Maintenance of Certification (MOC) is an American Board of Medical Specialties (ABMS) requirement for their 24 member boards. The MOC process has received much criticism, especially in recent years. To date, a 5-hour exam at a secure testing center every 10 years covering comprehensive vascular surgery knowledge has been the routine. This requirement had the surgeon take off a day from work for the exam, in addition to the time it took to prepare. Burnout, at least in part, is related to the sheer volume of busywork not directly relevant to being a practicing surgeon.

The American Board of Surgery is sensitive to both the relevance of MOC and needs of the diplomate, and is striving to make appropriate changes. Diplomates were surveyed regarding MOC and the accompanying exam in both 2016 and 2017. Using this input, the development of the 10-year exam format was studied carefully by the board directors and executive staff, all of whom are active in the clinical practice of surgery, and a new process now known as Continuous Certification was introduced. The intent of the new Continuous Certification Assessment (to replace the every-10-year MOC exam) is to be an activity that is convenient, timely, and more reflective of the surgeon’s daily practice. The assessment is to be done every 2 years and is online, open book, and taken at a place of the examinee’s choosing, such as the home or in the office. Another key feature of the continuous certification process is that the total number of CME required is decreased and the self-assessment requirement is eliminated.

In November 2018, I took the first General Surgery Continuous Certification Assessment. There was approximately a 2-month window to register, and online registration was simple, taking only about 15 minutes to complete. All the references were listed on the ABS website and the vast majority were open access and directly linked to the article. For those articles that were not open access, there was a link to the PubMed abstract. I downloaded all of the articles (actually this part my assistant did) and requested five articles from the library. I did not review the articles in advance, but used them when going sequentially through the assessment questions. Depending on the article, I read it or looked up the specific aspect I was looking for. I worked on the test three different times – at the airport during a long layover, at home, and at my office. After answering each question, I received feedback on what was the correct answer and a one-paragraph explanation which I read completely. After completing all 40 questions, each question for which I had an incorrect answer (not more than one or two of course, Ha!) was shown again with the opportunity to answer the question. The total time took me was about 4.5 hours. All in all, it was a good experience, and I learned something.

The general surgery assessment is modular. Twenty questions (half) were core surgery topics, and the other twenty questions came from one of four specialty modules of the examinee’s choice – breast, abdomen, alimentary tract, or comprehensive general surgery. I took the core and the abdomen modules. The core topics were, for the most part, areas that a surgeon who does patient care would find relevant (for example, perioperative management of a patient on corticosteroids, postoperative delirium, and prophylaxis for venous thromboembolism).

A couple of other details should be mentioned about this new process. From the time of initiation of the assessment, there are 2 weeks allocated for completion. One needs 80% correct to pass. If the examinee receives less than 80% but higher than 40% on the first assessment attempt, he/she will have a second attempt to answer the questions that were incorrect on the first try. If a cumulative score of less than 80% is achieved after the second attempt, a grace year will be provided, which is an extension of certification for 1 year with the opportunity to take the next year’s assessment. If after the grace year (four attempts) the diplomate is unsuccessful, then a secure exam is required to regain certification.

Overall, there has been much positive feedback. Of the 2,164 diplomates taking the Continuous Certification Assessment, only 21 were unsuccessful. Therefore, the pass rate was over 99% for the inaugural year. The average examinee took just over 3 hours to complete the assessment.

In 2018, the 10-year recertification examination in vascular surgery with 10 years of credit was given for the last time. The Vascular Surgery Continuous Certification Assessment is in preparation now and will roll out in the fall of 2019. It will follow a format similar to general surgery with 40 questions on a number of topics in vascular surgery. However, the vascular surgery assessment will not be modular. This activity will incorporate general knowledge (for example, from consensus guidelines), as well as late breaking trials. So far, this process looks to be a better one, as well as more efficient and relevant for the busy surgeon.

Dr. Gahtan is professor and chief, division of vascular surgery and endovascular services, State University of New York Upstate Medical University, Syracuse.

Maintenance of Certification (MOC) is an American Board of Medical Specialties (ABMS) requirement for their 24 member boards. The MOC process has received much criticism, especially in recent years. To date, a 5-hour exam at a secure testing center every 10 years covering comprehensive vascular surgery knowledge has been the routine. This requirement had the surgeon take off a day from work for the exam, in addition to the time it took to prepare. Burnout, at least in part, is related to the sheer volume of busywork not directly relevant to being a practicing surgeon.

The American Board of Surgery is sensitive to both the relevance of MOC and needs of the diplomate, and is striving to make appropriate changes. Diplomates were surveyed regarding MOC and the accompanying exam in both 2016 and 2017. Using this input, the development of the 10-year exam format was studied carefully by the board directors and executive staff, all of whom are active in the clinical practice of surgery, and a new process now known as Continuous Certification was introduced. The intent of the new Continuous Certification Assessment (to replace the every-10-year MOC exam) is to be an activity that is convenient, timely, and more reflective of the surgeon’s daily practice. The assessment is to be done every 2 years and is online, open book, and taken at a place of the examinee’s choosing, such as the home or in the office. Another key feature of the continuous certification process is that the total number of CME required is decreased and the self-assessment requirement is eliminated.

In November 2018, I took the first General Surgery Continuous Certification Assessment. There was approximately a 2-month window to register, and online registration was simple, taking only about 15 minutes to complete. All the references were listed on the ABS website and the vast majority were open access and directly linked to the article. For those articles that were not open access, there was a link to the PubMed abstract. I downloaded all of the articles (actually this part my assistant did) and requested five articles from the library. I did not review the articles in advance, but used them when going sequentially through the assessment questions. Depending on the article, I read it or looked up the specific aspect I was looking for. I worked on the test three different times – at the airport during a long layover, at home, and at my office. After answering each question, I received feedback on what was the correct answer and a one-paragraph explanation which I read completely. After completing all 40 questions, each question for which I had an incorrect answer (not more than one or two of course, Ha!) was shown again with the opportunity to answer the question. The total time took me was about 4.5 hours. All in all, it was a good experience, and I learned something.

The general surgery assessment is modular. Twenty questions (half) were core surgery topics, and the other twenty questions came from one of four specialty modules of the examinee’s choice – breast, abdomen, alimentary tract, or comprehensive general surgery. I took the core and the abdomen modules. The core topics were, for the most part, areas that a surgeon who does patient care would find relevant (for example, perioperative management of a patient on corticosteroids, postoperative delirium, and prophylaxis for venous thromboembolism).

A couple of other details should be mentioned about this new process. From the time of initiation of the assessment, there are 2 weeks allocated for completion. One needs 80% correct to pass. If the examinee receives less than 80% but higher than 40% on the first assessment attempt, he/she will have a second attempt to answer the questions that were incorrect on the first try. If a cumulative score of less than 80% is achieved after the second attempt, a grace year will be provided, which is an extension of certification for 1 year with the opportunity to take the next year’s assessment. If after the grace year (four attempts) the diplomate is unsuccessful, then a secure exam is required to regain certification.

Overall, there has been much positive feedback. Of the 2,164 diplomates taking the Continuous Certification Assessment, only 21 were unsuccessful. Therefore, the pass rate was over 99% for the inaugural year. The average examinee took just over 3 hours to complete the assessment.

In 2018, the 10-year recertification examination in vascular surgery with 10 years of credit was given for the last time. The Vascular Surgery Continuous Certification Assessment is in preparation now and will roll out in the fall of 2019. It will follow a format similar to general surgery with 40 questions on a number of topics in vascular surgery. However, the vascular surgery assessment will not be modular. This activity will incorporate general knowledge (for example, from consensus guidelines), as well as late breaking trials. So far, this process looks to be a better one, as well as more efficient and relevant for the busy surgeon.

Dr. Gahtan is professor and chief, division of vascular surgery and endovascular services, State University of New York Upstate Medical University, Syracuse.

Maintenance of Certification (MOC) is an American Board of Medical Specialties (ABMS) requirement for their 24 member boards. The MOC process has received much criticism, especially in recent years. To date, a 5-hour exam at a secure testing center every 10 years covering comprehensive vascular surgery knowledge has been the routine. This requirement had the surgeon take off a day from work for the exam, in addition to the time it took to prepare. Burnout, at least in part, is related to the sheer volume of busywork not directly relevant to being a practicing surgeon.

The American Board of Surgery is sensitive to both the relevance of MOC and needs of the diplomate, and is striving to make appropriate changes. Diplomates were surveyed regarding MOC and the accompanying exam in both 2016 and 2017. Using this input, the development of the 10-year exam format was studied carefully by the board directors and executive staff, all of whom are active in the clinical practice of surgery, and a new process now known as Continuous Certification was introduced. The intent of the new Continuous Certification Assessment (to replace the every-10-year MOC exam) is to be an activity that is convenient, timely, and more reflective of the surgeon’s daily practice. The assessment is to be done every 2 years and is online, open book, and taken at a place of the examinee’s choosing, such as the home or in the office. Another key feature of the continuous certification process is that the total number of CME required is decreased and the self-assessment requirement is eliminated.

In November 2018, I took the first General Surgery Continuous Certification Assessment. There was approximately a 2-month window to register, and online registration was simple, taking only about 15 minutes to complete. All the references were listed on the ABS website and the vast majority were open access and directly linked to the article. For those articles that were not open access, there was a link to the PubMed abstract. I downloaded all of the articles (actually this part my assistant did) and requested five articles from the library. I did not review the articles in advance, but used them when going sequentially through the assessment questions. Depending on the article, I read it or looked up the specific aspect I was looking for. I worked on the test three different times – at the airport during a long layover, at home, and at my office. After answering each question, I received feedback on what was the correct answer and a one-paragraph explanation which I read completely. After completing all 40 questions, each question for which I had an incorrect answer (not more than one or two of course, Ha!) was shown again with the opportunity to answer the question. The total time took me was about 4.5 hours. All in all, it was a good experience, and I learned something.

The general surgery assessment is modular. Twenty questions (half) were core surgery topics, and the other twenty questions came from one of four specialty modules of the examinee’s choice – breast, abdomen, alimentary tract, or comprehensive general surgery. I took the core and the abdomen modules. The core topics were, for the most part, areas that a surgeon who does patient care would find relevant (for example, perioperative management of a patient on corticosteroids, postoperative delirium, and prophylaxis for venous thromboembolism).

A couple of other details should be mentioned about this new process. From the time of initiation of the assessment, there are 2 weeks allocated for completion. One needs 80% correct to pass. If the examinee receives less than 80% but higher than 40% on the first assessment attempt, he/she will have a second attempt to answer the questions that were incorrect on the first try. If a cumulative score of less than 80% is achieved after the second attempt, a grace year will be provided, which is an extension of certification for 1 year with the opportunity to take the next year’s assessment. If after the grace year (four attempts) the diplomate is unsuccessful, then a secure exam is required to regain certification.

Overall, there has been much positive feedback. Of the 2,164 diplomates taking the Continuous Certification Assessment, only 21 were unsuccessful. Therefore, the pass rate was over 99% for the inaugural year. The average examinee took just over 3 hours to complete the assessment.

In 2018, the 10-year recertification examination in vascular surgery with 10 years of credit was given for the last time. The Vascular Surgery Continuous Certification Assessment is in preparation now and will roll out in the fall of 2019. It will follow a format similar to general surgery with 40 questions on a number of topics in vascular surgery. However, the vascular surgery assessment will not be modular. This activity will incorporate general knowledge (for example, from consensus guidelines), as well as late breaking trials. So far, this process looks to be a better one, as well as more efficient and relevant for the busy surgeon.

Dr. Gahtan is professor and chief, division of vascular surgery and endovascular services, State University of New York Upstate Medical University, Syracuse.

There has been an increasing demand for achieving noninvasive skin lifting and tightening around aging knees and elbows. The cosmetic industry improves techniques for tightening faces, hands, necks, and decolletes; meanwhile, sagging elbows and knees, once ignored, also are a visible sign of aging. Modifying techniques commonly used for the face and neck can yield significant improvements in the elbows and knees. The elbows and knees naturally have looser skin to allow for joint movement; over time, the skin over these joints is exposed to sun damage, friction, and recurrent extension and flexion, which cause skin laxity and aging.

A combination approach addressing skin texture, collagen damage, rhytides, and fat deposition is the most effective method for knee and elbow rejuvenation.

For knees and elbows with loose skin and rhytides, in-office noninvasive and minimally invasive radio-frequency and light energy treatments are helpful in increasing collagen production and tissue tightening. Similarly, microfocused ultrasound has been shown to be a safe and effective skin tightening treatment for the knees. In comparison to the face, however, the skin around the elbows and knees can be thinner and has fewer sebaceous glands. Caution should be used particularly with minimally invasive radio-frequency techniques in order to protect the epidermal skin. Often, treatments have to be repeated to give optimal results, which are not apparent until 3-6 months after the initial procedure.

For knee skin with severe laxity, a comprehensive approach using polydioxanone (PDO) or poly-l-lactic acid (PLLA) threads in both the upper thighs and circumferentially around the knees provides collagen production and tightening of the loose skin. Treatment of the upper thighs is essential in providing a vector that lifts the skin of the knees. Treatments can be repeated, with results seen after 90 days. Thread lifts of the knees and thighs are highly effective, noninvasive procedures with little to no downtime and can be used for severe skin laxity, wrinkling, and thinning of the knee skin.

Lily Talakoub, MD

Loose, roughened knee and elbow skin can also be treated with nonablative factional resurfacing, radio-frequency microneedling, or a series of monthly treatments with PLLA and hyaluronic acid fillers injected in the superficial to mid-dermis. Both fractional resurfacing and dermal filler injections help stimulate collagen production and improve both fine rhytides and dermatoheliosis.

Adipose tissue around the knees can be treated with monthly deoxycholic acid injections (for a video of this procedure, go to https://drive.google.com/file/d/1rhw-nESy15AoDhKUrc25DDjKEun7RL4i/view). The volume of injection, however, is significantly higher than that recommended in the submental area. Two to four times the volume is needed per knee over a series of 3-6 treatments, depending on the amount of fat in the knees.

Cryolipolysis is also an effective option for fat pockets around the knees; however, in my experience, it can be difficult to fit the applicators onto the area of concern appropriately unless smaller applicators are applied.

With the increasing demand for body rejuvenation techniques, providers are adapting techniques used for the face and neck to lift, tighten, thin, and sculpt the knees and elbows. A combination approach using lasers, ultrasound, fillers, threads, and cryolipolysis can be effective for these areas. Results are obtainable when repeat treatments are performed; however, one must be patient because results are not seen for 6 months or more.

Dr. Lily Talakoub and Dr. Naissan Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

References

Macedo O. et al. J Am Acad Dermatol. 2014;70(Suppl 1), Abstract P800, page AB193.
 

There has been an increasing demand for achieving noninvasive skin lifting and tightening around aging knees and elbows. The cosmetic industry improves techniques for tightening faces, hands, necks, and decolletes; meanwhile, sagging elbows and knees, once ignored, also are a visible sign of aging. Modifying techniques commonly used for the face and neck can yield significant improvements in the elbows and knees. The elbows and knees naturally have looser skin to allow for joint movement; over time, the skin over these joints is exposed to sun damage, friction, and recurrent extension and flexion, which cause skin laxity and aging.

A combination approach addressing skin texture, collagen damage, rhytides, and fat deposition is the most effective method for knee and elbow rejuvenation.

For knees and elbows with loose skin and rhytides, in-office noninvasive and minimally invasive radio-frequency and light energy treatments are helpful in increasing collagen production and tissue tightening. Similarly, microfocused ultrasound has been shown to be a safe and effective skin tightening treatment for the knees. In comparison to the face, however, the skin around the elbows and knees can be thinner and has fewer sebaceous glands. Caution should be used particularly with minimally invasive radio-frequency techniques in order to protect the epidermal skin. Often, treatments have to be repeated to give optimal results, which are not apparent until 3-6 months after the initial procedure.

For knee skin with severe laxity, a comprehensive approach using polydioxanone (PDO) or poly-l-lactic acid (PLLA) threads in both the upper thighs and circumferentially around the knees provides collagen production and tightening of the loose skin. Treatment of the upper thighs is essential in providing a vector that lifts the skin of the knees. Treatments can be repeated, with results seen after 90 days. Thread lifts of the knees and thighs are highly effective, noninvasive procedures with little to no downtime and can be used for severe skin laxity, wrinkling, and thinning of the knee skin.

Lily Talakoub, MD

Loose, roughened knee and elbow skin can also be treated with nonablative factional resurfacing, radio-frequency microneedling, or a series of monthly treatments with PLLA and hyaluronic acid fillers injected in the superficial to mid-dermis. Both fractional resurfacing and dermal filler injections help stimulate collagen production and improve both fine rhytides and dermatoheliosis.

Adipose tissue around the knees can be treated with monthly deoxycholic acid injections (for a video of this procedure, go to https://drive.google.com/file/d/1rhw-nESy15AoDhKUrc25DDjKEun7RL4i/view). The volume of injection, however, is significantly higher than that recommended in the submental area. Two to four times the volume is needed per knee over a series of 3-6 treatments, depending on the amount of fat in the knees.

Cryolipolysis is also an effective option for fat pockets around the knees; however, in my experience, it can be difficult to fit the applicators onto the area of concern appropriately unless smaller applicators are applied.

With the increasing demand for body rejuvenation techniques, providers are adapting techniques used for the face and neck to lift, tighten, thin, and sculpt the knees and elbows. A combination approach using lasers, ultrasound, fillers, threads, and cryolipolysis can be effective for these areas. Results are obtainable when repeat treatments are performed; however, one must be patient because results are not seen for 6 months or more.

Dr. Lily Talakoub and Dr. Naissan Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

References

Macedo O. et al. J Am Acad Dermatol. 2014;70(Suppl 1), Abstract P800, page AB193.
 

There has been an increasing demand for achieving noninvasive skin lifting and tightening around aging knees and elbows. The cosmetic industry improves techniques for tightening faces, hands, necks, and decolletes; meanwhile, sagging elbows and knees, once ignored, also are a visible sign of aging. Modifying techniques commonly used for the face and neck can yield significant improvements in the elbows and knees. The elbows and knees naturally have looser skin to allow for joint movement; over time, the skin over these joints is exposed to sun damage, friction, and recurrent extension and flexion, which cause skin laxity and aging.

A combination approach addressing skin texture, collagen damage, rhytides, and fat deposition is the most effective method for knee and elbow rejuvenation.

For knees and elbows with loose skin and rhytides, in-office noninvasive and minimally invasive radio-frequency and light energy treatments are helpful in increasing collagen production and tissue tightening. Similarly, microfocused ultrasound has been shown to be a safe and effective skin tightening treatment for the knees. In comparison to the face, however, the skin around the elbows and knees can be thinner and has fewer sebaceous glands. Caution should be used particularly with minimally invasive radio-frequency techniques in order to protect the epidermal skin. Often, treatments have to be repeated to give optimal results, which are not apparent until 3-6 months after the initial procedure.

For knee skin with severe laxity, a comprehensive approach using polydioxanone (PDO) or poly-l-lactic acid (PLLA) threads in both the upper thighs and circumferentially around the knees provides collagen production and tightening of the loose skin. Treatment of the upper thighs is essential in providing a vector that lifts the skin of the knees. Treatments can be repeated, with results seen after 90 days. Thread lifts of the knees and thighs are highly effective, noninvasive procedures with little to no downtime and can be used for severe skin laxity, wrinkling, and thinning of the knee skin.

Lily Talakoub, MD

Loose, roughened knee and elbow skin can also be treated with nonablative factional resurfacing, radio-frequency microneedling, or a series of monthly treatments with PLLA and hyaluronic acid fillers injected in the superficial to mid-dermis. Both fractional resurfacing and dermal filler injections help stimulate collagen production and improve both fine rhytides and dermatoheliosis.

Adipose tissue around the knees can be treated with monthly deoxycholic acid injections (for a video of this procedure, go to https://drive.google.com/file/d/1rhw-nESy15AoDhKUrc25DDjKEun7RL4i/view). The volume of injection, however, is significantly higher than that recommended in the submental area. Two to four times the volume is needed per knee over a series of 3-6 treatments, depending on the amount of fat in the knees.

Cryolipolysis is also an effective option for fat pockets around the knees; however, in my experience, it can be difficult to fit the applicators onto the area of concern appropriately unless smaller applicators are applied.

With the increasing demand for body rejuvenation techniques, providers are adapting techniques used for the face and neck to lift, tighten, thin, and sculpt the knees and elbows. A combination approach using lasers, ultrasound, fillers, threads, and cryolipolysis can be effective for these areas. Results are obtainable when repeat treatments are performed; however, one must be patient because results are not seen for 6 months or more.

Dr. Lily Talakoub and Dr. Naissan Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

References

Macedo O. et al. J Am Acad Dermatol. 2014;70(Suppl 1), Abstract P800, page AB193.
 

© ASH/Luke Franke 2018

SAN DIEGO—An interim analysis from the MAIA trial showed that adding daratumumab to lenalidomide and dexamethasone could significantly improve progression-free survival (PFS) in older patients with multiple myeloma (MM) who were ineligible for transplant.

The 30-month PFS rate was 71% in patients who received daratumumab plus lenalidomide and dexamethasone (DRd) and 56% in patients who received only lenalidomide and dexamethasone (Rd).

“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” said Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille in France.

Dr. Facon presented results from MAIA during the late-breaking abstracts session at the 2018 ASH Annual Meeting (abstract LBA-2).

The phase 3 trial (NCT02252172) enrolled 737 transplant-ineligible patients with newly diagnosed MM.

The patients were randomly assigned to DRd or Rd. Daratumumab was given at 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression.

Lenalidomide was given at 25 mg orally per day on days 1-21 until disease progression, and dexamethasone was given at 40 mg orally or intravenously weekly until disease progression.

The median patient age was 73 years, and 99% of all patients were 65 or older. Demographic and clinical characteristics were well balanced between the treatment arms.

Results

The primary endpoint of PFS was superior with DRd.

At a median follow-up of 28 months, the median PFS had not been reached in the DRd arm and was 31.9 months in the Rd arm.

The 30-month PFS rate was 71% in the DRd arm and 56% in the Rd arm (hazard ratio [HR]=0.56; P<0.0001).

DRd was associated with a significantly higher overall response rate than Rd—93% and 81%, respectively (P<0.0001).

The complete response rates were 48% and 25%, respectively (P<0.0001). The rates of very good partial response or better were 79% and 53%, respectively (P<0.0001). And the rates of minimal residual disease negativity were 24% and 7%, respectively (P<0.0001).

DRd was associated with infusion-related reactions in 41% of patients, and 3% were grade 3 or 4 in severity.

Hematologic treatment-emergent adverse events of grade 3 or higher that were more common with DRd than Rd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%).

Conversely, grade 3/4 thrombocytopenia (7% vs. 9%) and anemia (12% vs. 20%) were more frequent with Rd.

Nonhematologic treatment-emergent adverse events that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia.

Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the treatment arms.

Janssen funded this study. Dr. Facon reported relationships with Celgene, Janssen, Takeda, Sanofi, Amgen, Karyopharm, and Oncopeptides.

© ASH/Luke Franke 2018

SAN DIEGO—An interim analysis from the MAIA trial showed that adding daratumumab to lenalidomide and dexamethasone could significantly improve progression-free survival (PFS) in older patients with multiple myeloma (MM) who were ineligible for transplant.

The 30-month PFS rate was 71% in patients who received daratumumab plus lenalidomide and dexamethasone (DRd) and 56% in patients who received only lenalidomide and dexamethasone (Rd).

“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” said Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille in France.

Dr. Facon presented results from MAIA during the late-breaking abstracts session at the 2018 ASH Annual Meeting (abstract LBA-2).

The phase 3 trial (NCT02252172) enrolled 737 transplant-ineligible patients with newly diagnosed MM.

The patients were randomly assigned to DRd or Rd. Daratumumab was given at 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression.

Lenalidomide was given at 25 mg orally per day on days 1-21 until disease progression, and dexamethasone was given at 40 mg orally or intravenously weekly until disease progression.

The median patient age was 73 years, and 99% of all patients were 65 or older. Demographic and clinical characteristics were well balanced between the treatment arms.

Results

The primary endpoint of PFS was superior with DRd.

At a median follow-up of 28 months, the median PFS had not been reached in the DRd arm and was 31.9 months in the Rd arm.

The 30-month PFS rate was 71% in the DRd arm and 56% in the Rd arm (hazard ratio [HR]=0.56; P<0.0001).

DRd was associated with a significantly higher overall response rate than Rd—93% and 81%, respectively (P<0.0001).

The complete response rates were 48% and 25%, respectively (P<0.0001). The rates of very good partial response or better were 79% and 53%, respectively (P<0.0001). And the rates of minimal residual disease negativity were 24% and 7%, respectively (P<0.0001).

DRd was associated with infusion-related reactions in 41% of patients, and 3% were grade 3 or 4 in severity.

Hematologic treatment-emergent adverse events of grade 3 or higher that were more common with DRd than Rd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%).

Conversely, grade 3/4 thrombocytopenia (7% vs. 9%) and anemia (12% vs. 20%) were more frequent with Rd.

Nonhematologic treatment-emergent adverse events that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia.

Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the treatment arms.

Janssen funded this study. Dr. Facon reported relationships with Celgene, Janssen, Takeda, Sanofi, Amgen, Karyopharm, and Oncopeptides.

© ASH/Luke Franke 2018

SAN DIEGO—An interim analysis from the MAIA trial showed that adding daratumumab to lenalidomide and dexamethasone could significantly improve progression-free survival (PFS) in older patients with multiple myeloma (MM) who were ineligible for transplant.

The 30-month PFS rate was 71% in patients who received daratumumab plus lenalidomide and dexamethasone (DRd) and 56% in patients who received only lenalidomide and dexamethasone (Rd).

“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” said Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille in France.

Dr. Facon presented results from MAIA during the late-breaking abstracts session at the 2018 ASH Annual Meeting (abstract LBA-2).

The phase 3 trial (NCT02252172) enrolled 737 transplant-ineligible patients with newly diagnosed MM.

The patients were randomly assigned to DRd or Rd. Daratumumab was given at 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression.

Lenalidomide was given at 25 mg orally per day on days 1-21 until disease progression, and dexamethasone was given at 40 mg orally or intravenously weekly until disease progression.

The median patient age was 73 years, and 99% of all patients were 65 or older. Demographic and clinical characteristics were well balanced between the treatment arms.

Results

The primary endpoint of PFS was superior with DRd.

At a median follow-up of 28 months, the median PFS had not been reached in the DRd arm and was 31.9 months in the Rd arm.

The 30-month PFS rate was 71% in the DRd arm and 56% in the Rd arm (hazard ratio [HR]=0.56; P<0.0001).

DRd was associated with a significantly higher overall response rate than Rd—93% and 81%, respectively (P<0.0001).

The complete response rates were 48% and 25%, respectively (P<0.0001). The rates of very good partial response or better were 79% and 53%, respectively (P<0.0001). And the rates of minimal residual disease negativity were 24% and 7%, respectively (P<0.0001).

DRd was associated with infusion-related reactions in 41% of patients, and 3% were grade 3 or 4 in severity.

Hematologic treatment-emergent adverse events of grade 3 or higher that were more common with DRd than Rd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%).

Conversely, grade 3/4 thrombocytopenia (7% vs. 9%) and anemia (12% vs. 20%) were more frequent with Rd.

Nonhematologic treatment-emergent adverse events that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia.

Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the treatment arms.

Janssen funded this study. Dr. Facon reported relationships with Celgene, Janssen, Takeda, Sanofi, Amgen, Karyopharm, and Oncopeptides.

Some measures of the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) were associated with lower levels of ability to give consent in patients with bipolar disorder, according to Christina C. Klein and her associates.

A total of 50 patients who were enrolled in a clinical trial of approved, standard treatments for bipolar disease were included in the consent study. The MacCAT-CR was administered after patients had given consent to be included in the trial, but before the trial had started. Four patients lacked the ability to provide consent for the trial after receiving the MacCAT-CR. After these patients were reeducated and went through the consent process a second time, three were enrolled and one declined enrollment.

Patients with higher Schedule for Assessment of Positive Symptoms scores were more likely to have worse MacCAT-CR Understanding and Appreciation subscale scores; lower Hamilton Depression Rating Scale and higher Clinical Global Impression–Severity scores were associated with worse Reasoning and Understanding subscale scores.

Comorbid ADHD, sex, IQ scores, and age at onset of bipolar disorder were not correlated with any subscale scores. In addition, a history of substance use disorder was associated with higher Appreciation and Reasoning subscale scores.

“The current study provides important information for clinicians and researchers to consider when obtaining informed consent from an individual with bipolar disorder. The MacCAT-CR may serve to identify patients, specifically those with higher psychotic symptoms or global illness severity, as needing additional education regarding informed consent,” the investigators concluded.

Three study coauthors reported conflicts of interest with numerous pharmaceutical companies.

[email protected]

SOURCE: Klein CC et al. J Affect Disord. 2018 Aug 13. doi: 10.1016/j.jad.2018.08.049.

Some measures of the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) were associated with lower levels of ability to give consent in patients with bipolar disorder, according to Christina C. Klein and her associates.

A total of 50 patients who were enrolled in a clinical trial of approved, standard treatments for bipolar disease were included in the consent study. The MacCAT-CR was administered after patients had given consent to be included in the trial, but before the trial had started. Four patients lacked the ability to provide consent for the trial after receiving the MacCAT-CR. After these patients were reeducated and went through the consent process a second time, three were enrolled and one declined enrollment.

Patients with higher Schedule for Assessment of Positive Symptoms scores were more likely to have worse MacCAT-CR Understanding and Appreciation subscale scores; lower Hamilton Depression Rating Scale and higher Clinical Global Impression–Severity scores were associated with worse Reasoning and Understanding subscale scores.

Comorbid ADHD, sex, IQ scores, and age at onset of bipolar disorder were not correlated with any subscale scores. In addition, a history of substance use disorder was associated with higher Appreciation and Reasoning subscale scores.

“The current study provides important information for clinicians and researchers to consider when obtaining informed consent from an individual with bipolar disorder. The MacCAT-CR may serve to identify patients, specifically those with higher psychotic symptoms or global illness severity, as needing additional education regarding informed consent,” the investigators concluded.

Three study coauthors reported conflicts of interest with numerous pharmaceutical companies.

[email protected]

SOURCE: Klein CC et al. J Affect Disord. 2018 Aug 13. doi: 10.1016/j.jad.2018.08.049.

Some measures of the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) were associated with lower levels of ability to give consent in patients with bipolar disorder, according to Christina C. Klein and her associates.

A total of 50 patients who were enrolled in a clinical trial of approved, standard treatments for bipolar disease were included in the consent study. The MacCAT-CR was administered after patients had given consent to be included in the trial, but before the trial had started. Four patients lacked the ability to provide consent for the trial after receiving the MacCAT-CR. After these patients were reeducated and went through the consent process a second time, three were enrolled and one declined enrollment.

Patients with higher Schedule for Assessment of Positive Symptoms scores were more likely to have worse MacCAT-CR Understanding and Appreciation subscale scores; lower Hamilton Depression Rating Scale and higher Clinical Global Impression–Severity scores were associated with worse Reasoning and Understanding subscale scores.

Comorbid ADHD, sex, IQ scores, and age at onset of bipolar disorder were not correlated with any subscale scores. In addition, a history of substance use disorder was associated with higher Appreciation and Reasoning subscale scores.

“The current study provides important information for clinicians and researchers to consider when obtaining informed consent from an individual with bipolar disorder. The MacCAT-CR may serve to identify patients, specifically those with higher psychotic symptoms or global illness severity, as needing additional education regarding informed consent,” the investigators concluded.

Three study coauthors reported conflicts of interest with numerous pharmaceutical companies.

[email protected]

SOURCE: Klein CC et al. J Affect Disord. 2018 Aug 13. doi: 10.1016/j.jad.2018.08.049.

In a new comment letter to FDA, AGA commends FDA’s recent draft guidance – “Policy Regarding Quantitative Labeling of Dietary Supplements Containing Live Microbials” – clarifying the expectations of probiotics manufacturers who choose to specify the amount of a live microbial component in their product in colony forming units (CFUs).

Though manufacturers are not currently required to report CFUs, AGA feels strongly that all manufacturers of probiotic supplements should voluntarily report the composition of live microbials in their products as CFUs.

However, reporting CFUs alone provides insufficient information to consumers and health care professionals who may recommend probiotic supplements to their patients. In our comment letter, AGA encourages FDA to expand what information manufacturers are required to include. In addition to the conditions already outlined in FDA’s draft guidance, AGA recommends including the conditions of storage as well as an expiration or “use by” date.

We acknowledge that researchers are evaluating other methods and units of measure besides CFUs for not only live microbials but also microbial bioactivity. However, in the absence of a widely accepted alternative, which may take several years to develop and adopt, AGA strongly encourages FDA and manufacturers to take the small step forward of using CFUs now rather than waiting for another solution to emerge.

Probiotics have been an important focus for the AGA Center for Gut Microbiome Research and Education due to the need for evidence-based guidance for health care providers and their patients. The center will continue to work to educate physicians, patients and industry on best practices to ensure safe use of probiotics.
 

[email protected]

In a new comment letter to FDA, AGA commends FDA’s recent draft guidance – “Policy Regarding Quantitative Labeling of Dietary Supplements Containing Live Microbials” – clarifying the expectations of probiotics manufacturers who choose to specify the amount of a live microbial component in their product in colony forming units (CFUs).

Though manufacturers are not currently required to report CFUs, AGA feels strongly that all manufacturers of probiotic supplements should voluntarily report the composition of live microbials in their products as CFUs.

However, reporting CFUs alone provides insufficient information to consumers and health care professionals who may recommend probiotic supplements to their patients. In our comment letter, AGA encourages FDA to expand what information manufacturers are required to include. In addition to the conditions already outlined in FDA’s draft guidance, AGA recommends including the conditions of storage as well as an expiration or “use by” date.

We acknowledge that researchers are evaluating other methods and units of measure besides CFUs for not only live microbials but also microbial bioactivity. However, in the absence of a widely accepted alternative, which may take several years to develop and adopt, AGA strongly encourages FDA and manufacturers to take the small step forward of using CFUs now rather than waiting for another solution to emerge.

Probiotics have been an important focus for the AGA Center for Gut Microbiome Research and Education due to the need for evidence-based guidance for health care providers and their patients. The center will continue to work to educate physicians, patients and industry on best practices to ensure safe use of probiotics.
 

[email protected]

In a new comment letter to FDA, AGA commends FDA’s recent draft guidance – “Policy Regarding Quantitative Labeling of Dietary Supplements Containing Live Microbials” – clarifying the expectations of probiotics manufacturers who choose to specify the amount of a live microbial component in their product in colony forming units (CFUs).

Though manufacturers are not currently required to report CFUs, AGA feels strongly that all manufacturers of probiotic supplements should voluntarily report the composition of live microbials in their products as CFUs.

However, reporting CFUs alone provides insufficient information to consumers and health care professionals who may recommend probiotic supplements to their patients. In our comment letter, AGA encourages FDA to expand what information manufacturers are required to include. In addition to the conditions already outlined in FDA’s draft guidance, AGA recommends including the conditions of storage as well as an expiration or “use by” date.

We acknowledge that researchers are evaluating other methods and units of measure besides CFUs for not only live microbials but also microbial bioactivity. However, in the absence of a widely accepted alternative, which may take several years to develop and adopt, AGA strongly encourages FDA and manufacturers to take the small step forward of using CFUs now rather than waiting for another solution to emerge.

Probiotics have been an important focus for the AGA Center for Gut Microbiome Research and Education due to the need for evidence-based guidance for health care providers and their patients. The center will continue to work to educate physicians, patients and industry on best practices to ensure safe use of probiotics.
 

[email protected]

Opioid prescriptions after gynecologic surgery can be significantly reduced without impacting postoperative pain scores or complication rates, according to a paper published in JAMA Network Open.

A tertiary care comprehensive care center implemented an ultrarestrictive opioid prescription protocol (UROPP) then evaluated the outcomes in a case-control study involving 605 women undergoing gynecologic surgery, compared with 626 controls treated before implementation of the new protocol.

The ultrarestrictive protocol was prompted by frequent inquiries from patients who had used very little of their prescribed opioids after surgery and wanted to know what to do with the unused pills.

The new protocol involved a short preoperative counseling session about postoperative pain management. Following that, ambulatory surgery, minimally invasive surgery, or laparotomy patients were prescribed a 7-day supply of nonopioid pain relief. Laparotomy patients were also prescribed a 3-day supply of an oral opioid.

Any patients who required more than five opioid doses in the 24 hours before discharge were also prescribed a 3-day supply of opioid pain medication as needed, and all patients had the option of requesting an additional 3-day opioid refill.

Researchers saw no significant differences between the two groups in mean postoperative pain scores 2 weeks after surgery, and a similar number of patients in each group requested an opioid refill. There was also no significant difference in the number of postoperative complications between groups.

Implementation of the ultrarestrictive protocol was associated with significant declines in the mean number of opioid pills prescribed dropped from 31.7 to 3.5 in all surgical cases, from 43.6 to 12.1 in the laparotomy group, from 38.4 to 1.3 in the minimally invasive surgery group, and from 13.9 to 0.2 in patients who underwent ambulatory surgery.

“These data suggest that the implementation of a UROPP in a large surgical service is feasible and safe and was associated with a significantly decreased number of opioids dispensed during the perioperative period, particularly among opioid-naive patients,” wrote Jaron Mark, MD, of the department of gynecologic oncology at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and his coauthors. “The opioid-sparing effect was also marked and statistically significant in the laparotomy group, where most patients remained physically active and recovered well with no negative sequelae or elevated pain score after surgery.”

The researchers also noted that patients who were discharged home with an opioid prescription were more likely to call and request a refill within 30 days, compared with patients who did not receive opioids at discharge.

The study was supported by the Roswell Park Comprehensive Cancer Center, the National Cancer Institute and the Roswell Park Alliance Foundation. Two authors reported receiving fees and nonfinancial support from the private sector unrelated to the study.

SOURCE: Mark J et al. JAMA Netw Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5452.
 

Opioid prescriptions after gynecologic surgery can be significantly reduced without impacting postoperative pain scores or complication rates, according to a paper published in JAMA Network Open.

A tertiary care comprehensive care center implemented an ultrarestrictive opioid prescription protocol (UROPP) then evaluated the outcomes in a case-control study involving 605 women undergoing gynecologic surgery, compared with 626 controls treated before implementation of the new protocol.

The ultrarestrictive protocol was prompted by frequent inquiries from patients who had used very little of their prescribed opioids after surgery and wanted to know what to do with the unused pills.

The new protocol involved a short preoperative counseling session about postoperative pain management. Following that, ambulatory surgery, minimally invasive surgery, or laparotomy patients were prescribed a 7-day supply of nonopioid pain relief. Laparotomy patients were also prescribed a 3-day supply of an oral opioid.

Any patients who required more than five opioid doses in the 24 hours before discharge were also prescribed a 3-day supply of opioid pain medication as needed, and all patients had the option of requesting an additional 3-day opioid refill.

Researchers saw no significant differences between the two groups in mean postoperative pain scores 2 weeks after surgery, and a similar number of patients in each group requested an opioid refill. There was also no significant difference in the number of postoperative complications between groups.

Implementation of the ultrarestrictive protocol was associated with significant declines in the mean number of opioid pills prescribed dropped from 31.7 to 3.5 in all surgical cases, from 43.6 to 12.1 in the laparotomy group, from 38.4 to 1.3 in the minimally invasive surgery group, and from 13.9 to 0.2 in patients who underwent ambulatory surgery.

“These data suggest that the implementation of a UROPP in a large surgical service is feasible and safe and was associated with a significantly decreased number of opioids dispensed during the perioperative period, particularly among opioid-naive patients,” wrote Jaron Mark, MD, of the department of gynecologic oncology at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and his coauthors. “The opioid-sparing effect was also marked and statistically significant in the laparotomy group, where most patients remained physically active and recovered well with no negative sequelae or elevated pain score after surgery.”

The researchers also noted that patients who were discharged home with an opioid prescription were more likely to call and request a refill within 30 days, compared with patients who did not receive opioids at discharge.

The study was supported by the Roswell Park Comprehensive Cancer Center, the National Cancer Institute and the Roswell Park Alliance Foundation. Two authors reported receiving fees and nonfinancial support from the private sector unrelated to the study.

SOURCE: Mark J et al. JAMA Netw Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5452.
 

Opioid prescriptions after gynecologic surgery can be significantly reduced without impacting postoperative pain scores or complication rates, according to a paper published in JAMA Network Open.

A tertiary care comprehensive care center implemented an ultrarestrictive opioid prescription protocol (UROPP) then evaluated the outcomes in a case-control study involving 605 women undergoing gynecologic surgery, compared with 626 controls treated before implementation of the new protocol.

The ultrarestrictive protocol was prompted by frequent inquiries from patients who had used very little of their prescribed opioids after surgery and wanted to know what to do with the unused pills.

The new protocol involved a short preoperative counseling session about postoperative pain management. Following that, ambulatory surgery, minimally invasive surgery, or laparotomy patients were prescribed a 7-day supply of nonopioid pain relief. Laparotomy patients were also prescribed a 3-day supply of an oral opioid.

Any patients who required more than five opioid doses in the 24 hours before discharge were also prescribed a 3-day supply of opioid pain medication as needed, and all patients had the option of requesting an additional 3-day opioid refill.

Researchers saw no significant differences between the two groups in mean postoperative pain scores 2 weeks after surgery, and a similar number of patients in each group requested an opioid refill. There was also no significant difference in the number of postoperative complications between groups.

Implementation of the ultrarestrictive protocol was associated with significant declines in the mean number of opioid pills prescribed dropped from 31.7 to 3.5 in all surgical cases, from 43.6 to 12.1 in the laparotomy group, from 38.4 to 1.3 in the minimally invasive surgery group, and from 13.9 to 0.2 in patients who underwent ambulatory surgery.

“These data suggest that the implementation of a UROPP in a large surgical service is feasible and safe and was associated with a significantly decreased number of opioids dispensed during the perioperative period, particularly among opioid-naive patients,” wrote Jaron Mark, MD, of the department of gynecologic oncology at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and his coauthors. “The opioid-sparing effect was also marked and statistically significant in the laparotomy group, where most patients remained physically active and recovered well with no negative sequelae or elevated pain score after surgery.”

The researchers also noted that patients who were discharged home with an opioid prescription were more likely to call and request a refill within 30 days, compared with patients who did not receive opioids at discharge.

The study was supported by the Roswell Park Comprehensive Cancer Center, the National Cancer Institute and the Roswell Park Alliance Foundation. Two authors reported receiving fees and nonfinancial support from the private sector unrelated to the study.

SOURCE: Mark J et al. JAMA Netw Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5452.
 

CHICAGO – Firibastat, a first-in-class oral antihypertensive drug, proved safe, effective, and well-tolerated in NEW-HOPE, a phase 2b clinical trial focused on an understudied and underserved patient population composed largely of overweight or obese, high-risk, hypertensive racial minorities,

Firibastat is the first brain aminopeptidase A inhibitor. It selectively and specifically inhibits conversion of angiotensin II to angiotensin III, which exerts tonic stimulation over blood pressure. Decreased angiotensin III means less release of vasopressin, reduced sympathetic nervous system activity, and increased baroreflex activity, all of which add up to lower blood pressure, Keith C. Ferdinand, MD, explained at the American Heart Association scientific sessions.

NEW-HOPE (Novel Evaluation With QGC001 in Hypertensive Overweight Patients of Multiple Ethnic origins) was an open-label multicenter study including 254 middle-aged or older hypertensive patients. Two-thirds were obese, the rest overweight. Participants had a mean body mass index of 33 kg/m² and a baseline automated office blood pressure (AOBP) of 153.9/91.5 mm Hg. A total of 46% were women, and 38% were black. Indeed, blacks and other minorities made up 54% of the NEW-HOPE population.

“Minority populations in many of the clinical trials in hypertension have been underrepresented,” observed Dr. Ferdinand, professor of medicine at Tulane University in New Orleans.

After a 2-week washout period, all patients were placed on firibastat at 250 mg b.i.d. for 2 weeks. If at that point their AOBP was more than 140/90 mm Hg they were bumped up to 500 mg b.i.d. Hydrochlorothiazide at 25 mg/day could be added 1 month into the trial if a patient’s systolic blood pressure was 160 mm Hg or more or their diastolic blood pressure was at least 100 mm Hg. Of note, 85% of patients were able to remain on firibastat monotherapy throughout the study.

The primary endpoint was change from baseline in systolic AOBP at 8 weeks. By week 8, the mean systolic blood pressure (SBP) had fallen by 9.7 mm Hg from a baseline of 153.9, which in hypertension circles is deemed a clinically meaningful improvement. Mean diastolic AOBP fell from 91.5 to 87.2 mm Hg, for a 4.3–mm Hg reduction.

“The diastolic number was smaller, but remember, this was a middle-aged and older population, and SBP is the most important endpoint in patients of that age, not just in clinical trials but in terms of its effects on morbidity and mortality,” Dr. Ferdinand said.

A word about the rigorous AOBP protocol used in NEW-HOPE: It was similar to that used in the landmark SPRINT trial. Patients were required to rest seated with back support in a quiet room with no talking for 5 minutes. Then six measurements were taken at 1-minute intervals, with patients’ legs uncrossed and feet on the floor the whole time. The first measurement was discarded, and the next five were averaged.

“This correlates very well with daytime ambulatory blood pressure, which is the gold standard,” the cardiologist noted.

In a prespecified subgroup analysis, systolic AOBP was reduced significantly more in obese than in overweight patients. Black patients averaged a 10.5–mm Hg decrease, nonblacks a 4.1–mm Hg reduction. But black patients also averaged a 2.0 kg/m² higher body mass index.

“ACE inhibitors and angiotensin receptor blockers have been shown to be less efficacious in black patients. Firibastat, however, had similar effects in both black and nonblack patients. And this is probably one of the main take-away points of the study: This is a drug based on the phenotype of obesity and increased blood pressure, and the drug had efficacy regardless of self-identified race,” the cardiologist continued.

The most common treatment-emergent adverse events were headache in 4% of patients and skin reactions in 3%. There were no cases of angioedema. The only serious adverse event was one case of erythema multiforme. There were no clinically meaningful changes in any laboratory parameters.

Based upon these encouraging results, a pivotal phase 3 clinical trial is being planned in patients with difficult-to-treat or resistant hypertension. Dr. Ferdinand sees firibastat as being particularly useful as part of a two-drug treatment strategy, probably with the addition of a calcium channel blocker or potent diuretic, since “two drugs is the way to go in resistant hypertension.”

Audience members called the study “very hopeful,” but wondered about the absence of a placebo control arm. Reservations were also voiced about the need for twice-daily dosing of firibastat because it’s well established that adherence drops off when an antihypertensive agent has to be taken more than once daily.

Dr. Ferdinand said the lack of a placebo arm in NEW-HOPE was endorsed by the Food and Drug Administration because of ethical concerns surrounding use of a placebo in a high-risk population such as this. Obesity is known to increase the risk of resistant hypertension fivefold. Obesity is more common in blacks and Hispanics, with a prevalence of 47%, than in whites, where the prevalence is 38%.

As for the b.i.d. dosing, Quantum Genomics, the company that sponsored NEW-HOPE, is developing a sustained-release, once-daily formulation of firibastat that’s better suited for clinical practice, he added.

NEW-HOPE was carried out in collaboration with the Association of Black Cardiologists. Dr. Ferdinand reported serving as a consultant to Quantum Genomics and a handful of other pharmaceutical companies.

[email protected]

CHICAGO – Firibastat, a first-in-class oral antihypertensive drug, proved safe, effective, and well-tolerated in NEW-HOPE, a phase 2b clinical trial focused on an understudied and underserved patient population composed largely of overweight or obese, high-risk, hypertensive racial minorities,

Firibastat is the first brain aminopeptidase A inhibitor. It selectively and specifically inhibits conversion of angiotensin II to angiotensin III, which exerts tonic stimulation over blood pressure. Decreased angiotensin III means less release of vasopressin, reduced sympathetic nervous system activity, and increased baroreflex activity, all of which add up to lower blood pressure, Keith C. Ferdinand, MD, explained at the American Heart Association scientific sessions.

NEW-HOPE (Novel Evaluation With QGC001 in Hypertensive Overweight Patients of Multiple Ethnic origins) was an open-label multicenter study including 254 middle-aged or older hypertensive patients. Two-thirds were obese, the rest overweight. Participants had a mean body mass index of 33 kg/m² and a baseline automated office blood pressure (AOBP) of 153.9/91.5 mm Hg. A total of 46% were women, and 38% were black. Indeed, blacks and other minorities made up 54% of the NEW-HOPE population.

“Minority populations in many of the clinical trials in hypertension have been underrepresented,” observed Dr. Ferdinand, professor of medicine at Tulane University in New Orleans.

After a 2-week washout period, all patients were placed on firibastat at 250 mg b.i.d. for 2 weeks. If at that point their AOBP was more than 140/90 mm Hg they were bumped up to 500 mg b.i.d. Hydrochlorothiazide at 25 mg/day could be added 1 month into the trial if a patient’s systolic blood pressure was 160 mm Hg or more or their diastolic blood pressure was at least 100 mm Hg. Of note, 85% of patients were able to remain on firibastat monotherapy throughout the study.

The primary endpoint was change from baseline in systolic AOBP at 8 weeks. By week 8, the mean systolic blood pressure (SBP) had fallen by 9.7 mm Hg from a baseline of 153.9, which in hypertension circles is deemed a clinically meaningful improvement. Mean diastolic AOBP fell from 91.5 to 87.2 mm Hg, for a 4.3–mm Hg reduction.

“The diastolic number was smaller, but remember, this was a middle-aged and older population, and SBP is the most important endpoint in patients of that age, not just in clinical trials but in terms of its effects on morbidity and mortality,” Dr. Ferdinand said.

A word about the rigorous AOBP protocol used in NEW-HOPE: It was similar to that used in the landmark SPRINT trial. Patients were required to rest seated with back support in a quiet room with no talking for 5 minutes. Then six measurements were taken at 1-minute intervals, with patients’ legs uncrossed and feet on the floor the whole time. The first measurement was discarded, and the next five were averaged.

“This correlates very well with daytime ambulatory blood pressure, which is the gold standard,” the cardiologist noted.

In a prespecified subgroup analysis, systolic AOBP was reduced significantly more in obese than in overweight patients. Black patients averaged a 10.5–mm Hg decrease, nonblacks a 4.1–mm Hg reduction. But black patients also averaged a 2.0 kg/m² higher body mass index.

“ACE inhibitors and angiotensin receptor blockers have been shown to be less efficacious in black patients. Firibastat, however, had similar effects in both black and nonblack patients. And this is probably one of the main take-away points of the study: This is a drug based on the phenotype of obesity and increased blood pressure, and the drug had efficacy regardless of self-identified race,” the cardiologist continued.

The most common treatment-emergent adverse events were headache in 4% of patients and skin reactions in 3%. There were no cases of angioedema. The only serious adverse event was one case of erythema multiforme. There were no clinically meaningful changes in any laboratory parameters.

Based upon these encouraging results, a pivotal phase 3 clinical trial is being planned in patients with difficult-to-treat or resistant hypertension. Dr. Ferdinand sees firibastat as being particularly useful as part of a two-drug treatment strategy, probably with the addition of a calcium channel blocker or potent diuretic, since “two drugs is the way to go in resistant hypertension.”

Audience members called the study “very hopeful,” but wondered about the absence of a placebo control arm. Reservations were also voiced about the need for twice-daily dosing of firibastat because it’s well established that adherence drops off when an antihypertensive agent has to be taken more than once daily.

Dr. Ferdinand said the lack of a placebo arm in NEW-HOPE was endorsed by the Food and Drug Administration because of ethical concerns surrounding use of a placebo in a high-risk population such as this. Obesity is known to increase the risk of resistant hypertension fivefold. Obesity is more common in blacks and Hispanics, with a prevalence of 47%, than in whites, where the prevalence is 38%.

As for the b.i.d. dosing, Quantum Genomics, the company that sponsored NEW-HOPE, is developing a sustained-release, once-daily formulation of firibastat that’s better suited for clinical practice, he added.

NEW-HOPE was carried out in collaboration with the Association of Black Cardiologists. Dr. Ferdinand reported serving as a consultant to Quantum Genomics and a handful of other pharmaceutical companies.

[email protected]

CHICAGO – Firibastat, a first-in-class oral antihypertensive drug, proved safe, effective, and well-tolerated in NEW-HOPE, a phase 2b clinical trial focused on an understudied and underserved patient population composed largely of overweight or obese, high-risk, hypertensive racial minorities,

Firibastat is the first brain aminopeptidase A inhibitor. It selectively and specifically inhibits conversion of angiotensin II to angiotensin III, which exerts tonic stimulation over blood pressure. Decreased angiotensin III means less release of vasopressin, reduced sympathetic nervous system activity, and increased baroreflex activity, all of which add up to lower blood pressure, Keith C. Ferdinand, MD, explained at the American Heart Association scientific sessions.

NEW-HOPE (Novel Evaluation With QGC001 in Hypertensive Overweight Patients of Multiple Ethnic origins) was an open-label multicenter study including 254 middle-aged or older hypertensive patients. Two-thirds were obese, the rest overweight. Participants had a mean body mass index of 33 kg/m² and a baseline automated office blood pressure (AOBP) of 153.9/91.5 mm Hg. A total of 46% were women, and 38% were black. Indeed, blacks and other minorities made up 54% of the NEW-HOPE population.

“Minority populations in many of the clinical trials in hypertension have been underrepresented,” observed Dr. Ferdinand, professor of medicine at Tulane University in New Orleans.

After a 2-week washout period, all patients were placed on firibastat at 250 mg b.i.d. for 2 weeks. If at that point their AOBP was more than 140/90 mm Hg they were bumped up to 500 mg b.i.d. Hydrochlorothiazide at 25 mg/day could be added 1 month into the trial if a patient’s systolic blood pressure was 160 mm Hg or more or their diastolic blood pressure was at least 100 mm Hg. Of note, 85% of patients were able to remain on firibastat monotherapy throughout the study.

The primary endpoint was change from baseline in systolic AOBP at 8 weeks. By week 8, the mean systolic blood pressure (SBP) had fallen by 9.7 mm Hg from a baseline of 153.9, which in hypertension circles is deemed a clinically meaningful improvement. Mean diastolic AOBP fell from 91.5 to 87.2 mm Hg, for a 4.3–mm Hg reduction.

“The diastolic number was smaller, but remember, this was a middle-aged and older population, and SBP is the most important endpoint in patients of that age, not just in clinical trials but in terms of its effects on morbidity and mortality,” Dr. Ferdinand said.

A word about the rigorous AOBP protocol used in NEW-HOPE: It was similar to that used in the landmark SPRINT trial. Patients were required to rest seated with back support in a quiet room with no talking for 5 minutes. Then six measurements were taken at 1-minute intervals, with patients’ legs uncrossed and feet on the floor the whole time. The first measurement was discarded, and the next five were averaged.

“This correlates very well with daytime ambulatory blood pressure, which is the gold standard,” the cardiologist noted.

In a prespecified subgroup analysis, systolic AOBP was reduced significantly more in obese than in overweight patients. Black patients averaged a 10.5–mm Hg decrease, nonblacks a 4.1–mm Hg reduction. But black patients also averaged a 2.0 kg/m² higher body mass index.

“ACE inhibitors and angiotensin receptor blockers have been shown to be less efficacious in black patients. Firibastat, however, had similar effects in both black and nonblack patients. And this is probably one of the main take-away points of the study: This is a drug based on the phenotype of obesity and increased blood pressure, and the drug had efficacy regardless of self-identified race,” the cardiologist continued.

The most common treatment-emergent adverse events were headache in 4% of patients and skin reactions in 3%. There were no cases of angioedema. The only serious adverse event was one case of erythema multiforme. There were no clinically meaningful changes in any laboratory parameters.

Based upon these encouraging results, a pivotal phase 3 clinical trial is being planned in patients with difficult-to-treat or resistant hypertension. Dr. Ferdinand sees firibastat as being particularly useful as part of a two-drug treatment strategy, probably with the addition of a calcium channel blocker or potent diuretic, since “two drugs is the way to go in resistant hypertension.”

Audience members called the study “very hopeful,” but wondered about the absence of a placebo control arm. Reservations were also voiced about the need for twice-daily dosing of firibastat because it’s well established that adherence drops off when an antihypertensive agent has to be taken more than once daily.

Dr. Ferdinand said the lack of a placebo arm in NEW-HOPE was endorsed by the Food and Drug Administration because of ethical concerns surrounding use of a placebo in a high-risk population such as this. Obesity is known to increase the risk of resistant hypertension fivefold. Obesity is more common in blacks and Hispanics, with a prevalence of 47%, than in whites, where the prevalence is 38%.

As for the b.i.d. dosing, Quantum Genomics, the company that sponsored NEW-HOPE, is developing a sustained-release, once-daily formulation of firibastat that’s better suited for clinical practice, he added.

NEW-HOPE was carried out in collaboration with the Association of Black Cardiologists. Dr. Ferdinand reported serving as a consultant to Quantum Genomics and a handful of other pharmaceutical companies.

[email protected]

SAN ANTONIO – Age alone should not be grounds for skipping adjuvant chemotherapy for early breast cancer, suggests an analysis of more than 160,000 patients aged 65 years or older captured in the National Cancer Database.

“Data for elderly patients in clinical trials is limited. The NCCN [National Comprehensive Cancer Network] guidelines note that there is limited data to make chemotherapy recommendations for those older than 70 years of age,” commented first author Shreya Sinha, MD, an oncology fellow at the State University of New York, Syracuse. Furthermore, the few studies assessing adjuvant chemotherapy benefit among geriatric breast cancer patients have had conflicting results.

In the new study, reported at the San Antonio Breast Cancer Symposium, older women with stage I-III breast cancer who received adjuvant chemotherapy had a nearly 40% reduction in the adjusted risk of death relative to counterparts who did not receive adjuvant chemotherapy. Benefit was seen across disease stages and across hormone receptor statuses.

Patients’ fitness to receive chemotherapy and their causes of death could not be determined, Dr. Sinha acknowledged. Therefore, chemotherapy’s role in the observed survival difference is not definitive.

“In general, when we are treating our elderly population, we have to take physiologic age into consideration when coming up with a treatment plan,” she said. However, “we also have to use chemotherapy toxicity prediction calculators,” such as the Cancer and Aging Research Group tool and the Chemotherapy Risk Assessment Scale for High-Age Patients.

In addition, gene-based assays, such as Oncotype DX and MammaPrint, which were not taken into account for the study, can be applied to estimate the likely benefit of chemotherapy and further inform the treatment decision.

“It can’t be that chemotherapy is making these patients live longer. It has to be that the doctors know not to give chemotherapy to those who are going to die soon,” speculated symposium attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York.

He therefore wondered if the amount of chemotherapy received was related to survival. “If it was a chemotherapy effect, then more is probably better, and if it’s a selection effect at the time of initiation, then more probably wouldn’t be better.”

“These are the issues we run into when we use the National Cancer Database or such large databases,” Dr. Sinha replied. “We don’t necessarily have the information on how much chemotherapy the patients received. It really is based on if they received chemotherapy or not.”

Study details

The 160,676 patients studied were treated for stage I-III breast cancer during 2004-2015 and were included regardless of hormone receptor status and HER2 status.

Overall, 60.45% received adjuvant chemotherapy, Dr. Sinha reported. Mean age was 70.7 years among chemotherapy recipients and 75.5 years among nonrecipients.

Women were more likely to receive adjuvant chemotherapy if they had a tumor grade of 2 or 3 (adjusted odds ratios, 1.88 and 3.51), had a tumor negative for both estrogen and progesterone receptors or just progesterone receptors (aOR, 2.72 and 1.70), had private insurance versus Medicaid or Medicare (aOR, 1.40 and 1.20), or received radiation therapy (aOR, 2.55).

Women were less likely to receive adjuvant chemotherapy if they had stage 1 or 2 disease (aOR, 0.23 and 0.56; P less than .0001 for each), were older than 80 years (aOR, 0.105; P less than .0001), had undergone lumpectomy versus mastectomy (aOR, 0.82; P = .0011), were treated in an academic versus community program (aOR, 0.93; P = .0007), or had a Charlson/Deyo comorbidity score of 3 or higher (aOR, 0.38; P less than .0001).

Median overall survival was 144.9 months with and 112.6 months without adjuvant chemotherapy. The difference translated to a significantly reduced risk of death for the women given adjuvant chemotherapy (adjusted hazard ratio, 0.617; P less than .0001). The corresponding 10-year overall survival rates were 59.5% and 46.7%.

The reduced risk of death with adjuvant chemotherapy was evident in women with stage 1 disease (aHR, 0.801), stage 2 disease (aHR, 0.608), and stage 3 disease (aHR, 0.666) (P less than .0001 for all). It was also evident in those with tumors positive for both estrogen and progesterone receptors (aHR, 0.649), negative for progesterone receptors only (aHR, 0.609), and negative for both (aHR, 0.547) (P less than .0001 for all).

“The HER2/neu patient unfortunately was not well defined since there was no data [on that marker] before 2010,” Dr. Sinha noted

Dr. Sinha reported no relevant conflicts of interest. The study received funding from the Research Foundation of SUNY.

SOURCE: Sinha S et al. SABCS 2018, Abstract GS2-02.

SAN ANTONIO – Age alone should not be grounds for skipping adjuvant chemotherapy for early breast cancer, suggests an analysis of more than 160,000 patients aged 65 years or older captured in the National Cancer Database.

“Data for elderly patients in clinical trials is limited. The NCCN [National Comprehensive Cancer Network] guidelines note that there is limited data to make chemotherapy recommendations for those older than 70 years of age,” commented first author Shreya Sinha, MD, an oncology fellow at the State University of New York, Syracuse. Furthermore, the few studies assessing adjuvant chemotherapy benefit among geriatric breast cancer patients have had conflicting results.

In the new study, reported at the San Antonio Breast Cancer Symposium, older women with stage I-III breast cancer who received adjuvant chemotherapy had a nearly 40% reduction in the adjusted risk of death relative to counterparts who did not receive adjuvant chemotherapy. Benefit was seen across disease stages and across hormone receptor statuses.

Patients’ fitness to receive chemotherapy and their causes of death could not be determined, Dr. Sinha acknowledged. Therefore, chemotherapy’s role in the observed survival difference is not definitive.

“In general, when we are treating our elderly population, we have to take physiologic age into consideration when coming up with a treatment plan,” she said. However, “we also have to use chemotherapy toxicity prediction calculators,” such as the Cancer and Aging Research Group tool and the Chemotherapy Risk Assessment Scale for High-Age Patients.

In addition, gene-based assays, such as Oncotype DX and MammaPrint, which were not taken into account for the study, can be applied to estimate the likely benefit of chemotherapy and further inform the treatment decision.

“It can’t be that chemotherapy is making these patients live longer. It has to be that the doctors know not to give chemotherapy to those who are going to die soon,” speculated symposium attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York.

He therefore wondered if the amount of chemotherapy received was related to survival. “If it was a chemotherapy effect, then more is probably better, and if it’s a selection effect at the time of initiation, then more probably wouldn’t be better.”

“These are the issues we run into when we use the National Cancer Database or such large databases,” Dr. Sinha replied. “We don’t necessarily have the information on how much chemotherapy the patients received. It really is based on if they received chemotherapy or not.”

Study details

The 160,676 patients studied were treated for stage I-III breast cancer during 2004-2015 and were included regardless of hormone receptor status and HER2 status.

Overall, 60.45% received adjuvant chemotherapy, Dr. Sinha reported. Mean age was 70.7 years among chemotherapy recipients and 75.5 years among nonrecipients.

Women were more likely to receive adjuvant chemotherapy if they had a tumor grade of 2 or 3 (adjusted odds ratios, 1.88 and 3.51), had a tumor negative for both estrogen and progesterone receptors or just progesterone receptors (aOR, 2.72 and 1.70), had private insurance versus Medicaid or Medicare (aOR, 1.40 and 1.20), or received radiation therapy (aOR, 2.55).

Women were less likely to receive adjuvant chemotherapy if they had stage 1 or 2 disease (aOR, 0.23 and 0.56; P less than .0001 for each), were older than 80 years (aOR, 0.105; P less than .0001), had undergone lumpectomy versus mastectomy (aOR, 0.82; P = .0011), were treated in an academic versus community program (aOR, 0.93; P = .0007), or had a Charlson/Deyo comorbidity score of 3 or higher (aOR, 0.38; P less than .0001).

Median overall survival was 144.9 months with and 112.6 months without adjuvant chemotherapy. The difference translated to a significantly reduced risk of death for the women given adjuvant chemotherapy (adjusted hazard ratio, 0.617; P less than .0001). The corresponding 10-year overall survival rates were 59.5% and 46.7%.

The reduced risk of death with adjuvant chemotherapy was evident in women with stage 1 disease (aHR, 0.801), stage 2 disease (aHR, 0.608), and stage 3 disease (aHR, 0.666) (P less than .0001 for all). It was also evident in those with tumors positive for both estrogen and progesterone receptors (aHR, 0.649), negative for progesterone receptors only (aHR, 0.609), and negative for both (aHR, 0.547) (P less than .0001 for all).

“The HER2/neu patient unfortunately was not well defined since there was no data [on that marker] before 2010,” Dr. Sinha noted

Dr. Sinha reported no relevant conflicts of interest. The study received funding from the Research Foundation of SUNY.

SOURCE: Sinha S et al. SABCS 2018, Abstract GS2-02.

SAN ANTONIO – Age alone should not be grounds for skipping adjuvant chemotherapy for early breast cancer, suggests an analysis of more than 160,000 patients aged 65 years or older captured in the National Cancer Database.

“Data for elderly patients in clinical trials is limited. The NCCN [National Comprehensive Cancer Network] guidelines note that there is limited data to make chemotherapy recommendations for those older than 70 years of age,” commented first author Shreya Sinha, MD, an oncology fellow at the State University of New York, Syracuse. Furthermore, the few studies assessing adjuvant chemotherapy benefit among geriatric breast cancer patients have had conflicting results.

In the new study, reported at the San Antonio Breast Cancer Symposium, older women with stage I-III breast cancer who received adjuvant chemotherapy had a nearly 40% reduction in the adjusted risk of death relative to counterparts who did not receive adjuvant chemotherapy. Benefit was seen across disease stages and across hormone receptor statuses.

Patients’ fitness to receive chemotherapy and their causes of death could not be determined, Dr. Sinha acknowledged. Therefore, chemotherapy’s role in the observed survival difference is not definitive.

“In general, when we are treating our elderly population, we have to take physiologic age into consideration when coming up with a treatment plan,” she said. However, “we also have to use chemotherapy toxicity prediction calculators,” such as the Cancer and Aging Research Group tool and the Chemotherapy Risk Assessment Scale for High-Age Patients.

In addition, gene-based assays, such as Oncotype DX and MammaPrint, which were not taken into account for the study, can be applied to estimate the likely benefit of chemotherapy and further inform the treatment decision.

“It can’t be that chemotherapy is making these patients live longer. It has to be that the doctors know not to give chemotherapy to those who are going to die soon,” speculated symposium attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York.

He therefore wondered if the amount of chemotherapy received was related to survival. “If it was a chemotherapy effect, then more is probably better, and if it’s a selection effect at the time of initiation, then more probably wouldn’t be better.”

“These are the issues we run into when we use the National Cancer Database or such large databases,” Dr. Sinha replied. “We don’t necessarily have the information on how much chemotherapy the patients received. It really is based on if they received chemotherapy or not.”

Study details

The 160,676 patients studied were treated for stage I-III breast cancer during 2004-2015 and were included regardless of hormone receptor status and HER2 status.

Overall, 60.45% received adjuvant chemotherapy, Dr. Sinha reported. Mean age was 70.7 years among chemotherapy recipients and 75.5 years among nonrecipients.

Women were more likely to receive adjuvant chemotherapy if they had a tumor grade of 2 or 3 (adjusted odds ratios, 1.88 and 3.51), had a tumor negative for both estrogen and progesterone receptors or just progesterone receptors (aOR, 2.72 and 1.70), had private insurance versus Medicaid or Medicare (aOR, 1.40 and 1.20), or received radiation therapy (aOR, 2.55).

Women were less likely to receive adjuvant chemotherapy if they had stage 1 or 2 disease (aOR, 0.23 and 0.56; P less than .0001 for each), were older than 80 years (aOR, 0.105; P less than .0001), had undergone lumpectomy versus mastectomy (aOR, 0.82; P = .0011), were treated in an academic versus community program (aOR, 0.93; P = .0007), or had a Charlson/Deyo comorbidity score of 3 or higher (aOR, 0.38; P less than .0001).

Median overall survival was 144.9 months with and 112.6 months without adjuvant chemotherapy. The difference translated to a significantly reduced risk of death for the women given adjuvant chemotherapy (adjusted hazard ratio, 0.617; P less than .0001). The corresponding 10-year overall survival rates were 59.5% and 46.7%.

The reduced risk of death with adjuvant chemotherapy was evident in women with stage 1 disease (aHR, 0.801), stage 2 disease (aHR, 0.608), and stage 3 disease (aHR, 0.666) (P less than .0001 for all). It was also evident in those with tumors positive for both estrogen and progesterone receptors (aHR, 0.649), negative for progesterone receptors only (aHR, 0.609), and negative for both (aHR, 0.547) (P less than .0001 for all).

“The HER2/neu patient unfortunately was not well defined since there was no data [on that marker] before 2010,” Dr. Sinha noted

Dr. Sinha reported no relevant conflicts of interest. The study received funding from the Research Foundation of SUNY.

SOURCE: Sinha S et al. SABCS 2018, Abstract GS2-02.

The entitlement, social isolation, and defectiveness early maladaptive schemas (EMSs) were associated with increased suicide risk and ideation in patients with bipolar disorder, according to Vahid Khosravani of Shahid Beheshti University of Medical Sciences, Tehran, Iran, and his associates.

“These findings were in line with previous studies (J Nerv Ment Dis. 2016 Mar. 204[3]:236-9) showing higher scores of social isolation and entitlement in [bipolar disorder] patients with suicide attempts than those without such attempts,” Mr. Khosravani and his associates wrote in Psychiatry Research.

For the study, 100 inpatients with bipolar disorder completed the Young Schema Questionnaire–Short Form (YSQ-SF), the Bipolar Depression Rating Scale (BDRS), the Young Mania Rating Scale (YMRS), and the Beck Scale for Suicidal Ideation (BSSI). Of that group, 59% had attempted suicide and 59% had a BSSI score of 6 or higher, indicating high suicidal risk, reported Mr. Khosravani and his associates.

Inpatients who had attempted suicide previously had higher test scores for the entitlement and social isolation EMSs, compared with those who had not; they also had higher levels of depressive and hypomanic/manic symptoms. Current suicide ideation was associated with higher entitlement and defectiveness EMS scores, as well as with increased hypomanic/manic symptoms.

“The findings suggest that manic symptoms as well as specific EMSs including social isolation, entitlement, and defectiveness emerge as potentially implicated in suicidality in BD patients,” the investigators noted. “Therefore, providing social support in the economic, social, political, cultural, and educational spheres may be a factor in preventing suicide.”

Mr. Khosravani and his associates said their study received no funding from public, commercial, or nonprofit agencies. The investigators declared no conflicts of interest.

[email protected]

SOURCE: Khosravani V et al. Psychiatry Res. 2019 Jan. (271):351-9.

The entitlement, social isolation, and defectiveness early maladaptive schemas (EMSs) were associated with increased suicide risk and ideation in patients with bipolar disorder, according to Vahid Khosravani of Shahid Beheshti University of Medical Sciences, Tehran, Iran, and his associates.

“These findings were in line with previous studies (J Nerv Ment Dis. 2016 Mar. 204[3]:236-9) showing higher scores of social isolation and entitlement in [bipolar disorder] patients with suicide attempts than those without such attempts,” Mr. Khosravani and his associates wrote in Psychiatry Research.

For the study, 100 inpatients with bipolar disorder completed the Young Schema Questionnaire–Short Form (YSQ-SF), the Bipolar Depression Rating Scale (BDRS), the Young Mania Rating Scale (YMRS), and the Beck Scale for Suicidal Ideation (BSSI). Of that group, 59% had attempted suicide and 59% had a BSSI score of 6 or higher, indicating high suicidal risk, reported Mr. Khosravani and his associates.

Inpatients who had attempted suicide previously had higher test scores for the entitlement and social isolation EMSs, compared with those who had not; they also had higher levels of depressive and hypomanic/manic symptoms. Current suicide ideation was associated with higher entitlement and defectiveness EMS scores, as well as with increased hypomanic/manic symptoms.

“The findings suggest that manic symptoms as well as specific EMSs including social isolation, entitlement, and defectiveness emerge as potentially implicated in suicidality in BD patients,” the investigators noted. “Therefore, providing social support in the economic, social, political, cultural, and educational spheres may be a factor in preventing suicide.”

Mr. Khosravani and his associates said their study received no funding from public, commercial, or nonprofit agencies. The investigators declared no conflicts of interest.

[email protected]

SOURCE: Khosravani V et al. Psychiatry Res. 2019 Jan. (271):351-9.

The entitlement, social isolation, and defectiveness early maladaptive schemas (EMSs) were associated with increased suicide risk and ideation in patients with bipolar disorder, according to Vahid Khosravani of Shahid Beheshti University of Medical Sciences, Tehran, Iran, and his associates.

“These findings were in line with previous studies (J Nerv Ment Dis. 2016 Mar. 204[3]:236-9) showing higher scores of social isolation and entitlement in [bipolar disorder] patients with suicide attempts than those without such attempts,” Mr. Khosravani and his associates wrote in Psychiatry Research.

For the study, 100 inpatients with bipolar disorder completed the Young Schema Questionnaire–Short Form (YSQ-SF), the Bipolar Depression Rating Scale (BDRS), the Young Mania Rating Scale (YMRS), and the Beck Scale for Suicidal Ideation (BSSI). Of that group, 59% had attempted suicide and 59% had a BSSI score of 6 or higher, indicating high suicidal risk, reported Mr. Khosravani and his associates.

Inpatients who had attempted suicide previously had higher test scores for the entitlement and social isolation EMSs, compared with those who had not; they also had higher levels of depressive and hypomanic/manic symptoms. Current suicide ideation was associated with higher entitlement and defectiveness EMS scores, as well as with increased hypomanic/manic symptoms.

“The findings suggest that manic symptoms as well as specific EMSs including social isolation, entitlement, and defectiveness emerge as potentially implicated in suicidality in BD patients,” the investigators noted. “Therefore, providing social support in the economic, social, political, cultural, and educational spheres may be a factor in preventing suicide.”

Mr. Khosravani and his associates said their study received no funding from public, commercial, or nonprofit agencies. The investigators declared no conflicts of interest.

[email protected]

SOURCE: Khosravani V et al. Psychiatry Res. 2019 Jan. (271):351-9.

CHICAGO – A measure of clarity regarding how the emerging class of oral Janus kinase inhibitors might fit into clinical practice for treatment of rheumatoid arthritis was supplied by a fusillade of five consecutive strongly positive phase 3 trials presented during a single session at the annual meeting of the American College of Rheumatology.

The session featured three randomized, double-blind, phase 3 trials of the Janus kinase inhibitor (JAKi) upadacitinib in more than 3,200 participants in three different clinical scenarios, known as the SELECT-COMPARE, SELECT-EARLY, and SELECT-MONOTHERAPY trials, along with two Japanese phase 3 trials of peficitinib, a JAK1 and -3 inhibitor, in a total of more than 1,000 rheumatoid arthritis patients.
 

Upadacitinib

SELECT-COMPARE: Roy M. Fleischmann, MD, presented the findings of this trial in which 1,629 patients with active RA inadequately responsive to methotrexate were randomized 2:2:1 to 26 weeks of once-daily oral upadacitinib at 15 mg, placebo, or 40 mg of adalimumab (Humira) by subcutaneous injection every 2 weeks, all on top of background stable doses of methotrexate.

Upadacitinib, a JAK1 selective agent, was the clear winner, trouncing placebo, unsurprisingly, but more importantly also proving statistically superior to adalimumab – the current go-to drug in patients with an insufficient response to methotrexate – in terms of across-the-board improvement in RA signs and symptoms, quality-of-life measures, and physical function. This result, coupled with the similarly positive findings of a trial of oral baricitinib (Olumiant) versus adalimumab in inadequate responders to methotrexate alone, and a third positive trial of oral tofacitinib (Xeljanz), have altered Dr. Fleischmann’s treatment philosophy.

“I think that these studies have changed the treatment paradigm. And I think if access – that is, costs – were the same, given a choice, if it were me, I would actually use a JAK inhibitor before I would use adalimumab, based on the results of these multiple studies in different populations,” said Dr. Fleischmann, a rheumatologist at the University of Texas Southwestern Medical Center, Dallas.

The two coprimary endpoints in SELECT-COMPARE were the week 12 American College of Rheumatology–defined 20% level of response (ACR 20) and a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The ACR 20 response rate was 70.5% with upadacitinib 15 mg, significantly better than the 63% rate with adalimumab and the 36.4% rate with placebo. Similarly, the ACR 50 rate at 12 weeks was 45.2% with upadacitinib versus 29.1% with adalimumab, and ACR 70 rates were 24.9% and 13.5%, respectively.

“These are not small differences,” the rheumatologist observed. “That ACR 70 rate is almost doubled with upadacitinib.”

The rate for DAS28-CRP less than 2.6 at week 12 was 28.7% with upadacitinib, compared with 18% with adalimumab.

Improvements in pain scores and the Health Assessment Questionnaire Disability Index were also significantly greater with the JAKi, both at weeks 12 and 26.

As in the other two SELECT phase 3 trials presented at the meeting, the response to upadacitinib was quick: The JAKi was superior to placebo on the efficacy endpoints by week 2, and superior to adalimumab by week 4.

The week-12 Boolean remission rate, a stringent measure, was 9.8% in the upadacitinib group, more than twice the 4% rate with adalimumab. At week 26, the rates were 18.1% and 9.8%, respectively, a finding Dr. Fleischmann deemed “very impressive.”

Radiographic disease progression as measured by change in modified total Sharp score (mTSS) at week 26 was 0.92 with placebo, 0.24 with upadacitinib, and slightly better at 0.1 with adalimumab. Adalimumab was also slightly better than baricitinib by this metric in a separate randomized trial. But that’s not a deal breaker for Dr. Fleischmann.

“It’s a 0.1–Sharp unit difference over 6 months. So by the time a patient would be able to tell the difference clinically, if my calculation is correct they’ll be 712 years old,” he quipped.

Serious infection rates through 26 weeks were similar in the upadacitinib and adalimumab study arms, with both being higher than placebo. Venous thromboembolism occurred in one patient on placebo, two on upadacitinib, and three on adalimumab.

Peficitinib

Yoshiya Tanaka, MD, PhD, professor and chairman of the department of internal medicine at the University of Occupational and Environmental Health in Kitakyushu, Japan, presented the findings of two pivotal phase 3, placebo-controlled, double-blind clinical trials of peficitinib at 100 or 150 mg once daily in 1,025 Asian patients with active RA insufficiently responsive to methotrexate or other disease-modifying antirheumatic drugs. Both studies were positive for all the key endpoints. Based upon these results, the drug’s developer, Astellas Pharma, has filed for Japanese regulatory approval of peficitinib.

Which oral JAKi to use?

Some audience members, numbed by the parade of positive results, asked the investigators for guidance as to which JAKi to choose, and when.

“The upadacitinib dataset mirrors the two approved oral JAKis. The data all look very similar,” said Stanley B. Cohen, MD, codirector of the division of rheumatology at Presbyterian Hospital in Dallas and a former ACR president. “All the JAKis are effective; the safety profiles are similar. Can you help clinicians know what differentiates them? Why should I choose one or the other?”

Dr. Tanaka replied that, although much gets made of the between-agent differences in selectivity for JAK1, 2, and/or 3 inhibition, “In the human body we cannot see much difference in safety and efficacy.”

If indeed such differences exist, head-to-head randomized trials will be required to ferret them out, noted Dr. Fleischmann.

Dr. Smolen indicated rheumatologists ought to rejoice in the looming prospect of a fistful of JAKis to choose from.

“I always wondered which beta-blocker to use, and I always wondered which cholesterol-lowering drug to use, and which NSAID to use – and interestingly enough, one NSAID will work in you but not in me, and another will work in me but not in you. So I think we should be pleased that we will have several oral JAKis to choose from,” he said.

Dr. Fleischmann got in the final word: “The answer to your question is the way we always answer it in the office. It’s access. Whichever one has the best access for the patient is the one you would select.”

The SELECT trials were sponsored by AbbVie, and all the upadacitinib investigators reported receiving research funds from and serving as paid consultants to that company and numerous others. Dr. Tanaka reported receiving research grants from and serving as a paid consultant to Astellas Pharma and close to a dozen other pharmaceutical companies.

[email protected]

CHICAGO – A measure of clarity regarding how the emerging class of oral Janus kinase inhibitors might fit into clinical practice for treatment of rheumatoid arthritis was supplied by a fusillade of five consecutive strongly positive phase 3 trials presented during a single session at the annual meeting of the American College of Rheumatology.

The session featured three randomized, double-blind, phase 3 trials of the Janus kinase inhibitor (JAKi) upadacitinib in more than 3,200 participants in three different clinical scenarios, known as the SELECT-COMPARE, SELECT-EARLY, and SELECT-MONOTHERAPY trials, along with two Japanese phase 3 trials of peficitinib, a JAK1 and -3 inhibitor, in a total of more than 1,000 rheumatoid arthritis patients.
 

Upadacitinib

SELECT-COMPARE: Roy M. Fleischmann, MD, presented the findings of this trial in which 1,629 patients with active RA inadequately responsive to methotrexate were randomized 2:2:1 to 26 weeks of once-daily oral upadacitinib at 15 mg, placebo, or 40 mg of adalimumab (Humira) by subcutaneous injection every 2 weeks, all on top of background stable doses of methotrexate.

Upadacitinib, a JAK1 selective agent, was the clear winner, trouncing placebo, unsurprisingly, but more importantly also proving statistically superior to adalimumab – the current go-to drug in patients with an insufficient response to methotrexate – in terms of across-the-board improvement in RA signs and symptoms, quality-of-life measures, and physical function. This result, coupled with the similarly positive findings of a trial of oral baricitinib (Olumiant) versus adalimumab in inadequate responders to methotrexate alone, and a third positive trial of oral tofacitinib (Xeljanz), have altered Dr. Fleischmann’s treatment philosophy.

“I think that these studies have changed the treatment paradigm. And I think if access – that is, costs – were the same, given a choice, if it were me, I would actually use a JAK inhibitor before I would use adalimumab, based on the results of these multiple studies in different populations,” said Dr. Fleischmann, a rheumatologist at the University of Texas Southwestern Medical Center, Dallas.

The two coprimary endpoints in SELECT-COMPARE were the week 12 American College of Rheumatology–defined 20% level of response (ACR 20) and a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The ACR 20 response rate was 70.5% with upadacitinib 15 mg, significantly better than the 63% rate with adalimumab and the 36.4% rate with placebo. Similarly, the ACR 50 rate at 12 weeks was 45.2% with upadacitinib versus 29.1% with adalimumab, and ACR 70 rates were 24.9% and 13.5%, respectively.

“These are not small differences,” the rheumatologist observed. “That ACR 70 rate is almost doubled with upadacitinib.”

The rate for DAS28-CRP less than 2.6 at week 12 was 28.7% with upadacitinib, compared with 18% with adalimumab.

Improvements in pain scores and the Health Assessment Questionnaire Disability Index were also significantly greater with the JAKi, both at weeks 12 and 26.

As in the other two SELECT phase 3 trials presented at the meeting, the response to upadacitinib was quick: The JAKi was superior to placebo on the efficacy endpoints by week 2, and superior to adalimumab by week 4.

The week-12 Boolean remission rate, a stringent measure, was 9.8% in the upadacitinib group, more than twice the 4% rate with adalimumab. At week 26, the rates were 18.1% and 9.8%, respectively, a finding Dr. Fleischmann deemed “very impressive.”

Radiographic disease progression as measured by change in modified total Sharp score (mTSS) at week 26 was 0.92 with placebo, 0.24 with upadacitinib, and slightly better at 0.1 with adalimumab. Adalimumab was also slightly better than baricitinib by this metric in a separate randomized trial. But that’s not a deal breaker for Dr. Fleischmann.

“It’s a 0.1–Sharp unit difference over 6 months. So by the time a patient would be able to tell the difference clinically, if my calculation is correct they’ll be 712 years old,” he quipped.

Serious infection rates through 26 weeks were similar in the upadacitinib and adalimumab study arms, with both being higher than placebo. Venous thromboembolism occurred in one patient on placebo, two on upadacitinib, and three on adalimumab.

Peficitinib

Yoshiya Tanaka, MD, PhD, professor and chairman of the department of internal medicine at the University of Occupational and Environmental Health in Kitakyushu, Japan, presented the findings of two pivotal phase 3, placebo-controlled, double-blind clinical trials of peficitinib at 100 or 150 mg once daily in 1,025 Asian patients with active RA insufficiently responsive to methotrexate or other disease-modifying antirheumatic drugs. Both studies were positive for all the key endpoints. Based upon these results, the drug’s developer, Astellas Pharma, has filed for Japanese regulatory approval of peficitinib.

Which oral JAKi to use?

Some audience members, numbed by the parade of positive results, asked the investigators for guidance as to which JAKi to choose, and when.

“The upadacitinib dataset mirrors the two approved oral JAKis. The data all look very similar,” said Stanley B. Cohen, MD, codirector of the division of rheumatology at Presbyterian Hospital in Dallas and a former ACR president. “All the JAKis are effective; the safety profiles are similar. Can you help clinicians know what differentiates them? Why should I choose one or the other?”

Dr. Tanaka replied that, although much gets made of the between-agent differences in selectivity for JAK1, 2, and/or 3 inhibition, “In the human body we cannot see much difference in safety and efficacy.”

If indeed such differences exist, head-to-head randomized trials will be required to ferret them out, noted Dr. Fleischmann.

Dr. Smolen indicated rheumatologists ought to rejoice in the looming prospect of a fistful of JAKis to choose from.

“I always wondered which beta-blocker to use, and I always wondered which cholesterol-lowering drug to use, and which NSAID to use – and interestingly enough, one NSAID will work in you but not in me, and another will work in me but not in you. So I think we should be pleased that we will have several oral JAKis to choose from,” he said.

Dr. Fleischmann got in the final word: “The answer to your question is the way we always answer it in the office. It’s access. Whichever one has the best access for the patient is the one you would select.”

The SELECT trials were sponsored by AbbVie, and all the upadacitinib investigators reported receiving research funds from and serving as paid consultants to that company and numerous others. Dr. Tanaka reported receiving research grants from and serving as a paid consultant to Astellas Pharma and close to a dozen other pharmaceutical companies.

[email protected]

CHICAGO – A measure of clarity regarding how the emerging class of oral Janus kinase inhibitors might fit into clinical practice for treatment of rheumatoid arthritis was supplied by a fusillade of five consecutive strongly positive phase 3 trials presented during a single session at the annual meeting of the American College of Rheumatology.

The session featured three randomized, double-blind, phase 3 trials of the Janus kinase inhibitor (JAKi) upadacitinib in more than 3,200 participants in three different clinical scenarios, known as the SELECT-COMPARE, SELECT-EARLY, and SELECT-MONOTHERAPY trials, along with two Japanese phase 3 trials of peficitinib, a JAK1 and -3 inhibitor, in a total of more than 1,000 rheumatoid arthritis patients.
 

Upadacitinib

SELECT-COMPARE: Roy M. Fleischmann, MD, presented the findings of this trial in which 1,629 patients with active RA inadequately responsive to methotrexate were randomized 2:2:1 to 26 weeks of once-daily oral upadacitinib at 15 mg, placebo, or 40 mg of adalimumab (Humira) by subcutaneous injection every 2 weeks, all on top of background stable doses of methotrexate.

Upadacitinib, a JAK1 selective agent, was the clear winner, trouncing placebo, unsurprisingly, but more importantly also proving statistically superior to adalimumab – the current go-to drug in patients with an insufficient response to methotrexate – in terms of across-the-board improvement in RA signs and symptoms, quality-of-life measures, and physical function. This result, coupled with the similarly positive findings of a trial of oral baricitinib (Olumiant) versus adalimumab in inadequate responders to methotrexate alone, and a third positive trial of oral tofacitinib (Xeljanz), have altered Dr. Fleischmann’s treatment philosophy.

“I think that these studies have changed the treatment paradigm. And I think if access – that is, costs – were the same, given a choice, if it were me, I would actually use a JAK inhibitor before I would use adalimumab, based on the results of these multiple studies in different populations,” said Dr. Fleischmann, a rheumatologist at the University of Texas Southwestern Medical Center, Dallas.

The two coprimary endpoints in SELECT-COMPARE were the week 12 American College of Rheumatology–defined 20% level of response (ACR 20) and a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The ACR 20 response rate was 70.5% with upadacitinib 15 mg, significantly better than the 63% rate with adalimumab and the 36.4% rate with placebo. Similarly, the ACR 50 rate at 12 weeks was 45.2% with upadacitinib versus 29.1% with adalimumab, and ACR 70 rates were 24.9% and 13.5%, respectively.

“These are not small differences,” the rheumatologist observed. “That ACR 70 rate is almost doubled with upadacitinib.”

The rate for DAS28-CRP less than 2.6 at week 12 was 28.7% with upadacitinib, compared with 18% with adalimumab.

Improvements in pain scores and the Health Assessment Questionnaire Disability Index were also significantly greater with the JAKi, both at weeks 12 and 26.

As in the other two SELECT phase 3 trials presented at the meeting, the response to upadacitinib was quick: The JAKi was superior to placebo on the efficacy endpoints by week 2, and superior to adalimumab by week 4.

The week-12 Boolean remission rate, a stringent measure, was 9.8% in the upadacitinib group, more than twice the 4% rate with adalimumab. At week 26, the rates were 18.1% and 9.8%, respectively, a finding Dr. Fleischmann deemed “very impressive.”

Radiographic disease progression as measured by change in modified total Sharp score (mTSS) at week 26 was 0.92 with placebo, 0.24 with upadacitinib, and slightly better at 0.1 with adalimumab. Adalimumab was also slightly better than baricitinib by this metric in a separate randomized trial. But that’s not a deal breaker for Dr. Fleischmann.

“It’s a 0.1–Sharp unit difference over 6 months. So by the time a patient would be able to tell the difference clinically, if my calculation is correct they’ll be 712 years old,” he quipped.

Serious infection rates through 26 weeks were similar in the upadacitinib and adalimumab study arms, with both being higher than placebo. Venous thromboembolism occurred in one patient on placebo, two on upadacitinib, and three on adalimumab.

Peficitinib

Yoshiya Tanaka, MD, PhD, professor and chairman of the department of internal medicine at the University of Occupational and Environmental Health in Kitakyushu, Japan, presented the findings of two pivotal phase 3, placebo-controlled, double-blind clinical trials of peficitinib at 100 or 150 mg once daily in 1,025 Asian patients with active RA insufficiently responsive to methotrexate or other disease-modifying antirheumatic drugs. Both studies were positive for all the key endpoints. Based upon these results, the drug’s developer, Astellas Pharma, has filed for Japanese regulatory approval of peficitinib.

Which oral JAKi to use?

Some audience members, numbed by the parade of positive results, asked the investigators for guidance as to which JAKi to choose, and when.

“The upadacitinib dataset mirrors the two approved oral JAKis. The data all look very similar,” said Stanley B. Cohen, MD, codirector of the division of rheumatology at Presbyterian Hospital in Dallas and a former ACR president. “All the JAKis are effective; the safety profiles are similar. Can you help clinicians know what differentiates them? Why should I choose one or the other?”

Dr. Tanaka replied that, although much gets made of the between-agent differences in selectivity for JAK1, 2, and/or 3 inhibition, “In the human body we cannot see much difference in safety and efficacy.”

If indeed such differences exist, head-to-head randomized trials will be required to ferret them out, noted Dr. Fleischmann.

Dr. Smolen indicated rheumatologists ought to rejoice in the looming prospect of a fistful of JAKis to choose from.

“I always wondered which beta-blocker to use, and I always wondered which cholesterol-lowering drug to use, and which NSAID to use – and interestingly enough, one NSAID will work in you but not in me, and another will work in me but not in you. So I think we should be pleased that we will have several oral JAKis to choose from,” he said.

Dr. Fleischmann got in the final word: “The answer to your question is the way we always answer it in the office. It’s access. Whichever one has the best access for the patient is the one you would select.”

The SELECT trials were sponsored by AbbVie, and all the upadacitinib investigators reported receiving research funds from and serving as paid consultants to that company and numerous others. Dr. Tanaka reported receiving research grants from and serving as a paid consultant to Astellas Pharma and close to a dozen other pharmaceutical companies.

[email protected]