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CHMP recommends mogamulizumab for MF, SS
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for mogamulizumab (Poteligeo).
Kyowa Kirin Limited is seeking European Commission (EC) approval for mogamulizumab as a treatment for adults with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.
The CHMP’s recommendation to approve mogamulizumab will be reviewed by the EC, and the EC is expected to make its decision about the drug by the end of this year.
The decision will apply to the European Union, Norway, Iceland, and Liechtenstein.
The CHMP’s recommendation for mogamulizumab is supported by the phase 3 MAVORIC trial. Results from this trial were published in The Lancet Oncology in August.
MAVORIC was a comparison of mogamulizumab and vorinostat in 372 adults with MF or SS who had received at least one prior systemic therapy.
Mogamulizumab provided a significant improvement in progression-free survival (PFS), the study’s primary endpoint.
According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).
According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).
There was a significant improvement in overall response rate (ORR) with mogamulizumab.
According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).
According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).
For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.
For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.
Grade 3 adverse events (AEs) in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).
Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for mogamulizumab (Poteligeo).
Kyowa Kirin Limited is seeking European Commission (EC) approval for mogamulizumab as a treatment for adults with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.
The CHMP’s recommendation to approve mogamulizumab will be reviewed by the EC, and the EC is expected to make its decision about the drug by the end of this year.
The decision will apply to the European Union, Norway, Iceland, and Liechtenstein.
The CHMP’s recommendation for mogamulizumab is supported by the phase 3 MAVORIC trial. Results from this trial were published in The Lancet Oncology in August.
MAVORIC was a comparison of mogamulizumab and vorinostat in 372 adults with MF or SS who had received at least one prior systemic therapy.
Mogamulizumab provided a significant improvement in progression-free survival (PFS), the study’s primary endpoint.
According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).
According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).
There was a significant improvement in overall response rate (ORR) with mogamulizumab.
According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).
According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).
For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.
For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.
Grade 3 adverse events (AEs) in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).
Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for mogamulizumab (Poteligeo).
Kyowa Kirin Limited is seeking European Commission (EC) approval for mogamulizumab as a treatment for adults with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.
The CHMP’s recommendation to approve mogamulizumab will be reviewed by the EC, and the EC is expected to make its decision about the drug by the end of this year.
The decision will apply to the European Union, Norway, Iceland, and Liechtenstein.
The CHMP’s recommendation for mogamulizumab is supported by the phase 3 MAVORIC trial. Results from this trial were published in The Lancet Oncology in August.
MAVORIC was a comparison of mogamulizumab and vorinostat in 372 adults with MF or SS who had received at least one prior systemic therapy.
Mogamulizumab provided a significant improvement in progression-free survival (PFS), the study’s primary endpoint.
According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).
According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).
There was a significant improvement in overall response rate (ORR) with mogamulizumab.
According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).
According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).
For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.
For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.
Grade 3 adverse events (AEs) in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).
Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).
Trifarotene cream for acne meets all endpoints in twin phase 3 trials
PARIS – A novel kinder, gentler topical retinoid met all of its primary and secondary endpoints in two identical phase 3 randomized trials totaling 2,420 patients with moderate acne vulgaris on both the face and trunk.
Trifarotene cream 50 mcg/g selectively targets the gamma retinoic acid receptor. This unique selectivity for just one of the three retinoic acid receptors results in less of the classic retinoid side effects – redness, scaling, dryness, stinging, burning – that can limit the clinical utility of existing retinoids. This was borne out by the high completion rates in trifarotene-treated participants in the two 12-week trials: 88.2% in the PERFECT 1 trial and 92.7% in PERFECT 2, compared with rates of 89.8% and 93.9% in vehicle-treated controls, Jerry K.L. Tan, MD, said at the annual congress of the European Academy of Dermatology and Venereology.
“Most adverse events involved local intolerance occurring at application sites and were mild and transient,” Dr. Tan, a dermatologist at the University of Western Ontario, Windsor, and head of Windsor Clinical Research, reported.
PERFECT 1 and 2 were multicenter, double-blind, randomized, vehicle-controlled, 12-week phase 3 trials. Of note, these were the first-ever large-scale randomized trials to simultaneously evaluate a topical therapy for treatment of both facial and truncal acne. This ambitious goal created some unique challenges, which Dr. Tan described.
Participants, all of whom had moderate acne vulgaris on the face and trunk, ranged in age from 9 to 58 years, with a mean age of 19 years. They were randomized to once-daily application of trifarotene cream 50 mcg/g or its vehicle in the evening.
Primary and secondary outcomes
One major efficacy endpoint on the face was achievement of Investigator Global Assessment success as defined by a score of 0 or 1, meaning clear or almost clear, coupled with at least a 2-grade improvement from baseline to week 12. In PERFECT 1 and 2 this was achieved by 29.7% and 42.8% of trifarotene cream-treated patients, response rates significantly better than the 20% and 25.8% in vehicle-treated controls.
Another endpoint for facial therapy were the absolute reductions from baseline in facial inflammatory and noninflammatory acne lesions. The mean reduction in inflammatory lesion count in trifarotene-treated patients was 19.6% in PERFECT 1 and 24.6% in PERFECT 2, both significantly better than the mean 15.8% and 19.6% decreases in controls. Noninflammatory facial lesion counts dropped by 26.7% and 30.4% with trifarotene, versus 18.9% and 22.3% with vehicle.
The efficacy yardsticks utilized on the trunk were the same as on the face except that Physician Global Assessment was the terminology utilized in lieu of Investigator Global Assessment. Physician Global Assessment success on the trunk was achieved by 35.8% and 41.1% of trifarotene-treated patients in the two trials, as compared with 25.7% and 30.1% of controls.
The mean reductions in truncal inflammatory lesion count obtained with trifarotene cream were 22% and 26.1%, both significantly better than the 18.8% and 20.3% rates with vehicle.
Treatment-emergent adverse events leading to study discontinuation occurred in 1.9% of trifarotene-treated patients in one trial and 1% in the other.
One audience member commented that the vehicle response rates looked too strong for that compound to be inert. Dr. Tan agreed. “The vehicle looks really good. One of the issues with vehicles is that many of them have to contain products to prevent decay, fermentation, and proliferation of yeast and bacteria. So I quite agree: I think many of our vehicles do have active ingredients,” he replied. “If you look at the topical dapsone trials, the vehicles look amazing.”
“The other possibility is that there’s what we call ‘investigator creep,’” the dermatologist continued. “It’s the notion that you have no idea what the patients are getting, but they look like maybe they’re getting better, so you grade it as better.”
Dr. Tan reported serving as an advisor and consultant to, speaker for, and recipient of research grants from Galderma, which sponsored the two phase 3 trials. The company is also developing trifarotene for the treatment of lamellar ichthyosis.
PARIS – A novel kinder, gentler topical retinoid met all of its primary and secondary endpoints in two identical phase 3 randomized trials totaling 2,420 patients with moderate acne vulgaris on both the face and trunk.
Trifarotene cream 50 mcg/g selectively targets the gamma retinoic acid receptor. This unique selectivity for just one of the three retinoic acid receptors results in less of the classic retinoid side effects – redness, scaling, dryness, stinging, burning – that can limit the clinical utility of existing retinoids. This was borne out by the high completion rates in trifarotene-treated participants in the two 12-week trials: 88.2% in the PERFECT 1 trial and 92.7% in PERFECT 2, compared with rates of 89.8% and 93.9% in vehicle-treated controls, Jerry K.L. Tan, MD, said at the annual congress of the European Academy of Dermatology and Venereology.
“Most adverse events involved local intolerance occurring at application sites and were mild and transient,” Dr. Tan, a dermatologist at the University of Western Ontario, Windsor, and head of Windsor Clinical Research, reported.
PERFECT 1 and 2 were multicenter, double-blind, randomized, vehicle-controlled, 12-week phase 3 trials. Of note, these were the first-ever large-scale randomized trials to simultaneously evaluate a topical therapy for treatment of both facial and truncal acne. This ambitious goal created some unique challenges, which Dr. Tan described.
Participants, all of whom had moderate acne vulgaris on the face and trunk, ranged in age from 9 to 58 years, with a mean age of 19 years. They were randomized to once-daily application of trifarotene cream 50 mcg/g or its vehicle in the evening.
Primary and secondary outcomes
One major efficacy endpoint on the face was achievement of Investigator Global Assessment success as defined by a score of 0 or 1, meaning clear or almost clear, coupled with at least a 2-grade improvement from baseline to week 12. In PERFECT 1 and 2 this was achieved by 29.7% and 42.8% of trifarotene cream-treated patients, response rates significantly better than the 20% and 25.8% in vehicle-treated controls.
Another endpoint for facial therapy were the absolute reductions from baseline in facial inflammatory and noninflammatory acne lesions. The mean reduction in inflammatory lesion count in trifarotene-treated patients was 19.6% in PERFECT 1 and 24.6% in PERFECT 2, both significantly better than the mean 15.8% and 19.6% decreases in controls. Noninflammatory facial lesion counts dropped by 26.7% and 30.4% with trifarotene, versus 18.9% and 22.3% with vehicle.
The efficacy yardsticks utilized on the trunk were the same as on the face except that Physician Global Assessment was the terminology utilized in lieu of Investigator Global Assessment. Physician Global Assessment success on the trunk was achieved by 35.8% and 41.1% of trifarotene-treated patients in the two trials, as compared with 25.7% and 30.1% of controls.
The mean reductions in truncal inflammatory lesion count obtained with trifarotene cream were 22% and 26.1%, both significantly better than the 18.8% and 20.3% rates with vehicle.
Treatment-emergent adverse events leading to study discontinuation occurred in 1.9% of trifarotene-treated patients in one trial and 1% in the other.
One audience member commented that the vehicle response rates looked too strong for that compound to be inert. Dr. Tan agreed. “The vehicle looks really good. One of the issues with vehicles is that many of them have to contain products to prevent decay, fermentation, and proliferation of yeast and bacteria. So I quite agree: I think many of our vehicles do have active ingredients,” he replied. “If you look at the topical dapsone trials, the vehicles look amazing.”
“The other possibility is that there’s what we call ‘investigator creep,’” the dermatologist continued. “It’s the notion that you have no idea what the patients are getting, but they look like maybe they’re getting better, so you grade it as better.”
Dr. Tan reported serving as an advisor and consultant to, speaker for, and recipient of research grants from Galderma, which sponsored the two phase 3 trials. The company is also developing trifarotene for the treatment of lamellar ichthyosis.
PARIS – A novel kinder, gentler topical retinoid met all of its primary and secondary endpoints in two identical phase 3 randomized trials totaling 2,420 patients with moderate acne vulgaris on both the face and trunk.
Trifarotene cream 50 mcg/g selectively targets the gamma retinoic acid receptor. This unique selectivity for just one of the three retinoic acid receptors results in less of the classic retinoid side effects – redness, scaling, dryness, stinging, burning – that can limit the clinical utility of existing retinoids. This was borne out by the high completion rates in trifarotene-treated participants in the two 12-week trials: 88.2% in the PERFECT 1 trial and 92.7% in PERFECT 2, compared with rates of 89.8% and 93.9% in vehicle-treated controls, Jerry K.L. Tan, MD, said at the annual congress of the European Academy of Dermatology and Venereology.
“Most adverse events involved local intolerance occurring at application sites and were mild and transient,” Dr. Tan, a dermatologist at the University of Western Ontario, Windsor, and head of Windsor Clinical Research, reported.
PERFECT 1 and 2 were multicenter, double-blind, randomized, vehicle-controlled, 12-week phase 3 trials. Of note, these were the first-ever large-scale randomized trials to simultaneously evaluate a topical therapy for treatment of both facial and truncal acne. This ambitious goal created some unique challenges, which Dr. Tan described.
Participants, all of whom had moderate acne vulgaris on the face and trunk, ranged in age from 9 to 58 years, with a mean age of 19 years. They were randomized to once-daily application of trifarotene cream 50 mcg/g or its vehicle in the evening.
Primary and secondary outcomes
One major efficacy endpoint on the face was achievement of Investigator Global Assessment success as defined by a score of 0 or 1, meaning clear or almost clear, coupled with at least a 2-grade improvement from baseline to week 12. In PERFECT 1 and 2 this was achieved by 29.7% and 42.8% of trifarotene cream-treated patients, response rates significantly better than the 20% and 25.8% in vehicle-treated controls.
Another endpoint for facial therapy were the absolute reductions from baseline in facial inflammatory and noninflammatory acne lesions. The mean reduction in inflammatory lesion count in trifarotene-treated patients was 19.6% in PERFECT 1 and 24.6% in PERFECT 2, both significantly better than the mean 15.8% and 19.6% decreases in controls. Noninflammatory facial lesion counts dropped by 26.7% and 30.4% with trifarotene, versus 18.9% and 22.3% with vehicle.
The efficacy yardsticks utilized on the trunk were the same as on the face except that Physician Global Assessment was the terminology utilized in lieu of Investigator Global Assessment. Physician Global Assessment success on the trunk was achieved by 35.8% and 41.1% of trifarotene-treated patients in the two trials, as compared with 25.7% and 30.1% of controls.
The mean reductions in truncal inflammatory lesion count obtained with trifarotene cream were 22% and 26.1%, both significantly better than the 18.8% and 20.3% rates with vehicle.
Treatment-emergent adverse events leading to study discontinuation occurred in 1.9% of trifarotene-treated patients in one trial and 1% in the other.
One audience member commented that the vehicle response rates looked too strong for that compound to be inert. Dr. Tan agreed. “The vehicle looks really good. One of the issues with vehicles is that many of them have to contain products to prevent decay, fermentation, and proliferation of yeast and bacteria. So I quite agree: I think many of our vehicles do have active ingredients,” he replied. “If you look at the topical dapsone trials, the vehicles look amazing.”
“The other possibility is that there’s what we call ‘investigator creep,’” the dermatologist continued. “It’s the notion that you have no idea what the patients are getting, but they look like maybe they’re getting better, so you grade it as better.”
Dr. Tan reported serving as an advisor and consultant to, speaker for, and recipient of research grants from Galderma, which sponsored the two phase 3 trials. The company is also developing trifarotene for the treatment of lamellar ichthyosis.
REPORTING FROM THE EADV CONGRESS
Key clinical point:
Major finding: Treatment-emergent adverse events leading to study discontinuation occurred in 1.9% of trifarotene cream–treated patients in one trial and 1% in the other.
Study details: PERFECT 1 and PERFECT 2 were identically designed 12-week phase 3 randomized trials including 2,420 patients with moderate facial and truncal acne.
Disclosures: The study presenter reported serving as an advisor, consultant to, speaker for, and recipient of research grants from Galderma, which sponsored the two phase 3 trials.
Expert shares his approach for aesthetic treatments of ethnic skin
SAN DIEGO – The United States is more .
“Unfortunately, one’s ethnic background is not always clear,” Ashish C. Bhatia, MD, said at the annual Masters of Aesthetics Symposium. “There’s a lot more blending, a lot more difficulty figuring out what people’s ethnicity is and how their skin is going to respond to different treatments.”
When consulting with patients, Dr. Bhatia, director of dermatologic and cosmetic surgery at Oak Dermatology, outside of Chicago, determines their Fitzpatrick skin type and asks about their heritage. “Some people who are adopted don’t know their heritage,” he said. “We also ask about their history of keloids, hypertrophic scars, postinflammatory hyperpigmentation or postinflammatory erythema.”
He also makes it a point to ask patients about blemishes. “If they get pimples, how long do the marks last, and what do they look like?” is one question he asks patients. “That dialogue gives you a lot of useful information. If they get hyperpigmentation, that’s one thing. But many times, people just get postinflammatory erythema, which is often a lot easier to treat.”
In his clinical experience, challenges and risks of performing aesthetic procedures on ethnic skin include postinflammatory hyperpigmentation and hypopigmentation, depigmentation, keloids, and hypertrophic scars. He explained that patients with darker skin types have bigger melanin granules and melanosomes, and more of them are deposited into keratinocytes.
“There’s a complex interaction that occurs between the melanocytes and the keratinocytes, where they phagocytize the ends and take up the melanosomes,” said Dr. Bhatia, also of the department of dermatology at Northwestern University, Chicago. “There’s an opportunity to block tyrosinase to prevent the production of melanin, but once the melanin is produced, what we really worry about is where that melanin ends up. It may end up in the epidermis in the form of light brown pigment. You can see this enhanced if you look at it with a Wood’s light. But if it ends up in the dermis, you don’t get enhancement and clinically it’s more of a bluish-gray pigment. The deeper melanin is much more difficult to treat. Often the postinflammatory hyperpigmentation people get is a combination of these two.”
To reduce the risks of hyperpigmentation and hypopigmentation from procedures, he generally advises against the use of intense pulsed light (IPL), fractional ablative lasers, shorter-wavelength lasers, and cryotherapy. “It’s not to say you can’t use them, but you have to be very careful,” he said. For clinicians with less experience treating skin of color, he recommends using procedures that spare the epidermis and the dermal/epidermal junction altogether. “This includes lasers with longer wavelengths such as the 1,064-nm Nd:YAG, always using generous cooling to avoid injury or trauma to the dermal/epidermal junction and using longer pulse durations.”
Nonlaser procedures to consider using for darker-skinned patients include superficial chemical peels, radiofrequency (RF) microneedling with semi-insulated needles, microfocused ultrasound, and noninvasive RF procedures that spare or cool the epidermis. “You should never be afraid to do a test spot,” he said. Adjunctive therapies to consider using include hydroquinone and other tyrosinase-receptor blockers, and preprocedural preparatory formulas. “Always advise sun protection and avoidance and administer HSV [herpes simplex virus] prophylaxis as indicated,” he added. “Ample evidence exists to show that currently available fillers and neuromodulators are safe to use in darker skin types. The issue here is more with postinflammatory hyperpigmentation, which can occur from needle punctures, so small-gauge needles and linear threading versus serial puncture is preferred.”
Adjunctive postprocedure preventative therapies include hydroquinone and other tyrosinase-receptor blockers; high-potency topical steroids such as clobetasol twice a day for 3 days and tapering to once a day for 3 days before halting; and postprocedural recovery/healing formulas.
Dr. Bhatia said that hypopigmentation can be treated with UV therapy, with bimatoprost topically combined with needling or low-density fractional lasers, as well as with epidermal microsuction grafting such as the CelluTome Epidermal Harvesting System. Hyperpigmentation can be treated with tyrosinase inhibitors, retinoids, chemical peels, and with microdermal/dermal infusion.
As for cosmeceuticals, sunscreens are necessary for keeping skin tone even. Retinoids are also helpful for maintenance, “but irritation can lead to postinflammatory hyperpigmentation, so go slow,” he said. Hyperpigmentation can be treated with hydroquinone, azelaic acid (Finacea), as well as many other preparations.
“Don’t be afraid to treat these patients,” Dr. Bhatia concluded. “As you get more used to performing procedures on people with darker skin types, you discover the limits of what you can and can’t do. But in general, we can do a lot to make these patients happy.”
Dr. Bhatia reported having research and financial ties to numerous pharmaceutical and device companies.
dbrunk@mdedge.com
SAN DIEGO – The United States is more .
“Unfortunately, one’s ethnic background is not always clear,” Ashish C. Bhatia, MD, said at the annual Masters of Aesthetics Symposium. “There’s a lot more blending, a lot more difficulty figuring out what people’s ethnicity is and how their skin is going to respond to different treatments.”
When consulting with patients, Dr. Bhatia, director of dermatologic and cosmetic surgery at Oak Dermatology, outside of Chicago, determines their Fitzpatrick skin type and asks about their heritage. “Some people who are adopted don’t know their heritage,” he said. “We also ask about their history of keloids, hypertrophic scars, postinflammatory hyperpigmentation or postinflammatory erythema.”
He also makes it a point to ask patients about blemishes. “If they get pimples, how long do the marks last, and what do they look like?” is one question he asks patients. “That dialogue gives you a lot of useful information. If they get hyperpigmentation, that’s one thing. But many times, people just get postinflammatory erythema, which is often a lot easier to treat.”
In his clinical experience, challenges and risks of performing aesthetic procedures on ethnic skin include postinflammatory hyperpigmentation and hypopigmentation, depigmentation, keloids, and hypertrophic scars. He explained that patients with darker skin types have bigger melanin granules and melanosomes, and more of them are deposited into keratinocytes.
“There’s a complex interaction that occurs between the melanocytes and the keratinocytes, where they phagocytize the ends and take up the melanosomes,” said Dr. Bhatia, also of the department of dermatology at Northwestern University, Chicago. “There’s an opportunity to block tyrosinase to prevent the production of melanin, but once the melanin is produced, what we really worry about is where that melanin ends up. It may end up in the epidermis in the form of light brown pigment. You can see this enhanced if you look at it with a Wood’s light. But if it ends up in the dermis, you don’t get enhancement and clinically it’s more of a bluish-gray pigment. The deeper melanin is much more difficult to treat. Often the postinflammatory hyperpigmentation people get is a combination of these two.”
To reduce the risks of hyperpigmentation and hypopigmentation from procedures, he generally advises against the use of intense pulsed light (IPL), fractional ablative lasers, shorter-wavelength lasers, and cryotherapy. “It’s not to say you can’t use them, but you have to be very careful,” he said. For clinicians with less experience treating skin of color, he recommends using procedures that spare the epidermis and the dermal/epidermal junction altogether. “This includes lasers with longer wavelengths such as the 1,064-nm Nd:YAG, always using generous cooling to avoid injury or trauma to the dermal/epidermal junction and using longer pulse durations.”
Nonlaser procedures to consider using for darker-skinned patients include superficial chemical peels, radiofrequency (RF) microneedling with semi-insulated needles, microfocused ultrasound, and noninvasive RF procedures that spare or cool the epidermis. “You should never be afraid to do a test spot,” he said. Adjunctive therapies to consider using include hydroquinone and other tyrosinase-receptor blockers, and preprocedural preparatory formulas. “Always advise sun protection and avoidance and administer HSV [herpes simplex virus] prophylaxis as indicated,” he added. “Ample evidence exists to show that currently available fillers and neuromodulators are safe to use in darker skin types. The issue here is more with postinflammatory hyperpigmentation, which can occur from needle punctures, so small-gauge needles and linear threading versus serial puncture is preferred.”
Adjunctive postprocedure preventative therapies include hydroquinone and other tyrosinase-receptor blockers; high-potency topical steroids such as clobetasol twice a day for 3 days and tapering to once a day for 3 days before halting; and postprocedural recovery/healing formulas.
Dr. Bhatia said that hypopigmentation can be treated with UV therapy, with bimatoprost topically combined with needling or low-density fractional lasers, as well as with epidermal microsuction grafting such as the CelluTome Epidermal Harvesting System. Hyperpigmentation can be treated with tyrosinase inhibitors, retinoids, chemical peels, and with microdermal/dermal infusion.
As for cosmeceuticals, sunscreens are necessary for keeping skin tone even. Retinoids are also helpful for maintenance, “but irritation can lead to postinflammatory hyperpigmentation, so go slow,” he said. Hyperpigmentation can be treated with hydroquinone, azelaic acid (Finacea), as well as many other preparations.
“Don’t be afraid to treat these patients,” Dr. Bhatia concluded. “As you get more used to performing procedures on people with darker skin types, you discover the limits of what you can and can’t do. But in general, we can do a lot to make these patients happy.”
Dr. Bhatia reported having research and financial ties to numerous pharmaceutical and device companies.
dbrunk@mdedge.com
SAN DIEGO – The United States is more .
“Unfortunately, one’s ethnic background is not always clear,” Ashish C. Bhatia, MD, said at the annual Masters of Aesthetics Symposium. “There’s a lot more blending, a lot more difficulty figuring out what people’s ethnicity is and how their skin is going to respond to different treatments.”
When consulting with patients, Dr. Bhatia, director of dermatologic and cosmetic surgery at Oak Dermatology, outside of Chicago, determines their Fitzpatrick skin type and asks about their heritage. “Some people who are adopted don’t know their heritage,” he said. “We also ask about their history of keloids, hypertrophic scars, postinflammatory hyperpigmentation or postinflammatory erythema.”
He also makes it a point to ask patients about blemishes. “If they get pimples, how long do the marks last, and what do they look like?” is one question he asks patients. “That dialogue gives you a lot of useful information. If they get hyperpigmentation, that’s one thing. But many times, people just get postinflammatory erythema, which is often a lot easier to treat.”
In his clinical experience, challenges and risks of performing aesthetic procedures on ethnic skin include postinflammatory hyperpigmentation and hypopigmentation, depigmentation, keloids, and hypertrophic scars. He explained that patients with darker skin types have bigger melanin granules and melanosomes, and more of them are deposited into keratinocytes.
“There’s a complex interaction that occurs between the melanocytes and the keratinocytes, where they phagocytize the ends and take up the melanosomes,” said Dr. Bhatia, also of the department of dermatology at Northwestern University, Chicago. “There’s an opportunity to block tyrosinase to prevent the production of melanin, but once the melanin is produced, what we really worry about is where that melanin ends up. It may end up in the epidermis in the form of light brown pigment. You can see this enhanced if you look at it with a Wood’s light. But if it ends up in the dermis, you don’t get enhancement and clinically it’s more of a bluish-gray pigment. The deeper melanin is much more difficult to treat. Often the postinflammatory hyperpigmentation people get is a combination of these two.”
To reduce the risks of hyperpigmentation and hypopigmentation from procedures, he generally advises against the use of intense pulsed light (IPL), fractional ablative lasers, shorter-wavelength lasers, and cryotherapy. “It’s not to say you can’t use them, but you have to be very careful,” he said. For clinicians with less experience treating skin of color, he recommends using procedures that spare the epidermis and the dermal/epidermal junction altogether. “This includes lasers with longer wavelengths such as the 1,064-nm Nd:YAG, always using generous cooling to avoid injury or trauma to the dermal/epidermal junction and using longer pulse durations.”
Nonlaser procedures to consider using for darker-skinned patients include superficial chemical peels, radiofrequency (RF) microneedling with semi-insulated needles, microfocused ultrasound, and noninvasive RF procedures that spare or cool the epidermis. “You should never be afraid to do a test spot,” he said. Adjunctive therapies to consider using include hydroquinone and other tyrosinase-receptor blockers, and preprocedural preparatory formulas. “Always advise sun protection and avoidance and administer HSV [herpes simplex virus] prophylaxis as indicated,” he added. “Ample evidence exists to show that currently available fillers and neuromodulators are safe to use in darker skin types. The issue here is more with postinflammatory hyperpigmentation, which can occur from needle punctures, so small-gauge needles and linear threading versus serial puncture is preferred.”
Adjunctive postprocedure preventative therapies include hydroquinone and other tyrosinase-receptor blockers; high-potency topical steroids such as clobetasol twice a day for 3 days and tapering to once a day for 3 days before halting; and postprocedural recovery/healing formulas.
Dr. Bhatia said that hypopigmentation can be treated with UV therapy, with bimatoprost topically combined with needling or low-density fractional lasers, as well as with epidermal microsuction grafting such as the CelluTome Epidermal Harvesting System. Hyperpigmentation can be treated with tyrosinase inhibitors, retinoids, chemical peels, and with microdermal/dermal infusion.
As for cosmeceuticals, sunscreens are necessary for keeping skin tone even. Retinoids are also helpful for maintenance, “but irritation can lead to postinflammatory hyperpigmentation, so go slow,” he said. Hyperpigmentation can be treated with hydroquinone, azelaic acid (Finacea), as well as many other preparations.
“Don’t be afraid to treat these patients,” Dr. Bhatia concluded. “As you get more used to performing procedures on people with darker skin types, you discover the limits of what you can and can’t do. But in general, we can do a lot to make these patients happy.”
Dr. Bhatia reported having research and financial ties to numerous pharmaceutical and device companies.
dbrunk@mdedge.com
REPORTING FROM MOAS 2018
Ablative fractional lasers treat scars like ‘a magic wand’
SAN DIEGO – .
“I tell patients it’s like boiling water in a tea kettle and watching the vapor form,” Dr. Waibel, a dermatologist with the Miami Dermatology and Laser Institute, said at the annual Masters of Aesthetics Symposium. “You literally ‘steam off’ their bad scar and the human body will heal that wound to almost normal skin. It’s the closest thing we have to a magic wand.”
In the not-too-distant past, dermatologists “were treating scars just to make them look better,” she said. However, thanks to groundbreaking work by clinicians at Naval Medical Center San Diego, the use of ablative fractional lasers to treat scars was found to improve range of motion in patients, as well as their pain and pruritus. “It represents a major innovation that heals in ways not previously possible,” said Dr. Waibel, who is also chief of dermatology at Baptist Hospital in Miami. “We’re not just healing the scar; we’re healing the skin back to its physiological normal place. A lot of these patients suffer quite a bit.”
Dr. Waibel likened her scar treatment approach to a three-course meal. Lesion color drives her choice of what device to use as an “appetizer” treatment. Most scars are either red (erythematous), brown (hyperpigmented), or white (hypopigmented). Though every scar is unique and individually evaluated for treatment, typically she uses pulsed dye laser, intense pulsed light, or broadband light therapy to treat erythematous/early scars; nonablative fractional lasers to treat atrophic scars, and the thulium or 1,470-nm laser to treat hyperpigmented scars. The “main course” device in her practice is an ablative fractional erbium or CO2 laser.
“Once I treat the scar three to five times, I might switch to a nonablative laser, but I’m really an ablative fractional user,” Dr. Waibel said. “Dessert” can be whatever adjunctive therapies you need, she continued. This may include triamcinolone acetonide, 5-fluorouracil, poly-l-lactic acid, hyaluronidase, Z-plasty, punch biopsies, shave biopsies, compression, chemical reconstruction of skin scars (CROSS), and subcision.
For erythematous surgical and trauma scars, she uses a combination of pulsed dye laser and ablative fractional laser. “Same day, same treatment; one after each other,” she said. She favors using intense pulsed light for donor sites because it has filters that address both melanin and hemosiderin, superiority for scar erythema, and deeper penetration with greater speed to treat large surface areas.
One recent advance in the vascular arena is the new 595-nm pulsed dye laser by Candela, known as the VBeam Prima. It features increased energy, a 15-nm spot size, a zoom hand piece, once-a-day calibration, and contact cooling, which may be better for pigmented and possibly microvascular structures. The device is cleared for treating conditions like rosacea, acne, spider veins, port-wine stains, wrinkles, warts and stretch marks, as well as photoaging and benign pigmented lesions.
Dr. Waibel’s go-to device for treating a hypertrophic, hyperpigmented surgical scar is a 1927-nm or 1470-nm nonablative fractional laser, followed by a fractional ablative laser and injection of 1-2 ccs of 5-fluorouracil only to elevated areas. Hypopigmented scars are “by far the toughest to treat,” she said. However, she has a formula for these, too, and recently conducted a trial comparing the efficacy of nonablative fractional laser, ablative fractional laser, and ablative fractional laser followed by laser-assisted delivery of bimatoprost (Latisse) to treat hypopigmentation.
Surgical scars get better on their own in many cases, but sometimes early intervention is warranted. “Most surgeons will tell patients, ‘Wait a year. What you have [in terms of scar formation] is what you have,’” Dr. Waibel said. “If a surgical scar becomes hypertrophic, it does so within a month of surgery. I don’t prophylactically treat surgical scars unless the patient has had multiple surgeries in the same location with trouble healing. But if it’s been 6 months to a year, or if the patient is developing hypertrophic scars, then I will treat.”
Acne scars are challenging, because patients want to look good right away. “With deep scars, it takes several treatments to see good improvements,” she said. “I tell all my acne scar patients it takes a year [to get good results].”
Most burn patients require three to six treatment sessions, “but sometimes you get remarkable improvement sooner,” she said. “That’s due to the patient’s healing.” She and her associates recently completed an unpublished study that examined early intervention of fractional ablative laser versus control in 20 subjects with acute burn injuries who ranged in age from 18 to 80 years. The subjects underwent treatment with an ablative fractional CO2 laser within 3 months of sustaining the burn injury, leaving an untreated control area for comparison. According to Dr. Waibel, 100% of the blinded physician evaluators graded the laser-treated area correctly, compared with the control area. In addition, a significant improvement in all points of the Manchester Scar Scale was observed in the laser-treated area. “The earlier you treat burn and trauma patients, the easier it is to get them back to normal,” she said.
Dr. Waibel disclosed that she has conducted clinical research for Aquavit, Cytrellis, Lumenis, Lutronic, Michelson Diagnostics, RegenX, Sciton, Sebacia, and Syneron/Candela. She is also a consultant for RegenX, Strata, and Syneron/Candela and is a member of the advisory board for Dominion Technologies, Sciton, and Sebacia.
SAN DIEGO – .
“I tell patients it’s like boiling water in a tea kettle and watching the vapor form,” Dr. Waibel, a dermatologist with the Miami Dermatology and Laser Institute, said at the annual Masters of Aesthetics Symposium. “You literally ‘steam off’ their bad scar and the human body will heal that wound to almost normal skin. It’s the closest thing we have to a magic wand.”
In the not-too-distant past, dermatologists “were treating scars just to make them look better,” she said. However, thanks to groundbreaking work by clinicians at Naval Medical Center San Diego, the use of ablative fractional lasers to treat scars was found to improve range of motion in patients, as well as their pain and pruritus. “It represents a major innovation that heals in ways not previously possible,” said Dr. Waibel, who is also chief of dermatology at Baptist Hospital in Miami. “We’re not just healing the scar; we’re healing the skin back to its physiological normal place. A lot of these patients suffer quite a bit.”
Dr. Waibel likened her scar treatment approach to a three-course meal. Lesion color drives her choice of what device to use as an “appetizer” treatment. Most scars are either red (erythematous), brown (hyperpigmented), or white (hypopigmented). Though every scar is unique and individually evaluated for treatment, typically she uses pulsed dye laser, intense pulsed light, or broadband light therapy to treat erythematous/early scars; nonablative fractional lasers to treat atrophic scars, and the thulium or 1,470-nm laser to treat hyperpigmented scars. The “main course” device in her practice is an ablative fractional erbium or CO2 laser.
“Once I treat the scar three to five times, I might switch to a nonablative laser, but I’m really an ablative fractional user,” Dr. Waibel said. “Dessert” can be whatever adjunctive therapies you need, she continued. This may include triamcinolone acetonide, 5-fluorouracil, poly-l-lactic acid, hyaluronidase, Z-plasty, punch biopsies, shave biopsies, compression, chemical reconstruction of skin scars (CROSS), and subcision.
For erythematous surgical and trauma scars, she uses a combination of pulsed dye laser and ablative fractional laser. “Same day, same treatment; one after each other,” she said. She favors using intense pulsed light for donor sites because it has filters that address both melanin and hemosiderin, superiority for scar erythema, and deeper penetration with greater speed to treat large surface areas.
One recent advance in the vascular arena is the new 595-nm pulsed dye laser by Candela, known as the VBeam Prima. It features increased energy, a 15-nm spot size, a zoom hand piece, once-a-day calibration, and contact cooling, which may be better for pigmented and possibly microvascular structures. The device is cleared for treating conditions like rosacea, acne, spider veins, port-wine stains, wrinkles, warts and stretch marks, as well as photoaging and benign pigmented lesions.
Dr. Waibel’s go-to device for treating a hypertrophic, hyperpigmented surgical scar is a 1927-nm or 1470-nm nonablative fractional laser, followed by a fractional ablative laser and injection of 1-2 ccs of 5-fluorouracil only to elevated areas. Hypopigmented scars are “by far the toughest to treat,” she said. However, she has a formula for these, too, and recently conducted a trial comparing the efficacy of nonablative fractional laser, ablative fractional laser, and ablative fractional laser followed by laser-assisted delivery of bimatoprost (Latisse) to treat hypopigmentation.
Surgical scars get better on their own in many cases, but sometimes early intervention is warranted. “Most surgeons will tell patients, ‘Wait a year. What you have [in terms of scar formation] is what you have,’” Dr. Waibel said. “If a surgical scar becomes hypertrophic, it does so within a month of surgery. I don’t prophylactically treat surgical scars unless the patient has had multiple surgeries in the same location with trouble healing. But if it’s been 6 months to a year, or if the patient is developing hypertrophic scars, then I will treat.”
Acne scars are challenging, because patients want to look good right away. “With deep scars, it takes several treatments to see good improvements,” she said. “I tell all my acne scar patients it takes a year [to get good results].”
Most burn patients require three to six treatment sessions, “but sometimes you get remarkable improvement sooner,” she said. “That’s due to the patient’s healing.” She and her associates recently completed an unpublished study that examined early intervention of fractional ablative laser versus control in 20 subjects with acute burn injuries who ranged in age from 18 to 80 years. The subjects underwent treatment with an ablative fractional CO2 laser within 3 months of sustaining the burn injury, leaving an untreated control area for comparison. According to Dr. Waibel, 100% of the blinded physician evaluators graded the laser-treated area correctly, compared with the control area. In addition, a significant improvement in all points of the Manchester Scar Scale was observed in the laser-treated area. “The earlier you treat burn and trauma patients, the easier it is to get them back to normal,” she said.
Dr. Waibel disclosed that she has conducted clinical research for Aquavit, Cytrellis, Lumenis, Lutronic, Michelson Diagnostics, RegenX, Sciton, Sebacia, and Syneron/Candela. She is also a consultant for RegenX, Strata, and Syneron/Candela and is a member of the advisory board for Dominion Technologies, Sciton, and Sebacia.
SAN DIEGO – .
“I tell patients it’s like boiling water in a tea kettle and watching the vapor form,” Dr. Waibel, a dermatologist with the Miami Dermatology and Laser Institute, said at the annual Masters of Aesthetics Symposium. “You literally ‘steam off’ their bad scar and the human body will heal that wound to almost normal skin. It’s the closest thing we have to a magic wand.”
In the not-too-distant past, dermatologists “were treating scars just to make them look better,” she said. However, thanks to groundbreaking work by clinicians at Naval Medical Center San Diego, the use of ablative fractional lasers to treat scars was found to improve range of motion in patients, as well as their pain and pruritus. “It represents a major innovation that heals in ways not previously possible,” said Dr. Waibel, who is also chief of dermatology at Baptist Hospital in Miami. “We’re not just healing the scar; we’re healing the skin back to its physiological normal place. A lot of these patients suffer quite a bit.”
Dr. Waibel likened her scar treatment approach to a three-course meal. Lesion color drives her choice of what device to use as an “appetizer” treatment. Most scars are either red (erythematous), brown (hyperpigmented), or white (hypopigmented). Though every scar is unique and individually evaluated for treatment, typically she uses pulsed dye laser, intense pulsed light, or broadband light therapy to treat erythematous/early scars; nonablative fractional lasers to treat atrophic scars, and the thulium or 1,470-nm laser to treat hyperpigmented scars. The “main course” device in her practice is an ablative fractional erbium or CO2 laser.
“Once I treat the scar three to five times, I might switch to a nonablative laser, but I’m really an ablative fractional user,” Dr. Waibel said. “Dessert” can be whatever adjunctive therapies you need, she continued. This may include triamcinolone acetonide, 5-fluorouracil, poly-l-lactic acid, hyaluronidase, Z-plasty, punch biopsies, shave biopsies, compression, chemical reconstruction of skin scars (CROSS), and subcision.
For erythematous surgical and trauma scars, she uses a combination of pulsed dye laser and ablative fractional laser. “Same day, same treatment; one after each other,” she said. She favors using intense pulsed light for donor sites because it has filters that address both melanin and hemosiderin, superiority for scar erythema, and deeper penetration with greater speed to treat large surface areas.
One recent advance in the vascular arena is the new 595-nm pulsed dye laser by Candela, known as the VBeam Prima. It features increased energy, a 15-nm spot size, a zoom hand piece, once-a-day calibration, and contact cooling, which may be better for pigmented and possibly microvascular structures. The device is cleared for treating conditions like rosacea, acne, spider veins, port-wine stains, wrinkles, warts and stretch marks, as well as photoaging and benign pigmented lesions.
Dr. Waibel’s go-to device for treating a hypertrophic, hyperpigmented surgical scar is a 1927-nm or 1470-nm nonablative fractional laser, followed by a fractional ablative laser and injection of 1-2 ccs of 5-fluorouracil only to elevated areas. Hypopigmented scars are “by far the toughest to treat,” she said. However, she has a formula for these, too, and recently conducted a trial comparing the efficacy of nonablative fractional laser, ablative fractional laser, and ablative fractional laser followed by laser-assisted delivery of bimatoprost (Latisse) to treat hypopigmentation.
Surgical scars get better on their own in many cases, but sometimes early intervention is warranted. “Most surgeons will tell patients, ‘Wait a year. What you have [in terms of scar formation] is what you have,’” Dr. Waibel said. “If a surgical scar becomes hypertrophic, it does so within a month of surgery. I don’t prophylactically treat surgical scars unless the patient has had multiple surgeries in the same location with trouble healing. But if it’s been 6 months to a year, or if the patient is developing hypertrophic scars, then I will treat.”
Acne scars are challenging, because patients want to look good right away. “With deep scars, it takes several treatments to see good improvements,” she said. “I tell all my acne scar patients it takes a year [to get good results].”
Most burn patients require three to six treatment sessions, “but sometimes you get remarkable improvement sooner,” she said. “That’s due to the patient’s healing.” She and her associates recently completed an unpublished study that examined early intervention of fractional ablative laser versus control in 20 subjects with acute burn injuries who ranged in age from 18 to 80 years. The subjects underwent treatment with an ablative fractional CO2 laser within 3 months of sustaining the burn injury, leaving an untreated control area for comparison. According to Dr. Waibel, 100% of the blinded physician evaluators graded the laser-treated area correctly, compared with the control area. In addition, a significant improvement in all points of the Manchester Scar Scale was observed in the laser-treated area. “The earlier you treat burn and trauma patients, the easier it is to get them back to normal,” she said.
Dr. Waibel disclosed that she has conducted clinical research for Aquavit, Cytrellis, Lumenis, Lutronic, Michelson Diagnostics, RegenX, Sciton, Sebacia, and Syneron/Candela. She is also a consultant for RegenX, Strata, and Syneron/Candela and is a member of the advisory board for Dominion Technologies, Sciton, and Sebacia.
REPORTING FROM MOAS 2018
Troponin I: Powerful all-cause mortality risk marker in COPD
PARIS – High relative even after researchers adjusted for all major cardiovascular and COPD prognostic indicators, according to a late-breaker presentation at the annual congress of the European Respiratory Society.
Troponin I is detectable in the plasma of most patients with COPD, but relative increases in troponin I correlate with greater relative increases in most cardiovascular and COPD risk factors, according to Benjamin Waschki, MD, Pulmonary Research Institute, LungenClinic, Grosshansdorf, Germany.
The relationship between increased troponin I and increased all-cause mortality was observed in an on-going prospective multicenter cohort of COPD patients followed at 31 centers in Germany. The cohort is called COSYCONET and it began in 2010. The current analysis evaluated 2,020 COPD patients without regard to stage of disease.
There were 136 deaths over the course of follow-up. Without adjustment, the hazard ratio (HR) for death was more than twofold higher in the highest quartile of troponin I (equal to or greater than 6.6 ng/mL), when compared with the lowest (under 2.5 ng/mL) (HR, 2.42; P less than .001). Graphically, the mortality curves for each of the quartiles began to separate at about 12 months, widening in a stepwise manner for greater likelihood of death from the lowest to highest quartiles.
The risk of death from any cause remained elevated for the highest relative to lowest troponin I quartiles after adjusting for cardiovascular risk factors and after adjusting for COPD severity. Again, there was a distinct stepwise separation of the mortality curves for each higher troponin quartile,
Of particular importance, troponin I remained predictive beyond the BODE index, which is a currently employed prognostic mortality predictor in COPD, according to Dr. Waschki. When defining elevated troponin as greater than 6 ng/ML and a high BODE score as greater than 4, mortality was higher for those with a high BODE and low troponin than a high troponin and low BODE, (P less than .001), but a high troponin I was associated with a higher risk of mortality when BODE was low (P less than .001). Moreover, when both troponin I and BODE were elevated, all-cause mortality was more than doubled, relative to those without either risk factor (HR, 2.56; P = .003), Dr. Waschki reported.
After researchers adjusted for major cardiovascular risk factors, such as history of MI and renal impairment, and for major COPD risk factors, such as 6-minute walk test and BODE index, those in the highest quartile had a more than 50% greater risk of death relative to those in the lower quartile over the 3 years of follow-up (HR, 1.69; P = .007), according to Dr. Waschki.
Although troponin I is best known for its diagnostic role in MI, it is now being evaluated as a risk stratifier for many chronic diseases, such as heart failure and chronic kidney disease, explained Dr. Waschki in providing background for this study. He reported that many groups are looking at this as a marker of risk in a variety of chronic diseases.
In fact, a group working independently published a study in COPD just weeks before the ERS Congress that was complementary to those presented by Dr. Waschki. In this study, the goal was to evaluate troponin I as a predictor of cardiovascular events and cardiovascular death (Adamson PD et al. J Am Coll Cardiol 2018;72:1126-37). Performed as a subgroup analysis of 1,599 COPD patients participating in a large treatment trial, there was an almost fourfold increase in the risk of cardiovascular events (HR, 3.7; P = .012) when those in the highest quintile of troponin I (greater than 7.7 ng/ML) were compared with those in the lowest quintile (less than 2.3 ng/mL).
When compared for cardiovascular death, the highest quintile, relative to the lowest quintile, had a more than 20-fold increased risk of cardiovascular death (HR 20.1; P = .005). In the Adamson et al. study, which evaluated inhaled therapies for COPD, treatment response had no impact on troponin I levels or on the risk of cardiovascular events or death.
Based on this study and his own data, Dr. Waschki believes troponin I, which is readily ordered laboratory value, appears to be a useful tool for identifying COPD patients at high risk of death.
“The major message is that after adjusting for all known COPD and cardiovascular risk factors, troponin I remains a significant independent predictor of mortality,” he said.
Dr. Waschki reports no relevant conflicts of interest.
PARIS – High relative even after researchers adjusted for all major cardiovascular and COPD prognostic indicators, according to a late-breaker presentation at the annual congress of the European Respiratory Society.
Troponin I is detectable in the plasma of most patients with COPD, but relative increases in troponin I correlate with greater relative increases in most cardiovascular and COPD risk factors, according to Benjamin Waschki, MD, Pulmonary Research Institute, LungenClinic, Grosshansdorf, Germany.
The relationship between increased troponin I and increased all-cause mortality was observed in an on-going prospective multicenter cohort of COPD patients followed at 31 centers in Germany. The cohort is called COSYCONET and it began in 2010. The current analysis evaluated 2,020 COPD patients without regard to stage of disease.
There were 136 deaths over the course of follow-up. Without adjustment, the hazard ratio (HR) for death was more than twofold higher in the highest quartile of troponin I (equal to or greater than 6.6 ng/mL), when compared with the lowest (under 2.5 ng/mL) (HR, 2.42; P less than .001). Graphically, the mortality curves for each of the quartiles began to separate at about 12 months, widening in a stepwise manner for greater likelihood of death from the lowest to highest quartiles.
The risk of death from any cause remained elevated for the highest relative to lowest troponin I quartiles after adjusting for cardiovascular risk factors and after adjusting for COPD severity. Again, there was a distinct stepwise separation of the mortality curves for each higher troponin quartile,
Of particular importance, troponin I remained predictive beyond the BODE index, which is a currently employed prognostic mortality predictor in COPD, according to Dr. Waschki. When defining elevated troponin as greater than 6 ng/ML and a high BODE score as greater than 4, mortality was higher for those with a high BODE and low troponin than a high troponin and low BODE, (P less than .001), but a high troponin I was associated with a higher risk of mortality when BODE was low (P less than .001). Moreover, when both troponin I and BODE were elevated, all-cause mortality was more than doubled, relative to those without either risk factor (HR, 2.56; P = .003), Dr. Waschki reported.
After researchers adjusted for major cardiovascular risk factors, such as history of MI and renal impairment, and for major COPD risk factors, such as 6-minute walk test and BODE index, those in the highest quartile had a more than 50% greater risk of death relative to those in the lower quartile over the 3 years of follow-up (HR, 1.69; P = .007), according to Dr. Waschki.
Although troponin I is best known for its diagnostic role in MI, it is now being evaluated as a risk stratifier for many chronic diseases, such as heart failure and chronic kidney disease, explained Dr. Waschki in providing background for this study. He reported that many groups are looking at this as a marker of risk in a variety of chronic diseases.
In fact, a group working independently published a study in COPD just weeks before the ERS Congress that was complementary to those presented by Dr. Waschki. In this study, the goal was to evaluate troponin I as a predictor of cardiovascular events and cardiovascular death (Adamson PD et al. J Am Coll Cardiol 2018;72:1126-37). Performed as a subgroup analysis of 1,599 COPD patients participating in a large treatment trial, there was an almost fourfold increase in the risk of cardiovascular events (HR, 3.7; P = .012) when those in the highest quintile of troponin I (greater than 7.7 ng/ML) were compared with those in the lowest quintile (less than 2.3 ng/mL).
When compared for cardiovascular death, the highest quintile, relative to the lowest quintile, had a more than 20-fold increased risk of cardiovascular death (HR 20.1; P = .005). In the Adamson et al. study, which evaluated inhaled therapies for COPD, treatment response had no impact on troponin I levels or on the risk of cardiovascular events or death.
Based on this study and his own data, Dr. Waschki believes troponin I, which is readily ordered laboratory value, appears to be a useful tool for identifying COPD patients at high risk of death.
“The major message is that after adjusting for all known COPD and cardiovascular risk factors, troponin I remains a significant independent predictor of mortality,” he said.
Dr. Waschki reports no relevant conflicts of interest.
PARIS – High relative even after researchers adjusted for all major cardiovascular and COPD prognostic indicators, according to a late-breaker presentation at the annual congress of the European Respiratory Society.
Troponin I is detectable in the plasma of most patients with COPD, but relative increases in troponin I correlate with greater relative increases in most cardiovascular and COPD risk factors, according to Benjamin Waschki, MD, Pulmonary Research Institute, LungenClinic, Grosshansdorf, Germany.
The relationship between increased troponin I and increased all-cause mortality was observed in an on-going prospective multicenter cohort of COPD patients followed at 31 centers in Germany. The cohort is called COSYCONET and it began in 2010. The current analysis evaluated 2,020 COPD patients without regard to stage of disease.
There were 136 deaths over the course of follow-up. Without adjustment, the hazard ratio (HR) for death was more than twofold higher in the highest quartile of troponin I (equal to or greater than 6.6 ng/mL), when compared with the lowest (under 2.5 ng/mL) (HR, 2.42; P less than .001). Graphically, the mortality curves for each of the quartiles began to separate at about 12 months, widening in a stepwise manner for greater likelihood of death from the lowest to highest quartiles.
The risk of death from any cause remained elevated for the highest relative to lowest troponin I quartiles after adjusting for cardiovascular risk factors and after adjusting for COPD severity. Again, there was a distinct stepwise separation of the mortality curves for each higher troponin quartile,
Of particular importance, troponin I remained predictive beyond the BODE index, which is a currently employed prognostic mortality predictor in COPD, according to Dr. Waschki. When defining elevated troponin as greater than 6 ng/ML and a high BODE score as greater than 4, mortality was higher for those with a high BODE and low troponin than a high troponin and low BODE, (P less than .001), but a high troponin I was associated with a higher risk of mortality when BODE was low (P less than .001). Moreover, when both troponin I and BODE were elevated, all-cause mortality was more than doubled, relative to those without either risk factor (HR, 2.56; P = .003), Dr. Waschki reported.
After researchers adjusted for major cardiovascular risk factors, such as history of MI and renal impairment, and for major COPD risk factors, such as 6-minute walk test and BODE index, those in the highest quartile had a more than 50% greater risk of death relative to those in the lower quartile over the 3 years of follow-up (HR, 1.69; P = .007), according to Dr. Waschki.
Although troponin I is best known for its diagnostic role in MI, it is now being evaluated as a risk stratifier for many chronic diseases, such as heart failure and chronic kidney disease, explained Dr. Waschki in providing background for this study. He reported that many groups are looking at this as a marker of risk in a variety of chronic diseases.
In fact, a group working independently published a study in COPD just weeks before the ERS Congress that was complementary to those presented by Dr. Waschki. In this study, the goal was to evaluate troponin I as a predictor of cardiovascular events and cardiovascular death (Adamson PD et al. J Am Coll Cardiol 2018;72:1126-37). Performed as a subgroup analysis of 1,599 COPD patients participating in a large treatment trial, there was an almost fourfold increase in the risk of cardiovascular events (HR, 3.7; P = .012) when those in the highest quintile of troponin I (greater than 7.7 ng/ML) were compared with those in the lowest quintile (less than 2.3 ng/mL).
When compared for cardiovascular death, the highest quintile, relative to the lowest quintile, had a more than 20-fold increased risk of cardiovascular death (HR 20.1; P = .005). In the Adamson et al. study, which evaluated inhaled therapies for COPD, treatment response had no impact on troponin I levels or on the risk of cardiovascular events or death.
Based on this study and his own data, Dr. Waschki believes troponin I, which is readily ordered laboratory value, appears to be a useful tool for identifying COPD patients at high risk of death.
“The major message is that after adjusting for all known COPD and cardiovascular risk factors, troponin I remains a significant independent predictor of mortality,” he said.
Dr. Waschki reports no relevant conflicts of interest.
REPORTING FROM ERS CONGRESS 2018
Key clinical point: Elevated troponin I identifies COPD patients with increased mortality risk independent of all other clinical risk markers.
Major finding: With high troponin I levels, all-cause mortality was increased 69% after researchers adjusted for other risk markers.
Study details: Analysis drawn from on-going multicenter cohort study
Disclosures: Dr. Waschki reports no relevant conflicts of interest.
Pregnancy registries are a valuable resource
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Other registries
Breast cancer
The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).
Epilepsy
The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).
Fabry disease
The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Hepatitis B
The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Hypercholesterolemia
Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.
Mucopolysaccharidosis
The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).
Multiple sclerosis
Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).
Narcolepsy and other sleep disorders
Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Others
Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).
GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
Psychiatric Drugs
The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).
The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).
The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).
Transplant patients
Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).
Vaccines
A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.
Because the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Other registries
Breast cancer
The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).
Epilepsy
The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).
Fabry disease
The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Hepatitis B
The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Hypercholesterolemia
Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.
Mucopolysaccharidosis
The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).
Multiple sclerosis
Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).
Narcolepsy and other sleep disorders
Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Others
Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).
GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
Psychiatric Drugs
The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).
The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).
The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).
Transplant patients
Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).
Vaccines
A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.
Because the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Other registries
Breast cancer
The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).
Epilepsy
The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).
Fabry disease
The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Hepatitis B
The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Hypercholesterolemia
Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.
Mucopolysaccharidosis
The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).
Multiple sclerosis
Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).
Narcolepsy and other sleep disorders
Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Others
Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).
GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
Psychiatric Drugs
The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).
The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).
The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).
Transplant patients
Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).
Vaccines
A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.
Because the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
GBS in T2DM patients: Study highlights pros and cons, need for better patient selection
ORLANDO – , according to a nationwide, matched, observational cohort study in Sweden.
After 9 years of follow-up, all-cause mortality was 49% lower among 5,321 patients with T2DM compared with 5,321 matched control (183 vs. 351 deaths; hazard ratio, 0.51), as has been reported in prior studies, Vasileios Liakopoulos, MD, of the University of Gothenburg (Sweden) reported at the annual scientific sessions of the American Diabetes Association.
Cardiovascular disease (CVD) risk was 34% lower (108 vs. 150 patients; HR, 0.66), fatal CVD risk was 66% lower (21 vs. 64 patients; HR, 0.34), acute myocardial infarction risk was 45% lower (51 vs. 85 events; HR, 0.55) congestive heart failure risk was 51% lower (109 vs. 225 events; HR, 0.49), and cancer risk was 22% lower (153 vs. 188 cases; HR, 0.78) in cases vs. controls, respectively.
“[As for] the diagnoses that related to diabetes, hyperglycemia was lower by 66%, admission to the hospital due to amputation was 49% lower, and we also found something relatively new – that renal disease was lower by 42%,” Dr. Liakopoulos said.
Renal disease occurred in 105 cases vs. 187 controls (HR, 0.58), with the difference between the groups intensifying after the third year of follow-up, he noted.
However, numerous adverse events occurred more often in case patients, he said.
For example, hospitalizations for psychiatric disorders were increased by 33% (317 vs. 268; HR, 1.33), alcohol-related diagnoses were nearly threefold higher (180 vs. 65; HR, 2.90), malnutrition occurred nearly three times more often (128 vs. 46 patients; HR, 2.81), and anemia occurred nearly twice as often (84 vs. 46 cases; HR, 1.92) in cases vs. controls.
Of course, all the surgery-related adverse events occurred more often in the case patients, but interestingly, those events – which included things like gastrointestinal surgery other than gastric bypass, abdominal pain, gallstones/pancreatitis, gastrointestinal ulcers and reflux, and bowel obstruction – did not occur more often in case patients than in gastric bypass patients without diabetes in other studies, he noted.
The findings were based on merged data from the Scandinavian Obesity Surgery Registry, the Swedish National Diabetes Register, and other national databases, and persons with T2DM who had undergone gastric bypass surgery between 2007 and 2013 were matched by propensity score (based on sex, age, body mass index, and calendar time from the beginning of the study) with obese individuals who were not surgically treated for obesity. The risks of postoperative outcomes were assessed using a Cox regression model adjusted for sex, age, body mass index, and socioeconomic status, Dr. Liakopoulos said.
This study, though limited by its observational nature, minor differences in patient characteristics between the cases and controls, and potential residual confounding, confirms the benefits of gastric bypass surgery in obese patients with T2DM but also characterizes an array of both short- and long-term adverse events after bariatric surgery in these patients, he said.
“The beneficial effects of gastric bypass have been presented in terms of weight reduction, improvements in risk factors and cardiovascular disease, and mortality reduction in people with or without diabetes,” he said, noting, however, that only a few reports have addressed long-term incidence of complications after gastric bypass – and type 2 diabetes has only been addressed in small randomized studies or in low proportions in large prospective studies.
“[Based on the findings] we suggest better selection of patients for bariatric surgery, and we think improved long-term postoperative monitoring might further improve the results of such treatment,” he concluded.
Dr. Liakopoulos reported having no disclosures.
SOURCE: Liakopoulos V et al. ADA 2018, Abstract 131-OR.
ORLANDO – , according to a nationwide, matched, observational cohort study in Sweden.
After 9 years of follow-up, all-cause mortality was 49% lower among 5,321 patients with T2DM compared with 5,321 matched control (183 vs. 351 deaths; hazard ratio, 0.51), as has been reported in prior studies, Vasileios Liakopoulos, MD, of the University of Gothenburg (Sweden) reported at the annual scientific sessions of the American Diabetes Association.
Cardiovascular disease (CVD) risk was 34% lower (108 vs. 150 patients; HR, 0.66), fatal CVD risk was 66% lower (21 vs. 64 patients; HR, 0.34), acute myocardial infarction risk was 45% lower (51 vs. 85 events; HR, 0.55) congestive heart failure risk was 51% lower (109 vs. 225 events; HR, 0.49), and cancer risk was 22% lower (153 vs. 188 cases; HR, 0.78) in cases vs. controls, respectively.
“[As for] the diagnoses that related to diabetes, hyperglycemia was lower by 66%, admission to the hospital due to amputation was 49% lower, and we also found something relatively new – that renal disease was lower by 42%,” Dr. Liakopoulos said.
Renal disease occurred in 105 cases vs. 187 controls (HR, 0.58), with the difference between the groups intensifying after the third year of follow-up, he noted.
However, numerous adverse events occurred more often in case patients, he said.
For example, hospitalizations for psychiatric disorders were increased by 33% (317 vs. 268; HR, 1.33), alcohol-related diagnoses were nearly threefold higher (180 vs. 65; HR, 2.90), malnutrition occurred nearly three times more often (128 vs. 46 patients; HR, 2.81), and anemia occurred nearly twice as often (84 vs. 46 cases; HR, 1.92) in cases vs. controls.
Of course, all the surgery-related adverse events occurred more often in the case patients, but interestingly, those events – which included things like gastrointestinal surgery other than gastric bypass, abdominal pain, gallstones/pancreatitis, gastrointestinal ulcers and reflux, and bowel obstruction – did not occur more often in case patients than in gastric bypass patients without diabetes in other studies, he noted.
The findings were based on merged data from the Scandinavian Obesity Surgery Registry, the Swedish National Diabetes Register, and other national databases, and persons with T2DM who had undergone gastric bypass surgery between 2007 and 2013 were matched by propensity score (based on sex, age, body mass index, and calendar time from the beginning of the study) with obese individuals who were not surgically treated for obesity. The risks of postoperative outcomes were assessed using a Cox regression model adjusted for sex, age, body mass index, and socioeconomic status, Dr. Liakopoulos said.
This study, though limited by its observational nature, minor differences in patient characteristics between the cases and controls, and potential residual confounding, confirms the benefits of gastric bypass surgery in obese patients with T2DM but also characterizes an array of both short- and long-term adverse events after bariatric surgery in these patients, he said.
“The beneficial effects of gastric bypass have been presented in terms of weight reduction, improvements in risk factors and cardiovascular disease, and mortality reduction in people with or without diabetes,” he said, noting, however, that only a few reports have addressed long-term incidence of complications after gastric bypass – and type 2 diabetes has only been addressed in small randomized studies or in low proportions in large prospective studies.
“[Based on the findings] we suggest better selection of patients for bariatric surgery, and we think improved long-term postoperative monitoring might further improve the results of such treatment,” he concluded.
Dr. Liakopoulos reported having no disclosures.
SOURCE: Liakopoulos V et al. ADA 2018, Abstract 131-OR.
ORLANDO – , according to a nationwide, matched, observational cohort study in Sweden.
After 9 years of follow-up, all-cause mortality was 49% lower among 5,321 patients with T2DM compared with 5,321 matched control (183 vs. 351 deaths; hazard ratio, 0.51), as has been reported in prior studies, Vasileios Liakopoulos, MD, of the University of Gothenburg (Sweden) reported at the annual scientific sessions of the American Diabetes Association.
Cardiovascular disease (CVD) risk was 34% lower (108 vs. 150 patients; HR, 0.66), fatal CVD risk was 66% lower (21 vs. 64 patients; HR, 0.34), acute myocardial infarction risk was 45% lower (51 vs. 85 events; HR, 0.55) congestive heart failure risk was 51% lower (109 vs. 225 events; HR, 0.49), and cancer risk was 22% lower (153 vs. 188 cases; HR, 0.78) in cases vs. controls, respectively.
“[As for] the diagnoses that related to diabetes, hyperglycemia was lower by 66%, admission to the hospital due to amputation was 49% lower, and we also found something relatively new – that renal disease was lower by 42%,” Dr. Liakopoulos said.
Renal disease occurred in 105 cases vs. 187 controls (HR, 0.58), with the difference between the groups intensifying after the third year of follow-up, he noted.
However, numerous adverse events occurred more often in case patients, he said.
For example, hospitalizations for psychiatric disorders were increased by 33% (317 vs. 268; HR, 1.33), alcohol-related diagnoses were nearly threefold higher (180 vs. 65; HR, 2.90), malnutrition occurred nearly three times more often (128 vs. 46 patients; HR, 2.81), and anemia occurred nearly twice as often (84 vs. 46 cases; HR, 1.92) in cases vs. controls.
Of course, all the surgery-related adverse events occurred more often in the case patients, but interestingly, those events – which included things like gastrointestinal surgery other than gastric bypass, abdominal pain, gallstones/pancreatitis, gastrointestinal ulcers and reflux, and bowel obstruction – did not occur more often in case patients than in gastric bypass patients without diabetes in other studies, he noted.
The findings were based on merged data from the Scandinavian Obesity Surgery Registry, the Swedish National Diabetes Register, and other national databases, and persons with T2DM who had undergone gastric bypass surgery between 2007 and 2013 were matched by propensity score (based on sex, age, body mass index, and calendar time from the beginning of the study) with obese individuals who were not surgically treated for obesity. The risks of postoperative outcomes were assessed using a Cox regression model adjusted for sex, age, body mass index, and socioeconomic status, Dr. Liakopoulos said.
This study, though limited by its observational nature, minor differences in patient characteristics between the cases and controls, and potential residual confounding, confirms the benefits of gastric bypass surgery in obese patients with T2DM but also characterizes an array of both short- and long-term adverse events after bariatric surgery in these patients, he said.
“The beneficial effects of gastric bypass have been presented in terms of weight reduction, improvements in risk factors and cardiovascular disease, and mortality reduction in people with or without diabetes,” he said, noting, however, that only a few reports have addressed long-term incidence of complications after gastric bypass – and type 2 diabetes has only been addressed in small randomized studies or in low proportions in large prospective studies.
“[Based on the findings] we suggest better selection of patients for bariatric surgery, and we think improved long-term postoperative monitoring might further improve the results of such treatment,” he concluded.
Dr. Liakopoulos reported having no disclosures.
SOURCE: Liakopoulos V et al. ADA 2018, Abstract 131-OR.
REPORTING FROM ADA 2018
Key clinical point: Bariatric surgery lowers mortality, CVD, and renal and other risks in obese T2DM patients but also has high complication rates.
Major finding: All-cause mortality, CVD, and renal disease risks were 49%, 34%, and 42% lower, respectively, in cases vs. controls.
Study details: A matched observational cohort study of 5,321 cases and 5,321 controls.
Disclosures: Dr. Liakopoulos reported having no disclosures.
Source: Liakopoulos V et al. ADA 2018, Abstract 131-OR.
Arthritis prevalent in older adults with any degree of depression
Arthritis is highly prevalent in older adults with any degree of depression, results of a recent study suggest.
Doctor-diagnosed arthritis was reported by more than 50% of older adults with mild depression, according to results of the study, which was based on data from the National Health and Nutrition Examination Survey (NHANES).
The prevalence of arthritis exceeded 60% in participants with moderate depression, and approached 70% for those with severe depression, according to the study, published in the International Journal of Geriatric Psychiatry.
Based on those findings, arthritis and depression need to be viewed as frequently co-occurring physical and psychosocial issues, reported Jessica M. Brooks, PhD, of the department of psychiatry at Dartmouth College, Lebanon, N.H., and her coauthors.
“It may be critical for mental health care providers to provide regular arthritis-related pain assessments and evidence‐based treatments for co‐occurring arthritis in older adults with or at risk for depression,” Dr. Brooks and her colleagues said in their report.
Their analysis was based on 2,483 women and 2,309 men aged 50 years and older (mean age, 64.5 years) who had participated in the NHANES survey between 2011 and 2014. Out of that sample, 2,094 participants (43.7%) said they had been told by a doctor that they had arthritis, the researchers said.
The rate of arthritis was 38.2% for participants with no depressive symptoms as indicated by a 0-4 score on the 9-item Patient Health Questionnaire (PHQ-9). By comparison, rates of arthritis were 55.0%, 62.9%, and 67.8% for those with mild, moderate, or severe depression by PHQ-9.
Individuals with arthritis had a significantly higher mean PHQ-9 score, at 4.6, compared with 2.6 for those without arthritis (P less than .001), the investigators said.
that controlled for age, gender, comorbid conditions, and other factors such as smoking history.
Establishing prevalence rates of arthritis in older adults with depression is an “important step” toward informing mental health professionals on the need to identify and treat arthritis-related pain, Dr. Brooks and her coauthors said.
“Addressing arthritis in mental health treatment and behavioral medicine may also help to reduce the overlapping cognitive, behavioral, and somatic symptoms in older adults with depressive symptoms and arthritis, which may be difficult for providers to disentangle through brief screening procedures and treat through conventional depression care,” they wrote.
The investigators cited several limitations. For example, the cross-sectional nature of the study makes it difficult to draw conclusions about causality. In addition, Dr. Brooks and her colleagues did not distinguish between different types of arthritis.
The researchers declared no conflicts of interest. The study was supported by several U.S. institutes, including the National Institute of Mental Health, and by numerous entities related to Dartmouth, including the Dartmouth Health Promotion and Disease Prevention Research Center. The Howard and Phyllis Schwartz Philanthropic Fund also provided funding.
SOURCE: Brooks JM et al. Int J Geriatr Psychiatry. 2018 Sep 19. doi: 10.1022/gps.4971.
Arthritis is highly prevalent in older adults with any degree of depression, results of a recent study suggest.
Doctor-diagnosed arthritis was reported by more than 50% of older adults with mild depression, according to results of the study, which was based on data from the National Health and Nutrition Examination Survey (NHANES).
The prevalence of arthritis exceeded 60% in participants with moderate depression, and approached 70% for those with severe depression, according to the study, published in the International Journal of Geriatric Psychiatry.
Based on those findings, arthritis and depression need to be viewed as frequently co-occurring physical and psychosocial issues, reported Jessica M. Brooks, PhD, of the department of psychiatry at Dartmouth College, Lebanon, N.H., and her coauthors.
“It may be critical for mental health care providers to provide regular arthritis-related pain assessments and evidence‐based treatments for co‐occurring arthritis in older adults with or at risk for depression,” Dr. Brooks and her colleagues said in their report.
Their analysis was based on 2,483 women and 2,309 men aged 50 years and older (mean age, 64.5 years) who had participated in the NHANES survey between 2011 and 2014. Out of that sample, 2,094 participants (43.7%) said they had been told by a doctor that they had arthritis, the researchers said.
The rate of arthritis was 38.2% for participants with no depressive symptoms as indicated by a 0-4 score on the 9-item Patient Health Questionnaire (PHQ-9). By comparison, rates of arthritis were 55.0%, 62.9%, and 67.8% for those with mild, moderate, or severe depression by PHQ-9.
Individuals with arthritis had a significantly higher mean PHQ-9 score, at 4.6, compared with 2.6 for those without arthritis (P less than .001), the investigators said.
that controlled for age, gender, comorbid conditions, and other factors such as smoking history.
Establishing prevalence rates of arthritis in older adults with depression is an “important step” toward informing mental health professionals on the need to identify and treat arthritis-related pain, Dr. Brooks and her coauthors said.
“Addressing arthritis in mental health treatment and behavioral medicine may also help to reduce the overlapping cognitive, behavioral, and somatic symptoms in older adults with depressive symptoms and arthritis, which may be difficult for providers to disentangle through brief screening procedures and treat through conventional depression care,” they wrote.
The investigators cited several limitations. For example, the cross-sectional nature of the study makes it difficult to draw conclusions about causality. In addition, Dr. Brooks and her colleagues did not distinguish between different types of arthritis.
The researchers declared no conflicts of interest. The study was supported by several U.S. institutes, including the National Institute of Mental Health, and by numerous entities related to Dartmouth, including the Dartmouth Health Promotion and Disease Prevention Research Center. The Howard and Phyllis Schwartz Philanthropic Fund also provided funding.
SOURCE: Brooks JM et al. Int J Geriatr Psychiatry. 2018 Sep 19. doi: 10.1022/gps.4971.
Arthritis is highly prevalent in older adults with any degree of depression, results of a recent study suggest.
Doctor-diagnosed arthritis was reported by more than 50% of older adults with mild depression, according to results of the study, which was based on data from the National Health and Nutrition Examination Survey (NHANES).
The prevalence of arthritis exceeded 60% in participants with moderate depression, and approached 70% for those with severe depression, according to the study, published in the International Journal of Geriatric Psychiatry.
Based on those findings, arthritis and depression need to be viewed as frequently co-occurring physical and psychosocial issues, reported Jessica M. Brooks, PhD, of the department of psychiatry at Dartmouth College, Lebanon, N.H., and her coauthors.
“It may be critical for mental health care providers to provide regular arthritis-related pain assessments and evidence‐based treatments for co‐occurring arthritis in older adults with or at risk for depression,” Dr. Brooks and her colleagues said in their report.
Their analysis was based on 2,483 women and 2,309 men aged 50 years and older (mean age, 64.5 years) who had participated in the NHANES survey between 2011 and 2014. Out of that sample, 2,094 participants (43.7%) said they had been told by a doctor that they had arthritis, the researchers said.
The rate of arthritis was 38.2% for participants with no depressive symptoms as indicated by a 0-4 score on the 9-item Patient Health Questionnaire (PHQ-9). By comparison, rates of arthritis were 55.0%, 62.9%, and 67.8% for those with mild, moderate, or severe depression by PHQ-9.
Individuals with arthritis had a significantly higher mean PHQ-9 score, at 4.6, compared with 2.6 for those without arthritis (P less than .001), the investigators said.
that controlled for age, gender, comorbid conditions, and other factors such as smoking history.
Establishing prevalence rates of arthritis in older adults with depression is an “important step” toward informing mental health professionals on the need to identify and treat arthritis-related pain, Dr. Brooks and her coauthors said.
“Addressing arthritis in mental health treatment and behavioral medicine may also help to reduce the overlapping cognitive, behavioral, and somatic symptoms in older adults with depressive symptoms and arthritis, which may be difficult for providers to disentangle through brief screening procedures and treat through conventional depression care,” they wrote.
The investigators cited several limitations. For example, the cross-sectional nature of the study makes it difficult to draw conclusions about causality. In addition, Dr. Brooks and her colleagues did not distinguish between different types of arthritis.
The researchers declared no conflicts of interest. The study was supported by several U.S. institutes, including the National Institute of Mental Health, and by numerous entities related to Dartmouth, including the Dartmouth Health Promotion and Disease Prevention Research Center. The Howard and Phyllis Schwartz Philanthropic Fund also provided funding.
SOURCE: Brooks JM et al. Int J Geriatr Psychiatry. 2018 Sep 19. doi: 10.1022/gps.4971.
FROM THE INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
Key clinical point: “It may be critical for mental health care providers to provide regular arthritis-related pain assessments” for older adults with or at risk for depression.
Major finding: Rates of arthritis were 55.0%, 62.9%, and 67.8% for those with mild, moderate, or severe depression, respectively, according to the 9-item Patient Health Questionnaire-9 scores.
Study details: Findings on 2,483 women and 2,309 men aged 50 years and older who participated in the National Health and Nutrition Examination Survey.
Disclosures: Dr. Brooks and her coauthors declared no conflicts of interest. The study was supported by several U.S. institutes, including the National Institute of Mental Health, and by numerous entities related to Dartmouth, including the Dartmouth Health Promotion and Disease Prevention Research Center. The Howard and Phyllis Schwartz Philanthropic Fund also provided funding.
Source: Brooks JM et al. Int J Geriatr Psychiatry. 2018 Sep 19. doi: 10.1002/gps.4971.
Cannabinoids may raise pain tolerance, not relieve pain itself
The belief that cannabinoids address chronic pain by relieving it has been challenged by a meta-analysis that finds cannabinoids have effects on pain thresholds that may, instead, make pain more tolerable.
The systematic review and meta-analysis comprised 18 placebo-controlled studies looking at the effect of plant-based or synthetic cannabinoids on experimental pain in 442 healthy participants. The conclusions were published Sept. 19 in JAMA Psychiatry.
“Cannabinoid drugs may prevent the onset of pain by producing small increases in pain thresholds,” wrote Martin J. De Vita and his colleagues, “but may not reduce the intensity of experimental pain already being experienced; instead, cannabinoids may make experimental pain feel less unpleasant and more tolerable, suggesting an influence on affective processes.”
Ten of the studies analyzed measured changes in pain thresholds and showed a small but significant association between cannabinoids and higher pain thresholds (95% confidence interval, 0.054-0.318; P = .006). Five studies examined pain unpleasantness, and showed that cannabinoids were associated with reduced unpleasantness ratings, compared with placebo (95% CI, 0.104-0.472; P = .002).
Among the eight studies that measured pain tolerance, a significant association was found between cannabinoid administration and higher pain tolerance (95% CI, 0.015-0.436; P = .04).
However, the 13 studies looking at pain intensity found no association between cannabinoid use and changes in the intensity of pain (CI, –0.120-0.154), nor were reductions in pain sensitivity to mechanical stimulation found in the three studies that measured mechanical hyperalgesia (95% CI, –0.059-0.244; P = .23).
The analysis did see significant effects according to the type of cannabinoid; plant-based cannabis had significantly stronger associations with reductions in pain unpleasantness compared to dronabinol and other synthetic THC preparations. However, both plant-based cannabis and dronabinol were associated with increases in pain tolerance, whereas other synthetic THC preparations were associated with significant reductions in pain tolerance.
Mr. De Vita, of the department of psychology at Syracuse (N.Y.) University, and his colleagues stressed that the systematic review and meta-analysis focused solely on studies of experimental pain, which “merely approximates features of clinical pain,” and specifically excluded individuals with chronic pain.
The absence of neuropathic pain data is “especially limiting, given that neuropathic pain is the primary condition for which modest empirical evidence exists that supports cannabinoid analgesia,” they wrote.
In particular, they drew attention to the finding that cannabinoids did not appear to have any effect on mechanical hyperalgesia, which they said suggests that cannabinoids might not address central sensitization in people with neuropathic pain.
The authors also raised the question of whether cannabinoids simply relieve pain by making people feel good or “high,” much like other intoxicating substances such as alcohol. They argued that the answer depends on what outcome is desired from treatment.
“If treatment aims to relieve pain without producing intoxication, psychoactive cannabinoids may not suffice,” they wrote. Ultimately, they said, the relief from pain experienced by some patients might be driven largely by an “affective rather than a sensory component.”
Among the limitations cited by the researchers is the focus on studies of experimental pain. “To produce evidence that supports the generalizability of the current findings, pain reactivity research must be conduced in clinical samples,” Mr. De Vita and his colleagues wrote.
The study was partly supported by the Syracuse University STEM Fellowship, and the National Institute on Alcohol Abuse and Alcoholism. No conflicts of interest were declared.
SOURCE: De Vita MJ et al. JAMA Psychiatry. 2018 Sep 19. doi: 10.1001/jamapsychiatry.2018.2503.
The belief that cannabinoids address chronic pain by relieving it has been challenged by a meta-analysis that finds cannabinoids have effects on pain thresholds that may, instead, make pain more tolerable.
The systematic review and meta-analysis comprised 18 placebo-controlled studies looking at the effect of plant-based or synthetic cannabinoids on experimental pain in 442 healthy participants. The conclusions were published Sept. 19 in JAMA Psychiatry.
“Cannabinoid drugs may prevent the onset of pain by producing small increases in pain thresholds,” wrote Martin J. De Vita and his colleagues, “but may not reduce the intensity of experimental pain already being experienced; instead, cannabinoids may make experimental pain feel less unpleasant and more tolerable, suggesting an influence on affective processes.”
Ten of the studies analyzed measured changes in pain thresholds and showed a small but significant association between cannabinoids and higher pain thresholds (95% confidence interval, 0.054-0.318; P = .006). Five studies examined pain unpleasantness, and showed that cannabinoids were associated with reduced unpleasantness ratings, compared with placebo (95% CI, 0.104-0.472; P = .002).
Among the eight studies that measured pain tolerance, a significant association was found between cannabinoid administration and higher pain tolerance (95% CI, 0.015-0.436; P = .04).
However, the 13 studies looking at pain intensity found no association between cannabinoid use and changes in the intensity of pain (CI, –0.120-0.154), nor were reductions in pain sensitivity to mechanical stimulation found in the three studies that measured mechanical hyperalgesia (95% CI, –0.059-0.244; P = .23).
The analysis did see significant effects according to the type of cannabinoid; plant-based cannabis had significantly stronger associations with reductions in pain unpleasantness compared to dronabinol and other synthetic THC preparations. However, both plant-based cannabis and dronabinol were associated with increases in pain tolerance, whereas other synthetic THC preparations were associated with significant reductions in pain tolerance.
Mr. De Vita, of the department of psychology at Syracuse (N.Y.) University, and his colleagues stressed that the systematic review and meta-analysis focused solely on studies of experimental pain, which “merely approximates features of clinical pain,” and specifically excluded individuals with chronic pain.
The absence of neuropathic pain data is “especially limiting, given that neuropathic pain is the primary condition for which modest empirical evidence exists that supports cannabinoid analgesia,” they wrote.
In particular, they drew attention to the finding that cannabinoids did not appear to have any effect on mechanical hyperalgesia, which they said suggests that cannabinoids might not address central sensitization in people with neuropathic pain.
The authors also raised the question of whether cannabinoids simply relieve pain by making people feel good or “high,” much like other intoxicating substances such as alcohol. They argued that the answer depends on what outcome is desired from treatment.
“If treatment aims to relieve pain without producing intoxication, psychoactive cannabinoids may not suffice,” they wrote. Ultimately, they said, the relief from pain experienced by some patients might be driven largely by an “affective rather than a sensory component.”
Among the limitations cited by the researchers is the focus on studies of experimental pain. “To produce evidence that supports the generalizability of the current findings, pain reactivity research must be conduced in clinical samples,” Mr. De Vita and his colleagues wrote.
The study was partly supported by the Syracuse University STEM Fellowship, and the National Institute on Alcohol Abuse and Alcoholism. No conflicts of interest were declared.
SOURCE: De Vita MJ et al. JAMA Psychiatry. 2018 Sep 19. doi: 10.1001/jamapsychiatry.2018.2503.
The belief that cannabinoids address chronic pain by relieving it has been challenged by a meta-analysis that finds cannabinoids have effects on pain thresholds that may, instead, make pain more tolerable.
The systematic review and meta-analysis comprised 18 placebo-controlled studies looking at the effect of plant-based or synthetic cannabinoids on experimental pain in 442 healthy participants. The conclusions were published Sept. 19 in JAMA Psychiatry.
“Cannabinoid drugs may prevent the onset of pain by producing small increases in pain thresholds,” wrote Martin J. De Vita and his colleagues, “but may not reduce the intensity of experimental pain already being experienced; instead, cannabinoids may make experimental pain feel less unpleasant and more tolerable, suggesting an influence on affective processes.”
Ten of the studies analyzed measured changes in pain thresholds and showed a small but significant association between cannabinoids and higher pain thresholds (95% confidence interval, 0.054-0.318; P = .006). Five studies examined pain unpleasantness, and showed that cannabinoids were associated with reduced unpleasantness ratings, compared with placebo (95% CI, 0.104-0.472; P = .002).
Among the eight studies that measured pain tolerance, a significant association was found between cannabinoid administration and higher pain tolerance (95% CI, 0.015-0.436; P = .04).
However, the 13 studies looking at pain intensity found no association between cannabinoid use and changes in the intensity of pain (CI, –0.120-0.154), nor were reductions in pain sensitivity to mechanical stimulation found in the three studies that measured mechanical hyperalgesia (95% CI, –0.059-0.244; P = .23).
The analysis did see significant effects according to the type of cannabinoid; plant-based cannabis had significantly stronger associations with reductions in pain unpleasantness compared to dronabinol and other synthetic THC preparations. However, both plant-based cannabis and dronabinol were associated with increases in pain tolerance, whereas other synthetic THC preparations were associated with significant reductions in pain tolerance.
Mr. De Vita, of the department of psychology at Syracuse (N.Y.) University, and his colleagues stressed that the systematic review and meta-analysis focused solely on studies of experimental pain, which “merely approximates features of clinical pain,” and specifically excluded individuals with chronic pain.
The absence of neuropathic pain data is “especially limiting, given that neuropathic pain is the primary condition for which modest empirical evidence exists that supports cannabinoid analgesia,” they wrote.
In particular, they drew attention to the finding that cannabinoids did not appear to have any effect on mechanical hyperalgesia, which they said suggests that cannabinoids might not address central sensitization in people with neuropathic pain.
The authors also raised the question of whether cannabinoids simply relieve pain by making people feel good or “high,” much like other intoxicating substances such as alcohol. They argued that the answer depends on what outcome is desired from treatment.
“If treatment aims to relieve pain without producing intoxication, psychoactive cannabinoids may not suffice,” they wrote. Ultimately, they said, the relief from pain experienced by some patients might be driven largely by an “affective rather than a sensory component.”
Among the limitations cited by the researchers is the focus on studies of experimental pain. “To produce evidence that supports the generalizability of the current findings, pain reactivity research must be conduced in clinical samples,” Mr. De Vita and his colleagues wrote.
The study was partly supported by the Syracuse University STEM Fellowship, and the National Institute on Alcohol Abuse and Alcoholism. No conflicts of interest were declared.
SOURCE: De Vita MJ et al. JAMA Psychiatry. 2018 Sep 19. doi: 10.1001/jamapsychiatry.2018.2503.
FROM JAMA PSYCHIATRY
Key clinical point: Cannabinoids might relieve experimental pain by making people feel good or “high,” much like other intoxicating substances such as alcohol.
Major finding: Cannabinoids improve pain thresholds (95% confidence interval, 0.054-0.3,18; P = .006) and pain unpleasantness (95% CI, 0.104-0.472; P = .002).
Study details: Systematic review and meta-analysis of 18 placebo-controlled studies of experimental pain.
Disclosures: The study was partly supported by the Syracuse University STEM Fellowship, and the National Institute on Alcohol Abuse and Alcoholism. No conflicts of interest were declared.
Source: De Vita MJ et al. JAMA Psychiatry. 2018 Sep 19. doi: 10.1001/jamapsychiatry.2018.2503.
Connecting at TCT 2018
The 30th anniversary of the Transcatheter Cardiovascular Therapeutics meeting in San Diego, sponsored by the Cardiovascular Research Foundation, will be the temporary home of more than 10,000 attendees. That’s up from about 9,400 last year.
Even so, that leaves a lot of folks who can’t be in sunny California. Keep in touch with friends near and far by using social media. Twitter hashtags for the meeting are #TCT2018 and #TCTConference.
The organizers encourage attendees to share their experiences and the educational content from the meeting, keeping in mind embargoes and some limitations, by posting photos, slides, or short video clips. Also, presentation slides will be online immediately after the sessions.
Attendees also can connect with each other using the the CRF Events app, available for free download here. But we recommend that meet outside if you can, considering the weather report.
The 30th anniversary of the Transcatheter Cardiovascular Therapeutics meeting in San Diego, sponsored by the Cardiovascular Research Foundation, will be the temporary home of more than 10,000 attendees. That’s up from about 9,400 last year.
Even so, that leaves a lot of folks who can’t be in sunny California. Keep in touch with friends near and far by using social media. Twitter hashtags for the meeting are #TCT2018 and #TCTConference.
The organizers encourage attendees to share their experiences and the educational content from the meeting, keeping in mind embargoes and some limitations, by posting photos, slides, or short video clips. Also, presentation slides will be online immediately after the sessions.
Attendees also can connect with each other using the the CRF Events app, available for free download here. But we recommend that meet outside if you can, considering the weather report.
The 30th anniversary of the Transcatheter Cardiovascular Therapeutics meeting in San Diego, sponsored by the Cardiovascular Research Foundation, will be the temporary home of more than 10,000 attendees. That’s up from about 9,400 last year.
Even so, that leaves a lot of folks who can’t be in sunny California. Keep in touch with friends near and far by using social media. Twitter hashtags for the meeting are #TCT2018 and #TCTConference.
The organizers encourage attendees to share their experiences and the educational content from the meeting, keeping in mind embargoes and some limitations, by posting photos, slides, or short video clips. Also, presentation slides will be online immediately after the sessions.
Attendees also can connect with each other using the the CRF Events app, available for free download here. But we recommend that meet outside if you can, considering the weather report.