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Lenalidomide now approved for newly diagnosed multiple myeloma
The Food and Drug Administration has expanded the approved indication for lenalidomide plus dexamethasone to include patients newly diagnosed with multiple myeloma, Celgene announced on Feb. 18.
Lenalidomide – a thalidomide analogue with immunomodulatory, antiangiogenic, and antineoplastic properties – was approved as a treatment for multiple myeloma in patients who have received at least one previous therapy in 2006. Celgene markets lenalidomide as Revlimid.
Approval of the expanded indication was based on phase III trials, including the FIRST trial, an open-label, randomized study, comparing lenalidomide plus dexamethasone continuously for 18 months to melphalan, prednisone, and thalidomide (MPT) in 1,623 patients newly diagnosed with multiple myeloma who were not candidates for a stem cell transplant, according to the Celgene statement announcing the approval. A secondary analysis involved a subgroup of patients treated with a fixed duration of 18 cycles of lenalidomide and dexamethasone.
The median progression-free survival (PFS), the primary endpoint, was 25.5 months among those on continuous lenalidomide and dexamethasone therapy, vs. 21.2 months among those treated with MPT, a statistically significant difference (hazard ratio, 0.72). An interim analysis of overall survival in March 2014 determined that the median overall survival was 58.9 months among those in the continuous lenalidomide-dexamethasone group, vs. 48.5 months among those in the MPT group (HR, 0.75).
Almost half of those on continuous treatment had diarrhea, vs. 16.5% of those on MPT. Other adverse events reported in 20% or more of patients included anemia in 44% and 42% and neutropenia in 35% and almost 61%, in these two groups respectively.
Lenalidomide is currently under review in Europe for treating adults with previously untreated multiple myeloma, who are not eligible for transplant, according to the company.
Lenalidomide is approved with a Risk Evaluation and Mitigation Strategy (REMS) to prevent embryo-fetal exposure and to inform patients, prescribers, and pharmacists about the serious risks associated with treatment.
The updated prescribing information is available at www.revlimid.com/wp-content/uploads/2013/11/PI.pdf.
The Food and Drug Administration has expanded the approved indication for lenalidomide plus dexamethasone to include patients newly diagnosed with multiple myeloma, Celgene announced on Feb. 18.
Lenalidomide – a thalidomide analogue with immunomodulatory, antiangiogenic, and antineoplastic properties – was approved as a treatment for multiple myeloma in patients who have received at least one previous therapy in 2006. Celgene markets lenalidomide as Revlimid.
Approval of the expanded indication was based on phase III trials, including the FIRST trial, an open-label, randomized study, comparing lenalidomide plus dexamethasone continuously for 18 months to melphalan, prednisone, and thalidomide (MPT) in 1,623 patients newly diagnosed with multiple myeloma who were not candidates for a stem cell transplant, according to the Celgene statement announcing the approval. A secondary analysis involved a subgroup of patients treated with a fixed duration of 18 cycles of lenalidomide and dexamethasone.
The median progression-free survival (PFS), the primary endpoint, was 25.5 months among those on continuous lenalidomide and dexamethasone therapy, vs. 21.2 months among those treated with MPT, a statistically significant difference (hazard ratio, 0.72). An interim analysis of overall survival in March 2014 determined that the median overall survival was 58.9 months among those in the continuous lenalidomide-dexamethasone group, vs. 48.5 months among those in the MPT group (HR, 0.75).
Almost half of those on continuous treatment had diarrhea, vs. 16.5% of those on MPT. Other adverse events reported in 20% or more of patients included anemia in 44% and 42% and neutropenia in 35% and almost 61%, in these two groups respectively.
Lenalidomide is currently under review in Europe for treating adults with previously untreated multiple myeloma, who are not eligible for transplant, according to the company.
Lenalidomide is approved with a Risk Evaluation and Mitigation Strategy (REMS) to prevent embryo-fetal exposure and to inform patients, prescribers, and pharmacists about the serious risks associated with treatment.
The updated prescribing information is available at www.revlimid.com/wp-content/uploads/2013/11/PI.pdf.
The Food and Drug Administration has expanded the approved indication for lenalidomide plus dexamethasone to include patients newly diagnosed with multiple myeloma, Celgene announced on Feb. 18.
Lenalidomide – a thalidomide analogue with immunomodulatory, antiangiogenic, and antineoplastic properties – was approved as a treatment for multiple myeloma in patients who have received at least one previous therapy in 2006. Celgene markets lenalidomide as Revlimid.
Approval of the expanded indication was based on phase III trials, including the FIRST trial, an open-label, randomized study, comparing lenalidomide plus dexamethasone continuously for 18 months to melphalan, prednisone, and thalidomide (MPT) in 1,623 patients newly diagnosed with multiple myeloma who were not candidates for a stem cell transplant, according to the Celgene statement announcing the approval. A secondary analysis involved a subgroup of patients treated with a fixed duration of 18 cycles of lenalidomide and dexamethasone.
The median progression-free survival (PFS), the primary endpoint, was 25.5 months among those on continuous lenalidomide and dexamethasone therapy, vs. 21.2 months among those treated with MPT, a statistically significant difference (hazard ratio, 0.72). An interim analysis of overall survival in March 2014 determined that the median overall survival was 58.9 months among those in the continuous lenalidomide-dexamethasone group, vs. 48.5 months among those in the MPT group (HR, 0.75).
Almost half of those on continuous treatment had diarrhea, vs. 16.5% of those on MPT. Other adverse events reported in 20% or more of patients included anemia in 44% and 42% and neutropenia in 35% and almost 61%, in these two groups respectively.
Lenalidomide is currently under review in Europe for treating adults with previously untreated multiple myeloma, who are not eligible for transplant, according to the company.
Lenalidomide is approved with a Risk Evaluation and Mitigation Strategy (REMS) to prevent embryo-fetal exposure and to inform patients, prescribers, and pharmacists about the serious risks associated with treatment.
The updated prescribing information is available at www.revlimid.com/wp-content/uploads/2013/11/PI.pdf.
New 9-valent HPV vaccine shown to be as effective as quadrivalent vaccine
The immunogenicity and efficacy of the recently approved 9-valent human papillomavirus vaccine were similar to that of the currently approved and recommended quadrivalent HPV vaccine, in an international study of over 14,000 women.
The study, published in the New England Journal of Medicine on Feb. 19, was the basis of the approval of the 9-valent vaccine in December 2014. The quadrivalent HPV vaccine is marketed as Gardasil and the 9-valent vaccine will be marketed as Gardasil-9.
The 9-valent vaccine covers the four HPV types (6, 11, 16, and 18) included in the quadrivalent vaccine; HPV-16 and HPV-18 are associated with about 70% of cervical cancers. The 9-valent vaccine, which includes five other oncogenic HPV types (31, 33, 45, 52, and 58), “offers the potential to increase overall prevention of cervical cancer ... to approximately 90%,” Dr. E. A. Joura of the department of gynecology and obstetrics at the Medical University of Vienna and associates said (N. Engl. J. Med. 2015;372:711-23 [doi:10.1056/NEJMoa1405044]).
In the Broad Spectrum HPV Vaccine Study, 14,215 women were randomized to receive the three recommended doses of the quadrivalent HPV vaccine or the 9-valent HPV vaccine and were followed with tests that included Pap tests, and swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue at baseline and periodically up to 4.5 years. Antibody responses to HPV types 6, 11, 16, and 18 (the types included in both vaccines) were similar in the two groups.
In both groups, the rate of high-grade cervical, vulvar, or vaginal disease associated with HPV types in the vaccines and those not in the vaccines was 14 cases per 1,000 person-years. In a subgroup of patients not infected with HPV at baseline, rates were 2.4% among those who received the 9-valent vaccine vs. 4.2% of those who received the quadrivalent vaccine.
The rate of high-grade cervical, vulvar, or vaginal disease associated with the five additional HPV types included in the 9-valent disease was 0.1 cases per 1,000 person-years, compared with 1.6 cases per 1,000 person-years among those who received the quadrivalent vaccine, a 97% reduced risk associated with the new vaccine.
As anticipated, injection-site reactions were more common among those who received the 9-valent vaccine (91% vs. 85%); most cases were mild to moderate. Other adverse events included dizziness, reported in about 3% in both groups.
The authors concluded that the study results showed that the 9-valent vaccine “prevented cervical, vulvar, and vaginal disease and persistent infection associated with HPV-31, 33, 45, 52, and 58,” and that the incidence of disease associated with HPV-6, 11, 16, and 18 were similar in the two groups. “The effect of vaccination on the burden of cancer remains to be determined,” they added.
The study was funded by Merck, manufacturer of the Gardasil vaccines. Dr. Joura disclosed having received advisory board and lecture fees from Merck and Sanofi Pasteur MSD, and grant support from Merck and GlaxoSmithKline. Other author disclosures included ties to Merck, GlaxoSmithKline, Gen-Probe Hologic, Becton Dickinson, and others. Other authors are Merck employees.
The CDC’s Advisory Committee on Immunization Practices (ACIP) is scheduled to vote on proposed recommendations regarding the use of the 9-valent vaccine at a meeting on Feb. 26.
Dr. Anne Schuchat referred to the expanded coverage of additional oncogenic HPV types with the 9-valent vaccine as “a milestone.” But, she added, “while HPV-related cancer coverage can now expand, other types of coverage present ongoing challenges.” She noted that 57% of girls aged 13-17 years have received the first dose of HPV vaccine, which could exceed 90% “if teenagers were offered and accepted HPV vaccination every time they received another vaccine.” Coverage is included in the Vaccines for Children program and has improved with the Affordable Care Act, although some barriers to access remain, “in practice, if not in statute,” she pointed out.
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Dr. Anne Schuchat |
“Vaccination of a much higher proportion of preteens is needed” and instead of a scenario where oncologists will have “thousands of new patients” every year with HPV-associated cancers, “I hope that in a few decades we will be able to tell a generation of adults who never had HPV-associated cancers or precancers that when they were teenagers, we had them covered,” she said.
Dr. Schuchat is director of the CDC’s National Center for Immunization and Respiratory Diseases, Atlanta. She made these comments in an editorial accompanying the article by Dr. Joura et al. (N. Engl. J. Med. 2015;372:775-6). She had no relevant financial disclosures.
Dr. Anne Schuchat referred to the expanded coverage of additional oncogenic HPV types with the 9-valent vaccine as “a milestone.” But, she added, “while HPV-related cancer coverage can now expand, other types of coverage present ongoing challenges.” She noted that 57% of girls aged 13-17 years have received the first dose of HPV vaccine, which could exceed 90% “if teenagers were offered and accepted HPV vaccination every time they received another vaccine.” Coverage is included in the Vaccines for Children program and has improved with the Affordable Care Act, although some barriers to access remain, “in practice, if not in statute,” she pointed out.
|
Dr. Anne Schuchat |
“Vaccination of a much higher proportion of preteens is needed” and instead of a scenario where oncologists will have “thousands of new patients” every year with HPV-associated cancers, “I hope that in a few decades we will be able to tell a generation of adults who never had HPV-associated cancers or precancers that when they were teenagers, we had them covered,” she said.
Dr. Schuchat is director of the CDC’s National Center for Immunization and Respiratory Diseases, Atlanta. She made these comments in an editorial accompanying the article by Dr. Joura et al. (N. Engl. J. Med. 2015;372:775-6). She had no relevant financial disclosures.
Dr. Anne Schuchat referred to the expanded coverage of additional oncogenic HPV types with the 9-valent vaccine as “a milestone.” But, she added, “while HPV-related cancer coverage can now expand, other types of coverage present ongoing challenges.” She noted that 57% of girls aged 13-17 years have received the first dose of HPV vaccine, which could exceed 90% “if teenagers were offered and accepted HPV vaccination every time they received another vaccine.” Coverage is included in the Vaccines for Children program and has improved with the Affordable Care Act, although some barriers to access remain, “in practice, if not in statute,” she pointed out.
|
Dr. Anne Schuchat |
“Vaccination of a much higher proportion of preteens is needed” and instead of a scenario where oncologists will have “thousands of new patients” every year with HPV-associated cancers, “I hope that in a few decades we will be able to tell a generation of adults who never had HPV-associated cancers or precancers that when they were teenagers, we had them covered,” she said.
Dr. Schuchat is director of the CDC’s National Center for Immunization and Respiratory Diseases, Atlanta. She made these comments in an editorial accompanying the article by Dr. Joura et al. (N. Engl. J. Med. 2015;372:775-6). She had no relevant financial disclosures.
The immunogenicity and efficacy of the recently approved 9-valent human papillomavirus vaccine were similar to that of the currently approved and recommended quadrivalent HPV vaccine, in an international study of over 14,000 women.
The study, published in the New England Journal of Medicine on Feb. 19, was the basis of the approval of the 9-valent vaccine in December 2014. The quadrivalent HPV vaccine is marketed as Gardasil and the 9-valent vaccine will be marketed as Gardasil-9.
The 9-valent vaccine covers the four HPV types (6, 11, 16, and 18) included in the quadrivalent vaccine; HPV-16 and HPV-18 are associated with about 70% of cervical cancers. The 9-valent vaccine, which includes five other oncogenic HPV types (31, 33, 45, 52, and 58), “offers the potential to increase overall prevention of cervical cancer ... to approximately 90%,” Dr. E. A. Joura of the department of gynecology and obstetrics at the Medical University of Vienna and associates said (N. Engl. J. Med. 2015;372:711-23 [doi:10.1056/NEJMoa1405044]).
In the Broad Spectrum HPV Vaccine Study, 14,215 women were randomized to receive the three recommended doses of the quadrivalent HPV vaccine or the 9-valent HPV vaccine and were followed with tests that included Pap tests, and swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue at baseline and periodically up to 4.5 years. Antibody responses to HPV types 6, 11, 16, and 18 (the types included in both vaccines) were similar in the two groups.
In both groups, the rate of high-grade cervical, vulvar, or vaginal disease associated with HPV types in the vaccines and those not in the vaccines was 14 cases per 1,000 person-years. In a subgroup of patients not infected with HPV at baseline, rates were 2.4% among those who received the 9-valent vaccine vs. 4.2% of those who received the quadrivalent vaccine.
The rate of high-grade cervical, vulvar, or vaginal disease associated with the five additional HPV types included in the 9-valent disease was 0.1 cases per 1,000 person-years, compared with 1.6 cases per 1,000 person-years among those who received the quadrivalent vaccine, a 97% reduced risk associated with the new vaccine.
As anticipated, injection-site reactions were more common among those who received the 9-valent vaccine (91% vs. 85%); most cases were mild to moderate. Other adverse events included dizziness, reported in about 3% in both groups.
The authors concluded that the study results showed that the 9-valent vaccine “prevented cervical, vulvar, and vaginal disease and persistent infection associated with HPV-31, 33, 45, 52, and 58,” and that the incidence of disease associated with HPV-6, 11, 16, and 18 were similar in the two groups. “The effect of vaccination on the burden of cancer remains to be determined,” they added.
The study was funded by Merck, manufacturer of the Gardasil vaccines. Dr. Joura disclosed having received advisory board and lecture fees from Merck and Sanofi Pasteur MSD, and grant support from Merck and GlaxoSmithKline. Other author disclosures included ties to Merck, GlaxoSmithKline, Gen-Probe Hologic, Becton Dickinson, and others. Other authors are Merck employees.
The CDC’s Advisory Committee on Immunization Practices (ACIP) is scheduled to vote on proposed recommendations regarding the use of the 9-valent vaccine at a meeting on Feb. 26.
The immunogenicity and efficacy of the recently approved 9-valent human papillomavirus vaccine were similar to that of the currently approved and recommended quadrivalent HPV vaccine, in an international study of over 14,000 women.
The study, published in the New England Journal of Medicine on Feb. 19, was the basis of the approval of the 9-valent vaccine in December 2014. The quadrivalent HPV vaccine is marketed as Gardasil and the 9-valent vaccine will be marketed as Gardasil-9.
The 9-valent vaccine covers the four HPV types (6, 11, 16, and 18) included in the quadrivalent vaccine; HPV-16 and HPV-18 are associated with about 70% of cervical cancers. The 9-valent vaccine, which includes five other oncogenic HPV types (31, 33, 45, 52, and 58), “offers the potential to increase overall prevention of cervical cancer ... to approximately 90%,” Dr. E. A. Joura of the department of gynecology and obstetrics at the Medical University of Vienna and associates said (N. Engl. J. Med. 2015;372:711-23 [doi:10.1056/NEJMoa1405044]).
In the Broad Spectrum HPV Vaccine Study, 14,215 women were randomized to receive the three recommended doses of the quadrivalent HPV vaccine or the 9-valent HPV vaccine and were followed with tests that included Pap tests, and swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue at baseline and periodically up to 4.5 years. Antibody responses to HPV types 6, 11, 16, and 18 (the types included in both vaccines) were similar in the two groups.
In both groups, the rate of high-grade cervical, vulvar, or vaginal disease associated with HPV types in the vaccines and those not in the vaccines was 14 cases per 1,000 person-years. In a subgroup of patients not infected with HPV at baseline, rates were 2.4% among those who received the 9-valent vaccine vs. 4.2% of those who received the quadrivalent vaccine.
The rate of high-grade cervical, vulvar, or vaginal disease associated with the five additional HPV types included in the 9-valent disease was 0.1 cases per 1,000 person-years, compared with 1.6 cases per 1,000 person-years among those who received the quadrivalent vaccine, a 97% reduced risk associated with the new vaccine.
As anticipated, injection-site reactions were more common among those who received the 9-valent vaccine (91% vs. 85%); most cases were mild to moderate. Other adverse events included dizziness, reported in about 3% in both groups.
The authors concluded that the study results showed that the 9-valent vaccine “prevented cervical, vulvar, and vaginal disease and persistent infection associated with HPV-31, 33, 45, 52, and 58,” and that the incidence of disease associated with HPV-6, 11, 16, and 18 were similar in the two groups. “The effect of vaccination on the burden of cancer remains to be determined,” they added.
The study was funded by Merck, manufacturer of the Gardasil vaccines. Dr. Joura disclosed having received advisory board and lecture fees from Merck and Sanofi Pasteur MSD, and grant support from Merck and GlaxoSmithKline. Other author disclosures included ties to Merck, GlaxoSmithKline, Gen-Probe Hologic, Becton Dickinson, and others. Other authors are Merck employees.
The CDC’s Advisory Committee on Immunization Practices (ACIP) is scheduled to vote on proposed recommendations regarding the use of the 9-valent vaccine at a meeting on Feb. 26.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: The 9-valent HPV vaccine is as safe and effective as the quadrivalent vaccine, and has the potential to increase protection against HPV-associated cancers to 90%.
Major finding: The rate of high-grade cervical, vulvar, or vaginal disease associated with the five additional HPV types included in the 9-valent vaccine was 0.1 cases per 1,000 person years vs. 1.6 cases per 1,000 person years among quadrivalent vaccine recipients, a 97% reduced risk associated with the new vaccine.
Data source: An international, randomized, double-blind, phase IIb-III study compared the efficacy and immunogenicity of the recently approved 9-valent HPV vaccine (Gardasil-9) and the currently approved and recommended quadrivalent vaccine (Gardasil) in over 14,000 women aged 16-26 years.
Disclosures: The study was funded by Merck, manufacturer of the Gardasil vaccines. Dr. Joura disclosed having received advisory board and lecture fees from Merck and Sanofi Pasteur MSD and grant support from Merck and GlaxoSmithKline. Other author disclosures included ties to Merck, GlaxoSmithKline, Gen-Probe Hologic, Becton Dickinson, and others. Other authors are Merck employees.
FDA allows marketing of vaginally inserted device for fecal incontinence
A vaginally inserted device that uses a balloon inflated by the patient to occlude the rectum has been cleared for marketing as a treatment for fecal incontinence in adult women, the Food and Drug Administration announced on Feb. 12.
The device is indicated for women aged 18-75 years who have had at least four episodes of fecal incontinence (FI) in a 2-week period, according to the FDA’s statement. The device includes a vaginal insert, placed in the same area as a tampon, and a pump that inflates and deflates a balloon on the insert. When inflated by the woman, the balloon “exerts pressure through the vaginal wall onto the rectal area, thereby reducing the number of FI episodes,” the statement said. The first time it is used, the clinician fits the device and inflates the balloon; subsequently, a patient deflates and inflates the device on her own, as needed. It will be marketed as the Eclipse System, by Pelvalon.
In the statement, Dr. William Maisel, deputy director for science and chief scientist in the FDA’s Center for Devices and Radiological Health, pointed out that treatment options for fecal incontinence currently include drugs, dietary changes, exercise, and surgery, and that the Eclipse System “provides an additional treatment option for women who suffer from this condition.”
Like many devices, this device did not go through the full approval process but was reviewed by the FDA through the “de novo classification process,” a pathway for making available some devices that have low to moderate risk and are not considered substantially equivalent to another available device.
The FDA reviewed nonclinical testing data and the main study that evaluated the device in 61 women with FI. One month after they started using the device, the number of FI episodes dropped by 50% in almost 80% of the women in the trial, according to the FDA statement. Pelvic cramping and discomfort; pelvic pain; vaginal abrasion, redness, or discharge; and urinary incontinence were among the adverse events associated with the device; all adverse events were mild or moderate. The LIFE study is scheduled to be published in the March 2015 issue of Obstetrics and Gynecology.
In a statement, the company said that it plans to release the Eclipse System later in 2015.
A vaginally inserted device that uses a balloon inflated by the patient to occlude the rectum has been cleared for marketing as a treatment for fecal incontinence in adult women, the Food and Drug Administration announced on Feb. 12.
The device is indicated for women aged 18-75 years who have had at least four episodes of fecal incontinence (FI) in a 2-week period, according to the FDA’s statement. The device includes a vaginal insert, placed in the same area as a tampon, and a pump that inflates and deflates a balloon on the insert. When inflated by the woman, the balloon “exerts pressure through the vaginal wall onto the rectal area, thereby reducing the number of FI episodes,” the statement said. The first time it is used, the clinician fits the device and inflates the balloon; subsequently, a patient deflates and inflates the device on her own, as needed. It will be marketed as the Eclipse System, by Pelvalon.
In the statement, Dr. William Maisel, deputy director for science and chief scientist in the FDA’s Center for Devices and Radiological Health, pointed out that treatment options for fecal incontinence currently include drugs, dietary changes, exercise, and surgery, and that the Eclipse System “provides an additional treatment option for women who suffer from this condition.”
Like many devices, this device did not go through the full approval process but was reviewed by the FDA through the “de novo classification process,” a pathway for making available some devices that have low to moderate risk and are not considered substantially equivalent to another available device.
The FDA reviewed nonclinical testing data and the main study that evaluated the device in 61 women with FI. One month after they started using the device, the number of FI episodes dropped by 50% in almost 80% of the women in the trial, according to the FDA statement. Pelvic cramping and discomfort; pelvic pain; vaginal abrasion, redness, or discharge; and urinary incontinence were among the adverse events associated with the device; all adverse events were mild or moderate. The LIFE study is scheduled to be published in the March 2015 issue of Obstetrics and Gynecology.
In a statement, the company said that it plans to release the Eclipse System later in 2015.
A vaginally inserted device that uses a balloon inflated by the patient to occlude the rectum has been cleared for marketing as a treatment for fecal incontinence in adult women, the Food and Drug Administration announced on Feb. 12.
The device is indicated for women aged 18-75 years who have had at least four episodes of fecal incontinence (FI) in a 2-week period, according to the FDA’s statement. The device includes a vaginal insert, placed in the same area as a tampon, and a pump that inflates and deflates a balloon on the insert. When inflated by the woman, the balloon “exerts pressure through the vaginal wall onto the rectal area, thereby reducing the number of FI episodes,” the statement said. The first time it is used, the clinician fits the device and inflates the balloon; subsequently, a patient deflates and inflates the device on her own, as needed. It will be marketed as the Eclipse System, by Pelvalon.
In the statement, Dr. William Maisel, deputy director for science and chief scientist in the FDA’s Center for Devices and Radiological Health, pointed out that treatment options for fecal incontinence currently include drugs, dietary changes, exercise, and surgery, and that the Eclipse System “provides an additional treatment option for women who suffer from this condition.”
Like many devices, this device did not go through the full approval process but was reviewed by the FDA through the “de novo classification process,” a pathway for making available some devices that have low to moderate risk and are not considered substantially equivalent to another available device.
The FDA reviewed nonclinical testing data and the main study that evaluated the device in 61 women with FI. One month after they started using the device, the number of FI episodes dropped by 50% in almost 80% of the women in the trial, according to the FDA statement. Pelvic cramping and discomfort; pelvic pain; vaginal abrasion, redness, or discharge; and urinary incontinence were among the adverse events associated with the device; all adverse events were mild or moderate. The LIFE study is scheduled to be published in the March 2015 issue of Obstetrics and Gynecology.
In a statement, the company said that it plans to release the Eclipse System later in 2015.
Ranibizumab now approved for diabetic retinopathy with macular edema
Ranibizumab, a vascular endothelial growth factor, or VEGF inhibitor, has been approved to treat diabetic retinopathy in patients with diabetic macular edema, the Food and Drug Administration announced on Feb 6.
This approval “gives patients with diabetic retinopathy and diabetic macular edema the first significant therapy to treat this vision-impairing complication,” Dr. Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in the statement. A 0.3-mg dose is administered by intravitreal injection once a month (roughly every 28 days), according to the updated prescribing information.
Approval was based on two studies of 759 patients, which found that after 2 years of treatment, those treated with ranibizumab had significant improvements in the severity of diabetic retinopathy, compared with controls. Bleeding of the conjunctiva, eye pain, floaters, and increased intraocular pressure were the most common adverse effects associated with treatment; endophthalmitis and retinal detachments were the most serious adverse effects, according to the FDA.
Ranibizumab was first approved in 2006, for neovascular (wet) age-related macular degeneration, followed by diabetic macular edema, and macular edema following retinal vein occlusion. It is marketed as Lucentis, by Genentech, a member of the Roche group. “The binding of ranibizumab to VEGF-A prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation,” according to the prescribing information.
Ranibizumab, a vascular endothelial growth factor, or VEGF inhibitor, has been approved to treat diabetic retinopathy in patients with diabetic macular edema, the Food and Drug Administration announced on Feb 6.
This approval “gives patients with diabetic retinopathy and diabetic macular edema the first significant therapy to treat this vision-impairing complication,” Dr. Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in the statement. A 0.3-mg dose is administered by intravitreal injection once a month (roughly every 28 days), according to the updated prescribing information.
Approval was based on two studies of 759 patients, which found that after 2 years of treatment, those treated with ranibizumab had significant improvements in the severity of diabetic retinopathy, compared with controls. Bleeding of the conjunctiva, eye pain, floaters, and increased intraocular pressure were the most common adverse effects associated with treatment; endophthalmitis and retinal detachments were the most serious adverse effects, according to the FDA.
Ranibizumab was first approved in 2006, for neovascular (wet) age-related macular degeneration, followed by diabetic macular edema, and macular edema following retinal vein occlusion. It is marketed as Lucentis, by Genentech, a member of the Roche group. “The binding of ranibizumab to VEGF-A prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation,” according to the prescribing information.
Ranibizumab, a vascular endothelial growth factor, or VEGF inhibitor, has been approved to treat diabetic retinopathy in patients with diabetic macular edema, the Food and Drug Administration announced on Feb 6.
This approval “gives patients with diabetic retinopathy and diabetic macular edema the first significant therapy to treat this vision-impairing complication,” Dr. Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in the statement. A 0.3-mg dose is administered by intravitreal injection once a month (roughly every 28 days), according to the updated prescribing information.
Approval was based on two studies of 759 patients, which found that after 2 years of treatment, those treated with ranibizumab had significant improvements in the severity of diabetic retinopathy, compared with controls. Bleeding of the conjunctiva, eye pain, floaters, and increased intraocular pressure were the most common adverse effects associated with treatment; endophthalmitis and retinal detachments were the most serious adverse effects, according to the FDA.
Ranibizumab was first approved in 2006, for neovascular (wet) age-related macular degeneration, followed by diabetic macular edema, and macular edema following retinal vein occlusion. It is marketed as Lucentis, by Genentech, a member of the Roche group. “The binding of ranibizumab to VEGF-A prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation,” according to the prescribing information.
No Increased Pancreatitis Risk Found With Incretin Therapy
No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.
To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.
The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.
The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])
Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).
In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.
The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.
Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.
Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.
The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.
No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.
To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.
The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.
The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])
Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).
In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.
The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.
Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.
Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.
The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.
No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.
To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.
The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.
The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])
Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).
In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.
The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.
Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.
Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.
The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.
No increased pancreatitis risk found with incretin therapy
No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.
To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.
The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.
The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])
Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).
In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.
The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.
Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.
Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.
The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.
No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.
To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.
The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.
The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])
Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).
In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.
The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.
Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.
Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.
The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.
No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.
To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.
The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.
The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])
Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).
In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.
The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.
Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.
Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.
The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.
Key clinical point: Neither GLP-1 receptor agonists nor DPP-4 inhibitors increase the risk of acute pancreatitis in type 2 diabetes patients.
Major finding: The risk of acute pancreatitis was not increased among Danes who had been treated with an incretin drug (odds ratio, 0.95), after adjustment for comorbidities and medications that can increase risk.
Data source: A population-based case-control study in 12,868 patients hospitalized for the first time with acute pancreatitis between 2005 and 2012, matched with 128,680 controls, from national medical databases.
Disclosures: The study was supported by the Clinical Epidemiological Research Foundation in Denmark. Most of the authors are at Danish institutions that receive funding and grants from Novo-Nordisk.
Dermal Filler Approved for Treating Acne Scars
A collagen dermal filler already on the market has been approved for improving the appearance of acne scars in people aged 21 years and older.
The filler, made of bovine collagen and nonabsorbable polymethylmethacrylate beads (PMMA microspheres), with a small amount of lidocaine, was approved for the correction of “moderate to severe, atrophic, distensible facial acne scars on the cheek in patients over the age of 21 years,” according to the Food and Drug Administration’s approval letter, dated Dec. 23, 2014.
The filler is marketed as Bellafill by Suneva Medical; it was formerly marketed as ArteFill. In December, the brand name was changed to Bellafill, according to the company. The filler was approved in 2006 for the correction of nasolabial folds and is the first permanent filler approved by the FDA for treating acne scars, an FDA spokesperson said.
In a clinical trial, one or two injections were needed to improve the appearance of acne scars, and the effect lasted more than 1 year, according to the FDA’s summary of approval-related information. Side effects included lumps at the injection site, redness, swelling, pain, tenderness, and itching. Contraindications included severe allergies, a positive response to the Bellafill skin test (which is required), allergies to lidocaine or cow tissue products, and bleeding disorders.
Approval was based on the multicenter U.S. study of patients aged 21 years and older with moderate to severe atrophic distensible facial acne scars on the cheek. The patients were randomized to Bellafill or sterile saline injections. Their mean age was 45 years, and about 60% were women.
At 6 months, 56 of 87 patients (64%) treated with Bellafill had at least a 2-point improvement on the 4-point Acne Scar Rating Scale for at least half of the treated scars (as assessed by a blinded evaluator), the primary endpoint. Of the 46 controls, 15 (33%) met this endpoint, and this difference was statistically significant.
Patient responses were among the endpoints evaluated in the study. At 6 months, 77% of those treated with Bellafill thought the appearance of scars had “improved” or had “much improved,” based on the Subject Global Aesthetic Improvement Scale ( a secondary endpoint), compared with 41% of controls.
Information on the approval is available on the FDA website at www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P020012S009.
Adverse events for this product or other drugs and devices should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/.
A collagen dermal filler already on the market has been approved for improving the appearance of acne scars in people aged 21 years and older.
The filler, made of bovine collagen and nonabsorbable polymethylmethacrylate beads (PMMA microspheres), with a small amount of lidocaine, was approved for the correction of “moderate to severe, atrophic, distensible facial acne scars on the cheek in patients over the age of 21 years,” according to the Food and Drug Administration’s approval letter, dated Dec. 23, 2014.
The filler is marketed as Bellafill by Suneva Medical; it was formerly marketed as ArteFill. In December, the brand name was changed to Bellafill, according to the company. The filler was approved in 2006 for the correction of nasolabial folds and is the first permanent filler approved by the FDA for treating acne scars, an FDA spokesperson said.
In a clinical trial, one or two injections were needed to improve the appearance of acne scars, and the effect lasted more than 1 year, according to the FDA’s summary of approval-related information. Side effects included lumps at the injection site, redness, swelling, pain, tenderness, and itching. Contraindications included severe allergies, a positive response to the Bellafill skin test (which is required), allergies to lidocaine or cow tissue products, and bleeding disorders.
Approval was based on the multicenter U.S. study of patients aged 21 years and older with moderate to severe atrophic distensible facial acne scars on the cheek. The patients were randomized to Bellafill or sterile saline injections. Their mean age was 45 years, and about 60% were women.
At 6 months, 56 of 87 patients (64%) treated with Bellafill had at least a 2-point improvement on the 4-point Acne Scar Rating Scale for at least half of the treated scars (as assessed by a blinded evaluator), the primary endpoint. Of the 46 controls, 15 (33%) met this endpoint, and this difference was statistically significant.
Patient responses were among the endpoints evaluated in the study. At 6 months, 77% of those treated with Bellafill thought the appearance of scars had “improved” or had “much improved,” based on the Subject Global Aesthetic Improvement Scale ( a secondary endpoint), compared with 41% of controls.
Information on the approval is available on the FDA website at www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P020012S009.
Adverse events for this product or other drugs and devices should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/.
A collagen dermal filler already on the market has been approved for improving the appearance of acne scars in people aged 21 years and older.
The filler, made of bovine collagen and nonabsorbable polymethylmethacrylate beads (PMMA microspheres), with a small amount of lidocaine, was approved for the correction of “moderate to severe, atrophic, distensible facial acne scars on the cheek in patients over the age of 21 years,” according to the Food and Drug Administration’s approval letter, dated Dec. 23, 2014.
The filler is marketed as Bellafill by Suneva Medical; it was formerly marketed as ArteFill. In December, the brand name was changed to Bellafill, according to the company. The filler was approved in 2006 for the correction of nasolabial folds and is the first permanent filler approved by the FDA for treating acne scars, an FDA spokesperson said.
In a clinical trial, one or two injections were needed to improve the appearance of acne scars, and the effect lasted more than 1 year, according to the FDA’s summary of approval-related information. Side effects included lumps at the injection site, redness, swelling, pain, tenderness, and itching. Contraindications included severe allergies, a positive response to the Bellafill skin test (which is required), allergies to lidocaine or cow tissue products, and bleeding disorders.
Approval was based on the multicenter U.S. study of patients aged 21 years and older with moderate to severe atrophic distensible facial acne scars on the cheek. The patients were randomized to Bellafill or sterile saline injections. Their mean age was 45 years, and about 60% were women.
At 6 months, 56 of 87 patients (64%) treated with Bellafill had at least a 2-point improvement on the 4-point Acne Scar Rating Scale for at least half of the treated scars (as assessed by a blinded evaluator), the primary endpoint. Of the 46 controls, 15 (33%) met this endpoint, and this difference was statistically significant.
Patient responses were among the endpoints evaluated in the study. At 6 months, 77% of those treated with Bellafill thought the appearance of scars had “improved” or had “much improved,” based on the Subject Global Aesthetic Improvement Scale ( a secondary endpoint), compared with 41% of controls.
Information on the approval is available on the FDA website at www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P020012S009.
Adverse events for this product or other drugs and devices should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/.
Dermal filler approved for treating acne scars
A collagen dermal filler already on the market has been approved for improving the appearance of acne scars in people aged 21 years and older.
The filler, made of bovine collagen and nonabsorbable polymethylmethacrylate beads (PMMA microspheres), with a small amount of lidocaine, was approved for the correction of “moderate to severe, atrophic, distensible facial acne scars on the cheek in patients over the age of 21 years,” according to the Food and Drug Administration’s approval letter, dated Dec. 23, 2014.
The filler is marketed as Bellafill by Suneva Medical; it was formerly marketed as ArteFill. In December, the brand name was changed to Bellafill, according to the company. The filler was approved in 2006 for the correction of nasolabial folds and is the first permanent filler approved by the FDA for treating acne scars, an FDA spokesperson said.
In a clinical trial, one or two injections were needed to improve the appearance of acne scars, and the effect lasted more than 1 year, according to the FDA’s summary of approval-related information. Side effects included lumps at the injection site, redness, swelling, pain, tenderness, and itching. Contraindications included severe allergies, a positive response to the Bellafill skin test (which is required), allergies to lidocaine or cow tissue products, and bleeding disorders.
Approval was based on the multicenter U.S. study of patients aged 21 years and older with moderate to severe atrophic distensible facial acne scars on the cheek. The patients were randomized to Bellafill or sterile saline injections. Their mean age was 45 years, and about 60% were women.
At 6 months, 56 of 87 patients (64%) treated with Bellafill had at least a 2-point improvement on the 4-point Acne Scar Rating Scale for at least half of the treated scars (as assessed by a blinded evaluator), the primary endpoint. Of the 46 controls, 15 (33%) met this endpoint, and this difference was statistically significant.
Patient responses were among the endpoints evaluated in the study. At 6 months, 77% of those treated with Bellafill thought the appearance of scars had “improved” or had “much improved,” based on the Subject Global Aesthetic Improvement Scale ( a secondary endpoint), compared with 41% of controls.
Information on the approval is available on the FDA website at www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P020012S009.
Adverse events for this product or other drugs and devices should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/.
A collagen dermal filler already on the market has been approved for improving the appearance of acne scars in people aged 21 years and older.
The filler, made of bovine collagen and nonabsorbable polymethylmethacrylate beads (PMMA microspheres), with a small amount of lidocaine, was approved for the correction of “moderate to severe, atrophic, distensible facial acne scars on the cheek in patients over the age of 21 years,” according to the Food and Drug Administration’s approval letter, dated Dec. 23, 2014.
The filler is marketed as Bellafill by Suneva Medical; it was formerly marketed as ArteFill. In December, the brand name was changed to Bellafill, according to the company. The filler was approved in 2006 for the correction of nasolabial folds and is the first permanent filler approved by the FDA for treating acne scars, an FDA spokesperson said.
In a clinical trial, one or two injections were needed to improve the appearance of acne scars, and the effect lasted more than 1 year, according to the FDA’s summary of approval-related information. Side effects included lumps at the injection site, redness, swelling, pain, tenderness, and itching. Contraindications included severe allergies, a positive response to the Bellafill skin test (which is required), allergies to lidocaine or cow tissue products, and bleeding disorders.
Approval was based on the multicenter U.S. study of patients aged 21 years and older with moderate to severe atrophic distensible facial acne scars on the cheek. The patients were randomized to Bellafill or sterile saline injections. Their mean age was 45 years, and about 60% were women.
At 6 months, 56 of 87 patients (64%) treated with Bellafill had at least a 2-point improvement on the 4-point Acne Scar Rating Scale for at least half of the treated scars (as assessed by a blinded evaluator), the primary endpoint. Of the 46 controls, 15 (33%) met this endpoint, and this difference was statistically significant.
Patient responses were among the endpoints evaluated in the study. At 6 months, 77% of those treated with Bellafill thought the appearance of scars had “improved” or had “much improved,” based on the Subject Global Aesthetic Improvement Scale ( a secondary endpoint), compared with 41% of controls.
Information on the approval is available on the FDA website at www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P020012S009.
Adverse events for this product or other drugs and devices should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/.
A collagen dermal filler already on the market has been approved for improving the appearance of acne scars in people aged 21 years and older.
The filler, made of bovine collagen and nonabsorbable polymethylmethacrylate beads (PMMA microspheres), with a small amount of lidocaine, was approved for the correction of “moderate to severe, atrophic, distensible facial acne scars on the cheek in patients over the age of 21 years,” according to the Food and Drug Administration’s approval letter, dated Dec. 23, 2014.
The filler is marketed as Bellafill by Suneva Medical; it was formerly marketed as ArteFill. In December, the brand name was changed to Bellafill, according to the company. The filler was approved in 2006 for the correction of nasolabial folds and is the first permanent filler approved by the FDA for treating acne scars, an FDA spokesperson said.
In a clinical trial, one or two injections were needed to improve the appearance of acne scars, and the effect lasted more than 1 year, according to the FDA’s summary of approval-related information. Side effects included lumps at the injection site, redness, swelling, pain, tenderness, and itching. Contraindications included severe allergies, a positive response to the Bellafill skin test (which is required), allergies to lidocaine or cow tissue products, and bleeding disorders.
Approval was based on the multicenter U.S. study of patients aged 21 years and older with moderate to severe atrophic distensible facial acne scars on the cheek. The patients were randomized to Bellafill or sterile saline injections. Their mean age was 45 years, and about 60% were women.
At 6 months, 56 of 87 patients (64%) treated with Bellafill had at least a 2-point improvement on the 4-point Acne Scar Rating Scale for at least half of the treated scars (as assessed by a blinded evaluator), the primary endpoint. Of the 46 controls, 15 (33%) met this endpoint, and this difference was statistically significant.
Patient responses were among the endpoints evaluated in the study. At 6 months, 77% of those treated with Bellafill thought the appearance of scars had “improved” or had “much improved,” based on the Subject Global Aesthetic Improvement Scale ( a secondary endpoint), compared with 41% of controls.
Information on the approval is available on the FDA website at www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P020012S009.
Adverse events for this product or other drugs and devices should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/.
Ties between adolescent cannabis use, mood disorders explored
AVENTURA, FLA. – Common risk factors, such as genetic risk or family dysfunction, might partly explain the association between higher rates of mood disorders and the use of marijuana among adolescents, Dr. Christopher Hammond said at the annual meeting of the American Academy of Addiction Psychiatry.
Evidence from different types of studies and populations of patients indicate that the rates of adolescents and adults who have an affective disorder and a cannabis-use related disorder or use cannabis “exceed the levels we would expect to see by chance alone,” noted Dr. Hammond of the Yale Child Study Center, Yale University, New Haven, Conn. In addition, over the past few decades, particularly in the last 5 years, cannabis use has increased, especially among adolescents, and to “a lesser extent,” there has also been an increase in depression and suicide rates among young people.
For affective disorders in general, the “evidence is less consistent and less convincing for a causal role” of cannabis than for psychotic symptoms and disorders, Dr. Hammond said. Adolescents and young adults who use cannabis might report that it reduces their anxiety or depression, however, “in controlled experimental studies, the findings are less conclusive,” he noted.
A systematic review of 35 studies from the 1970s through 2006 found that almost all reported an increase in affective outcomes among people who abused cannabis (Lancet 2007;370:319-28). But wide variations exist in the confidence intervals and small effect sizes, and most of the studies were underpowered to examine outcomes, Dr. Hammond said. Studies evaluating whether cannabis use is associated with an increased rate of affective disorders have used a variety of approaches with different study designs and varying levels of use (daily, weekly, monthly, yearly, or “ever”), so a metaanalysis is not possible, he pointed out.
Despite some inconsistent findings in the literature, most prospective longitudinal studies have found that regular early-onset cannabis use is associated with a “modest” increased risk of later depression, Dr. Hammond said. In a pooled analysis of the studies in the systematic review looking at depression, those who used cannabis the most frequently were at about a 1.5 times greater risk of depression than nonusers, and studies published since 2006 have further supported that association.
Cohort studies have made it possible to evaluate whether depression in adolescence and childhood predicts later cannabis use – the reverse causation hypothesis – and, “with few exceptions, [these] studies have failed to find a significant association between child and adolescent depression, and later-onset cannabis use,” he said. Negative studies have included a broad range of samples and are representative of the general population, including a longitudinal study of children in the United States with prepubertal depression.
The systematic review included eight studies that looked at anxiety outcomes, of which three – including two in adolescents – found an association with anxiety disorders and adolescent cannabis use, after controlling for confounding variables. In multiple studies, “the most common finding is that trauma and traumatic distress ... is really the only affective symptom that has been consistently found to predate adolescent cannabis use and to increase the risk of chronic cannabis use across a number of different studies,” he said. In addition, case series and anecdotal reports suggest that acute and chronic cannabis use, and cannabis withdrawal during attempts to stop use, might increase anxiety panic attacks and anxiety disorders in “vulnerable teens.”
Bipolar disorder has the highest rate of substance abuse comorbidity of any neuropsychiatric disorder, and cannabis is considered the “drug of choice” in people with bipolar disorder, but there is a paucity of research systematically examining this association, particularly in adolescents, Dr. Hammond said. The available data indicate that cannabis use appears to elevate the risk of developing mania in people diagnosed with or who are at risk of bipolar disorder, he said.
In studies that have evaluated risk in people with bipolar disorder with and without cannabis use disorder, those who use cannabis have an earlier age of onset of bipolar disorder and earlier age at first hospitalization for bipolar disorder; in one study, adolescents with bipolar disorder and cannabis use disorder had more abnormalities in the prefrontal lobes and temporal and subcortical structures, than those with bipolar disorder only (J. Child Adolesc. Psychopharmacol. 200818:557-63).
A “growing body of evidence” supports an association between adolescent-onset cannabis use and “both concurrent and later risk for suicidal behaviors,” even when controlling for confounding factors, according to Dr. Hammond. The data include a recently published study evaluating the association between levels of cannabis use before age 17 years and suicide and other outcomes up to age 30 in three cohorts of over 3,500 people, which found that those who used cannabis daily before age 17 were about seven times more likely to attempt suicide in young adulthood than those who did not use cannabis (Lancet Psychiatry 2014;4:286-93).
Biologically plausible reasons for why cannabis use and affective disorders might be related include the fact that the greatest density of cannabinoid-1 receptors in the brain are in regions that are “implicated in both cannabis use disorders but also affective disorders and other neuropsychiatric disorders,” he said. Shared risk genes is another biological explanation, he added, noting that a polymorphism in the gene that encodes for the cannabinoid-1 receptor (CNR1) gene “has been found to increase vulnerability for developing cannabis dependence, (posttraumatic stress disorder), as well as depression in Parkinson’s disease.”
The period of adolescence “does appear to be a vulnerable window specifically for the effects of cannabis use,” Dr. Hammond said, referring to preclinical data that include evidence of alterations in the maturation of the prefrontal cortex, as well as in neurotransmitter and stress-response systems in rodents exposed to exogenous cannabinoids during adolescence. Behavioral data echo “what we’re finding in the brains ... with exogenous cannabis exposure during adolescence altering emotional reactivity ... and producing in adulthood what would be considered a depressive-anxious phenotype,” in the rodent animal model, he said.
This phenotype is not evident when cannabis is administered chronically to older animals, which “suggests that there’s an age-dependent vulnerability specific to childhood and adolescence to the adverse effects of cannabinoids on the brain,” he added.
The association between cannabis use in adolescents, and anxiety disorders and bipolar disorders later in life has not been adequately studied but will be addressed in the Adolescent Brain Cognitive Development Study, Dr. Hammond said. The so-called ABCD study will enroll 10,000 subjects aged 10 through 12 years and will follow them through young adulthood, evaluating patterns of substance abuse, neurodevelopmental impact, and genetic factors. Currently, the study is in the planning stages.
Dr. Hammond disclosed receiving some research funding from a pilot research award from the American Academy of Child and Adolescent Psychiatry, and a child psychiatry fellowship award from the American Psychiatric Association.
AVENTURA, FLA. – Common risk factors, such as genetic risk or family dysfunction, might partly explain the association between higher rates of mood disorders and the use of marijuana among adolescents, Dr. Christopher Hammond said at the annual meeting of the American Academy of Addiction Psychiatry.
Evidence from different types of studies and populations of patients indicate that the rates of adolescents and adults who have an affective disorder and a cannabis-use related disorder or use cannabis “exceed the levels we would expect to see by chance alone,” noted Dr. Hammond of the Yale Child Study Center, Yale University, New Haven, Conn. In addition, over the past few decades, particularly in the last 5 years, cannabis use has increased, especially among adolescents, and to “a lesser extent,” there has also been an increase in depression and suicide rates among young people.
For affective disorders in general, the “evidence is less consistent and less convincing for a causal role” of cannabis than for psychotic symptoms and disorders, Dr. Hammond said. Adolescents and young adults who use cannabis might report that it reduces their anxiety or depression, however, “in controlled experimental studies, the findings are less conclusive,” he noted.
A systematic review of 35 studies from the 1970s through 2006 found that almost all reported an increase in affective outcomes among people who abused cannabis (Lancet 2007;370:319-28). But wide variations exist in the confidence intervals and small effect sizes, and most of the studies were underpowered to examine outcomes, Dr. Hammond said. Studies evaluating whether cannabis use is associated with an increased rate of affective disorders have used a variety of approaches with different study designs and varying levels of use (daily, weekly, monthly, yearly, or “ever”), so a metaanalysis is not possible, he pointed out.
Despite some inconsistent findings in the literature, most prospective longitudinal studies have found that regular early-onset cannabis use is associated with a “modest” increased risk of later depression, Dr. Hammond said. In a pooled analysis of the studies in the systematic review looking at depression, those who used cannabis the most frequently were at about a 1.5 times greater risk of depression than nonusers, and studies published since 2006 have further supported that association.
Cohort studies have made it possible to evaluate whether depression in adolescence and childhood predicts later cannabis use – the reverse causation hypothesis – and, “with few exceptions, [these] studies have failed to find a significant association between child and adolescent depression, and later-onset cannabis use,” he said. Negative studies have included a broad range of samples and are representative of the general population, including a longitudinal study of children in the United States with prepubertal depression.
The systematic review included eight studies that looked at anxiety outcomes, of which three – including two in adolescents – found an association with anxiety disorders and adolescent cannabis use, after controlling for confounding variables. In multiple studies, “the most common finding is that trauma and traumatic distress ... is really the only affective symptom that has been consistently found to predate adolescent cannabis use and to increase the risk of chronic cannabis use across a number of different studies,” he said. In addition, case series and anecdotal reports suggest that acute and chronic cannabis use, and cannabis withdrawal during attempts to stop use, might increase anxiety panic attacks and anxiety disorders in “vulnerable teens.”
Bipolar disorder has the highest rate of substance abuse comorbidity of any neuropsychiatric disorder, and cannabis is considered the “drug of choice” in people with bipolar disorder, but there is a paucity of research systematically examining this association, particularly in adolescents, Dr. Hammond said. The available data indicate that cannabis use appears to elevate the risk of developing mania in people diagnosed with or who are at risk of bipolar disorder, he said.
In studies that have evaluated risk in people with bipolar disorder with and without cannabis use disorder, those who use cannabis have an earlier age of onset of bipolar disorder and earlier age at first hospitalization for bipolar disorder; in one study, adolescents with bipolar disorder and cannabis use disorder had more abnormalities in the prefrontal lobes and temporal and subcortical structures, than those with bipolar disorder only (J. Child Adolesc. Psychopharmacol. 200818:557-63).
A “growing body of evidence” supports an association between adolescent-onset cannabis use and “both concurrent and later risk for suicidal behaviors,” even when controlling for confounding factors, according to Dr. Hammond. The data include a recently published study evaluating the association between levels of cannabis use before age 17 years and suicide and other outcomes up to age 30 in three cohorts of over 3,500 people, which found that those who used cannabis daily before age 17 were about seven times more likely to attempt suicide in young adulthood than those who did not use cannabis (Lancet Psychiatry 2014;4:286-93).
Biologically plausible reasons for why cannabis use and affective disorders might be related include the fact that the greatest density of cannabinoid-1 receptors in the brain are in regions that are “implicated in both cannabis use disorders but also affective disorders and other neuropsychiatric disorders,” he said. Shared risk genes is another biological explanation, he added, noting that a polymorphism in the gene that encodes for the cannabinoid-1 receptor (CNR1) gene “has been found to increase vulnerability for developing cannabis dependence, (posttraumatic stress disorder), as well as depression in Parkinson’s disease.”
The period of adolescence “does appear to be a vulnerable window specifically for the effects of cannabis use,” Dr. Hammond said, referring to preclinical data that include evidence of alterations in the maturation of the prefrontal cortex, as well as in neurotransmitter and stress-response systems in rodents exposed to exogenous cannabinoids during adolescence. Behavioral data echo “what we’re finding in the brains ... with exogenous cannabis exposure during adolescence altering emotional reactivity ... and producing in adulthood what would be considered a depressive-anxious phenotype,” in the rodent animal model, he said.
This phenotype is not evident when cannabis is administered chronically to older animals, which “suggests that there’s an age-dependent vulnerability specific to childhood and adolescence to the adverse effects of cannabinoids on the brain,” he added.
The association between cannabis use in adolescents, and anxiety disorders and bipolar disorders later in life has not been adequately studied but will be addressed in the Adolescent Brain Cognitive Development Study, Dr. Hammond said. The so-called ABCD study will enroll 10,000 subjects aged 10 through 12 years and will follow them through young adulthood, evaluating patterns of substance abuse, neurodevelopmental impact, and genetic factors. Currently, the study is in the planning stages.
Dr. Hammond disclosed receiving some research funding from a pilot research award from the American Academy of Child and Adolescent Psychiatry, and a child psychiatry fellowship award from the American Psychiatric Association.
AVENTURA, FLA. – Common risk factors, such as genetic risk or family dysfunction, might partly explain the association between higher rates of mood disorders and the use of marijuana among adolescents, Dr. Christopher Hammond said at the annual meeting of the American Academy of Addiction Psychiatry.
Evidence from different types of studies and populations of patients indicate that the rates of adolescents and adults who have an affective disorder and a cannabis-use related disorder or use cannabis “exceed the levels we would expect to see by chance alone,” noted Dr. Hammond of the Yale Child Study Center, Yale University, New Haven, Conn. In addition, over the past few decades, particularly in the last 5 years, cannabis use has increased, especially among adolescents, and to “a lesser extent,” there has also been an increase in depression and suicide rates among young people.
For affective disorders in general, the “evidence is less consistent and less convincing for a causal role” of cannabis than for psychotic symptoms and disorders, Dr. Hammond said. Adolescents and young adults who use cannabis might report that it reduces their anxiety or depression, however, “in controlled experimental studies, the findings are less conclusive,” he noted.
A systematic review of 35 studies from the 1970s through 2006 found that almost all reported an increase in affective outcomes among people who abused cannabis (Lancet 2007;370:319-28). But wide variations exist in the confidence intervals and small effect sizes, and most of the studies were underpowered to examine outcomes, Dr. Hammond said. Studies evaluating whether cannabis use is associated with an increased rate of affective disorders have used a variety of approaches with different study designs and varying levels of use (daily, weekly, monthly, yearly, or “ever”), so a metaanalysis is not possible, he pointed out.
Despite some inconsistent findings in the literature, most prospective longitudinal studies have found that regular early-onset cannabis use is associated with a “modest” increased risk of later depression, Dr. Hammond said. In a pooled analysis of the studies in the systematic review looking at depression, those who used cannabis the most frequently were at about a 1.5 times greater risk of depression than nonusers, and studies published since 2006 have further supported that association.
Cohort studies have made it possible to evaluate whether depression in adolescence and childhood predicts later cannabis use – the reverse causation hypothesis – and, “with few exceptions, [these] studies have failed to find a significant association between child and adolescent depression, and later-onset cannabis use,” he said. Negative studies have included a broad range of samples and are representative of the general population, including a longitudinal study of children in the United States with prepubertal depression.
The systematic review included eight studies that looked at anxiety outcomes, of which three – including two in adolescents – found an association with anxiety disorders and adolescent cannabis use, after controlling for confounding variables. In multiple studies, “the most common finding is that trauma and traumatic distress ... is really the only affective symptom that has been consistently found to predate adolescent cannabis use and to increase the risk of chronic cannabis use across a number of different studies,” he said. In addition, case series and anecdotal reports suggest that acute and chronic cannabis use, and cannabis withdrawal during attempts to stop use, might increase anxiety panic attacks and anxiety disorders in “vulnerable teens.”
Bipolar disorder has the highest rate of substance abuse comorbidity of any neuropsychiatric disorder, and cannabis is considered the “drug of choice” in people with bipolar disorder, but there is a paucity of research systematically examining this association, particularly in adolescents, Dr. Hammond said. The available data indicate that cannabis use appears to elevate the risk of developing mania in people diagnosed with or who are at risk of bipolar disorder, he said.
In studies that have evaluated risk in people with bipolar disorder with and without cannabis use disorder, those who use cannabis have an earlier age of onset of bipolar disorder and earlier age at first hospitalization for bipolar disorder; in one study, adolescents with bipolar disorder and cannabis use disorder had more abnormalities in the prefrontal lobes and temporal and subcortical structures, than those with bipolar disorder only (J. Child Adolesc. Psychopharmacol. 200818:557-63).
A “growing body of evidence” supports an association between adolescent-onset cannabis use and “both concurrent and later risk for suicidal behaviors,” even when controlling for confounding factors, according to Dr. Hammond. The data include a recently published study evaluating the association between levels of cannabis use before age 17 years and suicide and other outcomes up to age 30 in three cohorts of over 3,500 people, which found that those who used cannabis daily before age 17 were about seven times more likely to attempt suicide in young adulthood than those who did not use cannabis (Lancet Psychiatry 2014;4:286-93).
Biologically plausible reasons for why cannabis use and affective disorders might be related include the fact that the greatest density of cannabinoid-1 receptors in the brain are in regions that are “implicated in both cannabis use disorders but also affective disorders and other neuropsychiatric disorders,” he said. Shared risk genes is another biological explanation, he added, noting that a polymorphism in the gene that encodes for the cannabinoid-1 receptor (CNR1) gene “has been found to increase vulnerability for developing cannabis dependence, (posttraumatic stress disorder), as well as depression in Parkinson’s disease.”
The period of adolescence “does appear to be a vulnerable window specifically for the effects of cannabis use,” Dr. Hammond said, referring to preclinical data that include evidence of alterations in the maturation of the prefrontal cortex, as well as in neurotransmitter and stress-response systems in rodents exposed to exogenous cannabinoids during adolescence. Behavioral data echo “what we’re finding in the brains ... with exogenous cannabis exposure during adolescence altering emotional reactivity ... and producing in adulthood what would be considered a depressive-anxious phenotype,” in the rodent animal model, he said.
This phenotype is not evident when cannabis is administered chronically to older animals, which “suggests that there’s an age-dependent vulnerability specific to childhood and adolescence to the adverse effects of cannabinoids on the brain,” he added.
The association between cannabis use in adolescents, and anxiety disorders and bipolar disorders later in life has not been adequately studied but will be addressed in the Adolescent Brain Cognitive Development Study, Dr. Hammond said. The so-called ABCD study will enroll 10,000 subjects aged 10 through 12 years and will follow them through young adulthood, evaluating patterns of substance abuse, neurodevelopmental impact, and genetic factors. Currently, the study is in the planning stages.
Dr. Hammond disclosed receiving some research funding from a pilot research award from the American Academy of Child and Adolescent Psychiatry, and a child psychiatry fellowship award from the American Psychiatric Association.
EXPERT ANALYSIS FROM THE AAAP ANNUAL MEETING
Screening tools can identify gambling disorder patients
AVENTURA, FLA. – People with unrecognized gambling disorders may present with depression, anxiety, substance abuse, or other psychiatric symptoms, and screening patients with these symptoms can help make this connection, Dr. Timothy Fong said during a workshop at the annual meeting of the American Academy of Addiction Psychiatry.
Screening tools are essential in helping identify patients with a gambling disorder or subthreshold disorder, who typically do not bring up these problems with their physicians and often suffer in private, said Dr. Fong, a psychiatrist at the University of California, Los Angeles, and codirector of the UCLA Gambling Studies Program.
“By the time I see them, the screening has already happened; they have self-identified as having a problem,” he pointed out. “But when they’re coming to see the general psychiatrist,” problems like depression, difficulty sleeping, or problems with a spouse or family, “are the chief complaints, it’s not ‘I have a gambling problem.’ ”
Screening can help identify patients before they develop a full-blown gambling disorder, at an earlier stage, when it is simpler to treat and interventions are more effective “and you can prevent the progression to a more severe disorder,” he noted.
Another sign someone might have a gambling problem is failure to respond to medication, an indication that problem gambling “may be a hidden addiction that is driving the stress [or] depression,” Dr. Fong said, citing a patient with depression who does not respond to courses of selective serotonin reuptake inhibitors or other categories of antidepressants as an example.
During a workshop on gambling disorders held during the meeting, Dr. Fong and Dr. Iman Parhami, who is affiliated with the Delaware Division of Substance Abuse and Mental Health, New Castle, Del., referred to one such resource, a brief three-question screening tool available on the National Center for Responsible Gaming website.
Gambling behavior can be considered in three levels, recreational gambling, where there are no repercussions related to gambling; subthreshold gambling disorder, where the individual encounters gambling-related problems but does not meet the diagnostic threshold for a disorder, although is at an increased risk of developing a gambling disorder at some point in the future; and gambling disorder. A gambling disorder is characterized by “persistent, recurring and sometimes progressive maladaptive gambling behavior despite the negative consequences,” with behavior that has the greatest social, psychological, and medical impact. Those with a subthreshold gambling disorder are at a higher risk, but whether recreational gamblers are at increased risk is less clear, said Dr. Parhami, who formerly was affiliated with the UCLA gambling studies program.
In the DSM-5, gambling disorder now appears under “non substance-related disorders” in the substance-related and addictive disorders section, and is defined as “persistent and recurrent problematic gambling behavior leading to clinically significant impairment or distress,” as indicated by the individual exhibiting at least four of nine symptoms over a 12-month period: preoccupation, tolerance, withdrawal (developing symptoms like anxiety when they do not gamble), loss of control, escapism, dishonesty, risk-taking behaviors related to gambling, chasing (returning another day to get even after losing money gambling), and bailouts (relying on others to provide money to relieve a desperate financial situation caused by gambling). These symptoms are similar to other addictive disorders, and loss of control is probably the main symptom, Dr. Parhami said.
Identifying a patient with a gambling disorder at an earlier stage and preventing progression also can reduce the risk of developing a comorbid disorder, because any level of gambling is associated with an increased risk for developing comorbid mental disorders, according to Dr. Parhami and Dr. Fong, two of the authors of a recently published prospective study, which compared the incidence of new onset comorbid disorders among people at three levels of gambling behavior, to those who did not gamble at all.
Using longitudinal data from the National Epidemiologic Survey on Alcohol and Related Conditions, researchers divided respondents into three groups: those with a gambling disorder, those with a subthreshold gambling disorder, and those who were recreational gamblers. Three years after their initial interview for the survey, those in all three groups were at a statistically significantly increased risk of having any mood, anxiety, or substance abuse disorder, compared with controls who did not gamble at all (J. Psychiatr. Pract. 2014;20:207-19).
Overall, those in the three gambling behavior categories were at a more than twofold greater risk among those with gambling disorder diagnosis at baseline, with an odds ratio – adjusted for age, sex, marital status, annual income, and education – of 2.5. The risk also was significantly increased among those with a subthreshhold gambling disorder at baseline (odds ratio, 1.77) and even among those who were recreational gamblers at baseline (OR, 1.16).
When mood, anxiety, and substance abuse disorders were evaluated separately, a graded or dose-response relationship was found between different levels of gambling and risk, with the risks highest for those with the disorder and lowest for recreational gamblers, and the risk falling in between for the subthreshold gamblers, Dr. Fong said.
The risk of a mood disorder was increased by more than fourfold among those with a gambling disorder at baseline (OR, 4.38), and also was increased among those with a subthreshold gambling disorder at baseline (OR, 1.37). The risk of any anxiety disorder also followed the same pattern, significantly increased among those with a gambling disorder (OR, 3.11), subthreshold disorder (OR, 1.70), and recreational gamblers (OR, 1.10).
The risk of any substance use disorder also was significantly increased at all three levels. Among those with a gambling disorder at baseline, the risks of any alcohol-related disorder and alcohol dependence were increased among those with a gambling disorder at baseline (ORs, 3.90 and 4.66, respectively), and also were increased among those with a subthreshold disorder at baseline (OR, 1.97, 2.19), and among those who were recreational gamblers at baseline (OR 1.3, 1.29).
Dr. Fong and Dr. Parhami had no disclosures relevant to this presentation at the meeting.
AVENTURA, FLA. – People with unrecognized gambling disorders may present with depression, anxiety, substance abuse, or other psychiatric symptoms, and screening patients with these symptoms can help make this connection, Dr. Timothy Fong said during a workshop at the annual meeting of the American Academy of Addiction Psychiatry.
Screening tools are essential in helping identify patients with a gambling disorder or subthreshold disorder, who typically do not bring up these problems with their physicians and often suffer in private, said Dr. Fong, a psychiatrist at the University of California, Los Angeles, and codirector of the UCLA Gambling Studies Program.
“By the time I see them, the screening has already happened; they have self-identified as having a problem,” he pointed out. “But when they’re coming to see the general psychiatrist,” problems like depression, difficulty sleeping, or problems with a spouse or family, “are the chief complaints, it’s not ‘I have a gambling problem.’ ”
Screening can help identify patients before they develop a full-blown gambling disorder, at an earlier stage, when it is simpler to treat and interventions are more effective “and you can prevent the progression to a more severe disorder,” he noted.
Another sign someone might have a gambling problem is failure to respond to medication, an indication that problem gambling “may be a hidden addiction that is driving the stress [or] depression,” Dr. Fong said, citing a patient with depression who does not respond to courses of selective serotonin reuptake inhibitors or other categories of antidepressants as an example.
During a workshop on gambling disorders held during the meeting, Dr. Fong and Dr. Iman Parhami, who is affiliated with the Delaware Division of Substance Abuse and Mental Health, New Castle, Del., referred to one such resource, a brief three-question screening tool available on the National Center for Responsible Gaming website.
Gambling behavior can be considered in three levels, recreational gambling, where there are no repercussions related to gambling; subthreshold gambling disorder, where the individual encounters gambling-related problems but does not meet the diagnostic threshold for a disorder, although is at an increased risk of developing a gambling disorder at some point in the future; and gambling disorder. A gambling disorder is characterized by “persistent, recurring and sometimes progressive maladaptive gambling behavior despite the negative consequences,” with behavior that has the greatest social, psychological, and medical impact. Those with a subthreshold gambling disorder are at a higher risk, but whether recreational gamblers are at increased risk is less clear, said Dr. Parhami, who formerly was affiliated with the UCLA gambling studies program.
In the DSM-5, gambling disorder now appears under “non substance-related disorders” in the substance-related and addictive disorders section, and is defined as “persistent and recurrent problematic gambling behavior leading to clinically significant impairment or distress,” as indicated by the individual exhibiting at least four of nine symptoms over a 12-month period: preoccupation, tolerance, withdrawal (developing symptoms like anxiety when they do not gamble), loss of control, escapism, dishonesty, risk-taking behaviors related to gambling, chasing (returning another day to get even after losing money gambling), and bailouts (relying on others to provide money to relieve a desperate financial situation caused by gambling). These symptoms are similar to other addictive disorders, and loss of control is probably the main symptom, Dr. Parhami said.
Identifying a patient with a gambling disorder at an earlier stage and preventing progression also can reduce the risk of developing a comorbid disorder, because any level of gambling is associated with an increased risk for developing comorbid mental disorders, according to Dr. Parhami and Dr. Fong, two of the authors of a recently published prospective study, which compared the incidence of new onset comorbid disorders among people at three levels of gambling behavior, to those who did not gamble at all.
Using longitudinal data from the National Epidemiologic Survey on Alcohol and Related Conditions, researchers divided respondents into three groups: those with a gambling disorder, those with a subthreshold gambling disorder, and those who were recreational gamblers. Three years after their initial interview for the survey, those in all three groups were at a statistically significantly increased risk of having any mood, anxiety, or substance abuse disorder, compared with controls who did not gamble at all (J. Psychiatr. Pract. 2014;20:207-19).
Overall, those in the three gambling behavior categories were at a more than twofold greater risk among those with gambling disorder diagnosis at baseline, with an odds ratio – adjusted for age, sex, marital status, annual income, and education – of 2.5. The risk also was significantly increased among those with a subthreshhold gambling disorder at baseline (odds ratio, 1.77) and even among those who were recreational gamblers at baseline (OR, 1.16).
When mood, anxiety, and substance abuse disorders were evaluated separately, a graded or dose-response relationship was found between different levels of gambling and risk, with the risks highest for those with the disorder and lowest for recreational gamblers, and the risk falling in between for the subthreshold gamblers, Dr. Fong said.
The risk of a mood disorder was increased by more than fourfold among those with a gambling disorder at baseline (OR, 4.38), and also was increased among those with a subthreshold gambling disorder at baseline (OR, 1.37). The risk of any anxiety disorder also followed the same pattern, significantly increased among those with a gambling disorder (OR, 3.11), subthreshold disorder (OR, 1.70), and recreational gamblers (OR, 1.10).
The risk of any substance use disorder also was significantly increased at all three levels. Among those with a gambling disorder at baseline, the risks of any alcohol-related disorder and alcohol dependence were increased among those with a gambling disorder at baseline (ORs, 3.90 and 4.66, respectively), and also were increased among those with a subthreshold disorder at baseline (OR, 1.97, 2.19), and among those who were recreational gamblers at baseline (OR 1.3, 1.29).
Dr. Fong and Dr. Parhami had no disclosures relevant to this presentation at the meeting.
AVENTURA, FLA. – People with unrecognized gambling disorders may present with depression, anxiety, substance abuse, or other psychiatric symptoms, and screening patients with these symptoms can help make this connection, Dr. Timothy Fong said during a workshop at the annual meeting of the American Academy of Addiction Psychiatry.
Screening tools are essential in helping identify patients with a gambling disorder or subthreshold disorder, who typically do not bring up these problems with their physicians and often suffer in private, said Dr. Fong, a psychiatrist at the University of California, Los Angeles, and codirector of the UCLA Gambling Studies Program.
“By the time I see them, the screening has already happened; they have self-identified as having a problem,” he pointed out. “But when they’re coming to see the general psychiatrist,” problems like depression, difficulty sleeping, or problems with a spouse or family, “are the chief complaints, it’s not ‘I have a gambling problem.’ ”
Screening can help identify patients before they develop a full-blown gambling disorder, at an earlier stage, when it is simpler to treat and interventions are more effective “and you can prevent the progression to a more severe disorder,” he noted.
Another sign someone might have a gambling problem is failure to respond to medication, an indication that problem gambling “may be a hidden addiction that is driving the stress [or] depression,” Dr. Fong said, citing a patient with depression who does not respond to courses of selective serotonin reuptake inhibitors or other categories of antidepressants as an example.
During a workshop on gambling disorders held during the meeting, Dr. Fong and Dr. Iman Parhami, who is affiliated with the Delaware Division of Substance Abuse and Mental Health, New Castle, Del., referred to one such resource, a brief three-question screening tool available on the National Center for Responsible Gaming website.
Gambling behavior can be considered in three levels, recreational gambling, where there are no repercussions related to gambling; subthreshold gambling disorder, where the individual encounters gambling-related problems but does not meet the diagnostic threshold for a disorder, although is at an increased risk of developing a gambling disorder at some point in the future; and gambling disorder. A gambling disorder is characterized by “persistent, recurring and sometimes progressive maladaptive gambling behavior despite the negative consequences,” with behavior that has the greatest social, psychological, and medical impact. Those with a subthreshold gambling disorder are at a higher risk, but whether recreational gamblers are at increased risk is less clear, said Dr. Parhami, who formerly was affiliated with the UCLA gambling studies program.
In the DSM-5, gambling disorder now appears under “non substance-related disorders” in the substance-related and addictive disorders section, and is defined as “persistent and recurrent problematic gambling behavior leading to clinically significant impairment or distress,” as indicated by the individual exhibiting at least four of nine symptoms over a 12-month period: preoccupation, tolerance, withdrawal (developing symptoms like anxiety when they do not gamble), loss of control, escapism, dishonesty, risk-taking behaviors related to gambling, chasing (returning another day to get even after losing money gambling), and bailouts (relying on others to provide money to relieve a desperate financial situation caused by gambling). These symptoms are similar to other addictive disorders, and loss of control is probably the main symptom, Dr. Parhami said.
Identifying a patient with a gambling disorder at an earlier stage and preventing progression also can reduce the risk of developing a comorbid disorder, because any level of gambling is associated with an increased risk for developing comorbid mental disorders, according to Dr. Parhami and Dr. Fong, two of the authors of a recently published prospective study, which compared the incidence of new onset comorbid disorders among people at three levels of gambling behavior, to those who did not gamble at all.
Using longitudinal data from the National Epidemiologic Survey on Alcohol and Related Conditions, researchers divided respondents into three groups: those with a gambling disorder, those with a subthreshold gambling disorder, and those who were recreational gamblers. Three years after their initial interview for the survey, those in all three groups were at a statistically significantly increased risk of having any mood, anxiety, or substance abuse disorder, compared with controls who did not gamble at all (J. Psychiatr. Pract. 2014;20:207-19).
Overall, those in the three gambling behavior categories were at a more than twofold greater risk among those with gambling disorder diagnosis at baseline, with an odds ratio – adjusted for age, sex, marital status, annual income, and education – of 2.5. The risk also was significantly increased among those with a subthreshhold gambling disorder at baseline (odds ratio, 1.77) and even among those who were recreational gamblers at baseline (OR, 1.16).
When mood, anxiety, and substance abuse disorders were evaluated separately, a graded or dose-response relationship was found between different levels of gambling and risk, with the risks highest for those with the disorder and lowest for recreational gamblers, and the risk falling in between for the subthreshold gamblers, Dr. Fong said.
The risk of a mood disorder was increased by more than fourfold among those with a gambling disorder at baseline (OR, 4.38), and also was increased among those with a subthreshold gambling disorder at baseline (OR, 1.37). The risk of any anxiety disorder also followed the same pattern, significantly increased among those with a gambling disorder (OR, 3.11), subthreshold disorder (OR, 1.70), and recreational gamblers (OR, 1.10).
The risk of any substance use disorder also was significantly increased at all three levels. Among those with a gambling disorder at baseline, the risks of any alcohol-related disorder and alcohol dependence were increased among those with a gambling disorder at baseline (ORs, 3.90 and 4.66, respectively), and also were increased among those with a subthreshold disorder at baseline (OR, 1.97, 2.19), and among those who were recreational gamblers at baseline (OR 1.3, 1.29).
Dr. Fong and Dr. Parhami had no disclosures relevant to this presentation at the meeting.
EXPERT ANALYSIS FROM THE AAAP ANNUAL MEETING
