Smiling baby

Photo by Petr Kratochvil

Giving very preterm infants high-dose recombinant human erythropoietin (EPO) at birth does not improve neurodevelopmental outcomes at 2 years, according to a study published in JAMA.

Researchers found no significant differences between infants who received EPO and those who did not when it came to cognitive development, motor development, cerebral palsy, hearing or visual impairment, and anthropometric growth parameters.

Giancarlo Natalucci, MD, of the University of Zurich in Switzerland, and his colleagues conducted this study in 448 preterm infants who were born between 26 weeks’ gestation and 31 weeks 6 days’ gestation.

The subjects’ average gestational age was 29 weeks, and their average birth weight was 1210 g (2.7 lbs).

The infants were randomized to receive high-dose EPO (n=228) or placebo (saline, n=220) intravenously within 3 hours of birth, at 12 to 18 hours, and at 36 to 42 hours after birth.

Neurodevelopmental outcome data were available for 81% of the infants (n=365) at an average age of 23.6 months.

Cognitive development, as assessed with the Mental Development Index (MDI), was not significantly different between the EPO group and the placebo group. In an intent-to-treat analysis, the mean MDI was 93.5 in the EPO group and 94.5 in the placebo group (P=0.056). In the per-protocol analysis, the mean MDI was 93.9 and 94.5, respectively (P=0.70).

The researchers also found no significant differences between the treatment groups for secondary outcomes such as motor development, cerebral palsy, hearing or visual impairment, and anthropometric growth parameters.

The team assessed motor development using the psychomotor development index (PDI). In the intent-to-treat analysis, the mean PDI was 89.5 in the EPO group and 92.1 in the placebo group (P=0.15). In the per-protocol analysis, the mean PDI was 89.2 and 92.8, respectively (P=0.06).

In the intent-to-treat analysis, the incidence of cerebral palsy was 4% in the EPO group and 5% in the placebo group (P>0.99). In the per-protocol analysis, it was 5% for both groups (P=0.41).

In the intent-to-treat analysis, severe hearing impairment occurred in 1 EPO-treated patient and no placebo-treated patients (P>0.99). Severe visual impairment occurred in 2 and 0, respectively (P=0.50). The incidences were the same in the per-protocol analysis.

And there were no significant differences between the treatment groups (per-protocol or intent-to-treat) when it came to growth parameters such as head circumference, weight, or length.

The researchers said these results suggest that EPO may not have a neuroprotective role in very preterm infants, but follow-up is required to assess cognitive and physical problems that may not become evident until later in life.

Smiling baby

Photo by Petr Kratochvil

Giving very preterm infants high-dose recombinant human erythropoietin (EPO) at birth does not improve neurodevelopmental outcomes at 2 years, according to a study published in JAMA.

Researchers found no significant differences between infants who received EPO and those who did not when it came to cognitive development, motor development, cerebral palsy, hearing or visual impairment, and anthropometric growth parameters.

Giancarlo Natalucci, MD, of the University of Zurich in Switzerland, and his colleagues conducted this study in 448 preterm infants who were born between 26 weeks’ gestation and 31 weeks 6 days’ gestation.

The subjects’ average gestational age was 29 weeks, and their average birth weight was 1210 g (2.7 lbs).

The infants were randomized to receive high-dose EPO (n=228) or placebo (saline, n=220) intravenously within 3 hours of birth, at 12 to 18 hours, and at 36 to 42 hours after birth.

Neurodevelopmental outcome data were available for 81% of the infants (n=365) at an average age of 23.6 months.

Cognitive development, as assessed with the Mental Development Index (MDI), was not significantly different between the EPO group and the placebo group. In an intent-to-treat analysis, the mean MDI was 93.5 in the EPO group and 94.5 in the placebo group (P=0.056). In the per-protocol analysis, the mean MDI was 93.9 and 94.5, respectively (P=0.70).

The researchers also found no significant differences between the treatment groups for secondary outcomes such as motor development, cerebral palsy, hearing or visual impairment, and anthropometric growth parameters.

The team assessed motor development using the psychomotor development index (PDI). In the intent-to-treat analysis, the mean PDI was 89.5 in the EPO group and 92.1 in the placebo group (P=0.15). In the per-protocol analysis, the mean PDI was 89.2 and 92.8, respectively (P=0.06).

In the intent-to-treat analysis, the incidence of cerebral palsy was 4% in the EPO group and 5% in the placebo group (P>0.99). In the per-protocol analysis, it was 5% for both groups (P=0.41).

In the intent-to-treat analysis, severe hearing impairment occurred in 1 EPO-treated patient and no placebo-treated patients (P>0.99). Severe visual impairment occurred in 2 and 0, respectively (P=0.50). The incidences were the same in the per-protocol analysis.

And there were no significant differences between the treatment groups (per-protocol or intent-to-treat) when it came to growth parameters such as head circumference, weight, or length.

The researchers said these results suggest that EPO may not have a neuroprotective role in very preterm infants, but follow-up is required to assess cognitive and physical problems that may not become evident until later in life.

Smiling baby

Photo by Petr Kratochvil

Giving very preterm infants high-dose recombinant human erythropoietin (EPO) at birth does not improve neurodevelopmental outcomes at 2 years, according to a study published in JAMA.

Researchers found no significant differences between infants who received EPO and those who did not when it came to cognitive development, motor development, cerebral palsy, hearing or visual impairment, and anthropometric growth parameters.

Giancarlo Natalucci, MD, of the University of Zurich in Switzerland, and his colleagues conducted this study in 448 preterm infants who were born between 26 weeks’ gestation and 31 weeks 6 days’ gestation.

The subjects’ average gestational age was 29 weeks, and their average birth weight was 1210 g (2.7 lbs).

The infants were randomized to receive high-dose EPO (n=228) or placebo (saline, n=220) intravenously within 3 hours of birth, at 12 to 18 hours, and at 36 to 42 hours after birth.

Neurodevelopmental outcome data were available for 81% of the infants (n=365) at an average age of 23.6 months.

Cognitive development, as assessed with the Mental Development Index (MDI), was not significantly different between the EPO group and the placebo group. In an intent-to-treat analysis, the mean MDI was 93.5 in the EPO group and 94.5 in the placebo group (P=0.056). In the per-protocol analysis, the mean MDI was 93.9 and 94.5, respectively (P=0.70).

The researchers also found no significant differences between the treatment groups for secondary outcomes such as motor development, cerebral palsy, hearing or visual impairment, and anthropometric growth parameters.

The team assessed motor development using the psychomotor development index (PDI). In the intent-to-treat analysis, the mean PDI was 89.5 in the EPO group and 92.1 in the placebo group (P=0.15). In the per-protocol analysis, the mean PDI was 89.2 and 92.8, respectively (P=0.06).

In the intent-to-treat analysis, the incidence of cerebral palsy was 4% in the EPO group and 5% in the placebo group (P>0.99). In the per-protocol analysis, it was 5% for both groups (P=0.41).

In the intent-to-treat analysis, severe hearing impairment occurred in 1 EPO-treated patient and no placebo-treated patients (P>0.99). Severe visual impairment occurred in 2 and 0, respectively (P=0.50). The incidences were the same in the per-protocol analysis.

And there were no significant differences between the treatment groups (per-protocol or intent-to-treat) when it came to growth parameters such as head circumference, weight, or length.

The researchers said these results suggest that EPO may not have a neuroprotective role in very preterm infants, but follow-up is required to assess cognitive and physical problems that may not become evident until later in life.

Lab mice

Photo by Aaron Logan

Researchers say they have discovered a method for expanding natural killer T cells (NKTs) that ensures their persistence, thereby making NKTs more attractive as chimeric antigen receptor (CAR) carriers for cancer immunotherapy.

When transduced with a CD19-specific CAR, the researchers’ persistent NKTs produced sustained tumor regression in a mouse model of B-cell lymphoma.

The team described this work in the Journal of Clinical Investigation.

“NKT technology is quite powerful and offers a significant potential for treatment of cancer,” said study author Leonid Metelitsa, MD, PhD, of Baylor College of Medicine in Houston, Texas.

“But for it to be most effective, we have to find the best way to expand the cells ex vivo while preserving their ability to persist once delivered back to patients. If they can persist in the body for a long time, they have much longer therapeutic activity, and this is essential for fighting cancer.”

Molecule affects persistence

The researchers noted that central memory T cells are known for their ability to proliferate and persist, and these cells are characterized by expression of the surface molecule CD62L.

In this study, the team found that NKT cells freshly derived from blood did not express CD62L, or it was expressed at a very low level. However, after the researchers expanded NKT cells, they found that CD62L was expressed at higher levels.

“We consistently identified a subset of cells present at very high numbers after the first 12 days of expansion, and critical to this subset of cells was the presence of CD62L,” Dr Metelitsa said. “In fact, they became the majority of the new cells.”

In addition, Dr Metelitsa said that CD62L-positive NKT cells were responsible for further propagation of NKTs in culture, which is important for achieving large numbers of cells. However, extensive culture led to the eventual decline of CD62L expression in NKTs.

To test the role of CD62L in NKT-cell persistence, the researchers delivered CD62L-positive and CD62L-negative NKTs to immune-deficient NSG mice. They found that CD62L-positive NKTs persisted 5 times longer than CD62L-negative NKTs.

CAR-NKTs fight lymphoma

Next, the researchers transduced CD62L-positive and CD62L-negative NKTs with a CD19-specific CAR and delivered these cells to mice with B-cell lymphoma.

The team found that both CD62L-positve and CD62L-negative CAR-NKTs prolonged the survival of mice, when compared to controls (P<0.001).

However, only the CD62L-positive CAR-NKTs induced sustained tumor regression. Seven of 9 mice that received CD62L-positive CAR-NKTs lived, and 5 were tumor-free for at least 3 months. But all 10 mice that received CD62L-negative CAR-NKTs ultimately succumbed to tumor progression (P<0.001).

Costimulation improves NKTs/CAR-NKTs

The researchers then turned their focus to costimulation of NKTs in order to maintain the subset with a high percentage of CD62L-positive cells in prolonged culture. Costimulation involves the interaction of receptors on NKTs with activating molecules on an antigen-presenting cell to increase the NKTs’ immune functions.

“We have known that costimulation is an important part of immune response and immunotherapy, but, in this case, we did not know which costimulatory molecules would be important for the expansion and persistence of CD62L-positive NKT cells,” said Gengwen Tian, MD, of the Baylor College of Medicine.

After testing more than 100 combinations, the researchers discovered that combining an antigen-presenting molecule—CD1d—with 3 costimulatory molecules—CD86, 4-1BBL, and OX40L—induced prolonged persistence and better therapeutic activity of NKTs and CAR-NKTs in mouse models.

“When we developed an antigen-presenting cell clone that expressed CD1d with all of these costimulatory molecules at certain levels, NKT cells maintained a high percentage of CD62L even in a prolonged culture,” Dr Metelitsa said.

The researchers conducted in vivo testing of CAR-NKT cells that were expanded with the original method or with the costimulation method. And they found that costimulated cells had significantly higher therapeutic activity in mouse models of neuroblastoma and lymphoma.

“Our goal now is to optimize our NKT cell expansion protocol so that we can obtain FDA approval to initiate clinical trials,” Dr Metelitsa said.

Lab mice

Photo by Aaron Logan

Researchers say they have discovered a method for expanding natural killer T cells (NKTs) that ensures their persistence, thereby making NKTs more attractive as chimeric antigen receptor (CAR) carriers for cancer immunotherapy.

When transduced with a CD19-specific CAR, the researchers’ persistent NKTs produced sustained tumor regression in a mouse model of B-cell lymphoma.

The team described this work in the Journal of Clinical Investigation.

“NKT technology is quite powerful and offers a significant potential for treatment of cancer,” said study author Leonid Metelitsa, MD, PhD, of Baylor College of Medicine in Houston, Texas.

“But for it to be most effective, we have to find the best way to expand the cells ex vivo while preserving their ability to persist once delivered back to patients. If they can persist in the body for a long time, they have much longer therapeutic activity, and this is essential for fighting cancer.”

Molecule affects persistence

The researchers noted that central memory T cells are known for their ability to proliferate and persist, and these cells are characterized by expression of the surface molecule CD62L.

In this study, the team found that NKT cells freshly derived from blood did not express CD62L, or it was expressed at a very low level. However, after the researchers expanded NKT cells, they found that CD62L was expressed at higher levels.

“We consistently identified a subset of cells present at very high numbers after the first 12 days of expansion, and critical to this subset of cells was the presence of CD62L,” Dr Metelitsa said. “In fact, they became the majority of the new cells.”

In addition, Dr Metelitsa said that CD62L-positive NKT cells were responsible for further propagation of NKTs in culture, which is important for achieving large numbers of cells. However, extensive culture led to the eventual decline of CD62L expression in NKTs.

To test the role of CD62L in NKT-cell persistence, the researchers delivered CD62L-positive and CD62L-negative NKTs to immune-deficient NSG mice. They found that CD62L-positive NKTs persisted 5 times longer than CD62L-negative NKTs.

CAR-NKTs fight lymphoma

Next, the researchers transduced CD62L-positive and CD62L-negative NKTs with a CD19-specific CAR and delivered these cells to mice with B-cell lymphoma.

The team found that both CD62L-positve and CD62L-negative CAR-NKTs prolonged the survival of mice, when compared to controls (P<0.001).

However, only the CD62L-positive CAR-NKTs induced sustained tumor regression. Seven of 9 mice that received CD62L-positive CAR-NKTs lived, and 5 were tumor-free for at least 3 months. But all 10 mice that received CD62L-negative CAR-NKTs ultimately succumbed to tumor progression (P<0.001).

Costimulation improves NKTs/CAR-NKTs

The researchers then turned their focus to costimulation of NKTs in order to maintain the subset with a high percentage of CD62L-positive cells in prolonged culture. Costimulation involves the interaction of receptors on NKTs with activating molecules on an antigen-presenting cell to increase the NKTs’ immune functions.

“We have known that costimulation is an important part of immune response and immunotherapy, but, in this case, we did not know which costimulatory molecules would be important for the expansion and persistence of CD62L-positive NKT cells,” said Gengwen Tian, MD, of the Baylor College of Medicine.

After testing more than 100 combinations, the researchers discovered that combining an antigen-presenting molecule—CD1d—with 3 costimulatory molecules—CD86, 4-1BBL, and OX40L—induced prolonged persistence and better therapeutic activity of NKTs and CAR-NKTs in mouse models.

“When we developed an antigen-presenting cell clone that expressed CD1d with all of these costimulatory molecules at certain levels, NKT cells maintained a high percentage of CD62L even in a prolonged culture,” Dr Metelitsa said.

The researchers conducted in vivo testing of CAR-NKT cells that were expanded with the original method or with the costimulation method. And they found that costimulated cells had significantly higher therapeutic activity in mouse models of neuroblastoma and lymphoma.

“Our goal now is to optimize our NKT cell expansion protocol so that we can obtain FDA approval to initiate clinical trials,” Dr Metelitsa said.

Lab mice

Photo by Aaron Logan

Researchers say they have discovered a method for expanding natural killer T cells (NKTs) that ensures their persistence, thereby making NKTs more attractive as chimeric antigen receptor (CAR) carriers for cancer immunotherapy.

When transduced with a CD19-specific CAR, the researchers’ persistent NKTs produced sustained tumor regression in a mouse model of B-cell lymphoma.

The team described this work in the Journal of Clinical Investigation.

“NKT technology is quite powerful and offers a significant potential for treatment of cancer,” said study author Leonid Metelitsa, MD, PhD, of Baylor College of Medicine in Houston, Texas.

“But for it to be most effective, we have to find the best way to expand the cells ex vivo while preserving their ability to persist once delivered back to patients. If they can persist in the body for a long time, they have much longer therapeutic activity, and this is essential for fighting cancer.”

Molecule affects persistence

The researchers noted that central memory T cells are known for their ability to proliferate and persist, and these cells are characterized by expression of the surface molecule CD62L.

In this study, the team found that NKT cells freshly derived from blood did not express CD62L, or it was expressed at a very low level. However, after the researchers expanded NKT cells, they found that CD62L was expressed at higher levels.

“We consistently identified a subset of cells present at very high numbers after the first 12 days of expansion, and critical to this subset of cells was the presence of CD62L,” Dr Metelitsa said. “In fact, they became the majority of the new cells.”

In addition, Dr Metelitsa said that CD62L-positive NKT cells were responsible for further propagation of NKTs in culture, which is important for achieving large numbers of cells. However, extensive culture led to the eventual decline of CD62L expression in NKTs.

To test the role of CD62L in NKT-cell persistence, the researchers delivered CD62L-positive and CD62L-negative NKTs to immune-deficient NSG mice. They found that CD62L-positive NKTs persisted 5 times longer than CD62L-negative NKTs.

CAR-NKTs fight lymphoma

Next, the researchers transduced CD62L-positive and CD62L-negative NKTs with a CD19-specific CAR and delivered these cells to mice with B-cell lymphoma.

The team found that both CD62L-positve and CD62L-negative CAR-NKTs prolonged the survival of mice, when compared to controls (P<0.001).

However, only the CD62L-positive CAR-NKTs induced sustained tumor regression. Seven of 9 mice that received CD62L-positive CAR-NKTs lived, and 5 were tumor-free for at least 3 months. But all 10 mice that received CD62L-negative CAR-NKTs ultimately succumbed to tumor progression (P<0.001).

Costimulation improves NKTs/CAR-NKTs

The researchers then turned their focus to costimulation of NKTs in order to maintain the subset with a high percentage of CD62L-positive cells in prolonged culture. Costimulation involves the interaction of receptors on NKTs with activating molecules on an antigen-presenting cell to increase the NKTs’ immune functions.

“We have known that costimulation is an important part of immune response and immunotherapy, but, in this case, we did not know which costimulatory molecules would be important for the expansion and persistence of CD62L-positive NKT cells,” said Gengwen Tian, MD, of the Baylor College of Medicine.

After testing more than 100 combinations, the researchers discovered that combining an antigen-presenting molecule—CD1d—with 3 costimulatory molecules—CD86, 4-1BBL, and OX40L—induced prolonged persistence and better therapeutic activity of NKTs and CAR-NKTs in mouse models.

“When we developed an antigen-presenting cell clone that expressed CD1d with all of these costimulatory molecules at certain levels, NKT cells maintained a high percentage of CD62L even in a prolonged culture,” Dr Metelitsa said.

The researchers conducted in vivo testing of CAR-NKT cells that were expanded with the original method or with the costimulation method. And they found that costimulated cells had significantly higher therapeutic activity in mouse models of neuroblastoma and lymphoma.

“Our goal now is to optimize our NKT cell expansion protocol so that we can obtain FDA approval to initiate clinical trials,” Dr Metelitsa said.

HIV budding from a

cultured lymphocyte

Image courtesy of the CDC

A new study suggests that cancer patients with HIV are less likely to receive cancer treatment, regardless of insurance status and comorbidities.

Patients with HIV were less likely than their HIV-free peers to receive treatment for Hodgkin lymphoma, diffuse large B-cell lymphoma, and 7 solid tumor malignancies.

Gita Suneja, MD, of the University of Utah in Salt Lake City, and her colleagues reported these findings in Cancer.

The team used the National Cancer Data Base to study non-elderly US adults diagnosed with 10 common cancers from 2003 to 2011. There were a total of 10,265 HIV-infected patients and 2,219,232 HIV-free patients.

The researchers examined associations between HIV status and lack of cancer treatment, taking into account insurance status and comorbidities.

The results showed a lack of treatment among HIV patients for all of the cancers studied except anal cancer (relative risk [RR]=1.20, P=0.333).

So HIV-infected patients were more likely to lack cancer treatment for:

• Hodgkin lymphoma (RR=1.92, P<0.001)
• Diffuse large B-cell lymphoma (RR=1.82, P<0.001)
• Head and neck cancer (RR=1.48, P=0.013)
• Upper gastrointestinal tract cancer (RR=2.62, P<0.001)
• Colorectal cancer (RR=1.70, P=0.006)
• Lung cancer (RR=2.46, P<0.001)
• Breast cancer (RR=2.14, P=0.015)
• Cervical cancer (RR=2.81, P<0.001)
• Prostate cancer (RR=2.16, P<0.001).

The researchers said factors that predicted a lack of cancer treatment among HIV-infected individuals varied between those with solid tumors and those with lymphomas.

Advanced stage at the time of cancer diagnosis (stage IV vs stage I) meant HIV patients with solid tumors were less likely to receive cancer treatment, but lymphoma patients were more likely to receive cancer treatment.

Having a higher modified Charlson-Deyo comorbidity score (1 or 2+ vs 0) predicted a lack of cancer treatment for HIV-infected patients with lymphoma but not those with solid tumors.

And older age (45-64 vs 18-44) was associated with a lack of treatment for HIV-infected patients regardless of cancer type, but this was only significant for lymphoma patients.

For the entire cohort, black race (vs white) and a lack of private insurance (Medicaid, Medicare, uninsured, or unknown insurance status) were significant predictors for a lack of cancer treatment among HIV patients.

Still, the researchers noted that, even among privately insured patients, HIV-infected individuals were less likely to receive cancer treatment.

Dr Suneja and her colleagues said several factors may contribute to these findings. For one, HIV-infected patients have historically been excluded from cancer clinical trials, thereby limiting the applicability of trial results for this population.

In addition, cancer treatment guidelines specific to HIV-infected patients are not available for most cancer types. And clinicians may lack experience treating HIV-infected patients with cancer.

Furthermore, the psychosocial and economic challenges associated with the dual management of cancer and HIV treatment may make adherence to treatment a challenge.

HIV budding from a

cultured lymphocyte

Image courtesy of the CDC

A new study suggests that cancer patients with HIV are less likely to receive cancer treatment, regardless of insurance status and comorbidities.

Patients with HIV were less likely than their HIV-free peers to receive treatment for Hodgkin lymphoma, diffuse large B-cell lymphoma, and 7 solid tumor malignancies.

Gita Suneja, MD, of the University of Utah in Salt Lake City, and her colleagues reported these findings in Cancer.

The team used the National Cancer Data Base to study non-elderly US adults diagnosed with 10 common cancers from 2003 to 2011. There were a total of 10,265 HIV-infected patients and 2,219,232 HIV-free patients.

The researchers examined associations between HIV status and lack of cancer treatment, taking into account insurance status and comorbidities.

The results showed a lack of treatment among HIV patients for all of the cancers studied except anal cancer (relative risk [RR]=1.20, P=0.333).

So HIV-infected patients were more likely to lack cancer treatment for:

• Hodgkin lymphoma (RR=1.92, P<0.001)
• Diffuse large B-cell lymphoma (RR=1.82, P<0.001)
• Head and neck cancer (RR=1.48, P=0.013)
• Upper gastrointestinal tract cancer (RR=2.62, P<0.001)
• Colorectal cancer (RR=1.70, P=0.006)
• Lung cancer (RR=2.46, P<0.001)
• Breast cancer (RR=2.14, P=0.015)
• Cervical cancer (RR=2.81, P<0.001)
• Prostate cancer (RR=2.16, P<0.001).

The researchers said factors that predicted a lack of cancer treatment among HIV-infected individuals varied between those with solid tumors and those with lymphomas.

Advanced stage at the time of cancer diagnosis (stage IV vs stage I) meant HIV patients with solid tumors were less likely to receive cancer treatment, but lymphoma patients were more likely to receive cancer treatment.

Having a higher modified Charlson-Deyo comorbidity score (1 or 2+ vs 0) predicted a lack of cancer treatment for HIV-infected patients with lymphoma but not those with solid tumors.

And older age (45-64 vs 18-44) was associated with a lack of treatment for HIV-infected patients regardless of cancer type, but this was only significant for lymphoma patients.

For the entire cohort, black race (vs white) and a lack of private insurance (Medicaid, Medicare, uninsured, or unknown insurance status) were significant predictors for a lack of cancer treatment among HIV patients.

Still, the researchers noted that, even among privately insured patients, HIV-infected individuals were less likely to receive cancer treatment.

Dr Suneja and her colleagues said several factors may contribute to these findings. For one, HIV-infected patients have historically been excluded from cancer clinical trials, thereby limiting the applicability of trial results for this population.

In addition, cancer treatment guidelines specific to HIV-infected patients are not available for most cancer types. And clinicians may lack experience treating HIV-infected patients with cancer.

Furthermore, the psychosocial and economic challenges associated with the dual management of cancer and HIV treatment may make adherence to treatment a challenge.

HIV budding from a

cultured lymphocyte

Image courtesy of the CDC

A new study suggests that cancer patients with HIV are less likely to receive cancer treatment, regardless of insurance status and comorbidities.

Patients with HIV were less likely than their HIV-free peers to receive treatment for Hodgkin lymphoma, diffuse large B-cell lymphoma, and 7 solid tumor malignancies.

Gita Suneja, MD, of the University of Utah in Salt Lake City, and her colleagues reported these findings in Cancer.

The team used the National Cancer Data Base to study non-elderly US adults diagnosed with 10 common cancers from 2003 to 2011. There were a total of 10,265 HIV-infected patients and 2,219,232 HIV-free patients.

The researchers examined associations between HIV status and lack of cancer treatment, taking into account insurance status and comorbidities.

The results showed a lack of treatment among HIV patients for all of the cancers studied except anal cancer (relative risk [RR]=1.20, P=0.333).

So HIV-infected patients were more likely to lack cancer treatment for:

• Hodgkin lymphoma (RR=1.92, P<0.001)
• Diffuse large B-cell lymphoma (RR=1.82, P<0.001)
• Head and neck cancer (RR=1.48, P=0.013)
• Upper gastrointestinal tract cancer (RR=2.62, P<0.001)
• Colorectal cancer (RR=1.70, P=0.006)
• Lung cancer (RR=2.46, P<0.001)
• Breast cancer (RR=2.14, P=0.015)
• Cervical cancer (RR=2.81, P<0.001)
• Prostate cancer (RR=2.16, P<0.001).

The researchers said factors that predicted a lack of cancer treatment among HIV-infected individuals varied between those with solid tumors and those with lymphomas.

Advanced stage at the time of cancer diagnosis (stage IV vs stage I) meant HIV patients with solid tumors were less likely to receive cancer treatment, but lymphoma patients were more likely to receive cancer treatment.

Having a higher modified Charlson-Deyo comorbidity score (1 or 2+ vs 0) predicted a lack of cancer treatment for HIV-infected patients with lymphoma but not those with solid tumors.

And older age (45-64 vs 18-44) was associated with a lack of treatment for HIV-infected patients regardless of cancer type, but this was only significant for lymphoma patients.

For the entire cohort, black race (vs white) and a lack of private insurance (Medicaid, Medicare, uninsured, or unknown insurance status) were significant predictors for a lack of cancer treatment among HIV patients.

Still, the researchers noted that, even among privately insured patients, HIV-infected individuals were less likely to receive cancer treatment.

Dr Suneja and her colleagues said several factors may contribute to these findings. For one, HIV-infected patients have historically been excluded from cancer clinical trials, thereby limiting the applicability of trial results for this population.

In addition, cancer treatment guidelines specific to HIV-infected patients are not available for most cancer types. And clinicians may lack experience treating HIV-infected patients with cancer.

Furthermore, the psychosocial and economic challenges associated with the dual management of cancer and HIV treatment may make adherence to treatment a challenge.

Nivolumab (Opdivo)

Photo courtesy of Business Wire

The US Food and Drug Administration (FDA) has granted accelerated approval for the PD-1 inhibitor nivolumab (Opdivo) to treat classical Hodgkin lymphoma (cHL).

The drug is approved to treat patients with relapsed or refractory cHL who have received an autologous hematopoietic stem cell transplant (HSCT) and post-transplant brentuximab vedotin.

Nivolumab received accelerated approval because it has not yet shown a clinical benefit in these patients. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of nivolumab for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted nivolumab breakthrough therapy designation, priority review status, and orphan drug designation.

Dosing and precautions

The recommended dose and schedule of nivolumab for cHL patients is 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.

The FDA added a new “Warning and Precaution” to the label for nivolumab, regarding complications of allogeneic HSCT after nivolumab.

Transplant-related deaths have occurred. So the FDA said healthcare professionals should follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions.

The FDA has required the manufacturer of nivolumab, Bristol-Myers Squibb, to further study the safety of allogeneic HSCT after nivolumab.

Full prescribing information for the drug is available here.

Trials of nivolumab

The FDA granted nivolumab accelerated approval in cHL patients based on the results of 2 single-arm, multicenter trials—the phase 1 Checkmate 039 trial (presented at ICML last year) and the phase 2 CheckMate 205 trial (to be presented at ASCO 2016).

Efficacy

Thus far, researchers have evaluated the efficacy of nivolumab in 95 cHL patients from both trials. All of these patients previously received an autologous HSCT and post-transplant brentuximab vedotin. They received a median of 5 prior systemic regimens (range, 3 to 15).

The patients received a median of 17 doses of nivolumab (range, 3 to 48). The overall response rate was 65%, and the complete response rate was 7%.

The median time to response was 2.1 months (range, 0.7 to 5.7), and the estimated median duration of response was 8.7 months (range, 0+ to 23.1+).

Safety

Researchers evaluated the safety of nivolumab in 263 patients with relapsed or refractory cHL. Ninety-eight percent of these patients had received an autologous HSCT.  The patients received a median of 10 doses of nivolumab (range, 1 to 48) at the approved dose and schedule.

The most common (≥20%) adverse events (AEs) of any grade were fatigue, upper respiratory tract infection, cough, pyrexia, and diarrhea.

Additional common (≥10%) AEs included rash, pruritus, musculoskeletal pain, nausea, vomiting, abdominal pain, headache, peripheral neuropathy, arthralgia, dyspnea, infusion-related reactions, and hypothyroidism or thyroiditis.

Serious AEs were reported in 21% of patients. The most common, reported in 1% to 3% of patients, were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.

Nivolumab (Opdivo)

Photo courtesy of Business Wire

The US Food and Drug Administration (FDA) has granted accelerated approval for the PD-1 inhibitor nivolumab (Opdivo) to treat classical Hodgkin lymphoma (cHL).

The drug is approved to treat patients with relapsed or refractory cHL who have received an autologous hematopoietic stem cell transplant (HSCT) and post-transplant brentuximab vedotin.

Nivolumab received accelerated approval because it has not yet shown a clinical benefit in these patients. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of nivolumab for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted nivolumab breakthrough therapy designation, priority review status, and orphan drug designation.

Dosing and precautions

The recommended dose and schedule of nivolumab for cHL patients is 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.

The FDA added a new “Warning and Precaution” to the label for nivolumab, regarding complications of allogeneic HSCT after nivolumab.

Transplant-related deaths have occurred. So the FDA said healthcare professionals should follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions.

The FDA has required the manufacturer of nivolumab, Bristol-Myers Squibb, to further study the safety of allogeneic HSCT after nivolumab.

Full prescribing information for the drug is available here.

Trials of nivolumab

The FDA granted nivolumab accelerated approval in cHL patients based on the results of 2 single-arm, multicenter trials—the phase 1 Checkmate 039 trial (presented at ICML last year) and the phase 2 CheckMate 205 trial (to be presented at ASCO 2016).

Efficacy

Thus far, researchers have evaluated the efficacy of nivolumab in 95 cHL patients from both trials. All of these patients previously received an autologous HSCT and post-transplant brentuximab vedotin. They received a median of 5 prior systemic regimens (range, 3 to 15).

The patients received a median of 17 doses of nivolumab (range, 3 to 48). The overall response rate was 65%, and the complete response rate was 7%.

The median time to response was 2.1 months (range, 0.7 to 5.7), and the estimated median duration of response was 8.7 months (range, 0+ to 23.1+).

Safety

Researchers evaluated the safety of nivolumab in 263 patients with relapsed or refractory cHL. Ninety-eight percent of these patients had received an autologous HSCT.  The patients received a median of 10 doses of nivolumab (range, 1 to 48) at the approved dose and schedule.

The most common (≥20%) adverse events (AEs) of any grade were fatigue, upper respiratory tract infection, cough, pyrexia, and diarrhea.

Additional common (≥10%) AEs included rash, pruritus, musculoskeletal pain, nausea, vomiting, abdominal pain, headache, peripheral neuropathy, arthralgia, dyspnea, infusion-related reactions, and hypothyroidism or thyroiditis.

Serious AEs were reported in 21% of patients. The most common, reported in 1% to 3% of patients, were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.

Nivolumab (Opdivo)

Photo courtesy of Business Wire

The US Food and Drug Administration (FDA) has granted accelerated approval for the PD-1 inhibitor nivolumab (Opdivo) to treat classical Hodgkin lymphoma (cHL).

The drug is approved to treat patients with relapsed or refractory cHL who have received an autologous hematopoietic stem cell transplant (HSCT) and post-transplant brentuximab vedotin.

Nivolumab received accelerated approval because it has not yet shown a clinical benefit in these patients. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of nivolumab for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted nivolumab breakthrough therapy designation, priority review status, and orphan drug designation.

Dosing and precautions

The recommended dose and schedule of nivolumab for cHL patients is 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.

The FDA added a new “Warning and Precaution” to the label for nivolumab, regarding complications of allogeneic HSCT after nivolumab.

Transplant-related deaths have occurred. So the FDA said healthcare professionals should follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions.

The FDA has required the manufacturer of nivolumab, Bristol-Myers Squibb, to further study the safety of allogeneic HSCT after nivolumab.

Full prescribing information for the drug is available here.

Trials of nivolumab

The FDA granted nivolumab accelerated approval in cHL patients based on the results of 2 single-arm, multicenter trials—the phase 1 Checkmate 039 trial (presented at ICML last year) and the phase 2 CheckMate 205 trial (to be presented at ASCO 2016).

Efficacy

Thus far, researchers have evaluated the efficacy of nivolumab in 95 cHL patients from both trials. All of these patients previously received an autologous HSCT and post-transplant brentuximab vedotin. They received a median of 5 prior systemic regimens (range, 3 to 15).

The patients received a median of 17 doses of nivolumab (range, 3 to 48). The overall response rate was 65%, and the complete response rate was 7%.

The median time to response was 2.1 months (range, 0.7 to 5.7), and the estimated median duration of response was 8.7 months (range, 0+ to 23.1+).

Safety

Researchers evaluated the safety of nivolumab in 263 patients with relapsed or refractory cHL. Ninety-eight percent of these patients had received an autologous HSCT.  The patients received a median of 10 doses of nivolumab (range, 1 to 48) at the approved dose and schedule.

The most common (≥20%) adverse events (AEs) of any grade were fatigue, upper respiratory tract infection, cough, pyrexia, and diarrhea.

Additional common (≥10%) AEs included rash, pruritus, musculoskeletal pain, nausea, vomiting, abdominal pain, headache, peripheral neuropathy, arthralgia, dyspnea, infusion-related reactions, and hypothyroidism or thyroiditis.

Serious AEs were reported in 21% of patients. The most common, reported in 1% to 3% of patients, were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.

WASHINGTON – Physician organizations are calling on Congress to stop a proposed federal regulation that would test how Medicare pays for drugs administered in a physician’s office.

Subcommittee member Rep. Larry Bucshon (R-Ind.), a cardiothoracic surgeon, called the premise of the proposed rule – that physicians are making prescribing decisions based on the cost of drugs – “almost an insult to the medical profession.” He has introduced legislation, H.R. 5122, that would require the Centers for Medicare & Medicaid Services to rescind the proposed rule.

CMS argues in the proposed rule that the current payment formula – average sales price (ASP) plus 6% – incentivizes the use of expensive drugs over lower-cost alternatives. Therefore, the agency seeks to run a test – half of doctors would continue to receive ASP plus 6%, while others would receive ASP plus 2.5% and a flat fee of $16.80. The proposed rule also would test other value-based tools. At the May 17 hearing, physicians presented their concerns regarding the proposed rule.

“CMS has yet to produce any evidence indicating that physician prescribing patterns show any correlation to that of choosing higher priced drugs as opposed to appropriate therapeutic treatment for patients,” said Dr. Debra A. Patt, vice president of Texas Oncology. Dr. Patt testified on behalf of the American Society of Clinical Oncology, the Community Oncology Alliance, and the U.S. Oncology Network. “Additionally, there is no evidence that the payment changes contemplated by CMS’s model will improve the quality of care, or for that matter, ensure patients have access to the same level of care they are currently receiving.”Dr. Michael Schweitz, national advocacy chair of the Coalition of State Rheumatology Organizations (CSRO), cited CMS’s admission that this rule will likely have no impact on ASP.

“While we appreciate CMS’s attention to the topic of drug costs, we feel that this proposal is misguided,” Dr. Schweitz testified. “As CMS acknowledges in the rule, the proposed approach ‘does not directly address the manufacturer’s ASP, which is a more significant driver of drug expenditures than the add-on payment amount for Part B drugs.’ Given that a slash to the ASP add-on is unlikely to actually lower costs for patients ... and may jeopardize access, we have requested that CMS withdraw the model and we urge the committee to do the same.”

Dr. Patt also questioned ASP, noting that it is simply an average, and the prices actually paid by rural and small group providers could be higher than larger group and hospital practices – and that difference puts the smaller and rural practices at a potentially significant financial disadvantage.

“Average sales price is by its very nature an average,” Dr. Patt testified. “Some people will pay higher amounts for procurement and some people will pay lower amounts. Larger hospital systems and larger practices have the ability to have contracting arrangements where they purchase at a lower price. … Smaller practices disproportionately pay a higher amount.”

Small practices that are slated to receive ASP plus 2.5% and that flat fee “could be losing money on all of the drugs that they buy. It will be impossible for smaller practices in rural areas to be open,” she added, noting that such a situation could cause care to be shifted to hospital outpatient departments, raising costs as well as access issues. “Cutting provider reimbursement without addressing the ASP, the actual cost of the drug in the first place, is just the wrong approach,” Rep. Bucshon said.

According to the proposed rule, whether or not a practice is in the test or control group would be based on ZIP code. Dr. Patt also noted that if she were in a test ZIP code and a neighboring ZIP code was not, she might have to refer patients to that area still receiving ASP plus 6% and “not at my center.”

Witnesses at the hearing also condemned the way CMS devised the proposed tests. Unlike the recent work on the Medicare Access and CHIP Reauthorization Act regulations and more specialized programs like the Oncology Care Model, Dr. Schweitz and Dr. Patt both testified that CMS made no outreach to the provider community with regards to getting their input before issuing the proposed rule.

They also took exception to the scope of the proposed test, which covers 49 of the 50 states (Maryland is excluded) and provides no mechanism for physicians to opt out under the proposed rule.

“I do see this as an experiment, but we conduct clinical research at our cancer and patients have informed consent,” Dr Patt said.

Dr. Schweitz agreed. “When you look at the goals of this plan, initially it appeared that it was to direct a way to save costs. But in meeting with [the Center for Medicare & Medicaid Innovation], we were advised that this is budget neutral. … So the goal of the program is to collect information which makes it a study, a test. So if the goal is to collect information, and the patients are part of that process, they should be signing informed consent.”

Several physician organizations have called on CMS to withdraw the proposal.

“We are deeply concerned that because the new methodology will frequently not properly cover the cost of physician administration of infused drugs, they will be forced to stop offering patients the ability to receive infusion treatments,” the American College of Rheumatology wrote in comments submitted on the proposed rule. Likewise, CSRO “must oppose the Part B drug payment model as it suffers from serious procedural and substantive flaws that we believe render it unworkable – and it does nothing to actually address drug prices,” according its comments.

While the proposal has garnered backlash from several directions, rheumatologists are seeing it as particularly burdensome because of the high price of medications with very limited options to substitute for lower-cost alternatives.

“Although we certainly seek to control costs for patients and Medicare whenever possible, the proposed new methodology does not adequately consider the higher average cost many of our physicians have acquiring, handling, administering, and billing for drugs and biologics,” according to the comments submitted by the ACR.

Indeed, comments from CSRO point out that when factoring in budget sequestration, the actual reimbursement physicians are receiving is ASP plus 4.4%, and doctors are actually losing money on certain drug purchases.

Of additional concern is that the proposed rule does not address ASP itself.

“A far greater concern than the add-on percentage is the underlying ASP, and the steep, fast price increases that these medications show each quarter, according to comments from the CSRO.

From 2007 to 2016, first-quarter ASP for infliximab rose from $53.73 to $79.90; ASP for abatacept rose from $18.70 to $39.44, according to CSRO comments. “These ASP increases are unsustainable for both the Medicare program and its beneficiaries, and we would like to work with CMS to explore actual solutions to stem the increases in those underlying prices.”

In its comments, ACR proposed a number of potential paths forward, starting with certain practices that should be exempted from the proposed demonstration: physician groups with 25 or fewer physicians; physician-owned practices that are located in rural and medically underserved areas; reimbursement changes for drugs and biologics that do not have an alternative with more than a 20% ASP differential; and drugs and biologics where there are three or fewer members of the drug class or biologics.

ACR also proposed altering the add-on formula that takes into account the costs of storing and administering supplies.

“For example, CMS could use a formula for reimbursement of ASP plus 6% or $500 (whichever is lower),” ACR said in its comments. “This formula would allow CMS to effectively target spending on expensive drugs, while leaving in place reimbursement rates for cheaper drugs.”

Additionally, ACR called for CMS to delay the testing of more value-based tools until it understands the impact of the ASP changes that are to be tested under this proposal.

CSRO does not have any specific policy recommendations to replace or modify the proposed rule, but rather calls for CMS to bring together all stakeholders, including patients, providers, payers, and manufacturers to devise a system that would work to the benefit of all while ensuring the best outcomes for patients, Dr. Schweitz said in an interview.

[email protected]

WASHINGTON – Physician organizations are calling on Congress to stop a proposed federal regulation that would test how Medicare pays for drugs administered in a physician’s office.

Subcommittee member Rep. Larry Bucshon (R-Ind.), a cardiothoracic surgeon, called the premise of the proposed rule – that physicians are making prescribing decisions based on the cost of drugs – “almost an insult to the medical profession.” He has introduced legislation, H.R. 5122, that would require the Centers for Medicare & Medicaid Services to rescind the proposed rule.

CMS argues in the proposed rule that the current payment formula – average sales price (ASP) plus 6% – incentivizes the use of expensive drugs over lower-cost alternatives. Therefore, the agency seeks to run a test – half of doctors would continue to receive ASP plus 6%, while others would receive ASP plus 2.5% and a flat fee of $16.80. The proposed rule also would test other value-based tools. At the May 17 hearing, physicians presented their concerns regarding the proposed rule.

“CMS has yet to produce any evidence indicating that physician prescribing patterns show any correlation to that of choosing higher priced drugs as opposed to appropriate therapeutic treatment for patients,” said Dr. Debra A. Patt, vice president of Texas Oncology. Dr. Patt testified on behalf of the American Society of Clinical Oncology, the Community Oncology Alliance, and the U.S. Oncology Network. “Additionally, there is no evidence that the payment changes contemplated by CMS’s model will improve the quality of care, or for that matter, ensure patients have access to the same level of care they are currently receiving.”Dr. Michael Schweitz, national advocacy chair of the Coalition of State Rheumatology Organizations (CSRO), cited CMS’s admission that this rule will likely have no impact on ASP.

“While we appreciate CMS’s attention to the topic of drug costs, we feel that this proposal is misguided,” Dr. Schweitz testified. “As CMS acknowledges in the rule, the proposed approach ‘does not directly address the manufacturer’s ASP, which is a more significant driver of drug expenditures than the add-on payment amount for Part B drugs.’ Given that a slash to the ASP add-on is unlikely to actually lower costs for patients ... and may jeopardize access, we have requested that CMS withdraw the model and we urge the committee to do the same.”

Dr. Patt also questioned ASP, noting that it is simply an average, and the prices actually paid by rural and small group providers could be higher than larger group and hospital practices – and that difference puts the smaller and rural practices at a potentially significant financial disadvantage.

“Average sales price is by its very nature an average,” Dr. Patt testified. “Some people will pay higher amounts for procurement and some people will pay lower amounts. Larger hospital systems and larger practices have the ability to have contracting arrangements where they purchase at a lower price. … Smaller practices disproportionately pay a higher amount.”

Small practices that are slated to receive ASP plus 2.5% and that flat fee “could be losing money on all of the drugs that they buy. It will be impossible for smaller practices in rural areas to be open,” she added, noting that such a situation could cause care to be shifted to hospital outpatient departments, raising costs as well as access issues. “Cutting provider reimbursement without addressing the ASP, the actual cost of the drug in the first place, is just the wrong approach,” Rep. Bucshon said.

According to the proposed rule, whether or not a practice is in the test or control group would be based on ZIP code. Dr. Patt also noted that if she were in a test ZIP code and a neighboring ZIP code was not, she might have to refer patients to that area still receiving ASP plus 6% and “not at my center.”

Witnesses at the hearing also condemned the way CMS devised the proposed tests. Unlike the recent work on the Medicare Access and CHIP Reauthorization Act regulations and more specialized programs like the Oncology Care Model, Dr. Schweitz and Dr. Patt both testified that CMS made no outreach to the provider community with regards to getting their input before issuing the proposed rule.

They also took exception to the scope of the proposed test, which covers 49 of the 50 states (Maryland is excluded) and provides no mechanism for physicians to opt out under the proposed rule.

“I do see this as an experiment, but we conduct clinical research at our cancer and patients have informed consent,” Dr Patt said.

Dr. Schweitz agreed. “When you look at the goals of this plan, initially it appeared that it was to direct a way to save costs. But in meeting with [the Center for Medicare & Medicaid Innovation], we were advised that this is budget neutral. … So the goal of the program is to collect information which makes it a study, a test. So if the goal is to collect information, and the patients are part of that process, they should be signing informed consent.”

Several physician organizations have called on CMS to withdraw the proposal.

“We are deeply concerned that because the new methodology will frequently not properly cover the cost of physician administration of infused drugs, they will be forced to stop offering patients the ability to receive infusion treatments,” the American College of Rheumatology wrote in comments submitted on the proposed rule. Likewise, CSRO “must oppose the Part B drug payment model as it suffers from serious procedural and substantive flaws that we believe render it unworkable – and it does nothing to actually address drug prices,” according its comments.

While the proposal has garnered backlash from several directions, rheumatologists are seeing it as particularly burdensome because of the high price of medications with very limited options to substitute for lower-cost alternatives.

“Although we certainly seek to control costs for patients and Medicare whenever possible, the proposed new methodology does not adequately consider the higher average cost many of our physicians have acquiring, handling, administering, and billing for drugs and biologics,” according to the comments submitted by the ACR.

Indeed, comments from CSRO point out that when factoring in budget sequestration, the actual reimbursement physicians are receiving is ASP plus 4.4%, and doctors are actually losing money on certain drug purchases.

Of additional concern is that the proposed rule does not address ASP itself.

“A far greater concern than the add-on percentage is the underlying ASP, and the steep, fast price increases that these medications show each quarter, according to comments from the CSRO.

From 2007 to 2016, first-quarter ASP for infliximab rose from $53.73 to $79.90; ASP for abatacept rose from $18.70 to $39.44, according to CSRO comments. “These ASP increases are unsustainable for both the Medicare program and its beneficiaries, and we would like to work with CMS to explore actual solutions to stem the increases in those underlying prices.”

In its comments, ACR proposed a number of potential paths forward, starting with certain practices that should be exempted from the proposed demonstration: physician groups with 25 or fewer physicians; physician-owned practices that are located in rural and medically underserved areas; reimbursement changes for drugs and biologics that do not have an alternative with more than a 20% ASP differential; and drugs and biologics where there are three or fewer members of the drug class or biologics.

ACR also proposed altering the add-on formula that takes into account the costs of storing and administering supplies.

“For example, CMS could use a formula for reimbursement of ASP plus 6% or $500 (whichever is lower),” ACR said in its comments. “This formula would allow CMS to effectively target spending on expensive drugs, while leaving in place reimbursement rates for cheaper drugs.”

Additionally, ACR called for CMS to delay the testing of more value-based tools until it understands the impact of the ASP changes that are to be tested under this proposal.

CSRO does not have any specific policy recommendations to replace or modify the proposed rule, but rather calls for CMS to bring together all stakeholders, including patients, providers, payers, and manufacturers to devise a system that would work to the benefit of all while ensuring the best outcomes for patients, Dr. Schweitz said in an interview.

[email protected]

WASHINGTON – Physician organizations are calling on Congress to stop a proposed federal regulation that would test how Medicare pays for drugs administered in a physician’s office.

Subcommittee member Rep. Larry Bucshon (R-Ind.), a cardiothoracic surgeon, called the premise of the proposed rule – that physicians are making prescribing decisions based on the cost of drugs – “almost an insult to the medical profession.” He has introduced legislation, H.R. 5122, that would require the Centers for Medicare & Medicaid Services to rescind the proposed rule.

CMS argues in the proposed rule that the current payment formula – average sales price (ASP) plus 6% – incentivizes the use of expensive drugs over lower-cost alternatives. Therefore, the agency seeks to run a test – half of doctors would continue to receive ASP plus 6%, while others would receive ASP plus 2.5% and a flat fee of $16.80. The proposed rule also would test other value-based tools. At the May 17 hearing, physicians presented their concerns regarding the proposed rule.

“CMS has yet to produce any evidence indicating that physician prescribing patterns show any correlation to that of choosing higher priced drugs as opposed to appropriate therapeutic treatment for patients,” said Dr. Debra A. Patt, vice president of Texas Oncology. Dr. Patt testified on behalf of the American Society of Clinical Oncology, the Community Oncology Alliance, and the U.S. Oncology Network. “Additionally, there is no evidence that the payment changes contemplated by CMS’s model will improve the quality of care, or for that matter, ensure patients have access to the same level of care they are currently receiving.”Dr. Michael Schweitz, national advocacy chair of the Coalition of State Rheumatology Organizations (CSRO), cited CMS’s admission that this rule will likely have no impact on ASP.

“While we appreciate CMS’s attention to the topic of drug costs, we feel that this proposal is misguided,” Dr. Schweitz testified. “As CMS acknowledges in the rule, the proposed approach ‘does not directly address the manufacturer’s ASP, which is a more significant driver of drug expenditures than the add-on payment amount for Part B drugs.’ Given that a slash to the ASP add-on is unlikely to actually lower costs for patients ... and may jeopardize access, we have requested that CMS withdraw the model and we urge the committee to do the same.”

Dr. Patt also questioned ASP, noting that it is simply an average, and the prices actually paid by rural and small group providers could be higher than larger group and hospital practices – and that difference puts the smaller and rural practices at a potentially significant financial disadvantage.

“Average sales price is by its very nature an average,” Dr. Patt testified. “Some people will pay higher amounts for procurement and some people will pay lower amounts. Larger hospital systems and larger practices have the ability to have contracting arrangements where they purchase at a lower price. … Smaller practices disproportionately pay a higher amount.”

Small practices that are slated to receive ASP plus 2.5% and that flat fee “could be losing money on all of the drugs that they buy. It will be impossible for smaller practices in rural areas to be open,” she added, noting that such a situation could cause care to be shifted to hospital outpatient departments, raising costs as well as access issues. “Cutting provider reimbursement without addressing the ASP, the actual cost of the drug in the first place, is just the wrong approach,” Rep. Bucshon said.

According to the proposed rule, whether or not a practice is in the test or control group would be based on ZIP code. Dr. Patt also noted that if she were in a test ZIP code and a neighboring ZIP code was not, she might have to refer patients to that area still receiving ASP plus 6% and “not at my center.”

Witnesses at the hearing also condemned the way CMS devised the proposed tests. Unlike the recent work on the Medicare Access and CHIP Reauthorization Act regulations and more specialized programs like the Oncology Care Model, Dr. Schweitz and Dr. Patt both testified that CMS made no outreach to the provider community with regards to getting their input before issuing the proposed rule.

They also took exception to the scope of the proposed test, which covers 49 of the 50 states (Maryland is excluded) and provides no mechanism for physicians to opt out under the proposed rule.

“I do see this as an experiment, but we conduct clinical research at our cancer and patients have informed consent,” Dr Patt said.

Dr. Schweitz agreed. “When you look at the goals of this plan, initially it appeared that it was to direct a way to save costs. But in meeting with [the Center for Medicare & Medicaid Innovation], we were advised that this is budget neutral. … So the goal of the program is to collect information which makes it a study, a test. So if the goal is to collect information, and the patients are part of that process, they should be signing informed consent.”

Several physician organizations have called on CMS to withdraw the proposal.

“We are deeply concerned that because the new methodology will frequently not properly cover the cost of physician administration of infused drugs, they will be forced to stop offering patients the ability to receive infusion treatments,” the American College of Rheumatology wrote in comments submitted on the proposed rule. Likewise, CSRO “must oppose the Part B drug payment model as it suffers from serious procedural and substantive flaws that we believe render it unworkable – and it does nothing to actually address drug prices,” according its comments.

While the proposal has garnered backlash from several directions, rheumatologists are seeing it as particularly burdensome because of the high price of medications with very limited options to substitute for lower-cost alternatives.

“Although we certainly seek to control costs for patients and Medicare whenever possible, the proposed new methodology does not adequately consider the higher average cost many of our physicians have acquiring, handling, administering, and billing for drugs and biologics,” according to the comments submitted by the ACR.

Indeed, comments from CSRO point out that when factoring in budget sequestration, the actual reimbursement physicians are receiving is ASP plus 4.4%, and doctors are actually losing money on certain drug purchases.

Of additional concern is that the proposed rule does not address ASP itself.

“A far greater concern than the add-on percentage is the underlying ASP, and the steep, fast price increases that these medications show each quarter, according to comments from the CSRO.

From 2007 to 2016, first-quarter ASP for infliximab rose from $53.73 to $79.90; ASP for abatacept rose from $18.70 to $39.44, according to CSRO comments. “These ASP increases are unsustainable for both the Medicare program and its beneficiaries, and we would like to work with CMS to explore actual solutions to stem the increases in those underlying prices.”

In its comments, ACR proposed a number of potential paths forward, starting with certain practices that should be exempted from the proposed demonstration: physician groups with 25 or fewer physicians; physician-owned practices that are located in rural and medically underserved areas; reimbursement changes for drugs and biologics that do not have an alternative with more than a 20% ASP differential; and drugs and biologics where there are three or fewer members of the drug class or biologics.

ACR also proposed altering the add-on formula that takes into account the costs of storing and administering supplies.

“For example, CMS could use a formula for reimbursement of ASP plus 6% or $500 (whichever is lower),” ACR said in its comments. “This formula would allow CMS to effectively target spending on expensive drugs, while leaving in place reimbursement rates for cheaper drugs.”

Additionally, ACR called for CMS to delay the testing of more value-based tools until it understands the impact of the ASP changes that are to be tested under this proposal.

CSRO does not have any specific policy recommendations to replace or modify the proposed rule, but rather calls for CMS to bring together all stakeholders, including patients, providers, payers, and manufacturers to devise a system that would work to the benefit of all while ensuring the best outcomes for patients, Dr. Schweitz said in an interview.

[email protected]

CHICAGO – The stroke risk in patients with recent-onset atrial fibrillation is similar to that of patients with longer-standing atrial fibrillation, according to a new secondary analysis of the landmark ARISTOTLE trial.

“Our key message is that patients with recent-onset atrial fibrillation had a similar risk of stroke but higher mortality than patients with remotely diagnosed atrial fibrillation, suggesting that patients with recently diagnosed atrial fibrillation are not at low risk and therefore warrant stroke prevention strategies,” Dr. Patricia O. Guimaraes said in presenting the findings at the annual meeting of the American College of Cardiology.

Bruce Jancin/Frontline Medical News

“Sometimes we as physicians hesitate in beginning oral anticoagulation therapy for patients that we just diagnosed. And of course patients are often afraid of anticoagulation therapy. But once they present with atrial fibrillation they are already at risk, and that’s why we need to anticoagulate them promptly,” added Dr. Guimaraes of the Duke Clinical Research Institute in Durham, N.C.

The benefits of apixaban (Eliquis) over warfarin seen in the overall randomized ARISTOTLE trial (N Engl J Med. 2011; 365:981-92) were preserved in the recent-onset subset of the atrial fibrillation (AF) study population, she noted.

The rationale for this new post hoc analysis of ARISTOTLE is that virtually all of the evidence supporting anticoagulation for stroke prevention in AF is based on studies conducted in patients with permanent, persistent, or long-standing paroxysmal AF. Much less is known about stroke risk and the benefits of anticoagulation in patients with recent-onset AF, Dr. Guimaraes explained.

The 1,899 ARISTOTLE participants with AF onset within 30 days prior to enrollment comprised 10.5% of the total study population, all of whom had AF and at least one other stroke risk factor. The recent-onset subgroup was the same age as the 16,241 subjects in this analysis who had longer-standing AF, but the recent-onset group included a higher proportion of women, had a lower prevalence of CAD, and their cardiovascular risk factor profile differed from that of the remote-onset AF group.

The composite endpoint of stroke, systemic embolism, major bleeding, or all-cause mortality occurred at a rate of 8.69%/year in the recent-onset AF group, compared with 6.43%/year in the remote-onset group. However, in a multivariate regression analysis adjusted for potential confounders, the only significant differences in outcome between the two groups were in all-cause mortality – 5.15%/year in the recent-onset group, 3.15% in the remote-onset AF patients – and in the composite of stroke, systemic embolism, or all-cause mortality, which had an incidence of 6.46%/year in the recent-onset group, compared with 4.57%/year in remote-onset patients.

Turning to the impact of apixaban, Dr. Guimaraes noted that, as previously reported in the overall study, the primary endpoint of stroke or systemic embolism occurred in the apixaban group at a rate of 1.27%/year, compared with 1.6%/year with warfarin, for a 21% relative risk reduction in favor of the newer agent. She and her coinvestigators determined that in the remote-onset AF subgroup the relative risk reduction was 20%, while in the recent-onset subgroup the size of the effect was similar at 22%.

The composite safety endpoint of major or clinically relevant bleeding occurred in the remote-onset patients at a rate of 3.97%/year with apixaban versus 5.97%/year with warfarin, for a 33% relative risk reduction favoring the novel agent. In the recent-onset group, the rates were 5.04%/year with apixaban, compared with 6.4%/year with warfarin, for a 22% relative risk reduction.

Dr. Guimaraes observed an important limitation of this post hoc analysis is that the remote-onset AF group may have been selected for improved survival, since they didn’t die in the first 30 days after diagnosis.

Session co-chair Dr. Brian Olshansky commented that this analysis, which highlights the risks of recent-onset AF, argues for a strategy whereby a patient who presents to the ED with new-onset AF should get sent home on apixaban rather than being hospitalized for several days in order to be stabilized on warfarin.

“With recent-onset atrial fibrillation it’s going to take you several days to get anticoagulated with warfarin, whereas you’re immediately anticoagulated with apixaban,” said Dr. Olshansky, emeritus professor of internal medicine at the University of Iowa, Iowa City.

The ARISTOTLE trial was supported by Bristol-Myers Squibb and Pfizer. Dr. Guimaraes reported having no financial conflicts of interest.

[email protected]

CHICAGO – The stroke risk in patients with recent-onset atrial fibrillation is similar to that of patients with longer-standing atrial fibrillation, according to a new secondary analysis of the landmark ARISTOTLE trial.

“Our key message is that patients with recent-onset atrial fibrillation had a similar risk of stroke but higher mortality than patients with remotely diagnosed atrial fibrillation, suggesting that patients with recently diagnosed atrial fibrillation are not at low risk and therefore warrant stroke prevention strategies,” Dr. Patricia O. Guimaraes said in presenting the findings at the annual meeting of the American College of Cardiology.

Bruce Jancin/Frontline Medical News

“Sometimes we as physicians hesitate in beginning oral anticoagulation therapy for patients that we just diagnosed. And of course patients are often afraid of anticoagulation therapy. But once they present with atrial fibrillation they are already at risk, and that’s why we need to anticoagulate them promptly,” added Dr. Guimaraes of the Duke Clinical Research Institute in Durham, N.C.

The benefits of apixaban (Eliquis) over warfarin seen in the overall randomized ARISTOTLE trial (N Engl J Med. 2011; 365:981-92) were preserved in the recent-onset subset of the atrial fibrillation (AF) study population, she noted.

The rationale for this new post hoc analysis of ARISTOTLE is that virtually all of the evidence supporting anticoagulation for stroke prevention in AF is based on studies conducted in patients with permanent, persistent, or long-standing paroxysmal AF. Much less is known about stroke risk and the benefits of anticoagulation in patients with recent-onset AF, Dr. Guimaraes explained.

The 1,899 ARISTOTLE participants with AF onset within 30 days prior to enrollment comprised 10.5% of the total study population, all of whom had AF and at least one other stroke risk factor. The recent-onset subgroup was the same age as the 16,241 subjects in this analysis who had longer-standing AF, but the recent-onset group included a higher proportion of women, had a lower prevalence of CAD, and their cardiovascular risk factor profile differed from that of the remote-onset AF group.

The composite endpoint of stroke, systemic embolism, major bleeding, or all-cause mortality occurred at a rate of 8.69%/year in the recent-onset AF group, compared with 6.43%/year in the remote-onset group. However, in a multivariate regression analysis adjusted for potential confounders, the only significant differences in outcome between the two groups were in all-cause mortality – 5.15%/year in the recent-onset group, 3.15% in the remote-onset AF patients – and in the composite of stroke, systemic embolism, or all-cause mortality, which had an incidence of 6.46%/year in the recent-onset group, compared with 4.57%/year in remote-onset patients.

Turning to the impact of apixaban, Dr. Guimaraes noted that, as previously reported in the overall study, the primary endpoint of stroke or systemic embolism occurred in the apixaban group at a rate of 1.27%/year, compared with 1.6%/year with warfarin, for a 21% relative risk reduction in favor of the newer agent. She and her coinvestigators determined that in the remote-onset AF subgroup the relative risk reduction was 20%, while in the recent-onset subgroup the size of the effect was similar at 22%.

The composite safety endpoint of major or clinically relevant bleeding occurred in the remote-onset patients at a rate of 3.97%/year with apixaban versus 5.97%/year with warfarin, for a 33% relative risk reduction favoring the novel agent. In the recent-onset group, the rates were 5.04%/year with apixaban, compared with 6.4%/year with warfarin, for a 22% relative risk reduction.

Dr. Guimaraes observed an important limitation of this post hoc analysis is that the remote-onset AF group may have been selected for improved survival, since they didn’t die in the first 30 days after diagnosis.

Session co-chair Dr. Brian Olshansky commented that this analysis, which highlights the risks of recent-onset AF, argues for a strategy whereby a patient who presents to the ED with new-onset AF should get sent home on apixaban rather than being hospitalized for several days in order to be stabilized on warfarin.

“With recent-onset atrial fibrillation it’s going to take you several days to get anticoagulated with warfarin, whereas you’re immediately anticoagulated with apixaban,” said Dr. Olshansky, emeritus professor of internal medicine at the University of Iowa, Iowa City.

The ARISTOTLE trial was supported by Bristol-Myers Squibb and Pfizer. Dr. Guimaraes reported having no financial conflicts of interest.

[email protected]

CHICAGO – The stroke risk in patients with recent-onset atrial fibrillation is similar to that of patients with longer-standing atrial fibrillation, according to a new secondary analysis of the landmark ARISTOTLE trial.

“Our key message is that patients with recent-onset atrial fibrillation had a similar risk of stroke but higher mortality than patients with remotely diagnosed atrial fibrillation, suggesting that patients with recently diagnosed atrial fibrillation are not at low risk and therefore warrant stroke prevention strategies,” Dr. Patricia O. Guimaraes said in presenting the findings at the annual meeting of the American College of Cardiology.

Bruce Jancin/Frontline Medical News

“Sometimes we as physicians hesitate in beginning oral anticoagulation therapy for patients that we just diagnosed. And of course patients are often afraid of anticoagulation therapy. But once they present with atrial fibrillation they are already at risk, and that’s why we need to anticoagulate them promptly,” added Dr. Guimaraes of the Duke Clinical Research Institute in Durham, N.C.

The benefits of apixaban (Eliquis) over warfarin seen in the overall randomized ARISTOTLE trial (N Engl J Med. 2011; 365:981-92) were preserved in the recent-onset subset of the atrial fibrillation (AF) study population, she noted.

The rationale for this new post hoc analysis of ARISTOTLE is that virtually all of the evidence supporting anticoagulation for stroke prevention in AF is based on studies conducted in patients with permanent, persistent, or long-standing paroxysmal AF. Much less is known about stroke risk and the benefits of anticoagulation in patients with recent-onset AF, Dr. Guimaraes explained.

The 1,899 ARISTOTLE participants with AF onset within 30 days prior to enrollment comprised 10.5% of the total study population, all of whom had AF and at least one other stroke risk factor. The recent-onset subgroup was the same age as the 16,241 subjects in this analysis who had longer-standing AF, but the recent-onset group included a higher proportion of women, had a lower prevalence of CAD, and their cardiovascular risk factor profile differed from that of the remote-onset AF group.

The composite endpoint of stroke, systemic embolism, major bleeding, or all-cause mortality occurred at a rate of 8.69%/year in the recent-onset AF group, compared with 6.43%/year in the remote-onset group. However, in a multivariate regression analysis adjusted for potential confounders, the only significant differences in outcome between the two groups were in all-cause mortality – 5.15%/year in the recent-onset group, 3.15% in the remote-onset AF patients – and in the composite of stroke, systemic embolism, or all-cause mortality, which had an incidence of 6.46%/year in the recent-onset group, compared with 4.57%/year in remote-onset patients.

Turning to the impact of apixaban, Dr. Guimaraes noted that, as previously reported in the overall study, the primary endpoint of stroke or systemic embolism occurred in the apixaban group at a rate of 1.27%/year, compared with 1.6%/year with warfarin, for a 21% relative risk reduction in favor of the newer agent. She and her coinvestigators determined that in the remote-onset AF subgroup the relative risk reduction was 20%, while in the recent-onset subgroup the size of the effect was similar at 22%.

The composite safety endpoint of major or clinically relevant bleeding occurred in the remote-onset patients at a rate of 3.97%/year with apixaban versus 5.97%/year with warfarin, for a 33% relative risk reduction favoring the novel agent. In the recent-onset group, the rates were 5.04%/year with apixaban, compared with 6.4%/year with warfarin, for a 22% relative risk reduction.

Dr. Guimaraes observed an important limitation of this post hoc analysis is that the remote-onset AF group may have been selected for improved survival, since they didn’t die in the first 30 days after diagnosis.

Session co-chair Dr. Brian Olshansky commented that this analysis, which highlights the risks of recent-onset AF, argues for a strategy whereby a patient who presents to the ED with new-onset AF should get sent home on apixaban rather than being hospitalized for several days in order to be stabilized on warfarin.

“With recent-onset atrial fibrillation it’s going to take you several days to get anticoagulated with warfarin, whereas you’re immediately anticoagulated with apixaban,” said Dr. Olshansky, emeritus professor of internal medicine at the University of Iowa, Iowa City.

The ARISTOTLE trial was supported by Bristol-Myers Squibb and Pfizer. Dr. Guimaraes reported having no financial conflicts of interest.

[email protected]

ATLANTA – Nearly half of 2,100 multiple sclerosis (MS) patients enrolled at baseline in the Sonya Slifka Longitudinal Multiple Sclerosis Study reported experiencing emotional distress, and 9% of those patients reported difficulties with accessing mental health services.

Younger patients, those with more recently diagnosed illness, and those with more frequent MS relapses were more likely to experience emotional distress, Dr. Laura Safar of Brigham and Women’s Hospital, Boston, said at the annual meeting of the American Psychiatric Association.

HUNG KUO CHUN/Thinkstock

The Sonya Slifka study was an 8-year population-based cohort study that, at last report, included more than 4,000 MS patients from across the United States, with varying disease duration. Dr. Safar reported on baseline mental health data from the study.

Patients with MS may experience symptoms involving any part of the central nervous system, including psychiatric symptoms such as depression, anxiety, and cognitive disorders, she said, noting that these are highly prevalent, but often go unrecognized and untreated by primary care doctors and neurologists.

Prior studies have suggested that depression occurs in 25%-80% of patients, depending on the study setting. The rates are higher in those with MS than in the general population or in those with other neurologic and chronic medical conditions, she said.

In the Sonya Slifka study, 77% of patients were women with an average age of 50 years and disease duration ranging from 1 week to 64 years. Most were white. The disease distribution was representative of that seen in the general MS population, with most (57%) having relapsing-remitting disease, 25% having secondary progressive disease, and the remaining patients having primary progressive disease or progressing-relapsing disease (Mult Scler. 2006 Feb;12[1]:24-38).

Reported disability levels varied from none/very mild to severe and requiring a wheelchair or scooter or being bedridden.

Of the 48% of patients reporting emotional distress, most reported having mild to moderate distress, but 40% reported severe distress.

Nearly half (46%) of patients reported accomplishing less than normal because of emotional difficulties, and 31% said they worked less carefully than usual.

Emotional distress was more common in patients who were younger, divorced or never married, unemployed, and in those with lower education and income levels. Emotional distress was associated with shorter duration of illness, with having multiple relapses in the prior year (highest rates were among those with five or more relapses), and with moderate disability level.

Emotional distress was also associated with poorer perceived general health, and those with higher levels of emotional distress tended to experience all or many of the symptoms on the baseline questionnaire.

Further, those with emotional distress tended to lack health insurance and to have problems accessing health care and necessary prescription medications. About one-fourth of the patients had seen a mental health professional in the prior year and nearly 8% wanted to; 2% said they had been referred to a mental health professional, and 93% of these patients had emotional distress, including 6% with severe distress.

Reasons given by these patients for not seeing a mental health professional were cost, difficulty getting an appointment, and too long of a wait.

The findings suggest that in clinical settings it is important to screen MS patients for emotional distress and depression and to treat or refer accordingly, Dr. Safar said.

“As we know from other medical illnesses, this will improve adherence to MS treatment and will improve the prognosis,” she added.

Dr. Safar reported having no disclosures.

[email protected]

ATLANTA – Nearly half of 2,100 multiple sclerosis (MS) patients enrolled at baseline in the Sonya Slifka Longitudinal Multiple Sclerosis Study reported experiencing emotional distress, and 9% of those patients reported difficulties with accessing mental health services.

Younger patients, those with more recently diagnosed illness, and those with more frequent MS relapses were more likely to experience emotional distress, Dr. Laura Safar of Brigham and Women’s Hospital, Boston, said at the annual meeting of the American Psychiatric Association.

HUNG KUO CHUN/Thinkstock

The Sonya Slifka study was an 8-year population-based cohort study that, at last report, included more than 4,000 MS patients from across the United States, with varying disease duration. Dr. Safar reported on baseline mental health data from the study.

Patients with MS may experience symptoms involving any part of the central nervous system, including psychiatric symptoms such as depression, anxiety, and cognitive disorders, she said, noting that these are highly prevalent, but often go unrecognized and untreated by primary care doctors and neurologists.

Prior studies have suggested that depression occurs in 25%-80% of patients, depending on the study setting. The rates are higher in those with MS than in the general population or in those with other neurologic and chronic medical conditions, she said.

In the Sonya Slifka study, 77% of patients were women with an average age of 50 years and disease duration ranging from 1 week to 64 years. Most were white. The disease distribution was representative of that seen in the general MS population, with most (57%) having relapsing-remitting disease, 25% having secondary progressive disease, and the remaining patients having primary progressive disease or progressing-relapsing disease (Mult Scler. 2006 Feb;12[1]:24-38).

Reported disability levels varied from none/very mild to severe and requiring a wheelchair or scooter or being bedridden.

Of the 48% of patients reporting emotional distress, most reported having mild to moderate distress, but 40% reported severe distress.

Nearly half (46%) of patients reported accomplishing less than normal because of emotional difficulties, and 31% said they worked less carefully than usual.

Emotional distress was more common in patients who were younger, divorced or never married, unemployed, and in those with lower education and income levels. Emotional distress was associated with shorter duration of illness, with having multiple relapses in the prior year (highest rates were among those with five or more relapses), and with moderate disability level.

Emotional distress was also associated with poorer perceived general health, and those with higher levels of emotional distress tended to experience all or many of the symptoms on the baseline questionnaire.

Further, those with emotional distress tended to lack health insurance and to have problems accessing health care and necessary prescription medications. About one-fourth of the patients had seen a mental health professional in the prior year and nearly 8% wanted to; 2% said they had been referred to a mental health professional, and 93% of these patients had emotional distress, including 6% with severe distress.

Reasons given by these patients for not seeing a mental health professional were cost, difficulty getting an appointment, and too long of a wait.

The findings suggest that in clinical settings it is important to screen MS patients for emotional distress and depression and to treat or refer accordingly, Dr. Safar said.

“As we know from other medical illnesses, this will improve adherence to MS treatment and will improve the prognosis,” she added.

Dr. Safar reported having no disclosures.

[email protected]

ATLANTA – Nearly half of 2,100 multiple sclerosis (MS) patients enrolled at baseline in the Sonya Slifka Longitudinal Multiple Sclerosis Study reported experiencing emotional distress, and 9% of those patients reported difficulties with accessing mental health services.

Younger patients, those with more recently diagnosed illness, and those with more frequent MS relapses were more likely to experience emotional distress, Dr. Laura Safar of Brigham and Women’s Hospital, Boston, said at the annual meeting of the American Psychiatric Association.

HUNG KUO CHUN/Thinkstock

The Sonya Slifka study was an 8-year population-based cohort study that, at last report, included more than 4,000 MS patients from across the United States, with varying disease duration. Dr. Safar reported on baseline mental health data from the study.

Patients with MS may experience symptoms involving any part of the central nervous system, including psychiatric symptoms such as depression, anxiety, and cognitive disorders, she said, noting that these are highly prevalent, but often go unrecognized and untreated by primary care doctors and neurologists.

Prior studies have suggested that depression occurs in 25%-80% of patients, depending on the study setting. The rates are higher in those with MS than in the general population or in those with other neurologic and chronic medical conditions, she said.

In the Sonya Slifka study, 77% of patients were women with an average age of 50 years and disease duration ranging from 1 week to 64 years. Most were white. The disease distribution was representative of that seen in the general MS population, with most (57%) having relapsing-remitting disease, 25% having secondary progressive disease, and the remaining patients having primary progressive disease or progressing-relapsing disease (Mult Scler. 2006 Feb;12[1]:24-38).

Reported disability levels varied from none/very mild to severe and requiring a wheelchair or scooter or being bedridden.

Of the 48% of patients reporting emotional distress, most reported having mild to moderate distress, but 40% reported severe distress.

Nearly half (46%) of patients reported accomplishing less than normal because of emotional difficulties, and 31% said they worked less carefully than usual.

Emotional distress was more common in patients who were younger, divorced or never married, unemployed, and in those with lower education and income levels. Emotional distress was associated with shorter duration of illness, with having multiple relapses in the prior year (highest rates were among those with five or more relapses), and with moderate disability level.

Emotional distress was also associated with poorer perceived general health, and those with higher levels of emotional distress tended to experience all or many of the symptoms on the baseline questionnaire.

Further, those with emotional distress tended to lack health insurance and to have problems accessing health care and necessary prescription medications. About one-fourth of the patients had seen a mental health professional in the prior year and nearly 8% wanted to; 2% said they had been referred to a mental health professional, and 93% of these patients had emotional distress, including 6% with severe distress.

Reasons given by these patients for not seeing a mental health professional were cost, difficulty getting an appointment, and too long of a wait.

The findings suggest that in clinical settings it is important to screen MS patients for emotional distress and depression and to treat or refer accordingly, Dr. Safar said.

“As we know from other medical illnesses, this will improve adherence to MS treatment and will improve the prognosis,” she added.

Dr. Safar reported having no disclosures.

[email protected]

Doctors can detect evidence of a concussion up to one week after a patient is injured by using a simple blood test, according to a report published online ahead of print March 28 in JAMA Neurology. Researchers tested two blood biomarkers—glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1)—separately and together in patients with mild and moderate traumatic brain injury (TBI) within seven days of the injury. They examined the blood biomarkers with respect to diagnostic precision of TBI, presence of traumatic intracranial lesions detectable by CT, and need for neurosurgical intervention. Linda Papa, MDCM, MSc, and colleagues reported that GFAP performed consistently in detecting mild to moderate TBI, CT lesions, and the need for neurosurgical interventions across seven days. UCH-L1, they said, performed best in the early postinjury period.

Linda Papa, MDCM, MSc

“We have so many diagnostic blood tests for different parts of the body, like the heart, liver and kidneys, but there’s never been a reliable blood test to identify trauma in the brain,” said Dr. Papa, an emergency medicine physician at Orlando Health in Florid and lead author of the study. “We think this particular test could change that.”

Dr. Papa and colleagues designed a prospective cohort study that enrolled adults with trauma seen at a level 1 trauma center from March 1, 2010, to March 5, 2014. All patients underwent screening to determine whether they had experienced mild or moderate TBI, which was defined as blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9 to 15. Of 3,025 patients assessed, 1,030 met eligibility criteria for enrollment; 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within four hours of injury. Repeated blood sampling was conducted every four hours up to 24 hours postinjury, and then every 12 hours thereafter until 180 hours postinjury.

A total of 1,831 blood samples were drawn from 584 patients (mean age, 40; 62% male) over seven days. Both GFAP and UCH-L1 were detectible within one hour of injury. GFAP peaked at 20 hours postinjury and slowly declined over 72 hours. UCH-L1 rose rapidly and peaked at eight hours postinjury, then declined rapidly over 48 hours.

Over the course of one week, GFAP demonstrated a diagnostic range of areas under the curve for detecting mild to moderate TBI of 0.73 to 0.94, and UCH-L1 demonstrated a diagnostic range of 0.30 to 0.67. For detecting intracranial lesions on CT, the diagnostic ranges of areas under the curve were 0.80 to 0.97 for GFAP and 0.31 to 0.77 for UCH-L1. For distinguishing patients with and without the need for a neurosurgical intervention, the range for GFAP was 0.91 to 100 and the range for UCH-L1 was 0.50 to 0.92.

“In the context of developing a point-of-care test, the early and rapid rise of UCH-L1 could be used to detect TBI immediately at the scene of injury in settings such as in the ambulance, on the playing field, or at the battlefield,” the researchers wrote. “The longer half-life of GFAP makes it a favorable biomarker to use in both the acute and subacute phases of injury because it is able to detect CT lesions for up to seven days after injury. Although its rise is not as rapid as [that of] UCH-L1, it performs well for detecting mild TBI and CT lesions within one hour of injury.”

—Glenn S. Williams

Doctors can detect evidence of a concussion up to one week after a patient is injured by using a simple blood test, according to a report published online ahead of print March 28 in JAMA Neurology. Researchers tested two blood biomarkers—glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1)—separately and together in patients with mild and moderate traumatic brain injury (TBI) within seven days of the injury. They examined the blood biomarkers with respect to diagnostic precision of TBI, presence of traumatic intracranial lesions detectable by CT, and need for neurosurgical intervention. Linda Papa, MDCM, MSc, and colleagues reported that GFAP performed consistently in detecting mild to moderate TBI, CT lesions, and the need for neurosurgical interventions across seven days. UCH-L1, they said, performed best in the early postinjury period.

Linda Papa, MDCM, MSc

“We have so many diagnostic blood tests for different parts of the body, like the heart, liver and kidneys, but there’s never been a reliable blood test to identify trauma in the brain,” said Dr. Papa, an emergency medicine physician at Orlando Health in Florid and lead author of the study. “We think this particular test could change that.”

Dr. Papa and colleagues designed a prospective cohort study that enrolled adults with trauma seen at a level 1 trauma center from March 1, 2010, to March 5, 2014. All patients underwent screening to determine whether they had experienced mild or moderate TBI, which was defined as blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9 to 15. Of 3,025 patients assessed, 1,030 met eligibility criteria for enrollment; 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within four hours of injury. Repeated blood sampling was conducted every four hours up to 24 hours postinjury, and then every 12 hours thereafter until 180 hours postinjury.

A total of 1,831 blood samples were drawn from 584 patients (mean age, 40; 62% male) over seven days. Both GFAP and UCH-L1 were detectible within one hour of injury. GFAP peaked at 20 hours postinjury and slowly declined over 72 hours. UCH-L1 rose rapidly and peaked at eight hours postinjury, then declined rapidly over 48 hours.

Over the course of one week, GFAP demonstrated a diagnostic range of areas under the curve for detecting mild to moderate TBI of 0.73 to 0.94, and UCH-L1 demonstrated a diagnostic range of 0.30 to 0.67. For detecting intracranial lesions on CT, the diagnostic ranges of areas under the curve were 0.80 to 0.97 for GFAP and 0.31 to 0.77 for UCH-L1. For distinguishing patients with and without the need for a neurosurgical intervention, the range for GFAP was 0.91 to 100 and the range for UCH-L1 was 0.50 to 0.92.

“In the context of developing a point-of-care test, the early and rapid rise of UCH-L1 could be used to detect TBI immediately at the scene of injury in settings such as in the ambulance, on the playing field, or at the battlefield,” the researchers wrote. “The longer half-life of GFAP makes it a favorable biomarker to use in both the acute and subacute phases of injury because it is able to detect CT lesions for up to seven days after injury. Although its rise is not as rapid as [that of] UCH-L1, it performs well for detecting mild TBI and CT lesions within one hour of injury.”

—Glenn S. Williams

Doctors can detect evidence of a concussion up to one week after a patient is injured by using a simple blood test, according to a report published online ahead of print March 28 in JAMA Neurology. Researchers tested two blood biomarkers—glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1)—separately and together in patients with mild and moderate traumatic brain injury (TBI) within seven days of the injury. They examined the blood biomarkers with respect to diagnostic precision of TBI, presence of traumatic intracranial lesions detectable by CT, and need for neurosurgical intervention. Linda Papa, MDCM, MSc, and colleagues reported that GFAP performed consistently in detecting mild to moderate TBI, CT lesions, and the need for neurosurgical interventions across seven days. UCH-L1, they said, performed best in the early postinjury period.

Linda Papa, MDCM, MSc

“We have so many diagnostic blood tests for different parts of the body, like the heart, liver and kidneys, but there’s never been a reliable blood test to identify trauma in the brain,” said Dr. Papa, an emergency medicine physician at Orlando Health in Florid and lead author of the study. “We think this particular test could change that.”

Dr. Papa and colleagues designed a prospective cohort study that enrolled adults with trauma seen at a level 1 trauma center from March 1, 2010, to March 5, 2014. All patients underwent screening to determine whether they had experienced mild or moderate TBI, which was defined as blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9 to 15. Of 3,025 patients assessed, 1,030 met eligibility criteria for enrollment; 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within four hours of injury. Repeated blood sampling was conducted every four hours up to 24 hours postinjury, and then every 12 hours thereafter until 180 hours postinjury.

A total of 1,831 blood samples were drawn from 584 patients (mean age, 40; 62% male) over seven days. Both GFAP and UCH-L1 were detectible within one hour of injury. GFAP peaked at 20 hours postinjury and slowly declined over 72 hours. UCH-L1 rose rapidly and peaked at eight hours postinjury, then declined rapidly over 48 hours.

Over the course of one week, GFAP demonstrated a diagnostic range of areas under the curve for detecting mild to moderate TBI of 0.73 to 0.94, and UCH-L1 demonstrated a diagnostic range of 0.30 to 0.67. For detecting intracranial lesions on CT, the diagnostic ranges of areas under the curve were 0.80 to 0.97 for GFAP and 0.31 to 0.77 for UCH-L1. For distinguishing patients with and without the need for a neurosurgical intervention, the range for GFAP was 0.91 to 100 and the range for UCH-L1 was 0.50 to 0.92.

“In the context of developing a point-of-care test, the early and rapid rise of UCH-L1 could be used to detect TBI immediately at the scene of injury in settings such as in the ambulance, on the playing field, or at the battlefield,” the researchers wrote. “The longer half-life of GFAP makes it a favorable biomarker to use in both the acute and subacute phases of injury because it is able to detect CT lesions for up to seven days after injury. Although its rise is not as rapid as [that of] UCH-L1, it performs well for detecting mild TBI and CT lesions within one hour of injury.”

—Glenn S. Williams