Photo © ASCO/Scott Morgan 2017

CHICAGO—Results of an open-label phase 1b study of daratumumab combined with carfilzomib, lenalidomide, and dexamethasone (KRd) in newly diagnosed multiple myeloma (MM) patients have shown the combination to be highly effective, with an overall response rate of 100%.

Ninety-one percent of patients achieved a very good partial response (VGPR) or better, and 43% achieved a complete response (CR) or better.

Investigators had hypothesized that rather than using autologous stem cell transplant (ASCT) to improve results of treatment with KRd, the combination could alternatively be improved by incorporating daratumumab into a KRd regimen.

Andrzej Jakubowiak, MD, of the University of Chicago Medical Center in Illinois, presented the findings of the MMY1001 study at the 2017 ASCO Annual Meeting (abstract 8000*).

“I think what was one of the more important developments in myeloma last year,” Dr Jakubowiak said, “was data from randomized studies showing that adding daratumumab to either lenalidomide and dexamethasone in the POLLUX study or bortezomib and dexamethasone, a proteasome inhibitor, in the CASTOR study, improves responses, depth of response, and . . .  dramatically improved progression-free survival.”

“[W]e have now the rationale to potentially combine daratumumab with both an IMiD and proteasome inhibitor,” he explained, “which led to the development of this phase 1b study in which we combined daratumumab with KRd and evaluated tolerability and efficacy.”

Study design

Twenty-two transplant-eligible or -ineligible newly diagnosed MM patients were enrolled on the study.

Treatment duration was planned to be 13 cycles or less and patients had the option to move to transplant after 4 cycles.

They could have no clinically significant cardiac disease and echocardiogram was required prior to transplant.

The dosing schedule was the established dosing schema for daratumumab and KRd with 2 notable differences in the 28-day cycles.

First, the daratumumab dose was a split dose. So patients received 8 mg/kg on days 1-2 of cycle 1, 16 mg/kg a week on cycle 2, 16 mg/kg every 2 weeks on cycles 3 – 6, and every 4^th week thereafter.

The second difference was carfilzomib dosing was a weekly regimen with escalation from 20 mg/m² on day 1, cycle 1 to 70 mg/m² on day 8 of cycle 1.

Lenalidomide (25 mg on days 1-21 of each cycle) and dexamethasone (40 mg/week) were the standard regimens for these drugs.

The primary endpoint was safety and tolerability. The secondary endpoint was overall response rate (ORR), duration of response, time to response, and infusion-related reactions (IRR).

The study also had an exploratory endpoint of progression-free survival (PFS).

Baseline characteristics

Patients were a median age of 59.5 years (range 34 – 74). About two thirds were younger than 65 and one third were between 65 and 75.

A little over half were male and most (86%) were white.

A little more than half (55%) had an ECOG score of 0, 41% were ECOG 1, and 5% were ECOG 2.

Patient disposition

As of the cutoff date of March 24, 8 of the 22 patients enrolled (36%) discontinued treatment: 1 due to an adverse event (AE), 1 due to progressive disease, and 6 patients (27%) proceeded to ASCT.

Dr Jakubowiak pointed out that response was censored at this point for patients who proceeded to transplant.

The median follow-up was 10.8 months (range, 4.0 – 12.5) and the median number of treatment cycles was 11.5 (range, 1.0 – 13.0).

“What is of interest to many of us,” Dr Jakubowiak said, “is that patients were escalated to the planned dose of 70 mg/m² by cycle 2 except for 3 patients.”

Of the 3, 1 discontinued before day 1 of the second cycle due to toxicity, 1 had a dose reduction to 56 mg/m² at day of the second cycle, and 1 escalated to 70 mg/m² at day 8 of cycle 3.

Ultimately, all patients who remained on study were able to escalate to 70 mg/m².

Safety

The hematologic treatment-emergent adverse events (TEAE) generally followed what has been observed in similar studies before, Dr Jakubowiak noted.

Hematologic TEAEs of all grades occurring in 30% or more of patients were lymphopenia (68%), thrombocytopenia (55%), anemia (46%), leukopenia (41%), and neutropenia (32%).

The most common non-hematologic TEAEs of all grades occurring in 30% of patients or more were diarrhea (73%), upper respiratory infection (59%) cough, constipation, and fatigue (50% each), dyspnea and insomnia (46%), nausea, rash, and back pain (41%), muscle spasm (36%), and vomiting, pain in extremity, hyperglycemia, and increased ALT (32%).

The most common grade 3/4 TEAEs were infrequent and many events had none of grade 3/4 severity.

The safety profile is consistent with what was previously reported for daratumumab or KRd, Dr Jakubowiak affirmed.

Serious TEAEs

Serious TEAEs occurred in 10 patients (46%), with many occurring in just 1 patient. Pulmonary embolism (PE) was the most frequent, occurring in 3 patients.

All patients were required to be on aspirin prophylaxis and 1 of the patients who had a PE discontinued therapy.

The number of patients with a serious TEAE reasonably related to an individual study drug were 3 (14%) for daratumumab, 5 (23%) for carfilzomib, 5 (23%) for lenalidomide, and 2 (9%) for dexamethasone.

The TEAEs of interest—tachycardia, congestive heart failure, and hypertension—occurred in a single patient each.

Overall, serious TEAEs were consistent with previous reports from KRd studies.

Echocardiogram assessment

Investigators conducted 30 systemic evaluations on the impact of this regimen on heart function.  The investigators observed no change from baseline through the duration of treatment in patients’ left ventricular ejection fractions.

One patient developed congestive heart failure, possibly related to daratumumab or carfilzomib. This patient resumed treatment with a reduced carfilzomib dose, elected ASCT on study day 113, and ended treatment with a VGPR.

“In all,” Dr Jakubowiak said, “we feel that there is no apparent signal of adverse impact of the addition of daratumumab on cardiac function.”

Infusion times and reactions

Overall, IRRs occurred in 27% of the patients, “which appears lower than with previous daratumumab studies,” Dr Jakubowiak noted. And IRRs occurred more frequently during the first infusion than subsequent infusions.

The split-dose infusion time was very similar to that of second and subsequent cycles.

There were limited events related to infusions. All were grade 1 or 2 and most occurred in only a single patient.

Response rate

The median number of treatment cycles administered was 11.5 (range, 2.0 – 13.0). The best response was 100% PR or better, 91% achieved VGPR or better, 42% CR or better, and 29% a stringent CR.

The depth of response improved with duration of treatment. For example, the sCR rate increased from 5% after 4 cycles to 29% at the end of treatment.

PFS was an exploratory endpoint. One patient progressed at 10.8 months and the 12-month PFS rate was 94% with all patients alive.

Stem cell harvest and ASCT

“For many of us,” Dr Jakubowiak commented, “it’s also of interest how this regimen will impact stem cell harvest.”

Nineteen of 22 patients were deemed to be transplant eligible, and the median number of CD34+ cells collected from them was 10.4 x 10⁶ cells/kg.

Patients had a median of 5 treatment cycles prior to stem cell harvest, and 14 (74%) had a VGPR or better prior to harvest.

The investigators believe stem cell yield was consistent with previous KRd studies.

Dr Jakubowiak commented that the deepening of response over time “is a phenomenon we think is important. . . . In all, the data from this small phase 1b study provide support for further evaluation of this regimen in newly diagnosed myeloma."

The study was funded by Janssen Research and Development, LLC. 

*Data presented during the meeting differ from the abstract.

Photo © ASCO/Scott Morgan 2017

CHICAGO—Results of an open-label phase 1b study of daratumumab combined with carfilzomib, lenalidomide, and dexamethasone (KRd) in newly diagnosed multiple myeloma (MM) patients have shown the combination to be highly effective, with an overall response rate of 100%.

Ninety-one percent of patients achieved a very good partial response (VGPR) or better, and 43% achieved a complete response (CR) or better.

Investigators had hypothesized that rather than using autologous stem cell transplant (ASCT) to improve results of treatment with KRd, the combination could alternatively be improved by incorporating daratumumab into a KRd regimen.

Andrzej Jakubowiak, MD, of the University of Chicago Medical Center in Illinois, presented the findings of the MMY1001 study at the 2017 ASCO Annual Meeting (abstract 8000*).

“I think what was one of the more important developments in myeloma last year,” Dr Jakubowiak said, “was data from randomized studies showing that adding daratumumab to either lenalidomide and dexamethasone in the POLLUX study or bortezomib and dexamethasone, a proteasome inhibitor, in the CASTOR study, improves responses, depth of response, and . . .  dramatically improved progression-free survival.”

“[W]e have now the rationale to potentially combine daratumumab with both an IMiD and proteasome inhibitor,” he explained, “which led to the development of this phase 1b study in which we combined daratumumab with KRd and evaluated tolerability and efficacy.”

Study design

Twenty-two transplant-eligible or -ineligible newly diagnosed MM patients were enrolled on the study.

Treatment duration was planned to be 13 cycles or less and patients had the option to move to transplant after 4 cycles.

They could have no clinically significant cardiac disease and echocardiogram was required prior to transplant.

The dosing schedule was the established dosing schema for daratumumab and KRd with 2 notable differences in the 28-day cycles.

First, the daratumumab dose was a split dose. So patients received 8 mg/kg on days 1-2 of cycle 1, 16 mg/kg a week on cycle 2, 16 mg/kg every 2 weeks on cycles 3 – 6, and every 4^th week thereafter.

The second difference was carfilzomib dosing was a weekly regimen with escalation from 20 mg/m² on day 1, cycle 1 to 70 mg/m² on day 8 of cycle 1.

Lenalidomide (25 mg on days 1-21 of each cycle) and dexamethasone (40 mg/week) were the standard regimens for these drugs.

The primary endpoint was safety and tolerability. The secondary endpoint was overall response rate (ORR), duration of response, time to response, and infusion-related reactions (IRR).

The study also had an exploratory endpoint of progression-free survival (PFS).

Baseline characteristics

Patients were a median age of 59.5 years (range 34 – 74). About two thirds were younger than 65 and one third were between 65 and 75.

A little over half were male and most (86%) were white.

A little more than half (55%) had an ECOG score of 0, 41% were ECOG 1, and 5% were ECOG 2.

Patient disposition

As of the cutoff date of March 24, 8 of the 22 patients enrolled (36%) discontinued treatment: 1 due to an adverse event (AE), 1 due to progressive disease, and 6 patients (27%) proceeded to ASCT.

Dr Jakubowiak pointed out that response was censored at this point for patients who proceeded to transplant.

The median follow-up was 10.8 months (range, 4.0 – 12.5) and the median number of treatment cycles was 11.5 (range, 1.0 – 13.0).

“What is of interest to many of us,” Dr Jakubowiak said, “is that patients were escalated to the planned dose of 70 mg/m² by cycle 2 except for 3 patients.”

Of the 3, 1 discontinued before day 1 of the second cycle due to toxicity, 1 had a dose reduction to 56 mg/m² at day of the second cycle, and 1 escalated to 70 mg/m² at day 8 of cycle 3.

Ultimately, all patients who remained on study were able to escalate to 70 mg/m².

Safety

The hematologic treatment-emergent adverse events (TEAE) generally followed what has been observed in similar studies before, Dr Jakubowiak noted.

Hematologic TEAEs of all grades occurring in 30% or more of patients were lymphopenia (68%), thrombocytopenia (55%), anemia (46%), leukopenia (41%), and neutropenia (32%).

The most common non-hematologic TEAEs of all grades occurring in 30% of patients or more were diarrhea (73%), upper respiratory infection (59%) cough, constipation, and fatigue (50% each), dyspnea and insomnia (46%), nausea, rash, and back pain (41%), muscle spasm (36%), and vomiting, pain in extremity, hyperglycemia, and increased ALT (32%).

The most common grade 3/4 TEAEs were infrequent and many events had none of grade 3/4 severity.

The safety profile is consistent with what was previously reported for daratumumab or KRd, Dr Jakubowiak affirmed.

Serious TEAEs

Serious TEAEs occurred in 10 patients (46%), with many occurring in just 1 patient. Pulmonary embolism (PE) was the most frequent, occurring in 3 patients.

All patients were required to be on aspirin prophylaxis and 1 of the patients who had a PE discontinued therapy.

The number of patients with a serious TEAE reasonably related to an individual study drug were 3 (14%) for daratumumab, 5 (23%) for carfilzomib, 5 (23%) for lenalidomide, and 2 (9%) for dexamethasone.

The TEAEs of interest—tachycardia, congestive heart failure, and hypertension—occurred in a single patient each.

Overall, serious TEAEs were consistent with previous reports from KRd studies.

Echocardiogram assessment

Investigators conducted 30 systemic evaluations on the impact of this regimen on heart function.  The investigators observed no change from baseline through the duration of treatment in patients’ left ventricular ejection fractions.

One patient developed congestive heart failure, possibly related to daratumumab or carfilzomib. This patient resumed treatment with a reduced carfilzomib dose, elected ASCT on study day 113, and ended treatment with a VGPR.

“In all,” Dr Jakubowiak said, “we feel that there is no apparent signal of adverse impact of the addition of daratumumab on cardiac function.”

Infusion times and reactions

Overall, IRRs occurred in 27% of the patients, “which appears lower than with previous daratumumab studies,” Dr Jakubowiak noted. And IRRs occurred more frequently during the first infusion than subsequent infusions.

The split-dose infusion time was very similar to that of second and subsequent cycles.

There were limited events related to infusions. All were grade 1 or 2 and most occurred in only a single patient.

Response rate

The median number of treatment cycles administered was 11.5 (range, 2.0 – 13.0). The best response was 100% PR or better, 91% achieved VGPR or better, 42% CR or better, and 29% a stringent CR.

The depth of response improved with duration of treatment. For example, the sCR rate increased from 5% after 4 cycles to 29% at the end of treatment.

PFS was an exploratory endpoint. One patient progressed at 10.8 months and the 12-month PFS rate was 94% with all patients alive.

Stem cell harvest and ASCT

“For many of us,” Dr Jakubowiak commented, “it’s also of interest how this regimen will impact stem cell harvest.”

Nineteen of 22 patients were deemed to be transplant eligible, and the median number of CD34+ cells collected from them was 10.4 x 10⁶ cells/kg.

Patients had a median of 5 treatment cycles prior to stem cell harvest, and 14 (74%) had a VGPR or better prior to harvest.

The investigators believe stem cell yield was consistent with previous KRd studies.

Dr Jakubowiak commented that the deepening of response over time “is a phenomenon we think is important. . . . In all, the data from this small phase 1b study provide support for further evaluation of this regimen in newly diagnosed myeloma."

The study was funded by Janssen Research and Development, LLC. 

*Data presented during the meeting differ from the abstract.

Photo © ASCO/Scott Morgan 2017

CHICAGO—Results of an open-label phase 1b study of daratumumab combined with carfilzomib, lenalidomide, and dexamethasone (KRd) in newly diagnosed multiple myeloma (MM) patients have shown the combination to be highly effective, with an overall response rate of 100%.

Ninety-one percent of patients achieved a very good partial response (VGPR) or better, and 43% achieved a complete response (CR) or better.

Investigators had hypothesized that rather than using autologous stem cell transplant (ASCT) to improve results of treatment with KRd, the combination could alternatively be improved by incorporating daratumumab into a KRd regimen.

Andrzej Jakubowiak, MD, of the University of Chicago Medical Center in Illinois, presented the findings of the MMY1001 study at the 2017 ASCO Annual Meeting (abstract 8000*).

“I think what was one of the more important developments in myeloma last year,” Dr Jakubowiak said, “was data from randomized studies showing that adding daratumumab to either lenalidomide and dexamethasone in the POLLUX study or bortezomib and dexamethasone, a proteasome inhibitor, in the CASTOR study, improves responses, depth of response, and . . .  dramatically improved progression-free survival.”

“[W]e have now the rationale to potentially combine daratumumab with both an IMiD and proteasome inhibitor,” he explained, “which led to the development of this phase 1b study in which we combined daratumumab with KRd and evaluated tolerability and efficacy.”

Study design

Twenty-two transplant-eligible or -ineligible newly diagnosed MM patients were enrolled on the study.

Treatment duration was planned to be 13 cycles or less and patients had the option to move to transplant after 4 cycles.

They could have no clinically significant cardiac disease and echocardiogram was required prior to transplant.

The dosing schedule was the established dosing schema for daratumumab and KRd with 2 notable differences in the 28-day cycles.

First, the daratumumab dose was a split dose. So patients received 8 mg/kg on days 1-2 of cycle 1, 16 mg/kg a week on cycle 2, 16 mg/kg every 2 weeks on cycles 3 – 6, and every 4^th week thereafter.

The second difference was carfilzomib dosing was a weekly regimen with escalation from 20 mg/m² on day 1, cycle 1 to 70 mg/m² on day 8 of cycle 1.

Lenalidomide (25 mg on days 1-21 of each cycle) and dexamethasone (40 mg/week) were the standard regimens for these drugs.

The primary endpoint was safety and tolerability. The secondary endpoint was overall response rate (ORR), duration of response, time to response, and infusion-related reactions (IRR).

The study also had an exploratory endpoint of progression-free survival (PFS).

Baseline characteristics

Patients were a median age of 59.5 years (range 34 – 74). About two thirds were younger than 65 and one third were between 65 and 75.

A little over half were male and most (86%) were white.

A little more than half (55%) had an ECOG score of 0, 41% were ECOG 1, and 5% were ECOG 2.

Patient disposition

As of the cutoff date of March 24, 8 of the 22 patients enrolled (36%) discontinued treatment: 1 due to an adverse event (AE), 1 due to progressive disease, and 6 patients (27%) proceeded to ASCT.

Dr Jakubowiak pointed out that response was censored at this point for patients who proceeded to transplant.

The median follow-up was 10.8 months (range, 4.0 – 12.5) and the median number of treatment cycles was 11.5 (range, 1.0 – 13.0).

“What is of interest to many of us,” Dr Jakubowiak said, “is that patients were escalated to the planned dose of 70 mg/m² by cycle 2 except for 3 patients.”

Of the 3, 1 discontinued before day 1 of the second cycle due to toxicity, 1 had a dose reduction to 56 mg/m² at day of the second cycle, and 1 escalated to 70 mg/m² at day 8 of cycle 3.

Ultimately, all patients who remained on study were able to escalate to 70 mg/m².

Safety

The hematologic treatment-emergent adverse events (TEAE) generally followed what has been observed in similar studies before, Dr Jakubowiak noted.

Hematologic TEAEs of all grades occurring in 30% or more of patients were lymphopenia (68%), thrombocytopenia (55%), anemia (46%), leukopenia (41%), and neutropenia (32%).

The most common non-hematologic TEAEs of all grades occurring in 30% of patients or more were diarrhea (73%), upper respiratory infection (59%) cough, constipation, and fatigue (50% each), dyspnea and insomnia (46%), nausea, rash, and back pain (41%), muscle spasm (36%), and vomiting, pain in extremity, hyperglycemia, and increased ALT (32%).

The most common grade 3/4 TEAEs were infrequent and many events had none of grade 3/4 severity.

The safety profile is consistent with what was previously reported for daratumumab or KRd, Dr Jakubowiak affirmed.

Serious TEAEs

Serious TEAEs occurred in 10 patients (46%), with many occurring in just 1 patient. Pulmonary embolism (PE) was the most frequent, occurring in 3 patients.

All patients were required to be on aspirin prophylaxis and 1 of the patients who had a PE discontinued therapy.

The number of patients with a serious TEAE reasonably related to an individual study drug were 3 (14%) for daratumumab, 5 (23%) for carfilzomib, 5 (23%) for lenalidomide, and 2 (9%) for dexamethasone.

The TEAEs of interest—tachycardia, congestive heart failure, and hypertension—occurred in a single patient each.

Overall, serious TEAEs were consistent with previous reports from KRd studies.

Echocardiogram assessment

Investigators conducted 30 systemic evaluations on the impact of this regimen on heart function.  The investigators observed no change from baseline through the duration of treatment in patients’ left ventricular ejection fractions.

One patient developed congestive heart failure, possibly related to daratumumab or carfilzomib. This patient resumed treatment with a reduced carfilzomib dose, elected ASCT on study day 113, and ended treatment with a VGPR.

“In all,” Dr Jakubowiak said, “we feel that there is no apparent signal of adverse impact of the addition of daratumumab on cardiac function.”

Infusion times and reactions

Overall, IRRs occurred in 27% of the patients, “which appears lower than with previous daratumumab studies,” Dr Jakubowiak noted. And IRRs occurred more frequently during the first infusion than subsequent infusions.

The split-dose infusion time was very similar to that of second and subsequent cycles.

There were limited events related to infusions. All were grade 1 or 2 and most occurred in only a single patient.

Response rate

The median number of treatment cycles administered was 11.5 (range, 2.0 – 13.0). The best response was 100% PR or better, 91% achieved VGPR or better, 42% CR or better, and 29% a stringent CR.

The depth of response improved with duration of treatment. For example, the sCR rate increased from 5% after 4 cycles to 29% at the end of treatment.

PFS was an exploratory endpoint. One patient progressed at 10.8 months and the 12-month PFS rate was 94% with all patients alive.

Stem cell harvest and ASCT

“For many of us,” Dr Jakubowiak commented, “it’s also of interest how this regimen will impact stem cell harvest.”

Nineteen of 22 patients were deemed to be transplant eligible, and the median number of CD34+ cells collected from them was 10.4 x 10⁶ cells/kg.

Patients had a median of 5 treatment cycles prior to stem cell harvest, and 14 (74%) had a VGPR or better prior to harvest.

The investigators believe stem cell yield was consistent with previous KRd studies.

Dr Jakubowiak commented that the deepening of response over time “is a phenomenon we think is important. . . . In all, the data from this small phase 1b study provide support for further evaluation of this regimen in newly diagnosed myeloma."

The study was funded by Janssen Research and Development, LLC. 

*Data presented during the meeting differ from the abstract.

Clinical Question: What are the risks of nonthoracic MRI in patients with pacemakers or implantable cardioverter-defibrillators (ICD) who are not preapproved by the Food and Drug Administration for MRI scanning?

Background: Implantable cardiovascular devices could suffer heating in MRI magnetic fields leading to cardiac thermal injury and changes in pacing properties. The FDA approves “MRI-conditional devices” deemed safe for MRI, but up to six million patients worldwide (and two million in the United States) have non–MRI conditional devices.

Dr. Frederick is assistant clinical professor in the division of hospital Medicine, department of medicine, University of California, San Diego.

Clinical Question: What are the risks of nonthoracic MRI in patients with pacemakers or implantable cardioverter-defibrillators (ICD) who are not preapproved by the Food and Drug Administration for MRI scanning?

Background: Implantable cardiovascular devices could suffer heating in MRI magnetic fields leading to cardiac thermal injury and changes in pacing properties. The FDA approves “MRI-conditional devices” deemed safe for MRI, but up to six million patients worldwide (and two million in the United States) have non–MRI conditional devices.

Dr. Frederick is assistant clinical professor in the division of hospital Medicine, department of medicine, University of California, San Diego.

Clinical Question: What are the risks of nonthoracic MRI in patients with pacemakers or implantable cardioverter-defibrillators (ICD) who are not preapproved by the Food and Drug Administration for MRI scanning?

Background: Implantable cardiovascular devices could suffer heating in MRI magnetic fields leading to cardiac thermal injury and changes in pacing properties. The FDA approves “MRI-conditional devices” deemed safe for MRI, but up to six million patients worldwide (and two million in the United States) have non–MRI conditional devices.

Dr. Frederick is assistant clinical professor in the division of hospital Medicine, department of medicine, University of California, San Diego.

Managing diabetes is a complex undertaking, with an extensive regimen of self-care—including regular exercise, meal planning, blood glucose monitoring, medication scheduling, and multiple visits—that is critically linked to glycemic control and the prevention of complications. Incorporating all of these elements into daily life can be daunting.^1-3

In fact, nearly half of US adults with diabetes fail to meet the recommended targets.⁴ This leads to frustration, which often manifests in psychosocial problems that further hamper efforts to manage the ­disease.^5-10 The most notable is a psychosocial disorder known as diabetes distress, which affects close to 45% of persons with diabetes.^11,12

It is important to note that diabetes distress is not a psychiatric disorder; rather, it is a broad affective reaction to the stress of living with this chronic and complex disease.^13-15 By negatively affecting adherence to a self-care regimen, diabetes distress contributes to worsening glycemic control and increasing morbidity.^16-18

Recognizing that about 80% of those with diabetes are treated in primary care settings, this review is intended to call your attention to diabetes distress, alert you to brief screening tools that can easily be incorporated into clinic visits, and offer guidance in matching proposed interventions to the aspects of diabetes self-management that cause patients the greatest distress.¹⁹

DIABETES DISTRESS: WHAT IT IS, WHAT IT'S NOT

For patients with type 2 diabetes, diabetes distress centers around four main issues

• Frustration with the demands of self-care
• Apprehension about the future and the possibility of developing serious complications
• Concern about both the quality and the cost of required medical care
• Perceived lack of support from family and/or friends.^11,12,20

As mentioned earlier, diabetes distress is not a psychiatric condition and should not be confused with major depressive disorder (MDD). Here’s help in telling the difference.

For starters, a diagnosis of depression is symptom-based.¹³ MDD requires the presence of at least five of the nine symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth ed. (DSM-5)—eg, persistent feelings of worthlessness or guilt, sleep disturbances, lack of interest in normal activities—for at least two weeks.²¹ What’s more, the diagnostic criteria for MDD do not specify a cause or disease process. Nor do they distinguish between a pathological response and an expected reaction to a stressful life event.²² Further, depression measures reflect symptoms (eg, hyperglycemia), as well as stressful experiences resulting from diabetes self-care, which may contribute to the high rate of false positives or incorrect diagnoses of MDD and missed diagnoses of diabetes distress.²³

Unlike MDD, diabetes distress has a specific cause—diabetes—and can best be understood as an emotional response to a demanding health condition.¹³ And, because the source of the problem is identified, diabetes distress can be treated with specific interventions targeting the areas causing the highest levels of stress.

When a psychiatric condition and diabetes distress overlap

MDD, anxiety disorders, and diabetes distress are all common in patients with diabetes, and the co-occurrence of a psychiatric disorder and diabetes distress is high.^24,25Thus, it is important not only to identify cases of diabetes distress but also to consider comorbid depression and/or anxiety in patients with diabetes distress.

More often, though, it is the other way around, according to the Distress and Depression in Diabetes (3D) study. The researchers recently found that 84% of patients with moderate or high diabetes distress did not fulfill the criteria for MDD, but that 67% of diabetes patients with MDD also had moderate or high diabetes distress.^13,15,17,25

The data highlight the importance of screening patients with a dual diagnosis of diabetes and MDD for diabetes distress. Keep in mind that persons diagnosed with diabetes distress and a comorbid psychiatric condition may require more complex and intensive treatment than those with either diabetes distress or MDD alone.²⁵

SCREENING FOR DIABETES DISTRESS

Diabetes distress can be easily assessed using one of several patient-reported outcome measures. Six validated measures, ranging in length from one to 28 questions, are designed for use in primary care (see Table).^26-30 Some of the measures are easily accessible online; others require a subscription to MEDLINE.

Problem Areas in Diabetes (PAID). There are three versions of PAID—a 20-item screen assessing a broad range of feelings related to living with diabetes and its treatment, a five-item version (PAID-5) with high rates of sensitivity (95%) and specificity (89%), and a single-item test (PAID-1) that is highly correlated with the longer version.^26,27

Diabetes Distress Scale (DDS). This tool is available in a 17-item measure assessing diabetes distress as it relates to the emotional burden, physician-related distress, regimen-related distress, and interpersonal distress.²⁸ DDS is also available in a short form (DDS-2) with two items and a 28-item scale specifically for patients with type 1 diabetes.^29,30 T1-DDS, the only diabetes distress measure focused on this particular patient population, assesses the seven sources of distress found to be common among adults with type 1 diabetes: powerlessness, negative social perceptions, physician distress, friend/family distress, hypoglycemia distress, management distress, and eating distress.

Studies have shown that not only do those with type 1 diabetes experience different stressors compared with their type 2 counterparts, but also that they tend to experience distress differently. For patients with type 1 diabetes, for example, powerlessness ranked as the highest source of distress, followed by eating distress and hypoglycemia distress. These sources of distress differ from the regimen distress, emotional burden, interpersonal distress, and physician distress identified by those with type 2 diabetes.³⁰

HOW TO RESPOND TO DIABETES DISTRESS

Diabetes distress is easier to identify than to successfully treat. Few validated treatments for diabetes distress exist and, to our knowledge, only two studies have assessed interventions aimed at reduction of such distress.^31,32

The REDEEM trial recruited adults with type 2 diabetes and diabetes distress to participate in a 12-month randomized controlled trial (RCT).³¹ The trial had three arms, comparing the effectiveness of a computer-assisted self-management (CASM) program alone, a CASM program plus in-person diabetes distress­–specific problem-solving therapy, and a computer-assisted minimally supportive intervention. The main outcomes included diabetes distress (using the DDS scale and subscales), self-management behaviors, and A1C.

Participants in all three arms showed significant reductions in total diabetes distress and improvements in self-management behaviors, with no significant differences among the groups. No differences in A1C were found. However, those in the CASM program plus distress-specific therapy arm showed a larger reduction in regimen distress compared with the other two groups.³¹

The DIAMOS trial recruited adults who had type 1 or type 2 diabetes, diabetes distress, and subclinical depressive symptoms for a two-arm RCT.³² One group underwent cognitive behavioral interventions, while the controls had standard group-based diabetes education. The main outcomes included diabetes distress (measured via the PAID scale), depressive symptoms, well-being, diabetes self-care, diabetes acceptance, satisfaction with diabetes treatment, A1C, and subclinical inflammation.

The intervention group showed greater improvement in diabetes distress and depressive symptoms compared with the control group, but no differences in well-being, self-care, treatment satisfaction, A1C, or subclinical inflammation were observed.³²

Both studies support the use of problem-solving therapy and cognitive behavioral interventions for patients with diabetes distress. Future research should evaluate the effectiveness of these interventions in the primary care setting.

What else to offer when challenges mount?

Diabetes is a progressive disease, and most patients experience multiple challenges over time. These typically include complications and comorbidities, physical limitations, polypharmacy, hypoglycemia, and cognitive impairment, as well as changes in everything from medication and lifestyle to insurance coverage and social support.^33,34 All increase the risk for diabetes distress, as well as related psychiatric conditions.

Aging and diabetes are independent risk factors for cognitive impairment, for example, and the presence of both increases this risk.³⁵ What’s more, diabetes alone is associated with poorer executive function, the higher-level cognitive processes that allow individuals to engage in independent, purposeful, and flexible goal-related behaviors.^36-38 Both poor cognitive function and impaired executive function interfere with the ability to perform self-care behaviors such as adjusting insulin doses, drawing insulin into a syringe, or dialing an insulin dose with an insulin pen.³⁹ This in turn can lead to frustration and increase the likelihood of moderate to high diabetes distress.

Assessing diabetes distress in patients with cognitive impairment, poor executive functioning, or other psychological limitations is particularly difficult, however, as no diabetes distress measures take such deficits into account. Thus, primary care providers without expertise in neuropsychology should consider referring patients with such problems to specialists for assessment.

The progressive nature of diabetes also highlights the need for primary care providers to periodically screen for diabetes distress and engage in ongoing discussions about what type of care is best for individual patients, and why. When developing or updating treatment plans and making recommendations, it is crucial to consider the impact the treatment would likely have on the patient’s physical and mental health and to explicitly inquire about and acknowledge his or her values and preferences for care.^40-44

It is also important to remain aware of socioeconomic changes—in employment, insurance coverage, and living situations, for example—which are not addressed in the screening tools.

Moderate to high diabetes distress scores, as well as individual items patients identify as “very serious” problems, represent clinical red flags that should be the focus of careful discussion during a medical visit. Patients with moderate to high distress should be referred to a therapist trained in cognitive behavioral therapy or problem-solving therapy. Clinicians who lack access to such resources can incorporate cognitive behavioral and problem-solving techniques into patient discussions. (See “Directing Help Where It’s Most Needed.”) All patients should be referred to a certified diabetes educator—a key component of diabetes care.^45,46

Managing diabetes is a complex undertaking, with an extensive regimen of self-care—including regular exercise, meal planning, blood glucose monitoring, medication scheduling, and multiple visits—that is critically linked to glycemic control and the prevention of complications. Incorporating all of these elements into daily life can be daunting.^1-3

In fact, nearly half of US adults with diabetes fail to meet the recommended targets.⁴ This leads to frustration, which often manifests in psychosocial problems that further hamper efforts to manage the ­disease.^5-10 The most notable is a psychosocial disorder known as diabetes distress, which affects close to 45% of persons with diabetes.^11,12

It is important to note that diabetes distress is not a psychiatric disorder; rather, it is a broad affective reaction to the stress of living with this chronic and complex disease.^13-15 By negatively affecting adherence to a self-care regimen, diabetes distress contributes to worsening glycemic control and increasing morbidity.^16-18

Recognizing that about 80% of those with diabetes are treated in primary care settings, this review is intended to call your attention to diabetes distress, alert you to brief screening tools that can easily be incorporated into clinic visits, and offer guidance in matching proposed interventions to the aspects of diabetes self-management that cause patients the greatest distress.¹⁹

DIABETES DISTRESS: WHAT IT IS, WHAT IT'S NOT

For patients with type 2 diabetes, diabetes distress centers around four main issues

• Frustration with the demands of self-care
• Apprehension about the future and the possibility of developing serious complications
• Concern about both the quality and the cost of required medical care
• Perceived lack of support from family and/or friends.^11,12,20

As mentioned earlier, diabetes distress is not a psychiatric condition and should not be confused with major depressive disorder (MDD). Here’s help in telling the difference.

For starters, a diagnosis of depression is symptom-based.¹³ MDD requires the presence of at least five of the nine symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth ed. (DSM-5)—eg, persistent feelings of worthlessness or guilt, sleep disturbances, lack of interest in normal activities—for at least two weeks.²¹ What’s more, the diagnostic criteria for MDD do not specify a cause or disease process. Nor do they distinguish between a pathological response and an expected reaction to a stressful life event.²² Further, depression measures reflect symptoms (eg, hyperglycemia), as well as stressful experiences resulting from diabetes self-care, which may contribute to the high rate of false positives or incorrect diagnoses of MDD and missed diagnoses of diabetes distress.²³

Unlike MDD, diabetes distress has a specific cause—diabetes—and can best be understood as an emotional response to a demanding health condition.¹³ And, because the source of the problem is identified, diabetes distress can be treated with specific interventions targeting the areas causing the highest levels of stress.

When a psychiatric condition and diabetes distress overlap

MDD, anxiety disorders, and diabetes distress are all common in patients with diabetes, and the co-occurrence of a psychiatric disorder and diabetes distress is high.^24,25Thus, it is important not only to identify cases of diabetes distress but also to consider comorbid depression and/or anxiety in patients with diabetes distress.

More often, though, it is the other way around, according to the Distress and Depression in Diabetes (3D) study. The researchers recently found that 84% of patients with moderate or high diabetes distress did not fulfill the criteria for MDD, but that 67% of diabetes patients with MDD also had moderate or high diabetes distress.^13,15,17,25

The data highlight the importance of screening patients with a dual diagnosis of diabetes and MDD for diabetes distress. Keep in mind that persons diagnosed with diabetes distress and a comorbid psychiatric condition may require more complex and intensive treatment than those with either diabetes distress or MDD alone.²⁵

SCREENING FOR DIABETES DISTRESS

Diabetes distress can be easily assessed using one of several patient-reported outcome measures. Six validated measures, ranging in length from one to 28 questions, are designed for use in primary care (see Table).^26-30 Some of the measures are easily accessible online; others require a subscription to MEDLINE.

Problem Areas in Diabetes (PAID). There are three versions of PAID—a 20-item screen assessing a broad range of feelings related to living with diabetes and its treatment, a five-item version (PAID-5) with high rates of sensitivity (95%) and specificity (89%), and a single-item test (PAID-1) that is highly correlated with the longer version.^26,27

Diabetes Distress Scale (DDS). This tool is available in a 17-item measure assessing diabetes distress as it relates to the emotional burden, physician-related distress, regimen-related distress, and interpersonal distress.²⁸ DDS is also available in a short form (DDS-2) with two items and a 28-item scale specifically for patients with type 1 diabetes.^29,30 T1-DDS, the only diabetes distress measure focused on this particular patient population, assesses the seven sources of distress found to be common among adults with type 1 diabetes: powerlessness, negative social perceptions, physician distress, friend/family distress, hypoglycemia distress, management distress, and eating distress.

Studies have shown that not only do those with type 1 diabetes experience different stressors compared with their type 2 counterparts, but also that they tend to experience distress differently. For patients with type 1 diabetes, for example, powerlessness ranked as the highest source of distress, followed by eating distress and hypoglycemia distress. These sources of distress differ from the regimen distress, emotional burden, interpersonal distress, and physician distress identified by those with type 2 diabetes.³⁰

HOW TO RESPOND TO DIABETES DISTRESS

Diabetes distress is easier to identify than to successfully treat. Few validated treatments for diabetes distress exist and, to our knowledge, only two studies have assessed interventions aimed at reduction of such distress.^31,32

The REDEEM trial recruited adults with type 2 diabetes and diabetes distress to participate in a 12-month randomized controlled trial (RCT).³¹ The trial had three arms, comparing the effectiveness of a computer-assisted self-management (CASM) program alone, a CASM program plus in-person diabetes distress­–specific problem-solving therapy, and a computer-assisted minimally supportive intervention. The main outcomes included diabetes distress (using the DDS scale and subscales), self-management behaviors, and A1C.

Participants in all three arms showed significant reductions in total diabetes distress and improvements in self-management behaviors, with no significant differences among the groups. No differences in A1C were found. However, those in the CASM program plus distress-specific therapy arm showed a larger reduction in regimen distress compared with the other two groups.³¹

The DIAMOS trial recruited adults who had type 1 or type 2 diabetes, diabetes distress, and subclinical depressive symptoms for a two-arm RCT.³² One group underwent cognitive behavioral interventions, while the controls had standard group-based diabetes education. The main outcomes included diabetes distress (measured via the PAID scale), depressive symptoms, well-being, diabetes self-care, diabetes acceptance, satisfaction with diabetes treatment, A1C, and subclinical inflammation.

The intervention group showed greater improvement in diabetes distress and depressive symptoms compared with the control group, but no differences in well-being, self-care, treatment satisfaction, A1C, or subclinical inflammation were observed.³²

Both studies support the use of problem-solving therapy and cognitive behavioral interventions for patients with diabetes distress. Future research should evaluate the effectiveness of these interventions in the primary care setting.

What else to offer when challenges mount?

Diabetes is a progressive disease, and most patients experience multiple challenges over time. These typically include complications and comorbidities, physical limitations, polypharmacy, hypoglycemia, and cognitive impairment, as well as changes in everything from medication and lifestyle to insurance coverage and social support.^33,34 All increase the risk for diabetes distress, as well as related psychiatric conditions.

Aging and diabetes are independent risk factors for cognitive impairment, for example, and the presence of both increases this risk.³⁵ What’s more, diabetes alone is associated with poorer executive function, the higher-level cognitive processes that allow individuals to engage in independent, purposeful, and flexible goal-related behaviors.^36-38 Both poor cognitive function and impaired executive function interfere with the ability to perform self-care behaviors such as adjusting insulin doses, drawing insulin into a syringe, or dialing an insulin dose with an insulin pen.³⁹ This in turn can lead to frustration and increase the likelihood of moderate to high diabetes distress.

Assessing diabetes distress in patients with cognitive impairment, poor executive functioning, or other psychological limitations is particularly difficult, however, as no diabetes distress measures take such deficits into account. Thus, primary care providers without expertise in neuropsychology should consider referring patients with such problems to specialists for assessment.

The progressive nature of diabetes also highlights the need for primary care providers to periodically screen for diabetes distress and engage in ongoing discussions about what type of care is best for individual patients, and why. When developing or updating treatment plans and making recommendations, it is crucial to consider the impact the treatment would likely have on the patient’s physical and mental health and to explicitly inquire about and acknowledge his or her values and preferences for care.^40-44

It is also important to remain aware of socioeconomic changes—in employment, insurance coverage, and living situations, for example—which are not addressed in the screening tools.

Moderate to high diabetes distress scores, as well as individual items patients identify as “very serious” problems, represent clinical red flags that should be the focus of careful discussion during a medical visit. Patients with moderate to high distress should be referred to a therapist trained in cognitive behavioral therapy or problem-solving therapy. Clinicians who lack access to such resources can incorporate cognitive behavioral and problem-solving techniques into patient discussions. (See “Directing Help Where It’s Most Needed.”) All patients should be referred to a certified diabetes educator—a key component of diabetes care.^45,46

Managing diabetes is a complex undertaking, with an extensive regimen of self-care—including regular exercise, meal planning, blood glucose monitoring, medication scheduling, and multiple visits—that is critically linked to glycemic control and the prevention of complications. Incorporating all of these elements into daily life can be daunting.^1-3

In fact, nearly half of US adults with diabetes fail to meet the recommended targets.⁴ This leads to frustration, which often manifests in psychosocial problems that further hamper efforts to manage the ­disease.^5-10 The most notable is a psychosocial disorder known as diabetes distress, which affects close to 45% of persons with diabetes.^11,12

It is important to note that diabetes distress is not a psychiatric disorder; rather, it is a broad affective reaction to the stress of living with this chronic and complex disease.^13-15 By negatively affecting adherence to a self-care regimen, diabetes distress contributes to worsening glycemic control and increasing morbidity.^16-18

Recognizing that about 80% of those with diabetes are treated in primary care settings, this review is intended to call your attention to diabetes distress, alert you to brief screening tools that can easily be incorporated into clinic visits, and offer guidance in matching proposed interventions to the aspects of diabetes self-management that cause patients the greatest distress.¹⁹

DIABETES DISTRESS: WHAT IT IS, WHAT IT'S NOT

For patients with type 2 diabetes, diabetes distress centers around four main issues

• Frustration with the demands of self-care
• Apprehension about the future and the possibility of developing serious complications
• Concern about both the quality and the cost of required medical care
• Perceived lack of support from family and/or friends.^11,12,20

As mentioned earlier, diabetes distress is not a psychiatric condition and should not be confused with major depressive disorder (MDD). Here’s help in telling the difference.

For starters, a diagnosis of depression is symptom-based.¹³ MDD requires the presence of at least five of the nine symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth ed. (DSM-5)—eg, persistent feelings of worthlessness or guilt, sleep disturbances, lack of interest in normal activities—for at least two weeks.²¹ What’s more, the diagnostic criteria for MDD do not specify a cause or disease process. Nor do they distinguish between a pathological response and an expected reaction to a stressful life event.²² Further, depression measures reflect symptoms (eg, hyperglycemia), as well as stressful experiences resulting from diabetes self-care, which may contribute to the high rate of false positives or incorrect diagnoses of MDD and missed diagnoses of diabetes distress.²³

Unlike MDD, diabetes distress has a specific cause—diabetes—and can best be understood as an emotional response to a demanding health condition.¹³ And, because the source of the problem is identified, diabetes distress can be treated with specific interventions targeting the areas causing the highest levels of stress.

When a psychiatric condition and diabetes distress overlap

MDD, anxiety disorders, and diabetes distress are all common in patients with diabetes, and the co-occurrence of a psychiatric disorder and diabetes distress is high.^24,25Thus, it is important not only to identify cases of diabetes distress but also to consider comorbid depression and/or anxiety in patients with diabetes distress.

More often, though, it is the other way around, according to the Distress and Depression in Diabetes (3D) study. The researchers recently found that 84% of patients with moderate or high diabetes distress did not fulfill the criteria for MDD, but that 67% of diabetes patients with MDD also had moderate or high diabetes distress.^13,15,17,25

The data highlight the importance of screening patients with a dual diagnosis of diabetes and MDD for diabetes distress. Keep in mind that persons diagnosed with diabetes distress and a comorbid psychiatric condition may require more complex and intensive treatment than those with either diabetes distress or MDD alone.²⁵

SCREENING FOR DIABETES DISTRESS

Diabetes distress can be easily assessed using one of several patient-reported outcome measures. Six validated measures, ranging in length from one to 28 questions, are designed for use in primary care (see Table).^26-30 Some of the measures are easily accessible online; others require a subscription to MEDLINE.

Problem Areas in Diabetes (PAID). There are three versions of PAID—a 20-item screen assessing a broad range of feelings related to living with diabetes and its treatment, a five-item version (PAID-5) with high rates of sensitivity (95%) and specificity (89%), and a single-item test (PAID-1) that is highly correlated with the longer version.^26,27

Diabetes Distress Scale (DDS). This tool is available in a 17-item measure assessing diabetes distress as it relates to the emotional burden, physician-related distress, regimen-related distress, and interpersonal distress.²⁸ DDS is also available in a short form (DDS-2) with two items and a 28-item scale specifically for patients with type 1 diabetes.^29,30 T1-DDS, the only diabetes distress measure focused on this particular patient population, assesses the seven sources of distress found to be common among adults with type 1 diabetes: powerlessness, negative social perceptions, physician distress, friend/family distress, hypoglycemia distress, management distress, and eating distress.

Studies have shown that not only do those with type 1 diabetes experience different stressors compared with their type 2 counterparts, but also that they tend to experience distress differently. For patients with type 1 diabetes, for example, powerlessness ranked as the highest source of distress, followed by eating distress and hypoglycemia distress. These sources of distress differ from the regimen distress, emotional burden, interpersonal distress, and physician distress identified by those with type 2 diabetes.³⁰

HOW TO RESPOND TO DIABETES DISTRESS

Diabetes distress is easier to identify than to successfully treat. Few validated treatments for diabetes distress exist and, to our knowledge, only two studies have assessed interventions aimed at reduction of such distress.^31,32

The REDEEM trial recruited adults with type 2 diabetes and diabetes distress to participate in a 12-month randomized controlled trial (RCT).³¹ The trial had three arms, comparing the effectiveness of a computer-assisted self-management (CASM) program alone, a CASM program plus in-person diabetes distress­–specific problem-solving therapy, and a computer-assisted minimally supportive intervention. The main outcomes included diabetes distress (using the DDS scale and subscales), self-management behaviors, and A1C.

Participants in all three arms showed significant reductions in total diabetes distress and improvements in self-management behaviors, with no significant differences among the groups. No differences in A1C were found. However, those in the CASM program plus distress-specific therapy arm showed a larger reduction in regimen distress compared with the other two groups.³¹

The DIAMOS trial recruited adults who had type 1 or type 2 diabetes, diabetes distress, and subclinical depressive symptoms for a two-arm RCT.³² One group underwent cognitive behavioral interventions, while the controls had standard group-based diabetes education. The main outcomes included diabetes distress (measured via the PAID scale), depressive symptoms, well-being, diabetes self-care, diabetes acceptance, satisfaction with diabetes treatment, A1C, and subclinical inflammation.

The intervention group showed greater improvement in diabetes distress and depressive symptoms compared with the control group, but no differences in well-being, self-care, treatment satisfaction, A1C, or subclinical inflammation were observed.³²

Both studies support the use of problem-solving therapy and cognitive behavioral interventions for patients with diabetes distress. Future research should evaluate the effectiveness of these interventions in the primary care setting.

What else to offer when challenges mount?

Diabetes is a progressive disease, and most patients experience multiple challenges over time. These typically include complications and comorbidities, physical limitations, polypharmacy, hypoglycemia, and cognitive impairment, as well as changes in everything from medication and lifestyle to insurance coverage and social support.^33,34 All increase the risk for diabetes distress, as well as related psychiatric conditions.

Aging and diabetes are independent risk factors for cognitive impairment, for example, and the presence of both increases this risk.³⁵ What’s more, diabetes alone is associated with poorer executive function, the higher-level cognitive processes that allow individuals to engage in independent, purposeful, and flexible goal-related behaviors.^36-38 Both poor cognitive function and impaired executive function interfere with the ability to perform self-care behaviors such as adjusting insulin doses, drawing insulin into a syringe, or dialing an insulin dose with an insulin pen.³⁹ This in turn can lead to frustration and increase the likelihood of moderate to high diabetes distress.

Assessing diabetes distress in patients with cognitive impairment, poor executive functioning, or other psychological limitations is particularly difficult, however, as no diabetes distress measures take such deficits into account. Thus, primary care providers without expertise in neuropsychology should consider referring patients with such problems to specialists for assessment.

The progressive nature of diabetes also highlights the need for primary care providers to periodically screen for diabetes distress and engage in ongoing discussions about what type of care is best for individual patients, and why. When developing or updating treatment plans and making recommendations, it is crucial to consider the impact the treatment would likely have on the patient’s physical and mental health and to explicitly inquire about and acknowledge his or her values and preferences for care.^40-44

It is also important to remain aware of socioeconomic changes—in employment, insurance coverage, and living situations, for example—which are not addressed in the screening tools.

Moderate to high diabetes distress scores, as well as individual items patients identify as “very serious” problems, represent clinical red flags that should be the focus of careful discussion during a medical visit. Patients with moderate to high distress should be referred to a therapist trained in cognitive behavioral therapy or problem-solving therapy. Clinicians who lack access to such resources can incorporate cognitive behavioral and problem-solving techniques into patient discussions. (See “Directing Help Where It’s Most Needed.”) All patients should be referred to a certified diabetes educator—a key component of diabetes care.^45,46

NEW ORLEANS – The proportion of women with multiple sclerosis with a live birth receiving disease-modifying drug therapy was low and declined during the prepregnancy and pregnancy periods, results from a large analysis of national claims data found.

“Multiple sclerosis is up to three times more common in women than in men, and the clinical onset is often during childbearing years,” researchers led by Maria K. Houtchens, MD, wrote in an abstract presented during the annual meeting of the Consortium of Multiple Sclerosis Centers. “A better understanding of the ‘real world’ disease-modifying drug treatment patterns in women with MS and a pregnancy is essential in order to improve available clinical support, health care services, and quality of life for women with MS of childbearing age.”

[email protected]

NEW ORLEANS – The proportion of women with multiple sclerosis with a live birth receiving disease-modifying drug therapy was low and declined during the prepregnancy and pregnancy periods, results from a large analysis of national claims data found.

“Multiple sclerosis is up to three times more common in women than in men, and the clinical onset is often during childbearing years,” researchers led by Maria K. Houtchens, MD, wrote in an abstract presented during the annual meeting of the Consortium of Multiple Sclerosis Centers. “A better understanding of the ‘real world’ disease-modifying drug treatment patterns in women with MS and a pregnancy is essential in order to improve available clinical support, health care services, and quality of life for women with MS of childbearing age.”

[email protected]

NEW ORLEANS – The proportion of women with multiple sclerosis with a live birth receiving disease-modifying drug therapy was low and declined during the prepregnancy and pregnancy periods, results from a large analysis of national claims data found.

“Multiple sclerosis is up to three times more common in women than in men, and the clinical onset is often during childbearing years,” researchers led by Maria K. Houtchens, MD, wrote in an abstract presented during the annual meeting of the Consortium of Multiple Sclerosis Centers. “A better understanding of the ‘real world’ disease-modifying drug treatment patterns in women with MS and a pregnancy is essential in order to improve available clinical support, health care services, and quality of life for women with MS of childbearing age.”

[email protected]

The U.S. Supreme Court has ruled that biosimilar companies can take their versions of biological drugs to the market 6 months sooner in a precedential ruling that could mean quicker access to less expensive medications.

The unanimous ruling overturns an appeals court ruling in favor California-based Amgen that had barred competitor Sandoz from selling its biosimilar of Neupogen (filgrastim) until 6 months after Food and Drug Administration approval. Justices held that the Biologics Price Competition and Innovation Act of 2009 (BPCIA) allows biosimilar applicants to provide notice of commercial marketing prior to obtaining licensure by the FDA.

Carol Lynch, global head of Biopharmaceuticals at Sandoz, said the ruling helps to eliminate unnecessary barriers so that patients can access more affordable medicine in a more timely manner.

“Biosimilars offer significant value to patients, providers, and payers, increasing the number of treatment options available to patients across many disease areas at a reduced cost to the health care system,” Ms. Lynch said in a statement. “The justices’ unanimous ruling on the notice of commercial marketing will help expedite patient access to life-enhancing treatments. We also appreciate the clarity provided on the patent dance, which will help the

[email protected]

On Twitter @legal_med

The U.S. Supreme Court has ruled that biosimilar companies can take their versions of biological drugs to the market 6 months sooner in a precedential ruling that could mean quicker access to less expensive medications.

The unanimous ruling overturns an appeals court ruling in favor California-based Amgen that had barred competitor Sandoz from selling its biosimilar of Neupogen (filgrastim) until 6 months after Food and Drug Administration approval. Justices held that the Biologics Price Competition and Innovation Act of 2009 (BPCIA) allows biosimilar applicants to provide notice of commercial marketing prior to obtaining licensure by the FDA.

Carol Lynch, global head of Biopharmaceuticals at Sandoz, said the ruling helps to eliminate unnecessary barriers so that patients can access more affordable medicine in a more timely manner.

“Biosimilars offer significant value to patients, providers, and payers, increasing the number of treatment options available to patients across many disease areas at a reduced cost to the health care system,” Ms. Lynch said in a statement. “The justices’ unanimous ruling on the notice of commercial marketing will help expedite patient access to life-enhancing treatments. We also appreciate the clarity provided on the patent dance, which will help the

[email protected]

On Twitter @legal_med

The U.S. Supreme Court has ruled that biosimilar companies can take their versions of biological drugs to the market 6 months sooner in a precedential ruling that could mean quicker access to less expensive medications.

The unanimous ruling overturns an appeals court ruling in favor California-based Amgen that had barred competitor Sandoz from selling its biosimilar of Neupogen (filgrastim) until 6 months after Food and Drug Administration approval. Justices held that the Biologics Price Competition and Innovation Act of 2009 (BPCIA) allows biosimilar applicants to provide notice of commercial marketing prior to obtaining licensure by the FDA.

Carol Lynch, global head of Biopharmaceuticals at Sandoz, said the ruling helps to eliminate unnecessary barriers so that patients can access more affordable medicine in a more timely manner.

“Biosimilars offer significant value to patients, providers, and payers, increasing the number of treatment options available to patients across many disease areas at a reduced cost to the health care system,” Ms. Lynch said in a statement. “The justices’ unanimous ruling on the notice of commercial marketing will help expedite patient access to life-enhancing treatments. We also appreciate the clarity provided on the patent dance, which will help the

[email protected]

On Twitter @legal_med

BOSTON – New research finds that military veterans who suffered mild traumatic brain injuries (TBIs) faced more than 1.5 times the risk of developing Parkinson’s disease (PD), compared with other veterans over up to 12 years of follow-up. The risk doubled for those who suffered moderate to severe TBIs.

The findings don’t confirm a link between brain injury and PD, and the number of PD diagnoses remained small even among those who’d suffered the worst TBIs.

Still, the findings suggest that “mild TBI may have long-term consequences, including PD,” said study lead author Raquel C. Gardner, MD, a neurologist whose findings were released at the annual meeting of the American Academy of Neurology. “We need to ramp up efforts to prevent TBI and also make sure we are carefully screening TBI-exposed patients for some of these long-term consequences, for which we may be able to offer therapies to improve quality of life.”

3283197d_273/Thinkstock

[email protected]

BOSTON – New research finds that military veterans who suffered mild traumatic brain injuries (TBIs) faced more than 1.5 times the risk of developing Parkinson’s disease (PD), compared with other veterans over up to 12 years of follow-up. The risk doubled for those who suffered moderate to severe TBIs.

The findings don’t confirm a link between brain injury and PD, and the number of PD diagnoses remained small even among those who’d suffered the worst TBIs.

Still, the findings suggest that “mild TBI may have long-term consequences, including PD,” said study lead author Raquel C. Gardner, MD, a neurologist whose findings were released at the annual meeting of the American Academy of Neurology. “We need to ramp up efforts to prevent TBI and also make sure we are carefully screening TBI-exposed patients for some of these long-term consequences, for which we may be able to offer therapies to improve quality of life.”

3283197d_273/Thinkstock

[email protected]

BOSTON – New research finds that military veterans who suffered mild traumatic brain injuries (TBIs) faced more than 1.5 times the risk of developing Parkinson’s disease (PD), compared with other veterans over up to 12 years of follow-up. The risk doubled for those who suffered moderate to severe TBIs.

The findings don’t confirm a link between brain injury and PD, and the number of PD diagnoses remained small even among those who’d suffered the worst TBIs.

Still, the findings suggest that “mild TBI may have long-term consequences, including PD,” said study lead author Raquel C. Gardner, MD, a neurologist whose findings were released at the annual meeting of the American Academy of Neurology. “We need to ramp up efforts to prevent TBI and also make sure we are carefully screening TBI-exposed patients for some of these long-term consequences, for which we may be able to offer therapies to improve quality of life.”

3283197d_273/Thinkstock

[email protected]

Seven weeks of treatment with delta-9-atetrahydrocannabinol (THC) did not improve chronic abdominal pain in a placebo-controlled trial of 65 adults.

Treatment “was safe and well tolerated,” but did not significantly reduce pain scores or secondary efficacy outcomes, Marjan de Vries, MSc, and her associates wrote in the July issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.09.147). Studies have not clearly shown that THC improves central pain sensitization, a key mechanism in chronic abdominal pain, they noted. Future studies of THC and central sensitization include quantitative sensory testing or electroencephalography, they added.

Source: American Gastroenterological Association

Treatment-refractory chronic abdominal pain is common after abdominal surgery or in chronic pancreatitis, wrote Ms. de Vries of Radboud University Medical Center, Nijmegen, the Netherlands. Affected patients tend to develop central sensitization, or hyper-responsive nociceptive central nervous system pathways. When this happens, pain no longer couples reliably with peripheral stimuli, and therapy targeting central nociceptive pathways is indicated. The main psychoactive compound of Cannabis sativa is THC, which interacts with CB1 receptors in the central nervous system, including in areas of the brain that help regulate emotions, such as the amygdala. Emotion-processing circuits are often overactive in chronic pain, and disrupting them might help modify pain perception, the investigators hypothesized. Therefore, they randomly assigned 65 adults with at least 3 months of abdominal pain related to chronic pancreatitis or abdominal surgery to receive oral placebo or THC tablets three times daily for 50-52 days. The 31 patients in the THC group received step-up dosing (3 mg per dose for 5 days, followed by 5 mg per dose for 5 days) followed by stable dosing at 8 mg. Both groups continued other prescribed analgesics as usual, including oxycontin, fentanyl, morphine, codeine, tramadol, paracetamol, anti-epileptics, and nonsteroidal anti-inflammatories. All but two study participants were white, 25 were male, and 24 were female.

At baseline, all patients reported pain of at least 3 on an 11-point visual analogue scale (VAS). By days 50-52, average VAS scores decreased by 1.6 points (40%) in the THC group and by 1.9 points (37%) in the placebo group (P = .9). Although a strong placebo effect is common in studies of visceral pain, that did not prevent pregabalin from significantly outperforming placebo in another similarly designed randomized clinical trial of patients from this study group with chronic pancreatitis, the investigators noted.

The THC and placebo groups also resembled each other on various secondary outcome measures, including patient global impression of change, pain catastrophizing, pain-related anxiety, measures of depression and generalized anxiety, and subjective impressions of alertness, mood, feeling “high,” drowsiness, and difficulties in controlling thoughts. The only exception was that the THC group showed a trend toward improvement on the Short Form 36, compared with the placebo group (P = .051).

Pharmacokinetic analysis showed good oral absorption of THC. Dizziness, somnolence, and headache were common in both groups, but were more frequent with THC than placebo, as was nausea, dry mouth, and visual impairment. There were no serious treatment-related adverse events, although seven patients stopped THC because they could not tolerate the maximum dose.

Some evidence suggests that the shift from acute to chronic pain entails a transition from nociceptive to cognitive, affective, and autonomic sensitization, the researchers noted. “Therefore, an agent targeting particular brain areas related to the cognitive emotional feature of chronic pain, such as THC, might be efficacious in our chronic pain population, but might be better measured by using affective outcomes of pain,” they concluded.

The trial was supported by a grant from the European Union, the European Fund for Regional Development, and the Province of Gelderland. The THC was provided by Echo Pharmaceuticals, Nijmegen, the Netherlands. The investigators reported having no conflicts of interest.

Seven weeks of treatment with delta-9-atetrahydrocannabinol (THC) did not improve chronic abdominal pain in a placebo-controlled trial of 65 adults.

Treatment “was safe and well tolerated,” but did not significantly reduce pain scores or secondary efficacy outcomes, Marjan de Vries, MSc, and her associates wrote in the July issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.09.147). Studies have not clearly shown that THC improves central pain sensitization, a key mechanism in chronic abdominal pain, they noted. Future studies of THC and central sensitization include quantitative sensory testing or electroencephalography, they added.

Source: American Gastroenterological Association

Treatment-refractory chronic abdominal pain is common after abdominal surgery or in chronic pancreatitis, wrote Ms. de Vries of Radboud University Medical Center, Nijmegen, the Netherlands. Affected patients tend to develop central sensitization, or hyper-responsive nociceptive central nervous system pathways. When this happens, pain no longer couples reliably with peripheral stimuli, and therapy targeting central nociceptive pathways is indicated. The main psychoactive compound of Cannabis sativa is THC, which interacts with CB1 receptors in the central nervous system, including in areas of the brain that help regulate emotions, such as the amygdala. Emotion-processing circuits are often overactive in chronic pain, and disrupting them might help modify pain perception, the investigators hypothesized. Therefore, they randomly assigned 65 adults with at least 3 months of abdominal pain related to chronic pancreatitis or abdominal surgery to receive oral placebo or THC tablets three times daily for 50-52 days. The 31 patients in the THC group received step-up dosing (3 mg per dose for 5 days, followed by 5 mg per dose for 5 days) followed by stable dosing at 8 mg. Both groups continued other prescribed analgesics as usual, including oxycontin, fentanyl, morphine, codeine, tramadol, paracetamol, anti-epileptics, and nonsteroidal anti-inflammatories. All but two study participants were white, 25 were male, and 24 were female.

At baseline, all patients reported pain of at least 3 on an 11-point visual analogue scale (VAS). By days 50-52, average VAS scores decreased by 1.6 points (40%) in the THC group and by 1.9 points (37%) in the placebo group (P = .9). Although a strong placebo effect is common in studies of visceral pain, that did not prevent pregabalin from significantly outperforming placebo in another similarly designed randomized clinical trial of patients from this study group with chronic pancreatitis, the investigators noted.

The THC and placebo groups also resembled each other on various secondary outcome measures, including patient global impression of change, pain catastrophizing, pain-related anxiety, measures of depression and generalized anxiety, and subjective impressions of alertness, mood, feeling “high,” drowsiness, and difficulties in controlling thoughts. The only exception was that the THC group showed a trend toward improvement on the Short Form 36, compared with the placebo group (P = .051).

Pharmacokinetic analysis showed good oral absorption of THC. Dizziness, somnolence, and headache were common in both groups, but were more frequent with THC than placebo, as was nausea, dry mouth, and visual impairment. There were no serious treatment-related adverse events, although seven patients stopped THC because they could not tolerate the maximum dose.

Some evidence suggests that the shift from acute to chronic pain entails a transition from nociceptive to cognitive, affective, and autonomic sensitization, the researchers noted. “Therefore, an agent targeting particular brain areas related to the cognitive emotional feature of chronic pain, such as THC, might be efficacious in our chronic pain population, but might be better measured by using affective outcomes of pain,” they concluded.

The trial was supported by a grant from the European Union, the European Fund for Regional Development, and the Province of Gelderland. The THC was provided by Echo Pharmaceuticals, Nijmegen, the Netherlands. The investigators reported having no conflicts of interest.

Seven weeks of treatment with delta-9-atetrahydrocannabinol (THC) did not improve chronic abdominal pain in a placebo-controlled trial of 65 adults.

Treatment “was safe and well tolerated,” but did not significantly reduce pain scores or secondary efficacy outcomes, Marjan de Vries, MSc, and her associates wrote in the July issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.09.147). Studies have not clearly shown that THC improves central pain sensitization, a key mechanism in chronic abdominal pain, they noted. Future studies of THC and central sensitization include quantitative sensory testing or electroencephalography, they added.

Source: American Gastroenterological Association

Treatment-refractory chronic abdominal pain is common after abdominal surgery or in chronic pancreatitis, wrote Ms. de Vries of Radboud University Medical Center, Nijmegen, the Netherlands. Affected patients tend to develop central sensitization, or hyper-responsive nociceptive central nervous system pathways. When this happens, pain no longer couples reliably with peripheral stimuli, and therapy targeting central nociceptive pathways is indicated. The main psychoactive compound of Cannabis sativa is THC, which interacts with CB1 receptors in the central nervous system, including in areas of the brain that help regulate emotions, such as the amygdala. Emotion-processing circuits are often overactive in chronic pain, and disrupting them might help modify pain perception, the investigators hypothesized. Therefore, they randomly assigned 65 adults with at least 3 months of abdominal pain related to chronic pancreatitis or abdominal surgery to receive oral placebo or THC tablets three times daily for 50-52 days. The 31 patients in the THC group received step-up dosing (3 mg per dose for 5 days, followed by 5 mg per dose for 5 days) followed by stable dosing at 8 mg. Both groups continued other prescribed analgesics as usual, including oxycontin, fentanyl, morphine, codeine, tramadol, paracetamol, anti-epileptics, and nonsteroidal anti-inflammatories. All but two study participants were white, 25 were male, and 24 were female.

At baseline, all patients reported pain of at least 3 on an 11-point visual analogue scale (VAS). By days 50-52, average VAS scores decreased by 1.6 points (40%) in the THC group and by 1.9 points (37%) in the placebo group (P = .9). Although a strong placebo effect is common in studies of visceral pain, that did not prevent pregabalin from significantly outperforming placebo in another similarly designed randomized clinical trial of patients from this study group with chronic pancreatitis, the investigators noted.

The THC and placebo groups also resembled each other on various secondary outcome measures, including patient global impression of change, pain catastrophizing, pain-related anxiety, measures of depression and generalized anxiety, and subjective impressions of alertness, mood, feeling “high,” drowsiness, and difficulties in controlling thoughts. The only exception was that the THC group showed a trend toward improvement on the Short Form 36, compared with the placebo group (P = .051).

Pharmacokinetic analysis showed good oral absorption of THC. Dizziness, somnolence, and headache were common in both groups, but were more frequent with THC than placebo, as was nausea, dry mouth, and visual impairment. There were no serious treatment-related adverse events, although seven patients stopped THC because they could not tolerate the maximum dose.

Some evidence suggests that the shift from acute to chronic pain entails a transition from nociceptive to cognitive, affective, and autonomic sensitization, the researchers noted. “Therefore, an agent targeting particular brain areas related to the cognitive emotional feature of chronic pain, such as THC, might be efficacious in our chronic pain population, but might be better measured by using affective outcomes of pain,” they concluded.

The trial was supported by a grant from the European Union, the European Fund for Regional Development, and the Province of Gelderland. The THC was provided by Echo Pharmaceuticals, Nijmegen, the Netherlands. The investigators reported having no conflicts of interest.

Utilization of mesh in laparoscopic paraesophageal hernia repair (PEHR) remained steady from 2011 to 2014, despite a lack of evidence supporting its use, according to Francisco Schlottmann, MD, and his associates.

In an analysis of 9,590 laparoscopic PEHR performed from 2011 to 2014, 60.6% procedures were done without mesh and 39.4% were done with mesh. Over the 3-year study period, mesh utilization fell only 1.2% overall, with laparoscopic PEHR with mesh accounting for 39.4% of procedures in 2011 and 38.2% in 2014.

Patients who received mesh were slightly older and significantly more likely to be an inpatient admission. Postoperative urinary tract infection was less common in patients with mesh, occurring in 1% of patients, compared with 1.5% of patients without mesh. No significant difference in demographics was seen, and 30-day risk of comorbidity and mortality was the same. Mean length of stay was 2.7 days for PEHR with mesh and 2.5 days for PEHR without mesh.

“The use of mesh is associated with high expenses, and biomedical technology continues to offer newer and more expensive mesh products on the market. Given the progressive aging of the U.S. population, PEHR are expected to increase in the future. The indiscriminate and not supported by evidence use of mesh may determine unnecessary costs for the health care system,” the investigators noted.

Find the full study in the Journal of Gastrointestinal Surgery (2017 May 26. doi: 10.1007/s11605-017-3452-8).

[email protected]

Utilization of mesh in laparoscopic paraesophageal hernia repair (PEHR) remained steady from 2011 to 2014, despite a lack of evidence supporting its use, according to Francisco Schlottmann, MD, and his associates.

In an analysis of 9,590 laparoscopic PEHR performed from 2011 to 2014, 60.6% procedures were done without mesh and 39.4% were done with mesh. Over the 3-year study period, mesh utilization fell only 1.2% overall, with laparoscopic PEHR with mesh accounting for 39.4% of procedures in 2011 and 38.2% in 2014.

Patients who received mesh were slightly older and significantly more likely to be an inpatient admission. Postoperative urinary tract infection was less common in patients with mesh, occurring in 1% of patients, compared with 1.5% of patients without mesh. No significant difference in demographics was seen, and 30-day risk of comorbidity and mortality was the same. Mean length of stay was 2.7 days for PEHR with mesh and 2.5 days for PEHR without mesh.

“The use of mesh is associated with high expenses, and biomedical technology continues to offer newer and more expensive mesh products on the market. Given the progressive aging of the U.S. population, PEHR are expected to increase in the future. The indiscriminate and not supported by evidence use of mesh may determine unnecessary costs for the health care system,” the investigators noted.

Find the full study in the Journal of Gastrointestinal Surgery (2017 May 26. doi: 10.1007/s11605-017-3452-8).

[email protected]

Utilization of mesh in laparoscopic paraesophageal hernia repair (PEHR) remained steady from 2011 to 2014, despite a lack of evidence supporting its use, according to Francisco Schlottmann, MD, and his associates.

In an analysis of 9,590 laparoscopic PEHR performed from 2011 to 2014, 60.6% procedures were done without mesh and 39.4% were done with mesh. Over the 3-year study period, mesh utilization fell only 1.2% overall, with laparoscopic PEHR with mesh accounting for 39.4% of procedures in 2011 and 38.2% in 2014.

Patients who received mesh were slightly older and significantly more likely to be an inpatient admission. Postoperative urinary tract infection was less common in patients with mesh, occurring in 1% of patients, compared with 1.5% of patients without mesh. No significant difference in demographics was seen, and 30-day risk of comorbidity and mortality was the same. Mean length of stay was 2.7 days for PEHR with mesh and 2.5 days for PEHR without mesh.

“The use of mesh is associated with high expenses, and biomedical technology continues to offer newer and more expensive mesh products on the market. Given the progressive aging of the U.S. population, PEHR are expected to increase in the future. The indiscriminate and not supported by evidence use of mesh may determine unnecessary costs for the health care system,” the investigators noted.

Find the full study in the Journal of Gastrointestinal Surgery (2017 May 26. doi: 10.1007/s11605-017-3452-8).

[email protected]

CHICAGO – Androgen deprivation therapy (ADT) combined with radiation therapy can safely be reduced from 36 to 18 months without compromising outcomes or quality of life in patients with high-risk localized prostate cancer, according to the final results of a randomized phase III trial.

At a median of 9.4 year follow-up of 630 patients who were randomized to receive pelvic and prostate radiotherapy combined with either 36 or 18 months of ADT, the 10-year overall survival rate was 62.4% and 62.0% in the treatment arms, respectively (global hazard ratio, 1.024), Abdenour Nabid, MD, reported at the annual meeting of the American Society of Clinical Oncology.

Disease-free survival was 44.5% and 39.2% in the groups, respectively (HR, 0.835). This difference did not reach statistical significance, said Dr. Nabid of Centre Hospitalier Regional Universitaire, Sherbrooke, Quebec, Canada.

The disease-free survival curves separated over the course of the study, mainly because of a significant difference in biochemical failure between the groups, which favored the 36-month arm (24.8% vs. 31.0%; HR, 0.714), but this is not an unexpected finding with longer treatment, he explained.

“Does this biochemical control give you more control of the disease? I’m not sure,” he said, noting that bone metastases alone occurred in 23 and 24 patients in the 36 and 18 month treatment groups, respectively, and bone plus other site metastases occurred in 11 patients in each group. “At the end of the day, the P value (for disease-free survival) is not significant (.0768).”

Further, a quality of life analysis showed that patients in the 18-month treatment arm performed significantly better on 6 of 21 scales and 13 of 55 items addressing various quality of life factors. On two of these items – hot flushes and enjoyable sex – a clinically relevant difference of 10 or more points in mean scores was noted, he said.

Long-term ADT combined with radiotherapy is a standard treatment for patients with high-risk prostate cancer, but the optimal duration of treatment has not been defined, Dr. Nabid said.

The current trial looked at treatment duration in patients 80 years and younger (median of 71 in both groups) with T3-T4 disease, PSA levels greater than 20 mg/ml, and Gleason score greater than 7, with normal hepatic function and no regional disease or distant metastases. ADT included a 50 mg initial dose of bicalutamide daily for 1 month plus 10.8 mg of subcutaneous goserelin every 3 months, as well as pelvic and prostate radiotherapy.

On both univariate and multivariate analyses including age, Gleason score greater than 7, treatment duration, prostate-specific antigen greater than 20, T3-T4 disease, and biochemical failure during follow-up, only age and Gleason score were significantly associated with overall survival (HR, 1.05 for age in both analyses, and 1.40 and 1.42, respectively for Gleason score greater than 7 on univariate and multivariate analyses).

“In localized high-risk prostate cancer treated with radiotherapy and androgen deprivation therapy, androgen deprivation therapy duration can be safely reduced from 36 to 18 months,” Dr. Nabid said, adding that 18 months could represent a threshold effect in ADT duration and that side effects and treatment costs can be reduced with shorter duration of therapy.

“Eighteen months of ADT represents a new standard of care,” he concluded.

This study was funded by AstraZeneca Pharmaceuticals. Dr. Nabid has been a speaker, advisory board member, and/or received financial support from Janssen Canada, Sanofi, Astellas, and Bayer.

[email protected]

CHICAGO – Androgen deprivation therapy (ADT) combined with radiation therapy can safely be reduced from 36 to 18 months without compromising outcomes or quality of life in patients with high-risk localized prostate cancer, according to the final results of a randomized phase III trial.

At a median of 9.4 year follow-up of 630 patients who were randomized to receive pelvic and prostate radiotherapy combined with either 36 or 18 months of ADT, the 10-year overall survival rate was 62.4% and 62.0% in the treatment arms, respectively (global hazard ratio, 1.024), Abdenour Nabid, MD, reported at the annual meeting of the American Society of Clinical Oncology.

Disease-free survival was 44.5% and 39.2% in the groups, respectively (HR, 0.835). This difference did not reach statistical significance, said Dr. Nabid of Centre Hospitalier Regional Universitaire, Sherbrooke, Quebec, Canada.

The disease-free survival curves separated over the course of the study, mainly because of a significant difference in biochemical failure between the groups, which favored the 36-month arm (24.8% vs. 31.0%; HR, 0.714), but this is not an unexpected finding with longer treatment, he explained.

“Does this biochemical control give you more control of the disease? I’m not sure,” he said, noting that bone metastases alone occurred in 23 and 24 patients in the 36 and 18 month treatment groups, respectively, and bone plus other site metastases occurred in 11 patients in each group. “At the end of the day, the P value (for disease-free survival) is not significant (.0768).”

Further, a quality of life analysis showed that patients in the 18-month treatment arm performed significantly better on 6 of 21 scales and 13 of 55 items addressing various quality of life factors. On two of these items – hot flushes and enjoyable sex – a clinically relevant difference of 10 or more points in mean scores was noted, he said.

Long-term ADT combined with radiotherapy is a standard treatment for patients with high-risk prostate cancer, but the optimal duration of treatment has not been defined, Dr. Nabid said.

The current trial looked at treatment duration in patients 80 years and younger (median of 71 in both groups) with T3-T4 disease, PSA levels greater than 20 mg/ml, and Gleason score greater than 7, with normal hepatic function and no regional disease or distant metastases. ADT included a 50 mg initial dose of bicalutamide daily for 1 month plus 10.8 mg of subcutaneous goserelin every 3 months, as well as pelvic and prostate radiotherapy.

On both univariate and multivariate analyses including age, Gleason score greater than 7, treatment duration, prostate-specific antigen greater than 20, T3-T4 disease, and biochemical failure during follow-up, only age and Gleason score were significantly associated with overall survival (HR, 1.05 for age in both analyses, and 1.40 and 1.42, respectively for Gleason score greater than 7 on univariate and multivariate analyses).

“In localized high-risk prostate cancer treated with radiotherapy and androgen deprivation therapy, androgen deprivation therapy duration can be safely reduced from 36 to 18 months,” Dr. Nabid said, adding that 18 months could represent a threshold effect in ADT duration and that side effects and treatment costs can be reduced with shorter duration of therapy.

“Eighteen months of ADT represents a new standard of care,” he concluded.

This study was funded by AstraZeneca Pharmaceuticals. Dr. Nabid has been a speaker, advisory board member, and/or received financial support from Janssen Canada, Sanofi, Astellas, and Bayer.

[email protected]

CHICAGO – Androgen deprivation therapy (ADT) combined with radiation therapy can safely be reduced from 36 to 18 months without compromising outcomes or quality of life in patients with high-risk localized prostate cancer, according to the final results of a randomized phase III trial.

At a median of 9.4 year follow-up of 630 patients who were randomized to receive pelvic and prostate radiotherapy combined with either 36 or 18 months of ADT, the 10-year overall survival rate was 62.4% and 62.0% in the treatment arms, respectively (global hazard ratio, 1.024), Abdenour Nabid, MD, reported at the annual meeting of the American Society of Clinical Oncology.

Disease-free survival was 44.5% and 39.2% in the groups, respectively (HR, 0.835). This difference did not reach statistical significance, said Dr. Nabid of Centre Hospitalier Regional Universitaire, Sherbrooke, Quebec, Canada.

The disease-free survival curves separated over the course of the study, mainly because of a significant difference in biochemical failure between the groups, which favored the 36-month arm (24.8% vs. 31.0%; HR, 0.714), but this is not an unexpected finding with longer treatment, he explained.

“Does this biochemical control give you more control of the disease? I’m not sure,” he said, noting that bone metastases alone occurred in 23 and 24 patients in the 36 and 18 month treatment groups, respectively, and bone plus other site metastases occurred in 11 patients in each group. “At the end of the day, the P value (for disease-free survival) is not significant (.0768).”

Further, a quality of life analysis showed that patients in the 18-month treatment arm performed significantly better on 6 of 21 scales and 13 of 55 items addressing various quality of life factors. On two of these items – hot flushes and enjoyable sex – a clinically relevant difference of 10 or more points in mean scores was noted, he said.

Long-term ADT combined with radiotherapy is a standard treatment for patients with high-risk prostate cancer, but the optimal duration of treatment has not been defined, Dr. Nabid said.

The current trial looked at treatment duration in patients 80 years and younger (median of 71 in both groups) with T3-T4 disease, PSA levels greater than 20 mg/ml, and Gleason score greater than 7, with normal hepatic function and no regional disease or distant metastases. ADT included a 50 mg initial dose of bicalutamide daily for 1 month plus 10.8 mg of subcutaneous goserelin every 3 months, as well as pelvic and prostate radiotherapy.

On both univariate and multivariate analyses including age, Gleason score greater than 7, treatment duration, prostate-specific antigen greater than 20, T3-T4 disease, and biochemical failure during follow-up, only age and Gleason score were significantly associated with overall survival (HR, 1.05 for age in both analyses, and 1.40 and 1.42, respectively for Gleason score greater than 7 on univariate and multivariate analyses).

“In localized high-risk prostate cancer treated with radiotherapy and androgen deprivation therapy, androgen deprivation therapy duration can be safely reduced from 36 to 18 months,” Dr. Nabid said, adding that 18 months could represent a threshold effect in ADT duration and that side effects and treatment costs can be reduced with shorter duration of therapy.

“Eighteen months of ADT represents a new standard of care,” he concluded.

This study was funded by AstraZeneca Pharmaceuticals. Dr. Nabid has been a speaker, advisory board member, and/or received financial support from Janssen Canada, Sanofi, Astellas, and Bayer.

[email protected]

CHICAGO – CARs just keep getting better: In an early clinical trial, a chimeric antigen receptor (CAR) T-cell construct targeting B-cell maturation protein induced clinical remissions in 33 of 35 patients with relapsed/refractory multiple myeloma who were treated in an early clinical trial.

“In our current trials we have observed revolutionary, quick, and durable remissions in patients with multiple myeloma,” said Wanhong Zhao, MD, of the Second Affiliated Hospital of Xi’an (China) Jiaotong University.

CHICAGO – CARs just keep getting better: In an early clinical trial, a chimeric antigen receptor (CAR) T-cell construct targeting B-cell maturation protein induced clinical remissions in 33 of 35 patients with relapsed/refractory multiple myeloma who were treated in an early clinical trial.

“In our current trials we have observed revolutionary, quick, and durable remissions in patients with multiple myeloma,” said Wanhong Zhao, MD, of the Second Affiliated Hospital of Xi’an (China) Jiaotong University.

CHICAGO – CARs just keep getting better: In an early clinical trial, a chimeric antigen receptor (CAR) T-cell construct targeting B-cell maturation protein induced clinical remissions in 33 of 35 patients with relapsed/refractory multiple myeloma who were treated in an early clinical trial.

“In our current trials we have observed revolutionary, quick, and durable remissions in patients with multiple myeloma,” said Wanhong Zhao, MD, of the Second Affiliated Hospital of Xi’an (China) Jiaotong University.