema than were those without PTSD. In addition, participants with PTSD were 2 times more likely to report having hypercholesterolemia, insulin resistance, and angina than were those without PTSD. However, we also found that participants who had PTSD were less likely to develop other inflammation-related conditions like hypertension, type 1 diabetes mellitus, asthma, coronary heart disease, stroke, osteoporosis, and failing kidney.

Together, these associations suggest there is a strong link between PTSD and certain medical conditions, but the link may not be solely based on inflammation.⁸ Moreover, positive associations between PTSD and hypertension, asthma, and coronary heart disease disappeared when depression was controlled for. This finding points to depression as a major factor, consistent with previous findings that depression is associated with the development of various medical conditions and may be a stronger factor than PTSD.⁸

Nonetheless, findings concerning the increased risk for heart problems among adults with PTSD are striking and important given that heart disease is one of the main causes of death in the United States.⁹ Specifically, well over half a million people in the United States die of heart disease annually as the leading cause of death.¹⁷ Heart disease has been one of the top 2 leading causes of death for Americans since 1975.¹⁸  

In the veteran population, heart disease has also been found to be a leading cause of death, accounting for 20 percent of all deaths in veterans from 1993 to 2002.¹⁹ Posttraumatic stress disorder has been linked to a 55% increase in the chance of developing heart disease or dying from a heart-related medical problem.⁹ For example, data from the World Trade Center Registry showed that on average adults who developed PTSD from the 9/11 terrorist attack had a heightened risk for heart disease for 3 years after the event.⁹ Other studies of the U.S. veteran population have shown that veterans with PTSD are more likely to experience heart failure, myocardial infarction, and cardiac arrhythmia than other veterans.^10,20

Veteran-Specific Issues

In the US veteran population, there is a higher prevalence of PTSD and physical health conditions when compared with the general population.^21,21 The prevalence of combat-related PTSD in veterans ranges from 2% to 17%, compared with a 7% to 8% prevalence of PTSD in the general population.^1,22 In a study of veterans who were seen in patient-aligned care teams (PACTs) > 1 year, 9.3% were diagnosed with PTSD and many of those with PTSD also had other medical conditions.²¹ It was found that 43% of veterans seen by PACTs with chronic pain had PTSD, 33% with hypertension had PTSD, and 32% with diabetes mellitus had PTSD.²¹ In another study of combat veterans it was found that those who were trauma-exposed had more physical health problems, regardless of the amount of time spent in combat.¹⁹ Consequentially, veterans with PTSD have been found to make more frequent visits to primary care and specialty medical care clinics. ²¹

Integrated healthcare has been a main service model for the Department of Veteran Affairs (VA) and several programs have been created to integrate mental health and primary care. For example, the VA primary care-mental health integration (PCMHI) program places mental health services within primary care services.²¹ Assessments of this program have demonstrated that it improves the screening of psychological disorders and preventive care of patients who have psychological disorders.²¹ Specifically, it has been found that contact with PCMHI diminishes risks for poor outcomes among psychiatric patients.²¹ Another program called SCAN-ECHO, provides specialized training for VA general practitioners on treating specific health conditions through a specialty care team and video conferencing.²³ This VA program allows for patients in more remote locations to receive specialty care from generalists.²³ While there has not yet been a focus in SCAN-ECHO on PTSD, this may be considered in the future as a way to better train primary care and mental health providers about PTSD and common comorbid medical conditions.

Through their professional experiences, VA practitioners have knowledge of the link between PTSD and various medical conditions. The VA has already implemented screening for PTSD in primary care clinics, but it is important for mental health providers and medical practitioners to continue educating themselves about medical comorbidities and the possible exacerbation of medical conditions due to PTSD.²¹ Some physical manifestations of PTSD symptoms, such as sleep disturbances, avoidance of crowds, or hypervigilance, can affect overall health. Hypervigilance can result in over-activation of stress pathways, which puts patients with PTSD at a heighted risk for medical conditions.¹¹ Additionally, some of the cognitive symptoms of PTSD, such as sleep problems, may worsen current health problems. Therefore, further collaboration between primary care physicians and mental health providers is beneficial in treating clients that have PTSD.

Conclusion

Posttraumatic stress disorder is a prevalent condition among veterans that is often comorbid with other medical conditions, which may have important implications for VA healthcare teams.³ It can manifest both psychologically and physiologically, and can greatly affect a patient’s quality of life.³ Veterans with PTSD may be at increased risk for certain medical conditions, such as cardiovascular disease.^9,10,20  However, preventive screenings for medical conditions linked to PTSD and regular health assessments may reduce these risks.²¹ The VA’s infrastructure of integrated medical and mental healthcare can help provide comprehensive care to the many veterans who have both PTSD and serious medical conditions.²¹ While the relation between PTSD and inflammation remains unclear, it is clear that many people with PTSD have medical conditions that may be affected by PTSD symptoms.

Posttraumatic stress disorder (PTSD) develops after exposure to a traumatic event, which can involve witnessing the traumatic event or directly experiencing the trauma.¹ The prevalence of PTSD in the general population is approximately 7% to 8%.¹ However, not everyone who experiences trauma develops PTSD since the majority of men and women experience at least 1 traumatic event in their lifetimes but do not develop PTSD.¹

In order to be diagnosed with PTSD, a patient must meet several criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).² The patient is required to have exposure to trauma, begin having a certain number of prespecified symptoms, and these symptoms must persist for at least a month.² Symptoms of PTSD include re-experiencing the traumatic event, avoidance of stimuli associated with the trauma, negative cognitions and mood, and hyperarousal.^3,4 The hyperarousal that is associated with PTSD has been theorized to be either a result of the trauma experienced or exacerbation of a pre-existing tendency.⁵ This can manifest in various ways, such as hypervigilance, exaggerated startle response, trouble sleeping, problems concentrating, or irritability.^3,5 These symptoms can cause individuals with PTSD to have elevated levels of stress and to experience difficulties with completing everyday tasks.⁶

PTSD and Inflimmation-Related Medical Conditions

Posttraumatic stress disorder has been linked to various physical health problems. Studies have found that PTSD is often comorbid with cardiovascular, autoimmune, musculoskeletal, digestive, chronic pain and respiratory disorders.^3,7-11 Inflammation may be a contributing factor in the associations between PTSD and these conditions.^12-16 Studies have found that increases in pro-inflammatory cytokines and interferons are associated with PTSD, as well as changes in immune-related blood cells.^12-16

Considering that PTSD has been linked to many medical conditions that have inflammatory components, especially cardiovascular disease, inflammatory markers may be early indicators of PTSD.^12-16 Additionally, inflammatory markers such as cytokines and interferons can be targeted through medications, and potentially influence symptoms.¹³ However, the relation between PTSD and inflammation remains unclear. Associations between PTSD and inflammation-related medical conditions may be due to confounding variables, such as sociodemographic characteristics and health behaviors. Moreover, the list of inflammation-related medical conditions is long and there is no universal agreement of what conditions are related to inflammation.

We recently conducted an epidemiological study using a representative sample of residents living in New York City and found significant associations between PTSD and some inflammation-related medical conditions.⁸ We found that participants who had PTSD were more than 4 times more likely to report having had a heart attack or emphysema than were those without PTSD. In addition, participants with PTSD were 2 times more likely to report having hypercholesterolemia, insulin resistance, and angina than were those without PTSD. However, we also found that participants who had PTSD were less likely to develop other inflammation-related conditions like hypertension, type 1 diabetes mellitus, asthma, coronary heart disease, stroke, osteoporosis, and failing kidney.

Together, these associations suggest there is a strong link between PTSD and certain medical conditions, but the link may not be solely based on inflammation.⁸ Moreover, positive associations between PTSD and hypertension, asthma, and coronary heart disease disappeared when depression was controlled for. This finding points to depression as a major factor, consistent with previous findings that depression is associated with the development of various medical conditions and may be a stronger factor than PTSD.⁸

Nonetheless, findings concerning the increased risk for heart problems among adults with PTSD are striking and important given that heart disease is one of the main causes of death in the United States.⁹ Specifically, well over half a million people in the United States die of heart disease annually as the leading cause of death.¹⁷ Heart disease has been one of the top 2 leading causes of death for Americans since 1975.¹⁸  

In the veteran population, heart disease has also been found to be a leading cause of death, accounting for 20 percent of all deaths in veterans from 1993 to 2002.¹⁹ Posttraumatic stress disorder has been linked to a 55% increase in the chance of developing heart disease or dying from a heart-related medical problem.⁹ For example, data from the World Trade Center Registry showed that on average adults who developed PTSD from the 9/11 terrorist attack had a heightened risk for heart disease for 3 years after the event.⁹ Other studies of the U.S. veteran population have shown that veterans with PTSD are more likely to experience heart failure, myocardial infarction, and cardiac arrhythmia than other veterans.^10,20

Veteran-Specific Issues

In the US veteran population, there is a higher prevalence of PTSD and physical health conditions when compared with the general population.^21,21 The prevalence of combat-related PTSD in veterans ranges from 2% to 17%, compared with a 7% to 8% prevalence of PTSD in the general population.^1,22 In a study of veterans who were seen in patient-aligned care teams (PACTs) > 1 year, 9.3% were diagnosed with PTSD and many of those with PTSD also had other medical conditions.²¹ It was found that 43% of veterans seen by PACTs with chronic pain had PTSD, 33% with hypertension had PTSD, and 32% with diabetes mellitus had PTSD.²¹ In another study of combat veterans it was found that those who were trauma-exposed had more physical health problems, regardless of the amount of time spent in combat.¹⁹ Consequentially, veterans with PTSD have been found to make more frequent visits to primary care and specialty medical care clinics. ²¹

Integrated healthcare has been a main service model for the Department of Veteran Affairs (VA) and several programs have been created to integrate mental health and primary care. For example, the VA primary care-mental health integration (PCMHI) program places mental health services within primary care services.²¹ Assessments of this program have demonstrated that it improves the screening of psychological disorders and preventive care of patients who have psychological disorders.²¹ Specifically, it has been found that contact with PCMHI diminishes risks for poor outcomes among psychiatric patients.²¹ Another program called SCAN-ECHO, provides specialized training for VA general practitioners on treating specific health conditions through a specialty care team and video conferencing.²³ This VA program allows for patients in more remote locations to receive specialty care from generalists.²³ While there has not yet been a focus in SCAN-ECHO on PTSD, this may be considered in the future as a way to better train primary care and mental health providers about PTSD and common comorbid medical conditions.

Through their professional experiences, VA practitioners have knowledge of the link between PTSD and various medical conditions. The VA has already implemented screening for PTSD in primary care clinics, but it is important for mental health providers and medical practitioners to continue educating themselves about medical comorbidities and the possible exacerbation of medical conditions due to PTSD.²¹ Some physical manifestations of PTSD symptoms, such as sleep disturbances, avoidance of crowds, or hypervigilance, can affect overall health. Hypervigilance can result in over-activation of stress pathways, which puts patients with PTSD at a heighted risk for medical conditions.¹¹ Additionally, some of the cognitive symptoms of PTSD, such as sleep problems, may worsen current health problems. Therefore, further collaboration between primary care physicians and mental health providers is beneficial in treating clients that have PTSD.

Conclusion

Posttraumatic stress disorder is a prevalent condition among veterans that is often comorbid with other medical conditions, which may have important implications for VA healthcare teams.³ It can manifest both psychologically and physiologically, and can greatly affect a patient’s quality of life.³ Veterans with PTSD may be at increased risk for certain medical conditions, such as cardiovascular disease.^9,10,20  However, preventive screenings for medical conditions linked to PTSD and regular health assessments may reduce these risks.²¹ The VA’s infrastructure of integrated medical and mental healthcare can help provide comprehensive care to the many veterans who have both PTSD and serious medical conditions.²¹ While the relation between PTSD and inflammation remains unclear, it is clear that many people with PTSD have medical conditions that may be affected by PTSD symptoms.

The use of tyrosine kinase inhibitors (TKIs) sunitinib and pazopanib to treat metastatic clear cell renal cell carcinoma (RCC) is feasible and effective in Brazil, even though limitations of the public health system mean not all patients have access to these or other therapies, researchers wrote.

In a retrospective analysis of 222 patients with advanced clear cell RCC who were treated with either sunitinib (n = 109) or pazopanib (n = 113), overall survival was 15.2 months with sunitinib and 14.2 months with pazopanib, investigators reported in the Journal of Global Oncology.

Overall survival rates, based on Memorial Sloan Kettering Cancer Center risk categories, were 32.9 months for patients with low risk disease, 15.9 months for intermediate risk patients, and 8.1 months for patient with poor risk – which constituted 29% of the patient population.

Pedro I. Velho, MD, of Johns Hopkins University, Baltimore, and his coauthors noted that these survival rates were lower than those seen in phase 3 trials in the same population.

They suggested this could be caused by the fact that the patients in this real-world study had worse baseline prognoses than those seen in previous clinical trials.

However, they also pointed out that, in the Brazilian public health system, there was no standard systemic treatment option outside clinical trials for patients who have progressed on a TKI as a first-line treatment. Only around half the patients in this study (101) would have been eligible for participation in a clinical trial.

“In our opinion, it is crucial to extend the access to these TKIs for the Brazilian population and also patients in other countries with limited access to targeted therapies,” the authors wrote.

However, the 14 patients who were eligible for treatment with nivolumab under a compassionate use program showed a significantly better overall survival rate, compared with patients who did not have access to a second-line therapy (36.7 months vs. 13.6 months; P less than .001).

“Also, it is imperative to provide systemic sequential treatment options for this population as an attempt to improve survival and offer the best outcomes for patients with metastatic RCC.”

The median duration of treatment with sunitinib was 6.4 months, and with pazopanib, it was 6.7 months. Adverse events were responsible for discontinuation of treatment in 28.4% of patients on sunitinib and 22.1% of patients on pazopanib, with fatigue, diarrhea, nausea and vomiting as the most common toxicities in both groups.

Six authors declared honoraria, funding, expenses or consultancies with the pharmaceutical industry. Two authors had no conflicts of interest to declare.

SOURCE: Velho PI et al. J Glob Oncol. 2018 Sep 10. doi: 10.1200/JGO.18.00073.

The use of tyrosine kinase inhibitors (TKIs) sunitinib and pazopanib to treat metastatic clear cell renal cell carcinoma (RCC) is feasible and effective in Brazil, even though limitations of the public health system mean not all patients have access to these or other therapies, researchers wrote.

In a retrospective analysis of 222 patients with advanced clear cell RCC who were treated with either sunitinib (n = 109) or pazopanib (n = 113), overall survival was 15.2 months with sunitinib and 14.2 months with pazopanib, investigators reported in the Journal of Global Oncology.

Overall survival rates, based on Memorial Sloan Kettering Cancer Center risk categories, were 32.9 months for patients with low risk disease, 15.9 months for intermediate risk patients, and 8.1 months for patient with poor risk – which constituted 29% of the patient population.

Pedro I. Velho, MD, of Johns Hopkins University, Baltimore, and his coauthors noted that these survival rates were lower than those seen in phase 3 trials in the same population.

They suggested this could be caused by the fact that the patients in this real-world study had worse baseline prognoses than those seen in previous clinical trials.

However, they also pointed out that, in the Brazilian public health system, there was no standard systemic treatment option outside clinical trials for patients who have progressed on a TKI as a first-line treatment. Only around half the patients in this study (101) would have been eligible for participation in a clinical trial.

“In our opinion, it is crucial to extend the access to these TKIs for the Brazilian population and also patients in other countries with limited access to targeted therapies,” the authors wrote.

However, the 14 patients who were eligible for treatment with nivolumab under a compassionate use program showed a significantly better overall survival rate, compared with patients who did not have access to a second-line therapy (36.7 months vs. 13.6 months; P less than .001).

“Also, it is imperative to provide systemic sequential treatment options for this population as an attempt to improve survival and offer the best outcomes for patients with metastatic RCC.”

The median duration of treatment with sunitinib was 6.4 months, and with pazopanib, it was 6.7 months. Adverse events were responsible for discontinuation of treatment in 28.4% of patients on sunitinib and 22.1% of patients on pazopanib, with fatigue, diarrhea, nausea and vomiting as the most common toxicities in both groups.

Six authors declared honoraria, funding, expenses or consultancies with the pharmaceutical industry. Two authors had no conflicts of interest to declare.

SOURCE: Velho PI et al. J Glob Oncol. 2018 Sep 10. doi: 10.1200/JGO.18.00073.

The use of tyrosine kinase inhibitors (TKIs) sunitinib and pazopanib to treat metastatic clear cell renal cell carcinoma (RCC) is feasible and effective in Brazil, even though limitations of the public health system mean not all patients have access to these or other therapies, researchers wrote.

In a retrospective analysis of 222 patients with advanced clear cell RCC who were treated with either sunitinib (n = 109) or pazopanib (n = 113), overall survival was 15.2 months with sunitinib and 14.2 months with pazopanib, investigators reported in the Journal of Global Oncology.

Overall survival rates, based on Memorial Sloan Kettering Cancer Center risk categories, were 32.9 months for patients with low risk disease, 15.9 months for intermediate risk patients, and 8.1 months for patient with poor risk – which constituted 29% of the patient population.

Pedro I. Velho, MD, of Johns Hopkins University, Baltimore, and his coauthors noted that these survival rates were lower than those seen in phase 3 trials in the same population.

They suggested this could be caused by the fact that the patients in this real-world study had worse baseline prognoses than those seen in previous clinical trials.

However, they also pointed out that, in the Brazilian public health system, there was no standard systemic treatment option outside clinical trials for patients who have progressed on a TKI as a first-line treatment. Only around half the patients in this study (101) would have been eligible for participation in a clinical trial.

“In our opinion, it is crucial to extend the access to these TKIs for the Brazilian population and also patients in other countries with limited access to targeted therapies,” the authors wrote.

However, the 14 patients who were eligible for treatment with nivolumab under a compassionate use program showed a significantly better overall survival rate, compared with patients who did not have access to a second-line therapy (36.7 months vs. 13.6 months; P less than .001).

“Also, it is imperative to provide systemic sequential treatment options for this population as an attempt to improve survival and offer the best outcomes for patients with metastatic RCC.”

The median duration of treatment with sunitinib was 6.4 months, and with pazopanib, it was 6.7 months. Adverse events were responsible for discontinuation of treatment in 28.4% of patients on sunitinib and 22.1% of patients on pazopanib, with fatigue, diarrhea, nausea and vomiting as the most common toxicities in both groups.

Six authors declared honoraria, funding, expenses or consultancies with the pharmaceutical industry. Two authors had no conflicts of interest to declare.

SOURCE: Velho PI et al. J Glob Oncol. 2018 Sep 10. doi: 10.1200/JGO.18.00073.

The combination of a targeted antiangiogenic agent and denosumab (Xgeva) appears to significantly increase the risk for osteonecrosis of the jaw in patients with metastatic renal cell carcinoma (mRCC), French investigators cautioned.

Among 41 patients with RCC metastatic to bone treated with an antiangiogenic agent and denosumab, 7 (17%) developed osteonecrosis of the jaw (ONJ). All seven received the combination in the first line, reported Aline Guillot, MD, from the Institut de cancérologie Lucien Neuwirth in Saint-Priest-en-Jarez, France, and her colleagues.

“The incidence of ONJ was high in this real-life population of patients with mRCC treated with antiangiogenic therapies combined with denosumab. This toxicity signal should warn physicians about this combination in the mRCC population,” they wrote in Clinical Genitourinary Cancer.

Previous studies have shown that the combination of another bone-targeted therapy – zoledronic acid – with antiangiogenic tyrosine kinase inhibitors (TKIs) such as sunitinib (Sutent) is associated with increased risk for ONJ. In addition, ONJ with the combination of denosumab and antiangiogenic therapies “has been noticed but never estimated,” the authors noted.

To evaluate the incidence of hypocalcemia and ONJ in patients with RCC metastatic to bone treated with denosumab and a TKI or mammalian target of rapamycin inhibitor, the investigators gathered data retrospectively from 10 French centers.

They identified 25 men and 16 women with a median age of 62 years (range, 54-68 years). Of this group, 40 received denosumab in the first line in combination with either sunitinib (31 patients), pazopanib (6), everolimus (Afinitor and generics; 2), and temsirolimus (Torisel and generics; 1). The median duration of first-line therapy was 12 months.

Denosumab was given in the second line with axitinib (Inlyta) to nine patients, with everolimus to nine, and with sunitinib to three patients. The median duration of second-line therapy was 3 months.

Skeletal-related events occurred in 41% of patients prior to receiving denosumab and in 61% (25 patients) after denosumab. The events included clinical fracture, bone pain requiring radiation, and spinal compression.

Of the seven patients who developed ONJ, six received denosumab and sunitinib in the first line and one received denosumab plus temsirolimus, with a median duration of treatment of 11.8 months. Three of these patients also received denosumab in the second line with either axitinib, everolimus, or sunitinib, with a median duration of 9.8 months. Data on second-line therapy for the remaining four patients with ONJ were not available.

The investigators noted that the 17% incidence of ONJ was higher than the 10% rate seen in a study of patients with mRCC treated with a TKI and a bisphosphonate (Acta Clin Belg. 2018 Apr;73(2):100-9), and the 1.8% incidence seen in an analysis of three phase 3 trials in cancer patients with bone metastases (Ann Oncol. 2012 May;23(5):1341-7).

Although the etiology of ONJ is unknown, patient education and oral hygiene may reduce the risk in patients treated with denosumab and a TKI.

“The benefit of denosumab in this setting in regard [to] toxicity needs to be demonstrated in a prospective trial,” they wrote.

No conflicts of interest or disclosures were reported.

SOURCE: Guillot A et al. Clin Genitourin Cancer. 2018 Sep 6. doi: 10.1016/j.clgc.2018.08.006.

The combination of a targeted antiangiogenic agent and denosumab (Xgeva) appears to significantly increase the risk for osteonecrosis of the jaw in patients with metastatic renal cell carcinoma (mRCC), French investigators cautioned.

Among 41 patients with RCC metastatic to bone treated with an antiangiogenic agent and denosumab, 7 (17%) developed osteonecrosis of the jaw (ONJ). All seven received the combination in the first line, reported Aline Guillot, MD, from the Institut de cancérologie Lucien Neuwirth in Saint-Priest-en-Jarez, France, and her colleagues.

“The incidence of ONJ was high in this real-life population of patients with mRCC treated with antiangiogenic therapies combined with denosumab. This toxicity signal should warn physicians about this combination in the mRCC population,” they wrote in Clinical Genitourinary Cancer.

Previous studies have shown that the combination of another bone-targeted therapy – zoledronic acid – with antiangiogenic tyrosine kinase inhibitors (TKIs) such as sunitinib (Sutent) is associated with increased risk for ONJ. In addition, ONJ with the combination of denosumab and antiangiogenic therapies “has been noticed but never estimated,” the authors noted.

To evaluate the incidence of hypocalcemia and ONJ in patients with RCC metastatic to bone treated with denosumab and a TKI or mammalian target of rapamycin inhibitor, the investigators gathered data retrospectively from 10 French centers.

They identified 25 men and 16 women with a median age of 62 years (range, 54-68 years). Of this group, 40 received denosumab in the first line in combination with either sunitinib (31 patients), pazopanib (6), everolimus (Afinitor and generics; 2), and temsirolimus (Torisel and generics; 1). The median duration of first-line therapy was 12 months.

Denosumab was given in the second line with axitinib (Inlyta) to nine patients, with everolimus to nine, and with sunitinib to three patients. The median duration of second-line therapy was 3 months.

Skeletal-related events occurred in 41% of patients prior to receiving denosumab and in 61% (25 patients) after denosumab. The events included clinical fracture, bone pain requiring radiation, and spinal compression.

Of the seven patients who developed ONJ, six received denosumab and sunitinib in the first line and one received denosumab plus temsirolimus, with a median duration of treatment of 11.8 months. Three of these patients also received denosumab in the second line with either axitinib, everolimus, or sunitinib, with a median duration of 9.8 months. Data on second-line therapy for the remaining four patients with ONJ were not available.

The investigators noted that the 17% incidence of ONJ was higher than the 10% rate seen in a study of patients with mRCC treated with a TKI and a bisphosphonate (Acta Clin Belg. 2018 Apr;73(2):100-9), and the 1.8% incidence seen in an analysis of three phase 3 trials in cancer patients with bone metastases (Ann Oncol. 2012 May;23(5):1341-7).

Although the etiology of ONJ is unknown, patient education and oral hygiene may reduce the risk in patients treated with denosumab and a TKI.

“The benefit of denosumab in this setting in regard [to] toxicity needs to be demonstrated in a prospective trial,” they wrote.

No conflicts of interest or disclosures were reported.

SOURCE: Guillot A et al. Clin Genitourin Cancer. 2018 Sep 6. doi: 10.1016/j.clgc.2018.08.006.

The combination of a targeted antiangiogenic agent and denosumab (Xgeva) appears to significantly increase the risk for osteonecrosis of the jaw in patients with metastatic renal cell carcinoma (mRCC), French investigators cautioned.

Among 41 patients with RCC metastatic to bone treated with an antiangiogenic agent and denosumab, 7 (17%) developed osteonecrosis of the jaw (ONJ). All seven received the combination in the first line, reported Aline Guillot, MD, from the Institut de cancérologie Lucien Neuwirth in Saint-Priest-en-Jarez, France, and her colleagues.

“The incidence of ONJ was high in this real-life population of patients with mRCC treated with antiangiogenic therapies combined with denosumab. This toxicity signal should warn physicians about this combination in the mRCC population,” they wrote in Clinical Genitourinary Cancer.

Previous studies have shown that the combination of another bone-targeted therapy – zoledronic acid – with antiangiogenic tyrosine kinase inhibitors (TKIs) such as sunitinib (Sutent) is associated with increased risk for ONJ. In addition, ONJ with the combination of denosumab and antiangiogenic therapies “has been noticed but never estimated,” the authors noted.

To evaluate the incidence of hypocalcemia and ONJ in patients with RCC metastatic to bone treated with denosumab and a TKI or mammalian target of rapamycin inhibitor, the investigators gathered data retrospectively from 10 French centers.

They identified 25 men and 16 women with a median age of 62 years (range, 54-68 years). Of this group, 40 received denosumab in the first line in combination with either sunitinib (31 patients), pazopanib (6), everolimus (Afinitor and generics; 2), and temsirolimus (Torisel and generics; 1). The median duration of first-line therapy was 12 months.

Denosumab was given in the second line with axitinib (Inlyta) to nine patients, with everolimus to nine, and with sunitinib to three patients. The median duration of second-line therapy was 3 months.

Skeletal-related events occurred in 41% of patients prior to receiving denosumab and in 61% (25 patients) after denosumab. The events included clinical fracture, bone pain requiring radiation, and spinal compression.

Of the seven patients who developed ONJ, six received denosumab and sunitinib in the first line and one received denosumab plus temsirolimus, with a median duration of treatment of 11.8 months. Three of these patients also received denosumab in the second line with either axitinib, everolimus, or sunitinib, with a median duration of 9.8 months. Data on second-line therapy for the remaining four patients with ONJ were not available.

The investigators noted that the 17% incidence of ONJ was higher than the 10% rate seen in a study of patients with mRCC treated with a TKI and a bisphosphonate (Acta Clin Belg. 2018 Apr;73(2):100-9), and the 1.8% incidence seen in an analysis of three phase 3 trials in cancer patients with bone metastases (Ann Oncol. 2012 May;23(5):1341-7).

Although the etiology of ONJ is unknown, patient education and oral hygiene may reduce the risk in patients treated with denosumab and a TKI.

“The benefit of denosumab in this setting in regard [to] toxicity needs to be demonstrated in a prospective trial,” they wrote.

No conflicts of interest or disclosures were reported.

SOURCE: Guillot A et al. Clin Genitourin Cancer. 2018 Sep 6. doi: 10.1016/j.clgc.2018.08.006.